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Abstract Antenatal hydronephrosis (HN) impacts up to 5% of pregnancies and requires close, frequent follow-up monitoring to determine who may benefit from surgical intervention. To create an automated HN Severity Index (HSI) that helps guide clinical decision-making directly from renal ultrasound images. We applied a deep learning model to paediatric renal ultrasound images to predict the need for surgical intervention based on the HSI. The model was developed and studied at four large quaternary free-standing paediatric hospitals in North America. We evaluated the degree to which HSI corresponded with surgical intervention at each hospital using area under the receiver-operator curve, area under the precision-recall curve, sensitivity, and specificity. HSI predicted subsequent surgical intervention with > 90% AUROC, > 90% sensitivity, and > 70% specificity in a test set of 202 patients from the same institution. At three external institutions, HSI corresponded with AUROCs ≥ 90%, sensitivities ≥ 80%, and specificities > 50%. It is possible to automatically and reliably assess HN severity directly from a single ultrasound. The HSI stratifies low- and high-risk HN patients thus helping to triage low-risk patients while maintaining very high sensitivity to surgical cases. HN severity can be predicted from a single patient ultrasound using a novel image-based artificial intelligence system.

Abstract Microtubule-associated protein tau (MAPT/tau) accumulates in a family of neurodegenerative diseases, including Alzheimer’s disease (AD). In disease, tau is aberrantly modified by post-translational modifications (PTMs), including hyper-phosphorylation. However, it is often unclear which of these PTMs contribute to tau’s accumulation or what mechanisms might be involved. To explore these questions, we focus on a cleaved proteoform of tau (tauC3), which selectively accumulates in AD and was recently shown to be degraded by its direct binding to the E3 ubiquitin ligase, CHIP. Here, we find that phosphorylation of tauC3 at a single residue, pS416, is sufficient to weaken its interaction with CHIP. A co-crystal structure of CHIP bound to the C-terminus of tauC3 reveals the mechanism of this clash, allowing design of a mutation (CHIPD134A) that partially restores binding and turnover of pS416 tauC3. We confirm that, in our models, pS416 is produced by the known AD-associated kinase, MARK2/Par-1b, providing a potential link to disease. In further support of this idea, an antibody against pS416 co-localizes with tauC3 in degenerative neurons within the hippocampus of AD patients. Together, these studies suggest a molecular mechanism for how phosphorylation at a discrete site contributes to accumulation of a tau proteoform.

Abstract Background Celiac disease (CD) affects the small intestine and can hinder nutrient absorption. It is found worldwide and common in certain groups of people including individuals with Type 1 Diabetes Mellitus (T1DM). However, the prevalence of CD in the West African region is not documented. This study aimed to investigate the prevalence and pattern of CD autoimmunity in Nigerian children and adolescents diagnosed with T1DM. Methods This was a cross-sectional descriptive study of children and adolescents with T1DM at the Paediatric Endocrinology Clinic of seven selected tertiary health facilities in Nigeria. Information was collected on socio-demographics, clinical characteristics and anthropometrics. The subjects were screened for markers of CD autoimmunity using anti-tissue transglutaminase antibody (tTG) and anti-endomysial antibody (EMA). Endoscopy and duodenal biopsy were recommended for participants with elevated CD-specific antibodies. Results The study recruited a total of 104 children and adolescents with TIDM, out of which six participants (5.8%) had CD autoimmunity. All six participants were females, aged between 3 and 12 years, with a mean age of 9.2 ± 3.7 years. Participants with CD autoimmunity were more likely to have DM diagnosed before the age of 10 years compared to those without CD autoimmunity (83.3% vs. 37.7%, p = 0.149). Except for two participants, all individuals with CD autoimmunity experienced gastrointestinal symptoms such as nausea, vomiting, diarrhoea, and bloating. Conclusion This study highlights the occurrence of CD autoimmunity in Nigerian children and adolescents with TIDM. Healthcare providers should consider screening for celiac disease in children and adolescents with T1DM, particularly in females and when gastrointestinal symptoms are present. Additionally, the findings from this study suggest that there is a high probability of a significant burden of CD, even within the general population in Nigeria. Therefore, it’s important to maintain a high level of suspicion and to actively screen at-risk groups in clinical settings to ensure early diagnosis of CD.

Abstract Background Cytokines, known for their pro- and anti-inflammatory roles, are also key regulators of sleep–wake cycles. Classical pro-inflammatory cytokines, such as interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-α), are associated with increased sleep, particularly slow-wave sleep (SWS), while anti-inflammatory cytokines, like interleukin-10 (IL-10), generally reduce sleep duration. Given the essential role of sleep in memory consolidation, this study aimed to investigate whether interleukin-12 (IL-12), a pro-inflammatory cytokine, could increase sleep duration following a memory acquisition task and subsequently improve memory performance. Male Swiss mice were surgically implanted with electrodes for electrocorticogram (ECoG) and electromyogram (EMG) recordings to track their sleep–wake cycles. After a recovery period, baseline sleep–wake activity was recorded. The mice were then randomly assigned to two groups and treated with either IL-12 (0.5 µg, i.p.) or a phosphate-buffered saline (PBS, i.p.) control, administered immediately before the multiple-trial inhibitory avoidance (MTIA) task, a behavioral test used to assess memory performance. Following the memory acquisition session, sleep–wake activity was immediately recorded for a continuous 24-h period. Results Mice treated with IL-12 exhibited longer latency to cross into the dark compartment during the MTIA test, indicating improved memory retention compared to the control group. Interestingly, this improved performance was associated with prolonged wakefulness, particularly in the first three hours after task acquisition. Conclusion The study shows that IL-12 can improve memory retention through prolonged wake episodes rather than increased sleep. This finding challenges the conventional understanding that sleep is the primary state for memory consolidation, suggesting that under specific conditions, wakefulness may also play a key role in supporting memory processes. Further research is needed to explore the underlying mechanisms of IL-12's cognitive effects.

Abstract Background Lanthanide-based nanomaterials offer a promising alternative for cancer therapy because of their selectivity and effectiveness, which can be modified and predicted by leveraging the improved accuracy and enhanced decision-making of machine learning (ML) modeling. Methods In this study, erbium (Er3+) and ytterbium (Yb3+) were used to dope zinc oxide (ZnO) nanoparticles (NPs). Various characterization techniques and biological assays were employed to investigate the physicochemical and optical properties of the (Er, Yb)-doped ZnO NPs, revealing the influence of the lanthanide elements. Results The (Er, Yb)-doped ZnO NPs exhibited laminar-type morphologies, negative surface charges, and optical bandgaps that vary with the presence of Er3+ and Yb3+. The incorporation of lanthanide ions reduced the cytotoxicity activity of ZnO against HEPG-2, CACO-2, and U87 cell lines. Conversely, doping with Er3+ and Yb3+ enhanced the antioxidant activity of the ZnO against DPPH, ABTS, and H2O2 radicals. The extra tree (ET) and random forest (RF) models predicted the relevance of the characterization results vis-à-vis the cytotoxic properties of the synthesized NPs. Conclusion This study demonstrates, for the first time, the synthesis of ZnO NPs doped with Er and Yb via a solution polymerization route. According to characterization results, it was unveiled that the effect of optical bandgap variations influenced the cytotoxic performance of the developed lanthanide-doped ZnO NPs, being the undoped ZnO NPs the most cytotoxic ones. The presence alone or in combination of Er and Yb enhanced their scavenging capacity. ML models such as ET and RF efficiently demonstrated that the concentration and cell line type are key parameters that influence the cytotoxicity of (Er, Yb)-doped ZnO NPs achieving high accuracy rates of 98.96% and 98.67%, respectively. This study expands the knowledge of lanthanides as dopants of nanomaterials for biological and medical applications and supports their potential in cancer therapy by integrating robust ML approaches. Graphical abstract

Objective We explored the relationship between achievement of clinical disease control and improvements in and normative values for patient‐reported outcomes (PROs), including quality of life (QoL) measures, in patients with psoriatic arthritis (PsA). Methods This was a post hoc analysis of 104‐week data from the SELECT‐PsA 1 and 2 trials in adults with PsA and inadequate response to one or more conventional synthetic (SELECT‐PsA 1) or biologic (SELECT‐PsA 2) disease‐modifying antirheumatic drug. Patients were initially randomized to upadacitinib 15 mg once daily (QD) to placebo switched to upadacitinib 15 mg QD at week 24 or to adalimumab 40 mg every other week (SELECT‐PsA 1 only), and data were pooled across treatments and analyzed. We evaluated several clinical disease control measures (minimal disease activity [MDA]; very low disease activity [VLDA]; and low disease activity [LDA] and/or remission by Disease Activity in Psoriatic Arthritis [DAPSA], Psoriatic Arthritis Disease Activity Score [PASDAS], and Routine Assessment of Patient Index Data 3 [RAPID3]) and examined their associations with improvements and normative values for various PROs. Results A total of 1,069 and 317 patients were analyzed for SELECT‐PsA 1 and 2, respectively. In both studies, responders (patients who achieved MDA or VLDA, and DAPSA, PASDAS, and RAPID3 LDA or remission) at week 104 achieved more marked changes from baseline, and more responders achieved normative values in PROs compared with nonresponders (most nominal P < 0.0001). Furthermore, numerically larger proportions of responders achieved minimal clinically important differences across PROs compared with nonresponders in both studies. In addition, patients who achieved MDA or VLDA were more likely to achieve DAPSA, PASDAS, and RAPID3 LDA or remission (all nominal P < 0.0001) for upadacitinib 15 mg QD and when treatment arms were pooled. Conclusion Patients with PsA who achieve clinical disease control are more likely to achieve improvements and normative values in PROs and QoL measures, which reinforces disease control as a treatment target.

Se presenta el primer caso documentado en Colombia del síndrome PURA, una enfermedad neurológica rara. Esta afección resulta de mutaciones del gen PURA, localizado en el cromosoma 5, que producen haploinsuficiencia de la proteína PUR-α. Esta proteína es esencial para el desarrollo temprano del cerebro y la función neuronal. El paciente, un niño de siete años, comenzó a presentar movimientos distónicos de las manos a los 14 días de vida. A los seis años, se le diagnosticó retraso en el neurodesarrollo, hipotonía generalizada, episodios frecuentes de apnea y dificultad para la deglución. Aunque inicialmente se consideraron otras condiciones, como la distrofia muscular de Duchenne y la lipofuscinosis ceroidea neuronal, la secuenciación completa del exoma reveló la variante patógena c.692T>C (p.Phe231Ser) en el exón 1 del gen PURA, no registrada previamente en otros pacientes. Este hallazgo permitió un enfoque de manejo integral, con el cual se abordaron las características y alteraciones clínicas del paciente. Dado que el síndrome PURA no figura en la lista de enfermedades huérfanas o raras reconocidas por el Ministerio de Salud y Protección Social de Colombia, este reporte podría influir en su reconocimiento oficial. El caso demuestra la importancia de considerar diagnósticos raros en pacientes con síntomas neurológicos poco comunes y subraya la utilidad de la secuenciación genómica para el diagnóstico. Además, enfatiza la necesidad de colaboración en el área de la salud para optimizar el cuidado de los pacientes con síndrome PURA y otras enfermedades semejantes.

Abstract Background Prehospital point-of-care ultrasound allows an unstable patient to be rapidly and accurately assessed. However, we are concerned that an excessive focus on the ultrasound device, in an already demanding emergency medical service environment, may distract from patient care, potentially leading to reduced situational awareness and the neglect of other crucial instruments, such as the patient monitor. Thus, in this study, we examined the influence of prehospital ultrasound on situational awareness, by studying the degree to which physicians were distracted from the patient monitor. Methods We observed HEMS physicians in a simulated setting and analysed their gaze behaviour using an eye tracker placed on three areas of interests: the ultrasound device, the patient and the patient monitor. In the course of the experiment, the simulated patient desaturated, which was presented on the patient monitor. The primary outcome was the fraction of gaze distribution across the three areas of interest, while secondary outcomes were different gaze metrics (dwell time, revisits, average duration of visual intake and entry time) on the patient monitor. We then compared the participants who noticed the patient’s deterioration with those who did not. Results In 75% of cases, the severely decreased oxygen saturation went unnoticed during the test. Moreover, the gaze distribution of the two groups differed, with the group that recognised the deterioration focusing longer on the patient monitor (7.8% (95% CI 5–10.7) vs 0.1% (95% CI 0–0.3), p: 0.124). Conclusions The task of performing an ultrasound examination appears to overwhelm some participants and distract them from other aspects of the scenario. Efforts to mitigate distractions and optimise the use of prehospital ultrasound, such as education, a focus on human factors aspects and standardisation, are crucial for maximising the potential benefits of prehospital ultrasound.

Abstract Background Though the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is no more of a public health emergency, the experiences from burying SARS-CoV-2 infectious dead bodies may remain with the workers. For Environmental Health Officers (EHOs), dealing with decedents during the SARS-CoV-2 outbreak may arouse strong feelings of pity, horror, repulsion, disgust, and anger at the tragedy. Therefore, this study aims to explore the experiences of EHOs in disposing off of confirmed or suspected SARS-CoV-2 fatalities in Ghana. Methods Using an 18-item interview guide, we gathered data from 27 EHOs from three regions of Ghana. We followed the steps in Descriptive Phenomenology in conducting the data analysis. Results i. EHOs were confronted with several occupational health and safety (OHS) hazards like physical and chemical injuries, threat of harm, and psychological harm, ii. The officers also faced severe shortage of personal protective equipment (PPE). Unfortunately, they were not provided with any form of psychological support during the period. Conclusion The SARS-CoV-2 outbreak in Ghana exposed major fault lines in the health and safety/disaster and emergency preparedness of EHOs towards the burial of infectious disease dead bodies. Clearly, the disposal exercise failed to uphold the Sustainable Development Goals (SDGs) 4.4, 8.3, and 8.5, which advocate for the promotion of decent jobs for all. Recommendation Ghana’s Ministries of Health, Local Government, and Sanitation and Water Resources need to attach Clinical Psychologists and security personnel to the disposal teams in future exercises to provide psychological support and security to the team. Though studies on the disposal of infectious bodies in Africa exist, very little is known about the experiences of EHOs in the disposal of SARS-CoV-2 dead bodies during the outbreak.

Abstract Background A limitation of approved oncolytic viruses is their requirement for intratumoral (i.t.) injection. TILT-123 (igrelimogene litadenorepvec, Ad5/3-E2F-D24-hTNFα-IRES-hIL-2) is a chimeric oncolytic adenovirus suitable for intravenous (i.v.) delivery due to its capsid modification and dual selectivity devices. It is armed with tumor necrosis alpha and interleukin-2 for promoting T-cell activation and lymphocyte trafficking to tumors, thereby enhancing the antitumor immune response. Here, we present the findings after a single i.v. administration of TILT-123 in three phase I dose escalation clinical trials. Methods Patients with advanced solid tumors initially received a single i.v. dose of TILT-123 ranging from 3 × 109 to 4 × 1012 viral particles (VP). Blood was collected at baseline, 1, 16, and 192 h (7 days) post-treatment for bioavailability and serum analysis. Tumor biopsies were collected prior to treatment and 7 days post-treatment for analysis of viral presence and immunological effects. Patients did not receive any other cancer therapies during this period. Results Across all three trials (TUNIMO, TUNINTIL, and PROTA), 52 total patients were treated with i.v. TILT-123. Overall, TILT-123 was found to be well-tolerated, with no dose-limiting toxicities observed. Post-treatment tumor biopsies showed expression of viral genes, presence of TILT-123 adenovirus proteins or DNA, and changes in immune cell infiltration from baseline. Increased virus dose did not lead to increased virus detection in tumors. Median overall survival was longer in patients with confirmed presence of TILT-123 in post-treatment biopsies (280 versus 190 days, p = 0.0405). Conclusion TILT-123 demonstrated safety and significant intratumoral immunomodulation following a single i.v. administration, warranting further investigation. Trial registrations TUNIMO—NCT04695327. Registered 4 January 2021, https://clinicaltrials.gov/study/NCT04695327 . TUNINTIL—NCT04217473. Registered 19 December 2019, https://clinicaltrials.gov/study/NCT04217473 . PROTA—NCT05271318. Registered 4 February 2022, https://clinicaltrials.gov/study/NCT05271318 .

La agricultura convencional depende de la aplicación de fertilizantes con el fin de lograr mayores rendimientos; sin embargo, es necesario encontrar un equilibrio entre sus beneficios y las alteraciones que pudieran producir a los ecosistemas. Organizaciones internacionales regulan su uso y comercialización teniendo en cuenta la eficacia y seguridad. IHPLUS®, producido por la Estación Experimental de Pastos y Forrajes “Indio Hatuey” (Cuba), ha mostrado ser efectivo en diferentes cultivos y es objeto en este estudio evaluar los efectos sobre la calidad del agua en el bioindicador Poecilia reticulata. Los peces fueron expuestos al producto, en régimen estático durante 96 h, a la concentración efectiva en la agricultura (6 %) o diluido hasta 106 UFC/ml según recomienda la EPA OPPTS 885.4000. Asimismo, se incluyó un grupo tratado con el producto al 6 %, pero esterilizado y un grupo control que no recibió tratamiento alguno. Se observaron durante 30 días posinoculación y se evaluó el peso, la mortalidad y otros efectos subletales. Posteriormente, se determinó la concentración letal media (CL50) y la influencia del pH sobre la mortalidad de los peces. Se pudo comprobar que al 6 % provocó eventos clínicos adversos y efecto letal en el biomodelo. Las lesiones histopatológicas se corresponden tanto para el producto activado como para el inactivado. La CL50 fue de 3.19 %, asociándose la toxicidad al pH ácido y no a la carga microbiana presente en el bioproducto. Se concluye que IHPLUS® es seguro para Poecilia reticulata a concentraciones inferiores al 3 %.

Background: The benefits of exercise are well known; however, many of the underlying molecular mechanisms are not fully understood. Skeletal muscle secretes myokines, which mediate muscle–organ crosstalk. Myokines regulate satellite-cell proliferation and migration, inflammatory cascade, insulin secretion, angiogenesis, fatty oxidation, and cancer suppression. To date, the effects of different exercise modes (namely, aerobic and resistance exercise) on myokine response remain to be elucidated. This is crucial considering the clinical implementation of exercise to enhance general health and wellbeing and as a medical treatment. Methods: A systematic search was undertaken in PubMed, MEDLINE, CINAHL, Embase, SPORTDiscus, and Web of Science in April 2023. Eligible studies examining the effects of a single bout of exercise on interleukin15 (IL-15), irisin, secreted protein acidic and rich in cysteine (SPARC), oncostatin M (OSM), and decorin were included. A random-effects meta-analysis was also undertaken to quantify the magnitude of change. Results: Sixty-two studies were included (n = 1193). Overall, exercise appeared to induce small to large increases in myokine expression, with effects observed immediately after to 60 min post-exercise, although these were mostly not statistically significant. Both aerobic and resistance exercise resulted in changes in myokine levels, without any significant difference between training modes, and with the magnitude of change differing across myokines. Myokine levels returned to baseline levels within 180 min to 24 h post-exercise. However, owing to potential sources of heterogeneity, most changes were not statistically significant, indicating that precise conclusions cannot be drawn. Conclusion: Knowledge is limited but expanding with respect to the impact of overall and specific effects of exercise on myokine expression at different time points in the systemic circulation. Further research is required to investigate the effects of different exercise modes at multiple time points on myokine response.

Background Progress in hernia surgery in Nigeria is hampered by poor health-seeking behavior, poverty, and ignorance. The disparity in the quality of health care deliveries between urban and rural areas led to the greater proportions of rural dwellers being grossly underserved. Medical aid programs offer ample opportunities to reduce the burden of hernias in Nigeria. This study aimed to analyze the early outcomes of elective hernia repairs performed during medical outreach programs. Methods This is a retrospective study of 186 patients who had hernia repair between September and November 2019. Patients were recruited from six consecutive medical aid programs held in Niger Delta (Southern) region of Nigeria. Results Overall, 186 patients were evaluated: 159 (855%) males and 27 (14.5%) females. Approximately three-fourths (141, 75.8%) harbored inguinal hernia. Nylon-darn was utilized to repair all inguinal hernias while a simple closure technique was used for all midline hernias. Majority (180, 96.8%) were discharged within 24 h of repair. Spinal anesthesia accounted for 51.6% of all anesthetic techniques used. The overall postoperative complication rate was 17.2%. The most common postoperative morbidity was scrotal edema (8.1%) followed by seroma (4.3%). Age >64 years (P < 0.001), large hernias >3 cm defect (P < 0.001), lower cadre of surgeon (P < 0.001), local anesthesia (P < 0.001) and comorbidity (P < 0.001) were significantly associated with raised morbidity. No mortality was recorded. All complications were managed conservatively. Conclusion Majority of the hernias were of inguinal origin. Scrotal edema was the most frequent postoperative complication, followed by seroma. Advanced age, large hernias, lower cadre of surgeon, comorbidity and local anesthesia were associated with raised morbidity rates.

Abstract Air traveler numbers are predicted to reach 4.0 billion in 2024. Between 1/15,000–50,000 passengers will experience acute medical problems inflight with cardiac arrests requiring cardiopulmonary resuscitation (CPR) accounting for 0.3% of medical emergencies. Hypoxia in airplane cabins could impair oxygenation and physical performance of caregivers. We conducted a randomized controlled, double-blind study to test the hypothesis that hypoxia decreases the effectiveness in performing CPR. We randomized 24 healthcare professionals to two different study arms, each consisting of two conditions: arm (1) ‘hypoxia (FiO2 15%, equivalent to 2400 m altitude)’ versus ‘normoxia’; arm (2) ‘hypoxia + supplemental oxygen’ versus ‘normoxia + supplemental oxygen’. The order of conditions was counterbalanced and a minimum wash-out period of 24 h was granted between conditions. In each condition participants performed a 5-min cardiac compression only CPR (CCO-CPR) using a full-body manikin after one, three and six hours in an altitude chamber. Mixed ANOVAs with post-hoc false-discovery-rate adjusted pairwise comparisons indicated that although compression frequency was maintained, the number of compressions with correct depth was decreased at all times during hypoxia compared to normoxia (all p

Abstract The high penetration of renewable energy sources (RES) results in a low‐inertia, weak power grid. To mitigate this and restore system inertia, it has been widely proposed to operate the inverters of RES units to mimic synchronous generators; this technology is known as a virtual synchronous generator (VSG). In weak grids there is, however, strong coupling between active power (P) and reactive power (Q), and any VSG technique therefore requires PQ decoupling in order to operate effectively. This article proposes a new PQ decoupling technique based on the transformation of the PQ power circle of a VSG connected to a weak grid: first, the power circle is translated from its designed position to that of a conventional synchronous generator (SG) connected to a strong grid, achieving partial PQ decoupling. Then, to achieve full PQ decoupling, the authors propose further to modulate the radius of the translated PQ power circle; this is achieved using a series resistance‐capacitance–inductance (RCL) circuit which is virtually implemented in the VSG controller. The efficacy of the proposed scheme is validated using a modified synchronverter connected to the weak grid in representative loading scenarios. It is demonstrated that the technique achieves a decoupled PQ control for the synchronverter connected in a weak grid. Moreover, the modified synchronverter is capable of supporting frequency and voltage regulation in the grid without inducing large transient grid currents during mild frequency and voltage variations.

Abstract Season of birth, viral infections, HLA haplogenotypes and non-HLA variants are implicated in the development of celiac disease and celiac disease autoimmunity, suggesting a combined role of genes and environmental exposures. The aim of the study was to further decipher the biological pathways conveying the season of birth effect in celiac disease autoimmunity to gain novel insights into the early pathogenesis of celiac disease. Interactions between season of birth, genetics, and early-life environmental factors on the risk of celiac autoimmunity were investigated in the multicenter TEDDY birth cohort study. Altogether 6523 genetically predisposed children were enrolled to long-term follow-up with prospective sampling and data collection at six research centers in the USA, Germany, Sweden and Finland. Celiac disease autoimmunity was defined as positive tissue transglutaminase antibodies in two consecutive serum samples. There was a significant season of birth effect on the risk of celiac autoimmunity. The effect was dependent on polymorphisms in CD247 gene encoding for CD3ζ chain of TCR-CD3 complex. In particular, children with major alleles for SNP rs864537A > G, in CD247 (AA genotype) had an excess risk of celiac autoimmunity when born March–August as compared to other months. The interaction of CD247 with season of birth on autoimmunity risk was accompanied by interactions with febrile infections between the ages of 3–6 months. Considering the important role of TCR-CD3 complex in the adaptive immune response and our findings here, CD247 variants and their possible effect of subgroups in autoimmunity development could be of interest in the design of future gene-environment studies of celiac disease. ClinicalTrials.gov Identifier: NCT00279318.

Abstract Genome-wide association studies (GWAS) identify genetic variants underlying complex traits but are limited by stringent genome-wide significance thresholds. We present GRIN (Gene set Refinement through Interacting Networks), which increases confidence in the expanded gene set by retaining genes strongly connected by biological networks when GWAS thresholds are relaxed. GRIN was validated on both simulated interrelated gene sets as well as multiple GWAS traits. From multiple GWAS summary statistics of suicide attempt, a complex phenotype, GRIN identified additional genes that replicated across independent cohorts and retained biologically interrelated genes despite a relaxed significance threshold. We present a conceptual model of how these retained genes interact through neurobiological pathways that may influence suicidal behavior, and identify existing drugs associated with these pathways that would not have been identified under traditional GWAS thresholds. We demonstrate GRIN’s utility in boosting GWAS results by increasing the number of true positive genes identified from GWAS results.

Autonomous vehicles (AVs) have inspired tremendous interest in solving existing transportation sector difficulties, especially with recent breakthroughs in sustainable ways of transportation. However, theoretical frameworks or models to efficiently analyze the threats, challenges, opportunities, and sustainability associated with AVs’ usage remain limited in application. This study introduces the Problem-Cause-Solution-Sustainability-Advantage-Disadvantage-Threat-Opportunities (PC-SSADTO) conceptual framework, a modified form of the Strength-Weaknesses-Opportunities-Threats (SWOT) analysis to analyze AVs as a sustainable solution. This framework examines the difficulties, risks, and possibilities of using AVs in the transportation sector as well as how their worldwide implementation and integration might help lower carbon dioxide (CO2) emissions, enhance road safety, and improve mobility and accessibility, thus accelerating the accomplishment of Sustainable Development Goals (SDGs). The requirements of the PC-SSADTO framework are confirmed by a survey that gathers over 200 public answers on the present issues or challenges that AVs may address, such as lowering traffic congestion, greenhouse gas emissions, and climate change for an improved livelihood. Despite some uncertainty in human opinions about AVs systems, the application of totally autonomous operations appears to be essential for the effective integration of AVs. Therefore, high degrees of integration with public transportation and cooperative decision-making structures would favor practical AVs implementations and usage positively.

Abstract Background The increasing diversity of psychoactive substances on the unregulated drug market poses significant health, psychological, and social risks to people who use drugs (PWUD). To address these risks, various harm reduction (HR) policies have been implemented, including drug checking services (DCS). Many analytical methods are used for DCS. While qualitative methods (e.g., thin layer chromatography, spectroscopy) are easier to implement, they are not as accurate as quantitative methods (e.g., LC-UV, LC-MS). Some HR programmes have implemented high-performance liquid chromatography coupled with UV detection (LC-UV). This article presents the cross-validation of this quantitative method with a reference liquid chromatography coupled with high resolution mass spectrometry (LC-HRMS) method. Methods Drug samples were provided by PWUD to a DCS called DrugLab in Marseille, France. The samples were weighed and prepared through dissolution in methanol, followed by ultrasonic bathing. Samples were analysed onsite using LC-UV analysis. They were then subsequently analysed with the reference LC-HRMS method. The LC-UV instrument in DrugLab was calibrated after being purchased; analysis of standard solutions was routinely performed once a month and after maintenance operations. For the LC-HRMS instrument, calibration and quality control procedures followed European Medicines Agency (EMA) guidelines. Statistical analyses were conducted including Spearman correlation tests using IBM® SPSS® Statistics version 20. Results A total of 102 samples representing different product classes and cutting agents were cross-validated. Differences between both analyses methods for each molecule analysed were ≤ 20%, with significant correlations between both methods’ results for most substances. Notably, LC-HRMS provided lower concentration values for cocaine and acetaminophen, whereas it provided higher values for other substances. Correlations were significant for cocaine, ketamine, MDMA, heroin, amphetamine, caffeine, acetaminophen, and levamisole. Conclusions This study demonstrates that the results provided by DrugLab were accurate and reliable, making LC-UV an adaptable, stable, and suitable analytical method for simple matrices like drugs in a DCS context. However, this cross validation does not guarantee accuracy over time. A proficiency test project in HR laboratories across France is currently under development in order to address potential drifts in LC-UV accuracy.

Abstract Background Although mobile health (mHealth) interventions have shown promise in improving health outcomes, most of them rarely translate to scale. Prevailing mHealth studies are largely small-sized, short-term and donor-funded pilot studies with limited evidence on their effectiveness. To facilitate scale-up, several frameworks have been proposed to enhance the generic implementation of health interventions. However, there is a lack of a specific focus on the implementation and integration of mHealth interventions in routine care in low-resource settings. Our scoping review aimed to synthesize and develop a framework that could guide the implementation and integration of mHealth interventions. Methods We searched the PubMed, Google Scholar, and ScienceDirect databases for published theories, models, and frameworks related to the implementation and integration of clinical interventions from 1st January 2000 to 31st December 2023. The data processing was guided by a scoping review methodology proposed by Arksey and O’Malley. Studies were included if they were i) peer-reviewed and published between 2000 and 2023, ii) explicitly described a framework for clinical intervention implementation and integration, or iii) available in full text and published in English. We integrated different domains and constructs from the reviewed frameworks to develop a new framework for implementing and integrating mHealth interventions. Results We identified eight eligible papers with eight frameworks composed of 102 implementation domains. None of the identified frameworks were specific to the integration of mHealth interventions in low-resource settings. Two constructs (skill impartation and intervention awareness) related to the training domain, four constructs (technical and logistical support, identifying committed staff, supervision, and redesigning) from the restructuring domain, two constructs (monetary incentives and nonmonetary incentives) from the incentivize domain, two constructs (organizational mandates and government mandates) from the mandate domain and two constructs (collaboration and routine workflows) from the integrate domain. Therefore, a new framework that outlines five main domains—train, restructure, incentivize, mandate, and integrate (TRIMI)—in relation to the integration and implementation of mHealth interventions in low-resource settings emerged. Conclusion The TRIMI framework presents a realistic and realizable solution for the implementation and integration deficits of mHealth interventions in low-resource settings.

Abstract Purpose This scoping review aims to explore the current applications of ChatGPT in the retina field, highlighting its potential, challenges, and limitations. Methods A comprehensive literature search was conducted across multiple databases, including PubMed, Scopus, MEDLINE, and Embase, to identify relevant articles published from 2022 onwards. The inclusion criteria focused on studies evaluating the use of ChatGPT in retinal healthcare. Data were extracted and synthesized to map the scope of ChatGPT’s applications in retinal care, categorizing articles into various practical application areas such as academic research, charting, coding, diagnosis, disease management, and patient counseling. Results A total of 68 articles were included in the review, distributed across several categories: 8 related to academics and research, 5 to charting, 1 to coding and billing, 44 to diagnosis, 49 to disease management, 2 to literature consulting, 23 to medical education, and 33 to patient counseling. Many articles were classified into multiple categories due to overlapping topics. The findings indicate that while ChatGPT shows significant promise in areas such as medical education and diagnostic support, concerns regarding accuracy, reliability, and the potential for misinformation remain prevalent. Conclusion ChatGPT offers substantial potential in advancing retinal healthcare by supporting clinical decision-making, enhancing patient education, and automating administrative tasks. However, its current limitations, particularly in clinical accuracy and the risk of generating misinformation, necessitate cautious integration into practice, with continuous oversight from healthcare professionals. Future developments should focus on improving accuracy, incorporating up-to-date medical guidelines, and minimizing the risks associated with AI-driven healthcare tools.

Abstract Adiposity is an established risk factor for multiple diseases, but the causal relationships of different adiposity types with circulating protein biomarkers have not been systematically investigated. We examine the causal associations of general and central adiposity with 2923 plasma proteins among 3977 Chinese adults (mean BMI = 23.9 kg/m²). Genetically-predicted body mass index (BMI), body fat percentage (BF%), waist circumference (WC), and waist-to-hip ratio (WHR) are significantly (FDR

Abstract Riboswitches regulate gene expression by modulating their structure upon metabolite binding. These RNA orchestrate several layers of regulation to achieve genetic control. Although Escherichia coli riboswitches modulate translation initiation, several cases have been reported where riboswitches also modulate mRNA levels. Here, we characterize the regulation mechanisms of the thiamin pyrophosphate (TPP) tbpA riboswitch in E. coli. Our results indicate that the tbpA riboswitch modulates both levels of translation and transcription and that TPP sensing is achieved more efficiently cotranscriptionally than post-transcriptionally. The preference for cotranscriptional binding is also observed when monitoring the TPP-dependent inhibition of translation initiation. Using single-molecule approaches, we observe that the aptamer domain freely fluctuates between two main structures involved in TPP recognition. Our results suggest that translation initiation is controlled through the ligand-dependent stabilization of the riboswitch structure. This study demonstrates that riboswitch cotranscriptional sensing is the primary determinant in controlling translation and mRNA levels.

Abstract Background Interventions for preventing or reducing the development of lifestyle-related disorders should be investigated as these conditions are becoming increasingly prevalent and having large effects on quality of life and life expectancy globally. The aim of this pilot study was to prepare for a full-scale randomised controlled trial by evaluating the short-term changes resulting from a function-based preventive intervention aimed at lifestyle-related disorders on a small group of physically inactive 40-year-old people. Change in objectively measured physical activity, functional capacity according to a risk profile, and goal attainment were main outcomes. Methods Participants (n = 27) underwent functional examinations including tests of fitness, strength, mobility, balance, and posture as well as standard medical examinations including weight measures, blood pressure and blood tests and were randomised to two groups. The intervention group (n = 15) received feedback from all the examinations and lifestyle counselling based on a functional profile. The control group (n = 12) received feedback only from the standard medical examination. Follow-up was at 3–4 months. Changes in physical activity measured with accelerometers, functional levels on the functional profile, goal attainment and subjective assessments of health-related quality of life, motivation, function, and physical activity were examined, as were standard medical parameters. Results Change in mean time in moderate or more intense physical activity was 9 min higher in the intervention group (95% confidence interval -6.35, 24.51) and change in sedentary time was 42 min lower (-95.24, 11.32). The intervention group showed a higher increase in motivation for change 1.58 on 10-point scale (0.20, 2.97) and indicated more improvement on the functional risk levels concerning fitness (-0.06, 0.90). Correlation between objectively measured and self-assessed physical activity and function increased after the intervention. Most participants in the intervention group achieved some or all of their goals. Conclusions This small-scale pilot intervention with functional examinations and lifestyle counselling showed positive tendencies for change in short-term physical activity level. It seemed to lead to better understanding of personal functional capacity and increased motivation for lifestyle changes. Setting and fulfilling meaningful goals for lifestyle-related changes seemed to influence levels on the functional profile in positive directions. Research on larger and more diverse populations will be necessary to better understand the implications of the intervention. Trial registration ClinicalTrials.gov: NCT05535296 first posted on 10/09/2022.

Abstract Background The burden of sepsis worsens due to the continuation of emerging pathogens such as multidrug-resistant Pantoea species. Methods A multicenter study was conducted between October 2019 and September 2020 at four hospitals located in central, southern, and northern parts of Ethiopia. A total of 1416 sepsis patients were recruited and blood cultures were performed. At each study site, positive cultures were characterized by their colony characteristics, gram stain, and conventional biochemical tests. All Pantoea species were identified using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI TOF) and subjected to whole genome sequencing (WGS) using Illumina HiSeq 2500. The phylogeny structure of Pantoea isolates was calculated using IQ-TREE v1.6.12 from single-nucleotide polymorphisms detected by Snippy v.4.6.0 and filtered by Gubbins v.2.3.4. Average nucleotide identity was estimated by using OrthoANI v.0.93.1 on Shovill v.1.1.0 assemblies. Antimicrobial resistance genes and plasmid replicons were detected using ARIBA v.2.14.6. Phylogenetic trees were visualized using iTOLv.6.5.2. Results Multiple Pantoea species include: P. dispersa (n = 19), P. septica (n = 1), and a novel Pantoea spp. (n = 1), were identified among sepsis patients. All P. dispersa isolates and the novel Pantoea species were isolated at Dessie Referral Hospital and displayed phylogenetic clonality, including the ubiquity of an IncM1 plasmid and identical antimicrobial resistance (AMR) gene profiles, encoding bla CTX−M−15, bla TEM−1D, bla SCO−1, and aac(3)-lla. The novel Pantoea spp. isolate harboured bla CTX−M−9 and bla TEM−1D and carried an IncN3 plasmid replicon. The P. septica was isolated at Tikur Anbessa Specialized Hospital in Addis Ababa and carried no detectable acquired AMR genes. Conclusion The emerging Pantoea spp. carrying multiple AMR genes were identified from sepsis patients. Implementation of strong infection prevention strategies and building surveillance capacity with advanced bacteriology laboratories capable of identifying multidrug-resistant emerging pathogens is strongly recommended.

Abstract Addressing health inequity is a central component of the Sustainable Development Goals and a priority of the World Health Organization (WHO). WHO supports countries in strengthening their health information systems in order to better collect, analyze and report health inequality data. Improving information and research about health inequality is crucial to identify and address the inequalities that lead to poorer health outcomes. Building analytical capacities of individuals, particularly in low-resource areas, empowers them to build a stronger evidence-base, leading to more informed policy and programme decision-making. However, health inequality analysis requires a unique set of skills and knowledge. This paper describes three resources developed by WHO to support the analysis of inequality data by non-statistical users using Microsoft Excel, a widely used and accessible software programme. The resources include a practical eLearning course, which trains learners in the preparation and reporting of disaggregated data using Excel, an Excel workbook that takes users step-by-step through the calculation of 21 summary measures of health inequality, and a workbook that automatically calculates these measures with the user’s disaggregated dataset. The utility of the resources is demonstrated through an empirical example.

Abstract The current study aimed to analyze the validity and reliability of the T-Force and Chronojump systems to measure the movement velocity in the leg press (LP) and chest press (CP) exercises in older people. Eighteen older adults (6 men and 12 women, 79.9 ± 8.5 years) performed a set of procedures over three weeks: (i) the first week was to familiarize participants with the testing procedures, (ii) the second was to perform a progressive loading test until reaching one-repetition maximum (1RM) in the LP and CP, and (iii) in the third week, participants performed three repetitions against five loads (40, 50, 60, 70, and 80% of 1RM). The mean velocity of each repetition was recorded simultaneously through the T-Force and Chronojump devices. Linear regressions (coefficient of determination [r2] and standard error of the estimate [SEE]) analyzed the inter-device validity, and Bland-Altman plots illustrated the systematic differences between devices. A mixed-effects model estimated the mean velocity differences between devices. The relative reliability was analyzed by the intra-class correlation coefficient (ICC[1,k]), while the absolute reliability was by the standard error of measurement (SEM) and the coefficient of variation (CV). The results showed that the T-Force and Chronojump presented a high association level in measuring mean velocity in the LP and CP (r 2 range: 0.96–0.99; SEE range: 0.01–0.02 m·s− 1) and low systematic bias (0.02–0.03 m·s− 1). The mean velocity values of T-Force were significantly higher than Chronojump only for 40% 1RM (p = 0.04). Excellent reliability inter-device (ICC range: 0.95–0.98; CV range: 1.7–3.2%) and intra-device (ICC range: 0.90–0.97; CV range: 3.4–6.5%) was observed. This study shows that the T-Force and Chronojump systems are valid and reliable for measuring movement velocity in the CP and LP machines when used by older adults.

Abstract Introduction and importance Large bowel obstruction caused by volvulus poses a life-threatening risk without immediate intervention. Sigmoid colon volvulus is predominant (43–75%), followed by cecal volvulus 10–52%). Synchronous double colonic volvulus is extremely rare, with limited documented cases in academic literature. Case presentation We report a case of synchronous volvulus involving the sigmoid colon and cecum in a 45-year-old male of the Toro tribe from Fort Portal city in western Uganda who presented with acute abdominal pain, distension, and complete constipation for 2 days, accompanied by five episodes of non-bloody feculent vomiting and anorexia. Clinical discussion Upon admission, the patient presented with stable vital signs and a mildly tender, tympanic, distended abdomen with absent bowel sounds. Plain radiographs revealed the characteristic “coffee bean” sign, indicative of sigmoid volvulus. Following optimization, laparotomy confirmed synchronous volvulus involving both the sigmoid and cecum. Subsequently, a total colectomy with end ileostomy was performed, after which the patient experienced an uneventful recovery. Conclusion Synchronous double colonic volvulus, a rare condition, is frequently overlooked clinically. Timely recognition and intervention are crucial to address diagnostic challenges and prevent potentially fatal outcomes.

Abstract Background Genetic perturbation screens with single-cell readouts have enabled rich phenotyping of gene function and regulatory networks. These approaches have been challenging in vivo, especially in adult disease models such as cancer, which include mixtures of malignant and microenvironment cells. Glioblastoma (GBM) is a fatal cancer, and methods of systematically interrogating gene function and therapeutic targets in vivo, especially in combination with standard of care treatment such as radiotherapy, are lacking. Results Here, we iteratively develop a multiplex in vivo perturb-seq CRISPRi platform for single-cell genetic screens in cancer and tumor microenvironment cells that leverages intracranial convection enhanced delivery of sgRNA libraries into mouse models of GBM. Our platform enables potent silencing of drivers of in vivo growth and tumor maintenance as well as genes that sensitize GBM to radiotherapy. We find radiotherapy rewires transcriptional responses to genetic perturbations in an in vivo-dependent manner, revealing heterogenous patterns of treatment sensitization or resistance in GBM. Furthermore, we demonstrate targeting of genes that function in the tumor microenvironment, enabling alterations of ligand-receptor interactions between immune and stromal cells following in vivo CRISPRi perturbations that can affect tumor cell phagocytosis. Conclusion In sum, we demonstrate the utility of multiplexed perturb-seq for in vivo single-cell dissection of adult cancer and normal tissue biology across multiple cell types in the context of therapeutic intervention, a platform with potential for broad application.

Abstract Safe storage and utilisation of hydrogen is an ongoing area of research, showing potential to enable hydrogen becoming an effective fuel, substituting current carbon-based sources. Hydrogen storage is associated with a high energy cost due to its low density and boiling point, which drives a high price. Clathrates (gas hydrates) are water-based (ice-like) structures incorporating small non-polar compounds such as H2 in cages formed by hydrogen bonded water molecules. Since only water is required to construct the cages, clathrates have been identified as a potential solution for safe storage of hydrogen. In bulk, pure hydrogen clathrate (H2O-H2) only forms in harsh conditions, but confined in nanospaces the properties of water are altered and hydrogen storage at mild pressure and temperature could become possible. Here, specifically a hydrophobic mesoporous silica is proposed as a host material, providing a suitable nano-confinement for ice-like clathrate hydrate. The hybrid silica material shows an important decrease of the pressure required for clathrate formation (approx. 20%) compared to the pure H2O-H2 system. In-situ inelastic neutron scattering (INS) and neutron diffraction (ND) provided unique insights into the interaction of hydrogen with the complex surface of the hybrid material and demonstrated the stability of nano-confined hydrogen clathrate hydrate.

Abstract Marine silicate alteration exerts a major influence on marine carbon and cation cycles, but has proven difficult to quantify. In this context, silicon isotopes of marine pore fluids became an important tracer. However, poorly constrained silicon isotope signatures of precipitates produced during silicate alteration (i.e. authigenic clays) remain a major source of uncertainty. Here we present in situ silicon isotope analyses of marine authigenic clays (intergrown iron-smectites and iron-glauconites) occurring within recent sediments from the Oregon margin, eastern North Pacific. We identify a trend to lower silicon isotopes (from −2.24‰ to −3.17‰), accompanied by decreasing aluminum/silicon ratios and increasing potassium oxide contents, which we interpret as an isotopic shift caused by progressive clay maturation via dissolution-reprecipitation reactions. Our modelling suggests that this clay maturation pathway, together with mixing of other fluid sources, may induce pore fluid silicon isotope shifts of up to −1.7‰, if sufficient newly precipitated clays are re-dissolved. This could potentially produce silicon isotopes values significantly lower than seawater and implies that conventional isotope-based approaches underestimate the prevalence of marine silicate alteration. Our findings highlight that clay maturation must be considered when interpreting silicon isotope signatures in terms of marine silicate alteration and upscaling to global element cycles.

Abstract Heatwaves (HWs) pose a severe threat to human and ecological systems. Here we assess the projected changes in heatwaves over Latin America using bias corrected high-resolution regional climate simulations under two Representative Concentration Pathway scenarios (RCPs). Heatwaves are projected to be more frequent, long-lasting, and intense in the mid-century under both RCP2.6 and RCP8.5 scenarios, with severe increases under the RCP8.5 scenario. Even under the low emissions scenario of RCP2.6, the frequency of heatwaves doubles over most of the region. A three- to tenfold rise in population exposure to heatwave days is projected over Central and South America, with climate change playing a dominant role in driving these changes. Results show that following the low emission pathway would reduce 57% and 50% of heatwave exposure for Central and South American regions respectively, highlighting the need to control anthropogenic emissions and implement sustainable practices.

Abstract Male breast cancer (MBC) is a rare condition with unique characteristics compared to female breast cancer (FBC). Despite its scarceness, there is growing evidence that MBC should not be studied and treated as FBC due to factors like later diagnosis stage and distinct genetic makeup. Retrospective observational study in the EpiChron Cohort, selecting all the prevalent patients with breast cancer between 2010 and 2019. Logistic models were used to determine associated comorbidities. Between 2010 and 2019, 105 MBC and 11,657 FBC patients were found in the EpiChron Cohort. MBC patients had a high mean age at diagnosis and number of comorbidities. Paying attention to comorbidity prevalences in breast cancer patients, it was clear that MBC patients tended to be prone to cardio-metabolic coexisting diseases, while FBC patients were more prone to hormone-, bone- and mental diseases. There were nine chronic conditions associated to MBC patients, but after a year-by-birth matching only four associations remained. Two of them were associated previously [odds ratio (95% confidence interval)]: “Disorder of lipid metabolism” [1.65 (1.03–2.64)] and “Genitourinary symptoms and ill-defined conditions” [2.03 (1.07–3.87)]; and the other two were new, “Anxiety disorders” [2.05 (1.09–3.87)] and “Osteoporosis” [3.58 (1.26–10.14)]. After comparing associated comorbidities in FBC with those in MBC, it seems MBC patients share some of them, but they have their own particular set of coexisting diseases. In fact, once a year-by-birth matching was performed in MBC patient cohort, it was more obvious MBC comorbidities behave more similar to none-Breast-Cancer male population than to FBC patients. These findings highlight the distinct characteristics of the MBC patient population and the need for a tailored approach of managing MBC.

El 16 de abril de 2016 ocurrió un terremoto en Ecuador de magnitud 7.8 el cual causó enormes pérdidas humanas y materiales, y miles de personas heridas y desplazadas. Este evento sísmico forma parte de un conjunto de sismos en la provincia de Manabí en la región costera de Ecuador donde se produce la subducción de la placa de Nazca bajo la placa Sudamericana. Proponemos estudiar este conjunto de sismos desde la perspectiva de la mecánica estadística no extensiva utilizando el concepto de entropía propuesta por Tsallis en (Tsallis, 2009). Desarrollamos el cálculo del coeficiente de complejidad q para la magnitud de los sismos, parámetro que cuantifica el valor de complejidad de un sistema, y lo aplicamos al catálogo de terremotos en la zona de alto acoplamiento sísmico de Manabí-Esmeraldas en la zona de subducción de Ecuador. Los resultados muestran una relación entre los cambios en el coeficiente de complejidad q a través del tiempo y la ocurrencia de sismos de gran magnitud M>5. El terremoto del 16 de abril de 2016 acompaña un previo incremento en el valor de q el cual coincide con otros estudios anteriores como en (Papadakis et al., 2015).

Bartonella spp. are opportunistic, vectorborne bacteria that can cause disease in both animals and humans. We investigated the molecular occurrence of Bartonella spp. in 634 phlebotomine sand fly specimens, belonging to 44 different sand fly species, sampled during 2017–2021 in north and northeastern Brazil. We detected Bartonella sp. DNA in 8.7% (55/634) of the specimens by using a quantitative real-time PCR targeting the 16S-23S internal transcribed spacer intergenic region. Phylogenetic analysis positioned the Lutzomyia longipalpis sand fly–associated Bartonella gltA gene sequence in the same subclade as Bartonella ancashensis sequences and revealed a Bartonella sp. sequence in a Dampfomyia beltrani sand fly from Mexico. We amplified a bat-associated Bartonella nuoG sequence from a specimen of Nyssomyia antunesi sand fly. Our findings document the presence of Bartonella DNA in sand flies from Brazil, suggesting possible involvement of these insects in the epidemiologic cycle of Bartonella species.

INTRODUCTION: Age-related muscle changes, translated into a decrease both in muscle imass and functionality, are determinants of a decrease in strength and resistance to exercise in older adults. OBJECTIVE: To correlate the loss of muscle mass and functionality with the respiratory function in older adults. METHODS: Cross-sectional study including 18 volunteers with age above 65 years (13 women and 5 men) included in the AGA@4life Project. All participants performed functional respiratory tests with an Flowhandy ZAN 100 spirometer, and handgrip strength was assessed with an appropriate dynamometer. Nutritional profile was assessed and body composition was evaluated via bioimpedance. RESULTS: There was a significant association between the percentage of lean mass and several spirometric parameters, namely the FEV1, FVC, PEF25, PEF50, PEF25/75 and PEF. Significant associations were also found with the self-efficacy for exercise and the same respiratory parameters. A significant and positive correlation was observed between the percentage of lean mass and handgrip strength. CONCLUSIONS: The results show an association between respiratory function and functional and clinical parameters characteristic of sarcopenia, suggesting common pathophysiological mechanisms in the limitation observed with the worsening of these parameters.

RESUMEN Las producciones agropecuarias en la Región Pampeana (RP) han generado la reducción de bases y acidificación de suelos por extracción sin reposición de nutrientes y elevado uso de fertilizantes. Esta problemática en zonas templadas no ha sido estudiada minuciosamente como en zonas tropicales, afectando principalmente a cultivos de leguminosas. El uso de correctores y fertilizantes cálcicos ha demostrado resultados variables en la RP, evidenciando la complejidad de la práctica. El uso de fertilizantes podría ser una práctica coyuntural al uso de correctores. El objetivo fue evaluar fertilizantes y enmiendas cálcicas en suelos de la provincia de Buenos Aires sobre 1) producción de materia seca (MS) de biomasa aérea, concentración de calcio (Ca) (CCaB) y magnesio (Mg) (CMgB) y exportación de Ca (ECaB) y Mg (EMgB) de soja forrajera, 2) propiedades fisicoquímicas y químicas del suelo y 3) balance de calcio (BCaS). Se realizó un ensayo en invernáculo sobre soja en suelos de Bellocq e Inchausti con 50 kg ha-1 y 100 kg ha-1 de Ca como fertilizante, 1500 kg ha-1 de caliza (C1500) y un tratamiento testigo sin productos (T). El uso de 100 kg ha-1 de Ca con fertilizante incrementó la MS de soja asociado al incremento a valores de 4 meq l-1 de Ca en la fracción soluble-disponible del suelo (CaExt). La CCaB y CMgB en soja mostraron diferencias solamente entre suelos. La ECaS dependió exclusivamente de la producción de MS. El BCaS fue negativo solamente en el tratamiento donde no se aplicó producto. Estos resultados son importantes para entender la dinámica de nutrientes básicos en suelos de la RP, cuyos niveles en suelo están disminuyendo debido a los balances negativos, que incluso han generado acidificación de suelos. Además, podrían ser utilizados en planteos de manejo sitio-específico del suelo, garantizados por las amplias tecnologías disponibles relacionadas con la agricultura de precisión. Asimismo, mostraron que el CaExt podría ser un indicador de suficiencia cálcica.

Abstract Fermentation is the oldest biotechnology in which a metabolic process carried out without the involvement of oxygen. It is one of the food processing methods that improve the nutrient contents and sensorial properties with potentially reducing or eliminating pathogenic microorganisms and natural toxins. The aim of this review is to compare, contrast and summarize the scientific data on the effect of fermentation on physicochemical properties, anti-nutritional factors and sensory properties of cereal-based fermented foods and beverages. The results of this review showed that fermentation improves the nutritional value of some proximate composition such as crude protein and fat contents, while decreases the carbohydrate and crude fiber contents. It also improves the bioavailability, antioxidant activities and sensory properties of cereal-based foods and beverages. This review concluded that fermentation improves the nutritional quality of proximate composition, bioavailability of minerals and phytochemicals, and decrease the anti-nutritional factors of cereal-based fermented foods and beverages.

Abstract Background Human onchocerciasis remains a public health problem in Ghana. Mass drug administration (MDA) with ivermectin (IVM) has reduced disease morbidity and prevalence, but the transmission of onchocerciasis remains ongoing in several endemic foci. We investigated parasite transmission in some endemic communities in Ghana that had received > 18 rounds of annual MDA with IVM and determined the species composition of black fly (Simulium damnosum) vectors in these areas. Methods Adult female black flies were collected using human landing catches and identified as either forest or savanna species using morpho-taxonomic keys. The adult flies underwent dissection to determine their parity and detect any O. volvulus larvae, followed by the calculation of entomological indices. Simulium damnosum s.l. larvae were collected and preserved in freshly prepared Carnoy’s fixative and were later used for cytotaxonomic studies. Results A total of 9,983 adult flies were caught: 6,569 and 3,414 in the rainy and dry seasons respectively. Black fly biting activities over the study period showed bimodal or trimodal patterns. The highest monthly biting rate (MBR) of 10,578.75 bites/person/month was recorded in July in Beposo, while the highest monthly transmission potential of 100.69 infective bites/person/month was recorded in Asubende in August. Morphological analysis of 2,032 flies showed that 99.8% (2,028) of the flies were savanna species, with only 4 (0.2%) adult flies being of the forest species. Cytogenetic studies on 114 black fly larvae revealed three cytospecies (Simulium damnosum s.s., S. sirbanum and S. sanctipauli) in the study area. Conclusions The present studies confirmed an ongoing transmission of onchocerciasis in the study communities except Abua-1. It also provides further information on biting behaviors and onchocerciasis transmission indices in the study communities. Further, our data confirmed the savanna species (S. damnosum s.s. and S. sirbanum) of the S. damnosum s.l. to be the major vectors of onchocerciasis in the study areas, with only an occasional influx of forest cytotypes. Graphical Abstract

Abstract The Notch receptor is a pleiotropic signaling protein that translates intercellular ligand interactions into changes in gene expression via the nuclear localization of the Notch intracellular Domain (NICD). Using a combination of immunohistochemistry, RNA in situ, Optogenetics and super-resolution live imaging of transcription in human cells, we show that the N1ICD can form condensates that positively facilitate Notch target gene expression. We determined that N1ICD undergoes Phase Separation Coupled Percolation (PSCP) into transcriptional condensates, which recruit, enrich, and encapsulate a broad set of core transcriptional proteins. We show that the capacity for condensation is due to the intrinsically disordered transcriptional activation domain of the N1ICD. In addition, the formation of such transcriptional condensates acts to promote Notch-mediated super enhancer-looping and concomitant activation of the MYC protooncogene expression. Overall, we introduce a novel mechanism of Notch1 activity in which discrete changes in nuclear N1ICD abundance are translated into the assembly of transcriptional condensates that facilitate gene expression by enriching essential transcriptional machineries at target genomic loci.

Abstract Background Ensuring the availability of safe drinking water remains a critical challenge in developing countries, including Ethiopia. Therefore, this paper aimed to investigate the prevalence of fecal coliform and E. coli bacteria and, geographical, children availability, and seasonal exposure assessment through a meta-analysis. Methods Two independent review groups extensively searched internet databases for English-language research articles published between 2013 and 2023. This systematic review and meta-analysis followed PRISMA guidelines. The methodological quality of each included study was evaluated using the STROBE guidelines. Publication bias was assessed by visual inspection of a funnel plot and then tested by the Egger regression test, and meta-analysis was performed using DerSimonian and Laird random-effects models with inverse variance weighting. Subgroup analyses were also conducted to explore heterogeneity. Results Out of 48 potentially relevant studies, only 21 fulfilled the inclusion criteria and were considered for meta-analysis. The pooled prevalence of fecal coliform and E. coli was 64% (95% CI: 56.0–71.0%, I 2 = 95.8%) and 54% (95% CI: 45.7–62.3%, I 2 = 94.2%), respectively. Subgroup analysis revealed that the prevalence of fecal coliform bacteria increased during the wet season (70%) compared to the dry season (60%), particularly in households with under-five children (74%) compared to all households (61%), in rural (68%) versus urban (66%) areas, and in regions with high prevalence such as Amhara (71%), Gambela (71%), and Oromia (70%). Similarly, the prevalence of E. coli was higher in households with under-five children (66%) than in all households (46%). Conclusions The analysis highlights the higher prevalence of fecal coliform and E. coli within households drinking water, indicating that these bacteria are a significant public health concern. Moreover, these findings emphasize the critical need for targeted interventions aimed at improving drinking water quality to reduce the risk of fecal contamination and enhance public health outcomes for susceptible groups, including households with under-five children, in particular geographical areas such as the Amhara, Gambela, and Oromia regions, as well as rural areas, at point-of-use, and during the rainy season. Registration This review was registered on PROSPERO (registration ID - CRD42023448812).

In a specific area, fertilizer application for a crop depends on the soil type and profitability. Optimizing chemical fertilizer utilization in crop production is crucial from an environmental and economic point of view. However, there is limited information available on the optimum NPSB fertilizer rate for the production of wheat and barley in the study area. Thus, the study aimed to establish area-specific NPSB (18.9% N, 16.44% P, 6.95% S, and 0.1% B) blended fertilizer rate recommendations for the optimal grain yield and profitability of wheat and barley. The field experiment was conducted in two locations in the 2021 and 2022 cropping seasons using a randomized complete block design with three replications. The nine treatments included 0, 25, 50, 75, 100, 125, 150, 175, and 200 kg ha−1 NPSB fertilizer rates. Growth, yield, and yield component data in wheat and barley were collected from randomly selected individual plants and the net plot area. An economic analysis was conducted for grain yield using the procedure established by the International Maize and Wheat Improvement Center. The analysis of variance results showed that blended fertilizer significantly (p < 0.01) affected plant height, number of productive tillers, spike length, number of kernels, thousand seed weight, biomass yield, grain yield, and harvest index traits. The application of a 150 kg ha−1 NPSB rate produced the highest grain yield (5419.0 kg ha−1) in wheat, whereas the application of a 125 kg ha−1 NPSB rate gave the maximum grain yield (4708.0 kg ha−1) in food barley. The economic analysis revealed that the application of a 150 kg ha−1 NPSB fertilizer rate for wheat gave the highest net benefits (309711.50 ETB ha−1) and marginal rate of return (MRR) (4096.96%), while the application of a 125 kg ha−1 NPSB fertilizer rate for barley obtained the highest net benefits (184424.00 ETB ha−1) and MRR (2195.39%). Therefore, to optimize the productivity and profitability of wheat and barley in the study area and similar agroecologies, farmers are recommended to use 150 kg ha⁻¹ NPSB for wheat and 125 kg ha⁻¹ NPSB for barley.

Los gases arteriales son herramientas fundamentales para evaluar objetivamente a pacientes con patologías agudas y crónicas, dado que proporcionan información sobre los índices de oxigenación, ventilación, equilibrio ácido-base y el suministro de oxígeno a nivel celular. Interpretarlos adecuadamente tiene gran importancia clínica, dado que influye en la toma de decisiones permite evaluar la respuesta a intervenciones terapéuticas. Este artículo tiene como objetivo presentar al lector los conceptos básicos de la fisiología del intercambio gaseoso, los trastornos ácido-base más comunes y una interpretación práctica de los gases arteriales. Se utiliza una combinación de ilustraciones gráficas, tablas y algoritmos para facilitar la comprensión y el abordaje clínico de pacientes con alteraciones respiratorias y metabólicas.

Abstract Background There is no consensus on the cause and effect of systemic chronic inflammation (SCI) regarding chronic obstructive pulmonary disease (COPD). The impact of second-hand smoke (SHS) on COPD has reached inconsistent conclusions. Methods The China Kadoorie Biobank cohort was followed up from the 2004–08 baseline survey to 31 December 2018. Among the selected 445,523 participants in the final analysis, Cox and linear regressions were performed to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of tobacco exposure with COPD risk and baseline levels of log-transformed inflammatory factors [βs (95% CIs)], respectively. Results Participants were followed up for a median of 12.1 years and 11,825 incident COPD events were documented. Ever-smokers were associated with a higher risk of COPD than non-smokers with non-weekly SHS exposure. A younger age to start smoking, a greater amount of daily tobacco consumption, and deeper inhalation were associated with increased risk of COPD and correlated with elevated levels of plasma high-sensitivity C-reactive protein (hs-CRP, all P trend

Abstract We revisit Duff, Okun, and Veneziano’s divergent views on the number of fundamental constants and argue that the issue can be set to rest by having spacetime as the starting point. This procedure disentangles the resolution in what depends on the assumed spacetime (whether relativistic or not) from the theories built over it. By defining that the number of fundamental constants equals the minimal number of independent standards necessary to express all observables, as assumed by Duff, Okun, and Veneziano, it is shown that the same units fixed by the apparatuses used to construct the spacetimes are enough to express all observables of the physical laws defined over them. As a result, the number of fundamental constants equals one in relativistic spacetimes.

The methylenetetrahydrofolate reductase (MTHFR) gene 677C➔T polymorphism is capable of altering folate metabolism and can modify certain neoplasia risk. Reports have suggested that folate can have an influence on bone development and so it is of interest to know if the MTHFR 677C➔T polymorphism is associated with the malignant transformation process of this tissue. The polymorphism was determined in 55 patients with osteosarcoma and in 180 healthy individuals. Compared with C/T+C/C genotypes, a 3.7-fold reduction in osteosarcoma probability is possible with the T/T genotype (OR 0.27, CI 95% 0.07–0.82). Undoubtedly, further studies, utilizing large samples and carried out on different populations, are necessary to confirm these results.

Abstract Background Cerebral blood flow dynamics can be explored through analysis of endothelial frequencies. Our hypothesis posits a disparity in endothelial activity among neonates with perinatal asphyxia, stratified by the presence or absence of neuronal lesions. Methods We conducted a retrospective longitudinal study involving newborns treated with hypothermia for moderate to severe asphyxia. Participants were grouped based on the presence or absence of neuronal damage to investigate temporal endothelial involvement in cerebral blood flow regulation. Regional cerebral oxygen saturation (rScO2) was measured using near-infrared spectroscopy (NIRS), and temporal series were analyzed in the frequency domain, utilizing the original frequency of the INVOS™ device. Results The study included 88 patients, with 53% (47/88) being male and 33% (29/88) demonstrating brain lesions on magnetic resonance imaging. Among them, 86% (76/88) had a gestational age exceeding 37 weeks according to the Ballard scale, and 81% (71/88) had a birth weight exceeding 2500 g. Cohen’s d effect size was calculated to assess differences in endothelial frequency between groups, indicating a small effect size based on cerebral MRI findings (Cohen’s d values for Day 2 = 0.2351 and Day 3 = 0.2325). Conclusion NIRS represents a valuable tool for monitoring cerebral autoregulation in neonates affected by perinatal asphyxia, underscoring the utility of assessing endothelial frequency or energy on rScO2 measured by NIRS using the original INVOS™ device frequency.

Abstract Background The effectiveness of dengue control interventions depends on an effective integrated surveillance system that involves analysis of multiple variables associated with the natural history and transmission dynamics of this arbovirus. Entomological indicators associated with other biotic and abiotic parameters can assertively characterize the spatiotemporal trends related to dengue transmission risk. However, the unpredictability of the non-linear nature of the data, as well as the uncertainty and subjectivity inherent in biological data are often neglected in conventional models. Methods As an alternative for analyzing dengue-related data, we devised a fuzzy-logic approach to test ensembles of these indicators across categories, which align with the concept of degrees of truth to characterize the success of dengue transmission by Aedes aegypti mosquitoes in an endemic city in Brazil. We used locally gathered entomological, demographic, environmental and epidemiological data as input sources using freely available data on digital platforms. The outcome variable, risk of transmission, was aggregated into three categories: low, medium, and high. Spatial data was georeferenced and the defuzzified values were interpolated to create a map, translating our findings to local public health managers and decision-makers to direct further vector control interventions. Results The classification of low, medium, and high transmission risk areas followed a seasonal trend expected for dengue occurrence in the region. The fuzzy approach captured the 2020 outbreak, when only 14.06% of the areas were classified as low risk. The classification of transmission risk based on the fuzzy system revealed effective in predicting an increase in dengue transmission, since more than 75% of high-risk areas had an increase in dengue incidence within the following 15 days. Conclusions Our study demonstrated the ability of fuzzy logic to characterize the city’s spatiotemporal heterogeneity in relation to areas at high risk of dengue transmission, suggesting it can be considered as part of an integrated surveillance system to support timely decision-making.

Although advances in contemporary medical care have broadened access to healthcare and extended the human life span, deaths resulting from antimicrobial-resistant pathogens continue to increase. This minireview summarizes the evidence that AI and machine learning, coupled with precision medicine and alternative therapies, such as repurposing non-antibiotic drugs and the use of bacteriophages, has promise to halt this advance.