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Mangrove forests are commonly mapped using spaceborne remote sensing data due to the challenges of field endeavors in such harsh environments. However, these methods usually require a substantial level of manual processing for each image. Hence, conservation practitioners prioritize using cloud computing platforms to obtain accurate canopy classifications of large extensions of mangrove forests. The objective of this study was to analyze the spatial distribution and rate of change (area gain and loss) of the red mangrove (Rhizophora mangle) and other dominant mangrove species, mainly Avicennia germinans and Laguncularia racemosa, between 2015 and 2020 throughout the northwestern coast of Mexico. Bimonthly data of the Combined Mangrove Recognition Index (CMRI) from all available Sentinel-2 data were processed with the Google Earth Engine cloud computing platform. The results indicated an extension of 42865 ha of red mangrove and 139602 ha of other dominant mangrove species in the Gulf of California and the Pacific northwestern coast of Mexico for 2020. The mangrove extension experienced a notable decline of 1817 ha from 2015 to 2020, largely attributed to the expansion of aquaculture ponds and the destructive effects of hurricanes. Considering the two mangrove classes, the overall classification accuracies were 90% and 92% for the 2015 and 2020 maps, respectively. The advantages of the method compared to supervised classifications and traditional vegetation indices are discussed, as are the disadvantages concerning the spatial resolution and the minimum detection area. The work is a national effort to assist in decision-making to prioritize resource allocations for blue carbon, rehabilitation, and climate change mitigation programs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Valderrama-Landeros et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Atopic dermatitis (AD) is a common chronic inflammatory skin disease involving complex immune dysregulation, including the OX40-OX40L pathway. Rocatinlimab and amlitelimab, monoclonal antibodies targeting OX40 and OX40L, respectively, have shown promise in treating moderate-to-severe AD. Both therapies have demonstrated significant efficacy in reducing disease severity, with favorable safety profiles and no serious treatment-related adverse events. Both treatments outperformed placebo across key clinical endpoints, including skin clearance and symptom reduction, highlighting their potential as effective AD therapies. Although initial results are promising, further research is needed to evaluate the long-term effects, durability of response, and safety of these treatments. These findings support the therapeutic potential of targeting the OX40-OX40L pathway in AD, providing new options for patients with moderate-to-severe disease, with ongoing trials necessary to confirm their sustained benefits., Competing Interests: Declarations. Conflicts of Interest: Orhan Yilmaz has nothing to disclose. Asaad Abdelhalim has nothing to disclose. Mohamed Elshaikh Berair has nothing to disclose. Tiago Torres has received consultancy and/or speaker’s honoraria from and/or participated in clinical trials sponsored by AbbVie, Amgen, Almirall, Amgen, Arena Pharmaceuticals, Biocad, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Fresenius-Kabi, Janssen, LEO Pharma, Eli Lilly, MSD, Mylan, Novartis, Pfizer, Samsung-Bioepis, Sanofi-Genzyme, Sandoz and UCB. Tiago Torres is an Editorial Board member of Dermatology and Therapy. Tiago Torres was not involved in the selection of peer reviewers for the manuscript nor any of the subsequent editorial decisions. Ethical Approval: This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors., (© 2024. The Author(s).)

Targeted electrical stimulation to specific thalamic regions offers a therapeutic approach for patients with refractory focal and generalized epilepsy who are not candidates for resective surgery. However, clinical outcome varies significantly, in particular for focal epilepsy, influenced by several factors, notably the precise anatomical and functional alignment between cortical regions generating epileptic discharges and the targeted thalamic stimulation sites. Here we hypothesized that targeting thalamic nuclei with precise anatomical and functional connections to epileptic cortical areas (an approach that we refer to as hodological matching) could enhance neuromodulatory effects on focal epileptic discharges. To investigate this, we examined three thalamic subnuclei (pulvinar nucleus, anterior nucleus, and ventral intermediate nucleus/ventral oral posterior nuclei) in a retrospective study involving 32 focal epilepsy patients. Specifically, we first identified hodologically organized thalamocortical fibers connecting these nuclei to individual seizure onset zones (SOZs), combining neuroimaging and electrophysiological techniques. Further, analysis of 216 spontaneous seizures revealed the critical role of matched thalamic nuclei in seizure development and termination. Importantly, electrical stimulation of hodologically-matched thalamic nuclei immediately suppressed intracortical interictal epileptiform discharges, contrasting with ineffective outcomes from stimulation of unmatched targets. Finally, we retrospectively evaluated 7 patients with a chronic hodologically-matched neurostimulation system, which led to a clinically relevant reduction in seizure frequency (median reduction 86.5%), that outstands the current clinical practice of unmatched targets (39%). Our results underscore the potential of hodological thalamic targeting to modulate epileptiform activity in specific cortical regions, highlighting the promise of precision medicine in thalamic neuromodulation for focal refractory epilepsy.

Hidradenitis suppurativa (HS) is a chronic, debilitating, inflammatory dermatosis that significantly impacts patients' quality of life, primarily manifesting as inflammatory nodules, abscesses, and tunnels. The pathogenesis of HS is not fully understood and appears to be multifactorial, involving genetic, immunological, and endocrinological factors, as well as dysbiosis of skin microbiota. Increasing evidence highlights the role of the interleukin (IL)-17 pathway in the inflammatory process and pathogenesis of HS. Consequently, IL-17 inhibitors have emerged as a promising alternative to current therapies. Recently, secukinumab received approval from both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), while bimekizumab received approval from the EMA, for the treatment of moderate-to-severe HS in adults, with ongoing clinical trials aiming to further clarify the efficacy and safety of other drugs within this class. IL-17 inhibitors have shown effectiveness in treating moderate-to-severe HS, with safety profiles of drugs such as secukinumab and bimekizumab being comparable to their use in other dermatological conditions. On the other hand, innovative drugs such as sonelokimab and izokibep show promising results and are currently in phase III clinical trials. This review provides a comprehensive overview of current knowledge and scientific advances in HS, focusing on the IL-17 pathway's role and its inhibition as a treatment strategy, alongside examining the most recent and significant clinical studies on various IL-17 inhibitors in the treatment of HS., Competing Interests: Declarations. Funding: No sources of funding were used to conduct this study or prepare this article. Conflict of Interest: Orhan Yilmaz has no conflicts of interest. Gonçalo Pinto Salgueiro has no conflicts of interest. Miguel Nogueira has received consultancy and/or speaker’s honoraria from AbbVie and LEO Pharma. Tiago Torres has received consultancy and/or speaker’s honoraria from and/or participated in clinical trials sponsored by AbbVie, Amgen, Almirall, Arena Pharmaceuticals, Biocad, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Fresenius-Kabi, Janssen, LEO Pharma, Eli Lilly, MSD, Mylan, Novartis, Pfizer, Samsung-Bioepis, Sanofi-Genzyme, Sandoz, and UCB. Ethics Approval: Not applicable. Patient Consent to Participate/Publish: Not applicable. Data Availability: Data availability is not applicable to this article as no new data were created or analyzed in this study. This is a narrative review, and all sources of information are cited appropriately in the article. Code Availability: Not applicable. Author Contribution: All the authors contributed equally to the preparation of this review. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published., (© 2024. The Author(s).)

Not available.

Bottlenecks to the success of equine assisted reproductive technologies (ART) include suboptimal conditions for prolonged storage of stallion sperm. Shipped stallion sperm are transported in cooling devices designed to maintain temperature for up to 48 h. Increasing the storage time of cooled semen while maintaining acceptable motility would relieve logistical ART challenges. Experiments were conducted to test the hypothesis that external regulation of shipment container temperature would prolong storage time of cooled stallion semen. Initial experiments determined the effect of pre-freezing cooling cans at -20 °C or -80 °C on sperm motility. Fresh sperm was extended in INRA96 and placed in commercial Equitainers for 3.5 days (84 h). Quantification of sperm kinematics was determined every 12 h. Sperm held in Equitainers with -20°C cans maintained higher total and progressive motility than -80 °C conditions at 60 h (63 %, 29 % vs. 32 %, 17 %, respectively). Internal monitoring of Equitainers containing -20 °C freezer can temperature identified 20 °C as the threshold for rapidly decreased motility. In the second experiment, sperm were maintained in Equitainers containing -20 °C freezer cans and placed in two different conditions: 1) ambient temperature for 48 h (23 °C) or 2) 5 °C for external temperature regulation up to 8 days, or when total motility dropped below 50 %. Sperm kinematics was determined every 24 h. Total motility from samples held with external temperature regulation (5 °C) remained above 50 % for more than 7 days. These findings suggest that cooled stallion semen can be advanced beyond traditional 48 h constraints by improving temperature maintenance of storage conditions., Competing Interests: Declaration of competing interest None of the authors has any financial or personal relationships that could inappropriately influence or bias the content of the paper. Data Availability All data are available upon reasonable request to the corresponding author., (Published by Elsevier Inc.)

Background: Online learning is becoming increasingly essential for health professionals, and it is necessary to understand how this modality affects clinical nurses' learning of Evidence-Based Practice (EBP). For this reason, the present study sought to assess the effectiveness of an online training program in improving nurses' EBP competence., Methods: A quasi-experimental study with a pretest-posttest design was conducted with a control group and without randomization for a period of 6 months. The intervention was an online self-learning course based on Melnyk's seven steps of Evidence-Based Practice (EBP). The course was structured into sequential modules requiring 72 h of work, with task completions and tests necessary for progression. Participants had three months to complete the course. EBP competence was measured with the EBP-COQ Prof© questionnaire. Data analysis included percentages, means, standard deviations, chi-square tests, student's t-tests, and a two-way repeated measures analysis of covariance (ANCOVA)., Results: The analysis of the changes observed in each dimension and the overall EBP competence between the intervention group (IG) and the control group (CG) showed a significant group*time interaction in three of the four dimensions of the questionnaire. The results indicated that the online Evidence-Based Practice (EBP) course significantly improved knowledge, skills, and utilization three months after its completion. In the IG, the mean score was 44.04 (standard deviation (SD) = 7), compared to 37.83 (SD = 8.5) in the CG (p < 0.001). Regarding skills, the IG had a mean score of 24.24 (SD = 3.8), while the CG scored 23.01 (SD = 3.1) (p = 0.008). For utilization, the mean score in the IG was 36.77 (SD = 6.8), and the CG was 33.12 (SD = 6.3) (p = 0.005). Overall competence also showed a statistically significant difference, with the IG achieving a mean score of 141.22 (SD = 20.0) compared to the CG with a mean score of 130.34 (SD = 16.7) (p < 0.001)., Conclusions: Training through an online education platform for three months (72 h) is an effective tool for improving the competence in Evidence-Based Practice (EBP) of clinical nurses. A significant increase was observed in knowledge and moderate improvements in skills and the application of EBP. These online courses, adapted to the needs of professionals, can be an efficient way to prepare nurses and improve their application of EBP in a clinical setting., Competing Interests: Declarations Ethics approval and consent to participate The study was approved by the Ethics Committee of the University of Murcia (ID: 2540 /2019). The nurses were invited to participate voluntarily through the online survey. They were informed about the objectives of the study, clarifying that their participation was completely anonymous, that they could withdraw from the study at any time, and that by submitting the questionnaires, they were giving their consent to participate in the study. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Glucokinase (GK) catalyses the key regulatory step in glucose-stimulated insulin secretion. Correspondingly, hetero- and homozygous mutations in human GCK cause maturity-onset diabetes of the young (GCK-MODY) and permanent neonatal diabetes (PNDM), respectively. To explore the possible utility of glucokinase activators (GKA) and of glucagon-like receptor-1 (GLP-1) agonists in these diseases, we have developed a novel hypomorphic Gck allele in mice encoding an aberrantly spliced mRNA deleted for exons 2 and 3. In islets from homozygous knock-in (Gck KI/KI ) mice, GK immunoreactivity was reduced by >85%, and glucose-stimulated insulin secretion eliminated. Homozygous Gck KI/KI mice were smaller than wildtype littermates and displayed frank diabetes (fasting blood glucose >18 mmol/L; HbA1c ~12%), ketosis and nephropathy. Heterozygous Gck KI/+ mice were glucose intolerant (HbA1c ~5.5%). Abnormal glucose-stimulated Ca 2+ dynamics and beta cell-beta cell connectivity in Gck KI/+ islets were completely reversed by the recently-developed GKA, dorzagliatin, which was largely inactive in homozygous Gck KI/KI mouse islets. The GLP-1 receptor agonist exendin-4 improved glucose tolerance in male Gck KI/+ mice, an action potentiated by dorzagliatin, in male but not female mice. Sex-dependent additive effects of these agents were also observed on insulin secretion in vitro . Combined treatment with GKA and incretin may thus be useful in GCK -MODY or GCK -PNDM., Competing Interests: Duality of Interest. G.A.R. has received grant funding from, and is a consultant for, Sun Pharmaceuticals Inc. No other potential conflicts of interest relevant to this article were reported.

Introduction: Hemorrhage remains the leading cause of preventable death on the battlefield. The most effective means to increase survivability is early hemorrhage control and fluid resuscitation. Unfortunately, fluid resuscitation requires constant adjustments to ensure casualty is properly managed, which is often not feasible in the pre-hospital setting. In this study, we showed how an adaptive closed-loop controller for hemorrhage resuscitation can be used to automate hemodynamic management using a swine hemorrhagic shock injury model., Methods: The adaptive resuscitation controller (ARC) was previously developed to track pressure-volume responsiveness in real time and adjust its infusion rate to reach the target mean arterial pressure (MAP). Swine while maintained under a surgical plane of anesthesia and analgesia underwent a splenectomy, followed by two hemorrhage and resuscitation events. For the first resuscitation event, hemorrhage was induced to reduce the MAP to 35 mmHg until arterial lactate reached 4 mmol/L. The ARC system then infused whole blood (WB) to reach the target MAP and maintained the subject using crystalloids for 120 min. For the second resuscitation event, the subjects were hemorrhaged again but resuscitated using only crystalloid infusion to reach the target MAP and 120-min maintenance., Results: The ARC was effective at WB resuscitation, reaching the target MAP in 2.0 ± 1.0 min. The median performance error was 1.1% ± 4.6%, and target overshoot was 14.4% ± 7.0% of the target MAP. The ARC maintained all animals throughout the 120 min maintenance period. For the second crystalloid-based resuscitation, ARC required a longer time to reach the target MAP, at an average rise time of 4.3 ± 4.0 min. However, target overshoot was reduced to 8.4% ± 7.3% of the target MAP. Much higher flow rates were required to maintain the target MAP during the second resuscitation event than during the first resuscitation event., Discussion: The ARC was able to rapidly reach and maintain the target MAP effectively. However, this sometimes required large volumes of fluid as the ARC's only goal was to reach the target MAP. Further clinical insight is needed regarding the preferred aggression level to achieve the target MAP. In conclusion, the ARC was successful in its programmed objective of reaching and maintaining the target MAP for extended periods of time in vivo , a critical next step toward improving hemorrhage treatment in the pre-hospital environment., Competing Interests: ES and SV are co-inventors on a patent filed on the adaptive resuscitation controller technology (ISR 23-45-US02: 18/628,287). The remaining 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 Snider, Vega, Nessen, Hernandez Torres, Salazar, Berard and Salinas.)

Advanced systemic mastocytosis (AdvSM) encompasses heterogeneous mastocytosis subtypes and is associated with poor outcomes. Although midostaurin was the first tyrosine kinase inhibitor to be approved for AdvSM patients, long-lasting responses are limited. The mutation-Adjusted Risk Score (MARS), the International Prognostic Scoring System for mastocytosis (IPSM) and the Global Prognostic Score for Systemic Mastocytosis (GPSM) have been established to characterize the outcomes of patients with overall AdvSM. However, given the outcome's dependency on the AdvSM subtype, prognostic characterization within each subtype is critical. We aimed to study the predictive ability using Harrell's concordance index of prognostic scores according to the AdvSM subtype. We conducted a nationwide retrospective study using the French mastocytosis reference center's registry and included all midostaurin-treated patients with C finding. Overall, 170 patients were identified: 46 aggressive SM (ASM), 11 mast cell leukemia (MCL), and 113 SM with associated hematological neoplasm (SM-AHN). All risk scores improved their discriminative value for overall survival (OS) when combined with the AdvSM subtype. The best predictive value was for adjusted MARS (C-index = 0.689), followed by GPSM (C-index = 0.677) and IPSM (C-index = 0.618). In a multivariable analysis, MARS stratification and the AdvSM subtype were both prognostic for OS. Accordingly, five subgroups of patients with AdvSM and a different median OS were identified: 9.9 months for MCL, 24 months for intermediate/high-risk SM-AHN, 33 months for intermediate/high-risk ASM, 58 months for low-risk SM-AHN and was not reached for low-risk ASM (p < 0.001). The AdvSM subtype and the MARS are the most predictive of OS and should prompt specific management., (© 2024 The Author(s). American Journal of Hematology published by Wiley Periodicals LLC.)

Background: Venezuelan migration has experienced an unprecedented increase in the last decade, with approximately 7.7 million Venezuelan-born individuals residing in other countries as of 2024. Our study aims to identify the potential and actual demand for healthcare services (SRH) in the Venezuelan diaspora's four primary destinations within the Andean Countries: Colombia, Ecuador, Peru, and Chile., Methods: Using official data from administrative records, censuses, and sample surveys reported by the host countries and international agencies, we estimate the annual evolution of Venezuelan-born women of reproductive age (WRA) and their offspring. Additionally, we conduct two case studies focusing on Colombia and Chile to analyse the groups most vulnerable to unmet health needs., Results: The population of WRA has increased to between 5 and 6.8%, and births have risen to approximately 3-8% in host countries due to Venezuelan migration. Yet, we found a general decrease in health coverage for certain age groups of Venezuelan female migrants in host countries for the period 2017-2022, particularly in Chile. By 2022, an estimated 20% of healthcare needs remained unmet among children, girls, and younger Venezuelan women, contributing to greater health inequalities between Venezuelan-born adolescents and those from other countries of birth., Conclusions: Our findings highlight the escalating demand for and limited access to healthcare services among Venezuelan WRA in their destinations. Unmet healthcare needs are particularly prevalent among younger women by 2022, underscoring the urgency for health system to incorporate gender-responsive, equitable interventions and ensuring health rights for high-risk migrant groups such as infants, children, adolescents, and younger women. Addressing these challenges remains a critical task for the regional public health agenda in Latin America., (© 2024. The Author(s).)

This article presents the design of a control algorithm based on Artificial Neural Networks (ANNs) applied to a lower-limb exoskeleton, which is aimed to carry out walking trajectories during lower-limb rehabilitation. The interaction between the patient and the exoskeleton leads to model uncertainties and external disturbances that are always present. For this reason, the proposed control considers that the non-linear part of the model is unknown and is perturbed by external disturbances, which are estimated by an active disturbance rejection control via Artificial Neural Networks. To validate the proposed approach, a numerical simulation and an experimental implementation of the ANN-Controller are developed.

Background: The burden of Alzheimer's disease and related dementias (AD/ADRD) in Costa Rica is expected to become one of the highest in the region. Early detection will help optimize resources and improve primary care interventions. The Montreal Cognitive Assessment (MoCA) has shown good sensitivity for detecting mild cognitive impairment (MCI), but specificity varies depending on the population. This motivated the analysis of different cutoffs to minimize false-positive classifications in a Costa Rican sample for its use in clinical settings., Methods: Data was analyzed from 516 memory clinic outpatients (148 cognitively normal, 260 MCI, 108 mild AD/ADRD; mean age 66.3 ± 10.8 years) who underwent complete neurological and neuropsychological assessment and were diagnosed by consensus. Optimal MoCA cutoff scores were identified using a multiple cutoff approach., Results: Overall, a cutoff score of ≥ 23 showed better accuracy to distinguish between normal cognition (NC) and MCI (sensitivity 73%, specificity 83%). When analyzed by educational levels, a cutoff score of ≥ 21 showed better accuracy for ≤ 6 years (sensitivity 80%, specificity 76%), ≥23 for 7-12 years (sensitivity 86%, specificity 76%) and ≥ 24 for > 12 years (sensitivity 70%, specificity 85%). For distinguishing MCI from mild AD/ADRD, the optimal overall cutoff score was ≥ 15 (sensitivity 66%, specificity 85%). When stratified by years of education, cutoff scores of ≥ 14 showed better accuracy for ≤ 6 years (sensitivity 70%, specificity 88%), ≥15 for 7-12 years (sensitivity 46%, specificity 95%) and ≥ 17 for > 12 years (sensitivity 67%, specificity 93%)., Conclusions: A MoCA cutoff score of ≥ 23 in the Costa Rican population showed better diagnostic accuracy for detecting MCI and may reduce the false positive rate. Our findings may be helpful for primary care clinical settings and further referral criteria.

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 author(s) 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.

Background: Emphysematous osteomyelitis (EO) is a rare, rapidly progressing infection characterized by gas within bones, leading to severe morbidity if untreated. In the spine, EO can cause significant bone destruction and instability, requiring urgent surgical and medical intervention. Early diagnosis and a multidisciplinary approach are crucial for effective management and improved patient outcomes., Observations: The authors present a unique case of EO involving the lumbar spine in a 40-year-old male patient with a medical history of diabetes mellitus, hyperlipidemia, and hypertension. Magnetic resonance imaging and computed tomography revealed the formation of gas within the L4 vertebral body and spinal canal, which led to the diagnosis of EO. Blood cultures grew Streptococcus dysgalactiae. The patient underwent laminectomy, discectomy, and vertebral body abscess washout to prevent further spread of the infection and successfully recovered., Lessons: The authors report the first case of spinal EO caused by S. dysgalactiae, treated using laminectomy with debridement of the affected disc spaces. https://thejns.org/doi/10.3171/CASE24434.

Background: There is conflicting evidence regarding the presence and magnitude of exercise-induced muscle damage (EIMD) following low-load resistance training with blood flow restriction (LL+BFR), which may be related to the protocol implemented or exercise volume. Therefore, the purpose of this investigation was to examine the effects of a 75 repetition (BFR-75) (1×30, 3×15) and four sets to volitional failure (BFR-4x) protocols on indices of EIMD among untrained men., Methods: Twelve males with no history of lower-body resistance training during the previous six months volunteered for this investigation. One leg was randomly assigned to BFR-75, and the other to BFR-4x. Participants performed isokinetic, unilateral, concentric-eccentric, leg extension muscle actions at 30% of maximal strength with BFR. Indices of EIMD (limb circumference, perceived muscle soreness, pain pressure threshold [PPT], passive range of motion, and maximal strength [MVIC]) were recorded before exercise and 0, 24, 48, 72, and 96-hours post-exercise for each protocol., Results: There were no significant changes (P>0.05) in limb circumference, PPT, passive range of motion, or MVIC. For both BFR-75 and BFR-4x, perceived muscle soreness increased (P<0.001) similarly 24- (2.5±1.7 AU) and 48-hours (1.9±1.7 AU) post-exercise., Conclusions: There was an increase in muscle soreness 24-48 hours post-exercise for both conditions, which may be due to metabolic stress, but this did not affect the force-generating capacity of the muscle (MVIC), suggesting minimal EIMD. The conflicting evidence of EIMD following LL+BFR may be related to differences in restriction time or overall exercise time.

Background: The preplanned interim analysis of the COMMANDS trial showed greater efficacy of luspatercept than epoetin alfa for treating anaemia in erythropoiesis-stimulating agent (ESA)-naive patients with transfusion-dependent, lower-risk myelodysplastic syndromes. In this Article, we report the results of the primary analysis of the trial., Methods: COMMANDS is a phase 3, open-label, randomised, controlled trial conducted at 142 sites in 26 countries. Eligible patients were those aged 18 years or older, with myelodysplastic syndromes of very low risk, low risk, or intermediate risk (as defined by the Revised International Prognostic Scoring System), who were ESA-naive and transfusion dependent, and had a serum erythropoietin concentration of less than 500 U/L. Patients were stratified by baseline red blood cell transfusion burden, serum erythropoietin concentration, and ring sideroblast status, and randomly allocated (1:1) to receive luspatercept (1·0-1·75 mg/kg body weight, subcutaneously, once every 3 weeks) or epoetin alfa (450-1050 IU/kg body weight, subcutaneously, once a week; maximum total dose 80 000 IU) for at least 24 weeks. The primary endpoint was red blood cell transfusion independence lasting at least 12 weeks with a concurrent mean haemoglobin increase of at least 1·5 g/dL (weeks 1-24), evaluated in the intention-to-treat population. The safety population included all patients who received at least one dose of treatment. This trial is registered with ClinicalTrials.gov (NCT03682536; active, not recruiting)., Findings: Between Jan 2, 2019, and Sept 29, 2022, 363 patients were screened and randomly allocated: 182 (50%) to luspatercept and 181 (50%) to epoetin alfa. Median age was 74 years (IQR 69-80), 162 (45%) patients were female, and 201 (55%) were male. 289 (80%) were White, 44 (12%) were Asian, and two (1%) were Black or African American. 23 (6%) were Hispanic or Latino and 311 (86%) were not Hispanic or Latino. Median follow-up for the primary endpoint was 17·2 months (10·4-27·7) for the luspatercept group and 16·9 months (10·1-26·6) for the epoetin alfa group. A significantly greater proportion of patients in the luspatercept group reached the primary endpoint (110 [60%] vs 63 [35%]; common risk difference on response rate 25·4% [95% CI 15·8-35·0]; p<0·0001). Median follow-up for safety analyses was 21·4 months (IQR 14·2-32·4) for the luspatercept group and 20·3 months (12·7-30·9) for the epoetin alfa group. Common grade 3-4 treatment-emergent adverse events occurring among luspatercept recipients (n=182) were hypertension (19 [10%] patients), anaemia (18 [10%]), pneumonia (ten [5%]), syncope (ten [5%]), neutropenia (nine [5%]), thrombocytopenia (eight [4%]), dyspnoea (eight [4%]), and myelodysplastic syndromes (six [3%]); and among epoetin alfa recipients (n=179) were anaemia (14 [8%]), pneumonia (14 [8%]), neutropenia (11 [6%]), myelodysplastic syndromes (ten [6%]), hypertension (eight [4%]), iron overload (seven [4%]), and COVID-19 pneumonia (six [3%]). The most common serious treatment-emergent adverse events in both groups were pneumonia (nine [5%] luspatercept recipients and 13 [7%] epoetin alfa recipients) and COVID-19 (eight [4%] luspatercept recipients and ten [6%] epoetin alfa recipients). One death (due to acute myeloid leukaemia) considered to be luspatercept-related was reported at the interim analysis., Interpretation: Luspatercept represents a new standard of care for ESA-naive patients with transfusion-dependent, lower-risk myelodysplastic syndromes. Significantly more patients had red blood cell transfusion independence and haematological improvement with luspatercept than with epoetin alfa, with benefits observed across patient subgroups., Funding: Celgene and Acceleron Pharma., Competing Interests: Declaration of interests Editorial and medical writing support were funded by Bristol Myers Squibb. MGDP reports receiving honoraria from and advisory or data safety monitoring board fees from Bristol Myers Squibb. GG-M reports receiving consulting fees from Bristol Myers Squibb; research support from AbbVie, Astex, Bristol Myers Squibb, Chordia, Curis, Genentech, Novartis, Rigel Pharmaceuticals, and Zentalis; and honoraria from Astex and Curis. VS reports receiving honoraria from AbbVie, Bristol Myers Squibb, and Novartis; travel support from AbbVie and Jazz Pharmaceuticals; and advisory or data safety monitoring board fees from AbbVie, Bristol Myers Squibb, CTI BioPharma, Curis, Geron, Gilead, Keros, Menarini, Novartis, Servier, and Syros. AMZ reports receiving grant support from AbbVie, Amgen, Astex, Bristol Myers Squibb, Celgene, Geron, Kura, Novartis, Otsuka, Shattuck Labs, and Syros; and consulting fees and honoraria from AbbVie, Agios, Akeso Pharma, ALX Oncology, Amgen, Astellas Pharma, BeiGene, BioCryst, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Chiesi, Daiichi Sankyo, Epizyme, Faron, Genentech, Geron, Gilead, Glycomimetics, Hikma, Janssen, Karyopharma, Keros, Kura, Kyowa Kirin, Lava Therapeutics, Medus, Notable, Novartis, Orum, Otsuka, Pfizer, Regeneron, Rigel Pharmaceuticals, Schrodinger, Servier, Sumitomo Pharma, Syndax, Syros, Taiho, Takeda, Treadwell, Vincerx, and Zentalis. RSK reports receiving grant support from Bristol Myers Squibb; consulting fees from Geron, Janssen, and Sumitomo Pharma; speakers bureau fees from AbbVie, Jazz Pharmaceuticals, Pharma Essentia, Rigel Pharmaceuticals, Servio, and Sobi; and advisory or data safety monitoring board fees from AbbVie, Bristol Myers Squibb, DSI, Jazz Pharmaceuticals, Pharma Essentia, Rigel Pharmaceuticals, Servio, Sobi, and Sumitomo Pharma. JS reports receiving grant support from Amgen Australia, Astex Pharmaceuticals, and Bristol Myers Squibb; consulting fees paid to himself from Astellas Pharma, Mundipharma, Novartis, Otsuka, and Pfizer; speakers bureau fees paid to himself and his institution from Mundipharma and Novartis; support for meeting attendance from AstraZeneca (no payment to healthcare provider); being a named investigator on patent PCT/AU2021/050562 assigned to his institution; trial steering committee fees paid to his institution from Bristol Myers Squibb; and serving an unpaid appointment on the Australasia Leukaemia and Lymphoma Group Scientific Advisory Committee. DV reports receiving consulting fees from Amgen, Astellas Pharma, Bristol Myers Squibb, Jazz Pharmaceuticals, Kite Pharma, Merck Sharp & Dohme, Novartis, Sanofi, and Sobi; honoraria from Agios, Amgen, Astellas Pharma, Bristol Myers Squibb, Gebro, Grifols, Janssen, Jazz Pharmaceuticals, Kite Pharma, Merck Sharp & Dohme, Novartis, Pfizer, Sanofi, and Sobi; travel support from Bristol Myers Squibb, Jazz Pharmaceuticals, Novartis, Sanofi, and Sobi; and advisory or data safety monitoring board fees from Amgen, Bristol Myers Squibb, Grifols, Jazz Pharmaceuticals, Novartis, Servier, and Sobi. AJ reports receiving support for study materials from Bristol Myers Squibb; consulting fees from Bristol Myers Squibb; honoraria from AbbVie, Bristol Myers Squibb, and Novartis; travel support from AbbVie and Novartis; advisory or data safety monitoring board fees from AbbVie, Bristol Myers Squibb, GSK, and Novartis; and a leadership or fiduciary role as the head of the Czech MDS Group. JL, RP, SK, KLK, TP, and YL are employed by and own stock in Bristol Myers Squibb. JZ is employed by Bristol Myers Squibb. VP is employed by and owns stock in Bristol Myers Squibb and owns stock in Merck. SR is employed by, owns stock in, and has received travel support from Bristol Myers Squibb and owns stock in Celgene. AD reports receiving honoraria from Bristol Myers Squibb; travel support from Johnson & Johnson; and advisory or data safety monitoring board fees from Swixx BioPharma. TC reports receiving consulting fees from AbbVie, Agios, BluePrint, Bristol Myers Squibb/Celgene, Jazz Pharmaceuticals, Novartis, and Servier; honoraria from Astellas, Bristol Myers Squibb/Celgene, Incyte, Jazz Pharmaceuticals, Novartis, Servier, and Takeda; travel support from AbbVie, Bristol Myers Squibb/Celgene, Gilead, Novartis, Pfizer, and Servier; and advisory or data safety monitoring board fees from Astellas, Bristol Myers Squibb/Celgene, Incyte, Jazz Pharmaceuticals, Novartis, Servier, and Takeda. PF reports receiving grant support from AbbVie, Agios, Bristol Myers Squibb, and Novartis; and honoraria from AbbVie, Agios, Bristol Myers Squibb, and Novartis. UP reports receiving grant support paid to GWT-TUD, from Amgen and Janssen; grant support, paid to University of Leipzig, from Bristol Myers Squibb, Merck, and Novartis; consulting fees from AbbVie, Bristol Myers Squibb, Curis, Geron, Janssen, and Novartis; honoraria from Bristol Myers Squibb and Novartis; and fees for serving on a steering committee and travel support from Bristol Myers Squibb. 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.)

Atopic dermatitis (AD) is a chronic, inflammatory skin disease characterized by intense pruritus and eczematous lesions, significantly impacting physical health and quality of life. The pathogenesis of AD involves genetic predisposition, immune dysregulation, and environmental factors, with a defective skin barrier playing a crucial role. Treatment options for AD include both topical and systemic therapies, with advanced treatments like Janus kinase inhibitors and biologics offering significant improvements but facing limitations in safety and dosing frequency. Extended half-life antibodies represent a promising advancement for the management of immune-mediated inflammatory diseases, including AD. These antibodies, engineered for prolonged circulation and reduced dosing frequency, target key cytokines and immune pathways known to be involved in the pathogenesis of AD, offering potential for less frequent administration while maintaining efficacy. Currently, two such agents are in phase 2 trials. APG777, targeting interleukin-13 (IL-13), and IMG-007, targeting OX40 receptor, have shown promising preclinical and early clinical results. They demonstrated prolonged half-lives and the potential for less frequent dosage regimen, along with significant improvements in AD symptoms. These therapies could enhance patient adherence and reduce healthcare burdens by decreasing injection frequencies and clinic visits. As research continues, extended half-life antibodies could significantly improve AD management and patient quality of life. Further studies will determine the long-term safety and efficacy of extended half-life antibodies, with ongoing innovations in antibody engineering likely to broaden their applications and benefits., (© 2024. The Author(s).)

Background: Low-level Laser Therapy (LLLT) has demonstrated its potential in promoting fiber matrix maturation, collagen synthesis, and fibroblast proliferation, contributing to tissue regeneration. Our study aimed to investigate the impact of LLLT on collagen type I synthesis, cell proliferation, and viability in human ligament fibroblasts derived from the Anterior Cruciate Ligament (ACL)., Methods: Tissue samples were obtained from individuals undergoing arthroscopic ACL reconstruction surgery. Primary human fibroblasts were isolated, and immunohistochemical assays confirmed their characteristics. LLLT at 850 nm was administered in three groups: Low dose (1.0 J/cm²), High dose (5.0 J/cm²), and Control (0.0 J/cm²). Cell viability was calculated using a membrane integrity assay, proliferation was determined by automated counting, and collagen type I concentration in cell culture was measured using an immunoassay., Results: Fibroblasts showed decreased viability after low and high doses of LLLT, increased proliferation at the low dose, and increased collagen synthesis at the high dose on day 10 for both sexes after treatment., Conclusion: Our study demonstrated that LLLT may improve the early ligament healing process by increasing cell proliferation at the low dose and enhancing collagen type I synthesis at the high dose in human ligament fibroblasts., (© 2024. The Author(s).)

Not available.

Immune checkpoint inhibitors (ICIs) are an approved therapy for the management of various advanced neoplasms. Limited reviews focus on the influence of this therapy resulting in pancreatitis. This review discusses the relationship between ICIs and their effects on the pancreas, including the incidence of pancreatitis, immunotherapy, programmed cell death 1 (PD-1) receptors, driver mutations, programmed death ligand 1 (PD-L1), and immune-related adverse events. Additionally, it focuses on the clinical presentations, diagnosis, case studies, and mechanisms by which ICIs activate different pathways to cause pancreatitis. We conducted a comprehensive literature search using PubMed, Cochrane Library, and Google Scholar databases to identify relevant studies on ICI-associated pancreatitis. The review explores the incidence and epidemiology of ICI-induced pancreatitis, its clinical presentation, diagnostic criteria, and management strategies.The overall incidence of ICI-induced pancreatitis is estimated at 1-2%, with higher rates observed in combination therapy. Clinical presentations range from asymptomatic enzyme elevations to severe pancreatitis. Diagnosis relies on a combination of clinical symptoms, elevated pancreatic enzymes, and imaging findings, with MRI and endoscopic ultrasound showing promise in early detection. Management strategies include IV fluid administration, pain control, and nutritional support. The efficacy of corticosteroids remains controversial, and alternative immunosuppressants are being explored for steroid-refractory cases. Long-term monitoring is crucial due to the risk of chronic pancreatitis and pancreatic insufficiency. This review highlights the need for further research to elucidate the exact mechanisms of ICI-associated pancreatic injury, develop predictive biomarkers, and refine treatment protocols. As ICI use continues to expand, a thorough understanding of this adverse event is essential for optimizing patient care and outcomes in cancer immunotherapy., Competing Interests: 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, Nwankwo et al.)

Multivalent live-attenuated or inactivated vaccines are often used to control the bovine viral diarrhea disease (BVD). Still, they retain inherent disadvantages and do not provide the expected protection. This study developed a new vaccine prototype, including the external segment of the E2 viral protein from five different subgenotypes selected after a massive screening. The E2 proteins of every subgenotype (1aE2, 1bE2, 1cE2, 1dE2, and 1eE2) were produced in mammalian cells and purified by IMAC. An equimolar mixture of E2 proteins formulated in an oil-in-water adjuvant made up the vaccine candidate, inducing a high humoral response at 50, 100, and 150 µg doses in sheep. A similar immune response was observed in bovines at 50 µg. The cellular response showed a significant increase in the transcript levels of relevant Th1 cytokines, while those corresponding to the Th2 cytokine IL-4 and the negative control were similar. High levels of neutralizing antibodies against the subgenotype BVDV1a demonstrated the effectiveness of our vaccine candidate, similar to that observed in the sera of animals vaccinated with the commercial vaccine. These results suggest that our vaccine prototype could become an effective recombinant vaccine against the BVD.

Studies have found associations between sleep, nap duration, and bone mineral density (BMD). However, the longitudinal relationship between sleep, nap duration, and BMD has not been explored. We evaluated the association between the change in sleep and nap duration and BMD in Mexican adults. Data come from 1,337 adult participants of the Health Workers Cohort Study (341 were men and 996 were women, including 450 women < 45 years old and 546 ≥ 45 years old), with two study waves. At each wave, sleep and nap duration was assessed using self-administered questionnaires and BMD in g/cm 2 was determined by dual X-ray absorptiometry. We used fixed-effect regression models stratified by sex and adjusted for BMI, diet, physical activity, vitamin supplements, and hormone replacement therapy. Women who changed from < 7 to ≥ 7 h/day of sleep from baseline to follow-up were associated with increases in the total hip (β = 0.012 g/cm 2 ; 95% CI: 0.002, 0.022) and lumbar spine BMD (β = 0.024 g/cm 2 ; 95% CI: 0.009, 0.039). Furthermore, most of these associations were observed in women ≥ 45 years. For women, a changing from 0 to > 60 min/day of napping was associated with a significant increase in total hip BMD of 0.012 g/cm 2 (95% CI: 0.004, 0.024) and lumbar spine BMD of 0.027 g/cm 2 (95% CI: 0.009, 0.045). No significant associations were observed for men. Our results suggest that increased sleep and nap duration are associated with gains in BMD in Mexican women, emphasizing sleep's role in promoting bone health and supporting established recommendations., (© 2024. The Author(s).)

Background and Aims: Systemic mastocytosis (SM) is characterized by the accumulation of atypical mast cells (MCs) in organs. Liver histology of SM has been marginally described and accurate histological classification is critical, given the consequences of aggressive SM diagnosis. We aimed to describe the histological features associated with liver SM using updated tools., Methods: Using the database of the French Reference Centre for Mastocytosis, we retrospectively identified patients with a liver biopsy (LB) and a diagnosis of SM. All LB procedures were performed according to the local physician in charge and centrally reviewed by an expert pathologist., Results: A total of 28 patients were included: 6 had indolent SM, 9 had aggressive SM, and 13 had SM with an associated hematologic neoplasm. Twenty-five (89%) patients presented hepatomegaly, and 19 (68%) had portal hypertension. The LB frequently showed slight sinusoid dilatation (82%). Fibrosis was observed in 3/6 indolent SM and in almost all advanced SM cases (21/22), but none of them showed cirrhosis. A high MC burden (>50 MCs/high-power field) was correlated with elevated blood alkaline phosphatase levels (p = .030). The presence of portal hypertension was associated with a higher mean fibrosis grade (1.6 vs. 0.8 in its absence; p = .026). In advanced SM, the presence of nodular regenerative hyperplasia (NRH) was associated with decreased overall survival (9.5 vs. 46.3 months, p = .002)., Conclusions: MC infiltration induced polymorphic hepatic lesions and the degree of fibrosis is associated with portal hypertension. NRH identifies a poor prognosis subgroup of patients with advanced SM. Assessing liver histology can aid in SM prognostic evaluation., (© 2024 The Authors. Liver International published by John Wiley & Sons Ltd.)

Identifying major depression in children and adolescents is more challenging than in adults. Questionnaires are often used for screening or guiding clinical assessment. Several instruments of different lengths are used as equivalent measures in diagnostic decisions. In this paper, we explore to what extent 18 commonly used depression scales for children and adolescents explore depression clinical symptoms as established by standard DSM-5 diagnosis criteria. We analyzed scale content adequacy by examining the overlap between scale contents and consensus clinical symptoms, the diagnostic time frame for active symptom assessment, and readability for the target age group. The 18 scales encompassed 52 distinct symptoms. These scales included just 50% of clinical symptoms required for diagnosis. The content overlap was low; on average, 29% of symptoms coincide across scales. Half of the scales did not use the standard period for active symptom appraisal, and some did not include a period for assessment. The reading levels on six scales were inappropriate for the scale's target population age group. The substantial heterogeneity in defining the depressive syndrome, the low overlap among scales, different periods of a positive diagnosis, and mismatch of reading competence for detecting may lead to heterogeneity in clinical diagnoses when using different scales. Improving the content of self-report in terms of homogeneity of diagnostic criteria would lead to better diagnostic decisions and patient management., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Stigma looms over the disability community., Objective or Hypothesis: The aim of this paper is to gain a deeper understanding of how societal stigma impacts depression among wheelchair users., Methods: Mixed research methods were used on a sample of sixty full-time wheelchair users (M age = 43.78, SD = 15.50) whose disability was either acquired (n = 32) or congenital (n = 28). Data was collected via an anonymous Qualtrics survey. Qualitative and quantitative content analyses were performed., Results: Three major themes were identified from the qualitative analysis, including pity, discomfort, and invisibility which demonstrated that our participants felt frequently stigmatized in public. Several participants noted how assumptions were made about their competence, intellect, ability, and the entire disability experience based on the physical representation of their wheelchair. The quantitative results demonstrated a positive correlation between The Major Depression Index and the Able Privilege Scale-Revised, a scale constructed to examine personal power and privilege in relation to society depending on disability type., Conclusions: Wheelchair users feel stigmatized by members of society, which is associated with increased levels of depression and perceived pity, discomfort, and invisibility., Competing Interests: Declaration of competing interest The authors report no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Systemic mastocytosis (SM) corresponds to a rare and heterogeneous spectrum of diseases characterized by the accumulation of atypical mast cells (MCs). Advanced mastocytosis (Adv-SM) is associated with poor survival; in contrast, patients with non-advanced SM (non-Adv-SM) usually have a normal life expectancy but may experience poor quality of life. Despite recent therapeutic progress including tyrosine kinase inhibitors, new treatment options are needed for refractory and/or intolerant patients with both severely symptomatic and Adv-SM. In vitro, the mTOR pathway is activated in MCs from patients bearing the KIT D816V mutation. Furthermore, rapamycin induces the apoptosis of KIT D816V MCs selectively. In this nationwide study, we report the outcomes of patients diagnosed with SM and treated with a mammalian target of rapamycin inhibitor (imTOR) within the French National Reference Center for mastocytosis (CEREMAST). All patients registered were relapsing, treatment-refractory, or ineligible for other cytoreductive therapy. Non-Adv-SM patients received imTOR as a monotherapy (rapamycin/everolimus), and Adv-SM patients received imTOR as a monotherapy or in combination with cytarabine. The objective response rate (ORR) in non-Adv-SM was 60% (partial response in 40% and major response in 20%), including reductions in skin involvement, mediator release symptoms, and serum tryptase. In the Adv-SM group, the ORR was 20% (including one major response and one partial response, both in patients with a KIT D816V mutation), which enabled a successful bridge to allogeneic stem cell transplantation in one patient. Our results suggest that imTOR treatment has potential benefits in patients with SM harboring a KIT D816V mutation., (© 2024 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)

Background: Cassava roots are widely consumed in tropical regions of Asia, Africa, and Latin America. Although the protein, vitamin, carotenoid, and mineral content in the leaves makes them a nutritionally attractive option, their consumption is limited due to their high levels of cyanogenic compounds (CCs). In this study, the CC content in different parts of the plant (leaves, storage root cortex, and parenchyma) was assessed at harvest for 50 landrace genotypes representative of cassava diversity in Latin America. The changes in CC in leaves at different physiological ages (3, 6, 9, and 11 months after planting) were also investigated., Results: The average CC was higher in the cortex (804 ppm) and leaves (655 ppm) than in root parenchyma (305 ppm). Genotypes from different regions of Latin America, as identified by seven genetic diversity groups, differed significantly in CC levels. The Andean and Amazon groups had, respectively, the lowest (P = 0.0008) and highest (P < 0.0001) CC levels in all three parts of the plants. Cyanogenic compound concentrations were higher in leaves from young plants (P < 0.0001) and decreased with increasing physiological age., Conclusion: The results help to guide the selection of parental lines with low CC levels for breeding and to contribute to the expanded use of cassava and its by-products for food and feed. Cassava for fresh consumption, especially, requires varieties with low total CC content, especially in the root cortex and parenchyma. COL1108 (204, 213, and 174 ppm, respectively, in the parenchyma, cortex, and leaves) and PER297 (83, 238, and 299 ppm, respectively, in the parenchyma, cortex, and leaves) can fulfill this requirement. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry., (© 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.)

Background: High-risk human papillomavirus (hrHPV) detection in self-collected urine samples (SeCUS) may be a promising alternative for cervical cancer screening because of its greater acceptability, as long as it can offer comparable sensitivity to clinician-collected cervical samples (CCoS) for detecting precancer lesions., Objective: To evaluate the performance of the SeCUS compared to that of the CCoS for cervical intraepithelial neoplasia grade 3 (CIN3) detection among hrHPV-positive women receiving colposcopy in Mexico City using different specific extended HPV typing procedures: HPV16/18, HPV16/18/35/39/68 or HPV16/18/35/39/68/31., Methods: From March 2017 to August 2018, 4,158 female users of the cervical cancer screening program at Tlalpan Sanitary Jurisdiction in Mexico City were invited to participate in the FRIDA-Tlalpan study. All participants provided ≥ 30 mL of SeCUS, and then a CCoS was obtained with Cervex-Brush®, which was used for hrHPV typing. Participants who tested positive for hrHPV in CCoS were referred for colposcopy for diagnostic confirmation, and all SeCUS of these women were also tested for hrHPV typing., Results: In total, 561 hrHPV-positive women were identified by CCoS via colposcopy, and 82.2% of the SeCUS of these women were also hrHPV positive. From both CCoS and SeCUS, 7 cases of CIN3 were detected. Considering HPV16/18 typing, CCoS and SeCUS detected 4 cases of CIN3, but after HPV16/18/35/39/68/31 extension typing, both CCoS and SeCUS detected all 7 of the CIN3 cases among the hrHPV-positive women., Conclusions: Using extended hrHPV typing based on HPV16/18/35/39/68/31, our results suggest that the performance of SeCUS may be equivalent to that of CCoS for detecting CIN3 lesions. Although our results are inconclusive, they support the hypothesis that SeCUS may be an attractive alternative worthy of further research., (© 2024. The Author(s).)

In ICU settings, screening patients upon admission for potential multiresistant bacteria (BMR) carriers is crucial. Traditionally, clinical decisions relied on delayed culture results, but a rapid PCR molecular test called RealCycler-Rezero-U/G (Progenie-molecular©), emerged as an alternative. This study aimed to validate its effectiveness in detecting gram-negative BMR in rectal swabs at ICU admission. Over 24 months, an observational study was conducted on 1,234 admitted patients, with 217 meeting isolation criteria and undergoing both PCR and culture tests. Results showed a 17.5 % positive rate for screening. The PCR test exhibited impressive accuracy at 98.6 % and a strong negative predictive value of 99.4 %. The area under the ROC curve (AUC) was 0.98, indicating high reliability. Notably, PCR results were available 44.5 h earlier than culture. In conclusion, PCR-based molecular testing for gram-negative BMR offers excellent diagnostic performance and a valuable negative predictive value, making it a suitable screening tool for ICU admissions., 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.)

By incompletely understood mechanisms, type 2 (T2) inflammation present in the airways of severe asthmatics drives the formation of pathologic mucus which leads to airway mucus plugging. Here we investigate the molecular role and clinical significance of intelectin-1 (ITLN-1) in the development of pathologic airway mucus in asthma. Through analyses of human airway epithelial cells we find that ITLN1 gene expression is highly induced by interleukin-13 (IL-13) in a subset of metaplastic MUC5AC + mucus secretory cells, and that ITLN-1 protein is a secreted component of IL-13-induced mucus. Additionally, we find ITLN-1 protein binds the C-terminus of the MUC5AC mucin and that its deletion in airway epithelial cells partially reverses IL-13-induced mucostasis. Through analysis of nasal airway epithelial brushings, we find that ITLN1 is highly expressed in T2-high asthmatics, when compared to T2-low children. Furthermore, we demonstrate that both ITLN-1 gene expression and protein levels are significantly reduced by a common genetic variant that is associated with protection from the formation of mucus plugs in T2-high asthma. This work identifies an important biomarker and targetable pathways for the treatment of mucus obstruction in asthma., (© 2024. The Author(s).)

Background: COVID-19-induced diabetes is a novel and enigmatic disease. Our aim was to evaluate a possible relationship between post-COVID-19 syndrome (PCS) and increased insulin resistance (IR) in non-diabetic outpatients after mild COVID-19., Methods: Repeated measures design. Three evaluations [1E (pre-COVID, baseline), 2E (3 months post-COVID) and 3E (21 months post-COVID)] were performed, directed to PCS+ and PCS- subjects. Triglyceride-glucose (TyG) index ≥8.74 was considered IR, and albumin-to-globulin ratio (AGR) <1.50, inflammation., Results: We analyzed 112 individuals (median [IQR] age=44 [20] years, 58% women, 36 PCS+, 76 PCS-). PCS+ with very low basal IR (TyG <7.78, lowest quartile) showed a reduced inflammatory burden (basal AGR=1.81 [0.4] vs. 1.68 [0.2] in 2E; P=0.23), and increased TyG across evaluations (from basal 7.62 [0.2] to 8.29 [0.5]; P=0.018]. Conversely, PCS+ subjects with high basal TyG (TyG ≥8.65, highest quartile) did not show significant variations in TyG, but a greater inflammatory load (basal AGR=1.69 [0.3] vs. 1.44 [0.3] in 2E; P=0.10). In multivariable models addressing groups with reduced basal IR (TyG <8.01), PCS has been a consistent predictor for TyG, after adjusting for confounders. Partial correlation and multivariable analyses showed similarities involving acute polysymptomatic COVID-19 and PCS regarding IR., Conclusions: PCS was associated with increased IR, being more evident when the baseline degree of IR was very low. PCS and increased IR were separately associated with inflammation. Acute polysymptomatic COVID-19 and PCS could be clinical expressions of underlying inflammatory state, which in turn may also trigger IR.

Background This study investigates the impact of New York's relaxed alcohol consumption policies during the coronavirus disease (COVID-19) pandemic on alcohol-related traumatic brain injuries (TBIs) among patients admitted to a Level 1 trauma center in Queens. Given the limited research available, this study critically explores the link between public health policies and trauma care. It aims to address a significant gap in the literature and highlight the implications of alcohol regulations during global health emergencies. Methodology A retrospective analysis was conducted among trauma patients from 2019 to 2021. The study period was divided into the following three periods: pre-lockdown (March 7, 2019, to July 31, 2019), lockdown (March 7, 2020, to July 31, 2020), and post-lockdown (March 7, 2021, to July 31, 2021). Data on demographics, injury severity, comorbidities, and outcomes were collected. The study focused on assessing the correlation between New York's alcohol policies and alcohol-related TBI admissions during these periods. Results A total of 1,074 admissions were analyzed. The study found no significant changes in alcohol-positive patients over the full calendar years of 2019, 2020, and 2021 (42.65%, 38.91%, and 31.16% respectively; p = 0.08711). Specifically, during the lockdown period, rates of alcohol-positive TBI patients remained unchanged, despite the relaxed alcohol policies. There was a decrease in alcohol-related TBI admissions in 2021 compared to 2020 during the lockdown period. Conclusions Our study concludes that New York's specific alcohol policies during the COVID-19 pandemic were not correlated with an increase in alcohol-related TBI admissions. Despite the relaxation of alcohol consumption laws, there was no increase in alcohol positivity among TBI patients. The findings suggest a complex relationship between public policies, alcohol use, and trauma during pandemic conditions, indicating that factors other than policy relaxation might influence alcohol-related trauma incidences., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Jagtiani et al.)

Perceptions of gender inequality may motivate people to take action against inequality given its negative impact on various domains of people's everyday lives. Thus, it is crucial to develop reliable measures that consider the multidimensional nature of gender inequalities. In this research, we propose and assess the psychometric properties of the Multidimensional Gender Inequality Perception Scale (MuGIPS). This is a self-reported measure of perceived gender inequality in four domains: health, violence, household work and caregiving, and public sphere and power. Exploratory and confirmatory factor analyses were conducted to test the validity and reliability of the MuGIPS with Spanish participants in three samples (N = 1733). The analyses revealed that the MuGIPS had a good internal consistency and showed four factors associated with gender inequality in the four specified domains. Moreover, scores in all the dimensions positively correlated with feminist identity and feminist ideology, as much as with some attitudinal variables. In contrast, results showed a negative correlation with system-justifying ideologies. The MuGIPS shows adequate reliability and validity for measuring the perception of gender inequality in the health, violence, household work and caregiving, and public sphere and power domains among Spanish university and general population samples., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Schwartz-Salazar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Accurate assessment of evapotranspiration (ETa) and crop coefficient (Kc) is crucial for optimizing irrigation practices in water-scarce regions. While satellite-based surface energy balance models offer a promising solution, their application to sparse canopies like apple orchards requires specific validation. This study investigated the spatial and temporal dynamics of ETa and Kc in a drip-irrigated 'Pink Lady' apple orchard under Mediterranean conditions over three growing seasons (2012/13, 2013/14, 2014/15). The METRIC model, incorporating calibrated sub-models for leaf area index (LAI), surface roughness (Z om ), and soil heat flux (G), was employed to estimate ETa and Kc. These estimates were validated against field-scale Eddy Covariance data. Results indicated that METRIC overpredicted Kc and ETa with errors less than 10 %. These findings highlight the potential of the calibrated METRIC model as a valuable decision-making tool for irrigation management in apple orchards., 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. Published by Elsevier Ltd.)

Volatile organic compounds (VOCs), recognized as hazardous air contaminants, prompt the exploration of sustainable air purification methods. Solar photocatalytic oxidation emerges as a promising solution, utilizing semiconductor photocatalysts like titanium dioxide (TiO 2 ). However, the raw material crisis necessitates reduced TiO 2 usage, leading to investigations into TiO 2 modification techniques. The study introduces a novel approach by employing natural fibers, specifically loofah sponge, as a TiO 2 support. This method aims to maintain photocatalytic activity while minimizing TiO 2 content. The article explores using halloysite, a natural clay mineral, as a supportive material, enhancing mechanical strength and adsorption properties. The resulting TiO 2 /loofah-halloysite composites are evaluated for their efficacy in gas-phase photocatalytic oxidation of toluene and ethanol, chosen as representative VOCs. The conversion of toluene and ethanol on the composite was 88 % and 39 %, respectively, with high selectivity toward CO 2 . In addition to its high performance, the bio-composite was stable for several conversion cycles, keeping the conversion activity unchanged. The study contributes to developing green hybrid materials for VOC removal, showcasing potential applications across industries., (© 2024 Wiley‐VCH GmbH.)

Multidrug resistance (MDR) commonly leads to cancer treatment failure because cancer cells often expel chemotherapeutic drugs using ATP-binding cassette (ABC) transporters, which reduce drug levels within the cells. This study investigated the clinical characteristics and single nucleotide variant (SNV) in ABCB1 , ABCC1 , ABCC2 , ABCC4 , and ABCG2 , and their association with mortality in pediatric patients with central nervous system tumors (CNST). Using TaqMan probes, a real-time polymerase chain reaction genotyped 15 SNPs in 111 samples. Patients were followed up until death or the last follow-up day using the Cox proportional hazards model. An association was found between the rs1045642 ( ABCB1 ) in the recessive model (HR = 2.433, 95% CI 1.098-5.392, p = 0.029), and the ICE scheme in the codominant model (HR = 9.810, 95% CI 2.74-35.06, p ≤ 0.001), dominant model (HR = 6.807, 95% CI 2.87-16.103, p ≤ 0.001), and recessive model (HR = 6.903, 95% CI 2.915-16.544, p = 0.038) significantly increased mortality in this cohort of patients. An association was also observed between the variant rs3114020 ( ABCG2 ) and mortality in the codominant model (HR = 5.35, 95% CI 1.83-15.39, p = 0.002) and the dominant model (HR = 4.421, 95% CI 1.747-11.185, p = 0.002). A significant association between the ICE treatment schedule and increased mortality risk in the codominant model (HR = 6.351, 95% CI 1.831-22.02, p = 0.004, HR = 9.571, 95% CI 2.856-32.07, p ≤ 0.001), dominant model (HR = 6.592, 95% CI 2.669-16.280, p ≤ 0.001), and recessive model (HR = 5.798, 95% CI 2.411-13.940, p ≤ 0.001). The genetic variants rs3114020 in the ABCG2 gene and rs1045642 in the ABCB1 gene and the ICE chemotherapy schedule were associated with an increased mortality risk in this cohort of pediatric patients with CNST.

NK-lysin is a potent antimicrobial peptide (AMP) with antimicrobial activity against bacteria, fungi, viruses, and parasites. NK-lysin is a type of granulysin, a member of the saposin-like proteins family first isolated from a pig's small intestine. In previous work, for the first time, we identified four variants of nk-lysin from Atlantic salmon ( Salmo salar ) using EST sequences. In the present study, we reported and characterized two additional transcripts of NK-lysin from S. salar . Besides, we evaluated the tissue distribution of three NK-lysins from S. salar and assessed the antimicrobial, hemolytic, and immunomodulatory activities and signaling pathways of three NK-lysin-derived peptides. The synthetic peptides displayed antimicrobial activity against Piscirickettsia salmonis (LF-89) and Flavobacterium psychrophilum . These peptides induced the expression of immune genes related to innate and adaptive immune responses in vitro and in vivo . The immunomodulatory activity of the peptides involves the mitogen-activated protein kinases-mediated signaling pathway, including p38, extracellular signal-regulated kinase 1/2, and/or c-Jun N-terminal kinases. Besides, the peptides modulated the immune response induced by pathogen-associated molecular patterns (PAMPs). Our findings show that NK-lysin could be a highly effective immunostimulant or vaccine adjuvant for use in fish aquaculture., 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 Ortega, Carrera, Muñoz-Flores, Salazar, Villegas, Starck, Valenzuela, Agurto, Montesino, Astuya, Parra, Pérez, Santibáñez, Romero, Ruíz, Lamazares, Reyes, Sánchez, Toledo and Acosta.)

This paper proposes a new sensor using optical flow to stabilize a quadrotor when a GPS signal is not available. Normally, optical flow varies with the attitude of the aerial vehicle. This produces positive feedback on the attitude control that destabilizes the orientation of the vehicle. To avoid this, we propose a novel sensor using an optical flow camera with a 6DoF IMU (Inertial Measurement Unit) mounted on a two-axis anti-shake stabilizer mobile aerial gimbal. We also propose a robust algorithm based on Sliding Mode Control for stabilizing the optical flow sensor downwards independently of the aerial vehicle attitude. This method improves the estimation of the position and velocity of the quadrotor. We present experimental results to show the performance of the proposed sensor and algorithms.

Imitation that entails faithful reproduction of demonstrated behavior by reenacting a sequence of actions accurately is a fast and efficient way to acquire new skills as well as to conform to social norms. Previous studies reported that both culture and gender might impinge on young children's fidelity of imitation. We analyzed the imitative behavior of 87 children whose ages ranged from 3 to 6 years. An instrumental task was administered that offered partial (opaque apparatus) or total (transparent apparatus) information about causal connection between the demonstrated actions and their effect in achieving a desired reward. Imitative fidelity (imitating the actions that were demonstrated by an adult model yet were unnecessary for achieving the instrumental goal) increased as a function of age in boys, whereas no differences were found in girls. This lack of increase in girls can be ascribed to their displaying higher degrees of imitation fidelity at an earlier age., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Cervical laceration (CL), although infrequent, is an often-unrecognized complication of vaginal birth and can cause significant blood loss in the immediate postpartum period. The rate of clinically significant CL ranges from 0.14% to 0.2% of births. Nulliparity, operative vaginal birth, occiput posterior position of the fetus, induction of labor, and episiotomy have been cited as possible risk factors. Much of the available literature regarding CL, however, is dated or anecdotal, and there are varying and inconsistent risk associations with its occurrence. Given this unpredictability, CL should be considered in all women with immediate postpartum hemorrhage when there is difficulty obtaining hemostasis. Although midwives receive training about CLs, the low incidence may lead to delay in diagnosis and management. This Clinical Rounds case presents a composite case of postpartum hemorrhage caused by a CL. Risk factors, diagnosis and midwifery management are discussed., (© 2023 by the American College of Nurse‐Midwives.)

Mining has led to severe environmental pollution in countries with exhaustive mining production and inadequate industrial waste regulation. Microorganisms in contaminated sites, like mine tailings, have adapted to high concentrations of heavy metals, developing the capacity of reducing or removing them from these environments. Therefore, it is essential to thoroughly characterize bacteria present in these sites to find different ways of bioremediation. In this regard, in this study, an enrichment and isolation procedure were performed to isolate bacteria with lower nutritional requirements and high tolerance to Cu(II) and Fe(II) from two Sonoran River basin mining tails. Two Staphylococcus species and a Microbacterium ginsengisoli strain were isolated and identified from the San Felipe de Jesús mining tail. Also, three strains were isolated from the Nacozari de García mining tail: Burkholderia cenocepacia, Sphingomonas sp. and Staphylococcus warneri. Significant microbiological differences were found between the two sites. All these species exhibited tolerance up to 300 mg/L for Cu (II)-Fe (II) solutions, indicating their capacity to grow in these conditions. Moreover, a consortium of isolated bacteria was immobilized in two different biocomposites and the biocomposite with larger pore size achieved greater bacterial immobilization showcasing the potential of these bacteria in biotechnological applications., (© 2024. The Author(s).)

Poly(3-hydroxybutyrate- co -3-hydroxyvalerate) (PHBV) is a promising biodegradable bio-based material, which is designed for a vast range of applications, depending on its composite. This study aims to assess the degradability of a PHBV-based compound under different conditions. The research group followed different methodological approaches and assessed visual and mass changes, mechanical and morphological properties, spectroscopic and structural characterisation, along with thermal behaviour. The Ph-Stat (enzymatic degradation) test and total dry solids (TDS)/total volatile solids (TVS) measurements were carried out. Finally, the team experimentally evaluated the amount of methane and carbon dioxide produced, i.e., the degree of biodegradation under aerobic conditions. According to the results, different types of tests have shown differing effects of environmental conditions on material degradation. In conclusion, this paper provides a summary of the investigations regarding the degradation behaviour of the PHBV-based compound under varying environmental factors. The main strengths of the study lie in its multi-faceted approach, combining assessments of PHBV-based compound degradability under different conditions using various analytical tools, such as visual and mass changes, mechanical and morphological properties, spectroscopic and structural characterization, and thermal behavior. These methods collectively contribute to the robustness and reliability of the undertaken work., 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. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests., (© 2024 The Authors.)

The maternal decidua is a transient and dynamic tissue that functions as an immunoprivileged matrix related to nutritional and endocrine processes. The function of decidual cells is key to the success of embryo implantation and the maintenance of pregnancy with a positive maternal-fetal outcome. Therefore, establishing a method to optimize the isolation of primary decidual cells is essential. Our protocol described here provides a good yield of decidual cells in an optimized time., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Mastocytosis and monoclonal mast cell (MC) activation syndrome (MMAS) are heterogeneous conditions characterized by the accumulation of atypical MCs. Despite the recurrent involvement of KIT mutations, the pathophysiologic origin of mastocytosis and MMAS is unclear. Although hereditary α-tryptasemia (HαT, related to TPSAB1 gene duplication) is abnormally frequent in these diseases, it is not known whether the association is coincidental or causal., Objective: We evaluated the prevalence of HαT in all mastocytosis subtypes and MMAS and assessed the pathophysiologic association with HαT., Methods: Clinical data, laboratory data, KIT mutations, TPSAB1 duplication (assessed by droplet digital PCR), and HαT prevalence were retrospectively recorded for all patients with mastocytosis and MMAS registered in the French national referral center database and compared to a control cohort. To increase the power of our analysis for advanced systemic mastocytosis (advSM), we pooled our cohort with literature cases., Results: We included 583 patients (27 with MMAS and 556 with mastocytosis). The prevalence of HαT in mastocytosis was 12.6%, significantly higher than in the general population (5.7%, P = .002) and lower than in MMAS (33.3%, P = .02). HαT + patients were more likely to have anaphylactic reactions and less likely to have cutaneous lesions than HαT - patients (43.0% vs 24.4%, P = .006; 57.7% vs 75.6%, respectively, P = .006). In the pooled analysis, the prevalence of HαT was higher in advSM (11.5%) than in control cohorts (5.2%, P = .01)., Conclusion: Here we confirm the increase incidence of anaphylaxis in HαT + mastocytosis patients. The increased prevalence of HαT in all subtypes of systemic mastocytosis (including advSM) is suggestive of pathophysiologic involvement., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Tropaeolaceae (Brassicales) comprise ~100 species native to South and Central America. Tropaeolaceae flowers have a nectar spur, formed by a late expansion and evagination of the fused proximal region of the perianth (i.e. the floral tube). This spur is formed in the domain of the tube oriented towards the inflorescence axis, which corresponds to the adaxial floral region. However, little is known about the molecular mechanisms responsible for the evolution of spurs in Tropaeolaceae., Methods: In this study, we examined the spatio-temporal expression of genes putatively responsible for differential patterns of cell division between the adaxial and abaxial floral regions in Tropaeolaceae. These genes include previously identified TCP and KNOX transcription factors and the cell division marker HISTONE H4 (HIS4)., Key Results: We found a TCP4 homologue concomitantly expressed with spur initiation and elaboration. Tropaeolaceae possess two TCP4-like (TCP4L) copies, as a result of a Tropaeolaceae-specific duplication. The two copies (TCP4L1 and TCP4L2) in Tropaeolum longifolium show overlapping expression in the epidermis of reproductive apices (inflorescence meristems) and young floral buds, but only TlTCP4L2 shows differential expression in the floral tube at early stages of spur formation, restricted to the adaxial region. This adaxial expression of TlTCP4L2 overlaps with the expression of TlHIS4. Later in development, only TlTCP4L2 is expressed in the nectariferous tissue of the spur., Conclusions: Based on these results, we hypothesize that Tropaeolaceae TCP4L genes had a plesiomorphic role in epidermal development and that, after gene duplication, TCP4L2 acquired a new function in spur initiation and elaboration. To better understand spur evolution in Tropaeolaceae, it is critical to expand developmental genetic studies to their sister group, the Akaniaceae, which possess simultaneously an independent duplication of TCP4L genes and a spurless floral tube., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The coral microbiome conforms a proxy to study effects of changing environmental conditions. However, scarce information exists regarding microbiome dynamics and host acclimation in response to environmental changes associated to global-scale disturbances. We assessed El Niño Southern Oscillation (ENSO)-derived thermal anomalies shifts in the bacterial microbiome of Pacifigorgia cairnsi (Gorgoniidae: Octocorallia) from the remote island of Malpelo in the Tropical Eastern Pacific. Malpelo is a hot spot of biodiversity and lacks direct coastal anthropogenic impacts. We evaluated the community composition and predicted functional profiles of the microbiome during 2015, 2017 and 2018, including different phases of ENSO cycle. The bacterial community diversity and composition between the warming and cooling phase were similar, but differed from the neutral phase. Relative abundances of different microbiome core members such as Endozoicomonas and Mycoplasma mainly drove these differences. An acclimated coral holobiont is suggested not just to warm but also to cold stress by embracing similar microbiome shifts and functional redundancy that allow maintaining coral's viability under thermal stress. Responses of the microbiome of unperturbed sea fans such as P. cairnsi in Malpelo could be acting as an extended phenotype facilitating the acclimation at the holobiont level., (© 2023. The Author(s).)

Previously, we designed a subunit vaccine candidate based on three L. intracellularis antigens with promising results in pigs. In this study, antigens were produced individually to achieve an even antigen ratio in the formulation. The emulsion characterization included the drop size and the mechanical and thermal stability. Immune response was evaluated by indirect and sandwich ELISAs, qPCR, and flow cytometry. The vaccine candidate's safety was assessed by histopathology and monitoring the clinical behavior of animals. The average production yielded for the chimeric antigen as inclusion bodies was around 75 mg/L. The formulation showed mechanical and thermal stability, with a ratio Hu/Ho > 0.85 and a drop size under 0.15 nm. Antigens formulated at a ratio of 1:1:1 induced a significant immune response in inoculated pigs that persisted until the end of the experiment (week 14). The dose of 200 μg significantly activated cellular response measured by transcriptional and translational levels of cytokines. The cell proliferation assay revealed an increment of lymphocytes T CD4 + at the same dose. Animals gained weight constantly and showed proper clinical behavior during immunization assays. This research demonstrated the immunological robustness of the new subunit vaccine candidate against Porcine Proliferative Enteropathy evenly formulated with three chimeric antigens of L. intracellularis .