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Abstract Background Chad with 7,698 confirmed cases of infection and 194 deaths since the beginning of the COVID-19 pandemic, is one of the African countries with the lowest reported case numbers. However, this figure likely underestimates the true spread of the virus due to the low rate of diagnosis. The high rate of asymptomatic infections reflects the reality of SARS-CoV-2 transmission in Chad. In this study, we estimated the seroprevalence and identified factors associated with SARS-CoV-2 infection. Methods A cross-sectional study was conducted between September 2022 and February 2023. A total of 1,290 plasma samples were collected from outpatient attendees at Health Facilities located in 11 provinces of Chad and tested by ELISA method, for the presence of IgG antibodies to SARS-CoV2 nucleocapsid (N) protein. KoboToolbox was used to gather data from the participants and data were analyzed using STATA 16. Results The overall seroprevalence was 83.0% [95% CI = 81.6%—85.5%], with variations between provinces, ranging from 99.2% [95% CI = 94.0%—100%] in Moundou (Southern Chad) to 46.8% [95% CI = 36.0% -57.1%] in Biltine (Eastern Chad). Factors associated with the seroprevalence included military occupation (OR = 0.37 CI [0.80–1.77] p = 0.025) and age group between 55–64 years (OR = 0.33 CI [0.15–0.72] p = 0.005). While, other factors, such as gender and age were not significantly associated with seroprevalence. Conclusion Our results indicated that, the seroprevalence of COVID-19 in Chad is among the highest in Sub-Saharan Africa. These estimates could guide the response and public health policy decisions, enhancing the management of future outbreaks involving respiratory pathogens.

Abstract We have developed a new universal influenza B vaccination strategy based on inactivated influenza B viruses displaying mosaic hemagglutinins (mHAs). Recombinant mHA viruses were constructed by replacing the four major antigenic sites of influenza B virus HAs, with those from exotic avian influenza A virus HAs. Sequential vaccination of naïve mice with mHA-based vaccines elicited higher immune responses towards the immuno-subdominant conserved epitopes of the HA than vaccination with wildtype viruses. Among the different preparations tested, mHA split vaccines were less immunogenic than their whole inactivated virus counterparts. This lower immunogenicity was overcome by the combination with adjuvants. mHA split vaccines adjuvanted with a Toll-like receptor-9 agonist (CpG 1018) increased Th1 immunity and in vivo cross-protection, whereas adjuvanting with an MF59-like oil-in-water nano-emulsion (AddaVax) enhanced and broadened humoral immune responses and antibody-mediated cross-protection. The mHA vaccines with or without adjuvant were subsequently evaluated in mice that were previously immunized to closely mimic human pre-existing immunity to influenza B viruses and the contribution of innate and cellular immunity was evaluated in this model. We believe these preclinical studies using the mHA strategy represent a major step toward the evaluation of a universal influenza B virus vaccine in clinical trials.

Abstract The epigenetic landscape plays a critical role in cancer progression, yet its therapeutic potential remains underexplored. Glucocorticoids are essential components of treatments for lymphoid cancers, but resistance, driven in part by epigenetic changes at glucocorticoid-response elements, poses a major challenge to effective therapies. Here we show that glucocorticoid treatment induces distinct patterns of chromosomal organization in glucocorticoid-sensitive and resistant acute lymphoblastic leukemia xenograft models. These glucocorticoid-response elements are primed by the pioneer transcription factor PU.1, which interacts with the glucocorticoid receptor. Eviction of PU.1 promotes receptor binding, increasing the expression of genes involved in apoptosis and facilitating a stronger therapeutic response. Treatment with a PU.1 inhibitor enhances glucocorticoid sensitivity, demonstrating the clinical potential of targeting this pathway. This study uncovers a mechanism involving PU.1 and the glucocorticoid receptor, linking transcription factor activity with drug response, and suggesting potential therapeutic strategies for overcoming resistance.

Background: Suprascapular nerve decompression (SSND) remains a controversial procedure. In 2018, Momaya et al published the first systematic review of SSND noting satisfactory outcomes with low rates of complications; however, numerous studies published since have noted no benefit in routinely adding SSND to other arthroscopic surgeries, contributing to existing contention regarding the procedure. The purpose of this study is to provide an updated assessment of outcomes after SSND. Methods: To conduct this updated systematic review, a search of PubMed (MEDLINE) for relevant studies published prior to January 21, 2023 was conducted. Outcomes including patient-reported clinical outcomes, return to sport, preoperative and postoperative electrodiagnostic testing, and adverse events were collected and pooled for assessment. Studies were eligible for inclusion if they met Momaya et al’s inclusion criteria and/or reported outcomes following SSND at either the suprascapular notch or spinoglenoid notch. Results: In total, 730 patients from 33 studies were eligible for inclusion. All patient-reported outcome measure scores including American Shoulder Elbow Surgeon Standardized Shoulder Assessment; Constant-Murley score; Disabilities of the Arm, Shoulder, and Hand; Subjective Shoulder Value; University of California–Los Angeles shoulder; and visual analog scale pain scores improved significantly postoperatively, with improvements ranging from 53.5% to 102.6% of preoperative values. Ultimately, 98% (n = 90/92) of patients returned to sport or military duty and 96% of these patients returned at their previous level of activity (n = 48/50) without heterogeneity among rates between studies (P = .176, P = .238, respectively). Preoperative electrodiagnostic testing was conducted in 93% of patients, and 90% had associated abnormal findings. Continued symptoms were noted among 12% of patients (n = 39/322) with significantly different rates observed between studies. Complications from operative management not limited to SSND occurred in 11% of patients (n = 64/576) and reoperations occurred in 3.3% of patients (n = 15/455). Conclusion: Suprascapular neuropathy treated with SSND significantly improves patient-reported outcomes and is noninferior to similar procedures without SSND. Appropriate clinical diagnosis of suprascapular neuropathy is required as opposed to a routine adjunct procedure with other arthroscopic shoulder surgery. Ultimately, SSND is associated with high rates of return to sport and relatively low rates of adverse events; however, the risk of continued symptoms and electrodiagnostic test-related complications is an important point on preoperative counseling.

Studies have shown that eosinophilic COPD (eCOPD) is a distinct phenotype of the disease. It is well established that innate lymphoid cells are involved in the development of eosinophilic inflammation. Interleukin(IL)-25, thymic stromal lymphopoietin (TSLP) and IL-33 are a group of cytokines produced by epithelium in response to danger signals, e.g., cigarette smoke, and potent activators of ILC2s. In the present study, we examined circulating and sputum ILC2 numbers and expression of intracellular IL-5 as well as receptors for TSLP, IL-33 and IL-25 by ILC2s in non-atopic COPD patients with and without (neCOPD) airway eosinophilic inflammation and healthy smokers. In addition, we examined the association between ILC2s and clinical indicators of COPD burden (i.e., symptom intensity and risk of exacerbations). ILC2s were enumerated in peripheral blood and induced sputum by means of flow cytometry. We noted significantly greater numbers of airway IL-5+ILC2s and TSLPR+ILC2s in eCOPD compared with neCOPD (p < 0.05 and p < 0.01, respectively) and HSs (p < 0.001 for both). In addition, we showed that IL-5+ILC2s, IL-17RB+ILC2s and ST2+ILC2s are significantly increased in the sputum of eCOPD patients compared with HSs. In all COPD patients, sputum ILC2s positively correlated with sputum eosinophil percentage (r = 0.48, p = 0.002). We did not find any significant correlations between sputum ILC2s and dyspnea intensity as measured by the modified Medical Research Council scale (mMRC) and symptom intensity measured by the COPD Assessment Test (CAT). These results suggest the involvement of epithelial alarmin-activated ILC2s in the pathobiology of eosinophilic COPD.

Suad Abdikarim Isse,1 Ahmet Do&gbreve;an,2 Tigad Abdisad Ali,1 Jabir Abdullahi Wehlie,3 Abdirahim Ali Adam,4 Hüsna Öztürk5 1Department of Infect&inodot;on Prevent&inodot;on Control, Mogad&inodot;shu Somal&inodot; Turk&inodot;ye Recep Tayy&inodot;p Erdogan Tra&inodot;n&inodot;ng and Research Hosp&inodot;tal, Mogadishu, Somalia; 2Department of Infectious Diseases and Clinical Microbiology, Abant Izzet Baysal University Faculty of Medicine, Bolu, Turkiye; 3Department of Dermatology, New Vision Hospital, Mogadishu, Somalia; 4Department of Infectious Diseases and Clinical Microbiology, Mogadishu-Somalia-Turkiye Recep Tayyip Erdo&gbreve;an Training and Research Hospital, Mogadishu, Somalia; 5Department of Infectious Control Nurse Istanbul Ko&scedil;uyolu Yüksek &Idot;htisas E&gbreve;itim ve Ara&scedil;t&inodot;rma Hastanesi, Istanbul, TurkiyeCorrespondence: Suad Abdikarim Isse; Tigad Abdisad Ali, Email suadabdikarim89@gmail.com; tigaadvip@gmail.comBackground: Hand hygiene is a critical preventive measure for controlling infections, particularly in underdeveloped nations.Materials and Methods: A cross-sectional study was conducted in a hospital in Mogadishu, Somalia, from January to March 2024. This study aimed to assess compliance with hand hygiene practices and related factors among healthcare professionals.Results: The study population comprised 52% men and 47.3% women. Most participants held bachelor’s degrees, with the majority being nurses or midwives. A significant proportion had over five years of work experience. Almost all participants were knowledgeable about hand hygiene. Most reported cleaning and drying their hands before, during, and after contact with bodily fluids during aseptic procedures. Age, gender, educational status, marriage, working experience, type of occupation, receiving hand hygiene training and knowledge, and having the availability of water, soap, alcohol, and gloves significantly affected the overall uptake of infection control measures in Mogadishu (p< 0.05).Conclusion: The findings highlight an urgent need for targeted interventions to enhance hand hygiene practices in Somalia. Addressing training gaps and resource shortages is crucial for reducing infection rates and safeguarding patient health in this high-risk setting.Keywords: hand hygiene compliance, healthcare workers, Mogadishu, Somalia, infection control

Cowpea (Vigna unguiculata L. Walp) is one of Benin’s most cultivated and consumed grain legumes. However, drought remains one of the main causes of its decline in yield. The aim of this work was to identify superior cowpea genotypes tolerant to water deficit. Twenty-six (N = 26) genotypes (varieties and hybrids) were subjected to two water regime conditions (well-watered and stressed) in a greenhouse at the International Institute of Tropical Agriculture (IITA), Benin) during the 2021 dry season. The experiment was laid out in a split plot with 3 replicates. The results showed that proline content, chlorophyll content, number of pods per plant, number of seeds per pod, hundred-seed weight and seed yield were all significantly (P < 0.001) reduced under the effect of water deficit. However, the genotypes KVX396-18, Kpodjiguèguè x KVX 396-18, IT97K-206-1-1, IT99K573-1-1, IT07K-211-1-8 x IT97K-206-1-1, and F2_Kpodjiguèguè x Tawa provided the highest values under water deficit compared to unstressed plants which served as controls. These genotypes were the best water deficit tolerant and high-yielding genotypes. Low values were recorded for F2_ genotypes KVX61-1 x Tawa, IT07K-211-1-8 x Tawa, KVX61-1, IT07K-211-1-8 x IT99K-573-1-1, F2_IT07K-211-1-8 x IT99K-573-1-1, F2_IT06K242-3 x IT97K-206-1-1, KVX61-1 x Tawa, which are considered in this case as drought-sensitive and low-yielding genotypes. A correlation between plant height, leaf width, pod maturity days, pod length, number of pods per plant, and hundred seed weight and yield were observed. Number of pods per plant (NPP), grain yield per plant (GYP), hundred seed weight (100WS), pod length (PL), number of days to pod maturity (NDPM), number of seeds per pod (NSP), and number of leaves per plant (NLP) can therefore be exploited in cowpea breeding programs to improve yield and drought tolerance in susceptible and low-yielding genotypes.

Respiratory syncytial virus (RSV) causes acute lower and upper respiratory tract infections in all age groups. The clinical course of RSV infection differs depending on age and comorbidities. RSV infections are severe in the adult population; the highest risk of complications is seen in the elderly (age over 60 years) and in individuals with certain chronic disorders. Vaccination is the only currently available method of active prevention of RSV infections in adults. RSV vaccines stimulate both the humoral and the cell-mediated immunity and ensure a high level of protection against severe and complicated infection. Vaccination is recommended in all patients over the age of 60 years, particularly those with chronic disease (asthma, chronic obstructive pulmonary disease and other chronic respiratory tract disorders, ischaemic heart disease, heart failure, cardiac arrhythmias, diabetes, chronic kidney disease), immunodeficient individuals and nursing home residents.

Abstract Despite recent work linking mixed phenotype acute leukemia (MPAL) to certain genetic lesions, specific driver mutations remain undefined for a significant proportion of patients and no genetic subtype is predictive of clinical outcomes. Moreover, therapeutic strategy for MPAL remains unclear, and prognosis is overall poor. We performed multiomic single cell profiling of 14 newly diagnosed adult MPAL patients to characterize the inter- and intra-tumoral transcriptional, immunophenotypic, and genetic landscapes of MPAL. We show that neither genetic profile nor transcriptome reliably correlate with specific MPAL immunophenotypes. Despite this, we find that MPAL blasts express a shared stem cell-like transcriptional profile indicative of high differentiation potential. Patients with the highest differentiation potential demonstrate inferior survival in our dataset. A gene set score, MPAL95, derived from genes highly enriched in the most stem-like MPAL cells, is applicable to bulk RNA sequencing data and is predictive of survival in an independent patient cohort, suggesting a potential strategy for clinical risk stratification.

Sumac (Rhus coriaria) is a flowering plant that is widely consumed for its promoting health benefits and used in food preparations as a spice in the Mediterranean region. It is a high shrub or small tree with imparipinnate leaves, villus and red fruits with one-seeded drupe, and small greenish-white flowers. The nutraceutical and pharmaceutical potential of sumac makes it a remarkable functional food. In this review, the phytochemical and nutritional properties of sumac as an under valorized functional food have been discussed. Flavonoids, anthocyanins, phenolic acids, and organic acids have been reported as dominant phytochemicals in sumac, which are well known for their pharmacological properties that attract many consumers to commonly choose sumac in their diet as well as food preparations. The remarkable volatile compounds present in sumac give it a unique aroma that increases its acceptance by consumers and potential use in the food industry. Sumac has been evaluated for a broad range of nutritional and pharmacological activities such as antioxidant, antinociceptive, anti-inflammatory, anti-diabetic, hepatoprotective, cardioprotective, anticancer, anti-infertility, and neuroprotective potential. This review has also briefly outlined the safety concerns concerning the use of sumac in terms of toxicology and interactions.

This study aims to present an easily scalable, cost-efficient process of dECM extraction from porcine meniscus, dedicated to bioink preparation and 3D bioprinting. Due to its cartilage like structure and mechanical robustness, the meniscus is an exceptionally demanding tissue for extraction and decellularisation of its ECM. Its processing poses a great difficulty and renders the methods previously developed for soft tissues useless. A process, combining homogenisation, hydrolysis, supercritical CO2 (scCO2) extraction and lyophilisation, was developed to meet this challenge. This protocol allows for retaining its native compounds and biocompatibility while offering good printability and providing a stimulatory environment for cell proliferation and differentiation towards a meniscus-like phenotype. Also, this process is economically and ecologically friendly since it doesn't require the use of high amounts of solvents, detergents or expensive enzymes (DNase). The decellularisation process has been meticulously studied, demonstrating a substantial reduction in DNA content but still exceeding accepted thresholds. The study further explores the biocompatibility of the dECM, demonstrating no detrimental effects of remnant DNA on cell survival during extended in vitro culture, indicating excellent biocompatibility. These findings challenge the current definition of decellularisation effectiveness based solely on DNA content, proposing a broader assessment of biological effects.

Background and Purpose The management of acute ischemic stroke (AIS) due to distal medium vessel occlusion (DMVO) remains uncertain, particularly in comparing the effectiveness of intravenous thrombolysis (IVT) plus mechanical thrombectomy (MT) versus IVT alone. This study aimed to evaluate the safety and efficacy in DMVO patients treated with either MT-IVT or IVT alone. Methods This multinational study analyzed data from 37 centers across North America, Asia, and Europe. Patients with AIS due to DMVO were included, with data collected from September 2017 to July 2023. The primary outcome was functional independence, with secondary outcomes including mortality and safety measures such as types of intracerebral hemorrhage. Results The study involved 1,057 patients before matching, and 640 patients post-matching. Functional outcomes at 90 days showed no significant difference between groups in achieving good functional recovery (modified Rankin Scale 0–1 and 0–2), with adjusted odds ratios (OR) of 1.21 (95% confidence interval [CI] 0.81 to 1.79; P=0.35) and 1.00 (95% CI 0.66 to 1.51; P>0.99), respectively. Mortality rates at 90 days were similar between the two groups (OR 0.75, 95% CI 0.44 to 1.29; P=0.30). The incidence of symptomatic intracerebral hemorrhage was comparable, but any type of intracranial hemorrhage was significantly higher in the MT-IVT group (OR 0.43, 95% CI 0.29 to 0.63; P

Lentic waters are biogeochemical reactors, producing and receiving carbon (C) originally fixed by the terrestrial and aquatic biosphere, which is then buried in sediments or respired back to the atmosphere in the forms of carbon dioxide (CO2) and one of the more potent greenhouse gas (GHG) methane (CH4). Additionally, lakes serve as archives of terrestrial and aquatic carbon processes within their sediments, enabling the reconstruction of historical changes spanning thousands of years. These changes encompass alterations in land cover, indicated by pollen records, soil carbon erosion and shifts in lake productivity resulting from changes in land use and climate. Both the burial of C in lakes and the emissions of GHGs are recognised as important components of Earth's climate system, yet they remain poorly understood and constrained due to inadequate quantities and qualities of observations. In the case of GHG emissions from lakes, observations are often sporadic, failing to capture the significant spatial and temporal variations in emissions across diverse lentic systems. To address this challenge, process-based models that incorporate the interconnected biogeochemical processes occurring within lakes and their watersheds would arguably be the best tool to extrapolate from site-level observations to regional and finally global scales, to quantify the anthropogenic impact on these fluxes and to reconstruct long-term shifts in emissions and burial due to changes in land cover and climate. However, the development and evaluation of such models is hampered by the lack of observations in sufficient quality. In this project, we bring together a unique consortium of specialists in aquatic ecology, biogeochemistry, palynology, sedimentology and modelling of terrestrial and aquatic biogeochemistry. This project will put forth a national programme of systematic, long-term observations of lake GHG and C cycling processes of unmet detail, consistency and quality. First, at 40 pilot sites spanning typological and environmental gradients, there will be a comprehensive data acquisition endeavour to evaluate biological processes and mesological factors influencing the sequestration or recycling of organic carbon. This effort will be complemented with a synthesis of existing data (WP1). Second, based on well-dated sediment records, which include both newly-acquired and synthesised existing data, variability of lake C burial and their climate and land-use controls will be reconstructed over the past 150 years (WP2). For 15 of these pilot sites, reconstruction will go back until the mid-Holocene (5,000 years BP), allowing us to shed light on the anthropogenic perturbation of the C cycle in this earlier part of human history, which is commonly excluded from this type of research due to lack of information. The activities of these first two WPs will result in an open-source national database, guaranteeing valorisation of our research far beyond this project. In WP3, we will use the land surface model (LSM) ORCHIDEE C-lateral to assess C cycling in the terrestrial biosphere and the mobilisation of biospheric C into lakes, which is possible due to an explicit representation of soil C leaching and erosion processes and a downscaling scheme permitting us to assess C exports from watersheds at sub-grid scale. While LSMs are used to assess evolution of biospheric C budgets from the beginning of the Industrial Period, we will use it to hindcast the evolution since the mid-Holocene, using lake sediment records for model validation. Moreover, we will develop a new process-based lake C model supported by the database established in WPs 1 and 2, which we will couple to ORCHIDEE C-lateral to simulate lake C burial and GHG emissions in response to climate and processes in the lake watershed. This model set-up will first be used to better constrain contemporary large-scale lake GHG emissions and to disentangle the anthropogenic perturbation of these fluxes from the natural background flux. These estimates will be revolutionary, as they will allow attributing part of lake GHG emissions to anthropogenic emissions for national GHG budget reporting. Then, these models will be emulated to reconstruct evolution of lake GHG budgets and C budgets of the whole lake watershed since the mid-Holocene. While simulations will first be performed at the scales of France and Europe, the development of international partnerships to implement observations from other biomes (WP4) will finally support simulations at the global scale.

Abstract Missing covariate data is a common problem that has not been addressed in observational studies of gene expression. Here, we present a multiple imputation method that accommodates high dimensional gene expression data by incorporating principal component analysis of the transcriptome into the multiple imputation prediction models to avoid bias. Simulation studies using three datasets show that this method outperforms complete case and single imputation analyses at uncovering true positive differentially expressed genes, limiting false discovery rates, and minimizing bias. This method is easily implemented via an R Bioconductor package, RNAseqCovarImpute that integrates with the limma-voom pipeline for differential expression analysis.

Abstract Understanding the causes for discrepancies between modelled and observed regional climate trends is important for improving present-day climate simulation and reducing uncertainties in future climate projections. Here, we analyse the performance of coupled climate models in reproducing regional precipitation trends during the satellite era. We find statistically significant observed drying in southwestern North America and wetting in the Amazon during the period 1979–2014. Historical climate model simulations do not capture these observed precipitation trends. We trace this discrepancy to the inability of coupled simulations to capture the observed Pacific trade wind intensification over this period. A linear adjustment of free running historical simulations, based on the observed strengthening of the Pacific trade winds and modeled ENSO teleconnections, explains the discrepancy in precipitation trends. Furthermore, both the Pacific trade wind trends and regional precipitation trends are reproduced in climate simulations with prescribed observed sea surface temperatures (SST), underscoring the role of the tropical Pacific SST patterns.

Abstract Purpose The aim of this study was to identify factors that predict favorable functional outcomes in elderly patients with large-vessel occlusion acute ischemic stroke (LVO-AIS) who underwent mechanical thrombectomy (MT). Methods We conducted a retrospective observational study using the prospectively maintained Bigdata Observatory for Stroke of China (BOSC) to identify eligible patients who underwent MT for LVO-AIS at four comprehensive stroke centers between August 2019 and February 2022. Inclusion criteria included patients aged 80 years or older with a baseline modified Rankin Scale (mRS) 0–2, baseline National Institutes of Health Stroke Scale (NIHSS) > 6, baseline Alberta Stroke Program Early CT Score (ASPECTS) > 6 who received treatment within 24 h from symptom onset. Pertinent demographic, clinical, and procedural variables were collected. Multivariable regression analyses were performed to identify predictors of favorable long-term functional outcomes, defined as mRS 0–2 at 90 days. Results A total of 63 patients were included in the study with a mean age of 83 years. Patients with previous diagnosis of atrial fibrillation were more likely to have a favorable functional outcome (OR 2.09, 95% CI 2.09–407.33, p = 0.012), while a higher baseline NIHSS was associated with a less favorable functional outcome (OR 0.64, 95% CI 0.46–0.89, p = 0.007). In addition, there was an observed trend suggesting an association between higher baseline ASPECTS and favorable functional outcomes. This association did not reach statistical significance (OR 2.49, 95% CI 0.94–6.54, p = 0.065). Conclusion In this study, we identified factors that predicted a favorable functional outcome in elderly LVO-AIS patients undergoing MT. A higher baseline NIHSS decreased the odds of mRS 0–2 at 90 days, whereas a history of atrial fibrillation increased the odds of a favorable functional outcome. These results emphasize the complex relationship between clinical factors and functional recovery in this vulnerable population.

Abstract Background The pervasiveness of the Internet in everyday life, especially among young people, has raised concerns about its effects on mental health, education, and, recently, oral health. Previous research has suggested a complex relationship between Problematic Internet Use (PIU), lifestyles, and oral health-related quality of life, highlighting the need to examine these interactions further. This study seeks to explore the PIU as a predictor of oral health-related quality of life and examine the mediating role of lifestyles between both in a sample of Peruvian schoolchildren. Methods A cross-sectional study was carried out with 293 Peruvian students aged 12 to 17 years (M = 14.42, SD = 1.5), using structural equations to analyze the relationship between PIU, lifestyles, and quality of life related to oral health. The data collection procedure was through a face-to-face survey. Validated instruments measured PIU, lifestyles, and oral health-related quality of life. The study’s theoretical model was analyzed through structural equation modeling with the MLR estimator. The fit assessment was performed using the comparative fit index (CFI), root mean square error of approximation (RMSEA), and standardized root mean square residual (SRMR). Results They indicated significant correlations between PIU, lifestyles, and oral health-related quality of life. A negative influence of PIU on lifestyles (β = -0.30, p

Sesame production is important in agriculture, food industry, and the crop diversity due to its rich nutritional profile and health benefits. Despite its significant value, sesame is still an orphan crop that has received little scientific attention, resulting in low yield compared to other major oilseed crops. This review offers a comprehensive overview of the present state of production, knowledge, and research advancements concerning Sesamum indicum on a global scale. The FAOSTAT database was extensively used to examine the global trends from 1961 to 2021. In the past 60 years, global sesame production has substantially increased, with Asia and Africa being the primary producers. The integration of omics technologies and biotechnological interventions has revolutionized our understanding of the genetic basis of sesame, enhanced productivity, invigorated stress resilience, and improved seed quality. High-throughput sequencing methods such as RNA-seq, RAD-seq, SLAF-seq, and GBS technology are used in various studies, linkage mapping, and identification of trait-associated markers. Fine linkage maps, and multi-omics studies such as genomics, proteomics, transcriptomics, and metabolomics have been employed in sesame research for gene and QTL mapping. Proteins and metabolic pathways related to oil content, yield, and stress tolerance were reported. Genes and QTLs related to yield and its components, drought, salt, and osmotic stress tolerance were discovered. Candidate genes associated with capsule shattering and seed shattering were recently revealed. For more achievement in sesame, it is important to enhance sesame production efficiency through mechanization, advanced agricultural practices, and knowledge dissemination to farmers. MAS and multi-omics integration should be particularly reinforced. The advancements in sesame production present a significant and promising opportunity for farmers, governments, and stakeholders in the agricultural sector.

Nader Ahmed Mohammed,1 Abdulrahman OE Adam,2 Monzir Ahmed Hassan Osman,2,3 Hibatallah MA Abass,2,3 Awad MA Salih,2,3 Ameer AM Abaker,2,3 Alamin Mustafa,3,4 Mamoun Magoub5 1Department of Medicine, Faculty of Medicine, University of Kassala, Kassala, Sudan; 2Faculty of Medicine, Omdurman Islamic University, Omdurman, Sudan; 3Patient Support Organization Research Unit, Khartoum, Sudan; 4Faculty of Medicine, Al-Neelain University, Khartoum, Sudan; 5Department of Microbiology & Parasitology, Faculty of Medicine & Health Science, West Bank of Gash River, University of Kassala, Kassala, SudanCorrespondence: Mamoun Magoub, Department of Microbiology & Parasitology, Faculty of Medicine & Health Science, West Bank of Gash River, University of Kassala, Kassala, Sudan, Tel +24991291999, Email mamounmagzoub@kassalauni.edu.sd Alamin Mustafa, Faculty of Medicine, Al-Neelain University, JG37+2RM, 52nd St, Khartoum, Sudan, Tel +249902612984, Email alamin900005@gmail.comBackground: Ascaris lumbricoides is a common infectious parasite of the gastrointestinal tract worldwide, but the invasion of the pleural cavity is rare.Case Report: A 45-year-old man from Eastern Sudan presented to the emergency department complaining of breathlessness, cough stained with blood, and chest pain one month before his presentation. Also, he complained of high-grade fever for two weeks associated with sweating. Diagnosis of hydropneumothorax was made and a chest tube was inserted, two days later we found three adult A. lumbricoides worms in the chest drain.Conclusion: The patient was treated with Albendazole 200 mg, orally twice, daily for seven days, he improved and was referred to a cardiothoracic surgeon for more assessment. Our study highlights that internal medicine specialists should know about pleural ascariasis when patients present with respiratory signs and symptoms, especially in A. lumbricoides endemic regions like Eastern Sudan.Keywords: neglectable tropical diseases, pulmonology, pleural cavity, ascariasis, Ascaris lumbricoides

Abstract Objective Medical staff, especially nurses, suffered great anxiety and stress from the COVID-19 pandemic, which negatively affected their sleep quality. In this study, we aimed to analyze the sleep quality of nursing staff after terminating the Zero-COVID-19 policy in China. Methods 506 participants were involved in our study. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate the sleep status of the participants. Binary regression was performed to evaluate the impact factors related to sleep difficulty. Results The majority of participants (96.44%) suffered from sleep disturbances. There were significant differences in age, education level and front-line activity between participants with good sleep quality and sleep difficulty. Younger age (16–25 years old) was independently associated with less sleep difficulty, while front-line activity was independently associated with severe sleep difficulty. Conclusion Sleep disorder was very common among nurses after ending the Zero-COVID-19 policy in China. More front-line nurses suffered severe sleep difficulty in particular, which should be worthy of attention.

Abstract Temperature is a critical environmental cue that controls the development and lifespan of many animal species; however, mechanisms underlying low-temperature adaptation are poorly understood. Here, we describe cold-inducible diapause (CID), another type of diapause induced by low temperatures in Caenorhabditis elegans. A premature stop codon in heat shock factor 1 (hsf-1) triggers entry into CID at 9 °C, whereas wild-type animals enter CID at 4 °C. Furthermore, both wild-type and hsf-1(sy441) mutant animals undergoing CID can survive for weeks, and resume growth at 20 °C. Using epistasis analysis, we demonstrate that neural signalling pathways, namely tyraminergic and neuromedin U signalling, regulate entry into CID of the hsf-1 mutant. Overexpression of anti-ageing genes, such as hsf-1, XBP1/xbp-1, FOXO/daf-16, Nrf2/skn-1, and TFEB/hlh-30, also inhibits CID entry of the hsf-1 mutant. Based on these findings, we hypothesise that regulators of the hsf-1 mutant CID may impact longevity, and successfully isolate 16 long-lived mutants among 49 non-CID mutants via genetic screening. Furthermore, we demonstrate that the nonsense mutation of MED23/sur-2 prevents CID entry of the hsf-1(sy441) mutant and extends lifespan. Thus, CID is a powerful model to investigate neural networks involving cold acclimation and to explore new ageing mechanisms.

This study aimed to investigate the use of Sucrose acetate isobutyrate (SAIB) and Glyceryl monooleate (GMO) as co-formers for creating Cubosomes and SAIB-based nanodispersions of Rivaroxaban (RXB). The process utilized a modified melt dispersion technique with varying polymer: drug ratios (0.5:1, 0.75:1, and 1:1) and a fixed polymer: poloxamer 407 ratio (0.1:1). Particle size (PS), polydispersity index (PDI), zeta potential (ZP), and entrapment efficiency (EE) were measured to determine the optimal formulas. The best-lyophilized formulas were then analyzed using Fourier transform infrared spectroscopy (FT-IR), powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), dissolution testing, and Pharmacokinetic (PK) studies. The results revealed significant correlations between polymer concentrations and various variables in cubosomal and SAIB-based nanodispersions. An increase in GMO concentration led to a decrease in PS, PDI, and ZP but an increase in EE and yield. Maintaining optimal GMO concentration is crucial for consistent nanoparticle formulations. In contrast, increasing SAIB concentration led to a decrease in PS and PDI but an increase in EE and yield. The drug release rates of different preparations were measured during the dissolution test. The best-lyophilized cubosome (L4) and the best-lyophilized SAIB-based nanodispersions (L8) showed significantly improved drug release compared to XARELTO®. L4 displayed the best dissolution rate, and L8 also had a reasonable rate. A PK study demonstrated that L4 and L8 had significantly better bioavailability than XARELTO®, possibly due to their improved solubility. This study suggests that SAIB and GMO can significantly enhance the solubility and bioavailability of RXB in nano preparations, leading to more efficient drug delivery. This new approach can also reduce the required dosage for the desired therapeutic effect. However, further research is needed to fully understand these polymers' potential benefits and limitations.

IntroductionSpirometry devices, which are components of many anaesthesia machines, are commonly used to assess lung mechanics during anaesthesia. Spirometry calibration usually adheres to manufacturer recommendations without established guidelines. Although more accurate and less variable than inbuilt spirometry in certain General Electric anaesthesia ventilators, near-patient spirometry lacks adequate evaluation.MethodsWe assessed near-patient spirometers’ performance using Pedi-lite and D-lite flow sensors. Certified 1 L calibration syringes were used on 67 monitors located in 14 veterinary hospitals. Three consecutive inspired and expired volume values displayed by the monitors for each volume of the calibration syringe were recorded. Volumes studied were 50, 100, 150, 250, 300 mL for Pedi-lite and 150, 300, 450, 500, 750 mL for D-lite. Measured and targeted volumes were averaged, agreement error calculated. Accuracy was assessed plotting agreement errors against calibration volumes. A linear mixed-effects model was used to obtain linear regression between the error and the calibration volume. Mean, differential and proportional bias, limits of agreement, claimed accuracy and 10% clinical tolerance were calculated and displayed. Differences among monitors were evaluated using the Friedman rank sum test, differences between inspired and expired volumes using the Wilcoxon signed-rank.ResultsInter-monitor variability for inspired and expired volume readings using both sensors was high; intra-monitor variability was low. The error magnitude was independent of volumes evaluated. Using Pedi-lite, only a minority of measurements met manufacturer’s specification or a 10% clinical tolerance; both inspired and expired volumes were significantly underestimated. Using D-lite, superior performance was demonstrated for volumes between 300 and 750 mL (mean biases close to zero and the majority of measurements meeting manufacturer’s specifications and clinical tolerance). The difference between measured inspired and expired volumes with both sensors was significant.DiscussionThese results support caution when interpreting clinical measurements of lung volumes and mechanics in anaesthetised patients when using these sensors. This is particularly important in smaller patients where lung volumes are below 300 mL. Trends should be reliable.

Background Pretreatment computed tomography perfusion parameter relative cerebral blood volume (rCBV) lesion volume has been shown to predict 90‐day modified Rankin Scale score in small‐core strokes with Alberta Stroke Program Early Computed Tomography Score ≥5, including those with medium‐vessel occlusions (mid and distal M2 segment occlusions). Hence, in this study we aim to assess the performance of different rCBV lesion volume thresholds (rCBV

Abstract The boreal winter of 2022/23 was notable as a third consecutive winter in which La Niña had an influence on the European weather. The GloSea6 seasonal forecast system predicted a blocked circulation pattern in the North Atlantic in early winter (December), and then a transition through mid‐winter (January) into a more zonal pattern in late winter (February), consistent with the canonical La Niña teleconnection pattern seen previously. The seasonal forecast for the UK was an increased likelihood of near average temperatures, and drier‐ and calmer‐than‐average conditions. Both the predicted broad‐scale circulation patterns and UK winter mean weather conditions verified well against observations, and we show that seasonal forecasts of the North Atlantic Oscillation (NAO) over the last 10 winters show similar skill to previously reported hindcasts. Throughout the winter, the Madden–Julian Oscillation (MJO) was particularly active. On three occasions, it exhibited strong phases 6 and 7. There was also a sudden stratospheric warming (SSW) that occurred on 16th February. This was followed by colder conditions and associated impacts similar to the canonical negative NAO response over the UK, although the main impact fell in March and so did not affect the winter (December–January–February) mean conditions.

Background Ambient fine particulate matter (PM2.5) exposure adversely impacts child airway health; however, research on prenatal PM2.5 exposure, and child lung function is limited. We investigated these associations in the ECHO-PATHWAYS Consortium, focusing on the role of exposure timing during different phases of fetal lung development.Methods We included 675 children in the CANDLE cohort born between 2007 and 2011 in Memphis, TN, USA. Prenatal exposure to ambient PM2.5 was estimated using a spatiotemporal model based on maternal residential history and averaged over established prenatal periods of lung development. Forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) were measured by spirometry at age 8–9 years. We used linear regression and Bayesian Distributed Lag Interaction Models (BDLIM) to estimate associations between exposure and lung function z-scores, adjusting for maternal/child characteristics, prenatal/postnatal tobacco exposure, and birth year/season, and evaluating effect modification by child sex and allergic sensitization.Results The average ambient concentration of PM2.5 during pregnancy was 11.1 µg/m3 (standard deviation:1.0 µg/m3). In the adjusted linear regression and BDLIM models, adverse, but not statistically significant, associations were observed between exposure during the pseudoglandular (5–16 weeks of gestation) and saccular (24–36 weeks) phases of lung development and FEV1 and FVC. The strongest association was between a 2 μg/m3 higher concentration of PM2.5 during the saccular phase and FEV1 z-score (−0.176, 95% Confidence Interval [CI]: −0.361, 0.010). The FEV1/FVC ratio was not associated with PM2.5 in any exposure window. No effect modification by child sex or allergic sensitization was observed.Conclusions We did not find strong evidence of associations between prenatal ambient PM2.5 exposure and child lung function in a large, well-characterized study sample. However, there was a suggested adverse association between FEV1 and exposure during late pregnancy. The saccular phase of lung development might be an important window for exposure to PM2.5.

The computational thinking to learn sustainability learning progression aided in the development of a striper (Morone saxatilis) fishing project through standardized hook and line practices performed by students and researchers at a small liberal arts University in the Northeast United States. Computational thinking at a simple level supported the intersections of sustainability spheres (environmental and social) and problem-solving concepts (regulation, education and research) toward an interdisciplinary, literature-based framework. The objective of this project was the synthesis of new variables that contributed to Morone saxatilis catch efficiency through the assessment of relationships based on semi standardized angler logs in ways that are appealing and of service to both anglers and researchers as there is a need to bridge these stakeholder groups. The new variables of fish length, structural location, water body location, season, time of day, water temperature, moon phase, wind speed, wind direction and tide all showed some significance in that specific combinations resulted in higher probability of anglers catching striped bass. The findings define the overlap of variables of use to both communities and validate angler knowledge. We present new relationships of highest catch efficiency of our specific locale, including items such as larger fish tended to be caught at dusk, on bridges with low northwest wind during the fall. Implications of these findings provide a foundation of language and shared goals between recreational anglers and the scientific community particularly to support citizen science projects aimed at sustainable fisheries. Implications of bridging these communities include increased knowledge and collaboration on catch variables, appreciation for species specific research endeavors, and trust; all of which directly impact local ecological sustainability.

IntroductionIn clinical practice, evaluating dynamic compliance of the respiratory system (Cdyn) could provide valuable insights into respiratory mechanics. Reference values of Cdyn based on body weight have been reported, but various factors may affect them and the evidence is scanty. This study aimed to establish a reference interval for Cdyn and identify associated variables.MethodsData were collected from 515 client-owned dogs requiring anesthesia, excluding those with lower airway disease. The dogs were anesthetized, the tracheas intubated, and lungs ventilated at clinicians' discretion across 11 centers in six countries, with no restrictions on anesthesia protocols or ventilation settings, except avoiding inspiratory pauses. Three Cdyn measurements from three consecutive breaths per dog were recorded using a standardized form, which also documented factors affecting Cdyn identified through literature and an online survey. Various spirometry technologies were used. The substantial variance in Cdyn measurements led to a comprehensive analysis using a multiple linear regression model. Multicollinearity (variables highly correlated with each other) was addressed by investigating, transforming, or excluding factors. Initial simple linear regression assessed each variable's individual effect on Cdyn, followed by a multiple linear regression model constructed via stepwise forward selection and backward elimination.ResultsThe best-fitting model identified a linear relationship between Cdyn and body mass when the following conditions were met: high BCS (Body Condition Score), orotracheal tubes 80%) exposure for more than 10 minutes before Cdyn measurement. In cases where these conditions were not met, additional factors needed to be incorporated into the model. Low (1/9, 2/9, 3/9) and medium (4/9, 5/9) BCS, an orotracheal tube of the predicted size or larger and longer inspiratory times were associated with increased Cdyn. The use of alternative spirometry sensors, including Ped-lite, or prolonged exposure to high FIO2 levels resulted in decreased Cdyn.Conclusion and clinical relevanceEstablishing a reference interval for Cdyn proved challenging. A single reference interval may be misleading or unhelpful in clinical practice. Nevertheless, this study offers valuable insights into the factors affecting Cdyn in healthy anesthetized dogs, which should be considered in clinical assessments.

The aim of this research was to provide valuable insights on symmetrical α,β-unsaturated ketones as potential chemical ultraviolet (UV) filters from experimental data and theoretical aspects. Towards this end, density functional theory (DFT/B3LYP) calculations on a series of symmetrical α,β-unsaturated ketones, (1E,4E)-1,5-bis[4-(R)phenyl]penta-1,4-diene-3-one (R = methylthio, 1; R = dimethylamino, 2; R = ethyl, 3), were performed to determine the effect of different electron-donating substituents on their stability when exposed to solar UV radiation. Their molecular structures, and UV–visible, infrared (IR) and NMR (1H and 13C) spectra were theoretically obtained from their optimized geometries with the B3LYP/6–311++ G (d, p) basis set and were compared with the experimental results. Conformational analysis was performed and the most stable conformer of each compound was identified as the trans-trans conformer, which was further supported by experimental NMR data. The UV spectra and effect of solvent polarity and proticity were studied by the time-dependent-DFT (TD-DFT) approach with the B3LYP/6–311++G (d, p) level of theory. Furthermore, various molecular parameters like dipole moment, frontier molecular orbital (FMO) energies, ΔEHOMO-LUMO gap, lifetime of the first excited state (τ), global chemical reactivity descriptors, and natural bond orbital analysis were predicted at the same level of theory and compared with the experimental data. Inspection of the active FMOs revealed the photoinstability trends of 1 and 3 under UV irradiation. However, introducing a -N(CH3)2 substituent to 2 at the para-position improves its photostability towards simulated solar UV radiation. Thus, compound 2 has the potential to provide efficient broad-spectrum protection against UV radiation. This work has shown that molecular modelling strategies can assist to rationalize experimental findings and also support the identification of photoproducts of 1 and 3.

Background Acute ischemic stroke arising from medium vessel occlusions (MeVO) poses substantial challenges in treatment and management. This study aims to elucidate the outcomes and factors contributing to achieving excellent recanalization (modified Thrombolysis in Cerebral Infarction [mTICI] 2c–3) versus successful recanalization (mTICI 2b) in patients with MeVO stroke undergoing mechanical thrombectomy (MT). Methods We conducted a multinational study analyzing data from the MAD‐MT (Multicenter Analysis of Distal Medium Vessel Occlusions: Effect of Mechanical Thrombectomy) registry, encompassing 37 centers across North America, Asia, and Europe, collected between September 2017 and July 2023. The study included acute ischemic stroke patients with MeVO treated with MT, with or without intravenous thrombolysis, who achieved mTICI 2b–3 post‐MT. Results Among 1463 patients with successful recanalization (mTICI 2b–3), 523 achieved mTICI 2b recanalization, and 940 achieved mTICI 2c–3. Distal occlusions exhibited higher odds of excellent recanalization compared with proximal MeVO vessel occlusions (odds ratio, 1.58; 95% CI, 1.17–2.15; P = 0.003). Cardioembolic stroke pathogenesis was associated with a higher likelihood of excellent recanalization (1.67; 95% CI, 1.07–2.59; P = 0.018). Patients achieving mTICI 2c–3 recanalization demonstrated lower initial National Institutes of Health Stroke Scale scores, significant improvements in postprocedural National Institutes of Health Stroke Scale shift, and a higher percentage of favorable 90‐day outcomes compared with those with mTICI 2b. However, no significant difference in 90‐day mortality rates was observed. Conclusion This study underscores that among patients with MeVO stroke with successful recanalization (mTICI 2b–3) there is higher likelihood of achieving excellent recanalization (mTICI 2c–3) in distal occlusions and cardioembolic pathogenesis. mTICI 2c–3 scores post‐MT correlate with improved clinical outcomes compared with mTICI 2b, affirming the superiority of excellent recanalization over successful recanalization in patients with MeVO stroke. Further prospective studies and randomized controlled trials are warranted for validation.

Background Flow diversion has emerged as a promising treatment strategy for intracranial aneurysms, yet the influence of antiplatelet therapy on treatment outcomes remains uncertain. Regional and institutional variability in antiplatelet regimens further complicates treatment standardization. This survey aimed to investigate common practices of antiplatelet medication usage in flow diversion for intracranial aneurysms worldwide. Methods An anonymous online survey explored antiplatelet therapy regimens in flow diverter implantations, including agent selection, dosing, and duration. The survey was distributed through international neurointerventional societies and mailing lists. Results Participants included 442 from 53 countries, revealing that most practitioners agree on using dual antiplatelet therapy, with 67% combining low‐dose aspirin with clopidogrel. However, alternative P2Y12 inhibitors are increasingly being used with the main reasons for preferring ticagrelor (21%) over prasugrel (10%) being its availability and bleeding risk, whereas the main reason for using prasugrel over ticagrelor is patient compliance. Resistance testing for antiplatelet agents was conducted by 62% of survey respondents, with the VerifyNow system being the most common method. Strategies to manage resistance included dose escalation (17%) and switching (83%) to alternative agents. Interest in participating in future trials investigating antiplatelet therapy duration and dual antiplatelet therapy versus single antiplatelet therapy was high (77% and 58%, respectively). Conclusion Antiplatelet treatment strategies following flow diversion procedures vary globally, with a growing interest in alternative agents and a willingness to participate in future trials. Standardization efforts and further investigation are warranted for optimizing neurointerventional outcomes.

Objective: Abnormal lipid metabolism in mammalian tissues can be highly deleterious, leading to organ failure. Carnitine Palmitoyltransferase 2 (CPT2) deficiency is an inherited metabolic disorder affecting the liver, heart, and skeletal muscle due to impaired mitochondrial oxidation of long-chain fatty acids (mLCFAO) for energy production. Methods: However, the basis of tissue damage in mLCFAO disorders is not fully understood. Mice lacking CPT2 in skeletal muscle (Cpt2Sk−/−) were generated to investigate the nexus between mFAO deficiency and myopathy. Results: Compared to controls, ex-vivo contractile force was reduced by 70% in Cpt2Sk−/− oxidative soleus muscle despite the preserved capacity to couple ATP synthesis to mitochondrial respiration on alternative substrates to long-chain fatty acids. Increased mitochondrial biogenesis, lipid accumulation, and the downregulation of 80% of dystrophin-related and contraction-related proteins severely compromised the structure and function of Cpt2Sk−/− soleus. CPT2 deficiency affected oxidative muscles more than glycolytic ones. Exposing isolated sarcoplasmic reticulum to long-chain acylcarnitines (LCACs) inhibited calcium uptake. In agreement, Cpt2Sk−/− soleus had decreased calcium uptake and significant accumulation of palmitoyl-carnitine, suggesting that LCACs and calcium dyshomeostasis are linked in skeletal muscle. Conclusions: Our data demonstrate that loss of CPT2 and mLCFAO compromise muscle structure and function due to excessive mitochondrial biogenesis, downregulation of the contractile proteome, and disruption of calcium homeostasis.

Background and purposeEndovascular therapy (EVT) has been used as a standard treatment method for patients with large vessel ischemic stroke within 24 h of the onset. The extent of recanalization after EVT can be assessed using the modified thrombolysis in cerebral infarction (mTICI) scale as an accepted angiographic grading system. In this study, we aimed to investigate whether patients with a mTICI grade of 2b achieve similar outcomes compared to those with complete recanalization (mTICI of 3) following EVT for acute ischemic stroke.MethodsA retrospective analysis was conducted on 196 consecutive patients who underwent EVT in a comprehensive stroke center. In the final study, 176 patients were included based on the inclusion criteria. The primary outcome was the 3-month modified Rankin Scale (mRS) of 0–2 considered as a favorable outcome, while excellent outcomes were defined as mRS scores of 0–1.ResultsOur data showed that 59.46% of patients in the mTICI 2b group achieved a favorable outcome, comparable to 58.99% observed in the mTICI 3 group (p = 0.959). Additionally, 54.05% (n = 37) of patients with mTICI 2b achieved an excellent outcome, compared to 51.80% (n = 139) in the mTICI 3 group (p = 0.807). The case fatality rates were also comparable between the groups, with 8.11% in the mTICI 2b group and 10.79% in the mTICI 3 group (p = 0.632). Overall, there were no statistically significant differences between the two groups in terms of 3-month favorable outcomes, excellent outcomes, or mortality.ConclusionSimilar 3-month outcomes can be achieved for ischemic stroke patients undergoing EVT with a mTICI grade of 2b compared to those with a mTICI grade of 3. These data can help clinicians in setting realistic expectations and making informed decisions during EVT procedures.

Introduction A proportion of people develop Long Covid after acute COVID-19, but with most studies concentrated in high-income countries (HICs), the global burden is largely unknown. Our study aims to characterise long-term COVID-19 sequelae in populations globally and compare the prevalence of reported symptoms in HICs and low-income and middle-income countries (LMICs).Methods A prospective, observational study in 17 countries in Africa, Asia, Europe and South America, including adults with confirmed COVID-19 assessed at 2 to

Purpose To compare outcomes, between stemmed and stemless reverse shoulder arthroplasty (RSA) at a minimum follow-up of 5 years. Methods The authors retrospectively assessed a consecutive series of 45 patients that underwent RSA between September 2014 and October 2018 (23 stemless and 22 stemmed). All patients underwent plain anteroposterior and scapular Y-view radiographs for assessment immediately post-operatively and at final follow-up. At a minimum follow-up of 5 years, an independent observer assessed the clinical scores, including Constant score, QuickDASH score, and American Shoulder and Elbow Surgeons score. Results Of the 45 patients that underwent RSA, 5 patients died (11%), 2 were revised due to infection (4%), and 4 patients were lost to follow-up (9%). This left a final cohort of 34 patients (18 stemless and 16 stemmed). Significant differences between groups were found immediately post-operatively for lateralisation shoulder angle (LSA) (p = 0.021), but at 5 years post-operative for distalisation shoulder angle (DSA) (p = 0.017) and QuickDASH scores (p = 0.041) (Table 4), while the outcomes were comparable for absolute Constant scores, ASES score, and range of motion. Finally, stemless RSA had a 17% complication rate, while stemmed RSA had a 31% complication rate. Conclusion Stemless RSA had significantly more lateralisation, and significantly less distalisation, compared to stemmed RSA. Furthermore, at a 5-year follow-up, stemless RSA granted significantly greater QuickDASH scores. Finally, stemless RSA had comparable complication rates as stemmed RSA. The clinical relevance of this study is that stemless RSA is a safe alternative to stemmed RSA, while granting comparable or greater scores. Level of Evidence: III, Comparative Study

Background Lifelong continuity of care is essential for patients with congenital heart disease (CHD) to maximize health outcomes; unfortunately, gaps in care (GIC) are common. Trends in GIC and of social determinants of health factors contributing to GIC are poorly understood. Methods and Results This retrospective cohort study included patients with CHD, aged 0 to 34 years, who underwent surgery between January 2003 and May 2020, followed up at a pediatric subspeciality hospital. Patients were categorized as having simple, moderate, and complex CHD based on 2018 American Heart Association and American College of Cardiology guidelines. Social determinants of health, such as race, ethnicity, language, insurance status, and Child Opportunity Index, based on home address zip code, were analyzed. Of 2012 patients with CHD, a GIC of ≥3 years was identified in 56% (n=1119). The proportion of patients with GIC per year increased by 0.51% (P

Background: Despite global efforts to improve vaccination coverage, the number of zero-dose and under-immunized children has increased in Africa, particularly in Nigeria, which has over 2.1 million unvaccinated (zero dose) children, the highest in the continent. This scoping review systematically maps and summarizes existing literature on the barriers and facilitators of immunization in Nigeria, focusing on regional inequalities. Methods: A comprehensive search of electronic databases was conducted, encompassing all data from their inception to October 2023, to identify articles on the determinants of routine immunization uptake in Nigeria. Eligible studies were evaluated using predefined criteria, and the data were analyzed and visualized. Results: The results revealed distinct regional variations in factors influencing immunization practices across Nigeria’s six geopolitical zones. Identified barriers include logistical issues, socio-economic factors, cultural influences, and systemic healthcare deficiencies. Key facilitators across multiple zones are health literacy, maternal education, and community leader influence. However, unique regional differences were also identified. In the North-East, significant factors included peer influence, robust reminder systems, provision of additional security, and financial incentives for health facilities. In the North-West, perceived vaccine benefits, fear of non-immunization consequences, urban residence, health literacy, and antenatal care visits were reported as crucial. Perceived benefits of vaccines and trust in healthcare providers were identified as predominant factors in the North-Central zone In the South-East, maternal autonomy, health literacy, and fear of non-immunization consequences were important. In the South-South, peer influence and reminder systems like WhatsApp and SMS were notable, alongside higher maternal education levels. The South-West highlighted maternal autonomy, peer influence, health card usage, high maternal education, and supportive government policies as critical factors. Conclusion: Our findings underscore the need for region-specific interventions that address these unique barriers to improve immunization coverage across Nigeria. Tailored approaches that consider the socio-economic, cultural, and logistical challenges specific to each region are essential to bridge the immunization gap.

The ATP-dependent molecular chaperone, Hsp90, is crucial for the activity of hundreds of client proteins. Several of Hsp90 clients are involved in cancer cell growth and proliferation. Thus, numerous Hsp90 inhibitors have been developed to target Hsp90′s ATPase activity in cancer cells. CCT018159 is a pyrazole-based compound that successfully inhibited Hsp90 oncogenic activity by binding deeply to the ATP binding pocket in the Hsp90 N-terminal domain (N-Hsp90). In the present study, we utilized the CCT018159 structure to identify new potential Hsp90 inhibitors using a set of in-silico approaches. The ZINC database was virtually screened for CCT018159 analogs using the SwissSimilarity webpage. Ten molecules were selected for further investigation based on their drug-likeness, pharmacokinetics, and physiochemical properties. The molecular docking simulation analysis revealed that these ZINC compounds have Ligand Binding Energies (LBEs) ranging from −8.61 to −9.73 Kcal/mol, which reflects a high binding affinity compared to CCT018159 (LBE of −6.31 Kcal/mol). These compounds exhibited diverse interactions, including critical hydrogen bonds and hydrophobic contacts with crucial residues like Asn51, Ala55, and Leu107. Further optimization targeting unique interactions (e.g., ZINC000008973382 with Asp93, Met98, and Thr184) and exploiting the versatile Lys58 could lead to novel, potent anticancer agents targeting Hsp90.

Abstract Well-differentiated liposarcoma (WDLS) displays amplification of genes on chromosome 12 (Chr12) in supernumerary ring or giant marker chromosomes. These structures have been suggested to develop through chromothripsis, followed by circularization and breakage-fusion-bridge (BFB) cycles. To test this hypothesis, we compared WDLSs with Chr12 amplification in rod-shaped chromosomes with WDLSs with rings. Both types of amplicons share the same spectrum of structural variants (SVs), show higher SV frequencies in Chr12 than in co-amplified segments, have SVs that fuse the telomeric ends of co-amplified chromosomes, and lack interspersed deletions. Combined with the finding of cells with transient rod-shaped structures in tumors with ring chromosomes, this suggests a stepwise process starting with the gain of Chr12 material that, after remodeling which does not fit with classical chromothripsis, forms a dicentric structure with other chromosomes. Depending on if and when telomeres from other chromosomes are captured, circularized or linear gain of 12q sequences will predominate.

Abstract YAP and TAZ, the Hippo pathway terminal transcriptional activators, are frequently upregulated in cancers. In tumor cells, they have been mainly associated with increased tumorigenesis controlling different aspects from cell cycle regulation, stemness, or resistance to chemotherapies. In fewer cases, they have also been shown to oppose cancer progression, including by promoting cell death through the action of the p73/YAP transcriptional complex, in particular after chemotherapeutic drug exposure. Using HCT116 cells, we show here that oxaliplatin treatment led to core Hippo pathway down-regulation and nuclear accumulation of TAZ. We further show that TAZ was required for the increased sensitivity of HCT116 cells to oxaliplatin, an effect that appeared independent of p73, but which required the nuclear relocalization of TAZ. Accordingly, Verteporfin and CA3, two drugs affecting the activity of YAP and TAZ, showed antagonistic effects with oxaliplatin in co-treatments. Importantly, using several colorectal cell lines, we show that the sensitizing action of TAZ to oxaliplatin is dependent on the p53 status of the cells. Our results support thus an early action of TAZ to sensitize cells to oxaliplatin, consistent with a model in which nuclear TAZ in the context of DNA damage and p53 activity pushes cells towards apoptosis.

Since 1985 a community of wild Atlantic spotted dolphin (Stenella frontalis) have been observed underwater in the Bahamas. A human-worn, acoustic underwater two-way communication interface was developed and deployed from 2013-2016. Dolphins were exposed to an acoustic referentially based wearable underwater computer/interface. A model/rival system was used with dolphins and human participants during in-water sessions. Artificial and natural objects were labeled with computer generated sounds. Female juvenile spotted dolphins dominated the activity. Group size averaged seven dolphins for an average duration of 37 minute over 58 sessions. Of 243 video audio imitations and 56 Cetacean Hearing Augmentation Telemetry (CHAT) audio imitations, six potential response types were documented and measured. Stand-alone vocal contour mimics and Frequency Modulated Contours were the most common imitations. Within 5 sec of a computer-generated sound playing, of the 191 non-stand-alone vocal responses that were produced, 114 of them (59.7%) were judged as partial accurate matches, 3 of them (1.57%) were judged as non-matching partial imitations of a computer-generated sound, 67 of them (35.08%) were signature whistles, and seven of them (3.67%) were either non-signature whistle vocalizations or a mimic of the start or end tones. Thus, the majority of vocalizations produced by the dolphins within five seconds of a computer-generated sound were partial accurate imitations for the computer-generated sound played. Dolphins demonstrated both immediate and delayed vocal imitation and flexible attempts at imitation but did not show signs of a functional understanding of object labels. Atlantic spotted dolphins showed vocal flexibility in reaction to humans broadcasting computer generated sounds.

Minister of Education, Culture, Research, and Technology Regulation Number 17 of 2021 concerning National Assessment has become the main focus in improving the quality of education in Indonesia. This research aims to examine the implementation of these regulations by conducting a case study at Labuhan Batu State Elementary School. The research method used is descriptive-qualitative, with data collection techniques through observation, interviews, and documentation. The research results show that the implementation of the Ministerial Regulation at the Labuhan Batu State Elementary School has had a positive impact on the national assessment process. Teachers have been able to understand the national assessment guidelines better and integrate them into the school curriculum. Apart from that, the implementation of this regulation also increases awareness of the importance of assessment in improving the quality of learning and evaluation. However, challenges such as the availability of resources and a deep understanding of assessment concepts are still obstacles. This research provides an important contribution to understanding the implementation of Minister of Education Regulation Number 17 of 2021 at the elementary school level, as well as providing input for related parties in efforts to increase the effectiveness of national assessments in the future.

This research aims to determine the role of the sub-district head in improving the performance of village heads in the West Binjai sub-district area and to determine the factors inhibiting the sub-district head in improving the performance of village heads in the West Binjai sub-district area. The results of the research show that the role of the sub-district head in improving the performance of sub-district government officials in the West Binjai area is categorized as good with general implementation including active, participative, and passive roles. The obstacles to improving the performance of village heads are that the quality of resources is still low because most village officials are limited to high school, and junior high school and some have even finished elementary school; village government organizations' regulatory policies are not yet perfect; the arranging limit at the town head level is low; furthermore, the offices and framework supporting functional government organization are still extremely poor. restricted, aside from upsetting the productivity and adequacy of work execution, it additionally can lessen the inspiration of carrying out officials, in this way eventually obstructing the accomplishment of objectives, undertakings, and work.

Digitization in Indonesia has been on the rise since the Covid-19 pandemic, reshaping the lifestyle of the population with a shift from conventional to online shopping. E-commerce transactions, especially through smartphones, offer speed and convenience, making e-commerce the primary intermediary between businesses and consumers. For instance, Traveloka, despite the tourism industry's impact in 2021, remains a key developer, facing the staycation trend for continued transaction growth amid competition. Established in 2012, Traveloka Holding Ltd has successfully secured the top position in the Top Brand Awards. This study, conducted with 111 respondents in the Bekasi Regency, one of the largest metropolis city in the Indonesian capital region, aims to examine the impact of Traveloka's co-creation, currency, communal activation, and conversation on customer loyalty. Customer journey serves as a mediator, while the user interface does not significantly moderate the relationship. The results indicate that each element of the 4C Mix Marketing 4.0 directly contributes to enhancing user loyalty to Traveloka, although the mediating role of the customer journey tends to be low.

Introduction: Air pollution has numerous impacts on human health on a variety of time scales. Pollutants such as particulate matter—PM1 and PM2.5, carbon dioxide (CO2), nitrogen dioxide (NO2), and nitric oxide (NO) are exemplars of the wider human exposome. In this study, we adopted a unique approach by utilizing the responses of human autonomic systems to gauge the abundance of pollutants in inhaled air. Objective: To investigate how the human body autonomically responds to inhaled pollutants in microenvironments, including PM1, PM2.5, CO2, NO2, and NO, on small temporal and spatial scales by making use of biometric observations of the human autonomic response. To test the accuracy in predicting the concentrations of these pollutants using biological measurements of the participants. Methodology: Two experimental approaches having a similar methodology that employs a biometric suite to capture the physiological responses of cyclists were compared, and multiple sensors were used to measure the pollutants in the air surrounding them. Machine learning algorithms were used to estimate the levels of these pollutants and decipher the body’s automatic reactions to them. Results: We observed high precision in predicting PM1, PM2.5, and CO2 using a limited set of biometrics measured from the participants, as indicated with the coefficient of determination (R2) between the estimated and true values of these pollutants of 0.99, 0.96, and 0.98, respectively. Although the predictions for NO2 and NO were reliable at lower concentrations, which was observed qualitatively, the precision varied throughout the data range. Skin temperature, heart rate, and respiration rate were the common physiological responses that were the most influential in predicting the concentration of these pollutants. Conclusion: Biometric measurements can be used to estimate air quality components such as PM1, PM2.5, and CO2 with high degrees of accuracy and can also be used to decipher the effect of these pollutants on the human body using machine learning techniques. The results for NO2 and NO suggest a requirement to improve our models with more comprehensive data collection or advanced machine learning techniques to improve the results for these two pollutants.

Abstract Introduction Previous studies have reported controversial relationships between circulating vascular endothelial growth factors (VEGF) and ischemic stroke (IS). This study aims to demonstrate the causal effect between VEGF and IS using Mendelian randomization (MR). Methods Summary statistics data from two large-scale genome-wide association studies (GWAS) for 16,112 patients with measured VEGF levels and 40,585 patients with IS were downloaded from public databases and included in this study. A published calculator was adopted for MR power calculation. The primary outcome was any ischemic stroke, and the secondary outcomes were large-artery stroke, cardioembolic stroke, and small-vessel stroke. We used the inverse variance-weighted (IVW) method for primary analysis, supplemented by MR-Egger regression and the weighted median method. Results Nine SNPs were included to represent serum VEGF levels. The IVW method revealed no strong causal association between VEGF and any ischemic stroke (odds ratio [OR] 1.01, 95% CI 0.99–1.04, p = 0.39), cardioembolic stroke (OR 1.04, 95% CI 0.97–1.12, p = 0.28), large-artery stroke (OR 1.02, 95% CI 0.95–1.09, p = 0.62), and small-vessel stroke (OR 0.98, 95% CI 0.91–1.04, p = 0.46). These findings remained robust in sensitivity analyses. MR-Egger regression suggested no horizontal pleiotropy. Conclusions This Mendelian randomization study found no relationship between genetically predisposed serum VEGF levels and risks of IS or its subtypes.

Abstract As of 2023, the use of prescribed fire to manage ecosystems accounts for more than 50% of area burned annually across the United States. Prescribed fire is carried out when meteorological conditions, including temperature, humidity, and wind speed are appropriate for its safe and effective application. However, changes in these meteorological variables associated with future climate change may impact future opportunities to conduct prescribed fire. In this study, we combine climate projections with information on prescribed burning windows for ecoregions across the contiguous United States (CONUS) to compute the number of days when meteorological conditions allow for the safe and effective application of prescribed fire under present-day (2006–2015) and future climate (2051–2060) conditions. The resulting projections, which cover 57% of all vegetated area across the CONUS, indicate fewer days with conditions suitable for prescribed burning across ecoregions of the eastern United States due to rising maximum daily temperatures, but opportunities increase in the northern and northwestern United States, driven primarily by rising minimum temperatures and declining wind speeds.

Abstract Introduction The COVID-19 pandemic unveiled huge challenges in health workforce governance in the context of public health emergencies in Africa. Several countries applied several measures to ensure access to qualified and skilled health workers to respond to the pandemic and provide essential health services. However, there has been limited documentation of these measures. This study was undertaken to examine the health workforce governance strategies applied by 15 countries in the World Health Organization (WHO) Africa Region in responding to the COVID-19 pandemic. Methods We extracted data from country case studies developed from national policy documents, reports and grey literature obtained from the Ministries of Health and other service delivery agencies. This study was conducted from October 2020 to January 2021 in 15 countries - Angola, Burkina Faso, Chad, Eswatini, Ghana, Guinea, Guinea Bissau, Ivory Coast, Liberia, Mali, Mauritania, Niger, Nigeria, Senegal and Togo. Results All 15 countries had national multi-sectoral bodies to manage the COVID-19 response and a costed national COVID-19 response plan. All the countries also reflected human resources for health (HRH) activities along the different response pillars. These activities included training for health workers, and budget for the recruitment or mobilization of additional health workers to support the response, and for provision of financial and non-financial incentives for health workers. Nine countries recruited additional 35,812 health workers either on a permanent or temporary basis to respond to the COVID-19 with an abridged process of recruitment implemented to ensure needed health workers are in place on time. Six countries redeployed 3671 health workers to respond to the COVID-19. The redeployment of existing health workers was reported to have impacted negatively on essential health service provision. Conclusion Strengthening multi-sector engagement in the development of public health emergency plans is critical as this promotes the development of holistic interventions needed to improve health workforce availability, retention, incentivization, and coordination. It also ensures optimized utilization based on competencies, especially for the existing health workers.

Abstract Long-read genome sequencing (lrGS) is a promising method in genetic diagnostics. Here we investigate the potential of lrGS to detect a disease-associated chromosomal translocation between 17p13 and the 19 centromere. We constructed two sets of phased and non-phased de novo assemblies; (i) based on lrGS only and (ii) hybrid assemblies combining lrGS with optical mapping using lrGS reads with a median coverage of 34X. Variant calling detected both structural variants (SVs) and small variants and the accuracy of the small variant calling was compared with those called with short-read genome sequencing (srGS). The de novo and hybrid assemblies had high quality and contiguity with N50 of 62.85 Mb, enabling a near telomere to telomere assembly with less than a 100 contigs per haplotype. Notably, we successfully identified the centromeric breakpoint of the translocation. A concordance of 92% was observed when comparing small variant calling between srGS and lrGS. In summary, our findings underscore the remarkable potential of lrGS as a comprehensive and accurate solution for the analysis of SVs and small variants. Thus, lrGS could replace a large battery of genetic tests that were used for the diagnosis of a single symptomatic translocation carrier, highlighting the potential of lrGS in the realm of digital karyotyping.