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The walls of different types of caves under diverse geological settings (limestone, gypsum and volcanic) are colonized by biofilms of different colors: white, yellow, pink, grey, green to dark brown, but only a few colored biofilms such as the white, yellow and grey ones have been extensively studied. However, an assessment among the microbial communities originating these biofilms in different lithologies is lacking. Here we compare the yellow biofilms from two caves, Covadura and C3, in the Gypsum Karst of Sorbas in Spain, with those from two Spanish limestone caves (Pindal and Santian), and four volcanic caves in Spain and Italy (Viento, Honda del Bejenado, Grotta del Santo, Grotta di Monte Corruccio). The structure of yellow biofilms in gypsum caves closely resembles that found in other Spanish and European limestone caves. However, volcanic cave biofilms exhibit greater variability in their microbial community structure and morphologies. Biofilms from gypsum, limestone and volcanic caves were characterized by the abundance of the genera Crossiella and the gammaproteobacterial wb1-P19. The uncultured Euzebyaceae were abundant in gypsum and Spanish volcanic caves, while in the limestone and Italian volcanic caves, they were rare or absent. Nitrospira was also abundant in limestone and volcanic caves, but not in gypsum caves. Due to the abundances of Crossiella, gammaproteobacterial wb1-P19, and uncultured Euzebyaceae, in many different ecosystems, not only in caves, as recently reported, understanding the functional diversity in which these lineages are involved seems critical. Although we have studied a limited number of yellow biofilms from caves in Spain and Italy, data from other caves in USA and Russia also point out the existence of a similarity among the most abundant members composing the structure of yellow biofilms, suggesting that they share a common core., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Germline pathogenic variants in succinate dehydrogenase subunit B (SDHB) cause paraganglioma/pheochromocytoma syndrome type 4 (PGL-4). SDHB-associated pheochromocytomas (PCC) are thought to be rare and little data exist about their clinical behavior., Patients and Methods: Retrospective review of patients treated (1993-2023) at a tertiary cancer center for SDHB-associated PCC. Clinical and demographic variables were retrieved to characterize disease-free survival, disease progression, and overall survival., Results: In total, 90 SDHB-carriers were identified, 18% had PCC (n = 16). Median age at diagnosis of was 40 (19-76) years, 50% (n = 8) of patients were male, 25% (n = 4) had distant metastasis (DM) at diagnosis, and 13% (n = 2) had synchronous PGL. No patients had bilateral disease, and 94% of patients underwent surgery as initial treatment with a curative intent in 75%. Overall, 64% of patients underwent open resection. Recurrence occurred in 77% of patients (n = 10), 75% in minimally invasive surgery (MIS) versus 77% open, p = 0.63. Bone was the most common site of DM (100%, n = 13). Metaidobenzyleguanidine (MIBG) imaging was performed in 69% of patients, 91% of which were positive. Median time from surgery until recurrence was 36 months (1-295 months). Radiation therapy was the most common adjuvant treatment (44%) followed by Iobenguane I-131 (31%) and systemic therapy (31%). Median follow-up time was 56 months (1-408 months). Overall, 33% of patients were alive, 19% of patients were disease-free, and 50% of the patients with DM had stable disease at last follow-up., Conclusions: Overall, 18% of germline SDHB mutation-carriers were diagnosed with PCC, all of which were unilateral. SDHB-associated PCC was associated with advanced and recalcitrant disease and was often MIBG positive. More studies are needed to better understand the clinical behavior of PCC in PGL-4., (© 2024. Society of Surgical Oncology.)

Phaeochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumours that arise not only in adulthood but also in childhood and adolescence. Up to 70-80% of childhood PPGL are hereditary, accounting for a higher incidence of metastatic and/or multifocal PPGL in paediatric patients than in adult patients. Key differences in the tumour biology and management, together with rare disease incidence and therapeutic challenges in paediatric compared with adult patients, mandate close expert cross-disciplinary teamwork. Teams should ideally include adult and paediatric endocrinologists, oncologists, cardiologists, surgeons, geneticists, pathologists, radiologists, clinical psychologists and nuclear medicine physicians. Provision of an international Consensus Statement should improve care and outcomes for children and adolescents with these tumours., Competing Interests: Competing interests R.T.C. has received a Novartis speaker honorarium and is in an editorial position in Clinical Endocrinology. C.J. has received funding to his institution from Lantheus, Progenics, Exelixis, Merck Sharpe and Dohme and is a clinical adviser for Lantheus and Merck Sharpe and Dohme. S.D.M. is the Director of the NIHR Clinical Research Facility at Great Ormond Street Hospital, London. D.T. has received speaker and attendance honoraria from AAA/NOVARTIS. M.F. is an unpaid member of the ExCo of the European Society of Endocrinology. J.W.M.L. is an unpaid member of the advisory board of the Phaeochromocytoma and Paraganglioma Alliance., (© 2024. Crown.)

Introduction: There is a growing number of people with HIV who are aged 50 years or older, and the prevalence of loneliness and social isolation remains unknown., Methods: A multicentre study was conducted across 22 GeSIDA centres. A survey was carried out to assess loneliness [UCLA 3-item Loneliness Scale-3 (UCLA-3)] and social isolation [Lubben Social Network Scale-Revised (LSNS-R)], along with sociodemographic aspects, HIV-related factors, comorbidities, tobacco, alcohol and drug consumption, quality of life, anxiety and depression, and stigma. The prevalence of loneliness (UCLA-3 ≥ 6) and evident social isolation (LSNS-R ≤ 20) was calculated, and multivariable multinominal logistic regression models were used to identify associated factors., Results: A total of 399 people with HIV were included; 77.4% were men, of average age 59.9 years (SD 6.5); 45.1% were aged ≥60 years; 86% were born in Spain; 86.7% in urban areas; 56.4% with secondary or higher education; 4.5% living alone against their wishes. A total of 66.9% were infected through sexual transmission, with a median of 22.9 years since diagnosis [interquartile range (IQR): 12.6-29.5] and a median nadir CD4 count of 245 cells/μL (IQR: 89-440). Overall, 90.7% had viral load <50 copies/mL, 93.5% had adherence >95%, and 26.3% had a prior AIDS diagnosis. In all, 29.1% and 21% reported significant symptoms of anxiety and depression, respectively, 24.3% had mobility issues, and 40.8% reported pain. Overall, 77.7% of participants reported neither loneliness nor social isolation, 10.0% loneliness only, 5.8% social isolation only and 6.5% both. Multivariable analyses identified that being aged 50-59, unemployed or retired, living alone unwillingly, single, poor quality of life, anxiety, and HIV-related stigma were associated with loneliness. Meanwhile, lower education, living alone unwillingly, and depressive symptoms were associated with social isolation. Individuals living alone unwillingly, with depressive symptoms and experiencing HIV-related stigma were at higher risk for both loneliness and social isolation., Conclusions: There is a relatively high prevalence of loneliness and social isolation in our population. Living alone against one's wishes, being unmarried, and experiencing mobility issues could predispose individuals to feel lonely and socially isolated. Those with anxiety and stigma are more prone to loneliness, while individuals with depression are more predisposed to social isolation. It is necessary to develop strategies for the detection and management of loneliness and social isolation in people with HIV aged >50 years., (© 2024 British HIV Association.)

Pheochromocytomas and paragangliomas (PPGLs) are orphan tumors with the potential to spread to distant organs such as the lymph nodes, the skeleton, the lungs, and the liver. These metastatic tumors exhibit high rates of morbidity and mortality due to their frequently large tumor burden, the progression of the disease, and the excessive secretion of catecholamines that lead to cardiovascular disease and gastrointestinal dysmotility. Several molecular drivers responsible for the development of PPGLs have been described over the last 30 years. Although therapeutic options are limited, substantial progress has been made in the recognition of effective systemic therapies for these tumors. Successful clinical trials with radiopharmaceuticals such as high-specific-activity meta-iodobenzylguanidine and tyrosine kinase inhibitors such as cabozantinib and sunitinib have been recently published. This review will discuss the results of these studies and their impact on current clinical practices. In addition, this review will provide valuable information on how to design clinical trials to treat patients with metastatic PPGLs with novel medications., (© The Author(s), 2024.)

Background: Baseline prevalence surveys in Cameroon in 2010-2012 showed that trachoma was endemic primarily in the north of the country, with 23 evaluation units (EUs) requiring interventions against active (inflammatory) trachoma. This study presents data from prevalence surveys conducted in 2016-2022 following interventions against trachoma in the East, North, Far North and Adamaoua regions of Cameroon., Methods: EUs were created based on health district boundaries. Within each EU, clusters were selected using probability of selection proportional to population size. Participants were examined for trachomatous inflammation-follicular (TF) and trachomatous trichiasis (TT)., Results: A total of 151 800 people were examined in 45 surveys across 35 EUs. Based on the most recent survey results, TF prevalence was greater than the 5% TF elimination threshold in two EUs. Ten EUs had TT prevalence estimates greater than the 0.2% elimination threshold., Conclusions: Trachoma remains a public health problem in Cameroon. Continued interventions are needed in EUs with prevalence estimates greater than elimination thresholds, including antibiotic mass drug administration and improved access to TT surgery. Future surveys will be needed to determine when national elimination of trachoma as a public health problem has been achieved., (© The Author(s) 2024. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Introduction: Genetic variations impact drug response, driving the need for personalised medicine through pre-emptive pharmacogenetic testing. However, the adoption of pre-emptive pharmacogenetic testing for commonly prescribed drugs, such as statins, outside of tertiary hospitals is limited due to a lack of pharmacoeconomic evidence to support widespread implementation by healthcare policy-makers. The Spanish Consortium for the Implementation of Pharmacogenetics (iPHARMGx Consortium) addresses this by developing a clinical trial master protocol that will govern multiple nested adaptive clinical trials that compare genotype-guided treatments to standard care in specific drug-gene-population triads, asses their cost-efficacy and identify novel biomarkers through advanced sequencing techniques. The first of these studies aims to assess whether a pre-emptive statin therapy genotyping scheme reduces the incidence of statin-associated muscle symptoms (SAMS) in a population at risk of cardiovascular disease susceptible of receiving high-intensity or moderate-intensity doses of statins: The PREVESTATGx trial., Methods and Analysis: the PREVESTATGX trial is a multicentre, adaptive randomised controlled pragmatic phase IV clinical trial nested to the iPHARMGx master protocol with two parallel arms, aiming for superiority. Randomisation will be conducted on an individual basis with a centralised approach and stratification by centre. After inclusion in the trial and genotyping has been performed, subjects will be randomly allocated to experimental group (pharmacogenetic genotype-guided statin prescription) or standard-of-care statin prescription (as deemed by attending physician). The main objective is to assess the efficacy of a statin pre-emptive genotyping strategy in reducing the incidence of SAMS. A total of 225 subjects will be recruited among the 10 participating centres if no futility/efficacy boundary is reached in the prespecified interim analyses. Recruitment will be carried out during a 12-month period and subjects will be followed for a 9-month period., Ethics and Dissemination: The PREVESTATGx trial received ethical approval on 24 April 2024. Results will be disseminated via publication in peer-reviewed journals as well as presentation at international conferences. Trial results will be submitted for publication in an open-access peer-reviewed medical speciality-specific publication., Trial Registration Number: EU CT number: 2023-509418-12-00/Clinical trial Identifier (ClinicalTrials.gov): NCT06262685. Protocol version 1.2 12 April 2024 (includes non-substantial modification number 14 June 2024). Trial registration of this study can be located at both the EU Clinical Trials Register available from https:// euclinicaltrials.eu/search-for-clinical-trials/?lang=en and https://clinicaltrials.gov. Registration on both websites was done before the enrolment of the first patient complying with European regulations. EU Clinical Trials Register is a primary registry according to the WHO., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

A 3-year-old male neutered Golden Retriever with nasal swelling and lymphadenopathy was diagnosed with diffuse Mycobacterium avium infection. Treatment with 9 months of enrofloxacin, clarithromycin and rifampicin was successful, but relapsed 10 months later with lymphadenopathy, skin plaques and testicular involvement. Repeat treatment for 12 months was effective but 15 months later a second relapse responded to the same therapy which is ongoing with survival from diagnosis of 82 months. A 1-year-old male neutered Portuguese Podengo was diagnosed with polyarthritis and M. avium infection and treated with enrofloxacin, clarithromycin and rifampicin for 4 months but relapsed, subsequently responding to combined pradofloxacin, rifampicin, doxycycline and ethambutol. After 12 months of treatment, M. avium was detected and treatment extended to 17 months before stopping when no organism was detected. Relapse occurred after 6 weeks, responding to retreatment but relapsing (polyarthropathy, lymphadenomegaly) after 15 months, with euthanasia 38 months after diagnosis. Dogs with M. avium are challenging to treat with frequent relapse; however, long-term survival is possible., (© 2024 British Small Animal Veterinary Association.)

Background: Problematic mealtime behaviors and inadequate diet quality are pressing concerns for children with autism spectrum disorder (ASD). This study aimed to evaluate recruitment feasibility and baseline outcomes of the Autism Eats program for children under 3 years with ASD., Methods: Recruitment feasibility was assessed through reach and participation rates. The Healthy Eating Index (HEI-2015) scores were calculated from 3-day food records. Problematic mealtime behaviors were assessed with the Brief Autism Mealtime Behavior Inventory. Parental feeding practices were assessed using the Child Feeding Questionnaire. Anthropometric measurements of children and parents were taken. Weight-for-length percentiles were calculated based on the CDC growth charts. Descriptive statistics, one-sample t-tests, and Spearman's rho correlations were used for data analysis., Results: Of the contacted dyads, 74 % agreed to participate. All 51 enrolled dyads completed baseline survey (100 %), and 98 % completed 3-day food records and anthropometric measurements. Significantly higher problematic mealtime behaviors were observed, compared to the reference (e.g., Total score 55.7 vs. 32.5; p < .001). Children with ASD exhibited lower HEI-2015 scores than national data (e.g., Total score 59 vs. 62). A large proportion of the children (29 %) had a weight-for-length ≥ 95th percentile. Several significant associations were found among mealtime behaviors, diet quality, parental feeding practices, and weight status., Conclusion: Recruitment was highly feasible, and the findings suggest that early nutrition intervention may hold promise in addressing problematic mealtime behaviors and promoting healthier dietary habits in young children with ASD., Clinical Trial Registration: This trial has been registered at www., Clinicaltrials: gov (NCT05194345)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

ABSTRACT Justice-impacted persons may inconsistently access HIV testing. This cross-sectional secondary analysis investigates lifetime HIV testing prevalence among adults with prior histories of incarceration in Southern California, United States, participating in health-focused programming ( n  = 3 studies). Self-reported demographic and lifetime HIV testing data were collected between 2017-2023; descriptive analyses were conducted. Across the three samples, at least 74% of participants were male; Latino and African American individuals accounted for nearly two-thirds of participants. Lifetime HIV testing ranged from 72.8% to 84.2%. Males were significantly more likely than females to report never being tested in two samples and accounted for >95% of those never tested. No statistically significant differences in testing were observed by race/ethnicity. Single young adults (ages 18-26) were less likely than their partnered peers to report testing. HIV testing is critical for ensuring that individuals access prevention and treatment. HIV testing among justice-impacted adults in this study was higher than in the general population, potentially due to opt-out testing in correctional settings. Nevertheless, these findings underscore the importance of implementing targeted interventions to reduce structural (e.g., health insurance, access to self-testing kits) and social barriers (e.g., HIV stigma) to increase HIV testing among justice-impacted males and single young adults.

Mozambique is making progress towards elimination of trachoma as a public health problem, but in some districts trachomatous inflammation-follicular (TF) prevalence remains above the 5% elimination threshold despite years of various interventions, including antibiotic mass drug administration. To characterize transmission in four districts, we incorporated testing of ocular infection and serology into routine trachoma impact surveys (TIS) in August 2022. We examined residents aged ≥ 1 year for trachoma and collected information on household water, sanitation, and hygiene. Among children aged 1-9 years, we tested conjunctival swabs for Chlamydia trachomatis nucleic acid and dried blood spots for C. trachomatis antibodies. We modeled age-dependent seroprevalence to estimate seroconversion rate (SCR). We examined 4841 children aged 1-9 years. TF prevalence ranged between 1.1 and 6.0% with three districts below the 5% threshold. PCR-confirmed infection prevalence ranged between 1.1 and 4.8%, and Pgp3 seroprevalence ranged between 8.8 and 24.3%. Pgp3 SCR was 1.9 per 100 children per year in the district with the lowest TF prevalence. Two other districts with TF < 5% had SCR of 5.0 and 4.7. The district with TF ≥ 5% had a SCR of 6.0. This enhanced TIS furthered understanding of transmission in these districts and provides information on additional indicators for monitoring trachoma programs., (© 2024. The Author(s).)

Competing Interests: Conflicts of interest and sources of funding: none declared.

Pheochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumors derived from chromaffin cells in the autonomic nervous system. Depending on their location, these tumors are capable of excessive catecholamine production, which may lead to uncontrolled hypertension and other life-threatening complications. They are associated with a significant risk of metastatic disease and are often caused by an inherited germline mutation. Although surgery can cure localized disease and lead to remission, treatments for metastatic PPGL (mPPGL)-including chemotherapy, radiopharmaceutical agents, multikinase inhibitors, and immunotherapy used alone or in combination- aim to control tumor growth and limit organ damage. Substantial advances have been made in understanding hereditary and somatic molecular signaling pathways that play a role in tumor growth and metastasis. Treatment options for metastatic disease are rapidly evolving, and this paper aims to provide a brief overview of the management of mPPGL with a focus on therapy options., Competing Interests: Declaration of competing interest Jeena Varghese: None. Camilo Jimenez: Has received research support from Lantheus Pharmaceuticals, Progenics Pharmaceuticals, Excelixis and Merck MSD. Catherine Skefos: None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Alzheimer's disease (AD) affects various brain cell types, including astrocytes, which are the most abundant cell types in the central nervous system (CNS). Astrocytes not only provide homeostatic support to neurons but also actively regulate synaptic signaling and functions and become reactive in response to CNS insults through diverse signaling pathways including the JAK/STAT, NF-κB, and GPCR-elicited pathways. The advent of new technology for transcriptomic profiling at the single-cell level has led to increasing recognition of the highly versatile nature of reactive astrocytes and the context-dependent specificity of astrocyte reactivity. In AD, reactive astrocytes have long been observed in senile plaques and have recently been suggested to play a role in AD pathogenesis and progression. However, the precise contributions of reactive astrocytes to AD remain elusive, and targeting this complex cell population for AD treatment poses significant challenges. In this review, we summarize the current understanding of astrocyte reactivity and its role in AD, with a particular focus on the signaling pathways that promote astrocyte reactivity and the heterogeneity of reactive astrocytes. Furthermore, we explore potential implications for the development of therapeutics for AD. Our objective is to shed light on the complex involvement of astrocytes in AD and offer insights into potential therapeutic targets and strategies for treating and managing this devastating neurodegenerative disorder., (© 2023 International Society for Neurochemistry.)

Canola protein obtained from canola meal, a byproduct of the canola industry, is an economical biopolymer with promising film-forming properties. It has significant potential for use as a food packaging material, though it possesses some functional limitations that need improvement. Incorporating nanomaterials is an option to enhance functional properties. This study aims to produce canola protein films by integrating GO exfoliated at several oxidation times and weight ratios to optimize mechanical, thermal, and barrier properties. Oxidation alters the C/O ratio and adds functional groups that bond with the amino/carboxyl groups of protein, enhancing the film properties. Significant improvement was obtained in GO at 60 and 120 min oxidation time and 3% addition level. Tensile strength and elastic modulus increased 200% and 481.72%, respectively, compared to control. Control films showed a 37.57 × 10 -3 cm 3 m/m 2 /day/Pa oxygen permeability, and it was significantly reduced to 5.65 × 10 -3 cm 3 m/m 2 /day/Pa representing a 665% reduction., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests or personal relationships that have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

In plastic surgery, the reconstructive ladder is a systematic approach used to guide the planning and execution of reconstructive procedures. The use of autologous tissues is preferred in the breast reconstruction process due to the multiple advantages they offer. The latissimus dorsi musculocutaneous flap has been the therapeutic option of choice in these cases, replacing other surgical techniques because of the high adaptability and low complication rates. We report a case of a 69-year-old female who presented a lesion in the right breast reported as sarcoma, who underwent into an extended resection and reconstructive procedure with a latissimus dorsi musculocutaneous flap., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Villarreal-Salgado et al.)

Arctic sea ice volume (SIV) is a key climate indicator and memory source in sea ice predictions and projections, yet suffering from large observational and model uncertainty. Here, we test whether passive microwave (PMW) data constrain the long-term evolution of Arctic SIV, as recently hypothesized. We find many commonalities in Arctic SIV changes from a PMW sea ice thickness (SIT) 1992-2020 time series reconstructed with a neural network algorithm trained on lidar altimetry, and the reference PIOMAS reanalysis: relatively low differences in SIV mean (4615 km 3 , 37%), SIV trends (46 km 3 , 17%), and phased variability (r 2 =0.55). Key to reduced differences is the consistent evolution of many SIV contributors: seasonal and perennial ice coverage, their SIT contrast, whereas perennial SIT provides the largest remaining uncertainty source. We argue that PMW includes useful SIT information, reducing SIV uncertainty. We foresee progress from sea ice reanalyses combining dynamical models and data assimilation of PMW SIT estimates, in addition to the already assimilated PWM sea ice concentration., (© 2024. The Author(s).)

Background & Aims: The benefits of prophylactic antibiotics in patients with alcohol-associated hepatitis (AH) receiving steroids remain unclear. We aimed to assess the clinical impact of prophylactic antibiotics in AH patients receiving steroids., Methods: We systematically reviewed four electronic databases from inception to 30 November 2023. Pooled estimates were analysed using random-effects models. The primary outcome was 90-day survival. Secondary outcomes included infection at days 30 and 90 days, hepatorenal syndrome (HRS), acute kidney injury (AKI), hepatic encephalopathy (HE) and drug-related adverse events (AE). Trial sequential analyses were performed for the primary outcome of 90-day mortality., Results: We screened 419 articles and included six eligible studies (four RCTs and two matched cohort studies) with a total of 510 patients. Compared to standard medical treatment (SMT), prophylactic antibiotics were associated with a lower risk of infection at 30 days (OR: 0.35, 95%CI: 0.20-0.59, I 2  = 0%), infection at 90 days (OR: 0.26, 95%CI: 0.10-0.67, I 2  = 0%) and a lower rate of HE (OR: 0.32, 95%CI: 0.12-0.87, I 2  = 0%). However, prophylactic antibiotics did not improve 90-day survival, sepsis-related mortality, HRS, or AKI. The risks of drug-related AE and fungal infections were similar in patients with AH who received prophylactic antibiotics or SMT. Using trial sequential analysis, the minimum sample size required to detect a 15% relative risk reduction in 90 days mortality with prophylactic antibiotics was 1171., Conclusions: In hospitalized AH patients receiving steroid therapy, prophylactic antibiotics reduced the risk of infection and HE, but did not improve survival or prevent AKI compared to SMT., (© 2024 The Author(s). Liver International published by John Wiley & Sons Ltd.)

Metastatic pheochromocytomas and paragangliomas (PPGLs) are frequently associated with skeletal complications. Primary objective: to describe the frequency of adverse skeletal related events (SREs) in PPGL patients with bone metastases (BMs). Secondary objectives: to 1) identify predictive and prognostic factors for SREs and 2) obtain information on the effectiveness of bone resorption inhibitors in reducing SRE risk and improving outcomes in term of survival and SREs time onset. In this retrospective multicenter, multinational study, 294 PPGL patients were enrolled. SREs occurred in 90 patients (31 %). Fifty-five patients (19 %) had bone fractures, 47 (16 %) had spinal cord compression, and 11 (4 %) had hypercalcemia. Twenty-two patients (7 %) had more than one SRE. Sixty-four patients (22 %) underwent surgery, and 136 (46 %) underwent radiotherapy. SREs occurred a median of 4.4 months after diagnosis of BM (range, 0-246.6 months). Independent factors associated with reduced risk of SREs in multivariable analysis were I-131-MIBG radionuclide therapy (hazard ratio [HR], 0.536 [95 % CI, 0.309-0.932]; P = .027) and absence of liver metastases (HR, 0.638 [95 % CI, 0.410-0.992]; P = .046). The median overall survival duration was 5.3 year. In multivariable analysis, age younger than 48 years at PPGL diagnosis (HR, 0.558 [95 % CI, 0.3877-0.806]; P = .002), absence of liver metastases (HR, 0.618 [95 % CI, 0.396-0.965]; P = .034), treatment with bisphosphonates or denosumab (HR, 0.598 [95 % CI, 0.405-0.884]; P = .010), and MIBG radionuclide therapy (HR, 0.444 [95 % CI, 0.274-0.718]; P = .001) were associated with a reduced risk of death. SREs occur frequently and early in bone-metastatic PPGL patients but do not negatively impact survival. MIBG radionuclide therapy and treatment with bone resorption inhibitors are associated with favorable outcome., 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 Ltd.. All rights reserved.)

Although ischemia increases the abundance of plasminogen activator inhibitor-1 (PAI-1), its source and role in the ischemic brain remain unclear. We detected PAI-1-immunoreactive cells with morphological features of reactive astrocytes in the peri-ischemic cortex of mice after an experimentally-induced ischemic lesion, and of a chimpanzee that suffered a naturally-occurring stroke. We found that although the abundance of PAI-1 increases 24 hours after the onset of the ischemic injury in a non-reperfusion murine model of ischemic stroke, at that time-point there is no difference in astrocytic reactivity and the volume of the ischemic lesion between wild-type (Wt) animals and in mice either genetically deficient (PAI-1 -/- ) or overexpressing PAI-1 (PAI-1 Tg ). In contrast, 72 hours later astrocytic reactivity and the volume of the ischemic lesion were decreased in PAI-1 -/- mice and increased in PAI-1 Tg animals. Our immunoblottings and fractal analysis studies show that the abundance of astrocytic PAI-1 rises during the recovery phase from a hypoxic injury, which in turn increases the abundance of glial fibrillary acidic protein (GFAP) and triggers morphological features of reactive astrocytes. These studies indicate that cerebral ischemia-induced release of astrocytic PAI-1 triggers astrocytic reactivity associated with enlargement of the necrotic core., 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.

An intranasal tumour was diagnosed in a 5-year-old male neutered crossbreed dog following a 6-8 week history of intermittent epistaxis and nasal discharge. Computed tomography identified a mass in the right nasal cavity. Histologically, the mass was composed of sheets and indistinct clusters of predominantly clear or vacuolated round to polygonal cells; periodic acid-Schiff staining revealed glycogen granules within some tumour cells. Immunohistochemical labelling revealed that the tumour cells were immunopositive for vimentin and S100 and negative for pancytokeratin, Melan-A and PNL2, supporting a diagnosis of a clear cell variant of chondrosarcoma (CCC). Although the dog was treated with meloxicam, the owners opted for euthanasia 9 days after presentation. Considering that there is only one other reported case of a suspected CCC in a dog, also in the nasal cavity, this could represent a species-specific predilection site of this rare canine neoplasm., Competing Interests: Declaration of competing interests The authors declared no conflicts of interest in relation to the research, authorship or publication of this article., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Recently, the treatment landscape for metastatic pheochromocytomas and paragangliomas (MPPGL) has seen both progress and setbacks. We provide an up-to-date review of the multimodality management of MPPGL and discuss novel opportunities and current challenges in the treatment landscape. Given the unique clinical presentation of MPPGL, we discuss the management of hormone-related clinical sequelae and traditional modalities of therapy. Advances in the understanding of the molecular biology of these diverse tumors have enabled novel strategies such as augmenting DNA damage by targeted delivery of radionuclides such as 131 I and 177 Lu, abrogating tumor angiogenesis, hypoxia resistance, and DNA damage repair. Despite progress, we address the significant challenges still faced by patients and researchers engaged in efforts to improve outcomes in these rare cancers., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: V.S. reports research funding to the institution from Eli Lilly and Company and Crinetics Pharmaceuticals. He has served as a consultant to GE Oncology and has received speaking fees from Lantheus. He serves on the advisory board for Exelixis. N.P-T. has served as a consultant or advisory board member for and/or received honoraria from Actinium Pharma, Progenics, Medimmune/Astrazeneca, Illumina, and ImaginAb and conducts research institutionally supported by Y-mAbs, ImaginAb, BMS, Bayer, Clarity Pharma, Janssen, and Regeneron. C.J. reports receiving research funding to the institution from Exelixis, Lantheus Pharmaceuticals, Progenics Pharmaceuticals, and Merck Sharp and Dohme and is a scientific advisory board member for Lantheus Pharmaceuticals, Progenics Pharmaceuticals, and Merck Sharp and Dohme. K.P. was a one-time advisory board member of Exelixis, Lantheus, Ipsen, and Novartis., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Hematopoietic stem cell transplant (HSCT) recipients are among patients with highest risk of adverse coronavirus disease 2019 (COVID-19) outcomes., Objective: We compared clinical outcomes in post-HSCT patients with COVID-19 before and during the Omicron period., Study Design: This was a retrospective study including patients post-HSCT with severe acute respiratory syndrome coronavirus 2 infection from April 2020 to March 2023 at Instituto Nacional de Cancerología, Mexico City. We describe their clinical characteristics and report the variables associated with severe clinical disease, hospitalization, and death., Results: Fifty-three patients were included; 31 (58.5%) from the pre-Omicron period and 22 (41.5%) from the Omicron period. Median age was 42-years old (interquartile range 26-53), and 31 patients (59%) were men. Only four patients (16%) had received a vaccine prior to COVID-19 diagnosis in the pre-Omicron period versus 20 (91%) in the Omicron period (p < 0.001). COVID-19 severe cases were more common before Omicron: seven patients (23%) versus two patients (9%). Only one patient (3%) received an antiviral in the pre-Omicron period compared to 11 patients (50%) during the Omicron period (p < 0.01). COVID-19-associated mortality was almost double in the pre-Omicron period (16% vs. 9%, p = 0.6)., Conclusions: This study reports patients with a high proportion of severe outcomes during the first 2 years of the pandemic. Outcomes improved during Omicron with better access to vaccines and antivirals and no in-hospital cases. Variables associated with worse outcomes were similar to other reports. Strengthening infection control measures in the hospital and better access to preventive strategies and therapeutic options are mandatory in these high-risk patients., (© 2024 Wiley Periodicals LLC.)

Little is known about the effectiveness of online preventive interventions for paternal perinatal depression (PPD). This systematic review (SR) and meta-analysis (MA) of randomized controlled trials (RCTs) evaluated the effectiveness of online psychological interventions to prevent PPD in fathers and non-birthing partners. The PRISMA 2020 guidelines were followed. The search was conducted in eight electronic databases and other sources from inception to 12 May 2023. The pooled standardized mean difference (SMD) was computed using random-effect models. Seven RCTs were included in the SR and 6 were included in the MA, representing 1.042 fathers from five different countries. No trials focused on non-birthing partners were found. The pooled SMD was -0.258 [95 % confidence interval - 0.513 to -0.004; p  < 0.047]. The heterogeneity was moderate (I2 = 51 %; 95%CI [0 % to 81 %]) and nonsignificant ( p  = 0.070). However, sensitivity analyses showed that the effectiveness was stable only when the fixed effect model and the Egger's g were used to estimate the pooled SMD. No publication bias was found. Only two RCTs had an overall low risk of bias assessed by using the Cochrane ROB 2.0 tool. The quality of evidence based on GRADE was very low. In conclusion, online psychological interventions may be effective for the prevention of PPD. More high-quality evidence is warranted., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Venous thromboembolism (VTE) is a leading cause of death in patients with cancer. Limited data exist about VTE in patients with adrenocortical carcinoma (ACC). The primary objective of this study was to identify the prevalence of VTE in a cohort of patients with ACC. Secondary objectives were to determine the impact of VTE events on overall survival (OS) and to describe the characteristics of VTE in patients with ACC., Patients and Methods: We retrospectively reviewed data from 289 patients with ACC cared for at a major referral center from February 2010 to June 2022., Results: VTE prevalence was 18.7% (54 events). Thirty patients (55.6%) had pulmonary embolism (PE); 12 patients (22.2%) had deep vein thrombosis (DVT); and 12 patients (22.2%) had both PE and DVT. VTE occurred after ACC diagnosis in 50 patients (92.6%) including 44 patients (88%) with stage 3 or 4 ACC. VTEs were CTCAE grade ≤2 in 32 cases (59.3%), grade 3 in 17 (31.5%), and grade 4 in 2 (3.7%). Thirteen patients (24%) died within 6 months after VTE diagnosis, although there was no statistically significant association between VTE and overall survival., Conclusion: Despite the potential to underestimate the prevalence of VTEs, we found a high frequency of VTE events in patients with ACC. A majority of VTEs occurred in the context of advanced ACC and we observed high short-term mortality. Further studies are needed to validate our findings and investigate mechanisms associated with VTE in ACC., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Photography could be used to train individuals to diagnose trachomatous inflammation-follicular (TF) as trachoma prevalence decreases and to ensure accurate field TF grading in trachoma prevalence surveys. We compared photograph and field TF grading and determined the acceptability and feasibility of eyelid photography to community members and trachoma survey trainers., Methods: A total of 100 children ages 1-9 y were examined for TF in two Maasai villages in Tanzania. Two images of the right everted superior tarsal conjunctiva of each child were taken with a smartphone and a digital single-lens reflex (DSLR) camera. Two graders independently graded all photos. Focus group discussions (FGDs) were conducted with community members and Tropical Data trainers., Results: Of 391 photos, one-fifth were discarded as ungradable. Compared with field grading, photo grading consistently underdiagnosed TF. Compared with field grading, DSLR photo grading resulted in a higher prevalence and sensitivity than smartphone photo grading. FGDs indicated that communities and trainers found photography acceptable and preferred smartphones to DSLR in terms of practicalities, but image quality was of paramount importance for trainers., Conclusions: Photography is acceptable and feasible, but further work is needed to ensure high-quality images that enable accurate and consistent grading before being routinely implemented in trachoma surveys., (© The Author(s) 2023. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

While the role of autobiographical memory in self-representation is well established, the identity function of future thinking has received much less attention. Yet, most people commonly imagine future events that convey meaningful information about the person they wish or expect to become. In three experiments, we assessed the extent to which thinking about such self-defining future events influences the current content of self-representation (i.e., the working self-concept). Participants were asked to think about either a past or future self-defining event, or a control topic, before describing aspects of their identity in the form of "I am" statements (Experiments 1 and 3) or completing scales assessing self-related dimensions (Experiments 2 and 3). We found that thinking about a future self-defining event led participants to conceptualise themselves more in terms of their psychological traits, as did thinking about a past self-defining event. Furthermore, thinking about a future self-defining event increased the sense of present-future self-continuity, whereas thinking about a past self-defining event increased the sense of past-present self-continuity. These results suggest that self-representations are fuelled not only by autobiographical memories, but also by projections into the future.

Patients and Methods: The primary endpoints were objective response rate (ORR) and disease control rate (DCR). Secondary endpoints were duration of response, blood pressure control, safety, overall and progression-free survival rates, MIBG uptake, and correlations with genetic background., Results: The study included 25 patients. Twenty-four patients had distant metastases, 17 (68%) had hormonally active tumors, and 13 (52%) had previously received antineoplastic treatment. In 24 evaluable patients, the ORR was 38%, including 2 patients with complete response, and the DCR was 83%; median time to response was 12.5 months (95% confidence interval, 4.6-25.1). Twelve patients had sporadic disease, among whom the ORR was 25% and DCR was 83%. Twelve patients had hereditary disease ( SDHB , VHL , RET ); among these, the ORR was 50%, and DCR was 83%. Plasma metanephrines normalized in 30% of patients and improved by greater than 50% in 46%. Sixteen patients had hormonally active tumors and hypertension; in 9 (56%) of these, blood pressure normalized, leading to discontinuation of antihypertensive therapy.The most common adverse events were grades 1-2 nausea/vomiting and transient bone marrow suppression. One patient developed premature ovarian failure. Reversible grades 3-4 myelosuppression were seen in 7 patients (28%). One patient had fatal pneumonitis., Conclusions: HSA- 131 I-MIBG is associated with a high DCR in patients with MPPGL, regardless of underlying genetic mutation., Competing Interests: Conflicts of interest and sources of funding: YL has received research support from Lantheus Pharmaceuticals. CJ has received research support from Progenics/Lantheus Pharmaceuticals, Exelixis, and MSD. RAW, VBB, SS, CLP, GX, SGW, JV, and MAH do not have disclosures., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: The United States Centers for Disease Control and Prevention (CDC) advises testing individuals for COVID-19 after exposure or if they display symptoms. However, a deeper understanding of demographic factors associated with testing hesitancy is necessary., Methods: A US nationwide cross-sectional survey of adults with risk factors for developing severe COVID-19 ("high-risk" individuals) was conducted from August 18-September 5, 2023. Objectives included characterizing demographics and attitudes associated with COVID-19 testing. Inverse propensity weighting was used to weight the data to accurately reflect the high-risk adult US population as reflected in IQVIA medical claims data. We describe here the weighted results modeled to characterize demographic factors driving hesitancy., Results: In the weighted sample of 5019 respondents at high risk for severe COVID-19, 58.2% were female, 37.8% were ≥ 65 years old, 77.1% were White, and 13.9% had a postgraduate degree. Overall, 67% were Non-testers (who indicated that they were unlikely or unsure of their likelihood of being tested within the next 6 months); these respondents were significantly more likely than Testers (who indicated a higher probability of testing within 6 months) to be female (60.2 vs. 54.1%; odds ratio [OR] [95% confidence interval (CI)], 1.3 [1.1‒1.4]), aged ≥ 65 years old (41.5 vs. 30.3%; OR [95% CI] compared with ages 18‒34 years, 0.6 [0.5‒0.7]), White (82.1 vs. 66.8%; OR [95% CI], 1.4 [1.1‒1.8]), and to identify as politically conservative (40.9 vs. 18.1%; OR [95% CI], 2.6 [2.3‒2.9]). In contrast, Testers were significantly more likely than Non-testers to have previous experience with COVID-19 testing, infection, or vaccination; greater knowledge regarding COVID-19 and testing; greater healthcare engagement; and concerns about COVID-19., Conclusions: Older, female, White, rural-dwelling, and politically conservative high-risk adults are the most likely individuals to experience COVID-19 testing hesitancy. Understanding these demographic factors will help guide strategies to improve US testing rates., (© 2024. The Author(s).)

Purpose: The Zoster Eye Disease Study (ZEDS) is a multicenter randomized clinical trial (RCT) funded by the National Eye Institute aiming to determine the efficacy of suppressive valacyclovir treatment in herpes zoster ophthalmicus (HZO) that enrolled fewer participants than planned (527/780, 67.6%). Understanding reasons for nonparticipation of likely eligible prescreened patients provides insights into patient populations that are not represented by ZEDS and barriers in clinical trials., Methods: In this retrospective cohort study, HZO adults likely eligible for ZEDS with a history of a typical rash and a medical record within the past year of an episode of epithelial or stromal keratitis or iritis were prescreened at activated Participating Clinical Centers from 2017 to 2022 using a standard prescreening log. De-identified data including demographic information, reasons for exclusion because of ineligibility, and patient refusal were retrospectively entered into REDCap and analyzed., Results: Prescreening logs with reasons for nonconsent (1244/1706, 72.9%) were included in the data set. Patients were excluded from the study (915/1244, 73.6%) because they did not meet all inclusion criteria (619/915, 67.7%) or met an exclusion criterion (296/915, 32.3%). Among the 12 exclusion criteria for the ZEDS study, immunocompromise (76/296, 25.7%) and renal insufficiency (50/296, 16.9%) were most frequently reported. Patient refusal to participate (327/1,244, 26.3%) was common., Conclusion: The most common reasons for ineligibility were immunocompromise and renal insufficiency. There may be benefits to long-term antiviral use in these populations not captured in ZEDS. A quarter (26.3%) of prescreened patients refused participation, showing the substantial impact of patient preferences on trial participation., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Contact Lens Association of Ophthalmologists.)

Development of fluorescent cholesterol analogs to better understand subcellular cholesterol trafficking is of great interest for cell biology and medicine. Our approach utilizes a bifunctional 1,8-naphthalimide scaffold with a push-pull character, modified on one side with a head group and a linker on the other side connecting it to cholesterol via an ester bond. Through structure-function studies, we've explored how different substituents-linkers and head groups-affect the ability of these fluorescent cholesterol naphthalimide analogs (CNDs) to mimic natural cholesterol behavior at both molecular and cellular levels. We categorized the resulting analogs into three groups: neutral, charged, and those featuring a hydroxyl group. Each compound was assessed for its solvatochromic behavior in organic solvents and model membranes. Extensive all-atom molecular dynamics simulations helped us examine how these analogs perform in model membranes compared to cholesterol. Additionally, we investigated the partitioning of these fluorescent probes in phase-separated giant unilamellar vesicles. We evaluated the uptake and distribution of these probes within mouse fibroblast cells and astrocytes, for their subcellular distributions in lysosomes and compared that to BODIPY-cholesterol, a well-regarded fluorescent cholesterol analog. The internalization efficiency of the fluorescent probes varies in different cell types and is affected mainly by the head groups. Our results demonstrate that the modular design significantly simplifies the creation of fluorescent cholesterol probes bearing distinct spectral, biophysical, and cellular targeting features, which makes it a valuable toolkit for the investigation of subcellular distribution and trafficking of cholesterol and its derivatives.

Competing Interests: Su Wang received grants from Gilead. Carla S. Coffin consults for and received grants from Gilead and GSK. She received grants from Janssen Pharmaceuticals, Roche, and Altimmune. Chari Cohen advises and received grants from Gilead. She advises GSK. She received grants from Roche/Genentech and VBI Vaccines. The remaining authors have no conflicts to report.

Background: Trabecular metal augments (TMAs) have been extensively used in revision total hip arthroplasty (THA) to address acetabular bone defects. However, limited data exists regarding TMA utilization during primary THA. This study aims to assess the clinical and radiographic outcomes of TMAs used during primary THA., Methods: A single-institution retrospective case series of primary THA patients treated with TMA between 2010 and 2019 was performed. Patient demographics, complications, and revisions were recorded. Cup position, center of rotation, leg length, and radiolucent lines were assessed radiographically. The Kaplan-Meier method was used to compute implant survivorship., Results: Twenty-six patients (30 hips) were included with average age of 52.6 ± 15.3 years (range: 22-78) and mean follow-up of 4.1 ± 2.1 years (range: 2.0-8.9). Most TMAs were indicated for developmental dysplasia of the hip (n = 18; 60.0%). On average, hip center of rotation was lowered 1.5 ± 1.3 cm and lateralized 1.2 ± 1.5 cm, while leg length and global offset were increased by 2.4 ± 1.2 cm and 0.4 ± 1.0 cm, respectively. At final follow-up, 3 hips (10.0%) required revision: one (3.3%) for aseptic loosening and 2 (6.7%) for instability. No patients had progressive radiolucent lines at final follow-up. Five-year survival with aseptic loosening and all-cause revision as endpoints was 100% (95% confidence interval: 90.0%-100.0%) and 92.1% (95% confidence interval: 81.3%-100.0%), respectively. One patient required revision for aseptic loosening after the 5-year mark., Conclusions: Trabecular metal augmentation during primary THA demonstrates satisfactory early to mid-term outcomes. TMA is a viable option for complex primary THA when bone loss is encountered or secondary support is required., Level of Evidence: Level IV., (© 2024 The Authors.)

Objective: Targeting bacterial translocation in cirrhosis is limited to antibiotics with risk of antimicrobial resistance. This study explored the therapeutic potential of a non-absorbable, gut-restricted, engineered carbon bead adsorbent, Yaq-001 in models of cirrhosis and acute-on-chronic liver failure (ACLF) and, its safety and tolerability in a clinical trial in cirrhosis., Design: Performance of Yaq-001 was evaluated in vitro . Two-rat models of cirrhosis and ACLF, (4 weeks, bile duct ligation with or without lipopolysaccharide), receiving Yaq-001 for 2 weeks; and two-mouse models of cirrhosis (6-week and 12-week carbon tetrachloride (CCl4)) receiving Yaq-001 for 6 weeks were studied. Organ and immune function, gut permeability, transcriptomics, microbiome composition and metabolomics were analysed. The effect of faecal water on gut permeability from animal models was evaluated on intestinal organoids. A multicentre, double-blind, randomised, placebo-controlled clinical trial in 28 patients with cirrhosis, administered 4 gr/day Yaq-001 for 3 months was performed., Results: Yaq-001 exhibited rapid adsorption kinetics for endotoxin. In vivo , Yaq-001 reduced liver injury, progression of fibrosis, portal hypertension, renal dysfunction and mortality of ACLF animals significantly. Significant impact on severity of endotoxaemia, hyperammonaemia, liver cell death, systemic inflammation and organ transcriptomics with variable modulation of inflammation, cell death and senescence in the liver, kidneys, brain and colon was observed. Yaq-001 reduced gut permeability in the organoids and impacted positively on the microbiome composition and metabolism. Yaq-001 regulated as a device met its primary endpoint of safety and tolerability in the clinical trial., Conclusions: This study provides strong preclinical rationale and safety in patients with cirrhosis to allow clinical translation., Trial Registration Number: NCT03202498., Competing Interests: Competing interests: JMacNaughtan: Shareholder in Yaqrit—no payments received; LM: Yaqrit Employee; KC: Yaqrit consultant; CM: Full-time employee of Yaqrit—salary, Share options in Yaqrit Discovery—no payment received; TA: Full-time employee of Yaqrit—Salary; MK: Full-time employee of Yaqrit—salary, Shares and Share options in Yaqrit Discovery—no payment received; DG: Share options—Yaqrit; AG: Shareholder—Yaqrit; RPM: Shareholder in Yaqrit —No payments received; SShoaie: Co-founder of Gigabiome, Bash Biotech and DAS Microbiome; JMarchesi: JMarchesi has received consultancy fees from EnteroBiotix and Cultech, and speaker fees from Falk Forum; RJ: RJ is the inventor of OPA, which has been patented by UCL and licensed to Mallinckrodt Pharma. He is also the founder of Yaqrit Discovery, Hepyx (spin out companies from University College London), and Cyberliver. He has research collaborations with Yaqrit Discovery. Yaq-001 was licensed by Yaqrit from UCL., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

The Gypsum Karst of Sorbas, Almeria, southeast Spain, includes a few caves whose entrances are open and allow the entry and roosting of numerous bats. Caves are characterized by their diversity of gypsum speleothems, such as stalactites, coralloids, gypsum crusts, etc. Colored biofilms can be observed on the walls of most caves, among which the Covadura and C3 caves were studied. The objective was to determine the influence that bat mycobiomes may have on the fungal communities of biofilms. The results indicate that the fungi retrieved from white and yellow biofilms in Covadura Cave (Ascomycota, Mortierellomycota, Basidiomycota) showed a wide diversity, depending on their location, and were highly influenced by the bat population, the guano and the arthropods that thrive in the guano, while C3 Cave was more strongly influenced by soil- and arthropod-related fungi (Ascomycota, Mortierellomycota), due to the absence of roosting bats., (© 2024. The Author(s).)

Trachoma is targeted for elimination as a public health problem worldwide by 2030. In Nigeria, elimination activities are implemented at the local government area (LGA) level. They started in 2002 by conducting baseline population-based prevalence surveys (PBPSs), which continued in a systematic manner with engagement from the Global Trachoma Mapping Project in 2013, and subsequently Tropical Data. The results led to the development of Nigeria's first trachoma action plan and its subsequent revision with additional information. Following 449 baseline PBPSs, 122 LGAs had an active trachoma prevalence above the elimination threshold, requiring interventions, while 231 LGAs required community-based interventions for trichiasis management. By 2021, >34 million antibiotic treatments had been provided in 104 LGAs, with 89 LGAs eliminating active trachoma. Nationally, water and sanitation coverages increased by 3% and 18%, respectively, in 7 y. Systematic trichiasis case finding and management were carried out in 231 LGAs, resulting in the management of 102 527 people. Fifty-four LGAs decreased trichiasis prevalence unknown to the health system to <0.2% in persons ≥15 y of age. Where this elimination prevalence threshold was reached, trichiasis services were transitioned to routine eye/healthcare systems. Such progress relied on strong leadership and coordination from the national trachoma program and tremendous support provided by partners. Attaining elimination of trachoma as a public health problem in Nigeria by 2030 is feasible if funding support is sustained., (© The Author(s) 2024. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Assessment and management of burns require nuanced, timely interventions in high-stake settings, creating challenges for trainees. Simulation-based education has become increasingly popular in surgical and nonsurgical subspecialties to supplement training without compromising patient safety. This study aimed to systematically review the literature on existing burn management-related simulations. A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Articles describing burn-specific surgical and nonsurgical simulation models were included. The model type, study description, simulated skills, assessment methods, fidelity, cost, and outcomes were collected. Of 3,472 articles, 31 met inclusion criteria. The majority of simulations were high-fidelity (n=17, 54.8%). Most were immersive (n=17, 54.8%) and used synthetic benchtop models (n=13, 41.9%), whereas none were augmented/virtual reality. Simulations of acute and early surgical intervention techniques (n=16, 51.6%) and burn wound assessments (n=15, 48.4%) were the most common, whereas burn reconstruction was the least common (n=3, 9.7%). Technical skills were taught more often (n=29, 93.5%) than non-technical skills (n=15, 48.4%). Subjective assessments (n=18, 58.1%) were used more often than objective assessments (n=23, 74.2%). Of the studies that reported costs, 91.7% (n=11) reported low costs. This review identified the need to expand burn simulator options, especially for burn reconstruction, and highlighted the paucity of animal, cadavers, and augmented/virtual reality models. Developing validated, accessible burn simulations to supplement training may improve education, patient safety, and outcomes., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Invasive species pose serious threats to ecosystems. To reduce ecological and economic consequences of invasions, efforts are made to control invaders and evaluating the effects of such efforts is paramount. Lionfishes (Pterois volitans and Pterois miles) are native to the Indo-Pacific Ocean and pose a major threat to local ecosystems in the invaded Atlantic and Mediterranean. Culling via spearfishing is a widespread measure to limit lionfish population size in invaded ranges. However, like most hunted fishes, lionfish alter their behavior after repeated culling, potentially decreasing the effectiveness of future culls. Previous studies on lionfish in the Caribbean have shown that lionfish are less bold after repeated culling. However, the impact of culling on lionfish in their newest invasive range, the Mediterranean, remains enigmatic. To determine the behavioral changes in response to culling in this second area of invasion, we tested for effects of culling on the behavior of lionfish in Cyprus, a region heavily impacted by the lionfish invasion in the Mediterranean. We compared the response of lionfish to an approaching free diver holding a metal pole (imitating a spear fisher) between protected areas where spearfishing is restricted and areas where culls are frequently conducted. We also assessed whether activity, hiding pattern, and site fidelity differed between these culled and unculled sites. Overall, we found limited effects of culling on the traits measured, indicating surprising resistance to culling-induced behavioral changes in Mediterranean lionfish. Future studies should monitor invasive lionfish population densities and the effects of culling in more detail to tailor management plans and reduce the negative effects of these fish in specific invaded ranges., (© 2024 The Authors. Journal of Fish Biology published by John Wiley & Sons Ltd on behalf of Fisheries Society of the British Isles.)

Background: Adrenocortical carcinoma is a rare malignancy with poor response to systemic chemotherapy. Mitotane is the only approved therapy for adrenocortical carcinoma. Cabozantinib is a multikinase inhibitor approved in multiple malignancies. This is the first prospective trial to explore the anti-tumour activity, safety, and pharmacokinetic profile of cabozantinib in patients with advanced adrenocortical carcinoma., Methods: This investigator-initiated, single-arm, phase 2 trial in adult patients (aged ≥18 years) with advanced adrenocortical carcinoma was done at the University of Texas MD Anderson Cancer Center (Houston, TX, USA). Eligible patients had histologically confirmed adrenocortical carcinoma, were not candidates for surgery with curative intent, had measurable disease, had an estimated life expectancy of at least 3 months, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 with adequate organ function. Patients who had used mitotane within 6 months of study participation were required to have a serum mitotane level of less than 2 mg/L. Patients were given oral cabozantinib 60 mg daily with the option of dose reduction to manage adverse events. The primary endpoint was progression-free survival at 4 months, assessed in all patients who received at least one dose of study drug per protocol. This study is registered with ClinicalTrials.gov, NCT03370718, and is now complete., Findings: Between March 1, 2018, and May 31, 2021, we enrolled 18 patients (ten males and eight females), all of whom received at least one dose of study treatment. Of the 18 patients, eight (44%) had an ECOG performance status of 0, nine (50%) patients had a performance status of 1, and one (6%) patient had a performance status of 2. Median follow-up was 36·8 months (IQR 30·2-50·3). At 4 months, 13 (72·2%; 95% CI 46·5-90·3) of 18 patients had progression-free survival and median progression-free survival was 6 months (95% CI 4·3 to not reached). One patient remains on treatment. Treatment-related adverse events of grade 3 or worse occurred in 11 (61%) of 18 patients. The most common grade 3 adverse events were lipase elevation (three [17%] of 18 patients), elevated γ-glutamyl transferase concentrations (two [11%] patients), elevated alanine aminotransferase concentrations (two [11%] patients), hypophosphatemia (two [11%] patients), and hypertension (two [11%] patients). One (6%) of 18 patients had grade 4 hypertension. No treatment related deaths occurred on study., Interpretation: Cabozantinib in advanced adrenocortical carcinoma showed promising efficacy with a manageable and anticipated safety profile. Further prospective studies with cabozantinib alone and in combination with immune checkpoint therapy are ongoing., Funding: Exelixis., Competing Interests: Declaration of interests MTC reports institutional research funding from ApricityHealth, AstraZeneca, Exelixis, Janssen, Pfizer, SeaGen, and the United States Department of Defense; speaker's Bureau participation with Curio Science, Dava Oncology, and MJH Life Sciences; and advisory board fees or honorarium from Exelixis, Eisai, and SeaGen. CJ reports research grants paid to their institution from Exelixis, Merck Sharp & Dohme, Progenics pharmaceuticals, and Lantheus pharmaceuticals; and participation of scientific advisory boards for Merck Sharp & Dohme and Lantheus pharmaceuticals. CH reports research grants to their institution from Avenge Bio, Dragonfly Therapeutics, BTG, Sanofi, and Iovance; stock options from BriaCell as a scientific advisory board member; and travel expenses or honoraria from the Hope Foundation and the Society for Immunotherapy of Cancer, outside the scope of the submitted work. MAH reports research grants to their institution from Exelixis, Merck, and Corcept; and honoraria from HRA pharma. All other authors declare no competing interests., (© 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Metastatic phaeochromocytomas and paragangliomas (MPPGs) are orphan diseases. Up to 50% of MPPGs are associated with germline pathogenic variants of the SDHB gene. These tumours and many non-familial MPPGs exhibit a phenotype that is characterised by abnormal angiogenesis. We aimed to assess the activity and safety of cabozantinib, an antiangiogenic multi-tyrosine kinase inhibitor, in patients with MPPGs., Methods: The Natalie Trial is a single-arm, phase 2 clinical trial being conducted at The University of Texas MD Anderson Cancer Center (Houston, TX, USA). Patients aged 18 years or older with histologically confirmed, progressive, and unresectable MPPGs, with an Eastern Cooperative Oncology Group performance status of 0-2, were treated with oral cabozantinib 60 mg/day. The primary endpoint was the investigator-assessed overall response rate per the Response Evaluation Criteria in Solid Tumours version 1.1 criteria. All outcomes were assessed in all evaluable participants who received any amount of study treatment. The trial is registered with ClinicalTrials.gov (NCT02302833) and is active but not recruiting., Findings: From March 10, 2015, to May 11, 2021, 17 patients (13 male participants and four female participants) were enrolled. The median follow-up was 25 months (IQR 18-49). The overall response rate was 25·0% (95% CI 7·3-52·4; four of 16 patients). Seven grade 3 adverse events were reported in six patients, including single cases of hand-and-foot syndrome, hypertension, rectal fistula, QT prolongation, and asymptomatic hypomagnesaemia, and two cases of asymptomatic elevations of amylase and lipase. There were no grade 4 adverse events and no patient died on-study., Interpretation: Cabozantinib shows promising activity in patients with MPPGs., Funding: Team NAT Foundation, Margaret Cazalot, and Clarence P Cazalot., Competing Interests: Declaration of interests CJ reports receiving research funding to the institution from Exelixis, Lantheus Pharmaceuticals, Progenics Pharmaceuticals, and Merck Sharp and Dohme and is a scientific advisory board member for Lantheus Pharmaceuticals, Progenics Pharmaceuticals, and Merk Sharp and Dohme. MAH reports receiving research funding to the institution from Exelixis, Merck, and Corcept and Honoraria from HRA pharma. MC reports receiving research funding to the institution from Exelixis, SeaGen, ApricityHealth, US Department of Defense, Janssen, Pfizer, and AstraZeneca; is a scientific advisory board member for Exelixis, Eisai, and SeaGen; and is a member of the speaker's bureau for Curio Science, Dava Oncology, and MJH Life Sciences. YL reports receiving research funding to the institution from Lantheus Pharmaceuticals. All other authors declare no competing interests., (© 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Introduction: In March 2020, a temporary federal regulatory exemption for opioid treatment programs (OTPs) was issued, allowing for a greater number of take-home methadone doses than was previously permitted. In the same month, to address financial sustainability, New York State (NYS) Medicaid also transitioned to a bundle reimbursement methodology for OTPs. We examined methadone dosing schedules in NYS before and after these regulatory and financing changes., Methods: We conducted a retrospective cohort study using NYS OTP patient data from two sources: the client data system for a baseline period (February 2020) and survey data collected after regulatory and financing changes (May 2020 to August 2021, 64 weekly surveys). We compared methadone dosing schedules over time using chi-square tests and Poisson regression., Result: At baseline, data were available for 78% (n=77/99) of OTPs including 90.9% (n=26,225/28,839) of their enrolled patients. During the survey period, 99 OTPs completed 93.1% (n=5901/6336) of weekly surveys, with a mean statewide weekly patient census of 38,904 (SD=1214.5). Between February and May 2020, daily dosing significantly decreased from 55.4% to 16.3% of patients (-39.1 percentage points [95%CI: -39.8 to -38.4]), although it significantly increased subsequently (3.33%/4-weeks [95%CI: 3.28, 3.39]). In addition, weekly-to-monthly dosing significantly increased from 26.9% to 54.5% of patients (27.6 percentage points [95%CI: 26.9, 28.4]), although it significantly decreased subsequently (-1.19%/4-weeks [95%CI: -1.23, -1.15])., Discussion: Despite large initial changes, we found a trend toward gradual return to more restrictive dosing schedules. OTPs need further support in leveraging new opportunities to improve methadone treatment and outcomes., Competing Interests: Declaration of Competing Interest None, (Published by Elsevier B.V.)

Smoldering multiple myeloma (SMM) precedes multiple myeloma (MM). The risk of progression of SMM patients is not uniform, thus different progression-risk models have been developed, although they are mainly based on clinical parameters. Recently, genomic predictors of progression have been defined for untreated SMM. However, the usefulness of such markers in the context of clinical trials evaluating upfront treatment in high-risk SMM (HR SMM) has not been explored yet, precluding the identification of baseline genomic alterations leading to drug resistance. For this reason, we carried out next-generation sequencing and fluorescent in-situ hybridization studies on 57 HR and ultra-high risk (UHR) SMM patients treated in the phase II GEM-CESAR clinical trial (NCT02415413). DIS3, FAM46C, and FGFR3 mutations, as well as t(4;14) and 1q alterations, were enriched in HR SMM. TRAF3 mutations were specifically associated with UHR SMM but identified cases with improved outcomes. Importantly, novel potential predictors of treatment resistance were identified: NRAS mutations and the co-occurrence of t(4;14) plus FGFR3 mutations were associated with an increased risk of biological progression. In conclusion, we have carried out for the first time a molecular characterization of HR SMM patients treated with an intensive regimen, identifying genomic predictors of poor outcomes in this setting., (© 2024. The Author(s).)

Purpose: To analyse the relationship between the different habits that occur in childhood and the different malocclusions in the three planes of space., Material and Methods: A clinical examination of 106 children between 5 and 12 years of age was carried out and a survey validated by professors of the Faculty of Dentistry of the University of Seville was made for the parents in order to identify the habits and relate them to the possible malocclusions detected in the child's mouth., Results: 72.64% of the sample presented a malocclusion in at least one of the three planes of space, with a similar distribution. When correlating the variables, statistically significant relationships were observed in the vertical plane with atypical swallowing ( p = 0 < 0.05; V > 0.3) and lip sucking ( p = 0 < 0.05; V > 0.3) and in the horizontal plane with oral breathing ( p = 0 < 0.05; V > 0.3), atypical swallowing ( p = 0 < 0.05; V < 0.3) and digital sucking ( p = 0 < 0.05; V < 0.3)., Conclusions: It has been observed that the prevalence and prolongation of habits in childhood is increasing, so it is essential to detect pernicious habits at an early age to prevent the establishment of malocclusions and to favour the correct craniofacial growth of the child.

A flood event affecting Pindal Cave, a UNESCO World Heritage site, introduced a substantial amount of external sediments and waste into the cave. This event led to the burial of preexisting sediments, altering the biogeochemical characteristics of the cave ecosystem by introducing heightened levels of organic matter, nitrogen compounds, phosphorus, and heavy metals. The sediments included particulate matter and waste from a cattle farm located within the water catchment area of the cavity, along with diverse microorganisms, reshaping the cave microbial community. This study addresses the ongoing influence of a cattle farm on the cave ecosystem and aims to understand the adaptive responses of the underground microbial community to the sudden influx of waste allochthonous material. Here, we show that the flood event had an immediate and profound effect on the cave microbial community, marked by a significant increase in methanogenic archaea, denitrifying bacteria, and other microorganisms commonly associated with mammalian intestinal tracts. Furthermore, our findings reveal that one year after the flood, microorganisms related to the flood decreased, while the increase in inorganic forms of ammonium and nitrate suggests potential nitrification, aligning with increased abundances of corresponding functional genes involved in nitrogen cycling. The results reveal that the impact of pollution was neither recent nor isolated, and it was decisive in stopping livestock activity near the cave. The influence of the cattle farm has persisted since its establishment over the impluvium area, and this influence endures even a year after the flood. Our study emphasizes the dynamic interplay between natural events, anthropogenic activities, and microbial communities, offering insights into the resilience of cave ecosystems. Understanding microbial adaptation in response to environmental disturbances, as demonstrated in this cave ecosystem, has implications for broader ecological studies and underscores the importance of considering temporal dynamics in conservation efforts., 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 B.V. All rights reserved.)

Background and Objective: Ulcerative colitis (UC) is a chronic disease characterized by recurrent symptoms and significant morbidity. The exact cause of the disease remains unknown. The selection of current treatment options for ulcerative colitis depends on the severity and location of the disease in each patient. Therefore, developing a fully automated endoscopic images for evaluating UC is crucial for guiding treatment plans and facilitating early prevention efforts., Methods: We propose a network called ulcerative colitis evaluation based on fine-grained lesion learner and noise suppression gating (UCFNNet). UCFNNet contains three novel modules. Firstly, a fine-grained lesion feature learner (FG-LF Learner) is proposed by integrating local features and a Softmax category prediction (SCP) module to improve the feature accuracy in small lesion areas. Subsequently, a graph convolutional feature combiner (GCFC) is developed to connect features across adjacent convolutional layers and to incorporate short connections between input and output, thereby mitigating feature loss during transmission. Thereafter, a noise suppression gating (NS gating) technique is designed by implementing a grid attention mechanism and a feature gating (FG) module to prioritize significant lesion features and suppress irrelevant and noisy regions in the input feature map., Results: We evaluate the performance of the proposed network on both privately-collected and publicly-available datasets. The evaluation of UC achieves excellent results on privately-collected dataset, with an accuracy (ACC) of 89.57 %, Matthews correlation coefficient (MCC) of 85.52 %, precision of 89.26 %, recall of 89.48 %, and F1-score of 89.78 %. The results are also impressive on publicly-available dataset, with ACC of 85.47 %, MCC of 80.42 %, precision of 85.62 %, recall of 84.00 %, and F1-score of 84.53 %, surpassing the performance of state-of-the-art techniques., Conclusion: Our proposed model introduces three innovative algorithm modules, which outperform the current state-of-the-art methods and achieve high ACC and F1-score. This indicates that our method has superior performance compared to traditional machine learning and existing deep methods, which means that our method has good application prospects. Meanwhile, it has been verified that the proposed model demonstrates good interpretability. The source code is available at github.com/YinLeRenNB/UCFNNet., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interests regarding the publication of this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Cueva del Viento, located in the Canary Islands, Spain, is the Earth's sixth-longest lava tube, spanning 18,500 m, and was formed approximately 27,000 years ago. This complex volcanic cave system is characterized by a unique geomorphology, featuring an intricate network of galleries. Despite its geological significance, the geomicrobiology of Cueva del Viento remains largely unexplored. This study employed a combination of culture-dependent techniques and metabarcoding data analysis to gain a comprehensive understanding of the cave's microbial diversity. The 16S rRNA gene metabarcoding approach revealed that the coloured microbial mats (yellow, red and white) coating the cave walls are dominated by the phyla Actinomycetota, Pseudomonadota and Acidobacteriota. Of particular interest is the high relative abundance of the genus Crossiella, which is involved in urease-mediated biomineralization processes, along with the presence of genera associated with nitrogen cycling, such as Nitrospira. Culture-dependent techniques provided insights into the morphological characteristics of the isolated species and their potential metabolic activities, particularly for the strains Streptomyces spp., Paenarthrobacter sp. and Pseudomonas spp. Our findings underscore the potential of Cueva del Viento as an ideal environment for studying microbial diversity and for the isolation and characterization of novel bacterial species of biotechnological interest., (© 2024 The Authors. Environmental Microbiology Reports published by John Wiley & Sons Ltd.)