In this paper, a distributed algorithm is proposed to solve a consensus convex optimization problem. It is a Jacobi-proximal alternating direction method of multipliers with a damping parameter $\gamma$ in the iteration of multiplier. Compared with existing algorithms, it has the following nice properties: (1) The restriction on proximal matrix is relaxed substantively, thus alleviating the weight of the proximal term. Therefore, the algorithm has a faster convergence speed. (2) The convergence analysis of the algorithm is established for any damping parameter $\gamma\in(0,2]$, which is larger ones in the literature. In addition, some numerical experiments and an application to a logistic regression problem are provided to validate the effectiveness and the characteristics of the proposed algorithm.

The drug discovery process tends to be grueling, lengthy and expensive, with cost estimates approximating $2.6 billion, consuming over 10 years to complete. Such drawbacks have set many eyes locked onto reducing the costs and accelerating the development. The emergence of Deep Reinforced Learning (DRL) within cheminformatics and bioinformatics has broadens the horizons of de novo drug design. Realizing the full potential of DRL in molecular generation requires selecting the appropriate reinforcement learning (RL) algorithm. In this work, we address these problems by utilizing Proximal Policy Optimization (PPO) algorithm within the DRL framework for molecular generation. We proposed a new method by utilizing PPO algorithm within the DRL framework, termed PSQ, to enable the generation of new chemical compounds with desired properties. This methodology has demonstrated significant potential in exploring and generating specific molecules by optimizing for targeted characteristics. The PPO algorithm's superior performance in exploring the chemical space and generating compounds with diverse pharmacophore features, functional groups, and biological activities underscores its potential in drug discovery and chemical synthesis. By systematically comparing the outputs of PPO and REINFORCE, we highlighted the robustness and efficiency of PPO in optimizing molecular properties for targeted therapeutic applications.

Background: The aim of the present study was to determine the correlation between obesity, serum levels of leptin and proximal gastric cancer. Methods: Sixty-four gastric cancer patients operated on with curative intent were included in the study. We determined the correlation between the preoperative serum levels of leptin and the tumor`s location. Results: Serum leptin levels were correlated significantly with the proximal third location (p = 0.04), gastric outlet obstructing tumors (p < 0.0001), CRP levels (p = 0.03) and BMI (p < 0.0001). Patients with high serum levels of leptin had significantly more intestinal types of gastric cancer (p = 0.033) and better differentiation compared to patients with low serum leptin levels (p = 0.009). The linear regression model determined the proximal tumor location (beta: 0.467; p = 0.045), BMI (beta: 0.657; p = 0.001), high preoperative serum albumin (beta: 0.563; p = 0.016) and the presence of pyloric stenosis (beta: 0.525; p = 0.006) as related significantly to serum leptin levels. The Cox proportional hazard model identified age (HR: 0.003; 95%CI: 0-0.794; p = 0.041), preoperative serum levels of leptin (HR: 0.125; 95%CI: 0.018-0.887; p = 0.037) and the number of extracted LNs (HR: 0.001; 95%CI: 0-0.677; p = 0.038) as independent prognostic factors. Conclusions: Serum levels of leptin were significantly elevated in patients with proximal gastric cancer, suggesting that the leptin`s effect might be due to its systemic secretion. This might explain the higher incidence of proximal gastric cancer in obese patients. Elevated serum leptin levels were an independent prognostic factor.

A strategy to reduce qualitative and quantitative losses in crop-yields refers to early and accurate detection of insect-damage caused in plants. Remote sensing systems like hyperspectral proximal sensors are a promising strategy for managing crops. In this aspect, machine learning predictions associated with clustering techniques may be an interesting approach mainly because of its robustness to evaluate high dimensional data. In this paper, we model the spectral response of insect-herbivory-damage in maize plants and propose an approach based on machine learning and a clustering method to predict whether the plant is herbivore-attacked or not using leaf reflectance measurements. We differentiate insect-type damage based on the spectral response and indicate the most contributive wavelengths to perform it. For this, we used a maize experiment in semi-field conditions. The maize plants were submitted to three different treatments: control (health plants); plants submitted to Spodoptera frugiperda herbivory-damage, and; plants submitted to Dichelops melacanthus herbivory-damage. The leaf spectral response of all plants (controlled and submitted to herbivory) was measured with a FieldSpec 3.0 Spectroradiometer from 350 to 2500 nm for eight consecutive days. We evaluated the performance of different learners like random forest (RF), support vector machine (SVM), extreme gradient boost (XGB), neural networks (MLP), and measured the impact of a day-by-day analysis into the prediction. We proposed a novel framework with a ranking strategy, based on the accuracy returned by predictions, and a clusterization method based on a self-organizing map (SOM) to identify important regions in the reflectance measurement. Our results indicated that the RF-based framework algorithm is the overall best learner to deal with this type of data. After the 5th day of analysis, the accuracy of the algorithm improved substantially. It separated the three treatments into different groups with an F-measure equal to 0.967, 0.917, and 0.881, respectively. We also verified that the most contributive spectral regions are situated in the near-infrared domain. We conclude that the proposed approach with machine learning methods is adequate to monitor herbivory-damage of S. frugiperda and stink bugs like Dichelops melacanthus in maize, differentiating the types of insect-attack early on. We also demonstrate that the framework proposed for the analysis of the most contributive wavelengths is suitable to highlight spectral regions of interest.

Visible and near-infrared reflectance (Vis–NIR) techniques are a plausible method to soil analyses. The main objective of the study was to investigate the capacity to predicting soil properties Al, Ca, K, Mg, Na, P, pH, total carbon (TC), H and N, by using different spectral (350–2500 nm) pre-treatments and machine learning algorithms such as Artificial Neural Network (ANN), Random Forest (RF), Partial Least-squares Regression (PLSR) and Cubist (CB). The 300 soil samples were sampled in the upper part of the Itatiaia National Park (INP), located in Southeastern region of Brazil. The 10 K-fold cross validation was used with the models. The best spectral pre-treatment was the Inverse of Reflectance by a Factor of 104 (IRF4) for TC with CB, giving an averaged R² among the folds of 0.85, RMSE of 1.96; and 0.67 with 0.041 respectively for H. Into the K-folds models of TC, the highest prediction had a R² of 0.95. These results are relevant for the INP management plan, and also to similar environments. The good correlation with Vis–NIR techniques can be used for remote sense monitoring, especially in areas with very restricted access such as INP.

Aquaporin-11 (AQP11) is an intracellular water channel expressed at the endoplasmic reticulum (ER) of the kidney proximal tubule. Its gene disruption in mice leads to intracellular vacuole formation at one week old and the subsequent development of polycystic kidneys at three week old. As the damaged proximal tubular cells with intracellular vacuoles later form cysts, autophagy may play a role in their survival. We examined the autophagy activity before and after the development of cysts in AQP11(-/-) kidneys. We first observed an enhanced expression of LC3 gene (Map1lc3b) as well as other autophagy-related genes in AQP11(-/-) mice by quantitative PCR analysis. We then examined the formation of autophagosomes visualized by a green fluorescent fusion protein, GFP–LC3 in its transgenic mice. The expression of GFP-LC3 puncta was increased in the proximal tubule of AQP11(-/-) mice before the cyst formation. Interestingly, they were also observed in the cyst-lining epithelial cell. Further PCR analyses revealed the enhanced expression of apoptosis- and ER stress-related caspase genes before and after the cyst formation suggesting that ER stress may have enhanced autophagy. We conclude that autophagy will play an important role in the development and the survival of the kidney cysts in AQP11(-/-) mice.

We compared two approaches to non-invasive proximal sensing of the early changes in fresh-cut lettuce leaf quality: hyperspectral imaging and imaging PAM-fluorometry of chlorophyll contained in the leaves. The assessments made by the imaging techniques were confronted with the quality assessments made by traditional biochemical assays: relative water content and foliar pigment (chlorophyll and carotenoid) composition. The hyperspectral imaging-based approach provided the highest sensitivity to the decline of fresh-cut lettuce leaf quality taking place within 24 h from cutting. Using of the imaging PAM was complicated by (i) weak correlation of the spatial distribution pattern of the Qy parameter with the actual physiological condition of the plant object and (ii) its high degree of heterogeneity. Accordingly, the imaging PAM-based approach was sensitive only to the manifestations of leaf quality degradation only at advanced stages of the process. Sealing the leaves in the polyethylene bags slowed down the leaf quality degradation at the initial stages (&lt; 3 days) but promoted its rate at more advanced stages, likely due to build-up of ethylene in the bags. An approach was developed to the processing of hyperspectral data for non-invasive monitoring of the lettuce leaves with a potential for implementation in greenhouses and packinghouses.

Many mathematical models of strategic play or better choice overlook adjustment costs. Rather often, the modeler's concern is just with improvement of objectives. This optic doesn't quite fit agents somewhat attached to status quo. They reason whether moving to another state be worth their while. For that, the realized gains must outweigh the inconveniences of the move. This note offers some observations on the fact that change usually entails cost.

The aim of this retrospective study was to compare the clinical outcomes of treating isolated surgical neck fractures of the humerus using either the intramedullary nail or the MIROS (Minimally Invasive Reduction and Osteosynthesis System®) system. The study included 42 patients who underwent surgical treatment at the Polyclinic from January 2014 to June 2020. The results indicated that both treatments were effective; however, the MIROS system exhibited a higher complication rate. Intramedullary nailing was more reliable, thus recommended as the primary treatment method. This study underscores the importance of selecting the appropriate fixation technique to minimize complications and enhance patient outcomes.

Dent disease type 1 is a rare inherited renal disorder affecting mainly young males, generally leading to end-stage renal failure and for which there is no cure. It is caused by inactivating mutations in the gene encoding ClC-5, a 2Cl-/H+ exchanger found on endosomes in the renal proximal tubule. This transporter participates in reabsorbing all filtered plasma proteins which justifies why proteinuria is commonly observed when ClC-5 is defective. In the context of Dent disease type 1, a proximal tubule dedifferentiation was shown to be accompanied by a dysfunctional cell metabolism. However, the exact mechanisms linking such alterations to chronic kidney disease are still unclear. In this review, we gather knowledge from several Dent disease type 1 models to summarize the current hypotheses generated to understand the progression of this disorder. We also highlight some urinary biomarkers for Dent disease type 1 suggested in different studies.

In theory and applications, it is often inevitable to work with projectors onto convex sets, where a linear transform is involved. In this article, a novel projector is presented, which generalizes previous results in that it admits a broader family of linear transforms, but on the other hand it is limited to box-type convex sets in the transformed domain. The new projector has an explicit formula and it can be interpreted within the framework of proximal optimization. The benefit of the new projector is demonstrated on an example from signal processing, where it was possible to speed up the convergence of a signal declipping algorithm by a factor of more than two.

Biostimulants are organic agents employed for crop yield enhancement, quality improvement, and environmental stress mitigation, reducing, at the same time, reliance on inorganic inputs. With advancements in sustainable agriculture, data acquisition technologies have become crucial for monitoring the effects of such inputs. This study evaluates the impact of four biostimulant application rates on grapevines, using vegetation indices derived from Unmanned Aerial Systems (UAS), proximal and manual sensing tools, and qualitative and quantitative production assessments. The research was conducted over two seasons in a Malvasia Bianca vineyard in Sardinia, Italy. Results indicated that UAS-derived vegetation indices, consistent with traditional ground-based measurements, effectively monitored vegetative growth over time but revealed no significant differences between treatments, suggesting either a lack of vegetative indices sensitivity or that the applied biostimulant rates were insufficient to elicit a measurable response in the cultivar. Among the tools employed, only the SPAD 502 meter demonstrated the sensitivity required to detect treatment differences, primarily reflected in grape production outcomes. Future research will focus on validating these technologies for precision viticulture, particularly on long-term benefits.

This study is a retrospective analysis aimed to understand the incidence and risk factors of proximal junctional kyphosis (PJK) following long instrumented spinal fusion from L1 to the sacrum in patients with mild to moderate sagittal imbalance. It recruited consecutive patient undergone instrumented fusion from L1 to the sacrum for degenerative lumbar disease between June 2006 and November 2019 in a single institution. The patients’ preoperative clinical data, muscle status at T12-L1 on magnetic resonance images, and sagittal spinopelvic parameters were analyzed. Univariate analysis was used to compare clinical and radiographic data between PJK and non-PJK patients. Logistic regression analysis was used to investigate the independent risk factors for PJK. A total of 56 patients were included in the study. The mean age at surgery was 67.3 years and mean follow-up period was 37.3 months. Seven were male and 34 were female. PJK developed in 23 (41.1%) out of 56; of these patients, 20 (87.0%) developed PJK within postoperative 1 year. On univariate analysis between PJK and non-PJK patients, PJK group showed more frequent osteoporosis, lower body mass index, smaller cross-sectional area (CSA) and more fat infiltration (FI) in erector spinae muscle at T12-L1, larger preoperative TLK and PT with statistical significance (p&lt;0.05). On logistic regression analysis, severe (&gt;50%) FI in erector spinae muscle (OR=43.60, CI 4.10-463.06, R2N =0.730, p=0.002) and osteoporosis (OR=20.49, CI 1.58-264.99, R2N =0.730, p=0.021) were statistically significant. Preexisting severe (&gt;50%) fat infiltration in erector spinae muscle and osteoporosis were significant independent risk factors associated with PJK following instrumented fusion from L1 to the sacrum, but age was not a risk factor.

This contribution illustrates the training evaluation system developed within the Master’s Program in Family and Community Mediation at Università Cattolica del Sacro Cuore in Milan. This is an interim evaluation, which focuses on the training process and which considers fundamental the collaboration with the subjects of the training. The peculiarity of this work concerns the possibility of inserting research within the training process, following a logic of mutual enrichment both in terms of content and learning. The contribution illustrates in detail the outcome and the process evaluation system, defining the perspective, the objectives, and the methodology of implementation. In particular, the outcome evaluation focuses on the distal and proximal outcomes of the training, while the process analysis focuses on the dynamics within the group of participants. Although further evaluations involving different training groups and other training processes are needed, this training evaluation system allows to shed light on both the topic and the context in which training is delivered. The integration between different points of view and several levels of analysis allows the researchers to deepen the individual path of each participant as well as to have feedbacks on the progress of the training group as a whole.

Variable nitrogen(N) rate fertilization based on remote sensing is challenging for cotton production fields, but active crop canopy sensors (ACS) appear as an alternative to make this practical on farm since they can be used at night as well. The crop spatial variability in inherent in crop production in general, and not on-the-go solutions can be used with this type of active sensing technologies. Thus, the purpose of this study was to investigate the potential of two vegetation indices to identify the N requirement variability for cotton plants and to develop prototype algorithms for topdressing nitrogen variable rate on commercial and experimental areas, using the N-sufficiency methodology based on virtual reference. The concept of virtual reference is to use a histogram to characterize the vegetation index of properly fertilized plants without establishing an N-rich plot as a reference strip. The experiment was conducted in strips with four different N rates (0, 45, 90 and 180 kgN ha^-1) during the 2015, 2016, 2017 and 2018 crop seasons in partnership with large cotton producers in Mato Grosso and also in experimental area of Embrapa Agrosilvopastoral. Two algorithms for variable rate nitrogen fertilization for cotton were developed, namely: 1) N recommendation algorithm for cotton in commercial production system: N rate (kg.N ha^-1) = -234.79 ISN² + 49,879 ISN + 195.15; R² = 0.97; and 2) for cotton grown in experimental area: N dose (kgN ha^-1) = -174.73 ISN² - 107.21 ISN + 306.78; R² = 0.94.

Diatraea saccharalis (Fabricius) is one of the main pests of rice crops and its early detection, that is, before the plants show damage, is essential to avoid yield losses and define effective and rational control. This work aimed to model the infrared-thermal responses of rice cultivars to D. saccharalis infestation levels. Between 2019 and 2020, two experiments were conducted in a protected environment with the cultivars IR 40 and BR IRGA 409, which presented, in a previous study, different resistance reactions. Rice plants grown in pots were manually infested with first-instar larvae of D. saccharalis, from 0 to 10 caterpillars/plant, with the plants kept in cages covered with voile fabric throughout the test. With the adjustment of regression models, it was noticed that the leaf surface temperature is related to the level of infestation and could be used to detect which IR 40 is susceptible.

We aimed to investigate the ability of children aged 5–14 years old (preschoolers, primary schoolers, and preteens) to assess and anticipate time intervals. 287 Russian children aged 5–14 years old and 26 adults of control group participated in our study. The neuropsychological assessment, Wechsler Intelligence Scale for Children and a battery of time-related tests were applied. All groups of children overestimated the event’s duration, although the accuracy of the second estimations increased among the participants aged 6–8 years after a prompt was offered. A zone of proximal development for time anticipation task was detected for children aged 9-11 years, when the prompt could significantly improve the accuracy of time perception. The participants overestimated the duration of both upcoming and past events, with the degree of overestimation being found to be negatively correlated with age. Further, a higher degree of accuracy in terms of time estimation was found to be correlated with higher scores on the attention and memory tests, and accuracy of time anticipation was associated with scores of praxis test.

Addressing within field spatial variability for nitrogen management to avoid over and under-use of nitrogen is crucial for optimizing crop productivity and ensuring environmental sustainability. In this study we investigated the economic, environmental and agronomic benefits of variable rate nitrogen application in potato (Solanum tuberosum). An online visible and near infrared (vis-NIR) spectroscopy sensor we utilized to predict soil moisture content (MC), pH, total organic carbon (TOC), extractable phosphorus (P), potassium (K), magnesium (Mg), and cation exchange capacity (CEC) using a partial least squares regression (PLSR) models. The crop's normalized difference vegetation Index (NDVI) from Sentinel-2 satellite images was incorporated to online measured soil data to derive fertility management zones (MZs) maps, after homogenous raster and clustering analyses. The MZs maps were categorized into high fertile (VR-H), medium-high fertile (VR-MH), medium-low fertile (VR-ML), and low fertile (VR-L) zones. A parallel strip experiment compared variable rate nitrogen (VR-N) with uniform rate (UR) treatments, adjusting nitrogen levels based on fertility zones as: 50% less for VR-H, 25% less for VR-MH, 25% more for VR-ML, and 50% more for VR-L zones compared to the UR treatment. Results showed that the VR-H zone received a 50% reduction in N fertilizer input and demonstrated a significantly higher crop yield compared to the UR treatment. This implies a potential reduction in negative environmental impact by lowering fertilizer costs while maintaining robust crop yields. In total, the VR -N treatment received an additional 1.2 Kg/ha of nitrogen input, resulting in a crop yield increase of 1.89 tons/ha. The relative gross margin for the VR-N treatment compared to the UR treatment 374.83 €/ha, indicating substantial profitability for the farmer. To further optimize environmental benefits and profitability, additional research is needed to explore site-specific application of all farm resources through precision agricultural technologies.

Many large-scale studies revealed that exogenous erythropoietin, erythropoie-sis-stimulating agents, have no renoprotective effects. We investigated the effects of en-dogenous erythropoietin on renal function in ischemic reperfusion injury (IRI) of kidney using prolyl hydroxylase domaine (PHD) inhibitor, Roxadustat (ROX). 4 hr hypoxia (7% O2) and 4 hr treatment by ROX prior to IRI did not improve renal function. In contrast, 24-72 hr pre-treatment by ROX largely improved the decline of renal function by IRI. Hy-poxia and 4 hr ROX increased interstitial cells-derived Epo production by 75 and 6-fold, respectively, before IRI and worked as exogenous Epo. 24-72 hr ROX treatment increased Epo production during IRI by 9-fold. Immunohistochemistry revealed that 24 hr ROX caused Epo production in proximal and distal tubules and worked as endogenous Epo. Our data show that 24-72 hr ROX-induced tubular endogenous Epo production results in renoprotection but peritubular exogenous Epo production by interstitial cells-derived in-duced by hypoxia and 4 hr ROX did not. Stimulation of tubular but not peritubular Epo production may link to renoprotection.

Hyperspectral reflectance imaging is an emerging method for rapid non-invasive quantitative screening of plant traits. This method is essential for high-throughput phenotyping and hence for accelerated breeding of crop plants as well as for precision agriculture practices. However, extraction of sensible information from reflectance images is hindered by the complexity of plant optical properties, especially when they are measured in the field. We propose using reflectance indices (Plant Senescence Reflectance Index, PSRI; Anthocyanin Reflectance Index, ARI; and spectral deconvolution) previously developed for remote sensing of vegetation and point-based reflectometers to infer the spatially resolved information on plant development and biochemical composition using ripening apple fruit as the model. Specifically, the proposed approach enables capturing data on distribution of chlorophylls and primary carotenoids as well as secondary carotenoids (both linked with fruit ripening and leaf senescence during plant development) as well as the information on spatial distribution of anthocyanins (known as stress pigments) over the plant surface. We argue that the proposed approach would enrich the phenotype assessments made on the base of reflectance image analysis with valuable information on plant physiological condition, stress acclimation state, and the progression of the plant development.

Purpose: Proximal Femur Fractures (PFFs) in elder patients lead to decreased productivity. Skilled nursing facilities (SNFs) and inpatient rehabilitation facilities (IRFs) are non-home destinations for post-discharge disposition. This study aims to evaluate the loss of independence (LOI) following PFFs and examine the economic impact it entails. Method: Literature from various databases was collected and analyzed retrospectively. The inclusion criteria included patients age >18 years and articles published after 1990. All studies were screened and a PRISMA chart was used to demonstrate the search process. 24 studies were finally used for review. Results: LOI following PFFs significantly increases with age. Fractures in geriatrics avail a significant amount of post-care resources and had longer lengths of stay. Furthermore, six pre-operative risk factors were identified for non-home disposition including age >75, female, non-Caucasian race, Medicare status, prior depression, Charlson Comorbidity Index. Patients discharged directly to home have lower total cost compared to those discharged to rehabilitation units. Loss of independence increases with advancing age. Discussion: PFFs can lead to serious loss of independence among elderly patients with direct impact on economic, social, psychological aspects and the healthcare system.

(1) Background: The chemotherapeutic drug cisplatin exerts toxic side effects causing acute kidney injury. Mesenchymal stromal cells can ameliorate cisplatin-induced kidney injury. We hypothe-size that the MSC secretome orchestrates the vicious cycle of injury and inflammation by acting on proximal tubule epithelial cells (PTECs) and macrophages individually, but further by coun-teracting their cellular crosstalk. (2) Methods: Conditioned medium (CM) from adipose stromal cells was used, first assessing its effect on cisplatin injury in PTECs. Second, effects of cisplatin and CM on macrophages were measured. Lastly, in an indirect co-culture system the interplay between the two cell types was assessed. (3) Results: First, CM rescued PTECs from cisplatin-induced apoptosis by reducing oxidative stress and expression of nephrotoxicity genes. Second, while cisplatin exerted only minor effects on macrophages, CM skewed macrophage phenotypes to the anti-inflammatory M2-like phenotype and increased phagocytosis. Finally, in the co-culture system, CM suppressed PTEC death by inhibiting apoptosis and nuclei fragmentation. CM lowered TNF-α release. While cisplatin inhibited macrophage phagocytosis, PTECs, and CM to a greater extent, enhanced it. CM strongly dampened the inflammatory macrophage cytokine secretion triggered by PTECs. (4) Conclusion: ASC-CM surpasses the PTEC-macrophage cross-talk in cisplatin injury. The positive effects on reducing cisplatin cytotoxicity, on polarizing mac-rophages and on fine-tuning cytokine secretion underscores MSCs CM benefit to prevent kidney injury progression.

Gastroesophageal (GE) junction adenocarcinoma is an aggressive malignancy of growing incidence and is associated with public health issues such as obesity and GERD. Management has evolved over the last 2 decades to incorporate a multidisciplinary approach including endoscopic intervention, and neoadjuvant chemotherapy/ chemoradiation and minimally invasive or more limited surgical approaches. Surgical approaches include esophagectomy, total gastrectomy, and more recently proximal gastrectomy. This review analyzes the evidence for and applicability of these varied approaches in management as well areas of continued controversy and investigation.

Proximal Junctional Kyphosis (PJK) as one of the most discussed problems after corrective surgery in adolescent idiopathic scoliosis (AIS), is still not fully clarified and seems to be multifactorial. Biome-chanical and few clinical studies have shown the influence of destruction of posterior ligaments by re-section of spinous processes and some parameters concerning rod contouring as risk factors for PJK. To verify these results 192 patients with AIS and corrective surgery via posterior approach between 2009 and 2017 were included. Radiographic parameters were analyzed preoperatively (preOP), postoperatively (postOP), and with a mean follow up (FU) of 27 months. The participants were divided into two groups (PJK group and non-PJK group). The incidence of PJK was 15.6%. Contrary to the results of biomechanical studies, we could not find any significant influence of the spinous process resection. However, the PJK group had significantly larger preOP T4-T12 kyphosis (31.1°±13.93° vs. 23.3°±14.93°, p=.016). Furthermore, the PJK group showed a significantly larger rod contour angle (RCA) (8.0°±4.44° vs. 5.9°±3.28°, p=.003) and mismatch of postOP proximal junctional angle (PJA) and RCA (3.5°±5.72° vs. 0.9°±4.86°, p=.010) compared to the non-PJK group. An increase of the mismatch of postOP PJA and RCA (OR=1.14, p=.008) and a high RCA are risk factors for PJK and need to be focused on by surgeons.

Acute kidney injury (AKI) caused by ischemia followed by reperfusion (I/R) is characterized by intense anion superoxide (O2•-) production and oxidative damage. We investigated whether extracellular vesicles secreted by adipose tissue mesenchymal cells (EVs) administrated during reperfusion can suppress the exacerbated mitochondrial O2•- formation after I/R. We used Wistar rats submitted to bilateral renal arterial clamping (30 min) followed by 24 h of reperfusion. The animals received EVs (I/R+EVs group) or saline, I/R group) in the kidney subcapsular space. The 3rd group was of the false-operated rats (SHAM). Mitochondria were isolated from proximal tubule cells and immediately used. Amplex Red™ was used to measure mitochondrial O2•- formation and MitoTracker® Orange to evaluate Δψ. In vitro studies were carried out by using human renal proximal tubular cells (HK-2) co-cultured or not with EVs under hypoxia conditions. Administration of EVs restored O2•- formation to SHAM levels in all mitochondrial functional conditions. The expression of catalase and superoxide dismutase remained unmodified; transcription of heme oxygenase-1 (HO-1) was upregulated. The co-cultures of HK-2 cells with EVs revealed an intense decrease in apoptosis. We conclude that the mechanisms by which EVs recover the renal structure and function after I/R are related to the normalization of the mitochondrial redox environment. The intravesicular catalase is central in the preservation mechanisms that, with the aid of the upregulated antioxidant HO-1/Nuclear factor erythroid 2-related factor 2 system, depress early processes of cell death after I/R and open new vistas for the treatment of AKI.

The proximal part of the colon offers opportunities to prolong the absorption window following oral administration of a drug. In this work, we used computer simulations to understand how the hydrodynamics in the proximal colon might affect the release from dosage forms designed to target the colon. For this purpose, we developed and compared three different models: a completely-filled colon, a partially-filled colon and a partially-filled colon with a gaseous phase present (gas-liquid model).The highest velocities of the liquid were found in the completely-filled model, which also shows the best mixing profile, defined by the distribution of tracking particles over time. No significant differences with regard to the mixing and velocity profiles were found between the partially-filled model and the gas-liquid model. The fastest transit time of an undissolved tablet was found in the completely-filled model. The velocities of the liquid in the gas-liquid model are slightly higher along the colon than in the partially-filled model. The filling level has an impact on the exsisting shear forces and shear rates, which are decisive factors in the development of new drugs and formulations.

Peptides are promising drug development frameworks thanks to their high target selectivity, tolerability and relatively low production cost. However, despite the fact that several thousand potentially therapeutic peptides reported, only sixty have arrived at the market. This concerning low proportion is partially explained by undesired properties such as peptide-induced hemolytic activity. Hence, we aim to get a better insight into the chemical space of hemolytic peptides using a novel approach based on network science and interactive data mining as an alternative to design more effective peptide drugs with low hemolytic activity. Metadata networks (METNs) were used to characterize and find general patterns associated to hemolytic peptides, whereas Half-Space Proximal Networks (HSPNs), created using five different two-way dissimilarity measures, represented the hemolytic peptide space. Then, using the best candidate HSPNs, we extracted various scaffolds that capture information of almost all the chemical space but avoiding peptide overrepresentation. Such scaffolds can have many applications, such as training accurate ML-based prediction models, constructing one-class multi-query similarity searching models and characterizing the diversity of hemolytic peptides using a manageable set of peptides. Finally, by means of an alignment-free approach, we reported 47 putative hemolytic motifs, which might provide hints about the mechanisms of hemolysis and can also be used as toxic signatures when developing novel peptide-based drugs.

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2/2019-nCoV) infection is an emerging pandemic. The virus binds to angiotensin converting enzyme 2 (ACE2) and TMPRSS2 which are abundantly expressed on various human cells including lung epithelial cells and intestinal cells and the virus can infect these cells. Currently no specific treatments or vaccines are available for this disease. A per oral live attenuated vaccine can be beneficial in SARS-Cov-2 infection because the attenuated virus initially infects the gut, stimulates the mucosa associated immune system sparing the respiratory system during the initial immune response. The live virus can also spread in the community boosting herd immunity.

We extended our model of the S1 tubular segment to address the mechanisms by which SGLT1 interacts with lateral Na/K pumps and tight junctional complexes to generate isosmotic fluid reabsorption via tubular segment S3. The strategy applied allowed simulation of laboratory experiments. Reproducing known experimental results constrained the range of acceptable model outputs and contributed to minimizing the free parameter space. 1. In experimental conditions, published Na and K concentrations of proximal kidney cells were found to deviate substantially from their normal physiological levels. Analysis of the mechanisms involved suggested insufficient oxygen supply as the cause and indirectly, that a main function of the Na/H exchanger (NHE3) is to extrude protons stemming from mitochondrial energy metabolism. 2. The water path from the lumen to the peritubular space is through aquaporins on the cell membrane and claudin-2 at paracellular tight junctions, with a smaller additional contribution to water transport by the coupling of 1 glucose:2 Na:200 H2O in SGLT1. 3. A Na+-uptake component passed through paracellular junctions by solvent drag in Na- and water-permeable claudin-2, thus bypassing the Na/K-pump, in agreement with the findings of early studies. 4. Electrical cross talk between apical rheogenic SGLT1 and lateral rheogenic Na/K pumps results in tight coupling of luminal glucose uptake and transepithelial water flow. 5. Isosmotic transport is achieved by Na-mediated ion recirculation at the peritubular membrane.

Clear cell renal cell carcinoma (ccRCC) is the most frequent form of kidney cancer. Metastatic stages of ccRCC reduce the five-year survival rate to 15%. In this report we analyze the ccRCC-induced remodeling of the five KEGG-constructed excretory functional pathways in a surgically removed right kidney and its metastasis in the chest wall from the perspective of the Genomic Fabric Paradigm (GFP). GFP characterizes every single gene in each region by the independent variables: average expression level (AVE), relative expression variability (REV) and expression correlation (COR) with each other gene. While traditional approach is limited to only AVE analysis, the novel REV analysis indicates genes whose correct expression level is critical for cell survival and proliferation. COR analysis determines the real gene networks responsible for functional pathways. The analyses covered the pathways: aldosterone-regulated sodium reabsorption, collecting duct acid secretion, endocrine and other factor-regulated sodium reabsorption, proximal tubule bicarbonate reclamation, and vasopressin-regulated water reabsorption. The present study confirms the conclusion of our previously published articles on prostate and kidney cancers that even equally graded cancer nodules from the same tumor have different transcriptomic topologies. Therefore, the personalization of the anti-cancer therapy should go beyond the individual to his/her major cancer nodules.