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The mammalian intestine is colonized by trillions of microorganisms that are collectively referred to as the gut microbiota. The majority of symbionts have co-evolved with their host in a mutualistic relationship that benefits both. Under certain conditions, such as in Crohn's disease, a subtype of inflammatory bowel disease, some symbionts bloom to cause disease in genetically susceptible hosts. Although the identity and function of disease-causing microorganisms or pathobionts in Crohn's disease remain largely unknown, mounting evidence from animal models suggests that pathobionts triggering Crohn's disease-like colitis inhabit certain niches and penetrate the intestinal tissue to trigger inflammation. In this Review, we discuss the distinct niches occupied by intestinal symbionts and the evidence that pathobionts triggering Crohn's disease live in the mucus layer or near the intestinal epithelium. We also discuss how Crohn's disease-associated mutations in the host disrupt intestinal homeostasis by promoting the penetration and accumulation of pathobionts in the intestinal tissue. Finally, we discuss the potential role of microbiome-based interventions in precision therapeutic strategies for the treatment of Crohn's disease., (© 2024. Springer Nature Limited.)

Background: Screening for depression remains a priority for people living with HIV (PLWH) accessing care. The nine-item Patient Health Questionnaire (PHQ-9) is a widely used depression screening tool, but has limited accuracy when applied across various cultural contexts. We aimed to evaluate the performance of alternative PHQ-9 scoring algorithms in sub-Saharan African PLWH., Setting: five HIV programs in Cameroon, Côte d'Ivoire, Kenya, Senegal and the Republic of Congo., Methods: Adult PLWH were screened for depression during the 2018-2022 period. Diagnosis confirmation was done by psychiatrist blinded clinical evaluation (gold standard). Diagnostic performances, including sensitivity, and area under the curve (AUC)) of the traditional PHQ-9 scoring (positive screening - score≥10) was compared to alternative scoring algorithms including: i) the presence of ≥1 mood symptom (PHQ-9 items 1&2) combined with ≥2 other symptoms listed in the PHQ-9, and ii) a simplified recoding of each 4-response item into two categories (absence/presence)., Results: A total of 735 participants were included (54% female, median age 42 years [IQR 34-50]). Depression was diagnosed by a psychiatrist in 95(13%) participants. Alternative scoring sensitivities (0.59 to 0.74) were higher than that of the traditional score's (0.39). Compared to traditional scoring, AUC were significantly higher for PHQ-9 alternative scoring. Across settings, alternative scoring algorithms increased sensitivity and reduced variability., Conclusion: As a primary screening test, new scoring algorithms appeared to improve the PHQ-9 sensitivity in identifying depression and reduce heterogeneity across settings. This alternative might be considered to identify PLWH in need of referral for further diagnostic evaluations., Competing Interests: The authors report no conflicts of interest related to this work., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To determine the factors associated with an increased risk of cesarean scar defect formation., Methods: A systematic literature search was performed up to July 2022 in PubMed databases following the PRISMA recommendations. All available English-language clinical studies presenting one or more factors that may affect the risk of cesarean scar defect were included., Results: 39 studies meeting the selection criteria were identified. An association was found between the number of previous cesarean sections and a significant increase in the risk of cesarean scar defect formation. Regarding patient age, gestational age at cesarean section, birth weight and emergency context did not appear to influence the risk of cesarean scar defect. However, cesarean sections performed during labor advanced stages of labor, may increase the risk. The data remain too limited to conclude on the impact of BMI, flexion uterine, and pregnancy pathologies (gestational diabetes, preeclampsia, premature rupture of membranes), the use of oxytocic, or infectious and hemorrhagic complications. Regarding the surgical technique, the literature suggested that a lower hysterotomy is associated with an increased risk of scar defect. However, the single- or double-layer suture technique did not provide a change in risk, and the data were too limited to conclude on the impact of the type of thread or suture used., Conclusion: The present systematic review of the literature suggests that several factors may increase the risk of developing a cesarean scar defect, such as the number of previous cesarean sections, a cesarean section performed during advanced labor, and a lower hysterotomy. However, the current state of the literature does not allow definitive conclusions to be drawn on most other factors., Competing Interests: Declaration of 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., (Copyright © 2024. Published by Elsevier Masson SAS.)

Background: Limited data is available concerning the patterns of antifungal use and invasive fungal infection (IFI)-associated mortality risk factors prior to and during the COVID-19 pandemic in a resource-limited setting., Methods: A single center retrospective cohort study was conducted to evaluate the patterns of antifungal use and IFI-associated mortality risk factors in a resource-limited setting prior to and during the COVID-19 pandemic. All patients age >18 years diagnosed with IFI were prospectively followed during a 3-year pre-COVID-19 pandemic period (period 1: 1/1/2017-12/31/2019) and a 3-year during COVID-19 pandemic period (period 2: 1/1/2020-12/31/2022). Patient characteristics, patterns of antifungal use, IFI-associated mortality risk factors, and adverse drug events were collected. Multivariate analysis was performed to identify IFI-associated mortality risk factors., Results: There was a total of 133 patients in this study: 60 (45.1%) in period 1 and 73 (54.9%) in period 2. Pre-emptive antifungal therapy was commonly practiced in period 2 (21.7% vs 37%, p=0.05). The presence of a central venous catheter (CVC) (aOR 3.19, p=0.007), hematologic adverse drug events (aOR 17.9, p=0.008) were potentially preventable risks for the overall IFI mortality in both periods. Appropriate antifungal use was protective against the overall IFI mortality in period 2 (aOR 0.09, p=0.009)., Conclusion: Several preventable IFI-associated mortality risk factors including the presence of CVC and inappropriate antifungal use were identified and served as key target changes for improvement of infection prevention, national policy to access appropriate antifungal agents, and antifungal stewardship in a resource-limited setting during the COVID-19 pandemic., (Copyright © 2024. Published by Elsevier Inc.)

Degeneracy is defined as multiple sets of solutions that can produce very similar system performance. Degeneracy is seen across phylogenetic scales, in all kinds of organisms. In neuroscience, degeneracy can be seen in the constellation of biophysical properties that produce a neuron's characteristic intrinsic properties and/or the constellation of mechanisms that determine circuit outputs or behavior. Here, we present examples of degeneracy at multiple levels of organization, from single-cell behavior, small circuits, large circuits, and, in cognition, drawing conclusions from work ranging from bacteria to human cognition. Degeneracy allows the individual-to-individual variability within a population that creates potential for evolution., Competing Interests: The authors declare no competing financial interest., (Copyright © 2024 the authors.)

Introduction: Due to the increased effectiveness of and access to antiretroviral therapy (ART), people with HIV (PWH) are living longer. As a result, the population of older PWH has increased. Mental and substance use disorders (MSDs) are common and frequently co-occurring among PWH and are associated with poor HIV care outcomes. Research into the prevalence and co-occurrence of MSDs among ageing PWH remains limited, particularly in low- and middle-income countries (LMICs)., Methods: We analysed data collected between 2020 and 2022 from the International epidemiology Databases to Evaluate AIDS (IeDEA) Sentinel Research Network cohort of PWH aged 40 years or older on ART at 11 HIV clinics in Brazil, Côte d'Ivoire, India, Kenya, Mexico, Uganda, Rwanda, Togo, Vietnam, Zambia and Zimbabwe. We estimated the prevalence and co-occurrence of unhealthy alcohol use (AUDIT-C ≥3 for women, ≥4 for men), unhealthy drug use (ASSIST >3 for cannabis, cocaine, amphetamines, inhalants, sedatives, hallucinogens and/or opioids), and moderate to severe symptoms of depression (PHQ-9 ≥10), anxiety (GAD-7 ≥10) and post-traumatic stress disorder (PTSD) (PCL-5 ≥33). Psychiatric multimorbidity was defined as having symptoms of two or more disorders assessed. Log binomial models assessed the association between socio-demographic and HIV care characteristics and symptoms of anxiety, depression, PTSD or unhealthy substance use., Results: Of 2821 participants, the prevalence of unhealthy alcohol and drug use was 21% and 5%, respectively. The prevalence of moderate to severe symptoms of depression, anxiety and PTSD was 14%, 9% and 6%, respectively. Overall, the prevalence of psychiatric multimorbidity was 11%. Among those with symptoms of at least one mental health or substance use outcome assessed (n = 1036), the prevalence of psychiatric multimorbidity was 31%. In binomial models, the prevalence of symptoms of depression and anxiety was higher, while the prevalence of unhealthy alcohol and drug use was lower among women than men., Conclusions: Unhealthy alcohol use and symptoms of depression were most commonly reported, among this cohort of PWH aged 40 or older across 11 LMICs. Integration of MSD screening and treatment into HIV care should be prioritized. The effectiveness and implementation of transdiagnostic or multi-focus mental health treatment approaches in HIV care settings should be examined., (© 2024 The Author(s). Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of International AIDS Society.)

Background: Lower extremity injuries account for an enormous portion of sports medicine cases in the United States each year. Unfortunately, there are no uniform criteria for athletes to complete prior to returning to sport (RTS) following a lower extremity injury. Therefore, the purpose of this systematic review is to review current literature for joint-specific and global lower extremity testing to determine the most valid functional test that can be utilized to reduce the risk of re-injury as athletes RTS., Methods: A systematic search of PubMed, PubMed Central, Cochrane Library, OVID, and Embase databases was conducted for studies prior to May 2024 following PRISMA guidelines. ROBINS-I Tool was utilized for the risk of bias assessment., Results: Of 19,189 studies, 114 (0.6%) studies published prior to May of 2024 met inclusion criteria and were analyzed. Eighty five percent of articles discussed RTS for individuals with knee pathology. Furthermore, 82% specifically analyzed RTS following ACL reconstruction. The most common RTS test was isokinetic dynamometry testing which is seen in 73% of studies. Only 6.2% of studies analyzed RTS for individuals with hip pathology and only two studies analyzed RTS for patients with ankle injuries., Conclusion: Even with the enormous amount of literature that exists regarding ACL injuries and testing there is no standardized criterion for RTS clearance. The suggested test batteries from this review can serve as a framework for future research and validation for joint-specific RTS functional testing., 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 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Pharmacovigilance (PV), or the ongoing safety monitoring after a medication has been licensed, plays a crucial role in pregnancy, as clinical trials often exclude pregnant people. It is important to understand how pregnancy PV projects operate in low- and middle-income countries (LMICs), where there is a disproportionate lack of PV data yet a high burden of adverse pregnancy outcomes. We conducted a scoping review to assess how exposures and outcomes were measured in recently published pregnancy PV projects in LMICs., Methods: We utilized a search string, secondary review, and team knowledge to review publications focusing on therapeutic or vaccine exposures among pregnant people in LMICs. We screened abstracts for relevance before conducting a full text review, and documented measurements of exposures and outcomes (categorized as maternal, birth, or neonatal/infant) among other factors, including study topic, setting, and design, comparator groups, and funding sources., Results: We identified 31 PV publications spanning at least 24 LMICs, all focusing on therapeutics or vaccines for infectious diseases, including HIV (n = 17), tuberculosis (TB; n = 9), malaria (n = 7), pertussis, tetanus, and diphtheria (n = 1), and influenza (n = 3). As for outcomes, n = 15, n = 31, and n = 20 of the publications covered maternal, birth, and neonatal/infant outcomes, respectively. Among HIV-specific publications, the primary exposure-outcome relationship of focus was exposure to maternal antiretroviral therapy and adverse outcomes. For TB-specific publications, the main exposures of interest were second-line drug-resistant TB and isoniazid-based prevention therapeutics for pregnant people living with HIV. For malaria-specific publications, the primary exposure-outcome relationship of interest was antimalarial medication exposure during pregnancy and adverse outcomes. Among vaccine-focused publications, the exposure was assessed during a specific time during pregnancy, with an overall interest in vaccine safety and/or efficacy. The study settings were frequently from Africa, designs varied from cohort or cross-sectional studies to clinical trials, and funding sources were largely from high-income countries., Conclusion: The published pregnancy PV projects were largely centered in Africa and concerned with infectious diseases. This may reflect the disease burden in LMICs but also funding priorities from high-income countries. As the prevalence of non-communicable diseases increases in LMICs, PV projects will have to broaden their scope. Birth and neonatal/infant outcomes were most reported, with fewer reporting on maternal outcomes and none on longer-term child outcomes; additionally, heterogeneity existed in definitions and ascertainment of specific measures. Notably, almost all projects covered a single therapeutic exposure, missing an opportunity to leverage their projects to cover additional exposures, add scientific rigor, create uniformity across health services, and bolster existing health systems. For many publications, the timing of exposure, specifically by trimester, was crucial to maternal and neonatal safety. While currently published pregnancy PV literature offer insights into the PV landscape in LMICs, further work is needed to standardize definitions and measurements, integrate PV projects across health services, and establish longer-term monitoring., (© 2024. The Author(s).)

Objective: The aim of this study was to assess the performance of the nine-item Patient Health Questionnaire (PHQ-9) against psychiatrist diagnosis in people with HIV (PWH)., Design: Cross-sectional analysis of data collected between January 2018 and July 2022 across five sites in Cameroon, Cote d'Ivoire, Kenya, Senegal, and the Republic of Congo. Participants were ≥18 years and receiving HIV care at the participating site. PHQ-9 was administered by study staff followed by a psychiatrist's evaluation within 3 days., Results: Overall, 778 participants with complete data were included: 297 (38.2%) in Cameroon, 132 (17.0%) in Congo, 148 (19.0%) in Cote d'Ivoire, 98 (12.6%) in Kenya, and 103 (13.2%) in Senegal. The area under the curve for PHQ-9 score was generally high ranging from 0.935 [95% confidence interval (CI): 0.893, 0.977] in Cote d'Ivoire to 0.768 (95% CI: 0.589, 0.947) in Congo. However, for the common cut-off score ≥10, sensitivity was low: 50% or lower in Cameroon, Congo and Senegal, 66.7% in Kenya and 70.6% in Cote d'Ivoire. But negative predictive values (NPV) were high: 98.9% (95% CI: 96.9%, 99.8%) in Cameroon, 96.1 (95% CI: 91.1, 98.7) in Cote d'Ivoire, 96.3% (95% CI: 89.7%, 99.2%) in Kenya, 95.7% (95% CI: 90.2%, 98.6%) in Congo, and 89.0% (95% CI: 81.2%, 94.4%) in Senegal., Interpretation: Across all countries, PHQ-9 score ≥10 performed very poorly (low sensitivity) as a tool to identify psychiatrist diagnosed depression. However, the observed high NPV suggests it can be used to rule out depression., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: Spinocerebellar ataxia 27B due to GAA repeat expansions in the fibroblast growth factor 14 (FGF14) gene has recently been recognized as a common cause of late-onset hereditary cerebellar ataxia. Here we present the first report of this disease in the US population, characterizing its clinical manifestations, disease progression, pathological abnormalities, and response to 4-aminopyridine in a cohort of 102 patients bearing GAA repeat expansions., Methods: We compiled a series of patients with SCA27B, recruited from 5 academic centers across the United States. Clinical manifestations and patient demographics were collected retrospectively from clinical records in an unblinded approach using a standardized form. Post-mortem analysis was done on 4 brains of patients with genetically confirmed SCA27B., Results: In our cohort of 102 patients with SCA27B, we found that SCA27B was a late-onset (57 ± 12.5 years) slowly progressive ataxia with an episodic component in 51% of patients. Balance and gait impairment were almost always present at disease onset. The principal finding on post-mortem examination of 4 brain specimens was loss of Purkinje neurons that was most severe in the vermis most particularly in the anterior vermis. Similar to European populations, a high percent of patients 21/28 (75%) reported a positive treatment response with 4-aminopyridine., Interpretation: Our study further estimates prevalence and further expands the clinical, imaging and pathological features of SCA27B, while looking at treatment response, disease progression, and survival in patients with this disease. Testing for SCA27B should be considered in all undiagnosed ataxia patients, especially those with episodic onset. ANN NEUROL 2024., (© 2024 The Author(s). Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

In addressing human reasoning biases, "easy-fix" attentional focus interventions have shown that we can prompt reasoners to align responses with logico-mathematical principles. The current study aimed to test the impact of such interventions on both intuitive and deliberate responses on base-rate items. Using a two-response paradigm, participants provided initial intuitive responses under time constraints and cognitive load, followed by deliberate responses. During the intervention, we used attentional focus manipulations with base-rate items that aimed to redirect participants' attention toward the "logical" base-rate cue (i.e., the logical intervention) or toward the "heuristic" descriptive cue (i.e., the heuristic intervention). The results indicate that the logical intervention led to improved alignment with logico-mathematical principles in both intuitive and deliberate responses, albeit with a modest effect size. Conversely, the heuristic intervention had no discernible impact on accuracy. This indicates that our attentional focus manipulation is more effective at getting reasoners to respect rather than to override base-rates., (© 2024. The Psychonomic Society, Inc.)

Post-translational modifications (PTMs), such as phosphorylation and O-N-acetyl-β-d-glucosaminylation (O-GlcNAcylation), are involved in the fine spatiotemporal regulation of protein functions, and their dynamic interplay is at the heart of protein language. The coexistence of phosphorylation and O-GlcNAcylation on a protein leads to the diversification of proteoforms. It is therefore essential to decipher the phosphorylation/O-GlcNAcylation interplay on protein species that orchestrates cellular processes in a specific physiological or pathophysiological context. However, simultaneous visualization of phosphorylation and O-GlcNAcylation patterns on a protein of interest remains a challenge. To map the proteoforms of a protein, we have developed an easy-to-use two-dimensional electrophoresis method with a single sample processing permitting simultaneous visualization of the phosphorylated and the O-GlcNAcylated forms of the protein of interest. This method, we termed 2D-WGA-Phos-tag-PAGE relies on proteoforms retardation by affinity gel electrophoresis. With this novel approach, we established the cartography of phospho- and glycoforms of αB-crystallin and desmin in the whole extract and the cytoskeleton protein subfraction in skeletal muscle cells. Interestingly, we have shown that the pattern of phosphorylation and O-GlcNAcylation depends of the subcellular subfraction. Moreover, we have also shown that proteotoxic stress condition increased the complexity of the pattern of PTMs on αB-crystallin., (© 2024 Wiley‐VCH GmbH.)

Background and study aim Liver cirrhosis causes portal hypertension that leads to dysfunction of the gastrointestinal tract, which may result in complications including upper gastrointestinal (UGI) bleeding. This study sought to determine the prevalence and the clinical correlates of these UGI abnormalities in patients with liver cirrhosis receiving care at the Komfo Anokye Teaching Hospital in Kumasi, Ghana. Patients and methods One hundred and forty-five participants with liver cirrhosis were consecutively sampled and clinically evaluated for symptoms and signs of liver cirrhosis and then underwent esophagogastroduodenoscopy (EGD). Results The mean age of the respondents was 46.50 ± 12.14 years, with the majority being males (106, 73.10%) and in Child-Pugh class C (111, 76.55%). Fatigue (128, 88.28%) and ascites (127, 87.59%) were the most common symptoms and signs, respectively. Fatigue, itch, and ascites were significantly correlated with the severity of liver cirrhosis, with an adjusted odd ratio (AOR) (confidence interval (CI)) of 3.56 (1.11-11.47), p-value of 0.03, 4.35 (1.34-14.18), p-value of 0.02 and 22.50 (4.88-103.77), p-value < 0.01, respectively. Esophageal varices were the most common UGI endoscopic findings, occurring in 102 (70.34%) patients, and correlated with the severity of liver cirrhosis, AOR (CI) of 5.19 (1.70-15.87), p-value of 0.01. Other common findings included gastritis in 71 (48.97%), portal hypertensive gastropathy in 67 (46.2%), duodenitis in 49 (33.79%), and peptic ulcer in 46 (31.72%). Conclusions Fatigue, ascites, and esophageal varices were the most common symptoms, signs, and EGD findings, respectively. Fatigue, itch, ascites, esophageal varices, duodenitis, and gastric antral vascular ectasia correlate with the severity of liver cirrhosis., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Committee of Human Research Publication and Ethics (CHRPE) of Kwame Nkrumah University of Science and Technology and Komfo Anokye Teaching Hospital issued approval CHRPE/AP/045/19. Ethical approval for this study was obtained from the Committee of Human Research Publication and Ethics (CHRPE) of Kwame Nkrumah University of Science and Technology and Komfo Anokye Teaching Hospital (CHRPE/AP/045/19). The principles of informed consent and confidentiality were ensured throughout the study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. 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, Oppong et al.)

Hyalomma marginatum is an invasive tick species recently established in mainland southern France. This tick is known to host a diverse range of human and animal pathogens. While information about the dynamics of these pathogens is crucial to assess disease risk and develop effective monitoring strategies, few data on the spatial dynamics of these pathogens are currently available. We collected ticks in 27 sites in the Occitanie region to characterize spatial patterns of H. marginatum -borne pathogens. Several pathogens have been detected: Theileria equi (9.2%), Theileria orientalis (0.2%), Anaplasma phagocytophilum (1.6%), Anaplasma marginale (0.8%), and Rickettsia aeschlimannii (87.3%). Interestingly, we found a spatial clustered distribution for the pathogen R. aeschlimannii between two geographically isolated areas with infection rates and bacterial loads significantly lower in Hérault/Gard departments (infection rate 78.6% in average) compared to Aude/Pyrénées-Orientales departments (infection rate 92.3% in average). At a smaller scale, R. aeschlimannii infection rates varied from one site to another, ranging from 29% to 100%. Overall, such high infection rates (87.3% on average) and the effective maternal transmission of R. aeschlimannii might suggest a role as a tick symbiont in H. marginatum . Further studies are thus needed to understand both the status and the role of R. aeschlimannii in H. marginatum ticks.IMPORTANCETicks are obligatory hematophagous arthropods that transmit pathogens of medical and veterinary importance. Pathogen infections cause serious health issues in humans and considerable economic loss in domestic animals. Information about the presence of pathogens in ticks and their dynamics is crucial to assess disease risk for public and animal health. Analyzing tick-borne pathogens in ticks collected in 27 sites in the Occitanie region, our results highlight clear spatial patterns in the Hyalomma marginatum -borne pathogen distribution and strengthen the postulate that it is essential to develop effective monitoring strategies and consider the spatial scale to better characterize the circulation of tick-borne pathogens., Competing Interests: The authors declare no conflict of interest.

Abstract: Expression of the thrombomodulin (TM) variant c.1611C>A (p.Cys537Stop) leads to the synthesis of a protein with no cytoplasmic tail and a transmembrane domain shortened by 3 amino acids (TM536). However, little is known regarding the release mechanism and properties of TM536. Using umbilical vein endothelial cells and peripheral blood-derived endothelial colony-forming cells from a heterozygous carrier of the TM536 variant as well as overexpression cell models, we demonstrated that TM536 is released from cells by an unusual mechanism. First, TM536 is inserted into the endoplasmic reticulum (ER) membrane, then, because of the low hydrophobicity of its intramembrane domain, it escapes from it and follows the conventional secretory pathway to be released into the extracellular compartment without the involvement of proteolysis. This particular secretion mechanism yields a soluble TM536, which is poorly modified by chondroitin sulfate glycosaminoglycan compared with conventionally secreted soluble forms of TM, and therefore has a suboptimal capacity to mediate thrombin-dependent activation of protein C (PC). We also showed that TM536 cellular trafficking was altered, with retention in the early secretory pathway and increased sensitivity to ER-associated degradation. As expected, activation of ER-associated degradation increased TM536 degradation and reduced its release. The expression of TM536 at the cell surface was low, and its distribution in lipid raft-like membrane microdomains was altered, resulting in low thrombin-dependent PC activation on the cell surface., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background and Purpose: To evaluate the impact of a deep learning (DL)-assisted interactive contouring tool on inter-observer variability and the time taken to complete tumour contouring., Materials and Methods: Nine clinicians contoured the gross tumour volume (GTV) using the PET-CT scans of 10 non-small cell lung cancer (NSCLC) patients, either using DL-assisted or manual contouring tools. After contouring a case using one contouring method, the same case was contoured one week later using the other method. The contours and time taken were compared., Results: Use of the DL-assisted tool led to a statistically significant decrease in active contouring time of 23 % relative to the standard manual segmentation method (p < 0.01). The mean observation time for all clinicians and cases made up nearly 60 % of interaction time for both contouring approaches. On average the time spent contouring per case was reduced from 22 min to 19 min when using the DL-assisted tool. Additionally, the DL-assisted tool reduced contour variability in the parts of tumour where clinicians tended to disagree the most, while the consensus contour was similar whichever of the two contouring approaches was used., Conclusions: A DL-assisted interactive contouring approach decreased active contouring time and local inter-observer variability when used to delineate lung cancer GTVs compared to a standard manual method. Integration of this tool into the clinical workflow could assist clinicians in contouring tasks and improve contouring efficiency., 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 The Author(s). Published by Elsevier B.V. All rights reserved.)

Potential associations between periconception dolutegravir (DTG) exposure and neural tube defects (NTDs) reported in 2018 caused shifting international and national antiretroviral treatment (ART) guidelines. They sometimes required women to use contraception prior to initiating DTG. To better understand the tensions between ART and family planning (FP) choices, and explore the decision-making processes of women living with HIV (WLHIV) and their healthcare providers (HCPs) employed, we conducted interviews with WLHIV exposed to DTG and their providers in western Kenya from July 2019 to August 2020. For the interviews with WLHIV, we sampled women at varying ages who either continued using DTG, switched to a different ART, or became pregnant while using DTG. We utilized inductive coding and thematic analysis. We conducted 44 interviews with WLHIV and 10 with providers. We found four dominant themes: (1) a range of attitudes about birth defects, (2) nuanced knowledge of DTG and its potential risk of birth defects, (3) significant tensions at the intersection of DTG and FP use with varying priorities amongst WLHIV and their providers for navigating the tensions, and (4) WLHIV desiring autonomy, and provider support for this, in such decision-making. Variations in beliefs were noted between WLHIV and HCPs. WLHIV highlighted the impact of community and social beliefs when discussing their attitudes while HCPs generally reported more medicalized views towards DTG utilization, potential adverse outcomes, and FP selection. Decisions pertaining to ART and FP selection are complex, and HIV treatment guidelines need to better support women's agency and reproductive health justice., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Infection is a serious complication in neurosurgical patients who undergo external ventricular drain (EVD) insertion., Methods: We conducted a quasi-experimental study in patients who underwent EVD insertion to evaluate the impact of a multi-modal strategy to reduce the incidence of external ventricular drain associated infections (EVDAIs). The study was divided into 2 periods; (1) the pre-intervention period when techniques for EVD insertion and maintenance were up to the discretion of the neurosurgeons and (2) the post-intervention after implementation of a multi-modal strategy (cefazolin antibiotic prophylaxis, preoperative chlorhexidine showers, application of postoperative chlorhexidine-impregnated dressing, limited manipulation of the EVD, and meticulous EVD management). The primary outcome was the incidence rate of EVDAIs; secondary outcomes included in-hospital mortality rate, the hospital length of stay., Results: In total, 135 patients were included. The incidence rate of EVDAIs was significantly reduced in the post-intervention period (5.6 cases/1,000 EVD-days) compared with the pre-intervention period (18.2 cases/1,000 EVD-days; P=0.026). There were no differences in all secondary outcomes analyzed. This multi-modal strategy was associated with high satisfaction among health care personnel., Conclusions: Implementation of a multi-modal strategy was associated with a reduction in the incidence of EVDAIs. This was in line with our goal of promoting a new culture of safety despite being in a resource-limited setting., (Copyright © 2024 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: The therapeutic potential of relaxin for heart failure and renal disease in clinical trials is hampered by the short half-life of serelaxin. Optimization of fatty acid-acetylated single-chain peptide analogues of relaxin culminated in the design and synthesis of R2R01, a potent and selective RXFP1 agonist with subcutaneous bioavailability and extended half-life., Experimental Approach: Cellular assays and pharmacological models of RXFP1 activation were used to validate the potency and selectivity of R2R01. Increased renal blood flow was used as a translational marker of R2R01 activity. Human mastocytes (LAD2 cells) were used to study potential pseudo-allergic reactions and CD4+ T-cells to study immunogenicity. The pharmacokinetics of R2R01 were characterized in rats and minipigs., Key Results: In vitro, R2R01 had comparable potency and efficacy to relaxin as an agonist for human RXFP1. In vivo, subcutaneous administration of R2R01 increased heart rate and renal blood flow in normotensive and hypertensive rat and did not show evidence of tachyphylaxis. R2R01 also increased nipple length in rats, used as a chronic model of RXFP1 engagement. Pharmacokinetic studies showed that R2R01 has a significantly extended terminal half-life. The in vitro assays with LAD2 cells and CD4+ T-cells showed that R2R01 had low potential for pseudo-allergic and immunogenic reactions, respectively., Conclusion and Implications: R2R01 is a potent RXFP1 agonist with an extended half-life that increases renal blood flow in various settings including normotensive and hypertensive conditions. The preclinical efficacy and safety data supported clinical development of R2R01 as a potential new therapy for renal and cardiovascular diseases., (© 2024 British Pharmacological Society.)

Increased consumer awareness for healthier and more sustainable products has driven the search for naturally sourced compounds as substitutes for chemically synthesized counterparts. Research on pigments of natural origin, such as carotenoids, particularly lutein, has been increasing for over three decades. Lutein is recognized for its antioxidant and photoprotective activity. Its ability to cross the blood-brain barrier allows it to act at the eye and brain level and has been linked to benefits for vision, cognitive function and other conditions. While marigold flower is positioned as the only crop from which lutein is extracted from and commercialized, microalgae are proposed as an alternative with several advantages over this terrestrial crop. The main barrier to scaling up lutein production from microalgae to the commercial level is the low productivity compared to the high costs. This review explores strategies to enhance lutein production in microalgae by emphasizing the overall productivity over lutein content alone. Evaluation of how culture parameters, such as light quality, nitrogen sufficiency, temperature and even stress factors, affect lutein content and biomass development in batch phototrophic cultures was performed. Overall, the total lutein production remains low under this metabolic regime due to the low biomass productivity of photosynthetic batch cultures. For this reason, we describe findings on microalgal cultures grown under different metabolic regimes and culture protocols (fed-batch, pulse-feed, semi-batch, semi-continuous, continuous). After a careful literature examination, two-step heterotrophic or mixotrophic cultivation strategies are suggested to surpass the lutein productivity achieved in single-step photosynthetic cultures. Furthermore, this review highlights the urgent need to develop technical feasibility studies at a pilot scale for these cultivation strategies, which will strengthen the necessary techno-economic analyses to drive their commercial production., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Chronic kidney disease can lead to end-stage renal disease, and the prevalence is increasing. Many patients starting hemodialysis require central venous catheters (CVCs). Catheter-related bloodstream infections (CRBSIs) are a common complication and lead to significant morbidity and mortality. Interventions to prevent CRBSI include antimicrobial lock therapy but concern for the development of antimicrobial resistance and adverse effects. Nonantimicrobial antiseptics as catheter lock solutions have also been used. Taurolidine and heparin catheter lock solution is first approved by the Food and Drug Administration for the prevention of CRBSI in patients on hemodialysis. Taurolidine has a unique mechanism of action and favorable safety profile., Mechanism of Action, Pharmacodynamics, and Pharmacokinetics: Taurolidine and heparin catheter lock solution have both antimicrobial and anticoagulant properties. Taurolidine is derivative of the amino acid taurine, and heparin is derived from porcine intestinal mucosa. Taurolidine not only damages microbial cell walls but also prevents the adherence of microorganisms to biological surfaces, preventing biofilm formation. Taurolidine and heparin catheter lock solution is intended to be used intraluminally within the catheter and should be aspirated. Because it is used locally, limited pharmacokinetic and pharmacodynamic data are available., Clinical Trials: The LOCK-IT-100 trial is a randomized, double-blind, phase 3 study, which included 795 end-stage renal disease patients on hemodialysis with CVC. Taurolidine and heparin was compared with the control heparin alone. The results of the study showed a 71% risk reduction in CRBSI for taurolidine and heparin arm (95% confident interval, 38%-86%, P = 0.0006). Other studies have also shown that taurolidine lock solution leads to decreased CRBSI episodes. Several systematic reviews and meta-analysis consisted of taurolidine in adult, and pediatric populations also showed reduction in the incidence of CRBSIs., Therapeutic Advance: Taurolidine and heparin lock solution represents a novel preventive strategy for those undergoing hemodialysis through a CVC by reducing the risk of CRBSI. This is significant progress because there are no other similar options available for patients for whom catheters are the only options for their life-saving treatment., Competing Interests: T. Nguyen: no conflict of interest. B. C. Camins: Advisor for Applied UV, Inc and Premier, Inc. D. A. Butler is currently receiving a grant (#23020) from CorMedix, Inc., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: People living with HIV (PLWH) live longer and face new health challenges resulting from the confluence of chronic HIV infection and the natural effect of aging and comorbidities. However, there is a dearth of information on the long-term impact of HIV infection on the health and wellbeing of PLWH in sub-Saharan Africa. This research aimed to fill this gap by reporting on physical, functional and social outcomes among PLWH treated at a referral center in Abidjan, Ivory Coast, and comparing them with those of a control group., Methods: Body composition, functional capacity, sarcopenia, limitations in daily activities and social participation were assessed among 300 PLWH (aged ≥ 30 years) and 200 uninfected adults of similar age and sex. The associations between these outcomes and participants' socioeconomic characteristics, HIV history and physical activity level were assessed using generalized additive models adjusted for age and sex., Results: The median age was 51 years, and the median antiretroviral therapy duration was 15 years. Compared to controls, PLWH reported higher levels of physical activity (p < 0.0001). They had a lower muscle index (adjusted p < 0.0001) and grip strength (adjusted p < 0.0001) but achieved similar performance on the 6-min walk test (6MWT, p = 0.2). Among PLWH, physical activity level was positively associated with better performance in the 6MWT (p = 0.006) and greater hand grip strength (p = 0.04). The difference in physical performance according to the level of physical activity appeared mainly after the age of 60. PLWH reported similar rates of activity limitations (p = 0.8), lower depression levels and greater scores for social functioning (p = 0.02)., Conclusion: In this study, PLWH achieved high levels of physical activity, which may explain why they maintained good physical performance and social functioning despite having a higher risk of sarcopenia. These results have important implications for resource-limited health systems and show avenues for chronic care models., Trial Registration: This study was registered on the ClinicalTrials.gov website (NCT05199831, first registration the 20/01/2022)., (© 2024. The Author(s).)

After often gruelling journeys, some refugees arrive at secure locations with severe injury or illness. Others find themselves shortly thereafter facing a life-limiting health condition. Palliative care has been the focus of recent research, and of academic and aid sector dialogue. In this study, we ask: What are experiences and needs of patients and care providers? What opportunities and obstacles exist to enhance or introduce means of reducing suffering for patients facing serious illness and injury in crisis settings? We present findings of a qualitative sub-study within a larger programme of research exploring moral and practical dimensions of palliative care in humanitarian crisis contexts. This paper presents vignettes about palliative care from refugees and care providers in two refugee camps in Rwanda, and is among the first to provide empirical evidence on first-hand experiences of individuals who have fled protracted conflict and face dying far from home. Along with narratives of their experiences, participants provided a range of recommendations from small (micro) interventions that are low cost, but high impact, through to larger (macro) changes at the systems and societal levels of benefit to policy developers and decision-makers.

Background: 2-[ 18 F]fluoro-2-deoxy-D-glucose ([ 18 F]FDG) positron emission tomography combined with low-dose computed tomography (PET/CT) can be used at diagnosis to identify myeloma-defining events and also provides prognostic factors. The aim of this study was to assess the prognostic significance of baseline [ 18 F]FDG PET/CT visual IMPeTUs (Italian myeloma criteria for PET Use)-based parameters and/or total metabolic tumor volume (TMTV) in a single-center population of patients with newly diagnosed multiple myeloma (NDMM) eligible for transplantation., Methods: Patients with MM who underwent a baseline [ 18 F]FDG PET/CT were retrospectively selected from a large internal database of the University Hospital of Liege (Liege, Belgium). Initially, all PET/CT images were visually analyzed using IMPeTUs criteria, followed by delineation of TMTV using a semi-automatic lesion delineation workflow, including [ 18 F]FDG-positive MM focal lesions (FL) with an absolute SUV threshold set at 4.0. In a first step, to ensure PET/CT scans accurate reporting, the agreement between two nuclear medicine physicians with distinct experience was assessed. In the second step, univariable and multivariable analyses were conducted to determine the prognostic significance of [ 18 F]FDG PET/CT parameters on progression free survival (PFS) and overall survival (OS), respectively., Results: A total of 40 patients with NDMM were included in the study. The observers agreement in the analysis [18F]FDG PET/CT images was substantial for the presence of spine FL, extra spine FL, at least one fracture and paramedullary disease (Cohen's kappa 0.79, 0.87, 0.75 and 0.64, respectively). For the presence of skull FL and extramedullary disease the agreement was moderate (Cohen's kappa 0.56 and 0.53, respectively). Among [ 18 F]FDG PET/CT parameters, a high number of delineated volumes of interest (VOI) using the SUV4.0 threshold was the only independent prognostic factor associated with PFS [HR (95% CI): 1.03 (1.004-1.05), P = 0.019] while a high number of FL (n > 10; F group 4) was the only independent prognostic factor associated with OS [HR (95% CI): 19.10 (1.90-191.95), P = 0.01]., Conclusion: Our work confirms the reproducibility IMPeTUs criteria. Furthermore, it demonstrates that a high number of FL (n > 10; IMPeTUs F group 4), reflecting a high [ 18 F]FDG-avid tumor burden, is an independent prognostic factor for OS. The prognostic value of the TMTV delineated using a SUV4.0 threshold was not significant. Nevertheless, the count of delineated [ 18 F]FDG-avid lesions VOI using a SUV4.0 threshold was an independent prognostic factor for PFS., (© 2024. The Author(s).)

RNAs are essential molecules involved in numerous biological functions. Understanding RNA functions requires the knowledge of their 3D structures. Computational methods have been developed for over two decades to predict the 3D conformations from RNA sequences. These computational methods have been widely used and are usually categorised as either ab initio or template-based. The performances remain to be improved. Recently, the rise of deep learning has changed the sight of novel approaches. Deep learning methods are promising, but their adaptation to RNA 3D structure prediction remains difficult. In this paper, we give a brief review of the ab initio , template-based and novel deep learning approaches. We highlight the different available tools and provide a benchmark on nine methods using the RNA-Puzzles dataset. We provide an online dashboard that shows the predictions made by benchmarked methods, freely available on the EvryRNA platform: https://evryrna.ibisc.univ-evry.fr/evryrna/state&#95;of&#95;the&#95;rnart/., (© The Author(s) 2024. Published by Oxford University Press on behalf of NAR Genomics and Bioinformatics.)

Introduction: Speech Language Therapy First Point of Contact Clinic (SLT-FPOCC) models can assist assessment of low-risk patient populations referred to ear, nose and throat (ENT) services. To further improve ENT waitlist management and compliance with best-practice care, consideration of other low-risk populations that could be safely managed through this service model is needed. The aims of this paper are to evaluate the clinical and service outcomes of completing vocal cord check (VCC) assessments for patients' pre and post thyroid/parathyroid surgery within an SLT-FPOCC model and examine consumer perceptions., Methods & Procedures: The service followed existing SLT-FPOCC procedures, with ENT triaging referrals, then SLT completing pre- and postoperative VCC assessment (interview, perceptual assessment, flexible nasendoscopy), with assessment data later reviewed by ENT to diagnose laryngeal pathology. Clinical and service outcomes were collected prospectively. Patients completed an anonymous post-service satisfaction survey., Results: Of the first 100 patients referred for preoperative VCCs, SLT assessment identified 42 with dysphonia and 30 reporting dysphagia, while ENT confirmed 9 with significant preoperative anatomical findings. Eighty-three underwent surgery, with 63 (95 nerves at surgical risk) returning for a postoperative VCC. Postoperative VCC identified three temporary neuropraxias (3.2%) and three unilateral vocal fold paresis (3.2%). Patients were highly satisfied with the service. All 163 pre-/postoperative VCCs were completed with no adverse events., Conclusion & Implications: The current data support SLT-FPOCC service expansion to include pre and post thyroid/parathyroid surgery VCC checks, with positive consumer perception. The model supports delivery of best practice management (i.e., pre- and postoperative VCC) for patients receiving surgery for thyroid/parathyroid dysfunction, and associated efficiencies for ENT services., What This Paper Adds: What is already known Assessment of laryngeal function via flexible nasoendoscopy is recommended best practice for patients pre and postthyroid/parathyroid surgery, as recurrent laryngeal nerve injury is a low incidence (<10%), yet well-recognised risk of these surgeries. Traditionally, general surgeons refer presurgical patients to ear, nose and throat (ENT) for vocal cord check (VCC) assessment. However, with access to specialist outpatient services under increasing pressure, there is growing support for utilisation of other health professionals, such as speech-language therapists working in first point of contact (FPOCC) models, to assist with the administration of pre- and postsurgical assessments of such low-risk populations. What this study adds This work expands on the emerging body of evidence for speech language therapy (SLT) led FPOCC models within ENT outpatient services, providing clinical and service outcomes to support the safety of a new model designed to administer VCCs for patients pre and post thyroid/parathyroid surgery. Adopting a similar model to a prior published SLT-led FPOCC model, the trained SLT completes the pre- and postsurgical VCC including flexible nasoendoscopy and videostroboscopy, with images and clinical information then presented to ENT for diagnosis and management planning. This study also provides the first data on consumer perceptions of this type of service model. Clinical implications of this study Data on 100 consecutive presurgical patients revealed positive service findings, supporting the safety of this model. Nature and incidence of clinical findings pre and post surgery were consistent with previously published studies using traditional models of care (i.e., ENT completing the flexible nasendoscopy). Consumer perception was positive. This model enables delivery of pre-and postsurgical assessments for patients receiving thyroid/parathyroid surgery, consistent with best practice care, and reduces burden on ENT services. In total 163 ENT appointments were avoided with this model, with positive implications for ENT waitlist management., (© 2023 The Authors. International Journal of Language & Communication Disorders published by John Wiley & Sons Ltd on behalf of Royal College of Speech and Language Therapists.)

Background: Animal models and human data have suggested macrophage-driven immune dysregulation in diabetic gastroparesis (DG). Translocator protein (TSPO) upregulation has been suggested to indicate activated state of macrophages and ER176 is a high affinity third generation TSPO-specific radioligand. The aim of this study was to determine feasibility of dynamic 11 C-ER 176 PET to identify macrophage activation in DG., Methods: Twelve patients, all females, were recruited (4 DG, 4 diabetics, and 4 healthy volunteers) for 11 C-ER 176 PET/CT scanning. The standardized uptake value (SUV max ) in the gastric fundus, body, pylorus, and descending part of the duodenum were compared between three groups using Kruskal-Wallis test to perform the comparisons, and a p-value of 0.05 was considered statistically significant., Key Results: Age was comparable among the three groups with a median of 53 years. The uptake was higher in pylorus in diabetics compared to DG and healthy (SUV max healthy 4.6 ± 0.2, diabetics 8.4 ± 4.1, DG 5.5 ± 1.0, p = 0.04). The uptake was similar in gastric fundus (9.0 ± 1.6, 13.1 ± 8.3, 7.8 ± 1.9 respectively, p = 0.3), body (7.7 ± 1.9, 13 ± 9.2, 7.8 ± 1.9 respectively, p = 0.8), and duodenum (6.2 ± 2.1, 9.5 ± 6.8, 7.0 ± 1.8 respectively, p = 0.6). No correlation was observed between SUV max uptake and either HbA1C or fasting blood glucose., Conclusions and Inferences: Female diabetic gastroparesis patients did not demonstrate increased TSPO ligand 11 C-ER 176 uptake in the stomach. Possible explanations include lack of specificity of ligand for specific macrophage phenotypes in DG, sex effect, or small sample size. Further studies investigating non-invasive ways of analyzing immune dysregulation in neurogastrointestinal disorders are warranted., (© 2024 John Wiley & Sons Ltd.)

Saline-alkaline lakes often shelter high biomasses despite challenging conditions, owing to the occurrence of highly adapted phototrophs. Dziani Dzaha (Mayotte) is one such lake characterized by the stable co-dominance of the cyanobacterium Limnospira platensis and the picoeukaryote Picocystis salinarum throughout its water column. Despite light penetrating only into the uppermost meter, the prevailing co-dominance of these species persists even in light- and oxygen-deprived zones. Here, a depth profile of phototrophs metatranscriptomes, annotated using genomic data from isolated strains, is employed to identify expression patterns of genes related to carbon processing pathways including photosynthesis, transporters and fermentation. The findings indicate a prominence of gene expression associated with photosynthesis, with a peak of expression around 1 m below the surface, although the light intensity is very low and only red and dark red wavelengths can reach it, given the very high turbidity linked to the high biomass of L. platensis . Experiments on strains confirmed that both species do grow under these wavelengths, at rates comparable to those obtained under white light. A decrease in the expression of photosynthesis-related genes was observed in L. platensis with increasing depth, whereas P. salinarum maintained a very high pool of psb A transcripts down to the deepest point as a possible adaptation against photodamage, in the absence and/or very low levels of expression of genes involved in protection. In the aphotic/anoxic zone, expression of genes involved in fermentation pathways suggests active metabolism of reserve or available dissolved carbon compounds. Overall, L. platensis seems to be adapted to the uppermost water layer, where it is probably maintained thanks to gas vesicles, as evidenced by high expression of the gvp A gene. In contrast, P. salinarum occurs at similar densities throughout the water column, with a peak in abundance and gene expression levels which suggests a better adaptation to lower light intensities. These slight differences may contribute to limited inter-specific competition, favoring stable co-dominance of these two phototrophs., 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. The authors declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Duperron, Halary, Bouly, Roussel, Hugoni, Bruto, Oger, Duval, Woo, Jézéquel, Ader, Leboulanger, Agogué, Grossi, Troussellier and Bernard.)

Mycobacterium abscessus is an emerging opportunistic pathogen responsible for chronic lung diseases, especially in patients with cystic fibrosis. Treatment failure of M. abscessus infections is primarily associated with intrinsic or acquired antibiotic resistance. However, there is growing evidence that antibiotic tolerance, i.e., the ability of bacteria to transiently survive exposure to bactericidal antibiotics through physiological adaptations, contributes to the relapse of chronic infections and the emergence of acquired drug resistance. Yet, our understanding of the molecular mechanisms that underlie antibiotic tolerance in M. abscessus remains limited. In the present work, a mutant with increased cross-tolerance to the first- and second-line antibiotics cefoxitin and moxifloxacin, respectively, has been isolated by experimental evolution. This mutant harbors a mutation in serB2 , a gene involved in L-serine biosynthesis. Metabolic changes caused by this mutation alter the intracellular redox balance to a more reduced state that induces overexpression of the transcriptional regulator WhiB7 during the stationary phase, promoting tolerance through activation of a WhiB7-dependant adaptive stress response. These findings suggest that alteration of amino acid metabolism and, more generally, conditions that trigger whiB7 overexpression, makes M. abscessus more tolerant to antibiotic treatment.

Small Heat Shock Proteins are considered as the first line of defense when proteostasis fails. Among them, αB-crystallin is expressed in striated muscles in which it interacts with desmin intermediate filaments to stabilize them, maintaining cytoskeleton's integrity and muscular functionalities. Desmin is a key actor for muscle health; its targeting by αB-crystallin is thus crucial, especially in stress conditions. αB-crystallin is phosphorylated and O-GlcNAcylated. Its phosphorylation increases consecutively to various stresses, correlated with its recruitment for cytoskeleton's safeguarding. However, phosphorylation as unique signal for cytoskeleton translocation remains controversial; indeed, O-GlcNAcylation was also proposed to be involved. Thus, there are still some gaps for a deeper comprehension of how αB-crystallin functions are finely regulated by post-translational modifications. Furthermore, desmin also bears both post-translational modifications; while desmin phosphorylation is closely linked to desmin intermediates filaments turnover, it is unclear whereas its O-GlcNAcylation could impact its proper function. In the herein paper, we aim at identifying whether phosphorylation and/or O-GlcNAcylation are involved in αB-crystallin targeting towards cytoskeleton in proteotoxic stress induced by proteasome inhibition in C2C12 myotubes. We demonstrated that proteotoxicity led to αB-crystallin's phosphorylation and O-GlcNAcylation patterns changes, both presenting a dynamic interplay depending on protein subfraction. Importantly, both post-translational modifications showed a spatio-temporal variation correlated with αB-crystallin translocation towards cytoskeleton. In contrast, we did not detect any change of desmin phosphorylation and O-GlcNAcylation. All together, these data strongly support that αB-crystallin phosphorylation/O-GlcNAcylation interplay rather than changes on desmin is a key regulator for its cytoskeleton translocation, preserving it towards stress., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)

To elucidate how time of day, sex, and age affect functional connectivity (FC) in mice, we aimed to examine whether the mouse functional connectome varied with the day/night cycle and whether it depended on sex and age. We explored C57Bl6/J mice (6♀ and 6♂) at mature age (5 ± 1 months) and middle-age (14 ± 1 months). Each mouse underwent Blood Oxygen-Level-Dependent (BOLD) resting-state functional MRI (rs-fMRI) on a 7T scanner at four different times of the day, two under the light condition and two under the dark condition. Data processing consisted of group independent component analysis (ICA) and region-level analysis using resting-state networks (RSNs) derived from literature. Linear mixed-effect models (LMEM) were used to assess the effects of sex, lighting condition and their interactions for each RSN obtained with group-ICA (RSNs-GICA) and six bilateral RSNs adapted from literature (RSNs-LIT). Our study highlighted new RSNs in mice related to day/night alternation in addition to other networks already reported in the literature. In mature mice, we found sex-related differences in brain activation only in one RSNs-GICA comprising the cortical, hippocampal, midbrain and cerebellar regions of the right hemisphere. In males, brain activity was significantly higher in the left hippocampus, the retrosplenial cortex, the superior colliculus, and the cerebellum regardless of lighting condition; consistent with the role of these structures in memory formation and integration, sleep, and sex-differences in memory processing. Experimental constraints limited the analysis to the impact of light/dark cycle on the RSNs for middle-aged females. We detected significant activation in the pineal gland during the dark condition, a finding in line with the nocturnal activity of this gland. For the analysis of RSNs-LIT, new variables "sexage" (sex and age combined) and "edges" (pairs of RSNs) were introduced. FC was calculated as the Pearson correlation between two RSNs. LMEM revealed no effect of sexage or lighting condition. The FC depended on the edges, but there were no interaction effects between sexage, lighting condition and edges. Interaction effects were detected between i) sex and lighting condition, with higher FC in males under the dark condition, ii) sexage and edges with higher FC in male brain regions related to vision, memory, and motor action. We conclude that time of day and sex should be taken into account when designing, analyzing, and interpreting functional imaging studies in rodents., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Aix-Marseille University. Published by Elsevier Inc. All rights reserved.)

Blood flow restriction (BFR) is a commonly used training modality that has been demonstrated to enhance muscle characteristics such as size and function. The purpose of this study was to determine if a 4-week walking program with or without BFR in healthy, active adults has an effect on body composition, anaerobic, and aerobic running performance. Thirty-three participants, randomized among three groups, completed the walking program, which included five sets of 2 min walking intervals with 1 min rest, with or without BFR, or 10 min walking with BFR. Assessments completed before and after the walking program included body composition, 40-yard sprints, and a VO 2MAX test on a treadmill. A two-way ANOVA revealed no changes among the groups nor for any variables at any time ( p > 0.05). Additionally, one main effect for time indicated the VO 2 at V-slope threshold was greater following training for all groups combined ( p = 0.001). The results demonstrate that low volume and intensity walking with BFR for 4 weeks did not provide a sufficient stimulus for changing body composition or performance metrics in a group of very active adults. Longer or more isolated exposure of BFR on the limbs may contribute to more pronounced adaptations.

Abstract: Indiana was the first state to pass legislation severely restricting access to abortion care following the Dobbs v. Jackson Women's Health Organization decision. Indiana Senate Enrolled Act 1 (SEA 1) outlaws all abortions with few exceptions. Indiana University Health (IU Health), the largest and only academic health system in the state, has a unique relationship with the Indiana University School of Medicine and a vision to improve the health of Indiana residents. IU Health employed the Hospital Incident Command System model to create a plan to ensure its patients continue to have access to safe, high-quality family planning, maternal, and neonatal care services and that clinicians are protected against criminal penalties and threats to personal safety. This article provides an overview of the Incident Command structure used to rapidly work across many disciplines, tackle complex issues, respond to concerns, and design and implement changes. The article also outlines the key considerations and decisions made by Incident Command leaders, such as where abortions that met the new law's criteria should be performed, changes to clinical workflows and protocols, and the creation of a rapid response team. The article then examines the operational, legal, and clinical challenges encountered by clinicians and health care team members, including a lack of peer support or idea sharing with other health systems in the state; accurate estimation of abortion, live birth, and neonatal intensive care unit volumes; and ambiguity in the law and lack of guidance from the state government. Recommendations regarding communication with clinicians and other health care team members and engaging information technology early are offered for health systems and medical schools that may face legislative barriers to health care delivery in the future. Finally, IU Health's commitment to tracking the impact of SEA 1 on patients, clinicians, employees, and the state is outlined., (Copyright © 2024 the Association of American Medical Colleges.)

Cell membranes, mediator of many biological mechanisms from adhesion and metabolism up to mutation and infection, are highly dynamic and heterogeneous environments exhibiting a strong coupling between biochemical events and structural re-organisation. This involves conformational changes induced, at lower scales, by lipid order transitions and by the micro-mechanical interplay of lipids with transmembrane proteins and molecular diffusion. Particular attention is focused on lipid rafts, ordered lipid microdomains rich of signalling proteins, that co-localise to enhance substance trafficking and activate different intracellular biochemical pathways. In this framework, the theoretical modelling of the dynamic clustering of lipid rafts implies a full multiphysics coupling between the kinetics of phase changes and the mechanical work performed by transmembrane proteins on lipids, involving the bilayer elasticity. This mechanism produces complex interspecific dynamics in which membrane stresses and chemical potentials do compete by determining different morphological arrangements, alteration in diffusive walkways and coalescence phenomena, with a consequent influence on both signalling potential and intracellular processes. Therefore, after identifying the leading chemo-mechanical interactions, the present work investigates from a modelling perspective the spatio-temporal evolution of raft domains to theoretically explain co-localisation and synergy between proteins' activation and raft formation, by coupling diffusive and mechanical phenomena to observe different morphological patterns and clustering of ordered lipids. This could help to gain new insights into the remodelling of cell membranes and could potentially suggest mechanically based strategies to control their selectivity, by orienting intracellular functions and mechanotransduction., (© 2023. The Author(s).)

Introduction: Artificial urinary sphincter (AUS) is the standard treatment for severe stress urinary incontinence in men. While the perineal access is considered the gold standard, some authors have proposed penoscrotal AUS in order to facilitate the procedure. The main objective of our study was to evaluate the duration of survival without revision surgery (SSRC) according to the surgical approach for primary implantation., Material and Methods: Data from 1179 patients implanted in France between 1991 and 2020 with an AMS 800 AUS were retrospectively analyzed. A total of 762 men were implanted perineally (VP) and 417 penoscrotally (VPS)., Results: Median follow-up was 20 vs. 25months respectively. The groups were equivalent overall, apart from the use of anticoagulants (11% VP vs. 6.3% VPS P=0.014). In our population, 54% patients were considered as "dry" in the case of VPS vs. 42% for VP. There was no significant difference in terms of survival time without reoperation, revision, replacement or explantation. In univariate and multivariate analysis, age over 70years was predictive of more reinterventions, whereas the use of a 4.5cm cuff was protective, with hazard ratios of 1.42 (P=0.001) and 0.78 (P=0.04), respectively., Conclusion: The penoscrotal approach does not appear to be associated with more complications, has good functional results and no significant difference in reoperation-free survival. A prospective multicenter non-inferiority study could be of interest to confirm our findings., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

This article points out deficiencies in present-day definitions of public health surveillance, which include data collection, analysis, interpretation and dissemination, but not public health action. Controlling a public health problem of concern requires a public health response that goes beyond information dissemination. It is undesirable to have public health divided into data generation processes (public health surveillance) and data use processes (public health response), managed by two separate groups (surveillance experts and policy-makers). It is time to rethink the need to modernize the definition of public health surveillance, inspired by the authors' enhanced Data, Information, Knowledge, Intelligence and Wisdom model. Our recommendations include expanding the scope of public health surveillance beyond information dissemination to comprise actionable knowledge (intelligence); mandating surveillance experts to assist policy-makers in making evidence-informed decisions; encouraging surveillance experts to become policy-makers; and incorporating public health literacy training - from data to knowledge to wisdom - into the curricula for all public health professionals. Work on modernizing the scope and definition of public health surveillance will be a good starting point., Competing Interests: Conflicts of interest. The authors have no conflicts of interest to declare.

Background: The rising trend of providing palliative care to residents in Canadian long-term care facilities places additional demands on care staff, increasing their risk of burnout. Interventions and strategies to alleviate burnout are needed to reduce its impact on quality of patient care and overall functioning of healthcare organizations., Aim: To examine the feasibility of implementing online modules with the primary goal of determining recruitment and retention rates, completion time and satisfaction with the modules. A secondary goal was to describe changes in burnout and related symptoms associated with completing the modules., Setting: This single-arm, nonrandomized feasibility study was conducted in five long-term care sites of a publicly-funded healthcare organization in Vancouver, British Columbia, Canada. Eligible participants were clinical staff who worked at least 1 day per month., Results: A total of 103 study participants consented to participate, 31 (30.1%) of whom were lost to follow-up. Of the remaining 72 participants, 64 (88.9%) completed the modules and all questionnaires. Most participants completed the modules in an hour (89%) and found them easy to understand (98%), engaging (84%), and useful (89%). Mean scores on burnout and secondary traumatic stress decreased by .9 (95% CI: .1-1.8; d = .3) and 1.4 (95% CI: .4-2.4; d = .4), respectively; mean scores on compassion satisfaction were virtually unchanged., Conclusions: Modules that teach strategies to reduce burnout among staff in long-term care are feasible to deliver and have the potential to reduce burnout and related symptoms. Randomized controlled trials are needed to assess effectiveness and longer-term impact., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Heterogeneity in outcomes reported in trials of interventions for the treatment of neonatal encephalopathy (NE) makes evaluating the effectiveness of treatments difficult. Developing a core outcome set for NE treatment would enable researchers to measure and report the same outcomes in future trials. This would minimise waste, ensure relevant outcomes are measured and enable evidence synthesis. Therefore, we aimed to develop a core outcome set for treating NE., Methods: Outcomes identified from a systematic review of the literature and interviews with parents were prioritised by stakeholders (n = 99 parents/caregivers, n = 101 healthcare providers, and n = 22 researchers/ academics) in online Delphi surveys. Agreement on the outcomes was achieved at online consensus meetings attended by n = 10 parents, n = 18 healthcare providers, and n = 13 researchers/ academics., Results: Seven outcomes were included in the final core outcome set: survival; brain injury on imaging; neurological status at discharge; cerebral palsy; general cognitive ability; quality of life of the child, and adverse events related to treatment., Conclusion: We developed a core outcome set for the treatment of NE. This will allow future trials to measure and report the same outcomes and ensure results can be compared. Future work should identify how best to measure the COS., Impact: We have identified seven outcomes that should be measured and reported in all studies for the treatment of neonatal encephalopathy. Previously, a core outcome set for neonatal encephalopathy treatments did not exist. This will help to reduce heterogeneity in outcomes reported in clinical trials and other studies, and help researchers identify the best treatments for neonatal encephalopathy., (© 2023. The Author(s).)

During NREM sleep, hippocampal sharp-wave ripple (SWR) events are thought to stabilize memory traces for long-term storage in downstream neocortical structures. Within the neocortex, a set of distributed networks organized around retrosplenial cortex (RS-network) interact preferentially with the hippocampus purportedly to consolidate those traces. Transient bouts of slow oscillations and sleep spindles in this RS-network are often observed around SWRs, suggesting that these two activities are related and that their interplay possibly contributes to memory consolidation. To investigate how SWRs interact with the RS-network and spindles, we combined cortical wide-field voltage imaging, Electrocorticography, and hippocampal LFP recordings in anesthetized and sleeping mice. Here, we show that, during SWR, "up-states" and spindles reliably co-occur in a cortical subnetwork centered around the retrosplenial cortex. Furthermore, retrosplenial transient activations and spindles predict slow gamma oscillations in CA1 during SWRs. Together, our results suggest that retrosplenial-hippocampal interaction may be a critical pathway of information exchange between the cortex and hippocampus., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Noisy vibrotactile signals transmitted during tactile explorations of an object provide precious information on the nature of its surface. Understanding the link between signal properties and how they are interpreted by the tactile sensory system remains challenging. In this paper, we investigated human perception of broadband, stationary vibrations recorded during exploration of textures and reproduced using a vibrotactile actuator. Since intensity is a well-established perceptual attribute, we here focused on the relevance of the spectral content. The stimuli were first equalized in perceived intensity and subsequently used to identify the most salient spectral features using dissimilarity estimations between pairs of successive vibration. Based on dimensionally reduced spectral representations, models of dissimilarity ratings showed that the balance between low and high frequencies was the most important cue. Formal validation of this result was achieved through a Mushra experiment, in which participants assessed the fidelity of resynthesized vibrations with various distorted frequency balances. These findings offer valuable insights into human vibrotactile perception and establish a computational framework for analyzing vibrations as humans do. Moreover, they pave the way for signal synthesis and compression based on sparse representations, holding significance for applications involving complex vibratory feedback.

Introduction: Unlike orthopedic or visceral surgeons, French military neurosurgeons are not permanently deployed on the conflict zone. Thus, craniocerebral war casualties are often managed by general surgeons in the mobile field surgical team. The objective of the study was to provide the feedback of French military surgeons who operated on craniocerebral injuries during their deployment in a role 2 surgical hospital without a neurosurgeon., Materials and Methods: A cross-sectional survey was conducted by phone in March 2020, involving every military surgeon currently working in the French Military Training Hospitals, with an experience of cranial surgery without the support of a neurosurgeon during deployment. We strived to obtain contextual, clinical, radiological, and surgical data., Results: A total of 33 cranial procedures involving 64 surgeons were reported from 1993 to 2018. A preoperative CT scan was not available in 18 patients (55%). Half of the procedures consisted in debridement of craniocerebral wounds (52%, n = 17), followed by decompressive craniectomies (30%, n = 10), craniotomy with hematoma evacuation (15%, n = 5), and finally one (3%) surgery with exploratory burr holes were performed. The 30-day survival rate was 52% (n = 17) and 50% (n = 10/20) among the patients who sustained severe traumatic brain injury., Conclusions: This survey demonstrates the feasibility and the plus-value of a neurosurgical damage control procedure performed on the field by a surgeon nonspecialized in cranial surgery. The stereotyped neurosurgical techniques used by the in-theater surgeon were learned during a specific predeployment training course. However, the use of a live telemedicine neurosurgical support seems indispensable and could benefit the general surgeon in strained resources setting., (© The Association of Military Surgeons of the United States 2022. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Integration of information across heterogeneous sources creates added scientific value. Interoperability of data, tools and models is, however, difficult to accomplish across spatial and temporal scales. Here we introduce the toolbox Parallel Co-Simulation, which enables the interoperation of simulators operating at different scales. We provide a software science co-design pattern and illustrate its functioning along a neuroscience example, in which individual regions of interest are simulated on the cellular level allowing us to study detailed mechanisms, while the remaining network is efficiently simulated on the population level. A workflow is illustrated for the use case of The Virtual Brain and NEST, in which the CA1 region of the cellular-level hippocampus of the mouse is embedded into a full brain network involving micro and macro electrode recordings. This new tool allows integrating knowledge across scales in the same simulation framework and validating them against multiscale experiments, thereby largely widening the explanatory power of computational models., 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 Kusch, Diaz-Pier, Klijn, Sontheimer, Bernard, Morrison and Jirsa.)

Purpose: To systematically review the literature and provide a detailed summary of the current treatments and outcomes for arthrofibrosis following knee arthroscopy and anterior cruciate ligament reconstruction (ACLR) and to compare the treatment strategies in pediatric and adult populations., Methods: A systematic review was performed in March 2022 using PubMed, EMBASE, and Cochrane Library Databases per Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Search terms consisted of variations of the following: ("arthrofibrosis" OR "stiffness" OR "stiff" OR "complications") AND ("arthroscopy" OR "arthroscop" OR "ACL" OR "anterior cruciate") AND ("treat" OR "care" OR "management" AND "knee"). The inclusion criteria were studies that were written in English, were published since 2000, and that reported outcomes of knee arthroscopy or ACLR for treatment of arthrofibrosis of the knee. The study quality was assessed, and data about the patients and treatments were recorded. Treatments were compared between pediatric and adult patients., Results: A total of 1,208 articles were identified in the initial search, 42 (3.48%) of which met eligibility criteria, involving treatment regimens for arthrofibrosis following knee arthroscopy or ACLR. Of the 42 studies included, 29 (69.0%) were reported data for adults and 13 (31.0%) reported data for pediatric patients. Thirty-nine studies (92.8%) discussed manipulation under anesthesia and/or lysis of adhesions (LOA) as treatment for arthrofibrosis of the knee, whereas 2 (4.8%) described the use of medications., Conclusions: Within orthopaedic sports medicine literature, there is variability in the reported treatment options for arthrofibrosis of the knee. Most studies identified manipulation under anesthesia and/or LOA as the treatment among both adult and pediatric patients. Other variants include notchplasty, open posterior arthrolysis, total graft resection, removal of hardware with LOA, dynamic splinting, casting in extension, bracing, and medications., Level of Evidence: Level IV, systematic review of Level I-IV studies., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: M.K.M. reports personal fees from 10.13039/100007307Arthrex, outside the submitted work; 10.13039/100009885American Academy of Orthopaedic Surgeons, 10.13039/100005382American Orthopaedic Association, 10.13039/100011549American Orthopaedic Society for Sports Medicine, Arthroscopy Association of North American, International Society of Arthroscopy, Knee Surgery, and Orthopaedic Sports Medicine, 10.13039/100013880Ruth Jackson Orthopaedic Society, and The Forum: board or committee member; and American Journal of Sports Medicine-Electronic Media, Arthroscopy, and Ortho Info: editorial or governing board. B.G.V. reports personal fees from Artelon, Spinal Simplicity stock options, Altior stock options, Carbon 22 stock options, American Orthopedic Foot and Ankle Society Board or Committee member. All other authors (R.R., C.B., A.T., T.M., M.L.V.) declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Full ICMJE author disclosure forms are available for this article online, as supplementary material., (© 2024 The Authors.)

Memorializes Richard L. Miller (1945-2023). In the 1990s, Rick began a 24-year tenure at the University of Nebraska at Kearney. As department chair, Rick led the University of Nebraska at Kearney Psychology Department to the system-wide University of Nebraska Outstanding Teaching Department Award. In 2014, Rick moved to Texas A&M University-Kingsville, where he served as department chair. At Texas A&M University-Kingsville, he was recognized for teaching, mentorship, and scholarship, including the A&M Piper Professor Teaching Award. He served in many leadership roles, including the presidencies of the Society for the Teaching of Psychology (APA Division 2) and the Rocky Mountain Psychological Association. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Crimean-Congo haemorrhagic fever (CCHF), a potentially severe zoonotic viral disease causing fever and haemorrhagic manifestations in humans. As the Crimean-Congo haemorrhagic fever virus (CCHFV) has been detected in ticks in Spain and antibodies against the virus in ruminant sera in Corsica, it was necessary to know more about the situation in France. In 2022-2023, CCHFV was detected in 155 ticks collected from horses and cattle in southern France.

Pulmonary homograft dysfunction is challenging to treat in patients with a previous Ross procedure, and results in significant morbidity and mortality in case of reoperation. We report the case of a patient with early severe pulmonary homograft stenosis 18 months after a Ross procedure and successful management using transcatheter pulmonary valve replacement.