Miracle-dz/UniFAR-FTUs huggingface dataset:
Genome-wide analysis of Schistosoma mansoni reveals limited population structure and possible praziquantel drug selection pressure within Ugandan hot-spot communities

Populations within schistosomiasis control areas, especially those in Africa, are recommended to receive regular mass drug administration (MDA) with praziquantel (PZQ) as the main strategy for controlling the disease. The impact of PZQ treatment on schistosome genetics remains poorly understood, and is limited by a lack of high-resolution genetic data on the population structure of parasites within these control areas. We generated whole-genome sequence data from 174 individual miracidia collected from both children and adults from fishing communities on islands in Lake Victoria in Uganda that had received either annual or quarterly MDA with PZQ over four years, including samples collected immediately before and four weeks after treatment. Genome variation within and between samples was characterised and we investigated genomic signatures of natural selection acting on these populations that could be due to PZQ treatment. The parasite population on these islands was more diverse than found in nearby villages on the lake shore. We saw little or no genetic differentiation between villages, or between the groups of villages with different treatment intensity, but slightly higher genetic diversity within the pre-treatment compared to post-treatment parasite populations. We identified classes of genes significantly enriched within regions of the genome with evidence of recent positive selection among post-treatment and intensively treated parasite populations. The differential selection observed in post-treatment and pre-treatment parasite populations could be linked to any reduced susceptibility of parasites to praziquantel treatment.
Cross-Cultural Performance Validity Testing: Managing False Positives in Examinees with Limited English Proficiency

ABSTRACT Base rates of failure (BR Fail ) on performance validity tests (PVTs) were examined in university students with limited English proficiency (LEP). BR Fail was calculated for several free-standing and embedded PVTs. All free-standing PVTs and certain embedded indicators were robust to LEP. However, LEP was associated with unacceptably high BR Fail (20–50%) on several embedded PVTs with high levels of verbal mediation (even multivariate models of PVT could not contain BR Fail ). In conclusion, failing free-standing/dedicated PVTs cannot be attributed to LEP. However, the elevated BR Fail on several embedded PVTs in university students suggest an unacceptably high overall risk of false positives associated with LEP.
Dry powder inhalation, part 1: ancient history and precursors to modern dry powder inhalers

ABSTRACT Introduction Inhalation of herbs and other compounds has a long history but habits for medical treatment are intertwined with rituals to obtain hallucinatory effects and pleasurable sensations. Several examples of inhaled herbs, and the diseases they were used for, based on early translations of ancient manuscripts related to inhalation were found to be speculative and inconsistent with each other in literature. They needed to be reconsidered and verified with the original sources of information. Areas covered Examples of ancient inhalation and the development of early dry powder inhalers up to and including the first half of the twentieth century. Databases used for literature about historic events, ancient habits, and ancient science, included SmartCat, JSTOR, and ANDAT; various facts were verified via personal communication with historians and custodians of historic manuscripts and artifacts. Expert opinion Inhalation does not necessarily require active creation of inhalable aerosols, smokes or fumes. Inhaling ‘healthy air’ with volatile and gaseous components, or fine aerosols in pine forests, on volcano slopes and at the seaside must be considered as inhalation therapy too. From this viewpoint, inhalation therapy may have been much more common and widespread and have a longer history than is currently known from written evidence.
Designing drugs when there is low data availability: one-shot learning and other approaches to face the issues of a long-term concern

ABSTRACT Introduction Modern drug discovery is generally accessed by useful information from previous large databases or uncovering novel data. The lack of biological and/or chemical data tends to slow the development of scientific research and innovation. Here, approaches that may help provide solutions to generate or obtain enough relevant data or improve/accelerate existing methods within the last five years were reviewed. Areas covered One-shot learning (OSL) approaches, structural modeling, molecular docking, scoring function space (SFS), molecular dynamics (MD), and quantum mechanics (QM) may be used to amplify the amount of available data to drug design and discovery campaigns, presenting methods, their perspectives, and discussions to be employed in the near future. Expert opinion Recent works have successfully used these techniques to solve a range of issues in the face of data scarcity, including complex problems such as the challenging scenario of drug design aimed at intrinsically disordered proteins and the evaluation of potential adverse effects in a clinical scenario. These examples show that it is possible to improve and kickstart research from scarce available data to design and discover new potential drugs.
A theory-based behavioural change communication intervention to decrease the provision of water to infants under 6 months of age in the Republic of Guinea

Abstract Objective: In many countries, the provision of water in the early months of a baby’s life jeopardises exclusive breast-feeding (EBF). Using a behavioural theory, this study assessed the impact of a behaviour change intervention on mothers’ intention to act and, in turn, on the water provision in addition to breast milk to their infants under 6 months of age (IU6M) in two regions of Guinea. Design: A quasi-experimental design. Data on individual and environmental factors of the theoretical framework, sociodemographic and outcomes were collected using validated questionnaires before and after the intervention. The outcomes examined were the intention to provide water to IU6M, the provision of water and EBF. Path analyses were performed to investigate pathways by which psychosocial and environmental factors influenced the water provision in addition to breast milk. Setting: Four health centres were assigned randomly to each study’s arm (one control/CG and one intervention group/IG per region). Participants: The sample included 300 mothers of IU6M: 150 per group. Results: In IG, the proportion of mothers providing water decreased from 61 % to 29 % before and after the intervention (P < 0·001), while no difference was observed in CG (P = 0·097). The EBF rate increased in IG (from 24·0 % to 53·8 %, P < 0·001) as opposed to CG (36·7 % to 45·9 %, P = 0·107). An association (P < 0·001) between the intention and the behaviour was observed in both groups. Conclusions: An intervention developed using a sound framework reduces the provision of water among IU6M and improves EBF.
The complex interplay between diabetes mellitus and atrial fibrillation

ABSTRACT Introduction A growing body of evidence suggests that diabetes mellitus (DM) is associated with an increased risk of new-onset atrial fibrillation (AF) and contributes to suboptimal arrhythmia control and poor prognosis in patients with AF. The high prevalence of AF among patients with DM is primarily attributed to common risk factors, shared pathophysiological mechanisms, and associated atrial remodeling and autonomic dysfunction. Areas covered This comprehensive review covers the current data on the role of DM in the development and prognosis of AF. In addition, we review the impact of anti-DM medications on AF prevention and the role of anticoagulation in patients with coexisting DM and AF. Expert opinion DM is independently associated with new-onset AF, and the coexistence of these two conditions contributes to poor outcomes, from reduced quality of life to increased risks of thromboembolic events, heart failure, and mortality. Despite this strong link, the current evidence is insufficient to recommend routine screening for AF in patients with DM. Although some observations exist on preventing AF with anti-DM medications, randomized controlled trials are warranted to explore the proposed benefits of novel anti-DM medicines in reducing the risk of incident AF.
Analysis and Prediction of the Survival Trends of Patients with Clear-Cell Renal Cell Carcinoma: A Model-Based Period Analysis, 2001-2015

Background Clear-cell renal cell carcinoma (ccRCC) is one of the most common malignant tumors worldwide whose poor prognosis results in a serious disease burden on patients. The changing trend of the long-term relative survival rates (RSRs) of patients with ccRCC was analyzed in this study to evaluate their treatment results over a 15-year period. Methods This study is a retrospective study, which assessed and predicted the 1-, 3-, and 5-year survival rates of patients with ccRCC during 2001-2005, 2006-2010, 2011-2015, and 2016-2020 using data extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Period analysis was used in this study to analyze the data from the SEER database and to assess survival differences according to age, sex, race, and socioeconomic status (SES) during the 15-year study period by comparing Kaplan-Meier curves. Results During 2001-2015, the 5-year RSR of patients with ccRCC increased from 78.4% to 83.0%, and the generalized linear model predicted that the 5-year RSR increased to 85.7% during 2016-2020. The RSR of patients with ccRCC differed significantly with SES, race, sex, and age. Compared with male patients, the survival advantage of female patients decreased as their age increased. The RSR of all patients with ccRCC was also lower in patients with a lower SES and of black race. Conclusion This study found an improvement in the RSR of patients with ccRCC during 2001-2020. Understanding the change trend of the survival rate of patients with ccRCC is helpful to improve the design of clinical trials. It also provides basic data and a scientific basis for evaluating the harm of ccRCC on the health of affected patients and the effect of cancer prevention, and developing cancer prevention plans.
Blunt force homicides in Denmark 1992–2016

Blunt force trauma is a common homicide method, inflicted in three different ways: bodily force, assault with blunt objects of various types and falls from height. The objective of this study is to provide thorough information on blunt force homicides with data on the victims, the offenders, the surrounding circumstances, the injury methods, the extent of injuries, and survival time, which will help inform the inexperienced as well as the seasoned forensic pathologist in their daily work with death investigation and as expert witnesses in court. We have analyzed autopsy reports and available case files of 311 blunt force homicides, making up 21.9% of all homicides in Denmark during 1992–2016. Most victims and offenders were male. Altercation in the setting of nightlife and intoxication was common in male victims, while most female victims were killed in a domestic setting. Bodily force was the most common primary homicide method, followed by assault with a blunt object and fall from height. The head was the region that most often had external injuries, with no noteworthy difference between cases with bodily force and blunt objects. Two out of three victims had one or more lacerations, most often located on the head and more often on the front. Brain injury was the primary cause of death in at least 72.0% victims. Compared to bodily force victims of blunt object assault were especially prone to skull and brain injuries, had a higher trauma score, and more died at the crime scene and had a shorter survival time.
FKBP4 regulates 5-fluorouracil sensitivity in colon cancer by controlling mitochondrial respiration

FKBP4 controls mitochondrial respiration via modulating COA6-mediated biogenesis and activity of mitochondrial complex IV, thereby regulating 5-fluorouracil sensitivity in colon cancer. Mitochondrial respiration and metabolism play a key role in the pathogenesis and progression of colon adenocarcinoma (COAD). Here, we report a functional pool of FKBP4, a co-chaperone protein, in the mitochondrial intermembrane space (IMS) of colon cancer cells. We found that IMS-localized FKBP4 is essential for the maintenance of mitochondrial respiration, thus contributing to the sensitivity of COAD cells to 5-fluorouracil (5-FU). Mechanistically, FKBP4 interacts with COA6 and controls the assembly of the mitochondrial COA6/SCO1/SCO2 complex, thereby governing COA6-regulated biogenesis and activity of mitochondrial cytochrome c oxidase (complex IV). Thus, our data reveal IMS-localized FKBP4 as a novel regulator of 5-FU sensitivity in COAD, linking mitochondrial respiration to 5-FU sensitivity in COAD.
T2DM patients with depression have higher levels of hyperglycemia and cognitive decline than T2DM patients

The cognitive impairment, depression, a decrease in the ability to perform activities of daily living (ADLs), and salivary gland dysfunction, as indicated by the reduction of alpha-amylase activity, have been reported in patients with type 2 diabetes (T2DM). However, the effects of depression on cognitive function, salivary alpha-amylase activity, and ADLs in T2DM patients have never been investigated. In this study, 115 participants were divided into three groups, including 30 healthy people, 50 T2DM patients without depression, and 35 T2DM patients with depression. Then, the cognitive function, the level of depression, salivary-alpha amylase activity, ADLs, and metabolic parameters were determined. Results showed that T2DM patients had hyperglycemia and cognitive impairment. A decrease in the salivary alpha-amylase activity was observed in T2DM patients. Interestingly, T2DM patients with depression had higher level of hyperglycemia and cognitive impairment than T2DM patients. Additionally, cognitive function was associated with the salivary-alpha amylase activity in T2DM without depression, while the severity of depression was associated with the salivary-alpha amylase activity in T2DM patients with depression. Therefore, we concluded that T2DM caused the impairment of metabolism, decreased salivary alpha-amylase activity, and cognitive impairment. Furthermore, T2DM patients with depression had higher level of hyperglycemia and cognitive decline than T2DM patients.
Global Transformer and Dual Local Attention Network via Deep-Shallow Hierarchical Feature Fusion for Retinal Vessel Segmentation

Clinically, retinal vessel segmentation is a significant step in the diagnosis of fundus diseases. However, recent methods generally neglect the difference of semantic information between deep and shallow features, which fail to capture the global and local characterizations in fundus images simultaneously, resulting in the limited segmentation performance for fine vessels. In this article, a global transformer (GT) and dual local attention (DLA) network via deep-shallow hierarchical feature fusion (GT-DLA-dsHFF) are investigated to solve the above limitations. First, the GT is developed to integrate the global information in the retinal image, which effectively captures the long-distance dependence between pixels, alleviating the discontinuity of blood vessels in the segmentation results. Second, DLA, which is constructed using dilated convolutions with varied dilation rates, unsupervised edge detection, and squeeze-excitation block, is proposed to extract local vessel information, consolidating the edge details in the segmentation result. Finally, a novel deep-shallow hierarchical feature fusion (dsHFF) algorithm is studied to fuse the features in different scales in the deep learning framework, respectively, which can mitigate the attenuation of valid information in the process of feature fusion. We verified the GT-DLA-dsHFF on four typical fundus image datasets. The experimental results demonstrate our GT-DLA-dsHFF achieves superior performance against the current methods and detailed discussions verify the efficacy of the proposed three modules. Segmentation results of diseased images show the robustness of our proposed GT-DLA-dsHFF. Implementation codes will be available on https://github.com/YangLibuaa/GT-DLA-dsHFF.
Young South Asian women in the United Kingdom show evidence of blunted endothelium-dependent dilatation: implications for future cardiovascular disease

Introduction: Prevalence of cardiovascular disease (CVD) is higher in South Asians than white Europeans. The offspring of hypertensive parents (OH) have greater risk of hypertension than offspring of normotensive parents (ON). We hypothesized that endothelium-dependent dilatation is already blunted in young South Asians, relative to young white European women, particularly in South Asian OH women. Methods: In young white European ON, South Asian ON and OH women (18–25 years old; 10 per group) who were normotensive, we recorded cutaneous perfusion by laser Doppler fluximetry during reactive hyperaemia and iontophoresis of acetylcholine (ACh), before and after inhibiting NO synthesis (NOS) or/and cyclooxygenase (COX). In these and an additional 135 age-matched South Asian and white European women, physical activity and life-style factors were assessed by questionnaire. Results: ACh-evoked dilatation was blunted in young South Asians, relative to white European women. It was attenuated by NOS or COX inhibition in white European ON; by NOS inhibition only in South Asian ON, but not OH women. After combined NOS and COX inhibition, ACh-evoked dilatations were similar to control ACh responses. Similar findings were made for reactive hyperaemia. Questionnaire data indicated young South Asians have lower physical activity levels, fresh fruit and vegetable intake than white European women, South Asian OH being lower than white European ON, or OH women. Conclusion: Endothelium-dependent dilatation is blunted in young South Asians, relative to white European women, especially in South Asian OH in whom NO-dependent and prostaglandin-dependent dilatation is blunted. We suggest improved diet and greater physical activity could be particularly effective in improving endothelium-dependent dilatation and reducing future CVD risk in young South Asian OH women.
Change in Seizure Incidence in Febrile Children With COVID-19 in the Era of Omicron Variant of Concern.

In this single-center retrospective observational study, we report that the incidence of seizures in febrile children with COVID-19 was significantly higher in the Omicron era than in the pre-Omicron era (14.6% vs 1.7%, P < .001). One-third of the cases in the Omicron era were older than 5 years.
Typhoid fever control in the 21st century: where are we now?

Purpose of review Momentum for achieving widespread control of typhoid fever has been growing over the past decade. Typhoid conjugate vaccines represent a potentially effective tool to reduce the burden of disease in the foreseeable future and new data have recently emerged to better frame their use-case. Recent findings We describe how antibiotic resistance continues to pose a major challenge in the treatment of typhoid fever, as exemplified by the emergence of azithromycin resistance and the spread of Salmonella Typhi strains resistant to third-generation cephalosporins. We review efficacy and effectiveness data for TCVs, which have been shown to have high-level efficacy (≥80%) against typhoid fever in diverse field settings. Data from randomized controlled trials and observational studies of TCVs are reviewed herein. Finally, we review data from multicountry blood culture surveillance studies that have provided granular insights into typhoid fever epidemiology. These data are becoming increasingly important as countries decide how best to introduce TCVs into routine immunization schedules and determine the optimal delivery strategy. Summary Continued advocacy is needed to address the ongoing challenge of typhoid fever to improve child health and tackle the rising challenge of antimicrobial resistance.
Preliminary validation of the Norwegian version of misophonia questionnaire (MQ-NOR)

Abstract Objective To perform a psychometric validation of a Norwegian version of the Misophonia Questionnaire (MQ-NOR) and to test the link between the personality trait neuroticism and misophonia assessed with the MQ-NOR. Design Participants completed online versions of the MQ-NOR on two occasions about two weeks apart and the neuroticism scale from BFI-20. Study sample Two-hundred and twenty-seven (T1) and 173 (T2) participants with self-reported misophonia. Results The MQ-NOR was found to comprise two factors: Symptom Scale and Emotions and Behaviours Scale. Overall, the MQ-NOR evidenced good internal consistency and test-retest reliability. Regression analyses supported a positive relationship between misophonia and neuroticism that was moderated by participant age, but not gender. Conclusion The MQ-NOR demonstrates good psychometric properties, but until more extensively validated, it is cautiously recommended for use by clinicians in Norway to assessing misophonia. Future validation studies should be carried out.
Elevated risk of acute epiglottitis in patients with chronic obstructive pulmonary disease: A nationwide cohort study

Objective In individuals with epiglottitis, chronic obstructive pulmonary disease (COPD) is a common comorbidity; however, the impact of COPD under such circumstances is not well documented. Therefore, we performed this population-based study to determine whether, in adults, COPD is a risk factor for epiglottitis. Methods In this retrospective matched-cohort study, data obtained from the Taiwan National Health Insurance Research Database were analyzed. We identified all patients newly diagnosed as having COPD in 2000–2011 and performed frequency matching and propensity-score matching for every patient with COPD individually to another patient without a COPD diagnosis. We used epiglottitis occurrence as the study endpoint, and we investigated the hazard ratio of epiglottitis by using the Cox proportional hazards model after adjustment for potential confounders. Results In the frequency matching, the cumulative epiglottitis incidence was significantly higher (p = 0.005) in the COPD cohort. According to the adjusted Cox proportional hazard model, COPD exhibited a significant association with elevated epiglottitis incidence (adjusted hazard ratio: 1.76; 95% confidence interval: 1.15–2.70, p = 0.009). Similar trend was observed in the propensity-score matching analysis (adjusted hazard ratio: 1.50; 95% confidence interval: 0.99–2.29, p = 0.057). Our subgroup analysis revealed COPD to be an epiglottitis risk factor in male patients and those aged 40–64 years. Conclusions This is the first nationwide matched-cohort research to examine the association of COPD with epiglottitis. Our results revealed that COPD may be a potential risk factor for epiglottitis; thus, clinicians should be mindful of the potential increased risk of epiglottitis following COPD.