Background and Objectives: The burdened symptomatology accompanying advanced non-small cell lung cancer (NSCLC) is associated with poor prognosis and lower quality of life (QoL). Although both chemotherapy and immunotherapy increase survival, they are still associated with reduced functionality due to their toxicity. This study aimed to estimate the QoL and symptom burden of NSCLC patients receiving second-line chemotherapy compared to patients receiving second-line immunotherapy. Materials and Methods: This comparative, prospective study, conducted from January 2020 to December 2021, included 111 NSCLC patients who were divided into two groups: 61 patients receiving second-line chemotherapy and 50 patients receiving second-line immunotherapy. Patients QoL and symptom burden were estimated using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ C-30) (value range 0 - 100) from treatment cycle 1 to 6. Results: The QoL (mean score > 50) and functionality dimensions (mean score > 50) were moderate to good in both treatment groups, while the symptoms burden did not appear to be a serious problem (mean score < 50). From cycle 3 to cycle 5, the QoL was significantly better in the immunotherapy group. From cycle 3, role and social functioning scores were higher in the immunotherapy group, while emotional and cognitive functioning were higher from cycle 2 (p < 0.05). The chemotherapy group experienced higher levels of nausea/vomiting, constipation and financial difficulties in all cycles (p < 0.05). Fatigue and appetite loss were significantly greater from cycle 2 and insomnia was significantly greater from cycle 3. On the contrary, the immunotherapy group experienced higher levels of diarrhea in cycles 5 and 6 (p < 0.05). Conclusions: Although both therapy groups did not report significantly impaired QoL and severe symptoms, it seems that QoL improved in the immunotherapy group, which reported less symptom burden compared to the chemotherapy group.

Nasal tumors are one of the most common tumors in aged golden retrievers. Adenocarcinomas or carcinomas are diagnosed in the majority of nasal tumors. Radiation therapy is the first option to decrease the size of tumor, and oral or intravenous chemotherapy is administered depending on the prognosis. Therefore, it is important to select the most appropriate drug for chemotherapy considering the price and the presence of concurrent disease. Anticancer drugs include first-generation chemotherapies, second-generation targeted anticancer drugs, and third-generation immunotherapy drugs. Considering their price and effectiveness, first- or second-generation anticancer drugs are mainly used.We report a first case in which a retriever with a nasal tumor was successfully treated and managed using a metronomic combination of chlorambucil (4mg/day, SID) and prednisolone (10mg/day) orally for 9 months at a general practice. A 35 kg spayed female golden retriever aged 8 years and 8 months visited the Bundang New York Animal Hospital in July 2023. A protocol of 4 weeks of chemotherapy followed by 1 week of rest was repeated, and the nasal exudate was significantly reduced. The size of the nasal tumor was monitored using Computed Tomography (CT) imaging at a referral hospital, and the images were taken in the following order: 1. before radiation therapy at the referral hospital and before chemotherapy; 2. after radiation therapy and before chemotherapy; and 3. after radiation therapy and after chemotherapy. Since the first occurrence of epistaxis, 12 months have passed (as of July 24). The nasal exudate is barely visible, and the retriever’s vital signs and weight remain stable. The size of the nasal tumor significantly decreased after 9 months of chemotherapy without moderate side effects. This study demonstrates that a prednisolone/chlorambucil metronomic combination can be an alternative to kinase inhibitor drugs as it is the cheapest and most effective way to manage tumors along with conventional radiation therapy.

In recent years, the treatment of locally-advanced rectal cancer (LARC) has been spotlighted in a number of landmark, practice-changing trials, heralding in the age of so-termed “total neoadjuvant therapy” (TNT). However, the lack of a common control arm, standard inclusion criteria, or, indeed, definition of TNT necessitates further study in this field, particularly using real-world data. We conducted a retrospective analysis of all patients treated for LARC at a single Canadian academic cancer centre between July 1st 2019 and July 14th 2022. This includes the June 2020 incorporation of TNT. 290 patients were included in the final analysis, and 124 variables were collected on each patient, including demographics, treatment type, adverse events, response to treatment, surgery versus watchful waiting and survival. Our findings demonstrate that both TNT and non-TNT regimens are highly toxic, with regards to both overall toxicity and grade 2+ adverse effects. 62 (96.9%) of patients on TNT experienced toxicities, compared to 186 (82.3%) of the non-TNT patients. Grade 2+ toxicities were 46 (71.9%) and 143 (63.3%), respectively. TNT, however, was associated with improved rates of complete response, compared to non-TNT treatment regimens (44% vs 24%). These findings suggest that TNT harbours both benefit and risk in a real-world population, and both of these aspects should be considered when deciding on a treatment approach for an individual patient. More work in the area is needed to determine longer term survival, as well as impact of surgery versus organ preservation approach on patient outcomes.

Introduction: Neoadjuvant chemotherapy in breast cancer offers the possibility to facilitate breast and axillary surgery, it is a test of chemosensibility in vivo with significant prognostic value and may tailor adjuvant treatment according to response. Material and Methods: a retrospective single institution of 482 stage II and III breast cancer patients treated with neoadjuvant chemotherapy based on anthracycline and taxans plus antiHEr2 in those Her2 positive cases. Survival was calculated at 5 and 10 years. Kaplan Meier with log rank test were calculated for difference according to TNM, pathological and molecular surrogated subtype, TILs cut-off 20%, response to chemotherapy and the presence of vascular invasion. Results: In the univariate those factors that influenced long-term patient outcome were TNM (p=0.000); pathologic subtype (p=0.003); Tils cut off 20%; achieving pCR (p=0.000), RCB (p=0.000) and vascular invasion (p=0.000). After a mean follow up of 126 months, Luminal tumors presented a substantial difference of survival rates calculated at 5 or 10 years (81.2% compared to 74.7%) whereas for TNBC was 75.3 and 73.5, respectively. The greatest difference was seen according to response those patients with pCR presented a 10yDDFS of 95.5 vs 72.4% for those patients without pCR. This difference was especially meaningful in TNBC were 10y DDFS according to the RCB 0 to 3 was 100%, 80.6%, 69% and 49.2% respectively. Patients with a special bad prognosis in our series were lobular carcinomas with 10y DDFS of 42.9% vs 79.7%, p= 0.001 for ductal carcinomas; and those patients with vascular invasion at the surgical specimen with a 10yDDFS of 59.2% vs 83.6, p=0.,000 for those patients without vascular invasion. Conclusion: long-term outcomes after neoadjuvant chemotherapy can help patient and clinician make well-informed decisions.

Introduction: Gastric cancer (GC) is one of the most frequently diagnosed cancers in the world. Although the incidence is decreasing in developed countries, treatment results are still unsatisfactory. The standard treatment for locally advanced gastric cancer (LAGC) is gastrectomy with perioperative chemotherapy. Aim: Assessment of selected microRNAs (miRNAs) in chemoresistance in archival material from LAGC. Material and method: The research group consisted of archival material from 10 patients with LAGC. Histological material from each patient was used from a biopsy performed during gastroscopy and after surgery preceded by 4 cycles of neoadjuvant chemotherapy (NAC) according to the FLOT or FLO regimen. The expression of selected miRNAs was assessed in the tissue material, such as miRNA-21-3p, miRNA-21-5p, miRNA-106a-5p, miRNA-122-3p, miRNA-122-5p, miRNA-143-3p, miRNA-143-5p, miRNA-203a-3p, miRNA-203-5p, miRNA-551b-3p, miRNA-551b-5p and miRNA-574-3p. miRNA expression was assessed by quantitative chain reaction polymerase reverse transcriptase (qRT-PCR). The response to NAC was assessed by computed tomography of the abdomen, chest and histopathology after gastrectomy. The statistical analyses were performed using GraphPad Prism 9.The significance limit was set at p

Purpose: This study aimed to identify the risk factors for acute pancreatitis (AP) and its impact on outcomes in Polish children treated for ALL. Methods: The study group included 2303 children who received intensive chemotherapy for ALL. The group was subdivided into patients with at least one episode of AP and those who did not develop AP following treatment for ALL. Results: The cumulative incidence of AP in the study group was 4.08%. Older age was an independent risk factor for AP development (OR 1.05; 95%CI: 1.006 – 1.098; p=0.03). The overall mortality related to AP was 2.13%. The probabilities of disease-free survival (p-DFS) and event-free survival (p-EFS) were 0.84 vs. 0.86, log-rank: p=0.65 and 0.75 vs. 0.80, log-rank: p=0.12, respectively in both subgroups. A total of 22 out of 94 patients (23.4%) with AP were re-exposed to asparaginase (ASP) during the subsequent phases of the treatment. Only one re-exposed to ASP patient (4.5%) developed a second episode of AP. There were no significant differences in p-DFS and p-EFS between patients re-exposed and not re-exposed to asparaginase (0.78 vs. 0.86, log-rank p=0.27 and 0.63 vs. 0.79, log-rank p=0.09 respectively). Conclusions: The incidence of AP in children with ALL is low and related to the patient’s age. AP development doesn’t seem to impact p-DFS and p-EFS in children with ALL. The recurrence of AP following re-exposure to asparaginase in patients with ALL and a history of AP is low (4.5%). Re-exposure to asparaginase after the first episode of AP doesn’t improve either p-DFS or p-EFS in children with ALL.

Background/Objectives: Laryngeal squamous cell carcinoma (LSCC) is the most prevalent form, accounting for nearly 95% of laryngeal cancer. This study evaluates the effectiveness of chemotherapy and radiation therapy combined for treating LSCC, along with exploring miR-449a as a potential biomarker for predicting treatment response and prognosis in LSCC patients. Patients and Methods: The study had 81 patients with advanced laryngeal cancer and 50 healthy controls. Chemotherapy was given for two cycles, followed by an evaluation of the response. Disease progression cases had surgical resection and radiation therapy. Positive responders had radiation therapy after a third cycle. The study also assessed miR-449a expression levels in tumor tissue, normal tissue, and serum samples from control subjects. Results: 31% achieved a complete response, and 49% showed a partial response. 31% of complete response participants maintained laryngeal integrity and vocal function. After radiation therapy, 74% of 65 patients responded completely and preserved laryngeal functions. Lower MiR-449a levels found in LSCC tissues and serum samples were correlated with aggressive tumor behavior, poor prognostic markers, and decreased survival. Conversely, elevated levels were seen in treatment responders. Conclusions: Combined chemo and radiotherapy preserve vocal function and improve outcomes in LSCC. MiR-449a is a promising indicator for diagnosis and treatment efficacy in LSCC.

The prognosis of cancer patients has greatly improved in the last years, owing to the development of novel chemotherapeutic agents. However, this progress comes with an increasing occurrence of cardiovascular adverse reactions. A serious side effect is arterial hypertension, which is the most frequent comorbidity encountered in cancer patients, influencing the outcomes in cancer survivors. Even though secondary hypertension related to specific chemotherapeutic agents, such as vascular endothelial growth factor inhibitors, is usually mild and reversible, in rare instances it can be severe, leading to discontinuation of chemotherapy. In addition, hypertension per se has been studied as a potential risk factor for cancer development. The relationship is even more complex than previously thought, as concerning evidence recently highlighted the potential oncogenic effects of antihypertensive drugs, such as thiazide diuretics predisposing to skin cancer. As a result, under the light of the similar risk factors and overlapping pathophysiological mechanisms between hypertension and cancer, a promising concept of onco-hypertension has emerged, aiming to improve the understanding of the complicated interplay between these two pathologies and maintain a balance between the efficacy and risks of both antihypertensive drugs and chemotherapy agents.

Abstract: Cervical cancer, which is the fourth most common malignancy and the fourth greatest cause of cancer-related deaths in women globally, continues to be a serious issue for global health. Despite advancements in treatment techniques, particularly the implementation of concomitant chemoradiation therapy, predicting the prognosis of locally advanced cervical cancer, especially for stage III, remains challenging. In recent years, neoadjuvant chemotherapy (NACT) has gained interest as a viable treatment strategy. The objective of this review paper is to scrutinize the clinical data and outcomes associated with NACT in the management of stage 3 cervical cancer. Electronic databases were used to perform a comprehensive literature search, and research up to 2023 were included. The findings suggest that NACT followed by irradiation may have advantages such as lowering tumor size, pelvic architectural distortion, and subclinical distant metastases, therefore enhancing radiation delivery. However, several studies have produced conflicting findings, raising questions regarding toxicity and finding no appreciable survival benefit over radiation alone. NACT followed by radical surgery has demonstrated more promising outcomes compared to surgery alone in terms of increasing rates of overall survival (OS) and progression-free survival (PFS). Additionally, NACT has been associated with decreased tumor growth, parametrial infiltration, nodal, metastases, and vascular space invasion. These findings suggest adjuvant radiation treatment. Although the overall survival rate has been markedly increased by concomitant chemoradiation treatment, metastatic disease continues to be a major factor in the death rate from cervical cancer. Therefore, improving outcomes in locally advanced cervical cancer requires investigating novel systemic treatments, such as NACT. The study also emphasizes how crucial it is to research factors like cisplatin dose-intensity and cycle lengths in order to maximize NACT's efficacy. To prevent the need for subsequent treatments and cumulative toxicity, more study should concentrate on patient selection for NACT followed by surgery.

Chloroquine (CQ) and its derivate hydroxychloroquine (HCQ), the compounds with recognized ability to suppress autophagy, have been tested in experimental works and in clinical trials as adjuvant therapy for the treatment of cancers of different origin to increase the efficacy of cytotoxic agents. Such strategy can be effective to overcome the resistance to standard chemotherapy or anti-angiogenic therapy. This review presents the results of combined application of CQ/HCQ with conventional chemotherapy drugs (doxorubicin, paclitaxel, platinum-based compounds, gemcitabine, tyrosine kinases and PI3K/Akt/mTOR inhibitors, and other agents) for the treatment of different malignancies obtained in experiments on cultured cancer cells and on animal xenograft models, with a few examples of clinical trials. The effects of such approach on viability of cancer cells and tumor growth, as well as autophagy-dependent and independent molecular mechanisms underlying cellular responses of cancer cells to CQ/HCQ are summarized. Although the majority of experimental studies in vitro and in vivo have shown that CQ/HCQ can effectively sensitize the cancer cells to cytotoxic agents and increase the potential of chemotherapy, the results of clinical trials are often inconsistent. Although pharmacological suppression of autophagy remains a promising tool for increasing the efficacy of standard chemotherapy, the development of more specific compounds is required.

Treatment regimens are regularly evolving, together with novel therapies and drugs. Such evolution is necessary to circumvent resistance mechanisms and to give patients the best possible health care. When dealing with cancer, most regimens involve multiple treatments (surgery, radiation therapy, chemotherapy, immunotherapy, etc.). The purpose of this study was to associate in a single compound metal-based drugs and photosensitizers to combine chemotherapy and photodynamic therapy. Two arene-ruthenium tetrapyridylporphyrin compounds (2H-TPyP-arene-Ru and Zn-TPyP-arene-Ru) have been synthesized and evaluated on two colorectal cancer cell lines (HCT116 and HT-29). The cytotoxicity and phototoxicity have been evaluated. In addition, the anticancer mechanism and the cell death process mediated by the two compounds were studied. The results showed that the two arene-ruthenium photosensitizer-containing complexes have a strong phototoxic effect after photoactivation. The 2H-TPyP-arene-Ru induced outstanding cytotoxicity when compared to the Zn-TPyP-arene-Ru analogue. Moreover, under light, these two arene-ruthenium photosensitizers induce an apoptotic process in human colorectal cancer cell lines.

Evidence of the efficacy and safety of colorectal stent placement for palliation remains insufficient. This single-arm, prospective, multicenter study with WallFlex enteral colonic stent included 200 consecutive patients with malignant large bowl obstruction in the palliation cohort. The technical and clinical success, as well as stent patency and complications as short-term (≤ 7 days) and long-term (&gt; 7days) outcomes, of high axial force self-expandable metal stent (SEMS) placement was evaluated. The technical and clinical success rates were 98.5% and 94.5%, respectively. Non recurrent colorectal obstruction at 1 year was 63.9%, and 71.2% of the patients remained free of recurrent colorectal obstruction until death or the last follow-up. Fifty-six patients (28.0 %) received chemotherapy and five patients were administered bevacizumab after stent placement. The overall complication rate was 47%, including four (2.0%) early-onset and ten (5.0%) late-onset perforations, mostly due to stent-edge injury. Only the use of a long SEMS was a risk factor for perforation. In conclusion, endoscopic colorectal stenting using high axial force SEMS is an effective and safe procedure for palliation in patients with malignant colorectal obstruction. However, care should be taken to avoid perforation at the stent edge when using a long SEMS.

Acute myeloid leukemia (AML) is a hematological malignancy that predominantly affects the elderly. Prognosis declines with age. For those who cannot tolerate intensive chemotherapy, historically established treatment options have been hypomethylating agents (HMAs), low dose cytarabine (LDAC), and best supportive care (BSC). As the standard of care evolves for those unfit for intensive chemotherapy, there is a need to understand established treatment pathways, clinical outcomes and healthcare resource utilization in Canada. The CURRENT study was a retrospective chart review of AML patients not eligible for intensive chemotherapy who initiated first-line treatment between 1 January 2015 and 31 December 2018. Data were collected from 170 Canadian patients treated at six hematology centers, of whom 118 received systemic therapy and 52 received BSC as first-line treatment. Median overall survival was 8.58 months and varied from 2.96 months for BSC to 13.31 months for HMAs. Over 80% of patients had at least one outpatient visit, and 67% of patients receiving systemic therapy and 71% of those receiving BSC had at least one admission to hospital, during their first line of therapy. A total of 96 (81.4%) patients receiving first line systemic therapy and 39 (75.0%) of those receiving first line BSC had at least one red blood cell or platelet transfusion. These findings highlight the unmet need for novel therapies for patients ineligible for intensive chemotherapy.

Neoadjuvant systemic therapy has now become the the standard in early breast cancer management. Chemotherapy in combination with trastuzumab +/- pertuzumab targeted therapy can improve rates of pathologic complete response (pCR) in patients with HER2-positive breast cancer. Achieving a pCR is considered a good prognostic factor, in particular in patients with more aggressive breast cancer subtypes such as TNBC or HER2 positive cancers. Furthermore, most studies demonstrate that chemotherapy in combination with trastuzumab and pertuzumab is well tolerated. The retrospective analysis presented here concentrates on neoadjuvant therapy with the TCbH-P regimen, with a particular emphasis on patients over 60 years of age. We analysed the factors affecting the achievement of pCR and presented adverse effects of the applied therapies, which opened a discussion about optimizing the therapy of older patients with HER-2 positive breast cancer.

Skeletal myopathy encompasses both atrophy and dysfunction and is a prominent event in cancer and chemotherapy-induced cachexia. Here, we investigate the effects of chemotherapeutic agent, 5-fluorouracil (5FU), on skeletal muscle mass and function, and whether small molecule therapeutic candidate, BGP-15, could be protective against the chemotoxic challenge exerted by 5FU. Additionally, we explore the molecular signature of 5FU treatment. Male Balb/c mice received metronomic tri-weekly intraperitoneal delivery of 5FU (23 mg/kg), with and without BGP-15 (15 mg/kg), 6 times in total over a 15-day treatment period. We demonstrated that neither 5FU, nor 5FU combined with BGP-15, affected body composition indices, skeletal muscle mass or function. Adjuvant BGP-15 treatment did, however, prevent the 5FU-induced phosphorylation of p38 MAPK and p65 NF-κB subunit, signalling pathways involved in cell stress and inflammatory signalling, respectively. This as associated with mitoprotection. 5FU reduced the expression of the key cytoskeletal proteins, desmin and dystrophin, which was not prevented by BGP-15. Combined, these data show that metronomic delivery of 5FU does not elicit physiological consequences to skeletal muscle mass and function but is implicit in priming skeletal muscle with a molecular signature for myopathy. BGP-15 has modest protective efficacy against the molecular changes induced by 5FU.

Current oncological developments are based on improved understanding of genetics, and especially the discovery of genes whose alterations affect cell functions with consequences for the whole body. Our work is focused on the one of these genes, the BARD1 and its oncogenic role in breast cancer. Most importantly, the study points to new avenues in the treatment and prevention of the most frequent female cancer based on BARD1 research. The BARD1 and BRCA1 proteins have similar structures and functions, and they combine to form the new molecule BARD1-BRCA1 heterodimer. The BARD1-BRCA1 complex is involved in genetic stabilization at the cellular level. It allows to mark abnormal DNA fragments by attaching ubiquitin to them. In addition, it blocks (by ubiquitination of RNA polymerase II) the transcription of damaged DNA. Ubiquitination, as well as stabilizing chromatin, or regulating the number of centrosomes, confirms the protective cooperation of BARD1 and BRCA1 in the stabilization of the genome. The overexpression of the oncogenic isoforms BARD1β and BARD1δ permit cancer development. The introduction of routine tests, for instance, to identify the presence of the BARD1β isoform, would make it possible to detect patients at high risk of developing cancer. On the other hand, introducing BARD1δ isoform blocking therapy, which would reduce estrogen sensitivity, may be a new line of cancer therapy with potential to modulate responses to existing treatments. It is possible that the BARD 1 gene offers new hope for improving breast cancer therapy.

Current oncological developments are based on improved understanding of genetics, and especially the discovery of genes whose alterations affect cell functions with consequences for the whole body. Our work is focused on the most important of these genes, the BARD1 and its oncogenic role in breast cancer. Most importantly, the study points to new avenues in the treatment and prevention of the most frequent female cancer based on BARD1 research. The BARD1 and BRCA1 proteins have similar structures and functions, and they combine to form the new molecule BARD1-BRCA1 heterodimer. Through ubiquitination, this heterodimer has significant effects on individual proteins, enabling, among others, the destruction of damaged DNA fragments. Ubiquitination, as well as stabilizing chromatin, or regulating the number of centrosomes, confirms the protective cooperation of BARD1 and BRCA1 in the stabilization of the genome. The overexpression of the oncogenic isoforms BARD1β and BARD1δ permit cancer development. The introduction of routine tests, for instance, to identify the presence of the BARD1β isoform, would make it possible to detect patients at high risk of developing cancer. On the other hand, introducing BARD1δ isoform blocking therapy, which would reduce estrogen sensitivity, may be a new line of cancer therapy with potential to modulate responses to existing treatments. It is possible that the BARD 1 gene offers new hope for improving breast cancer therapy.

Recent preclinical studies have shown the potential benefits of short-term calorie reduction (SCR) on cancer treatment. In this integrative review, we aimed to identify and synthesize current evidence regarding the feasibility, process, and effects of SCR in cancer patients receiving chemotherapy. PubMed, Cumulative Index to Nursing and Allied Health Literature, Ovid Medline, PsychINFO, and Embase were searched for original research articles using various combinations of Medical Subject Heading terms. Among the 311 articles identified, seven studies met the inclusion criteria. The majority of the reviewed studies was small randomized controlled trials or cohort study with fair quality. The results suggest that SCR is safe and feasible. SCR is typically arranged around the chemotherapy with the duration ranging from 24 to 96 hours. Most studies examined the protective effects of SCR on normal cells during chemotherapy. The evidence supports that SCR had the potential to enhance both physical and psychological wellbeing of patients during chemotherapy. SCR is a cost-effective intervention with great potential. Future well-controlled studies with sufficient sample sizes are needed to examine the full and long-term effects of SCR and its mechanism of action.

This study aimed to identify the utility of diffusion-weighted magnetic resonance (MR) imaging with an apparent diffusion coefficient (ADC) map as a predictor of the intrahepatic response of hepatocellular carcinoma (HCC) to cisplatin-based hepatic arterial infusion chemotherapy (HAIC). We retrospectively evaluated 113 consecutive patients with HCC who underwent gadoxetic acid-enhanced and diffusion-weighted MR imaging. The appropriate cutoff for the tumor-to-liver ADC ratio was determined to be 0.741. Of the 113 patients, 51 (45%) presented with a tumor-to-liver ADC ratio < 0.741. Evaluation of the intrahepatic treatment response after 2-3 cycles of HAIC in these 51 patients revealed that 20 patients (39%) experienced an objective response to HAIC. On the other hand, only 10 of the 62 patients with a tumor-to-liver ADC ratio ≥ 0.741 (16%) experienced an objective response. Thus, the objective response rate was significantly higher in patients with a tumor-to-liver ADC ratio < 0.741 than in those with a tumor-to-liver ADC ratio ≥ 0.741 (P = 0.006). Multivariate logistic regression analysis using parameters including perfusion alteration, percentage of a non-enhancing portion, and tumor-to-liver ADC ratio revealed that a tumor-to-liver ADC ratio < 0.741 (odds ratio 3.03; P = 0.015) is the sole predictor of an objective response to HAIC. Overall survival rates were significantly higher in patients with objective responses to HAIC than in those without objective responses (P = 0.001 by log-rank test). In conclusion, patients with unresectable HCC with a tumor-to-liver ADC ratio < 0.741 showed a favorable intrahepatic response to HAIC. Therefore, diffusion-weighted MR imaging can play a critical role as a predictor of response to cisplatin-based HAIC in unresectable HCC.

Schistosomiasis, a crippling ailment that afflicts over 220 million people worldwide. Yet or up till now, there is no vaccine for schistosomiasis, and chemotherapy relies heavily on a single drug, the praziquantel. The present study was undertaken to investigate the therapeutic effect of Monophosphoryl Lipid A (MPLA) as an adjuvant in soluble egg antigen (SEA) vaccinated mice against the deleterious pathological impacts induced in hepatic tissues of mice by Schistosoma mansoni infection. In addition, to study the associated parasitological, immunological and biochemical parameters. Parasitological parameters showed that intraperitoneal injection of MPLA into SEA-vaccinated and S. mansoni-infected mice was effective to a significant degree in reducing the worm and egg burden, granuloma count and diameter as well as the total area of infection in their livers versus SEA-untreated but infected ones. In addition, MPLA showed ameliorative action on the elevated liver oxidative stress marker, including malondialdehyde (MDA) and decrease in the level of the antioxidant enzymes, reduced glutathione (GSH) and catalase (CAT) which may have a role in the liver damage and fibrosis due to S. mansoni infection. In conclusion, treatment with MPLA has multi-functions in attenuating the deleterious impacts of S. mansoni infection in mice livers. Its effects are mediated through a reduction of ova count, worm burden, granuloma diameter and amelioration of antioxidant defense systems, and liver function biomarkers.

Background In SILIUS (NCT01214343), combination of sorafenib and hepatic arterial infusion chemotherapy did not significantly improve overall survival in patients with advanced hepatocellular carcinoma (HCC) compared with sorafenib alone. In this study, we explored the relationship between objective response by mRECIST and overall survival (OS) in the sorafenib group, in the combination group and in all patients in the SILIUS trial. Methods Association between objective response and OS in patients treated with sorafenib (n=103), combination (n=102) and all patients (n=205) were analyzed. The median OS of responders was compared with that of non-responders. Landmark analyses were performed according to objective response at several fixed time points, as sensitivity analyses, and the effect on OS was evaluated by Cox regression analysis with objective response as a time-dependent covariate, with other prognostic factors was performed. Results In the sorafenib group, OS of responders (n = 18) was significantly better than that of non-responders (n = 78) (p < 0.0001), where median OS was 27.2 (95% CI, 16.0–not reached) months for responders and 8.9 (95% CI, 6.5–12.6) months for non-responders. HRs from landmark analyses at 4, 6, and 8 months were 0.45 (p=0.0330), 0.37 (p=0.0053), and 0.36 (p=0.0083), respectively. Objective response was an independent predictor of OS based on unstratified Cox regression analyses. In the all patients and the combination group, similar results were obtained. Conclusion In the SILIUS trial, objective response was an independent prognostic factor for OS in patients with HCC.

A platinum (II) complex stabilized by a pyridine and a N-heterocyclic carbene ligand featuring an anthracenyl moiety was prepared. The compound was fully characterized and its molecular structure was determined by single-crystal X-ray diffraction. The compound demonstrated high in vitro antiproliferative activities against cancer cell lines with IC50 ranging from 10 to 80 nM. The presence of the anthracenyl moiety on the NHC Pt complex was used as a luminescent tag to probe the metal interaction with the nucleobases of the DNA through a pyridine-nucleobase ligand exchange. Such interaction of the platinum complex with DNA was corroborated by optical tweezers techniques and liquid phase AFM microscopy. The results revealed a two-state interaction between the platinum complex and the DNA strands. This two-state behaviour was quantified from the different experiments due to contour length variations. At 24h incubation, the stretching curves revealed multiple structural breakages, and AFM imaging revealed a highly compact and dense structure of platinum complexes bridging the DNA strands.

Polyhedral cages (p-cages) describe the geometry of some families of artificial protein cages. We identify the p-cages made out of families of equivalent polygonal faces such that the faces of 1 family has 5 neighbours and P_1 edges, while those of the other family have 6 neighbours and P_2 edges. We restrict ourselves to polyhedral cages where the holes are adjacent to at most 4 faces. We characterise all the p-cages with a deformation of the faces, compared to regular polygons, not exceeding 10%.

Mevcut çalışmada, (p, q)−tam sayıya dayalı iki boyutlu Chlodovsky tipi Bernstein operatörlerini tanıtıyoruz. Yeni operatörümüzün yaklaşıklık özelliklerini Korovkin tipi teorem yardımıyla inceliyoruz. Ayrıca, yerel yaklaşıklık özelliklerini sunuyoruz ve süreklilik modülü ve Lipschitz tipi maksimal fonksiyon vasıtasıyla yakınsama oranlarını belirliyoruz. Ayrıca, bu operatörler için bir Voronovskaja tipi teorem veriyoruz. Ve, bu operatörlerin ağırlıklı yaklaşıklık özelliklerini inceliyoruz ve aynı uzayda yakınsama oranını tahmin ediyoruz. Son olarak, Maple'ın yardımıyla, açıklayıcı grafikler bu operatörlerin belirli fonksiyonlara yakınsama oranlarını göstermektedir. Sistem kontrolü sırasında operatörler tarafından yaklaşıklık hızlarının optimizasyonu, kararlılık ve performansta önemli iyileştirmeler sağlar. Sonuç olarak, dinamik sistemlerin kontrolü ve modellenmesi yenilikçi yöntemlerle daha verimli ve etkili hale gelir. Kesirli diferansiyel denklemlerin modellenmesi ve kontrol teorisi alanındaki bu gelişmeler, hem modelleme hem de optimizasyon süreçlerine önemli faydalar sunarak bu alanlardaki uygulama yelpazesini genişletmektedir.

In our previous study of 291 cancer patients, we showed that 20% did not respond to two doses of COVID-19 vaccine administered six weeks apart. Here we investigated if psychological factors (distress, anxiety and depressive symptoms) affected antibody response and markers of vaccine activation (D-dimer) after 6 months from initial vaccination. Overall, 31 subjects (14.2%) had no antibody response at 6 months. Our analysis revealed significant predictors of vaccine failure, including stage of metastatic disease and high stress levels (OR=2.46, 95% CI, 1.05-5.77, p=0.04). Notably, nonresponders showed twice the prevalence of distress than responders (21% vs. 10%, p=0.04). Longitudinal measurements of IgG levels indicated that participants with high depressive symptoms at baseline maintained lower antibody levels over six months (p=0.003). In addition, women with high anxiety showed reduced levels of D-dimer at 6 month time (p=0.03). The data also showed that smokers and former smokers had significantly lower antibody levels than their nonsmoking counterparts (p=0.0004). At baseline, the high discomfort rate (≥5) was 34.4% in women and 23.8% in men; only men experienced an increase in median discomfort during the observation period. Moreover, higher educational level was related to increased distress among women (p=0.046). These findings underscore a critical association between elevated psychological distress and reduced immune responses to the COVID-19 vaccine, emphasizing the urgent need for targeted psychological and behavioral support within this vulnerable population.

CO₂-soluble surfactant foam systems have garnered significant attention in the fields of enhanced oil and gas recovery, environmental protection, and greenhouse gas emission reduction. This review provides a comprehensive explanation of the basic theory of CO₂-soluble surfactant foam, the mechanism of enhanced oil recovery, and the classification and application of various CO₂-soluble surfactants.The mechanism of enhanced oil recovery by CO₂-soluble surfactant foam involves the effective reduction of CO₂ fluidity, the decrease in oil-air flow ratio, and the stabilization of the displacement front. Foam plays a vital role in mitigating the issues of channeling and gravity separation often caused by simple CO₂ injection. The reduction in gas fluidity can be attributed to the increase in apparent viscosity and trapped gas fraction.Future research should prioritize the development of more efficient and environmentally-friendly CO₂-soluble surfactants. It is essential to further explore the advantages and challenges associated with their practical applications in order to maximize their potential impact.

Objectives: Cardiogenic shock [CS] is associated with a high-mortality. Suitable patients maybe successfully bridged using newer intravascular micro-axial left-ventricular assist devices [M-LVAD] for recovery or determination of definitive therapy. Methods: Between January-2020 and July-2024, 107 patients underwent placement of M-LVAD for CS. The cohort was divided into 4 groups based on their destination; group-1: 34 patients [32%] receiving transplant; group-2: 25 patients [23%] receiving durable LVAD; group-3: 42 patients [39%] bridging from post-cardiotomy CS [PCCS]; and group-4: 6 patients [5.6%] bridging decision/recovery [these were excluded from analysis]. Multivariable logistic-regression [MLR] and Cox-regression [MCR] models identified predictors of early-hospital and late mortality, with data reported as odds ratios [ORs], and hazard ratios [HRs], respectively. P<0.05 was statistically significant. Results: Complications included device-malfunction [n=6, 6%], gastrointestinal bleed [n=9, 9%], stroke [n=11, 11%]; long-term hemodialysis [n=21, 21%]. Early-hospital mortality included 13 patients [13%]: 2 in group-1, 1 in group-2 and 10 in group-3 [p=0.02]. In the MLR model, the category of cardiogenic shock requiring M-LVAD placement was statistically significant [OR=4.7 (0.9-24), P=0.05]. Patients were followed for up to 4.5-years, and 23 deaths occurred; group-1: 3 patients, group-2: 5 patients, and group-3: 15 patients [p=0.019]. At 4.5-years, actuarial survival was 90.7±5.1% in group-1, 79.2±8.3% in group-2, and 62.8%±7.7% in group-3 [P=0.01]. In the MCR model, M-LVAD category [HR=3.63 (1.03-12.9) P=0.04], and long-term postoperative dialysis [HR=3.9 (1.6-9) P=0.002], emerged as statistically significant predictors of long-term mortality. Conclusions: In cardiogenic shock, our mid-term outcomes demonstrate good survival with M-LVADs as bridge to transplant and durable LVAD, and reasonable survival as bridge to recovery following cardiotomy, reduced ECMO usage and early ambulation/rehabilitation.

Antimalarial drug resistance has become a real public health problem despite WHO measures. New sequencing technologies make it possible to investigate genomic variations associated with resistant phenotypes at the genome-wide scale. Based on the use of hemisynthetic nanopores, the PromethION technology from Oxford Nanopore Technologies can produce long-read sequences, in contrast to previous short-read technologies used as gold-standard to sequence Plasmodium. Two clones of P.falciparum (Pf3D7 and PfW2) were sequenced in long-read using the PromethION sequencer from Oxford Nanopore Technologies without genomic amplification. This made it possible to create a processing analysis pipeline for human Plasmodium with ONT Fastq only. De novo assembly revealed N50 lengths of 18,488 kb and 17,502 kb for the Pf3D7 and PfW2, respectively. The genome size was estimated at 23,235,407 base pairs for the Pf3D7 clone and 21,712,038 base pairs for the PfW2 clone. The average genome coverage depth was estimated at 787X and 653X for the Pf3D7 and PfW2 clones, respectively. This study proposes an assembly processing pipeline for the human Plasmodium genome using software’s adapted to large ONT data and the high AT percentage of Plasmodium. This search provides all the parameters, which have been optimized, for use with the software selected in the pipeline.

The ever-growing student population and limited administrative resources strain traditional communication channels within educational institutions. Chatbot technology offers a promising solution, but current limitations can impede effective student-administration interaction. This paper proposes a hybrid chatbot model to enhance reliability in educational administration by addressing the limitations of generative models like ChatGPT. We investigate three individual chatbot approaches (rule-based, retrieval-based, and generative-based) to handle educational inquiries. An evaluation assessed their strengths, weaknesses, and user experience. Based on these findings, a hybrid model with an intelligent classifier for query routing was developed. This model leverages each approach's strengths and addresses uncertainty in the generative model to achieve increased accuracy and reliability. Our results demonstrate an accuracy improvement compared to individual models. This work contributes to developing adaptable chatbot systems capable of addressing a wider range of user inquiries, which is particularly beneficial in resource-constrained educational settings. Additionally, the proposed model demonstrates competitive performance when benchmarked against existing state-of-the-art administrative educational chatbots. Furthermore, by automating routine inquiries and offering 24/7 access to information and support, this model has the potential to reduce administrative workload and improve the overall student experience significantly. Moreover, the modular design of our hybrid model offers a foundation for future research on personalizing chatbot interactions and integrating domain-specific knowledge for enhanced communication within educational environments.

This paper explores the transformative impact of computational pharmaceutics, integrating AI, multi-scale modeling, quantum computing, AI-driven drug discovery, and blockchain frameworks. Molecular dynamics simulations provide insights into atomic behaviors crucial for drug design. Quantum computing reduces computational costs for simulating protein-drug interactions. AI and Graph Neural Networks accelerate drug discovery and personalized medicine. Blockchain frameworks facilitate secure pharmacogenetic data sharing. These advancements revolutionize drug development, offering unprecedented efficiency, innovation, and personalized treatments.

Abstract: Wildfires in forest ecosystems exert substantial ecological, economic, and social impacts. The effectiveness of fire management hinges on precise pre‐fire risk assessments to inform mitigation efforts. This study aims to investigate the relationship between predictions from pre‐fire risk assessments and outcomes observed through post‐fire burn severity analyses. In this study, forest fire risk was assessed with the Fuzzy Analytical Hierarchy Process, in which fire behavior factors were used as input. The degree of burn was determined using the Random Forest method using 11519 training points and 400 test points on Sentinel‐2 satellite images in three different classes. According to the results obtained from 266 selected test points located within the forest boundaries, all primary factors showed an increased effect in areas with high burn severity. Climate, in particular, emerged as the most influential factor, accounting for 52% of the overall impact. However, in cases of high fire severity, climate proved to be the most effective risk factor, ac‐counting for 67%. It followed by topography with 50% accuracy at high fire intensity. In the risk assessment is based on the FAHP method, climate was assigned the highest weight value among other factors with 32.2%. Topography emerged as the second most effective risk factor with 27 %. To evaluate the results more comprehensively both visually and statistically, two regions with different stand canopy characteristics were selected within the study area. While high burn severity had the highest accuracy in Case 1 area, moderate burn severity had the highest in Case 2 area. During the days when the fire continued, the direction of spread was obtained from MODIS images. In this way, the fire severity depending on the direction of fire progression was also interpreted. Through an analysis of various case studies and existing literature, the research underscores both the strengths and limitations inherent in predicting forest fire behavior‐based pre‐fire risk assessments. Furthermore, it emphasizes the necessity of continuous improvement to increase the success of forest fire management.

This study aims to explore methods for automating the replication of correlated portfolios across shares using various algorithms. The goal is to select one algorithm for implementation in a visualization tool that will facilitate portfolio building. The dynamics of the stock market provide a comprehensive view of the global economy, acting as a catalyst for stakeholders to participate and benefit various sectors financially, primarily through investments in companies that yield returns and contribute to the economy. The evaluation and comparison of these algorithms are crucial for making well-informed decisions regarding the core objectives of the study. Ultimately, a determination will be made as to whether the program can effectively analyse data from Yahoo finance to provide a quick overview of the financial market state of companies in the S&P 500 US stock prices.

Porphyromonas gingivalis is the major pathogenic bacteria found in the subgingival plaque of patients with periodontitis, leading to neuroinflammation. The bacteria destroy periodontal tissue through its virulence factors which are retained in the bacteria’s outer membrane vesicles (OMV). The purpose of this study was to determine the real time effect of intraperitoneal in-jection of P. gingivalis OMV on the production and expression of inflammatory markers as well as histopathological changes in the central nervous system (CNS) of adult zebrafish. Fol-lowing the LD50 (21 µg of OMV), the zebrafish were injected intraperitoneally with 18 µg of OMV and control group with normal saline at 7 different time points. Brains of experimental zebrafish were dissected at desired time points for colorimetric assays, ELISA and histology. This study discovered that nitric oxide and PGE2 were significantly increased at 45 minutes while IL-1β and IL-6 were expressed at subsequent 12- and 24-hours. respectively. Histopatho-logical changes such as blood coagulation, astrocytosis, oedema, spongiosis, and necrosis were also observed between 6- and 24-hours. The two apoptotic enzymes, caspases 3 and 9 were not expressed at any time point. In summary, the OMV induced neuroinflammatory responses and histopathological changes in adult zebrafish were time point dependent

Aluminum (Al) toxicity and low phosphorus availability (LP) are the top two co-existing edaphic constraints limiting agriculture productivity in acid soils. Plants have evolved versatile mechanisms to cope with the two stresses alone or simultaneously. However, the specific and common molecular mechanisms, especially those on flavonoids and carbohydrate metabolism, are still unclear. Laboratory studies were conducted on two wheat genotypes, Fielder (Al-tolerant and P-efficient) and Ardito (Al-sensitive and P-inefficient), exposed to 50 μM Al and 2 μM Pi (LP) in hydroponic solutions. After 4 days of stress, wheat roots were analyzed via transcriptomic and targeted metabolomic techniques. A total of 2296 differentially expressed genes (DEGs, 1535 up and 761 down) under Al and 3029 DEGs (1591 up and 1438 down) under LP were identified in Fielder. Similarly, 4404 DEGs (3191 up and 1213 down) under Al and 1430 DEGs (1176 up and 254 down) under LP were identified in Ardito. The GO annotation analysis results that 4079 DEGs annotated to the metabolic processes term. These DEGs were significantly enriched in the phenylpropanoid, flavonoid, flavone and flavonol biosynthesis, and carbohydrate metabolism pathways by performing the KEGG enrichment analysis. The targeted metabolome analysis detected 19 flavonoids and 15 carbohydrate components in Fielder and Ardito under Al and LP. More responsive genes and metabolites were involved in flavonoid metabolism under LP than Al in the Fielder, while an opposite trend in the Ardito. In the carbohydrate metabolism pathway, the genes and metabolites were higher in Fielder than in Ardito. The combined transcriptome and metabolome analysis revealed that the flavonoid and carbohydrate genes and metabolites differed between Fielder and Ardito under Al and LP, which may be an important reason for Fielder’s high Al and LP resistance. The results of this study lay a foundation for pyramiding genes and breeding multi-resistance varieties.

Flexible capacity applications demands to large energy storage density and high breakdown electric field strength of flexible films. Here, P(VDF-HFP) with ultra-thin Al2O3 nanosheets composite films were designed and fabricated through an electrospinning process followed by hot-pressing in sandwich structured. The results show that the insulating ultra-thin Al2O3 nanosheets and the sandwich structure can enhance the composites' breakdown field (by 24.8%) and energy density (by 30.6%) remarkedly to P(VDF-HFP) polymer matrix. An energy density of 23.5 J/cm3 at the ultrahigh breakdown field of 740kV/mm can be therefore realized. Insulating test and phase-field simulation results reveal that ultra-thin nanosheets insulating buffer layers can reduce the leakage current in composites, thus it effects the electric field spatial distribution to enhance breakdown strength. Our research provides a feasible method to increase the breakdown strength of ferroelectric polymers, which is comparable to those of non-ferroelectric polymers.

The role of biomarkers in the diagnosis of inflammatory bowel disease is not fully characterized. C-reactive protein has a short half-life and elevates quickly after the onset of an inflammatory process, the performance is better in Crohn’s disease than in ulcerative colitis. Erythrocyte sedimentation rate is easy to determine, widely available, and cheap but the long half-life the influence of age, anemia, smoking, and drugs limit its usefulness. Fecal markers have good specificity, but suboptimal accuracy. Microbial antibodies and novel immunological markers show promise but need further evidence before entering clinical practice. Proteomic methods could represent the dawn of a new era of stool protein/peptide biomarker panels able to select patients at risk of inflammatory bowel disease.

Background: Hypovitaminosis D is a public health problem due to its implications for various diseases. Vitamin D has numerous functions, such as modulating the metabolism of some cellular tissues, and is expressed through the VDR gene that may influence gene expression modulation, which plays an important role in vitamin D metabolism. Objective: To evaluate the effect of the genotypes of single nucleotide polymorphism (SNP) BsmI of the vitamin D receptor (VDR) gene on VDR, SOD2, and CYP24A1 gene expression in individuals with low serum vitamin D levels. Methods: This was a cross-sectional analytical study. Individuals were invited to participate and, after signing the informed consent form, answered a structured questionnaire with identification data. Blood was collected for biochemical analysis, and vitamin D was measured by chemiluminescence; BsmI polymorphism was determined using real-time polymerase chain reaction (PCR) assays with TaqMan allelic discrimination, and gene expression was conducted by qRT-PCR using QuantiFast SYBR® Green PCR Master Mix. Data were analyzed using the SPSS 20.0 software, and differences were considered significant at p&lt;0.05. Results: 98 individuals with vitamin D ≤20 ng/dL were evaluated, and the SNP BsmI of the VDR gene showed CYP24A1 overexpression and low SOD2 expression. Conclusion: SNP Bsm I of the VDR gene can modulate the expression of the genes evaluated without interfering with serum levels.

The multidrug efflux transporter ABCB1 is clinically important for drug absorption and distribution and can be a determinant of chemotherapy failure. Recent structure data shows that three glutamines donate hydrogen bonds to co-ordinate taxol in the drug binding pocket. This is consistent with earlier drug structure-activity relationships that implicated the importance of hydrogen bonds in drug recognition by ABCB1. By replacing the glutamines with alanines we have tested whether any or all of Q347, Q725 and Q990 are important for the transport of three different drug classes. Flow cytometric transport assays show that Q347A and Q990A act synergistically to reduce transport of Calcein-AM, BODIPY-verapamil and OREGON GREEN-taxol bisacetate but the magnitude of the effect was dependent on the test drug and no combination of mutations completely abrogated function. Surprisingly, Q725A mutants generally improved transport of Calcein-AM and BODIPY-verapamil, suggesting that engagement of the wild-type Q725 in a hydrogen bond is inhibitory for the transport mechanism. To test transport of unmodified taxol, stable expression of Q347/725A and the triple mutant was engineered and shown to confer equivalent resistance to the drug as the wild-type transporter, further indicating that none of these potential hydrogen bonds between transporter and transport substrate are critical for function of ABCB1. The implications of the data for plasticity of the drug binding pocket are discussed.

During their complex life cycles, the Apicomplexan parasites, Plasmodium falciparum and Toxoplasma gondii employ several genetic switches to regulate their gene expression. One such switch is mediated at the level of translation through upstream Open Reading Frames (uORFs). As uORFs are found in the upstream regions of a majority of genes in both the parasites, it is essential that their roles in translational regulation be appreciated to a greater extent. This review provides a comprehensive summary of studies that show uORF-mediated gene regulation in these parasites and highlights examples of clinically and physiologically relevant proteins that exhibit uORF-mediated regulation. In addition to these examples, several studies that use bioinformatics, transcriptomics, proteomics, and ribosome profiling also indicate the possibility of widespread translational regulation by uORFs. Further analysis of genome-wide datasets will reveal novel genes involved in key biological pathways such as cell-cycle progression, stress-response, and pathogenicity. The cumulative evidence from studies presented in this review suggests that uORFs will play crucial roles in regulating gene expression during clinical disease caused by these important human pathogens.

It was once thought that high QoS (Quality of Service) performance solves recurrent problems of low-quality multimedia services. Since then, solutions have been proposed to ensure a high level of QoE (Quality of Experience). In this document, the authors attempt to outline their understanding of an accurate meaning of quality of multimedia services. Starting from QoS and passing through generalised QoE, the authors focus on aspects of subjective and objective quality modelling and optimisation of visual performance for TRV (Target Recognition Video) applications (such as video surveillance), outlining the path of ITU-T standardisation in this area. The authors revised the ITU-T Recommendation P.912 to reflect improved subjective test techniques developed since this Recommendation was approved. The authors also attempt to predict at least some existing errors of reasoning, which are likely to become evident for the industry in the next decade.

Prediction and early detection of atrial fibrillation (AF) remain a permanent challenge in everyday practice. Timely identification of an increased risk for AF episodes (which are frequently asymptomatic) is essential in the primary and secondary prevention of cardioembolic events. One of the noninvasive modalities of AF prediction is represented by the electrocardiographic P-wave analysis. This includes the study and diagnosis of interatrial conduction block (Bachmann`s bundle block). Bayés’ Syndrome (named after its first descriptor) denotes the association between interatrial conduction defect and supraventricular arrhythmias (mainly AF) predisposing to cardioembolic events. Our short review presents an update of the most important data concerning this syndrome: brief history, main ECG features, pathophysiological background and clinical implications.

SARS-CoV-2 infections underlie the current Coronavirus disease (COVID-19) pandemic and are causative for a high death toll particularly among elderly subjects and those with comorbidities. Selenium (Se) is an essential trace element of high importance for human health and particularly for a well-balanced immune response. Mortality risk from severe disease like sepsis or polytrauma is inversely related to Se status. We hypothesized that this relation also applies to COVID-19. Serum samples (n=166) from COVID-19 patients (n=33) were collected consecutively and analysed for total Se by X-ray fluorescence and selenoprotein P (SELENOP) by a validated ELISA. Both biomarkers showed the expected strong correlation (r=0.7758, p<0.001), pointing to an insufficient Se status for optimal selenoprotein expression. In comparison to reference data from a European cross sectional analysis (EPIC, n=1915), the patients showed a pronounced deficit in total serum Se (mean±SD, 50.8±15.7 vs. 84.4±23.4 µg/L) and SELENOP (3.0±1.4 vs. 4.3±1.0 mg/L). A Se status below the 2.5th percentile of the reference population, i.e., [Se] < 45.7 µg/L and [SELENOP] < 2.56 mg/L was present in 43.4% and 39.2% of COVID samples, respectively. The Se status was significantly higher in samples from surviving COVID patients as compared to non-survivors (Se; 53.3±16.2 vs. 40.8±8.1 µg/L, SELENOP; 3.3±1.3 vs. 2.1±0.9 mg/L). We conclude that Se status analysis in COVID patients provides diagnostic information. However, causality remains unknown due to the observational nature of this study. Nevertheless, the findings strengthen the notion on a relevant role of Se for COVID convalescence, and support the discussion on adjuvant Se supplementation in severely diseased and Se-deficient patients.

P-glycoprotein (Pgp) determines resistance to a broad spectrum of drugs in glioblastoma multiforme (GB) because it is highly expressed in GB stem cells and in brain-blood barrier (BBB), the peculiar endothelium surrounding brain. Inhibiting Pgp activity in BBB and GB is still an open challenge. Here, we tested the efficacy of a small library of tetrahydroisoquinoline derivatives with an EC₅₀ for Pgp < 50 nM, in primary human BBB cells and in patients-derived GB, from which we isolated differentiated/adherent cells (AC, i.e. Pgp-negative/doxorubicin-sensitive cells) and stem cells (neurospheres, NS, i.e. Pgp-positive/doxorubicin-resistant cells). At 1 nM, 3 compounds increased the delivery of doxorubicin, a typical substrate of Pgp, across BBB monolayer, without altering expression and activity of other transporters. The compounds increased the drug accumulation within NS, restoring necrosis, apoptosis and reduction in cell viability induced by doxorubicin. In co-culture systems, the compounds added to the luminal face of BBB increased the delivery of doxorubicin to NS growing under BBB and rescued the drug’s cytotoxicity. Our work identified new ligands of Pgp active at low nanomolar concentrations, that effectively reduce Pgp activity in BBB and GB, and can improve chemotherapy efficacy in this tumor.

Possibilities of utilization of two frequencies synthetic aperture radar (SAR) operating simultaneously in P-band and S or L-band are considered. Advantages of such system are shown. They are caused by improvement of data interpretation and by decrease of ionosphere influence. Tasks of surface and subsurface sensing by the complex SAR were under investigation for vegetation, soil covers are given. As an example, the investigation results of coniferous forest areas backscattering by the spaceborne P-band SAR together with L-band SAR in the September-February period are presented. Studies have shown that the joint use of the results in L and P bands offer unique opportunities to explore the effects of changes in the backscattering properties of forest surfaces.

In winter 2008-2009, Lake Occhito, a strategic multiple-uses reservoir in South Italy, was affected by an extraordinary Planktothrix rubescens bloom. P. rubescens is a filamentous potentially toxic cyanobacterium which has recently colonized many environments in Europe. A number of studies is currently available on the use of remote sensing techniques to monitor different fresh water cyanobacteria species. By contrast no specific applications are available on the remote sensing monitoring of P. rubescens. In this paper we present a specific algorithm, based on Water Leaving Reflectances (WLR) from MERIS data, atmospherically corrected using the Aerosol Optical Thickness (AOT) retrieved by MODIS data, to detect P. rubescens blooms. The high accuracy in AOT data, provided by MOD09 surface reflectance product, at 1km spatial resolution, allowed obtaining a good correlation between the WLR and the P. rubescens chlorophyll-a concentrations measured in the field, through multiple stations fluorometric profiles. A modified Normalized Difference Chlorophyll index (NDCI) algorithm is presented. The performance of the proposed algorithm has been successfully compared with other specific algorithms for turbid productive waters. We demonstrated how important is to verify the spectral behaviour of bio-optical parameters in order to develop an ad hoc algorithm that better performs with respect to standard algorithms.

In this paper, we establish some inequalities bounding the ratio Г_p,k(x)/Г_p,k(y), where Г_p,k(.) is the (p,k)-analogue of the Gamma function. Consequently, some previous results are recovered from the obtained results.

In this data deposit, I describe a dataset that is the result of content mining 167,318 published articles for statistical test results. As a result of this content mining, 688,112 results from 50,845 articles were extracted. In order to provide a comprehensive set of data, the statistical results are supplemented with metadata from the article they originate from. The dataset is provided in a comma separated file (CSV) in long-format. For each of the 688,112 results, 20 variables are included, of which seven are article metadata and 13 pertain to the individual statistical results (e.g., reported and recalculated p-value). A five-pronged approach was taken to generate the dataset: (i) collect journal lists, (ii) spider journal pages for articles, (iii) download articles, (iv) add article metadata, and (v) mine articles for statistical results.

The increasing adoption of student-centred learning environs by the institutions of higher education in business, has led to new mechanisms and methodologies such as the Simulation-Based Learning (SBL), Problem-Based Learning (PBL) and Challenge-Based Learning (CBL). Literature has shown evidence of raising interest in these methodologies towards a more experiential paradigm with regard to upcoming events from the surrounding real-world context. This paper presents a Systematic Bibliographic Literature Review (SBLR) with respect to the integration and application of these innovative and collaborative methodologies in higher education. It aimed to identify its relevant advantages, challenges, and consequences for the future of business education. Bibliographic databases were searched for documents published up to May 2024 to categorize key topics discussed in the literature on SBL, PBL and CBL. The review process identified 89 empirical and non-empirical papers on SBL, PBL and CBL, business related paperwork, which resulted from the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) method. PRISMA is a framework with evidence-based data designed to help authors perform a systematic literature review. Data analysis revealed diverse subthemes for those methodologies uses in business higher education institutions. The research questions “What are the advantages, challenges and implications of SBL, PBL and CBL altogether, in the training of business students?” guided the study. The central output of the research is the discovery of the varying uses of SBL, PBL and CBL overall, to cope with diverse demands arising within environmental context. Future research directions are suggested.

Transcriptome assembly and functional annotation are essential for understanding gene expression and biological function. Nevertheless, many existing tools lack the flexibility to integrate both short- and long-read sequencing data or fail to provide a complete, customizable workflow for transcriptome analysis. Here, we present TrAnnoScope, a comprehensive transcriptome analysis pipeline that provides a complete, customizable workflow capable of efficiently processing and integrating short- and long-read sequencing data to generate high-quality, full-length transcripts with detailed functional annotation. The pipeline encompasses steps from quality control to functional annotation, employing a range of tools and established databases, such as SwissProt, Pfam, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes. As a case study, TrAnnoScope was applied to RNA-Seq data from zebra finch brain, ovary, and testis tissues. TrAnnoScope produced comprehensive transcriptome, demonstrating strong alignment with the reference genome (99.63%) and capturing a significant proportion of nearly complete protein sequences (92.7%). The functional annotation process yielded extensive matches to known protein databases and successfully assigned relevant functional terms to majority of the transcripts. As such, TrAnnoScope successfully integrates multiple sequencing technologies to generate comprehensive transcriptomes with minimal user input. Its modular design, flexibility, and ease of use make it a valuable tool for researchers working with complex datasets, particularly for non-model organisms.

Triple negative breast cancer (TNBC) is associated with a generally poor prognosis due to its highly aggressive and metastatic nature, lack of targetable receptors, as well as the frequent development of resistance to chemotherapy. We previously reported that AU1, a small molecule developed as an inhibitor of BPTF (bromodomain PHD finger containing transcription factor), was capable of sensitizing preclinical models of triple negative breast cancer to chemotherapy, in part via the promotion of autophagy. In studies reported here, we identify an additional property of this compound, specifically that sensitization is associated with inhibition of the P-glycoprotein efflux pump. In silico molecular docking studies indicate that AU1 binds to active regions of the efflux pump, in a manner consistent with inhibition of pump function. This work identifies a novel chemical structure that can influence multidrug efflux, an established mechanism of drug resistance in triple negative breast cancer, that has not yet been successfully addressed by clinical efforts.

We prove the continuous non-Archimedean (resp. p-adic) Banach space and Hilbert space versions of non-Archimedean (resp. p-adic) Welch bounds proved by M. Krishna. We formulate continuous non-Archimedean and p-adic functional Zauner conjectures.

We prove the non-Archimedean (resp. p-adic) Banach space version of non-Archimedean (resp. p-adic) Welch bounds recently obtained by M. Krishna. More precisely, we prove following results. \begin{enumerate}[\upshape(i)] \item Let $\mathbb{K}$ be a non-Archimedean (complete) valued field satisfying $\left|\sum_{j=1}^{n}\lambda_j^2\right|=\max_{1\leq j \leq n}|\lambda_j|^2$ for all $ \lambda_j \in \mathbb{K}, 1\leq j \leq n$, for all $n \in \mathbb{N}.$ Let $\mathcal{X}$ be a $d$-dimensional non-Archimedean Banach space over $\mathbb{K}$. If $\{\tau_j\}_{j=1}^n$ is any collection in $\mathcal{X}$ and $\{f_j\}_{j=1}^n$ is any collection in $\mathcal{X}^*$ (dual of $\mathcal{X}$) satisfying $f_j(\tau_j) =1$ for all $1\leq j \leq n$ and the operator $S_{f, \tau} : \text{Sym}^m(\mathcal{X})\ni x \mapsto \sum_{j=1}^nf_j^{\otimes m}(x)\tau_j^{\otimes m} \in \text{Sym}^m(\mathcal{X})$, is diagonalizable, then \begin{align}\label{NONFUNCTIONALWELCH} \max_{1\leq j,k \leq n, j \neq k}\{|n|, |f_j(\tau_k)f_k(\tau_j)|^{m} \}\geq \frac{|n|^2}{\left|{d+m-1 \choose m}\right| }. \end{align} We call Inequality (\ref{NONFUNCTIONALWELCH}) as non-Archimedean functional Welch bounds. \item For a prime $p$, let $\mathbb{Q}_p$ be the p-adic number field. Let $\mathcal{X}$ be a $d$-dimensional p-adic Banach space over $\mathbb{Q}_p$. If $\{\tau_j\}_{j=1}^n$ is any collection in $\mathcal{X}$ and $\{f_j\}_{j=1}^n$ is any collection in $\mathcal{X}^*$ (dual of $\mathcal{X}$) satisfying $f_j(\tau_j) =1$ for all $1\leq j \leq n$ and there exists $b \in \mathbb{Q}_p$ such that $ \sum_{j=1}^{n}f_j^{\otimes m}(x) \tau_j^{\otimes m} =bx$ for all $ x \in \text{Sym}^m(\mathcal{X}),$ then \begin{align}\label{PADICFUNCTIONALWELCH} \max_{1\leq j,k \leq n, j \neq k}\{|n|, |f_j(\tau_k)f_k(\tau_j)|^{m} \}\geq \frac{|n|^2}{\left|{d+m-1 \choose m}\right| }. \end{align} We call Inequality (\ref{PADICFUNCTIONALWELCH}) as p-adic functional Welch bounds. \end{enumerate} We formulate non-Archimedean functional and p-adic functional Zauner conjectures.

Interstitial pneumonia is a general term for diseases in which inflammation occurs mainly in the interstitium of the lung. It is also pointed out that interstitial pneumonia reduces alveolar function and makes it difficult to take in oxygen through inspiration, causing symptoms such as dyspnea and coughing, which may eventually lead to respiratory failure. It is At present, there is no effective treatment and only conservative treatment exists. This time, we report that the therapeutic effect was confirmed in patients with interstitial pneumonia who took platinum palladium. In this case, improvement tendencies were observed in patients with Idiopathic pulmonary fibrosis (IPF), but improvement tendencies were also observed in many other lung diseases. In order to explore the mechanism, AMPK was measured at the in vitro level, and blood KL-6 and hydrogen peroxide levels in the patient were measured at the in vivo level. AMPK values were significantly elevated by more than 800%, KL-6 and hydrogen peroxide levels were also significantly decreased by drinking platinum palladium. Platinum palladium exhibits a strong antioxidant effect and is the only substance in the world that can approach all four types of active oxygen. In addition, when it was actually administered to patients, there were cases of dramatic improvement, and it was confirmed that KL-6, a parameter of lung function, decreased in 16 out of 32 patients, and furthermore, oxygen inhalation was completed. patients were also seen. Although the number of cases is expected to increase in the future, the substance is expected to be effective as a drug, although it is currently classified as a soft drink.

Interstitial pneumonia is a general term for diseases in which inflammation occurs mainly in the interstitium of the lung. It is also pointed out that interstitial pneumonia reduces alveolar function and makes it difficult to take in oxygen through inspiration, causing symptoms such as dyspnea and coughing, which may eventually lead to respiratory failure. At present, there is no effective treatment and only conservative treatment exists. This time, we report that the therapeutic effect was confirmed in patients with interstitial pneumonia who took platinum-palladium. In this case, improvement tendencies were observed in patients with Idiopathic pulmonary fibrosis (IPF), but improvement tendencies were also observed in many other lung diseases. In order to explore the mechanism, AMPK was measured at the in vitro level, and blood KL-6 and hydrogen peroxide levels in the patient were measured at the in vivo level. AMPK values were significantly elevated by more than 800%, KL-6 and hydrogen peroxide levels were also significantly decreased by drinking platinum-palladium. Platinum-palladium exhibits a strong antioxidant effect and is the only substance in the world that can approach all four types of active oxygen. In addition, when it was actually administered to patients, there were cases of dramatic improvement, and it was confirmed that KL-6, a parameter of lung function, decreased in 16 out of 32 patients As the number of cases is expected to increase in the future, the substance is expected to be effective as a drug, although it is currently classified as a soft drink.

Triple-negative breast cancer (TNBC) lacks the expression of estrogen receptors, human epidermal growth factor receptor 2, and progesterone receptors (PR). TNBC has the poorest prognosis among breast cancer subtypes and is more likely to respond to immunotherapy due to its higher expression of PD-L1 and a greater percentage of tumor-infiltrating lymphocytes. Immunotherapy has revolutionized TNBC treatment, especially with the FDA's approval of pembrolizumab (Keytruda) combined with chemotherapy for advanced cases, opening new avenues for treating this deadly disease. Although, immunotherapy can significantly improve patient outcomes in a subset of patients, achieving the desired response rate for all remains an unmet clinical goal. Strategies that improve responses to immune checkpoint blockade, including combining immunotherapy with chemotherapy, molecularly targeted therapy, or radiotherapy may improve response rates and clinical outcomes.  In this review, we provide a short background on TNBC and immunotherapy and explore the different types of immunotherapy strategies that are currently being evaluated in TNBC. Additionally, we review why combination strategies may be beneficial, provide an overview of the combination strategies, and discuss the novel immunotherapeutic opportunities that may be approved in the near future for TNBC.

Caudal type homeobox transcription factor 2 (CDX2) is a gastrointestinal cancer biomarker that regulates epithelial development and differentiation. Absence or low levels of CDX2 have been associated with poor prognosis and proposed as a chemotherapy response predictor. Tumour tissue of 668 patients with stage I-IV colorectal cancer were stained for CDX2 and stratified into two subgroups according to expression levels. Statistical tests evaluated CDX2 relationship with survival and chemotherapy response. Of 646 samples successfully stained, 51 (7.9%) had low and 595 (92.1%) had high CDX2 levels. Low CDX2 staining was associated with poor differentiation, presence of lymphovascular or perineural invasion, and more common in colon and right sided tumours. Overall survival (p&lt;0.001) and disease-free survival (p=0.009) was lower in low CDX2 expressing patients. Multivariable analysis validated CDX2 as an independent poor prognostic factor after excluding confounding variables. There was no statistically significant improvement in survival with adjuvant chemotherapy in stage II colon cancer (p=0.11). In the rectal cohort, there was no relationship between CDX2 levels and therapy response. While confirming the prognostic utility of CDX2 in colorectal cancer, our study highlights larger studies are required to confirm utility as a predictive chemotherapy biomarker, especially in left sided and rectal cancers.

Drug resistance in melanoma is a major hindrance in cancer therapy. Growth hormone (GH) plays a pivotal role in contributing to resistance to chemotherapy. Knocking down or blocking the GH receptor has been shown to sensitize the tumor cells to chemotherapy. Extensive studies have demonstrated that exosomes, a subset of extracellular vesicles, play an important role in drug resistance by transferring key factors to sensitize cancer cells to chemotherapy. In this study, we explore how GH modulates exosomal cargoes from melanoma cells and their role in drug resistance. We treated the melanoma cells with GH, doxorubicin, and GHR antagonist, pegvisomant, and analyzed the exosomes released. Additionally, we administered these exosomes to recipient cells. The GH-treated melanoma cells released exosomes with elevated levels of ABC transporters (ABCC1 and ABCB1), N-cadherin and MMP2, enhancing drug resistance and migration in recipient cells. GHR antagonism reduced these exosomal levels, restoring drug sensitivity and attenuating migration. Overall, our findings highlight a novel role of GH in modulating exosomal cargoes that drive chemoresistance and metastasis in melanoma. This understanding provides insights to the mechanisms of GH in melanoma chemoresistance and suggests GHR antagonism as a potential therapy to overcome chemoresistance in melanoma treatment.

Glioblastoma (GBM) is an aggressive brain cancer characterized by significant molecular and cellular heterogeneity, complicating treatment efforts. Current standard therapies, including surgical resection, radiation, and temozolomide (TMZ) chemotherapy, often fail to achieve long-term remission due to tumor recurrence and resistance. A pro-oxidant environment is in-volved in glioma progression, with oxidative stress contributing to the genetic instability that leads to gliomagenesis. However, the generation of reactive oxygen species (ROS) results in the dysregulation of antioxidant defenses in GBM cells, creating a vulnerability that can be thera-peutically exploited. Evaluating pro-oxidant therapies in brain tumors is crucial due to their po-tential to selectively target and eradicate cancer cells by exploiting the elevated oxidative stress levels inherent in these malignant cells, thereby offering a novel and effective strategy for overcoming resistance to conventional therapies. This study investigates the therapeutic potential of doxorubicin (DOX) and photodynamic therapy (PDT) with Me-ALA, focusing on their effects on redox homeostasis. Basal ROS levels and antioxidant gene expression (NFE2L2, CAT, GSR) were quantitatively assessed across GBM cell lines, revealing significant variability probably linked to genetic differences. DOX and PDT treatments, both individually and in combination, were ana-lyzed for their efficacy in inducing oxidative stress and cytotoxicity. An in silico analysis further explored the relationship between gene mutations and oxidative stress in GBM patients, providing insights into the molecular mechanisms underlying treatment responses. Our findings suggest that pro-oxidant therapies, such as DOX and PDT in combination, could selectively target GBM cells, highlighting a promising avenue for improving therapeutic outcomes in GBM.

Wilms tumor (WT), the most prevalent type of renal cancer in children, exhibits overall survival rates exceeding 90%. However, chemotherapy resistance, which occurs in approximately 10% of WT cases, is a major challenge for the treatment of WT, particularly for advanced-stage patients. In this study, we aimed to discover potential mutation markers and drug targets associated with chemotherapy resistance in advanced stage WT. We performed exome sequencing to detect somatic mutations and molecular targets in 43 WT samples, comprising 26 advanced stage WTs, of which 7 cases are chemotherapy-resistant. Our analysis revealed four genes (ALPK2, C16orf96, PRKDC, and SVIL) that correlated with chemotherapy resistance and reduced disease-free survival in ad-vanced-stage WT. Additionally, we identified driver mutations in 55 genes within the chemo-therapy-resistant group, including 14 druggable cancer driver genes. Based on the mutation profile of the resistant WT samples, we propose potential therapeutic strategies involving platinum-based agents, PARP inhibitors, and antibiotic/antineoplastic agents. Our findings provide insights into the genetic landscape of WT and offer potential avenues for targeted treatment, particularly for patients with chemotherapy resistance.

There is rapidly emerging evidence from pre-clinical studies, patient samples and patient subpopulations that certain chemotherapeutics inadvertently produce prometastatic effects. Prior to this, we showed that doxorubicin and daunorubicin, stiffen cells before causing cell death, predisposing the cells to clogging and extravasation, the latter being a step in metastasis. Here, we investigate which other anti-cancer drugs might have similar prometastatic effects by altering the biophysical properties of cells. We treat myelogenous (K562) leukemic cancer cells with the drugs nocodazole and hydroxyurea, and then measure their mechanical properties using the microfluidic microcirculation mimetic (MMM) device, which mimics aspects of blood circulation and enables the measurement of cell mechanical properties via transit times through the device. We also quantify the morphological properties of cells to explore biophysical mechanisms underlying the MMM results. Results from MMM measurements show that nocodazole- and hydroxyurea-treated K562 cells exhibit significantly altered transit times. Nocodazole caused significant (p &lt; 0.01) increase in transit times, implying a stiffening of cells. This work shows the feasibility of using the MMM to explore possible biophysical mechanisms that might contribute to chemotherapy-induced metastasis. Our work also suggests cell mechanics as a therapeutic target for much needed antimetastatic strategies in general.

Cancer is a devastating disease, causing tremendous morbidity and mortality each year. Cancer can be considered as a genetic disease in the sense that instabilities in protooncogenes and tumor suppressor genes are among the hallmarks of cancer progression and metastasis. However, a particular cancer can express different proteins in different patients, making cancer a heterogeneous disease. This heterogeneity in part influences treatment resistance and failure. Therefore, it is crucial to understand the mechanism by which cancer cells develop and enhance resistance to different agents. This review aims to present the general paradigm and recent updates on cancer cell resistance to different antitumor agents. It demonstrates that tumor resistance results from a myriad of factors, including tumor microenvironment, supporting immune cells, and cancer stem cells. This interaction contributes to cancer cells overcoming the therapeutic effects of different classes of antitumor agents, such as cytotoxic chemotherapeutics, targeted agents, and immunotherapies. With the development of advanced molecular analysis, specialized genomic assessment has assisted clinicians and researchers in choosing selected agents combating cancer cells. Together, this approach can potentially reduce treatment toxicity, health system burden, and financial costs while improving patient quality of life. Understanding the exact mechanism of drug resistance in cancer cells can open the way to new effective and less toxic therapeutics.

Background: Pathologic complete response (pCR) of breast cancer after neoadjuvant chemotherapy (NAC) is highly related to molecular subtypes. Patients who achieved tumor pCR after NAC have a better prognosis. However, despite of better prognosis, pCR patients have a potential for recurrence. There is little evidence of risk factors of recurrence in patients with pCR. We aim to analyze factors associated with tumor recurrence in patients who achieved pCR. Methods: This study retrospectively reviewed the data of patients diagnosed with breast cancer who achieved pCR after receiving NAC between January 2009 and December 2018 in Samsung Medical Center. pCR was defined as no residual invasive cancer in the breast and axillary nodes even if there is residual ductal carcinoma in situ (ypT0 or ypTis with ypN0). Breast cancers are classified into 4 subtypes based on hormone receptors (HR) and human epithelial growth factor receptor 2 (HER2) status. Patients who had bilateral breast cancer, inflammatory breast cancer, distant metastasis, unknown subtype, and histologically unique case were excluded from the study. Results: In total 483 patients were included in this study except for patients who corresponded to the exclusion criteria. The median follow-up duration was 59.0 months (range, 0.5-153.3 months). Breast cancer recurred in 4.1% of patients (20 of 483). There was a significant difference in clinical T (p = .004) and clinical N (p = .034) stage in the Kaplan-Meier curve for disease-free survival. Molecular subtypes (p = .573), Ki67 (p = 1.000), and breast surgery type (p = .574) were not associated with tumor recurrence in patients who achieved pCR after NAC. In the clinical T stage and clinical N stage, there was a significant difference between recurrence and no-recurrence groups (clinical T stage; p = .045, clinical N stage; p = .002). Univariable Cox regression revealed statistical significance in the clinical T stage (p = .049) and clinical N stage (p = .010), while multivariable Cox regression demonstrated non-significance in the clinical T stage (p = .320) and clinical N stage (p = .073). Conclusion: Results in this study showed that clinical T, clinical N stage, and molecular subtypes were not statistically significant predictors of recurrence in patients who achieved pCR after NAC. It is hypothesized that a multicenter-based study would lead to the identification of factors as predictors of recurrence after achieving pCR.

Background: Anthracyclines form the backbone of many systemic chemotherapy regimens but dose-limiting cardiotoxicity can also lead to reduction in cardiac function and an increased risk of heart failure. Methods: This review was conducted in accordance with PRISMA guidelines and registered on PROSPERO (CRD42022373496). Results: 26 studies met the eligibility criteria including a total of 910 patients. Overall reduction in pooled mean left ventricular ejection fraction (LVEF) post‐anthracyclines in the placebo arms of included randomised-controlled trials was 4.6% (95% CI, 2.7 to 6.6). The trend in LVEF showed a progressive decline until approximately 180 days after which there was no significant change. Those receiving a cumulative anthracycline dose 300 mg/m2 experienced a more profound reduction. The risk of a 10% absolute decline in LVEF from baseline or decline to an LVEF below 50%, the overall pooled risk was 16% (95% CI: 11 to 21; I2 = 77%). Sensitivity analyses by baseline LVEF and trastuzumab treatment status did not yield significant differences. Conclusion: While the mean LVEF decline in patients without cardioprotective therapy was clinically small, a vulnerable subset experienced significant impairment. Further research to best identify those who benefit most from cardioprotective therapies when receiving anthracyclines are required.

Circulating tumor DNA (ctDNA), the tumor-derived cell-free DNA fragments in the bloodstream carrying tumor-specific genetic and epigenetic alterations, represents an emerging novel tool for minimal residual disease (MRD) assessment in patients with resected colorectal cancer (CRC). For many decades, precise risk-stratification following curative-intent colorectal surgery has remained an enduring challenge. The current risk stratification strategy relies on clinicopathologic characteristics of the tumors that lacks precision and results in over-and undertreatment in a significant proportion of patients. Consequently, a biomarker that can reliably identify patients harboring MRD would be of critical importance in refining patient selection for adjuvant therapy. Several prospective cohort studies have provided compelling data suggesting that ctDNA could be a robust biomarker for MRD that outperforms all existing clinicopathologic criteria. Numerous clinical trials are currently underway to validate the ctDNA-guided MRD assessment and adjuvant treatment strategies. Once validated, the ctDNA technology will likely transform the adjuvant therapy paradigm of colorectal cancer, supporting ctDNA-guided treatment escalation and de-escalation. The current article presents a comprehensive overview of the published studies supporting the utility of ctDNA for MRD assessment in patients with CRC. We also discuss ongoing ctDNA-guided adjuvant clinical trials that will likely shape future adjuvant therapy strategies for patients with CRC.

Triple-negative breast cancer (TNBC) is characterized by an active immune response. We evalu-ated intratumoral interrelation between FOXP3+ tumor-infiltrating lymphocytes and other cy-tokines in TNBC. Network analysis refined cytokines significantly correlate with FOPX3 in TNBC. Treatment response and prognosis imformation of patients and survival data from the TGCA and METABRIC databases were analyzed according to refined cytokines. Interleukin (IL)-33 was sig-nificantly expressed by TNBC cell lines than luminal cell lines (log2 fold change: 5.31, p <0.001) and IL-33 and TGFB2 showed a strong correlation with FOXP3 in the TNBC cell line. Immunohisto-chemistry demonstrated IL-33 high group was a significant predictor of complete response of neoadjuvant chemotherapy (odds ratio (OR) 4.12, p<0.05) and a favorable survival compared to IL-33 low group (OR 6.48, p<0.05) in TNBC. Survival data from TGCA and METABRIC revealed that FOXP3 was a significantly favorable marker in IL-33 high group com-pared to the low IL-33 low group (hazard ratio (HR) 2.1, p=0.02), and IL-33 high/TGFB2 high subgroup showed significant favorable prognosis in the FOXP3 high group compared to the FOPX3 low group in TNBC (HR 3.5, p=0.01). IL-33 and TGFB2 were key cytokines of intratumoral interrelation among FOXP3 in TNBC.

Several types of soft tissue sarcomas have peripheral infiltrative growth characteristics called tail-like lesions. The efficacy of neoadjuvant therapy for tumors with tail-like lesions has not been elucidated. From 2012 to 2019, we analyzed 36 patients with soft tissue sarcoma with tail-like lesions treated with neoadjuvant therapy, including chemotherapy, radiotherapy, or both. The ef-fect of neoadjuvant therapy on the tail sign was investigated by analyzing the change in tail-like lesions during neoadjuvant therapy and histological responses. The median length of the tail-like lesion reduced from 29.5 mm at initiation to 19.5 mm after neoadjuvant therapy. The extent of shrinkage in tail-like lesion was related to the histopathological responses in the main part. Com-plete disappearance of the tail-like lesion was observed in 12 patients; however, it was not related to achieving a microscopically negative margin. The oncologic outcomes did not significantly differ between cases with complete disappearance of tail-like lesions or not. This study indicated the shrinkage of tail-like lesions did not have significant effect on complete resection or improve-ment of clinical outcomes. A more comprehensive evaluation is needed to elaborate on the surgi-cal strategy.

In order to follow the Preventive Chemotherapy for the transmission control as recommended by WHO, Gabon initiated in 2014 the mapping of Schistosomiasis and Soil Transmitted Helminthiasis (STH). Here we report the results of the Northern and Eastern health regions, representing a third of the land area and 12% of its total population. All the 9 departments of the two regions were surveyed and from each, 5 schools were examined with 50 schoolchildren per school. The parasitological examinations were realized using the filtration method for urine and the Kato-Katz technique for stool samples. Overall 2245 schoolchildren (1116 girls and 1129 boys), mean aged 11.28 ± 0.04 years, were examined. Combined schistosomiasis and STH affected 1270 (56.6%) with variation between regions, departments and schools. For schistosomiasis, prevalence were 1.7% across the two regions, with no significant difference (p>0.05) between the Northern (1.5%) and the Eastern (1.9%). Schistosomiasis is mainly caused by Schistosoma haematobium with a prevalence of 1.5%, 1.9% and 1.7%, respectively in the North, East and globally. STH are more common than schistosomiasis, with an overall prevalence of 56.1% significantly different between the Northern (58.1%) and Eastern (53.6%) regions (p = 0.034). Trichuris trichiura is the most abundant infection with a prevalence of 43.7% followed by Ascaris lumbricoides 35.6% and hookworms 1.4%. According to these results, an appropriate mass drug administration strategy is given for the control of each neglected tropical disease group surveyed.

Gc protein-derived Macrophage Activating Factor (GcMAF), a powerful immunostimulant endowed with anti-cancer and anti-angiogenetic activities, offers significant advantages when combined with radiation therapy. A stronger immune response improves the effectiveness of radiation therapy by allowing the body to better eliminate residual cancer cells after treatment. In addition, by boosting the immune system, GcMAF mitigates some of the immunosuppressive side effects of radiation therapy, leading to faster recovery. In order to fully exploit the potential of GcMAF in cancer therapy, knowledge of the molecular interactions with its receptor is essential. This study proposes the first extracellular domain (residues 1-34) of the CCR1 protein as the GcMAF receptor. The CCR1 gene, expressed in monocytes and 168 other cell types or tissues, encodes this transmembrane protein. Electrostatic and hydrophobic interactions, along with hydrogen bonds mediate the molecular interactions between the TPT^420-GalNAcELAK (or TPK⁴²⁰ELAK) sequences of GcMAF (or Gc2 protein variant) and the TTEDYDTTT sequence of its receptor.

Alginate-silver nanocomposites in the form of spherical beads and films were prepared using a green approach by using the aqueous extract of Ajwa dates seeds. The nanocomposites were fabricated by in situ reduction and gelation method by ionotropic crosslinking using calcium ions in solution. The rich phytochemicals of the dates seeds extract played a dual role as reducing and stabilizing agent in the synthesis of silver nanoparticles. The formation of silver nanoparticles was studied using UV-Vis absorption spectroscopy and a distinct surface plasmon resonance (SPR) peak at 421 nm characteristic of silver nanoparticles confirmed the green synthesis of silver nanoparticles. The morphology of the nanocomposite beads and film was compact with even distribution of silver nanoclusters. The catalytic property of the nanocomposite beads was evaluated for the degradation of 2-nitrophenol in the presence of sodium borohydride. The degradation followed pseudo-first order kinetics with a rate constant of 1.40 ´ 10^-3 s^-1 at 23 °C with an activation energy of 18.45 kJ mol^-1. The thermodynamic parameters such as changes in enthalpy and entropy were evaluated to be 15.22 kJ mol^-1 and -197.50 J mol^-1 K^-1, respectively. The nanocomposite exhibited properties against three clinically important pathogens (Gram-positive and Gram-negative bacteria)

This paper explores the views of a group of young men aged 16–18, studying towards a Level 1 diploma in music in the North East area of England. It uses the conceptualization of “social haunting” to focus our discussions about how Level 1 learners articulated their experiences in the context of their learning journeys and perceived marginalization. The research took place at a large Further Education (FE) college and included a series of five “research encounters” with the group of Level 1 learners. These encounters included a range of activities, resulting in a variety of data being collected, including several activity worksheets, structured and unstructured focus group interviews, and questionnaires. This paper focusses on the outcomes of a single research activity that focused on exploring the topic of marginalization. We present a discussion on social haunting as one of the emerging findings from this research encounter, outlining how the reality of the social and cultural legacy of the UK’s industrial past can shape today’s youth and their futures. We will talk about the young men’s views of marginalization, their school-to-work transitions, the formation of masculinity in post-industrial communities and the role of Further Education in it. The paper concludes by discussing some insights for practice and future research.

We will apply Pascal’s hydrostatic pressure law to black holes and also to the Hubble sphere. Haug has recently demonstrated how hydrostatic pressure in water can be utilized to determine the Planck length. One can conceptualize the energy in the Hubble sphere as a type of superfluid, and if this is correct, then Blaise Pascal’s hydrostatic pressure formula may also be applicable to such a superfluid, even within the Hubble sphere. By employing the same method on the Hubble sphere and considering it as a Schwarzschild black hole with the critical Friedmann mass, we can estimate the Planck length based on its hypothetical hydrostatic pressure.

In the field of delta-sigma modulators, reducing system power consumption without sacrificing accuracy has become a challenge. The summing circuit, as the main part of the cascade-of-integrator-in-feedforward delta-sigma modulator, consumes a significant amount of power in active summing. On the other hand, passive summing circuits have low power consumption but can cause attenuation in the summing results. This article proposes a low-power multi-bit delta-sigma modulator based on passive and attenuationless summation scheme. The summation circuit achieves multiplication of the voltage signal carried on the summation capacitor through bidirectional sampling technique, compensating for the inherent attenuation caused by passive summation, thus eliminating the need for active OTA to achieve perfect summation. A 2-order delta-sigma modulator based on 4-bit 1-order passive noise-shaping (NS) SAR quantizer is designed to verify the scheme. By combining a passive NS SAR as the 4-bit quantizer and the third-stage integrator of the system, and incorporating an energy-efficient cascode floating inverter amplifier (FIA) structure as the core active OTA, these elements have significantly enhanced the energy-efficiency of the modulator. Simulation results show that at a supply voltage of 1.2 V and a bandwidth of 20 kHz, the SNDR reaches 102.62 dB, power consumption is only 148.32 μW, and Schreier figure-of-merit (FoM) of SNDR is 183.92 dB.

Dirac's Large Number Hypothesis (LNH), proposed in 1937, has captivated the scientific community with its exploration of profound correlations between cosmic and atomic scales. This hypothesis delves into the intricate interplay between the infinitesimally small and the vastly large, offering potential insights into the fundamental nature of the universe. As we continue to uncover the mysteries of the cosmos, the LNH oscillates on the precipice of scientific acceptance—neither fully validated nor entirely dismissed. In this review paper, we embark on a comprehensive journey through Dirac's LNH, shedding light on its theoretical underpinnings, its implications for universe models, and its resonance with the Anthropic Principle. We delve into the possibilities of variable gravitational constants and continuous mass creation, inviting further exploration into the intricacies of our cosmic symphony. By embracing the ongoing quest for understanding, we endeavor to unravel the profound harmonies that connect the infinitesimal with the infinite, contributing to the symphony of knowledge in theoretical physics and cosmology.

The main objective of the present study is to demonstrate the possibility of actively influencing the position of the bow shock wave and the main parameters of supersonic flow over a blunt body by organizing a gas discharge near the front surface, in the region between the body and the bow shock wave. The research is carried out using both experimental and numerical methods. The working gas was xenon. It is shown that the steady bow shock wave stand-off distance along with the current and power of the discharge, is associated with the change in the adiabatic index of the plasma created by the discharge, which, in turn, is determined by the plasma parameters, such as the degrees of nonequilibrium and the degree of ionization. It is shown that the adiabatic index with the power supplied to the impact zone in the range of 30-120 kW can both increase and de-crease in the range of 1.25-1.288. The study of the discharge created plasma zone was conducted and the correspondence between the discharge current and power, and the average parameters in the plasma zone created by the discharge is presented. A good agreement between the numerical and experimental data was shown. The results may be useful in developing control systems for high-speed civil aircrafts.

This paper explores the pivotal role of personalized product recommendations in enhancing the e-commerce experience. As online shopping becomes increasingly prevalent, the demand for tailored user experiences has surged, prompting the development of sophisticated recommendation systems. This study presents a comprehensive analysis of various methodologies employed to deliver personalized suggestions, including collaborative filtering, content-based filtering, and hybrid approaches. The implementation of a user-centric recommendation engine demonstrates significant improvements in user engagement, satisfaction, and conversion rates. Furthermore, the paper discusses the importance of real-time adaptation mechanisms and user feedback loops in optimizing recommendations. By providing insights into the challenges and solutions associated with recommendation systems, this research aims to equip e-commerce businesses with the tools necessary to leverage personalization effectively, ultimately leading to enhanced customer experiences and increased sales.

Programmed cell death 4 (Pdcd4) is a tumor suppressor, which has been demonstrated to efficiently suppress tumorigenesis. Biochemically, Pdcd4 binds with translation initiation factor 4A and represses protein translation. Beyond its role in tumor suppression, increasing evidence indicates that Pdcd4 enhances the chemosensitivity of several chemotherapeutic drugs. To date, several translational targets of Pdcd4 have been identified. These targets govern important signal transduction pathways, and their attenuation may enhance chemosensitivity or overcome drug resistance. This review will discuss the signal transduction pathways regulated by Pdcd4 and the potential mechanisms through which Pdcd4 enhances chemosensitivity or counteracts drug resistance.

A Pt(II) complex featuring chelating tridentate bis-aryloxide tetrahydropyrimidinium based N-heterocyclic carbene (NHC) was synthesized and characterized by using different techniques. The electrochemical properties of the complex were investigated by cyclic voltammetry as well as differential pulse voltammetry, which revealed two reversible one-electron oxidation processes. The chemical generation and isolation of one-electron-oxidized species were performed oxidizing the initial complex by means of AgBF4. The combined UV-Vis/NIR- and EPR-spectroscopy studies supported by density functional theory (DFT) calculations suggest the formation of Pt(II)-phenoxyl radical complex. The latter open-shell derivative was structurally characterized by means of X-ray diffraction analysis. Finally, the neutral platinum complex was tested as a mediator in the process of electrocatalytic oxidation of 2-(methylamino)ethanol (MEA).

Human immunodeficiency virus (HIV) and malaria, caused by infection with Plasmodium spp., are endemic in similar geographical locations. As a result, there is high potential for HIV/Plasmodium co-infection, which increases the pathology of both diseases. However, the immunological mechanisms underlying the exacerbated disease pathology observed in co-infected individuals are poorly understood. Here, we used the rhesus macaque (RM) model to characterize the immunopathogenic impact of Plasmodium fragile co-infection during antiretroviral therapy (ART)-treated simian immunodeficiency virus (SIV)-infection. We observed that P. fragile co-infection resulted in parasitemia and anemia, as well as persistently detectable viral loads (VL) and decreased absolute CD4+ T-cell counts despite daily ART treatment. Notably, P. fragile co-infection was associated with increased levels of inflammatory cytokines linked with neutrophil function, including monocyte chemoattractant protein 1 (MCP-1). P. fragile co-infection was associated with increased levels of neutrophil elastase, a plasma marker of neutrophil extracellular trap (NET) formation, but significant decreases in markers of neutrophil degranulation, potentially indicating a shift in neutrophil functionality during co-infection. Finally, we characterized levels of plasma markers of gastrointestinal (GI) barrier permeability and microbial translocation and observed significant correlations between indicators of GI dysfunction, clinical markers of SIV and Plasmodium infection, and neutrophil frequency and function. Taken together, these data indicate that neutrophil-driven inflammation and GI dysfunction may underlie heightened SIV/P. fragile co-infection pathogenesis.

Opuntia ficus-indica has always interacted with many phytophagous insects at its center of origin; two of them are Dactylopius coccus and D. opuntiae. D. coccus, or true cochineal, is produced to extract carminic acid, and D. opuntiae or wild cochineal is a key invasive pest of O. ficus-indica in more than 20 countries around the world. Despite the economic and environmental relevance of this cactus and, D. opuntiae and D. coccus, there are few studies that have explored volatile organic compounds (VOCs) derived from the plant-insect interaction. The aim of this work was to determine VOCs of D. coccus and D. opuntiae feeding on cultivars suitable for their development and to identify different VOCs in cladodes infested by each Dactylopius species. Volatiles were identified through their essential oils, which were obtained by hydrodistillation. A total of 66 VOCs from both Dactylopius species were identified, and 125 from the Esmeralda and Rojo Pelón cultivars infested by D. coccus and D. opuntiae, respectively, were determined. Differential VOCs production due to infestation by each Dactylopius species was also found. Some changes in methyl salicylate, terpenes such as linalool or the alcohol p-vinylguaiacol were related to Dactylopius feeding on cladodes of their respective cultivars. Changes in these VOCs and their probable role in plant defense mechanisms should receive more attention because this knowledge could improve D. coccus rearing, or to its inclusion in breeding programs for D. opuntiae control in regions where it is a key pest of O. ficus-indica.

In the recent past, the number of invasive species around the world has increased significantly due to increased globalization and climate change. Understanding biological invasions under climate change is crucial for sustainable conservation of biodiversity. The insect pest Pseudococcus viburni (Signoret) can cause damages to plants, resulting in leaf yellowing, leaf defoliation, and reduced plant growth. A serious attack by this insect post can even lead to the entire plant withering and dying, bringing huge economic and ecological losses. Despite these damages, the potential distribution range and management strategies for this insect pest are poorly understood. Based on historical distribution data and environmental factors, the present study predicted the potentially suitable areas for P. viburni spread under different climate change scenarios using MaxEnt (maximum entropy). The results showed that precipitation of the coldest quarter (Bio19), precipitation seasonality (Bio15), and mean temperature of the wettest quarter (Bio8) were the most important environmental factors determining the distribution of P. viburni. Under the current climate conditions, its potential suitable areas are southern China, the whole of Japan, North America (especially the eastern part of the United States), the southwestern part of South America, the Mediterranean coast and most of Europe, the central part of Africa i.e., the south of the Sahara Desert and most of the southern coast of Australia. The total area of habitats suitable for this insect pest is predicted to be increased in the future. In order to prevent P. viburni transmission and spread, there is a need to strengthen the monitoring and quarantine measures against this pest at the Southern ports.

Lignin, and its by-products in the effluent of most agrochemical-based industries like pulp and paper, increase environmental pollution. There is, therefore, an increasing demand to degrade lignin and its derivatives using bacteria-produced ligninolytic enzymes. This study focused on optimizing growth and lignin peroxidase production of ligninolytic potential bacterial strains (E. coli accession no: LR0250096.1 and P. aeruginosa accession no: CP031449.2) for the first time. A submerged fermentation process was used to simultaneously optimize growth and crude lignin peroxidase production using kraft lignin as the substrate. The E. coli and P. aeruginosa were separately cultured under different pH, temperature, lignin (substrate) concentration and incubation periods. It was observed that the enzyme production was growth dependent. The optimum conditions for E. coli were pH 7.5, temperature 30 °C and lignin concentration 1 g/L. For P. aeruginosa the best conditions were pH 6.5, temperature 40 °C and lignin concentration 1 g/L. The enzyme production peaked after 7 days of incubation for both organisms were 21.53 ± 3.11 mg/ml and 18.13 ± 2.1 mg/ml respectively. It is apparent that both E. coli (LR0250096.1) and P. aeruginosa (CP031449.2) are mesophiles bacteria. E. coli function best in alkaline pH while P. aeruginosa prefers a slightly acidic environment. Hence, they are promising candidates in the reduction of lignocellulosic wastes.

The development of good conductivity p-type β-Ga2O3 is critical to realize its devices and applications. The nitrogen-doped p-type β-Ga2O3 films with enhanced conductivity characteristics were prepared through the thermal oxidation of GaN in the N2O atmosphere. Further measurements were performed on the oxidized films at 1000, 1050, and 1100 °C to have insight into the underlying mechanism of the thermally activated transformation process. The room temperature photoluminescence (PL) spectra demonstrated a moderate ultraviolet emission peak at 246 nm, confirming the generation of gallium oxide with a band gap of ~5.0 eV. The normalized X-ray diffraction (XRD), the high-resolution transmission electron microscopy (HRTEM), and the selected area electron diffraction (SAED) patterns were used to confirm the characteristic of polycrystalline and anisotropic growth. Then, the effects of the oxidation temperature on the amount of incorporated nitrogen were analyzed using secondary ion mass spectrometry (SIMS). Moreover, the ionization energy of the acceptor of films oxidized at 1000, 1050, and 1100 °C was calculated and analyzed using the temperature-dependent Hall test results. The results showed that nitrogen doping was the main contributor to p-type electrical properties. The activation energy of the polycrystalline β-Ga2O3 prepared through thermal oxidation of GaN in the N2O atmosphere was estimated to be 147.175 kJ·mol-1 using the Arrhenius plot, which was considerably lower than that of both dry and wet oxidations of GaN in O2 ambient, thus confirming the efficiency of thermal oxidation of GaN in N2O.

The Mediterranean region offers good weather conditions for outdoor pig production (OPP), which is considered more environmentally friendly than intensive indoor production. However, the continuous input of food and pigs' excreta increases the soil organic matter (SOM) and phosphorus (P), increasing the risk of waterbodies eutrophication. This work aimed at evaluating in OPP areas soil P dynamics and the role of SOM on P sorption and P release. The experiment was done for two years, at an area of 2.8 ha with an animal charge of 9 adults ha-1. Georeferenced soil samples were taken at 0.20 m depth, and a soil P sorption experiment was carried out. At the end of the experiment, for the background value, the levels of SOM increased between 85–376%, and Olsen P values ranged between -82–884%. SOM levels above 2% caused a decrease in the binding energy of P sorption according to the linear model b=-15.541SOM+115.20 (p <0.01) as well as a decrease of the soil P sorption capacity Qmax=-41.272SOM+298.37 (p <0.01). To avoid the accumulation of SOM and P preventing hotspots for waterbodies eutrophication, an adequate animal charge together with soil cultivation for pig grazing can be a cost-effective practice.

Antisense technologies consist of the utilization of oligonucleotides or oligonucleotide analogs to interfere with undesirable biological processes, commonly through inhibition of expression of selected genes. This field holds a lot of promise for the treatment of a very diverse group of diseases including viral and bacterial infections, genetic disorders, and cancer. To date, drugs approved for utilization in clinics or in clinical trials target diseases other than bacterial infections. Although several groups and companies are working on different strategies, the application of antisense technologies to prokaryotes still lags with respect to those that target other human diseases. In those cases where the focus is on bacterial pathogens, a subset of the research is dedicated to produce antisense compounds that silence or reduce expression of antibiotic resistance genes. Therefore, these compounds will be adjuvants administered with the antibiotic to which they reduce resistance levels. A varied group of oligonucleotide analogs like phosphorothioate or phosphorodiamidate morpholino residues, as well as peptide nucleic acids, locked nucleic acids and bridge nucleic acids, the latter two in gapmer configuration, have been utilized to reduce resistance levels. The major mechanisms of inhibition include eliciting cleavage of the target mRNA by the host’s RNase H or RNase P, and steric hindrance. The different approaches targeted resistance to β-lactams including carbapenems, aminoglycosides, chloramphenicol, macrolides, and fluoroquinolones.

Adsorption is an effective strategy for the removal of pollutants from the wastewater. Herein, a 2-hydroxyterephthalic acid (HTC) modified hypercrosslinked polymer (HTC-HCP) is successfully synthesized via Friedel-Crafts reactions, and used as an adsorbent for the different types of pollutants including organic contaminants and heavy metal ions from wastewater. Excellent adsorption capacities are observed for amines (aniline, p-methylaniline (p-MA), p-chloroaniline (p-CA), and p-aminobenzoic acid (p-ABA)), phenols (phenol, p-chlorophenol (4-CP) Bisphenol A (BPA), 1-Naphthol (1-NP)), dyes (rhodamine B (RhB) and methyl orange (MO)), and metal ions (Pb2+, Hg2+, and Cd2+). The resulting polymers exhibited excellent adsorption performance towards these pollutants. Especially, the removal rate of aniline is above 95% in the concentration of 2.5 mg/L in 40 min at 25 °C. The interaction mechanism has been investigated, and confirmed by FTIR and the theoretical calculation results. It is due to surface complexation and chemisorption between adsorbent and adsorbate. The polymer exhibits good performance such as high adsorption capacity, high separation efficiency, biodegradable properties, and easy regeneration, suggesting that its potential technological applications for the removal of organic compounds and heavy metal ions from actual industrial effluent.

In these times electricity is big trouble of problem facing by the world. Therefore, there is necessitating for the property basis of energy that is employed for as bio-electricity. Many of the scientists and researchers are trying to find out the sustainable energy generates with the help of plant microbial fuel cell. Plant microbial fuel cell (P-MFCs) could be feasibility technology approach of bio-electricity generation which is mutualism interaction of the plants along with their rhizospheric bacteria. In the present study, Plant-microbial fuel cell was observed in grass e-table evaluated in term of bioelectricity generation from Cynodon dactylon (Dooba Ghas). This e-table was connected with electrode and different condition (physical and chemical) to detect the change in bioelectric potential. It was found that maximum voltage generated among all the conditions was 4.24 ±2V at 15 days by using Cynodon dactylon through P-MFCs. The potential difference generated through P-MFCs was measured using a multimeter. The generation of bioelectricity was observed under different conditions like exposure to light and shade condition measured for voltage was found to be significantly different parameters. The maximum recorded under light and shade conditions were 3.82 ±2 V and 4.25 ±2 V respectively at 15 days of incubation.

Alterations in root morphology and physiology are important strategies in plants to adapt to low-phosphorus (P) environments. Maize genotypes differed in nitrogen (N) efficiency may also respond differently to low P stress. This study aimed to investigate the responses of root morphological and physiological traits of these two maize cultivars to P deficit and how these traits were linked with the acquisition of soil P. Two maize cultivars, XY335 (N efficient) and ZD958 (N inefficient), were cultivated for 40 days in a calcareous loamy soil amended with (high P) or without (low P) P. Functional root traits were used to evaluate the morphological and physiological responses to low P supply. Two separate short-term experiments determined the correlation between P uptake rate and P supply intensity (hydroponic) or root hair length under two P treatments (rhizobox). Low P status significantly simulated biomass allocation to roots, specific root length and exudations of carboxylates, while decreased root diameter and rhizosphere pH in both maize cultivars. Two cultivars had different total root length and root surface area under low P stress: increased in ZD958 and decreased in XY335. Both genotypes developed longer root hair under P deficit. ZD958 (greater biomass and shoot P content) has a greater capability at accessing soil P than XY335. Rhizosphere exudation of citric acid was significantly higher in ZD958 than in XY335, while there was not significant genotypic difference in rhizosphere pH and exudation of malic acid and acid phosphatase activity. ZD958 had higher P uptake rate than XY335 when solution P was between 12.5 and 250 µM. This study identified ZD958 as a P-efficient genotype, which better adapted to low P stress by altering root physiological traits (exudation of citric acid and P uptake rate), rather than root morphological traits (total root length, root surface area, root hair length). Our results highlight the importance of analyzing root morphological and physiological traits to enhance our understanding of the physiological mechanisms of P acquisition.

The general-purpose Compact Muon Solenoid (CMS) detector at the Large Hadron Collider (LHC) at CERN studies a production of new particles in the proton-proton collisions at the LHC center of mass energy 13.6 TeV. The detector includes the magnet based on the 6 m diameter superconducting solenoid coil operating with the current of 18.164 kA. This current creates a central magnetic flux density of 3.8 T that allows to measure momenta of the produced in collisions charged particles with tracking and muon subdetectors at a high precision. The CMS magnet contains a 10,000 ton flux-return yoke made of construction steel that bends muons in steel blocks magnetized with the solenoid returned magnetic flux. To reconstruct the muon trajectories, and thus, to measure the muon momenta, the drift tube and cathode strip chambers are located between the layers of the steel blocks and serve for this purpose. To describe the distribution of the magnetic flux in the magnet yoke layers, a three-dimensional computer model of the CMS magnet is used. To prove the calculations, the special measurements are performed with the flux loops wound in 22 cross-sections of the flux-return yoke blocks. The measured voltages induced in the flux loops during the CMS magnet ramp ups and downs, as well as during the superconducting coil fast discharges with the 190 s time constant, are integrated over time to obtain the initial magnetic flux densities in the flux loop cross-sections. The measurements obtained during the seven standard ramp downs of the magnet have been analyzed in 2018. From that time three fast discharges are occurred during the standard ramp downs of the magnet. This allows to single out the contributions of the eddy currents, induced in steel, to the flux loop voltages registered during the fast discharges of the coil. Accounting for these contributions to the flux loop measurements during manually triggered fast discharges in 2006 allows to perform the validation of the CMS magnet computer model with a better precision. The technique of the flux loop measurements, and the obtained results are presented and discussed.

This paper examines the fundamental distinctions and complementary relationships between generative and descriptive methods in research and analysis. Through a systematic review of their applications across various fields, we explore how descriptive methods excel in capturing and characterizing existing phenomena, while generative methods enable the creation of new instances based on learned patterns. The analysis reveals that while these approaches serve different primary purposes, their integration often leads to more robust and comprehensive research outcomes. Our findings suggest that understanding the strengths and limitations of both methodologies is crucial for researchers and practitioners in choosing appropriate approaches for their specific contexts.

Background/Objectives: Post traumatic growth (PTG) has the potential to draw positive consequences from trauma. Hence, the interest of finding ways to promote PTG. Research has identified an attentional bias towards positive resilience-related words (e.g., “persistence”, “purpose”) in university students who report high PTG after experiencing adversities. Although people can respond to these experiences by showing low PTG, this bias seems to help with their struggle by making purposeful contents more accessible. Therefore, boosting attentional bias towards positive resilience-related words could help people with low PTG. Methods: In this study, the participants were thirty-six university students who had experienced bullying before entering university. Using a Stroop emotional task, they identified the color of resilience and neutral words, either positive or negative, before and after being submitted to transcranial direct current stimulation. Stimulation was targeted at the right temporal area involved in intentionality processing. Results: In the anodal condition, the results support a stimulation effect on the resilience attentional bias that could benefit participants with low PTG. A significant moderation of approach motivation for this effect was also found. Specifically, only when participants had medium or high approach motivation, did stimulation boost the attentional bias in students with low PTG. Conclusions: These results support that tDCS stimulation in this brain area is effective in enhancing resilience attentional bias in low PTG students. However, for this effect to occur it is necessary to have approach motivation, which is motivation related to goals.

This paper presents a comprehensive review of the transformative impact of 3D printing technology on smart cities. As cities face rapid urbanization, resource shortages, and environmental degradation, innovative solutions such as additive manufacturing (AM) offer potential pathways for sustainable urban development. By synthesizing 66 publications from 2015 to 2024, the study examines how 3D printing improves urban infrastructure, enhances sustainability, and fosters community engagement in city planning. Key benefits of 3D printing include reducing construction time and material waste, lowering costs, and enabling the creation of scalable, affordable housing solutions. The paper also addresses emerging areas such as the integration of 3D printing with digital twins (DT), machine learning (ML), and AI to optimize urban infrastructure and predictive maintenance. It highlights the use of smart materials and soft robotics for structural health monitoring (SHM), and repairs. Despite the promising advancements, challenges remain in terms of cost, scalability, and the need for interdisciplinary collaboration among engineers, urban planners, and policymakers. The findings suggest a roadmap for future research and practical applications of 3D printing in smart cities, contributing to the ongoing discourse on sustainable and technologically advanced urban development.

This article explores the use of vegetation indices (VIs) in remote sensing for estimating standing wood volume and volume increments in forest ecosystems. The study investigates the correlations between various VIs and wood volume across different forest stand age classes, focusing on the effectiveness of commonly used indices such as Squared Ratio Simple Red Edge (SQSR) and Red-Edge Ratio Vegetation Index (RERVI), as well as other typical indicators including Enhanced Vegetation Index (EVI), Red-Edge EVI (RE-EVI), and Green Normalized Difference Vegetation Index (GNDVI). Additionally, the analysis considers a pair of indicators based on blue and near-infrared channels, resembling the Blue-normalized Difference Vegetation Index (BNDVI). The research reveals that quadratic and power-law models of SQSR and RERVI demonstrate higher correlations (>0.40) with wood volume, especially in younger forest stands (>0.80). Furthermore, the study highlights the potential of NDII and NDWI indices for estimating volume increments in certain classes of forest stands (0.70). However, correlations vary across different forest stand classes, suggesting the need for further investigation into the reliability of VIs for monitoring wood volume and volume increments in forest ecosystems. Overall, this research contributes to the understanding of the applicability of VIs in remote sensing for forest management and ecosystem monitoring.

On using a 3D model to teach students a topic in astronomy, feedback was evaluated via a questionnaire. Analysis of students' responses to the questions revealed that user interface had a significant impact on their attitudes, which in turn could increase users' willingness to use immersive technology in e-learning. The results also showed that improving visual features through immersive technology and augmented reality tools were effective. The results confirm all hypotheses about positive relationships between facilitating conditions and usability of metaverse technology for students' attention and study motivation.

In recent years there has been an increasing interest in developing novel materials based on natural biopolymers as a renewable alternative of petroleum-based plastics. The availability of proteins derived from agricultural by-products, along with their favourable properties, has fostered a renewed interest in protein-based materials, promoting research in innovative technologies. In this study we propose the use of rapeseed protein-rich meal as main ingredient for the preparation of novel sustainable materials combining excellent environmental properties such as biodegradability and renewable origin. Application as sustainable products in the present high-tech society needs modification of basic native properties of these natural compounds. The original route proposed in this paper consists in the preparation via compression moulding of flexible biomaterials stabilized by crosslinkers/chain extenders. Investigation of the effects of different denaturing and disulfide bond reducing agents, crosslinkers, and preparation conditions on the material mechanical behaviour demonstrated that the novel materials have appreciable strength and stiffness. The results show the potential of utilizing full meal from vegetable by-products to prepare protein-based materials with granted ecofriendly characteristics and mechanical properties adequate to specific structural applications.

Simple Summary (148 words) There is increasing evidence, that cannabinoids may play an important and dual role in tumour therapy. On one hand, they are cytotoxic against cancer cells with a low toxicity against normal, healthy tissues, and on the other, they may reduce typical side effects of chemotherapy. Publications on the main motive for use of cannabis (cannabinoids) by cancer patients show that patients' expectations exceed scientific facts. This article briefly describes results of combinations of cannabinoids with standard antineoplastic drugs on tumours and on side effects of tumour therapy. Although observations are still limited to animal studies with very few experiences in patients, preliminary data suggest that adjuvant cannabinoids may improve the survival of glioblastoma and perhaps of patients with other tumours. Benefits have also been reported about chemotherapy-induced nausea and vomiting, chemotherapy-induced peripheral neuropathic pain, loss of appetite and anxiety. Although results are promising, much more research is necessary. Abstract (192 words) Cancer, one of the leading causes of death worldwide, is on the rise. The high toxicity of conventional chemotherapy, often applied as drug cocktails, and resistance development limits the use of anti-neoplastic drugs and reduces the quality of life. With an easier access, a growing number of patients are using cannabis (cannabinoids) for alleviation of their symptoms, and in the hope of improving survival. This narrative article summarizes results observed with combinations of phytocannabinoids and standard chemotherapeutic agents in animal tumour models and in patients. Preliminary data suggest that standard antineoplastic agents combined with cannabinoids exert increased anti-cancer actions, reduce resistance development and improve survival. Respective experiences in patients are still scarce and concern small numbers with glioblastoma, and pancreatic carcinoma. Further benefits of combinations with cannabinoids have also been reported for chemotherapy-induced nausea and vomiting, loss of appetite (dronabinol), chemotherapy-induced peripheral neuropathic pain and anxiety (cannabidiol). In addition, phytocannabinoids, in particular cannabidiol, may play a role in the protection of organs such as heart, lung or kidney against chemotherapy-induced toxicity. Although results are promising, much more research is needed to determine whether positive experiences of adjuvant cannabinoids outweigh eventual risks.

Febrile neutropenia (FN) is a major concern in patients undergoing chemotherapy for diffuse large B-cell lymphoma (DLBCL); however, the overall risk of FN is difficult to assess. This study aimed to develop a model for predicting the occurrence of FN in patients with DLBCL. In this multicenter, retrospective, observational analysis, a multivariate logistic regression model was used to analyze the association between FN incidence and pretreatment clinical factors. We included adult inpatients and outpatients (aged ≥ 18 years) diagnosed with DLBCL who were treated with chemotherapy. The study examined 246 patients. Considering FN occurring during the first cycle of chemotherapy as the primary outcome, a predictive model with a total score of 5 points was constructed as follows: 1 point each for viral hepatitis, extranodal involvement, and a high level of soluble interleukin-2 receptor and 2 points for lymphopenia. The area under the receiver operating characteristic curve of this model was 0.844 (95% confidence interval: 0.777–0.911). Our predictive model can assess the risk of FN before patients with DLBCL start chemotherapy, leading to better outcomes.

The BNT162b2 vaccine is globally used for preventing morbidity and mortality related to COVID-19. Cancer patients have had priority for receiving the vaccine due to their diminished immunity. This study reports the response of administering the 3rd and 4th vaccine doses to can-cer patients receiving active anti-neoplastic treatment. 142 patients have received two doses of the mRNA-based BNT162b2 COVID-19 vaccine, while 76 and 25 patients have received three and four doses, respectively. The efficacy of the humoral response following two vaccine doses was diminished in cancer patients, especially in the group of patients receiving chemotherapy. In a multivariate analysis, patients after three and four BNT162b2 vaccine doses were more likely to have antibody titers in the upper tertile compared to patients after two doses of the vaccine (odds ratio (OR) 7.62 (95% CI 1.38-42.12), p=0.02 and 17.15 (95% CI 5.01-58.7), p<0.01, respective-ly). Unlike the response after two doses, the 3rd and 4th BNT162b2 vaccine booster doses, had an increased efficacy of 95-100% in cancer patients while on active treatment. This result could be explained by different mechanisms including the development of memory B cells.

This study aimed to compare the prognosis and characteristics of patients with advanced hepatocellular carcinoma treated with first-line atezolizumab plus bevacizumab (AB) combination therapy and hepatic artery infusion chemotherapy (HAIC). We retrospectively assessed 179 and 72 patients treated with HAIC and AB combination therapy, respectively, between January 2018 and January 2023. The progression-free survival of patients treated with HAIC was significantly superior than that of patients treated with AB (P&lt;0.05), but there was no significant difference in overall survival and objective response rate (ORR) between the two groups (P=0.1056 and P=0.137, respectively). After propensity score matching (PSM), our data revealed that there was no significant difference in PFS between patients who received AB combination therapy and HAIC therapy (P=0.8888). However, patients who received AB combination therapy had significantly better overall survival than those who received HAIC therapy (P=0.0133). In addition, after PSM, significant differences in ORR and disease control rate were not observed. In conclusion, our propensity score study reveals that patients treated with AB therapy have a significantly longer OS than those treated with HAIC.

Targeted protein degradation is an attractive technology for cancer treatment due to its ability to overcome the unpredictability of small molecule inhibitors that cause resistance mutations. In recent years, various targeted protein degradation strategies have been developed based on the ubiquitin-proteasome system in the cytoplasm or the autophagy-lysosomal system during endocytosis. In this review, we describe and compare technologies for targeted inhibition and targeted degradation of the epidermal growth factor receptor (EGFR), one of the major proteins responsible for the onset and progression of many types of cancer. In addition, we have developed an alternative strategy, called alloAUTO, based on the binding of new heterocyclic compounds to an allosteric site located in close proximity to the EGFR catalytic site. These compounds cause targeted degradation of the transmembrane receptor, simultaneously activating both systems of protein degradation in cells. Damage to EGFR signaling pathways promotes inactivation of Bim sensor protein phosphorylation, which leads to disintegration of the cytoskeleton, followed by detachment of cancer cells from the extracellular matrix and, ultimately, to cancer cell death. This hallmark of targeted cancer cell death suggests an advantage over other targeted protein degradation strategies, namely that the fewer cancer cells survive, the fewer chemotherapy-resistant mutants appear.

Background A limited lymphadenectomy may make patients with esophageal squamous cell carcinoma (ESCC) at risk for missing occult nodal disease. This study aimed to determine an effective threshold of lymph nodes (LNs) for evaluation of the quality of lymphadenectomy and discuss the impact of adjuvant chemotherapy on pN0 patients. Methods Patients treated surgically for ESCC between 2010 and 2018 in Sichuan Cancer Hospital were included. NPV (Negative Predictive Value) based on a beta-binomial distribution was developed to assess the confidence of node-negative disease. Kaplan-Meier curves were plotted to compare survival differences among groups. Results When patients had >21 LNs examined, the probability of false-negative findings was estimated at <10%, and NPV was estimated at a high level (>86.5%). For patients with LNs removed ≤21, 5-year OS (or DFS) in postoperative chemotherapy group vs that in surgery group was 65.3% vs 54.6%, p = 0.041 (or 59.2% vs 46.6%, p = 0.033). But for patients with >21 LNs, there were no statistical differences (p = 0.683 for OS or p = 0.942 for DFS). Conclusion Only pN0 patients who were at high risk of occult lymph node metastasis (examined LNs ≤21) could benefit from postoperative chemotherapy.