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Purpose: The purpose of this study was to assess clinical and functional outcomes as well as the prosthesis survival rates of the U2 Knee system in primary total knee arthroplasty (TKA) with a minimum follow-up of four years., Methods: We retrospectively analyzed 560 consecutively primary TKA performed between 2015 and 2019 due to osteoarthritis with a mean follow-up of 5.4 ± 1.1 years. The clinical outcomes were assessed using the knee society score (KSS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Radiographic outcomes were assessed using the American knee society's roentgenographic evaluation system. Prosthetic survival was calculated using the Kaplan-Meier method., Results: Postoperative KSS showed significant improvement at one year (Clinical: 37.4 ± 4.1 vs. 91.9 ± 3.7; p < 0.01; Functional: 41.2 ± 3.3 vs. 90.6 ± 4.8; p =  < 0.01), with these improvements maintained throughout the follow-up period. The WOMAC score improved from 60 ± 10.1 preoperatively to 10.9 ± 8.3 (p = 0.02) at the end of the follow-up. There were 20 (3.7%) knees with radiolucent lines around the implant (< 2 mm), and none showed evidence of loosening. There were six (1.1%) revisions-four due to prosthetic joint infections and two due to periprosthetic femur fracture. The prosthetic survival was 97.8% at the study closure., Conclusion: The U2 knee system demonstrates effective and safe performance for primary TKA with significant improvements in functional scores, patient-reported outcomes, and a promising prosthesis survival rate at mid-term follow-up. We will continue with the series analysis to assess the long-term outcomes., (© 2024. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

The management of superior cerebellar aneurysms is still controversial. Although several techniques are available, the deep localization of the lesion and the limited number of cases increase the complexity of decision-making for optimal treatment. Only a few cases of dissecting and fusiform aneurysms of the superior cerebellar artery (SCA) are described in the literature, many of which are without long follow-ups. The study aims to offer an exhaustive retrospective analysis of patients affected by SCA fusiform and dissecting aneurysms treated at our institution from 2008 to 2023, highlighting outcomes and complications. Moreover, a comprehensive narrative review was performed. A total of seven patients were treated at our institution. After a title and abstract screen, fifty-five papers met the criteria for inclusion in the review. In our case series, conservative treatment was proposed as the first therapeutic option in four cases (57.1%), while endovascular treatment (EVT) was in three cases (42.9%). A good recovery was observed in 66% of patients presenting with subarachnoid hemorrhage (SAH), while every patient without SAH achieved a good clinical outcome. A poor outcome was observed only in one patient with a dissecting aneurysm causing SAH, who also suffered a pontine infarction. In the literature review, conservative treatment was proposed as a first therapeutic option in eleven cases (16.6%), open microsurgical techniques in 19 patients (28.8%), and EVT in 31 patients (46.9%). Fatal outcome was documented in five patients (7.5%), all characterized by the rupture of the vascular lesion, while 6.1% of cases had non-fatal poor outcomes., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Together with the molecular knowledge of genes and proteins, biological images promise to significantly enhance the scientific understanding of complex cellular systems and to advance predictive and personalized therapeutic products for human health. For this potential to be realized, quality-assured bioimage data must be shared among labs at a global scale to be compared, pooled, and reanalyzed, thus unleashing untold potential beyond the original purpose for which the data was generated. There are two broad sets of requirements to enable bioimage data sharing in the life sciences. One set of requirements is articulated in the companion White Paper entitled "Enabling Global Image Data Sharing in the Life Sciences," which is published in parallel and addresses the need to build the cyberinfrastructure for sharing bioimage data (arXiv:2401.13023 [q-bio.OT], https://doi.org/10.48550/arXiv.2401.13023). Here, we detail a broad set of requirements, which involves collecting, managing, presenting, and propagating contextual information essential to assess the quality, understand the content, interpret the scientific implications, and reuse bioimage data in the context of the experimental details. We start by providing an overview of the main lessons learned to date through international community activities, which have recently made generating community standard practices for imaging Quality Control (QC) and metadata (Faklaris et al., 2022; Hammer et al., 2021; Huisman et al., 2021; Microscopy Australia , 2016; Montero Llopis et al., 2021; Rigano et al., 2021; Sarkans et al., 2021). We then provide a clear set of recommendations for amplifying this work. The driving goal is to address remaining challenges and democratize access to common practices and tools for a spectrum of biomedical researchers, regardless of their expertise, access to resources, and geographical location., Competing Interests: Conflict of Interest Statements Below are the statements shared by contributors indicating potential conflict of interest. NameStatementUlrike BoehmUB’s contribution to this manuscript is a result of her voluntary involvement with QUAREP-LiMi and BINA, and does not reflect the position of Carl Zeiss AG on this matter.Josh Mooreholds equity in Glencoe Software.Denis SchapiroDS reports funding from GSK and received honorariums from Immunai, Noetik, Alpenglow and Lunaphore.Damir SudarDSu is employed by Quantitative Imaging Systems, a commercial entity developing imaging software.Siyuan (Steven) WangFounder, shareholder, consultant of Translura, Inc

Vanishing lung syndrome (VLS) is an uncommon condition characterized by idiopathic giant bullous emphysema, resulting in the lungs appearing abnormally small on radiological scans. Some case reports have suggested a potential association between the development of this condition in young males, individuals with a history of heavy tobacco smoking, methamphetamine, and marijuana use, and those previously diagnosed with HIV. The primary diagnostic tools for vanishing lung syndrome include initial x-rays and high-resolution CT scans, which play a crucial role in confirming the diagnosis. The management of vanishing lung syndrome varies based on several factors, including the patient's functional status and the size and location of the bullae, with treatment options ranging from conservative approaches to surgical interventions. In this case report, we present the case of a 42-year-old male who was a heavy tobacco smoker, had a history of methamphetamine and marijuana use, and was previously diagnosed with HIV. He initially presented to the emergency department seeking poly-substance detoxification but was incidentally found to have giant bullous emphysema on chest imaging. After stabilizing the patient, he was discharged with instructions to follow up with a pulmonologist in two months., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Cespedes Aguirre et al.)

Background: Specimens with incorrect patient information are both a critical safety error and difficult to identify. Estimates of sample mislabelling rely on subjective identification of mislabelling, with the possibility that not all mislabelled samples are being caught., Methods: We determined the blood type of two or more complete blood count specimens with the same patient label and assessed for discrepancies. We additionally determined the rate of identified sample mislabelling for the study period., Results: We found a rate of 3.17 per 1000 discrepancies over the study period. These discrepancies most likely represent occult, or unidentified, mislabelled samples. In contrast, the rate of identified sample mislabelling was 1.15 per 1000., Conclusions: This study suggests that specimens identified as, or known to be, mislabelled represent only a fraction of those mislabelled. These findings are currently being confirmed in our laboratory and are likely generalisable to other institutions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Klebsiella pneumoniae , Escherichia coli , and Enterobacter cloacae are associated with most nosocomial infections worldwide. Although gaps remain in the knowledge of their susceptibility patterns, these are in antimicrobial stewardship. This study aimed to describe antimicrobial susceptibility profiles of the above organisms isolated from postmortem blood from stillbirths and under-five children enrolled in the Child Health and Mortality Prevention Surveillance (CHAMPS) program in Sierra Leone. This was a surveillance study of bacteria isolates from postmortem blood cultures taken within 24 h of death from stillbirths and children aged 0-59 months between March 2019 and February 2022. This was followed by identification and antibiotic sensitivity testing using Becton Dickinson Phoenix M50 (USA). Descriptive analysis was used to characterize the isolates and their antimicrobial susceptibility patterns. Of 367 isolates, K. pneumoniae was the most frequently isolated organism ( n = 152; 41.4%), followed by E. coli ( n = 40; 10.9%) and E. cloacae ( n = 35; 9.5%). Using BACTEC™ FX 40 (Franklin Lakes, NJ, USA), 367 isolates were identified from blood using bacteriological methods. Extended spectrum beta-lactamase (ESBL) was observed in 143 (94.1%) of K. pneumoniae isolates and 27 (65.5%) of E. coli isolates. Carbapenem-resistant organisms (CRO) were seen in 31 (20.4%) of K. pneumoniae and 5 (12.5%) of E. coli isolates. A multidrug resistance (MDR) pattern was most prevalent in E.cloacae (33/35; 94.3%), followed by K. pneumoniae (138/152; 90.8%). Our study showed a high prevalence of multidrug resistance among bacterial isolates in the catchment areas under surveillance by the CHAMPS sites in Sierra Leone.

This manuscript describes and summarizes the Dominantly Inherited Alzheimer Network Observational Study (DIAN Obs), highlighting the wealth of longitudinal data, samples, and results from this human cohort study of brain aging and a rare monogenic form of Alzheimer's disease (AD). DIAN Obs is an international collaborative longitudinal study initiated in 2008 with support from the National Institute on Aging (NIA), designed to obtain comprehensive and uniform data on brain biology and function in individuals at risk for autosomal dominant AD (ADAD). ADAD gene mutations in the amyloid protein precursor ( APP ), presenilin 1 ( PSEN1 ), or presenilin 2 ( PSEN2 ) genes are deterministic causes of ADAD, with virtually full penetrance, and a predictable age at symptomatic onset. Data and specimens collected are derived from full clinical assessments, including neurologic and physical examinations, extensive cognitive batteries, structural and functional neuro-imaging, amyloid and tau pathological measures using positron emission tomography (PET), flurordeoxyglucose (FDG) PET, cerebrospinal fluid and blood collection (plasma, serum, and whole blood), extensive genetic and multi-omic analyses, and brain donation upon death. This comprehensive evaluation of the human nervous system is performed longitudinally in both mutation carriers and family non-carriers, providing one of the deepest and broadest evaluations of the human brain across decades and through AD progression. These extensive data sets and samples are available for researchers to address scientific questions on the human brain, aging, and AD.

Depression is a prevalent illness among the elderly, so psychotherapeutic interventions are needed to promote health and quality of life. This literature review aims to identify trials of any psychotherapeutic interventions aimed at reducing depressive symptoms in older adults. A systematic literature review with a meta-analysis will be carried out. The following databases will be searched: CINAHL Plus with Full Text, MedicLatina, MEDLINE with Full Text, and Psychology and Behavioral Sciences Collection. To minimize bias, four reviewers will independently assess the inclusion of studies. The fifth reviewer will be responsible for disaggregating inclusion and exclusion between two authors. The results of the analysis will be grouped in a table with the characteristics of the included studies, including author, year, sample, objectives, methods, assessment instruments, psychotherapeutic interventions, results, follow-up and a data compilation scheme. This scientific article is a systematic review protocol for which the data has already been extracted and is being analyzed. Examples of possible strategies to include cognitive restructuring and mental health programs for older adults in community settings. With this clear and direct identification of psychotherapeutic interventions, it will be clearer for mental health professionals to be able to intervene effectively to promote the mental health and well-being of older adults., Prospero Registration Number: CRD42023449190., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Morgado, Silva, Agostinho, Brás, Amaro, Lusquinhos, Schneider, Fonseca, Albacar-Riobóo and Pinho.)

We have studied the allele frequencies for 23 STR autosomal loci (CSF1PO, FGA, TH01, vWA, D1S1656, D2S1338, D2S441, D3S1358, D5S818, D7S820, D8S1179, D10S1248, D12S391, D13S317, D16S539, D18S51, D19S433, D21S11; with the purpose to increase the power of discrimination, the markers Penta D, Penta E, D22S1045, TPOX and SE33 were included), from a sample of 100 unrelated individuals of Lenca ethnic group in Honduras, Central America., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Pancreatic ductal adenocarcinoma (PDAC) is an extremely lethal tumor with increasing incidence, presenting numerous clinical challenges. The histopathological examination of novel, unexplored biomarkers offers a promising avenue for research, with significant translational potential for improving patient outcomes. In this study, we evaluated the prognostic significance of ferroptosis markers (TFRC, ALOX-5, ACSL-4, and GPX-4), circadian clock regulators (CLOCK, BMAL1, PER1, PER2), and KLOTHO in a retrospective cohort of 41 patients deceased by PDAC. Immunohistochemical techniques (IHC) and multiple statistical analyses (Kaplan-Meier curves, correlograms, and multinomial linear regression models) were performed. Our findings reveal that ferroptosis markers are directly associated with PDAC mortality, while circadian regulators and KLOTHO are inversely associated. Notably, TFRC emerged as the strongest risk marker associated with mortality (HR = 35.905), whereas CLOCK was identified as the most significant protective marker (HR = 0.01832). Correlation analyses indicate that ferroptosis markers are positively correlated with each other, as are circadian regulators, which also positively correlate with KLOTHO expression. In contrast, KLOTHO and circadian regulators exhibit inverse correlations with ferroptosis markers. Among the clinical variables examined, only the presence of chronic pathologies showed an association with the expression patterns of several proteins studied. These findings underscore the complexity of PDAC pathogenesis and highlight the need for further research into the specific molecular mechanisms driving disease progression.

Objectives: This study was designed to investigate clinical differences between pediatric patients who presented with chest pain, tachycardia, and/or tachypnea who subsequently were or were not diagnosed with myocarditis. The results were used to develop a decision tree to aid in rapid diagnosis of pediatric myocarditis., Methods: A retrospective case-control study was performed using the electronic medical records of children aged 0 to 18 years between the years 2003 and 2020 with a complaint of chest pain, tachycardia, and/or tachypnea. Patients included in the study were those diagnosed with myocarditis and those with suspected myocarditis, which was ultimately ruled out. Demographic and clinical differences between the research groups were analyzed. A decision tree was rendered using the rpart (Recursive Partitioning and Regression Trees) package., Results: Four thousand one hundred twenty-five patients were screened for eligibility. Seventy-three myocarditis patients and 292 nonmyocarditis patients were included. Compared with the control group, the study group was found to have a higher mean respiratory rate (37 ± 23 vs 23 ± 7 breaths per minute) and mean heart rate (121 ± 44 vs 97 ± 25 beats per minute) and lower mean systolic and diastolic blood pressure (102 ± 27/56 ± 17 mm Hg vs 114 ± 14/67 ± 10 mm Hg). The mean white blood cell count was greater in the case group (13 ± 6 vs 10 ± 5 × 10 3 /μL). A decision tree was rendered using simple demographic and clinical variables. The accuracy of the algorithm was 85.2%, with 100% accuracy in patients aged 0 to 2.5 years and 69% in patients aged 2.5 to 18 years., Conclusion: The clinical and laboratory characteristics described in this study were similar to what is described in the literature. The decision tree may aid in the diagnosis of myocarditis in patients 2.5 years and younger. In the population aged 2.5 to 18 years, the decision tree did not constitute an adequate tool for detecting myocarditis., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Intracranial abscess (IA) causes significant morbidity and mortality. The impact of baseline frailty status on post-operative outcomes of IA patients remains largely unknown. The present study evaluated if frailty status can be used to prognosticate outcomes in IA patients., Methods: We retrospectively reviewed all IA patients undergoing craniotomy at our institution from 2011 to 2018 (N.=18). These IA patients were age and gender matched with patients undergoing craniotomy for intracranial tumor (IT), an internal control for comparison. Demographic and clinical data were collected to measure frailty, using the modified frailty index-11 (mFI-11) and pre-operative American Society of Anesthesiologists Physical Status Classification System (ASA). Post-operative complications were measured by the Clavien-Dindo Grade (CDG)., Results: No significant difference in mFI-11 or ASA score was observed between the IA and IT groups (P=0.058 and P=0.131, respectively). IA patients had significantly higher CDG as compared with the control IT patients (P<0.001). There was a trend towards increasing LOS in the IA group as compared to the IT group (P=0.053). Increasing mFI and ASA were significant predictors of LOS by multiple linear regression in the IA group (P=0.006 and P=0.001, respectively), but not in the control IT group. Neither mFI-11 nor ASA were found to be predictors for CDG in either group. Within this case-control group of patients, we found an increase for odds of having IA with increasing mFI (OR=1.838, 95% CI: 1.016-3.362, P=0.044)., Conclusions: Frail IA patients tend to have more severe postoperative complications. The mFI-11 seems to predict increased resource utilization in the form of LOS. This study provides the initial retrospective data of another neurosurgical pathology where frailty leads to significantly worse outcomes. We also found that mFI may serve as a potential risk factor for severe disease.

Borosilicate glasses are widely used for radioactive waste disposal due to their ability to incorporate a variety of contaminants and radionuclides while exhibiting high durability in various disposal scenarios. This research evaluated the dissolution of borosilicate glass using both single-pass-flow-through (ASTM C1662-18) and product consistency test (ASTM C1285-21) methods with different solutions, including a cementitious-contacted water (called grout-contacted, GC, from this point) and solutions with varying levels of dissolved cementitious species such as Si, Ca, Al. The results indicated that the presence of Ca plays a crucial role in suppressing glass corrosion, as evidenced by the slower normalized dissolution rates, which were one order of magnitude lower for boron and two orders of magnitude lower for rhenium, observed in both Ca-amended and GC solutions compared to the pH 12 buffer solution. This effect is attributed to the formation of a dense, low-porosity, and strongly bonded calcium silicate hydrate (CSH) layer on the glass surface, which implies that a glass corrosion process is influenced by ion exchange involving alkali ions Na + , K + , Ca 2+ , and hydrogen-containing species. A small number of glass particles treated in the GC solution showed minor corrosion pits in the form of shallow craters with an average diameter of approximately 500 μm. This observation is correlated with a significant reduction, 2000 to 3000 times lower, in the cumulative volume of glass pores, indicating that smaller pore voids were "sealed" in the presence of Ca 2+ ions, likely attributed to the formation of CSH precipitation or other corrosion products such as calcium carbonate saturated from the grout solution. These findings suggest that the presence of dissolved Ca in the GC solution can slow down the dissolution of borosilicate glass, contrary to the expected trend of higher dissolution rates resulting from exposure to high alkaline and thus higher pH solutions.

Prior studies have identified various determinants of differential immune responses to COVID-19. This study focused on the Ig-G anti-RBD marker, analyzing its potential correlations with sex, vaccine type, body fat percentage, metabolic risk, perceived stress, and previous COVID-19 exposure. In this study, data (available in S1 Data) were obtained from 108 participants from the ESFUERSO cohort, who completed questionnaires detailing their COVID-19 experiences and stress levels assessed through the SISCO scale. IgG anti-RBD concentrations were quantified using an ELISA assay developed by UNAM. Multiple regression analysis was employed to control for covariates, including sex, age, body fat percentage, body mass index (BMI), and perceived stress. This sample comprised young individuals (average age of 21.4 years), primarily consisting of females (70%), with a substantial proportion reporting a family history of diabetes, hypertension, or obesity. Most students had received the Moderna or Pfizer vaccines, and 91% displayed a positive anti-RBD response. A noteworthy finding was the interaction between body fat percentage and sex. In males, increased adiposity was associated with decreased Ig-G anti-RBD concentration; in females, the response increased. Importantly, this pattern remained consistent regardless of the vaccine received. No significant associations were observed for dietary habits or perceived stress variables. This research reports the impact of sex and body fat percentage on the immune response through Ig-G anti-RBD levels to COVID-19 vaccines. The implications of these findings offer a foundation for educational initiatives and the formulation of preventive policies aimed at mitigating health disparities., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Perales-Torres et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Hospital readmission rates are used for quality and pay-for-performance initiatives. To identify readmissions from administrative data, two commonly employed methods are focusing either on unplanned readmissions (used by the Centers for Medicare & Medicaid Services, CMS) or potentially avoidable readmissions (used by commercial vendors such as SQLape or 3 M). However, it is not known which of these methods has higher criterion validity and can more accurately identify actually avoidable readmissions., Objectives: A manual record review based on data from seven hospitals was used to compare the validity of the methods by CMS and SQLape., Methods: Seven independent reviewers reviewed 738 single inpatient stays. The sensitivity, specificity, positive predictive value (PPV), and F1 score were examined to characterize the ability of an original CMS method, an adapted version of the CMS method, and the SQLape method to identify unplanned, potentially avoidable, and actually avoidable readmissions., Results: Both versions of the CMS method had greater sensitivity (92/86% vs. 62%) and a higher PPV (84/91% vs. 71%) than the SQLape method, in terms of identifying their outcomes of interest (unplanned vs. potentially avoidable readmissions, respectively). To distinguish actually avoidable readmissions, the two versions of the CMS method again displayed higher sensitivity (90/85% vs. 66%), although the PPV did not differ significantly between the different methods., Conclusions: Thus, the CMS method has both higher criterion validity and greater sensitivity for identifying actually avoidable readmissions, compared with the SQLape method. Consequently, the CMS method should primarily be used for quality initiatives., (© 2024 The Author(s). Journal of Hospital Medicine published by Wiley Periodicals LLC on behalf of Society of Hospital Medicine.)

Objective : To analyze the Glycemic Risk Index (GRI) and assess their possible differences according to coefficient of variation (CV) in a cohort of real-life type 1 diabetes mellitus (DM) patient users of intermittently scanned continuous glucose monitoring (isCGM). Patients and Methods : In total, 447 adult users of isCGM with an adherence ≥70% were included in a cross-sectional study. GRI was calculated with its hypoglycemia (CHypo) and hyperglycemia (CHyper) components. Multivariate linear regression analysis was performed to evaluate the factors associated with GRI. Results: Mean age was 44.6 years (standard deviation [SD] 13.7), 57.7% being male; age of DM onset was 24.5 years (SD 14.3) and time of evolution was 20.6 years (SD 12.3). In patients with CV >36% (52.8%) versus CV ≤36% (47.2%), differences were observed in relation to GRI (18.8% [SD 1.9]; P < 0.001), CHypo (2.9% [SD 0.3]; P < 0.001), CHyper (6.3% [SD 1.4]; P < 0.001), and all classical glucometric parameters except time above range level 1. The variables that were independently associated with GRI in patient with CV >36% were time in range (TIR) (β = -1.49; confidence interval [CI:] 95% -1.63 to -1.37; P < 0.001), glucose management indicator (GMI) (β = -7.22; CI: 95% -9.53 to -4.91; P < 0.001), and CV (β = 0.85; CI: 95% 0.69 to 1.02; P < 0.001). However, in patients with CV ≤36%, the variables were age (β = 0.15; CI: 95% 0.03 to 0.28; P = 0.019), age of onset (β = -0.15; CI: 95% -0.28 to -0.02; P = 0.023), TIR (β = -1.35; CI: 95% -1.46 to -1.23; P < 0.001), GMI (β = -6.67; CI: 95% -9.18 to -4.15; P < 0.001), and CV (β = 0.33; CI: 95% 0.11 to 0.56; P = 0.004). Conclusions : In this study, the factors independently associated with metabolic control according to GRI are modified by glycemic variability.

Background: Restoring joint congruence and maintaining reduction until healing is imperative in treating tibial plateau fractures (TPF). The main objective of this study was to evaluate the feasibility of augmentation with impacted bone allograft (IBA) to prevent loss of reduction in tibial plateau fractures during healing and to evaluate its incorporation., Methods: We retrospectively analyzed all patients with an acute, closed tibial plateau fracture (Schatzker II, III, IV) treated between 2010 and 2019 with open reduction and internal fixation (ORIF) and impacted bone allograft (IBA), with a minimum follow-up of 24 months. We evaluated the postoperative radiographs by drawing a line along the tibial axis and another perpendicular to the healthy plateau to measure the reduction and subsequent behavior. The incorporation of the allograft was evaluated by radiological analysis assessing its integration, non-union, resorption, or sclerosis. We used the clinical-radiological Rasmussen system and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) to objectify the outcomes., Results: 78 TPFs were included, with a median age of 51.5 (40.7-62.2) years and a median follow-up of 66 (24-89) months. Two (2.5 %) patients presented loss of joint reduction (subsidence) during the follow-up regarding the achieved in the surgery. Seventy-six (94.7 %) patients presented integration, two (2.5 %) resorption, and one (1.3 %) sclerosis. Seventy-two (92.3 %) patients presented excellent and good results in the Rasmussen radiological score, and 72 (92.3 %) patients presented excellent or good clinical scores. The mean WOMAC at two years postoperatively was 15 ± 6.5., Conclusion: Our results demonstrate that allograft is an adjuvant in maintaining a reduction in type II, III, and IV Schatzker's tibial plateau fractures. Low rates of loss of reduction during follow-up can be expected with its use., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Delhi Orthopedic Association. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Thermal epiglottitis, a non-infectious cause of epiglottitis, is a rare entity that shares some clinical features with infectious epiglottitis. This study presents 16 years of experience in diagnosing and managing thermal epiglottitis. A retrospective descriptive study in a tertiary center in southern Israel included confirmed cases of thermal epiglottitis in children (0-18 years) between 2004 and 2020 by endoscopy. Of approximately 600,000 pediatric ER admissions between 2004 and 2020, seven children were diagnosed by endoscopy with thermal epiglottitis (mean age 24 months, 71% males). Clinical presentation included stridor, respiratory distress, and drooling. Four children had fever and elevated inflammatory markers at presentation and were treated with systemic antibiotics. All were treated with systemic steroids. The median length of stay in the PICU was five days, and four patients required intubations. All fully recovered without experiencing any sequelae.  Conclusion: Thermal epiglottitis stands as a potential contributor to acute upper airway obstruction. Although it's rarity, it should be discussed in any child with acute upper airway obstruction. It is essential to inquire directly about the accidental intake of hot beverages, particularly in cases lacking fever or elevated inflammatory markers. What is Known: • Thermal epiglottitis is a rare, non-infectious condition sharing clinical features with infectious epiglottitis. • Common presentations include stridor, respiratory distress, and drooling. What is New: • Thermal epiglottitis is a potential contributor to acute upper airway obstruction, urging consideration even in the absence of fever or elevated markers. • Direct inquiry about hot beverage intake for diagnosis is essential for diagnosis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Constipation is among the most common symptoms prompting a consultation with a paediatric gastroenterologist. While most patients will respond to lifestyle and dietary changes and conventional therapy, some may require diagnostic studies., Aim: To review the diagnostics studies used to evaluate children with functional constipation., Materials and Methods: There is no evidence to support the routine use of abdominal X-rays in the evaluation of paediatric constipation. Colon transit by radiopaque markers (ROM) should be indicated when medical history does not match clinical findings, to guide colon manometry (CM) performance and to discriminate between faecal incontinence from functional constipation and non-retentive faecal incontinence. Colon scintigraphy may be useful as an alternative to ROM. Lumbar spine MRI may be indicated to evaluate for spinal abnormalities. The role of defecography has not been properly evaluated in children. Anorectal manometry in children is indicated primarily to evaluate anal resting pressure, presence and quality of the recto-anal inhibitory reflex and simulated defecation manoeuvres. The CM is indicated to guide surgical interventions after failing medical therapy., Conclusions: The goal of these studies is to identify treatable causes of constipation. Most of these studies are designed to evaluate anatomy, transit and/or colon/rectum motility function and are primarily indicated in those who fail to respond to conventional therapy., (© 2024 John Wiley & Sons Ltd.)

The practice of recreational scuba diving has increased worldwide, with millions of people taking part each year. The aquatic environment is a hostile setting that requires human physiology to adapt by undergoing a series of changes that stress the body. Therefore, physical fitness and control of cardiovascular risk factors are essential for practicing this sport. Medical assessment is not mandatory before participating in this sport and is only required when recommended by a health questionnaire designed for this purpose. However, due to the significance of cardiovascular disease, cardiology consultations are becoming more frequent. The aim of the present consensus document is to describe the cardiovascular physiological changes that occur during diving, focusing on related cardiovascular diseases, their management, and follow-up recommendations. The assessment and follow-up of individuals who practice diving with previous cardiovascular disease are also discussed. This document, endorsed by the Clinical Cardiology Association of the Spanish Society of Cardiology (SEC) and the SEC Working Group on Sports Cardiology of the Association of Preventive Cardiology, aims to assist both cardiologists in evaluating patients, as well as other specialists responsible for assessing individuals' fitness for diving practice., (Copyright © 2024 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Understanding the genetic basis of complex diseases is one of the most important challenges in current precision medicine. To this end, Genome-Wide Association Studies aim to correlate Single Nucleotide Polymorphisms (SNPs) to the presence or absence of certain traits. However, these studies do not consider interactions between several SNPs, known as epistasis, which explain most genetic diseases. Analyzing SNP combinations to detect epistasis is a major computational task, due to the enormous search space. A possible solution is to employ deep learning strategies for genomic prediction, but the lack of explainability derived from the black-box nature of neural networks is a challenge yet to be addressed. Herein, a novel, flexible, portable, and scalable framework for network interpretation based on transformers is proposed to tackle any-order epistasis. The results on various epistasis scenarios show that the proposed framework outperforms state-of-the-art methods for explainability, while being scalable to large datasets and portable to various deep learning accelerators. The proposed framework is validated on three WTCCC datasets, identifying SNPs related to genes known in the literature that have direct relationships with the studied diseases., (© 2024. The Author(s).)

The electronic behavior of polymerized fullerite structures, ranging from one-dimensional to three-dimensional polymers, was studied using density functional theory with the hybrid Heyd-Scuseria-Ernzerhof functional and a 6-31G(d,p) basis set. The bandgap across these structures decreases with the rise of sp 3 -carbon content until metallic behavior is observed. A further increase induces a reopening of the bandgap, revealing a reentrant semiconducting behavior in this class of materials. This behavior is understood in terms of the new electronic states originated by polymeric bonding and the effect of the volume reduction on the dispersion of sp 2 -states. This study highlights the fullerite polymers as a magnificent platform to tune electronic properties., (Creative Commons Attribution license.)

Outcomes for adult patients with a high-grade glioma continue to be dismal and new treatment paradigms are urgently needed. To optimize the opportunity for discovery, we performed a phase 0/1 dose-escalation clinical trial that investigated tumor pharmacokinetics, pharmacodynamics, and single nucleus transcriptomics following combined ribociclib (CDK4/6 inhibitor) and everolimus (mTOR inhibitor) treatment in recurrent high-grade glioma. Patients with a recurrent high-grade glioma (n = 24) harboring 1) CDKN2A / B deletion or CDK4 / 6 amplification, 2) PTEN loss or PIK3CA mutations, and 3) wild-type retinoblastoma protein (Rb) were enrolled. Patients received neoadjuvant ribociclib and everolimus treatment and no dose-limiting toxicities were observed. The median unbound ribociclib concentrations in Gadolinium non-enhancing tumor regions were 170 nM (range, 65 - 1770 nM) and 634 nM (range, 68 - 2345 nM) in patients receiving 5 days treatment at the daily dose of 400 and 600 mg, respectively. Unbound everolimus concentrations were below the limit of detection (< 0.1 nM) in both enhancing and non-enhancing tumor regions at all dose levels. We identified a significant decrease in MIB1 positive cells suggesting ribociclib-associated cell cycle inhibition. Single nuclei RNAseq (snRNA) based comparisons of 17 IDH-wild-type on-trial recurrences to 31 IDH-wild-type standard of care treated recurrences data demonstrated a significantly lower fraction of cycling and neural progenitor-like (NPC-like) malignant cell populations. We validated the CDK4/6 inhibitor-directed malignant cell state shifts using three patient-derived cell lines. The presented clinical trial highlights the value of integrating pharmacokinetics, pharmacodynamics, and single nucleus transcriptomics to assess treatment effects in phase 0/1 surgical tissues, including malignant cell state shifts. ClinicalTrials.gov identifier: NCT03834740 .

Background: Tebentafusp, a bispecific (gp100×CD3) ImmTAC, significantly improved overall survival (OS) outcomes for HLA-A*02:01+ adult patients with untreated metastatic uveal melanoma (mUM) and showed promising survival in previously treated mUM with 1-year OS of 62% in the primary analysis of study IMCgp100-102. Here we report long-term outcomes from this phase 1/2 study in pretreated mUM., Patients and Methods: Patients with previously treated mUM received tebentafusp weekly intravenous at 20 µg dose 1, 30 µg dose 2 and either 54, 64, 68, or 73 µg (phase 1) or 68 µg (phase 2) dose 3+. The primary objective was overall response rate. Secondary objectives included OS and safety. OS was estimated by Kaplan-Meier methods. Association between OS and baseline covariates, on-treatment Response Evaluation Criteria in Solid Tumors (RECIST) response, baseline tumor biopsy and circulating-tumor DNA (ctDNA) changes were assessed., Results: 146 patients were treated with tebentafusp: 19 in phase 1 and 127 in phase 2. With a median follow-up duration of 48.5 months, the median OS was 17.4 months (95% CI, 13.1 to 22.8), and the 1-year, 2-year, 3-year and 4-year OS rates were 62%, 40%, 23% and 14%, respectively. Improved survival was associated with lower ctDNA baseline levels and greater ctDNA reductions by week 9 on-treatment, with 100% 1-year, 73% 2-year and 45% 3-year OS rates for patients with ctDNA clearance. Baseline gp100 expression was not associated with survival, despite more RECIST responses among patients with higher expression. No new safety signals were reported with long-term dosing., Conclusions: This study represents the longest follow-up of a Tcell receptor bispecific to date and confirms the durable survival benefits achieved with tebentafusp in previously treated mUM with good tolerability long-term. A role for ctDNA reduction as an early indicator of clinical benefit was again suggested for patients treated with tebentafusp., Competing Interests: Competing interests: JJS discloses PI on clinical trial: Amgen, AstraZeneca, Bristol-Myers Squibb, Delcath Systems, Merck, Replimune, Transgene; Research Grant/Contract: AstraZeneca, Bristol-Myers Squibb, Immunocore; Consultant/Advisory Board: Bristol-Myers Squibb, Delcath Systems, Immunocore, Merck; Congress attendance: Bristol-Myers Squibb, Merck. RDC discloses Consultant: Aura Biosciences, Castle Biosciences, Chimeron, Immunocore, InxMed, Iovance, Merck, Oncosec, Pierre Fabre Pharmaceuticals Inc., PureTech Health, Regeneron Pharmaceuticals, Rgenix, Sanofi Genzyme, Sorrento Therapeutics, TriSalus; Stock Option: Aura Biosciences, Chimeron, Rgenix. MOB discloses Consultant/Advisory Board: Adaptimmune, Bristol-Myers Squibb Canada, GlaxoSmithKline, Immunocore, Instil Bio, Iovance Biotherapeutics, Merck, Novartis, Pfizer, Sanofi Pasteur Inc., Sun Pharma, IDEAYA Bio, Medison, Regeneron and Iovance.; Safety Review Committee: GlaxoSmithKline, Adaptimmune; Research Funding: Merck, Takara Bio, Novartis. ANS discloses Grant/Contract: Bristol-Myers Squibb, Immunocore, Novartis, Targovax, Pfizer, Alkermes, Checkmate Pharmaceuticals, Foghorn Therapeutics, Linnaeus Therapeutics, Prelude Therapeutics, Iovance Biotherapeutics, Bristol-Myers Squibb, Immunocore, Novartis, Pfizer, Polaris, Xcovery. JCH discloses Speaker: Amgen, Bristol-Myers Squibb, GSK, Immunocore, Merck Sharp and Dohme, Novartis Pharma, Pierre Fabre, Sanofi-Aventis U.S. LLC; Sunpharma; Research grant/contract: Bristol-Myers Squibb, Sanofi, Sunpharma; Consultant/Advisory Board: Bristol-Myers Squibb, GSK, Immunocore, Merck Sharp and Dohme, Novartis Pharma, Pierre Fabre Pharmaceuticals Inc., Philogen, Onkowissen, Sanofi-Aventis U.S. LLC, Sun Pharmaeutical Industries Inc. AI discloses Research Funding to Institution: Dynavax, GSK/Sarah Cannon, Immunocore, Merck, Neon Therapeutics/Sarah Cannon, Checkmate Pharmaceuticals. LH-A discloses Advisory/Consulting: BMS, Castle Bioscience; Research Funding to Institution: BMS, AstraZeneca, Merck, Amgen, Roche, Regeneron, Novartis, Immunocore, Merck-EMD, Corvus, Polynoma, Genentech, Foghorn. PN discloses Data and Safety Monitoring: 4SC, Achilles; Consultant/Advisory Board: 4SC, Bristol-Myers Squibb, Immunocore, Merck, Merck Sharp and Dohme, Novartis, Pfizer; Research Grant/Contract: Immunocore. OH discloses Contract: Aduro biotech, Akeso biotech, Amgen Inc., Beigene Ltd, Bioatla, Bristol-Myers Squibb, Genentech USA, Inc., GlaxoSmithKline, Idera Pharmaceuticals, Immunocore, Incyte Corporation, Janssen Global Services, LLC, Merck, Next Cure Inc., Novartis, Pfizer, Regeneron Pharmaceuticals Inc., Sanofi, Seattle Genetics, Tempus, Zelluna Immunotherapy; Contracted Research for Institution: Aduro biotech, Akeso biotech, Amgen Inc., Arcus Biosciences, Bioatla, Bristol-Myers Squibb, CytomX Therapeutics, Exelixis Inc., Genentech, GlaxoSmithKline, Idera Pharmaceuticals, Immunocore, Incyte Corporation, Iovance Biotherapeutics, Merck, Merck Serono, Moderna, NextCure Inc., Novartis, Pfizer, Regeneron Pharmaceuticals, Sanofi Genzyme, Seattle Genetics, Torque Pharma, Zelluna Immunotherapy; Speakers Bureau: Bristol-Myers Squibb, Novartis, Pfizer. MR discloses employment and stock ownership in Syapse Inc. DBJ discloses Advisory Boards/Consultant: Bristol-Myers Squibb, Catalyst Biopharma, Iovance, Jansen, Mallinckrodt, Merck, Mosaic ImmunoEngineering, Novartis, Oncosec, Pfizer, Targovax, and Teiko; Research Funding: Bristol-Myers Squibb, Incyte. JJL discloses DSMB: AbbVie, Agenus, Amgen, Immutep, Evaxion; Scientific Advisory Board: (no stock) 7 Hills, Affivant, Bright Peak, Exo, Fstar, Inzen, RefleXion, Xilio (stock) Actym, Alphamab Oncology, Arch Oncology, Duke Street Bio, Kanaph, Mavu, NeoTx, Onc.AI, OncoNano, physIQ, Pyxis, Saros, STipe, Tempest; Consultancy with compensation: AbbVie, Agenus, Alnylam, Atomwise, Bayer, Bristol-Myers Squibb, Castle, Checkmate, Codiak, Crown, Cugene, Curadev, Day One, Eisai, EMD Serono, Endeavor, Flame, G1 Therapeutics, Genentech, Gilead, Glenmark, HotSpot, Kadmon, KSQ, Janssen, Ikena, Inzen, Immatics, Immunocore, Incyte, Instil, IO Biotech, Macrogenics, Merck, Mersana, Nektar, Novartis, Partner, Pfizer, Pioneering Medicines, PsiOxus, Regeneron, Replimmune, Ribon, Roivant, Servier, STINGthera, Synlogic, Synthekine; Research Support: (all to institution for clinical trials unless noted) AbbVie, Astellas, AstraZeneca, Bristol-Myers Squibb, Corvus, Day One, EMD Serono, Fstar, Genmab, Ikena, Immatics, Incyte, Kadmon, KAHR, Macrogenics, Merck, Moderna, Nektar, Next Cure, Numab, Palleon, Pfizer, Replimmune, Rubius, Servier, Scholar Rock, Synlogic, Takeda, Trishula, Tizona, Xencor; Patents: (both provisional) Serial #15/612,657 (Cancer Immunotherapy), PCT/US18/36052 (Microbiome Biomarkers for Anti-PD-1/PD-L1 Responsiveness: Diagnostic, Prognostic and Therapeutic Uses Thereof). EE discloses Advisory Boards/Consultant: Immunocore. SL discloses Consulting: Bayer, Immunocore; Expenses: Bayer. LC discloses Employment and Stock: Immunocore. CH discloses Stock: Amgen Inc., Macrogenics; Employment: Immunocore. TS discloses advisory/consulting: Immunocore, Castle Biosciences; research funding to institution (clinical trials): Immunocore, Verastem, IDEAYA, TriSalus, and BMS., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Overuse of antimicrobials has greatly contributed to the increase in the emergence of multidrug-resistant bacteria, a situation that hinders the control and treatment of infectious diseases. This is the case with urinary tract infections (UTIs), which represent a substantial percentage of worldwide public health problems, thus the need to look for alternatives for their control and treatment. Previous studies have shown the usefulness of autologous bacterial lysates as an alternative for the treatment and control of UTIs. However, a limitation is the high cost of producing individual immunogens. At the same time, an important aspect of vaccines is their immunogenic amplitude, which is the reason why they must be constituted of diverse antigenic components. In the case of UTIs, the etiology of the disease is associated with different bacteria, and even Escherichia coli , the main causal agent of the disease, is made up of several antigenic variants. In this work, we present results on the study of a bacterial lysate composed of 10 serotypes of Escherichia coli and by Klebsiella pneumoniae , Klebsiella aerogenes , Enterococcus faecalis , Proteus mirabilis , Citrobacter freundii , and Staphylococcus haemolyticus . The safety of the compound was tested on cells in culture and in an animal model, and its immunogenic capacity by analysing in vitro human and murine macrophages (cell line J774 A1). The results show that the polyvalent lysate did not cause damage to the cells in culture or alterations in the animal model used. The immunostimulatory activity assay showed that it activates the secretion of TNF-α and IL-6 in human macrophages and TNF-α in murine cells. The obtained results suggest that the polyvalent lysate evaluated can be an alternative for the treatment and control of chronic urinary tract infections, which will reduce the use of antimicrobials.

Diagnosis and management of fungal infections are challenging in both animals and humans, especially in immunologically weakened hosts. Due to its broad spectrum and safety profile when compared to other antifungals, itraconazole (ITZ) has been widely used in the treatment and prophylaxis of fungal infections, both in human and veterinary medicine. The dose and duration of management depend on factors such as the type of fungal pathogen, the site of infection, sensitivity to ITZ, chronic stages of the disease, the health status of the hosts, pharmacological interactions with other medications and the therapeutic protocol used. In veterinary practice, ITZ doses generally vary between 3 mg/kg and 50 mg/kg, once or twice a day. In humans, doses usually vary between 100 and 400 mg/day. As human and veterinary fungal infections are increasingly associated, and ITZ is one of the main medications used, this review addresses relevant aspects related to the use of this drug in both clinics, including case reports and different clinical aspects available in the literature., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Masson SAS.)

Background: Two distinct histological growth patterns (HGPs) were described in patients with peritoneal metastasis of colorectal cancer origin (PMCRC) with limited Peritoneal Cancer Index (PCI) ≤ 6 who did not receive neoadjuvant chemotherapy (NAC) and were treated with cytoreductive surgery (CRS) ± hyperthermic intraperitoneal chemotherapy (HIPEC): pushing HGP (P-HGP) and infiltrating HGP (I-HGP). Patients with dominant P-HGP (> 50%) had significantly better disease-free survival (DFS) and overall survival (OS)., Objective: We aimed to determine whether these previous observations regarding the prognostic value of HGP in patients with PMCRC with low PCI (≤ 6) are also valid in all operable patients, regardless of whether they received NAC or not and regardless of PCI score., Methods: This was a retrospective study including 76 patients who underwent complete CRS ± HIPEC for PMCRC between July 2012 and March 2019. In each patient, up to five of the largest excised peritoneal nodules were analyzed for their tumor-to-peritoneum interface. Correlations between NAC, HGP, and prognosis were further explored., Results: Thirty-seven patients (49%) had dominant P-HGP and 39 (51%) had dominant I-HGP. On univariate analysis, patients with P-HGP ≤ 50% had significantly lower OS than those with dominant P-HGP > 50% (39 versus 60 months; p = 0.014) confirmed on multivariate analysis (hazard ratio 2.4, 95% confidence interval 1.3-4.5; p = 0.006). There were no significant associations between NAC and type of HGP., Conclusions: This study confirms the prognostic value and reproducibility of the two previously reported HGPs in PMCRC. Dominant P-HGP is associated with better DFS and OS in patients undergoing curative-intent CRS ± HIPEC compared with I-HGP, independently of the extent of peritoneal disease burden., (© 2024. The Author(s).)

Introduction: Serological surveys offer the most direct measurement to define the immunity status for numerous infectious diseases, such as COVID-19, and can provide valuable insights into understanding transmission patterns. This study describes seroprevalence changes over time in the context of the Democratic Republic of Congo, where COVID-19 case presentation was apparently largely oligo- or asymptomatic, and vaccination coverage remained extremely low., Methods: A cohort of 635 health care workers (HCW) from 5 health zones of Kinshasa and 670 of their household members was interviewed and sampled in 6 rounds between July 2020 and January 2022. At each round, information on risk exposure and a blood sample were collected. Serology was defined as positive when binding antibodies against SARS-CoV-2 spike and nucleocapsid proteins were simultaneously present., Results: The SARS-CoV-2 antibody seroprevalence was high at baseline, 17.3% (95% CI 14.4-20.6) and 7.8% (95% CI 5.5-10.8) for HCW and household members, respectively, and fluctuated over time, between 9% and 62.1%. Seropositivity was heterogeneously distributed over the health zones (p < 0.001), ranging from 12.5% (95% CI 6.6-20.8) in N'djili to 33.7% (95% CI 24.6-43.8) in Bandalungwa at baseline for HCW. Seropositivity was associated with increasing rounds adjusted Odds Ratio (aOR) 1.75 (95% CI 1.66-1.85), with increasing age aOR 1.11 (95% CI 1.02-1.20), being a female aOR 1.35 (95% CI 1.10-1.66) and being a HCW aOR 2.38 (95% CI 1.80-3.14). There was no evidence that HCW brought the COVID-19 infection back home, with an aOR of 0.64 (95% CI 0.46-0.91) of seropositivity risk among household members in subsequent surveys. There was seroreversion and seroconversion over time, and HCW had a lower risk of seroreverting than household members (aOR 0.60 (95% CI 0.42-0.86))., Conclusion: SARS-CoV-2 IgG antibody levels were high and dynamic over time in this African setting with low clinical case rates. The absence of association with health profession or general risk behaviors and with HCW positivity in subsequent rounds in HH members, shows the importance of the time-dependent, and not work-related, force of infection. Cohort seroprevalence estimates in a 'new disease' epidemic seem insufficient to guide policy makers for defining control strategies., (© 2024. The Author(s).)

Acute kidney injury (AKI) is defined as an injury to the renal parenchyma, with or without a decrease in kidney function, as reflected by accumulation of uremic toxins or altered urine production (i.e., increased or decreased). AKI might result from any of several factors, including ischemia, inflammation, nephrotoxins, and infectious diseases. AKI can be community- or hospital-acquired. The latter was not previously considered a common cause for AKI in animals; however, recent evidence suggests that the prevalence of hospital-acquired AKI is increasing in veterinary medicine. This is likely due to a combination of increased recognition and awareness of AKI, as well as increased treatment intensity (e.g., ventilation and prolonged hospitalization) in some veterinary patients and increased management of geriatric veterinary patients with multiple comorbidities. Advancements in the management of AKI, including the increased availability of renal replacement therapies, have been made; however, the overall mortality of animals with AKI remains high. Despite the high prevalence of AKI and the high mortality rate, the body of evidence regarding the diagnosis and the management of AKI in veterinary medicine is very limited. Consequently, the International Renal Interest Society (IRIS) constructed a working group to provide guidelines for animals with AKI. Recommendations are based on the available literature and the clinical experience of the members of the working group and reflect consensus of opinion. Fifty statements were generated and were voted on in all aspects of AKI and explanatory text can be found either before or after each statement., (Copyright © 2024. Published by Elsevier Ltd.)

The connection between physical activity and cognitive function has become a focus of attention in educational research in recent years. Regular exercise has been shown to have significant positive effects on physical health, but it also appears to have a significant impact on cognitive function and academic performance. Of all the exercise modalities, resistance training has drawn interest for its ability to improve cerebral abilities in addition to physical well-being. However, there is limited available knowledge exploring the relationship between resistance training regimens and academic performance. This narrative review aims to investigate the underlying mechanisms linking resistance training to academic performance. Firstly, we will examine the biological mechanisms and psychosocial links that potentially connect resistance training to academic performance to find and describe the different mechanisms by which resistance training improves academic performance. In the next part of the work, we delve into the existing observational and intervention studies that have explored the relationship between resistance training and academic performance. Lastly, we provide practical recommendations for including resistance training in institutional education settings, emphasizing the need of dispelling myths and addressing barriers to increase participation as well as the relevance of considering key training variables and adaptation of protocols to developmental stages, always guided by a properly trained professional. Overall, the available evidence supports that resistance training provides potential benefits to the academic performance of youth students with many biological and psychosocial factors that explain this relationship. However, most of the studies are observational, and broader interventional studies are needed to understand and maximize the benefits of this type of physical exercise., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Fraile-Martinez, García-Montero, Fraile-Martinez, Pekarek, Barrena-Blázquez, López-González, Álvarez-Mon, Pekarek, Casanova, Álvarez-Mon, Diaz, Saez and Ortega.)

Background: This study examined population genetics of Aedes aegypti in El Salvador and Honduras, two adjacent countries in Central America. Aedes aegypti is associated with yellow fever, dengue, chikungunya, and Zika. Each year, thousands of cases of dengue are typically reported in El Salvador and Honduras., Methods: In El Salvador, collections were obtained from five Departments. In Honduras, samples were obtained from six municipalities in four Departments. Mitochondrial DNA cytochrome oxidase I (COI) was sequenced, and consensus sequences were combined with available sequences from El Salvador to determine haplotype number, haplotype diversity, nucleotide diversity, and Tajima's D. A haplotype network was produced to examine the relationship between genotypes., Results: In El Salvador, there were 17 haplotypes, while in Honduras there were 4 haplotypes. In both El Salvador and Honduras, Haplotype 1 is most abundant and widespread. In El Salvador, haplotype H2 was also widespread in 10 of 11 sampled municipalities, but it was not present in Honduras. The capital of El Salvador (San Salvador) and the eastern region of ES had the highest haplotype diversity of regions sampled., Conclusions: Haplotype 1 and H2 each belong to different phylogenetic lineages of Ae. aegypti. The most geographically widespread haplotype (H1) may have been present the longest and could be a remnant from previous eradication programs. These data may contribute to future control programs for Ae. aegypti in the two countries., (© 2024. The Author(s).)

Scientific research of artificial intelligence (AI) in dermatology has increased exponentially. The objective of this study was to perform a systematic review and meta-analysis to evaluate the performance of AI algorithms for skin cancer classification in comparison to clinicians with different levels of expertise. Based on PRISMA guidelines, 3 electronic databases (PubMed, Embase, and Cochrane Library) were screened for relevant articles up to August 2022. The quality of the studies was assessed using QUADAS-2. A meta-analysis of sensitivity and specificity was performed for the accuracy of AI and clinicians. Fifty-three studies were included in the systematic review, and 19 met the inclusion criteria for the meta-analysis. Considering all studies and all subgroups of clinicians, we found a sensitivity (Sn) and specificity (Sp) of 87.0% and 77.1% for AI algorithms, respectively, and a Sn of 79.78% and Sp of 73.6% for all clinicians (overall); differences were statistically significant for both Sn and Sp. The difference between AI performance (Sn 92.5%, Sp 66.5%) vs. generalists (Sn 64.6%, Sp 72.8%), was greater, when compared with expert clinicians. Performance between AI algorithms (Sn 86.3%, Sp 78.4%) vs expert dermatologists (Sn 84.2%, Sp 74.4%) was clinically comparable. Limitations of AI algorithms in clinical practice should be considered, and future studies should focus on real-world settings, and towards AI-assistance., (© 2024. The Author(s).)

Embryo transfer (ET) in bovines was created with the purpose of increasing the pregnancy rate (PR) of animals with high genetic value; however, multiple factors have been found to affect the success of this reproductive biotechnology. These factors are frequently grouped in intrinsic and extrinsic factors. Thus, the objective of the present experiments was to assess the effect of intrinsic and extrinsic factors on the pregnancy rate under tropical conditions. To do this a total of 648 embryo transfer (ET) procedures were performed between January and December 2021. The intrinsic factors were size and location of the corpus luteum, body condition, genetic group, age and parity; while extrinsic factors were location of the farm, environmental comfort, season in which the ET was carried out, prevailing weather conditions, and the preservation, quality, and the development stage of embryos at the time of ET. A χi 2 was used for analysis of main effects, and logistic regression analysis to calculate the probability of pregnancy and the association between intrinsic or extrinsic factors; additionally, a multivariate analysis of data clusters was used to find a linkage between the effects. While recipient female age had a negative effect (Odds ratio = 0.345-0.871) on PR (p < 0.05), being higher in younger cows, the rest of the intrinsic factors did not affect the PR. The significant (p < 0.05) extrinsic factors were THI category, season of year and type of embryo preservation, showing that the highest PR (p < 0.05) was obtained in the comfort THI category, during the winter season and using fresh embryos for transfer. The clustering analysis did not show any linkage between PR and intrinsic factors, while a linkage (p < 0.05) was found with season of the year and embryo preservation as extrinsic factors. It is concluded that age of the recipient cow and environmental conditions at the time of the embryo transfer are key factors to be considered for a successful pregnancy rate from in-vitro ET programs using dual-purpose cows under tropical conditions., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Several screening strategies for identifying congenital CMV (cCMV) have been proposed; however, the optimal solution has yet to be determined. We aimed to determine the prevalence of cCMV by universal screening with saliva pool testing and to identify the clinical variables associated with a higher risk of cCMV to optimize an expanded screening strategy., Methods: We carried out a prospective universal cCMV screening (September/2022 to August/2023) of 2186 newborns, analyzing saliva samples in pools of five (Alethia-LAMP-CMV ® ) and then performed confirmatory urine CMV RT-PCR. Infants with risk factors (small for gestational age, failed hearing screening, HIV-exposed, born to immunosuppressed mothers, or <1000 g birth weight) underwent expanded screening. Multivariate analyses were used to assess the association with maternal/neonatal variables., Results: We identified 10 infants with cCMV (prevalence: 0.46%, 95% CI 0.22-0.84), with significantly higher rates (2.1%, 95% CI 0.58-5.3) in the high-risk group ( p = 0.04). False positives occurred in 0.09% of cases. No significant differences in maternal/neonatal characteristics were observed, except for a higher prevalence among infants born to non-Chilean mothers ( p = 0.034), notably those born to Haitian mothers (1.5%, 95% CI 0.31-4.34), who had higher odds of cCMV (OR 6.82, 95% CI 1.23-37.9, p = 0.04). Incorporating maternal nationality improved predictive accuracy (AUC: 0.65 to 0.83)., Conclusions: For low-prevalence diseases such as cCMV, universal screening with pool testing in saliva represents an optimal and cost-effective approach to enhance diagnosis in asymptomatic patients. An expanded screening strategy considering maternal nationality could be beneficial in resource-limited settings.

Preeclampsia, a serious and potentially life-threatening medical complication occurring during pregnancy, is characterized by hypertension and often accompanied by proteinuria and multiorgan dysfunction. It is classified into two subtypes based on the timing of diagnosis: early-onset (EO-PE) and late-onset preeclampsia (LO-PE). Despite being less severe and exhibiting distinct pathophysiological characteristics, LO-PE is more prevalent than EO-PE, although both conditions have a significant impact on placental health. Previous research indicates that different pathophysiological events within the placenta may contribute to the development of preeclampsia across multiple pathways. In our experimental study, we investigated markers of oxidative stress, ferroptosis, and lipid peroxidation pathways in placental tissue samples obtained from women with LO-PE ( n = 68) compared to healthy control pregnant women (HC, n = 43). Through a comprehensive analysis, we observed an upregulation of specific molecules associated with these pathways, including NADPH oxidase 1 (NOX-1), NADPH oxidase 2 (NOX-2), transferrin receptor protein 1 (TFRC), arachidonate 5-lipoxygenase (ALOX-5), acyl-CoA synthetase long-chain family member 4 (ACSL-4), glutathione peroxidase 4 (GPX4) and malondialdehyde (MDA) in women with LO-PE. Furthermore, increased ferric tissue deposition (Fe 3+ ) was observed in placenta samples stained with Perls' Prussian blue. The assessment involved gene and protein expression analyses conducted through RT-qPCR experiments and immunohistochemistry assays. Our findings underscore the heightened activation of inflammatory pathways in LO-PE compared to HC, highlighting the pathological mechanisms underlying this pregnancy disorder.

Background/Objective: Diabetes registries that enhance surveillance and improve medical care are uncommon in low- and middle-income countries, where most of the diabetes burden lies. We aimed to describe the methodological and technical aspects adopted in the development of a municipal registry of people with diabetes using local and national Brazilian National Health System databases. Methods: We obtained data between July 2018 and June 2021 based on eight databases covering primary care, specialty and emergency consultations, medication dispensing, outpatient exam management, hospitalizations, and deaths. We identified diabetes using the International Classification of Disease (ICD), International Classification of Primary Care (ICPC), medications for diabetes, hospital codes for the treatment of diabetes complications, and exams for diabetes management. Results: After data processing and database merging using deterministic and probabilistic linkage, we identified 73,185 people with diabetes. Considering that 1.33 million people live in Porto Alegre, the registry captured 5.5% of the population. Conclusions: With additional data processing, the registry can reveal information on the treatment and outcomes of people with diabetes who are receiving publicly financed care in Porto Alegre. It will provide metrics for epidemiologic surveillance, such as the incidence, prevalence, rates, and trends of complications and causes of mortality; identify inadequacies; and provide information. It will enable healthcare providers to monitor the quality of care, identify inadequacies, and provide feedback as needed.

In vitro induced T regulatory cells (iTregs) are promising for addressing inflammation-driven diseases. However, current protocols for the generation and expansion of iTregs fail to induce extensive demethylation of the Treg-specific demethylated region (TSDR) within the FOXP3 gene, recognized as the master regulator for regulatory T cells (Tregs). This deficiency results in the rapid loss of Foxp3 expression and an unstable regulatory phenotype. Nevertheless, inhibition of STAT6 signaling effectively stabilizes Foxp3 expression in iTregs. Thus, this study aimed to develop a protocol combining epigenetic editing with STAT6 deficiency to improve iTregs' ability to maintain stable suppressive function and a functional phenotype. Our findings demonstrate that the combination of STAT6 deficiency (STAT6-/-) with targeted demethylation of the TSDR using a CRISPR-TET1 tool leads to extensive demethylation of FOXP3-TSDR. Demethylation in STAT6-/- iTregs was associated with enhanced expression of Foxp3 and suppressive markers such as CTLA-4, PD-1, IL-10, and TGF-β. Furthermore, the edited STAT6-/- iTregs exhibited an increased capacity to suppress CD8+ and CD4+ lymphocytes and could more efficiently impair Th1-signature gene expression compared to conventional iTregs. In conclusion, the deactivation of STAT6 and TSDR-targeted demethylation via CRISPR-TET1 is sufficient to induce iTregs with heightened stability and increased suppressive capacity, offering potential applications against inflammatory and autoimmune diseases., (© 2024. The Author(s).)

GH-secreting tumors represent 15 % to 20 % of all pituitary neuroendocrine tumors (pitNETs), of which 95 % occur in a sporadic context, without an identifiable inherited cause. Recent multi-omic approaches have characterized the epigenomic, genomic, transcriptomic, proteomic and kynomic landscape of pituitary tumors. Transcriptomic analysis has allowed us to discover specific transcription factors driving the differentiation of pituitary tumors and gene expression patterns. GH-secreting, along with PRL- and TSH-secreting pitNETs are driven by POU1F1; ACTH-secreting tumors are determined by TBX19; and non-functioning tumors, which are predominantly of gonadotrope differentiation are conditioned by NR5A1. Upregulation of certain miRNAs, such as miR-107, is associated with tumor progression, while downregulation of others, like miR-15a and miR-16-1, correlates with tumor size reduction. Additionally, miRNA expression profiles are linked to treatment resistance and clinical outcomes, providing insights into potential therapeutic targets. Specific somatic mutations in GNAS, PTTG1, GIPR, HGMA2, MAST and somatic variants associated with cAMP, calcium signaling, and ATP pathways have also been associated with the development of acromegaly. This review focuses on the oncogenic mechanisms by which sporadic acromegaly can develop, covering a complex series of molecular alterations that ultimately alter the balance between proliferation and apoptosis, and dysregulated hormonal secretion., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest in the making of this article. None of the authors have any financial or personal relationships with individuals or organizations that could potentially bias the results or interpretation of this review., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Acne is a chronic inflammatory disorder of the pilosebaceous unit that is associated with a negative impact on quality of life, causing anxiety, depression, and poor self-esteem. The treatment of acne is not simple and presents some new challenges. This article addresses important issues faced by dermatologists on their daily, some of them specific for Latin America., Objective: To discuss daily practice recommendations when managing acne patients., Methods: A literature review was conducted by a group of eight experts with extensive experience in the field of acne. The results of the data review were presented at an initial kick-off meeting to align the consensus topics. Two e-surveys using the Delphi methodology and an interim group webinar meeting were held., Results: The expert panel reached a consensus on all proposed key statements, providing scientific support to help dermatologists and healthcare providers make acne management decisions on topics that can be challenging in the everyday practice of dermatology, such as the characteristics of Generation Z or the importance of the maintenance phase of adult acne treatment., Conclusion: This article provides current recommendations for managing acne patients. The high level of agreement achieved based on the latest evidence supports the best acne therapeutic choices in both established topics and new important issues that have emerged in recent years, such as the impact of social media, Generation Z characteristics, and transgender male patient specifics., (Copyright © 2024 Sociedade Brasileira de Dermatologia. Published by Elsevier España, S.L.U. All rights reserved.)

Heat stress (HS) during the dry period of dairy cows in hot and dry conditions compromises the physiological status and mammary gland development of dairy cows, thereby negatively affecting milk component yield in the subsequent lactation. Our objective was to evaluate the effects of cooling Holstein cows under moderate or higher HS conditions (i.e., ambient temperature higher than 30 °C, with a temperature-humidity index of 78.2 units) during the dry period on prepartum physiological status, postpartum productivity, and calf growth. Twenty-four multiparous Holstein cows were divided into two groups: one with a cooling system based on spray and fans under a pen shade (CL, n = 12) and the other not-cooled (NC, n = 12). The cooling system operated 10 h/d (09:00-19:00 h) for 60 d prepartum. During the morning, rectal temperature and respiration frequency were lower in CL cows, but not in the afternoon, which was attributed to higher (P < 0.01) dry matter intake by CL cows. Total serum protein was higher (P < 0.01) in CL cows, but hemoglobin was higher in NC cows (P < 0.01), with no differences in other electrolytes, hormones, hematological components, and metabolites. Milk fat and fat and fat-protein corrected milk were higher (P < 0.05) in CL cows. Female and birth weight trended (P = 0.08) to be higher in CL cows. Cooling cows during the dry period had a limited effect on physiology prepartum but increased postpartum productivity of Holstein cows under hot and dry conditions., (© 2024. The Author(s) under exclusive licence to International Society of Biometeorology.)

This study aimed to determine the influence of heat stress during the dry period on milk yield and reproductive performance of Holstein cows in a hot environment. Breeding and milk production records of cows, as well as meteorological data between 2017 and 2020 from a commercial dairy herd (n = 12,102 lactations), were used to determine the relationship between climatic conditions during the dry period (average of the temperature-humidity index (THI) at the beginning, middle, and end of the dry period) and reproductive efficiency and milk yield traits. THI was divided into < 70 (no heat stress), 70-80 (moderate heat stress), and > 80 (severe heat stress). First-service pregnancy rate of cows decreased (P < 0.01) with increasing hyperthermia during the dry period (9.5, 7.3, and 3.4% for THI < 70, 70-80, and > 80, respectively). All-service pregnancy rate was highest (P < 0.01) for cows not undergoing heat stress during the dry period (60.2%) and lowest (42.6%) for cows with severe heat stress during the dry period. Cows not experiencing heat stress during the dry period required a mean ± SD of 5.6 ± 3.8 services per pregnancy compared with 6.5 ± 3.6 (P < 0.01) for cows subjected to THI > 80 during the dry period. Cows not suffering heat stress during the dry period produced more (P < 0.01) 305-day milk (10,926 ± 1206 kg) than cows subjected to moderate (10,799 ± 1254 kg) or severe (10,691 ± 1297 kg) heat stress during the dry period. Total milk yield did not differ (P > 0.10) between cows not undergoing heat stress (13,337 ± 3346 kg) and cows subjected to severe heat stress during the dry period (13,911 ± 4018 kg). It was concluded that environmental management of dry cows during hot months is warranted to maximize reproductive performance and milk yield in the following lactation., (© 2024. The Author(s) under exclusive licence to International Society of Biometeorology.)

Experiments as Code (ExaC) is a concept for reproducible, auditable, debuggable, reusable, & scalable experiments. Experiments are a crucial tool to understand Human-Building Interactions (HBI) and build a coherent theory around it. However, a common concern for experiments is their auditability and reproducibility. Experiments are usually designed, provisioned, managed, and analyzed by diverse teams of specialists (e.g., researchers, technicians, engineers) and may require many resources (e.g., cloud infrastructure, specialized equipment). Although researchers strive to document experiments accurately, this process is often lacking. Consequently, it is difficult to reproduce these experiments. Moreover, when it is necessary to create a similar experiment, the "wheel is very often reinvented". It appears easier to start from scratch than trying to reuse existing work. Thus valuable embedded best practices and previous experiences are lost. In behavioral studies, such as in HBI, this has contributed to the reproducibility crisis. To tackle these challenges, we propose the ExaC paradigm, which not only documents the whole experiment, but additionally provides the automation code to provision, deploy, manage, and analyze the experiment. To this end, we define the ExaC concept, provide a taxonomy for the components of a practical implementation, and provide a proof of concept with an HBI desktop VR experiment that demonstrates the benefits of its "as code" representation, that is, reproducibility, auditability, debuggability, reusability, & scalability., (© 2024. The Author(s).)

Pancreatic cancer is a type of gastrointestinal tumor with a growing incidence and mortality worldwide. Pancreatic ductal adenocarcinoma (PDAC) constitutes 90% of cases, and late-stage diagnosis is common, leading to a 5-year survival rate of less than 10% in high-income countries. The use of biomarkers has different proven translational applications, facilitating early diagnosis, accurate prognosis and identification of potential therapeutic targets. Several studies have shown a correlation between the tissue expression levels of various molecules, measured through immunohistochemistry (IHC), and survival rates in PDAC. Following the hallmarks of cancer, epigenetic and metabolic reprogramming, together with immune evasion and tumor-promoted inflammation, plays a critical role in cancer initiation and development. In this study, we aim to explore via IHC and Kaplan-Meier analyses the prognostic value of various epigenetic-related markers (histones 3 and 4 (H3/H4), histone acetyl transferase 1 (HAT-1), Anti-Silencing Function 1 protein (ASF1), Nuclear Autoantigenic Sperm Protein (NASP), Retinol Binding Protein 7 (RBBP7), importin 4 (IPO4) and IPO5), metabolic regulators (Phosphoglycerate mutase (PGAM)) and inflammatory mediators (allograft inflammatory factor 1 (AIF-1), interleukin 10 (IL-10), IL-12A and IL-18) in patients with PDAC. Also, through a correlation analysis, we have explored the possible interconnections in the expression levels of these molecules. Our results show that higher expression levels of these molecules are directly associated with poorer survival rates in PDAC patients, except in the case of IL-10, which shows an inverse association with mortality. HAT1 was the molecule more clearly associated with mortality, with a hazard risk of 21.74. The correlogram demonstrates an important correlation between almost all molecules studied (except in the case of IL-18), highlighting potential interactions between these molecules. Overall, our study demonstrates the relevance of including different markers from IHC techniques in order to identify unexplored molecules to develop more accurate prognosis methods and possible targeted therapies. Additionally, our correlation analysis reveals potential interactions among these markers, offering insights into PDAC's pathogenesis and paving the way for targeted therapies tailored to individual patient profiles. Future studies should be conducted to confirm the prognostic value of these components in PDAC in a broader sample size, as well as to evaluate the possible biological networks connecting them.

The circadian rhythms generated by the master biological clock located in the brain's hypothalamus influence central physiological processes. At the molecular level, a core set of clock genes interact to form transcription-translation feedback loops that provide the molecular basis of the circadian rhythm. In animal models of disease, a desynchronization of clock genes in peripheral tissues with the central master clock has been detected. Interestingly, patients with vascular dementia have sleep disorders and irregular sleep patterns. These alterations in circadian rhythms impact hormonal levels, cardiovascular health (including blood pressure regulation and blood vessel function), and the pattern of expression and activity of antioxidant enzymes. Additionally, oxidative stress in vascular dementia can arise from ischemia-reperfusion injury, amyloid-beta production, the abnormal phosphorylation of tau protein, and alterations in neurotransmitters, among others. Several signaling pathways are involved in the pathogenesis of vascular dementia. While the precise mechanisms linking circadian rhythms and vascular dementia are still being studied, there is evidence to suggest that maintaining healthy sleep patterns and supporting proper circadian rhythm function may be important for reducing the risk of vascular dementia. Here, we reviewed the main mechanisms of action of molecular targets related to the circadian cycle and oxidative stress in vascular dementia.

The photoexcitation dynamics of molecular materials on the 10-100 nm length scale depend on complex interactions between electronic and vibrational degrees of freedom, rendering exact calculations difficult or intractable. The adaptive Hierarchy of Pure States (adHOPS) is a formally exact method that leverages the locality imposed by interactions between thermal environments and electronic excitations to achieve size-invariant scaling calculations for single-excitation processes in systems described by a Frenkel-Holstein Hamiltonian. Here, we extend adHOPS to account for arbitrary couplings between thermal environments and vertical excitation energies, enabling formally exact, size-invariant calculations that involve multiple excitations or states with shared thermal environments. In addition, we introduce a low-temperature correction and an effective integration of the noise to reduce the computational expense of including ultrafast vibrational relaxation in Hierarchy of Pure States (HOPS) simulations. We present these advances in the latest version of the open-source MesoHOPS library and use MesoHOPS to characterize charge separation at a one-dimensional organic heterojunction when both the electron and hole are mobile., (© 2024 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).)

Diabetes mellitus is a chronic metabolic condition marked by high blood glucose levels caused by inadequate insulin synthesis or poor insulin use. This condition affects millions of individuals worldwide and is linked to a variety of consequences, including cardiovascular disease, neuropathy, nephropathy, and retinopathy. Diabetes therapy now focuses on controlling blood glucose levels through lifestyle changes, oral medicines, and insulin injections. However, these therapies have limits and may not successfully prevent or treat diabetic problems. Several marine-derived chemicals have previously demonstrated promising findings as possible antidiabetic medicines in preclinical investigations. Peptides, polyphenols, and polysaccharides extracted from seaweeds, sponges, and other marine species are among them. As a result, marine natural products have the potential to be a rich source of innovative multitargeted medications for diabetes prevention and treatment, as well as associated complications. Future research should focus on the chemical variety of marine creatures as well as the mechanisms of action of marine-derived chemicals in order to find new antidiabetic medicines and maximize their therapeutic potential. Based on preclinical investigations, this review focuses on the next step for seaweed applications as potential multitargeted medicines for diabetes, highlighting the bioactivities of seaweeds in the prevention and treatment of this illness.