Abstract:

Intratumoral microbiota, the diverse community of microorganisms residing within tumor tissues, represent an emerging and intriguing field in cancer biology. These microbial populations are distinct from the well-studied gut microbiota, offering novel insights into tumor biology, cancer progression, and potential therapeutic interventions. Recent studies have explored the use of certain antibiotics to modulate intratumoral microbiota and enhance the efficacy of cancer therapies, showing promising results. Antibiotics can alter intratumoral microbiota’s composition, which may have a major role in promoting cancer progression and immune evasion. Certain bacteria within tumors can promote immunosuppression and resistance to therapies. By targeting these bacteria, antibiotics can help create a more favorable environment for chemotherapy, targeted therapy and immunotherapy to act effectively. Some bacteria within the tumor microenvironment produce immunosuppressive molecules that inhibit the activity of immune cells. The combination of antibiotics and other cancer therapies holds significant promise for creating a synergistic effect and enhancing the immune response against cancer. In this review we analyze several preclinical studies that have been conducted to demonstrate the synergy between antibiotics and other cancer therapies and discuss possible clinical implications.

Abstract:

We investigated whether microalgae or linseed supply during the early postpartum period affects ovarian restimulation and supports the first postpartum ovulation in lactating anovulatory goats. Thirty-eight An-glo-Nubian-crossbred adult goats were allocated into three groups: con-trol diet (n=12), fed a total mixed ration (TMR) comprising chopped elephant grass and concentrate; algal diet (n=13), fed TMR+green microalgae (1% dry matter); and linseed diet (n=13), TMR+linseed (12% dry matter). Supplements were furnished from the 2nd to 5th week (time of weaning). Goats were estrus synchronized on day 40 by insertion of an intravaginal CIDR device for 5 days, after which 0.075mg PGF2α was applied to in-duce ovulation, and estrus was monitored for 72 hours. From the 5th-15th day of ovulation induction, the corpus luteum (CL) area and progesterone rate were monitored. The algal and linseed groups showed lower feed intake (P<0.001) and higher (P<0.001) triglyceride levels/follicle numbers, respectively. After estrus induction, no differences were ob-served in estrus response; however, the linseed group showed more and larger growing follicles (P=0.016 and P<0.01), a higher ovulation rate (P<0.05), larger CL area (P<0.05), and higher progesterone levels (P<0.001). Linseed after delivery stimulates follicular growth before and after ovulation induction, favoring better CL quality during the first ovulation.

Abstract: Clinical reasoning is an essential competence of veterinary graduands. Unfortunately, clinical reasoning and, therefore, the quality of provided veterinary medical services, are prone to bias, difficulties, and errors. Literature on biases, difficulties, and errors in clinical reasoning in veterinary medical education is scarce or focused on theoretical rather than practical application. In this review, we address the practicality of learning and teaching biases, difficulties, and errors in clinical reasoning to veterinary learners utilizing a practical example of a cow with a prolapsed uterus, complicated by hypocalcemia and hypomagnesemia. Learners should be guided through all of the stages of clinical reasoning as much as possible under direct supervision. The common clinical biases, difficulties, or errors in veterinary medical encounters may differ between stages of development of the learner, with more difficulties occurring in earlier stages (Observer, Reporter, ± Interpreter) but more heuristic biases occurring at later stages (Manager, Educator, ± Interpreter). However, clinical errors may occur at any learner development stage. Therefore, remediation of clinical biases, difficulties, and errors in veterinary medical encounters should use strategies that are tailored to the level of development of the learner, but also to the specific encounter (e.g., client, patient, and context).

Abstract:

Objectives: To evaluate the impact of diabetes mellitus (DM) on the outcome of Schlemm’s canal based minimally invasive glaucoma surgery (MIGS). Methods: In a retrospective interventional cohort study, post- operative intraocular pressure (IOP) and intracameral bleeding were analyzed in 25 diabetic and 84 non-diabetic patients with primary open angle glaucoma (POAG) or ocular hypertension (OH). Results: The mean follow-up period for all 109 eyes was 35.3±24.8 months. There was no significant difference in pre-operative IOP between diabetic and non-diabetic cohorts. However, the post-surgical IOP between 3 months and 2 years was significantly higher in the diabetic cohort (P=0.019 to 0.001). The 3-year survival probability of achieving an IOP≦15 mmHg was 17.8±0.09% in diabetic patients, significantly lower than the 30.4±0.06% observed in non- diabetic patients (P=0.042 Log-rank test). The 3-year survival probability of achieving an IOP≦18 mmHg was 56.7±0.12% in diabetic patients compared to 79.5±0.05% in non-diabetic patients, indicating a marginally significant difference between diabetic and non-diabetic cohorts (P=0.065). When the random effect of diabetes mellitus (DM) was analyzed alongside the fixed effects of preoperative IOP, age, refractive error and extent of canal opening using a multivariate linear mixed model, DM emerged as a significant risk factor for higher postoperative IOP at both 6 and 12 months (P<0.001). Conclusions: Diabetes mellitus is a significant risk factor for poor outcomes following Schlemm’s canal based MIGS, particularly in achieving lower postoperative IOP.

Abstract: This research paper investigates the impact of psychological interventions on student performance, specifically within the MIT Integration Bee, a prestigious mathematics competition that challenges students with advanced calculus problems. Conducted across multiple high schools in Texas, the study explores how different motivational techniques, including intrinsic and extrinsic rewards, influence test scores and overall student engagement. The research design includes a comprehensive analysis of motivational strategies, encompassing both baseline and reward-based conditions to assess their effectiveness in enhancing student performance. By examining a diverse sample of high schools from urban and suburban areas, this study aims to provide a holistic understanding of the factors that drive academic achievement in competitive settings. The results have significant implications for educational strategies, particularly in the realm of mathematics education, and highlight the potential for tailored motivational interventions to optimize student engagement and achievement. These findings contribute to the broader discourse on educational psychology, offering insights that could inform the development of more effective teaching practices and policies aimed at fostering a conducive learning environment for students across different educational contexts. In addition, this can potentially be applied to universities as well, breaking way through an exciting part of academics.

Abstract:

Fluorescence is a remarkable property exhibited by many chemical compounds and biomolecules. Fluorescence has revolutionized analytical and biomedical sciences due to its wide-ranging applications in analytical and diagnostic tools of biological and environmental importance. Fluorescent molecules are frequently employed in drug delivery, optical sensing, cellular imaging and biomarker discovery. Cancer is a global challenge and fluorescence agents can function as diagnostic as well as monitoring tools both during early tumor progression and treatment monitoring. Many fluorescent compounds can be found in their natural form but recent developments in synthetic chemistry and molecular biology have allowed us to synthesize and tune fluorescents molecules which otherwise wouldn’t exist in the nature. Naturally derived fluorescent compounds are generally more biocompatible and environmentally friendly. They can also be modified in cost-effective and target-specific ways with the help of synthetic tools. Understanding their unique chemical structures and photophysical properties is key to harnessing their full potential in biomedical and analytical research. As drug discovery efforts require rigorous characterization of pharmacokinetics and pharmacodynamics, fluorescence-based detection accelerates the understanding of drug interactions via in vitro and in vivo assays. Herein, we provide a review of natural products and synthetic analogs that exhibit fluorescence properties and can be used as probes, detailing their photophysical properties. We have also provided some insights into the relationships between chemical structures and fluorescent properties. Finally, we have discussed the applications of fluorescent compounds in biomedical science; mainly in the study of tumor and cancer cells and analytical research, highlighting their pivotal role in advancing drug delivery, biomarkers, cell imaging, biosensing technologies, and as targeting ligands in the diagnosis of tumors.

Abstract:

A covariant classical theory of gravity is given assuming absolute flat spacetime and the strong equivalence principle (SEP). It is shown that adherence to these postulates requires that the gravitational field “dimensionally perturb” all physical objects at a location universally. Such perturbations are referred to as “gravity shifts,” and it is found that all gravitational phenomena may be given in terms of them. Two classes of observers emerge in “gravity shift theory”—“natural observers” using gravity shifted instruments as is, and “absolute observers” that correct for the gravity shifting applied to instruments. Absolute observers accurately measure quantities, including the absolute spacetime metric as it actually is. Natural observers do not accurately measure quantities, but their system of measurement is observationally consistent, yielding a curved “natural metric” to characterize spacetime. When a local gravitational system is surrounded by a “background system” with negligible curvature effects, its gravity shifting induces a diffeomorphism applied to the local system, yielding satisfaction of the SEP for natural observers. Using the naturally observed inertial form of physical law in free-fall frames, covariant formulation in all coordinates establishes the natural metric as the universally coupled “gravitational metric” in physical law. The unique field equation determining gravity shifts, and therefore the natural metric, is developed. The resultant bimetric theory is parameterless, complete, and self-consistent. The field equation yields the observed post-Newtonian natural metric and linearizes to the predictive linearized Einstein equation, which, along with SEP satisfaction, results in successful prediction of a wide variety of observed gravitational phenomena. A supplement is provided that extends the range of predictions to include low post-Newtonian order radiation cases, and also the strong-field cases consisting of the properties of black and neutron stars plus any nearby matter and light, where in all cases, the predictions are shown to be consistent with observations.

Abstract:

Suicide is a global phenomenon, with more than 700,000 people worldwide taking their own life yearly. Both natural and human-made disaster may have a detrimental effect on suicidal behaviors both in the short-term and in the long-term. Many studies focused on the acute impact of the COVID-19 pandemic on suicidality. The aim of the study was to analyze demographic and clinical features of subjects accessing the emergency rooms for suicidality during the second epidemic wave of COVID-19 in five emergency departments in Lombardy (Italy). A retrospective chart review was conducted in the five emergency departments for the period 4 June – 31 December 2020, and during the same time lapse in 2019. For all subjects accessing for suicidality, socio-demographic and clinical data were collected and compared between the two years. No differences between the two years were found for sex, triage priority level, history of substance abuse, factor triggering suicidality and discharge diagnosis. During 2020 a greater proportion of subjects did not show any previous mental disorder, however, more subjects were already taking anxiolytic medications before the admission. Among a range of possible risk factors, attempted suicide, depression diagnosis and taking medications before the admission were found to be predictor of admission to psychiatric inpatient units. Characterizing subjects prone to suicidality during the second wave of the COVID-19 pandemic, our study provides hints for mid-term causes of suicidality and possible preventive measures that could be helpful in the course and after massive infectious outbreaks.

Abstract:

Molecular biology is undergoing a transformative evolution through the integration of Artificial Intelligence (AI) and bioinformatics, which collectively empower researchers to analyze complex genomic datasets, uncover hidden patterns in genetic information, and advance the paradigm of precision medicine. Notable breakthroughs include AlphaFold’s revolutionary contribution to protein structure prediction, achieving near-experimental accuracy, and PolyPhen’s role in assessing the functional impact of genetic mutations, advancing precision diagnostics. These advancements demonstrate the potential of AI to accelerate discoveries in functional genomics and disease prediction models. However, the integration of these technologies also raises significant ethical concerns. For instance, issues related to genetic privacy have become increasingly critical, as the misuse of sensitive genomic data could lead to discrimination in healthcare and employment. This comprehensive review explores the dynamic intersection of AI and bioinformatics, emphasizing their roles in gene-disease association studies, protein structure prediction, and functional genomics. It also critically addresses challenges, including data quality issues, computational limitations, and the ethical implications of genetic privacy. Future research directions focus on enhancing AI model transparency, overcoming computational barriers, and developing robust ethical frameworks to ensure equitable benefits in clinical and research settings. By integrating cutting-edge AI technologies, such as explainable AI (XAI) and federated learning, with robust bioinformatics methodologies, this review highlights a roadmap for revolutionizing genetic research and fostering advancements in personalized medicine.

Abstract: A 2-year-old male neutered domestic shorthair cat was presented with a progressive history of tetraparesis, ataxia, and inappetence over 4 days. A physical exam revealed mucopurulent nasal discharge and stertor. Neurologic exam revealed a multifocal neurolocalization. The cat was non-ambulatory tetraparetic and developed seizures while in-hospital. Hematologic assessment revealed anemia, hypoalbuminemia and hyperglobulinemia. Magnetic resonance imaging (MRI) of the brain revealed multifocal meningeal contrast enhancement in the brainstem and cervical spine, as well as mandibular and retropharyngeal lymphadenopathy. Cerebrospinal fluid revealed marked neutrophilic pleocytosis, no infectious organisms were seen. Toxoplasma IgG/IgM and cryptococcus antigen latex agglutination were negative. Mandibular and abdominal lymph nodes were aspirated, and cytology revealed mixed inflammation. Nanopore sequencing specifically identified FCoV-1 RNA in spinal fluid and anal swab, but not in urine. This method serves as a novel and rapid PCR sequencing technique for the antemortem diagnosis of feline infectious peritonitis. The cat was treated with anticonvulsants (phenobarbital and levetiracetam), an antibiotic (ampicillin/clavulanic acid), and GS-441524. Neurologic signs did not improve on an antibiotic alone but improved significantly after two subcutaneous injections of GS-441524. The cat received an 84-day course of GS-441524 and, at the time of manuscript preparation (over 12 months after diagnosis), remained ambulatory and seizure-free without recurrence of neurologic signs and no detectable viral shedding in feces.