Miracle-dz/UniFAR-FTUs huggingface dataset:
Active close contact investigation of tuberculosis through computer-aided detection and stool Xpert MTB/RIF among people living in Oromia Region, Ethiopia (CADOOL Study): protocol for a prospective, cross-sectional study

Introduction Pulmonary tuberculosis (TB) is an infectious disease with high incidence in low-income countries (LICs); it remains one of the infectious diseases with the highest mortality in the world, especially in LICs. It is crucial to recognise and diagnose TB as soon as possible, but microbiological tests on sputum are not always sensitive enough. New methods for an early diagnosis of TB are needed. In this study, we will investigate the role of two different tests to detect TB in Ethiopia (where the prevalence of TB is high): molecular search for TB in stool samples with Xpert assay and detection of pulmonary TB signs on chest X-rays with CAD4TB technology. Methods and analysis A prospective diagnostic test accuracy study during TB active contact investigation will be conducted. In the referral hospital in Southwest Shoa Zone, Oromia Region, Ethiopia, patients with pulmonary TB and a sputum sample positive for Mycobacterium tuberculosis and household contacts of at least 4 years of age will be enrolled, with a target sample size of 231 patients. Trained staff will label household contacts as ‘possible TB’ cases or not according to their symptoms; when TB is possible, a stool Xpert and computer-aided detection on chest X-ray will be performed, alongside standard diagnostic methods, assessing the diagnostic accuracy of CAD4TB compared with Xpert MTB/RIF during TB contact investigation and the accuracy of stool Xpert compared with sputum Xpert. Ethics and dissemination This study has been approved by the Oromia Health Bureau Research Ethics Committee (ref no BFO/MBTFH/1-16/100023). All information obtained will be kept confidential. Selected investigators will have access to data, while international partners will sign a dedicated data protection agreement. Eligible participants will receive brief information about the study before being asked to participate and they will provide written informed consent. Results will be disseminated through peer-reviewed journals. Trial registration number NCT05818059.
The Disease Severity Index for Inflammatory Bowel Disease Is a Valid Instrument that Predicts Complicated Disease.

BACKGROUND The disease severity index (DSI) for inflammatory bowel disease (IBD) combines measures of disease phenotype, inflammatory activity, and patient-reported outcomes. We aimed to validate the DSI and assess its utility in predicting a complicated IBD course. METHODS A multicenter cohort of adults with IBD was recruited. Intraclass correlation coefficients (ICCs) and weighted Kappa assessed inter-rater reliability. Cronbach's alpha measured internal consistency of DSI items. Spearman's rank correlations compared the DSI with endoscopic indices, symptom indices, quality of life, and disability. A subgroup was followed for 24 months to assess for a complicated IBD course. Area under the receiver operating characteristics curve (AUROC) and multivariable logistic regression assessed the utility of the DSI in predicting disease progression. RESULTS Three hundred and sixty-nine participants were included (Crohn's disease [CD], n = 230; female, n = 194; mean age, 46 years [SD, 15]; median disease duration, 11 years [interquartile range, 5-21]), of which 171 (CD, n = 99; ulcerative colitis [UC], n = 72) were followed prospectively. The DSI showed inter-rater reliability for CD (ICC 0.93, n = 65) and UC (ICC 0.97, n = 33). The DSI items demonstrated inter-rater agreement (Kappa > 0.4) and internal consistency (CD, α > 0.59; UC, α > 0.75). The DSI was significantly associated with endoscopic activity (CDn=141, r = 0.65, P < .001; UCn=105, r = 0.80, P < .001), symptoms (CDn=159, r = 0.69, P < .001; UCn=132, r = 0.58, P < .001), quality of life (CDn=198, r = -0.59, P < .001; UCn=128, r = -0.68, P < .001), and disability (CDn=83, r = -0.67, P < .001; UCn=52, r = -0.74, P < .001). A DSI of 23 best predicted a complicated IBD course (AUROC = 0.82, P < .001) and was associated with this end point on multivariable analyses (aOR, 9.20; 95% confidence interval, 3.32-25.49). CONCLUSIONS The DSI reliably encapsulates factors contributing to disease severity and accurately prognosticates the longitudinal IBD course.
Does mixing inhaler devices lead to unchecked inhaler technique errors in patients with COPD? Findings from the cross-sectional observational MISMATCH study

Background Patients with chronic obstructive pulmonary disease (COPD) may be prescribed multiple inhalers that require different techniques for optimal performance. Mixing devices has been associated with poorer COPD outcomes suggesting that it leads to inappropriate inhaler technique. However, empirical evidence is lacking. Aims Compare the nature and frequency of dry powder inhaler (DPI) technique errors in patients with COPD using (1) a single DPI or (2) mixed-devices (a DPI and pressurised metered dose inhaler (pMDI)). Methods Data from the PIFotal study—a cross-sectional study on Peak Inspiratory Flow in patients with COPD using a DPI as maintenance therapy, capturing data from 1434 patients on demographic characteristics, COPD health status and inhaler technique—were used to select 291 patients using mixed-devices. Frequency matching based on country of residence and DPI device type was used to select 291 patients using a DPI-only for comparison. Predetermined checklists were used for the evaluation of DPI video recordings and complemented with additional errors that were observed in ≥10%. Error proportions were calculated for the (1) individual and total number of errors, (2) number of critical errors and (3) number of pMDI-related errors. Results The study sample contained 582 patients (mean (SD) age 69.6 (9.4) years, 47.1% female). DPI technique errors were common, but not significantly different between the groups. The majority of patients made at least one critical error (DPI-only: 90.7% vs mixed-devices: 92.8%). Proportions of total, ‘pMDI-related’ and critical errors did not significantly differ between the groups. Conclusion The nature and frequency of inhaler technique errors did not substantially differ between patients prescribed with a single DPI and mixed-devices. Currently, ‘pMDI-related errors’ in DPI use are not accounted for in existing checklists. Trial registration number ENCEPP/EUPAS48776.
Prevalence of SARS‐CoV‐2 in domestic cats (Felis catus) during COVID‐19 pandemic in Latvia

Abstract Background The causative agent of the COVID‐19 pandemic, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), is of zoonotic origin and has shown reverse zoonotic transmissibility. Objectives The aim of this cross‐sectional study was to investigate the serological and molecular prevalence of SARS‐CoV‐2 infection in the domestic cat (Felis catus) population from Latvia in natural conditions and subsequently perform viral genome analysis. Methods Oropharyngeal and rectal swabs and blood samples were collected from 273 domestic cats during the second wave of COVID‐19 infection in Latvia. Molecular prevalence was determined by using reverse transcriptase‐polymerase chain reaction (RT‐PCR). Serum samples were analysed via double antigen enzyme‐linked immunosorbent assay targeting the antibody against the nucleocapsid protein of SARS‐CoV‐2. Positive swab samples were analysed using whole viral genome sequencing and subsequent phylogenetic analysis of the whole genome sequencing data of the samples was performed. Results The overall SARS‐CoV‐2 RT‐PCR positivity and seroprevalence was 1.1% (3/273) and 2.6% (7/273), respectively. The SARS‐CoV‐2 genome sequences from three RT‐PCR positive cats were assigned to the three common lineages (PANGOLIN lineage S.1.; B.1.177.60. and B.1.1.7.) circulating in Latvia during the particular period of time. Conclusions These findings indicate that feline infection with SARS‐CoV‐2 occurred during the second wave of the COVID‐19 pandemic in Latvia, yet the overall prevalence was low. In addition, it seems like no special ‘cat’ pre‐adaptations were necessary for successful infection of cats by the common lineages of SARS‐CoV‐2.
Human-wildlife conflict and mobile phone use among Maasai pastoralists near Tarangire National Park, northern Tanzania

Mobile phones are transforming many aspects of rural areas in the developing world. Much of the early research on phones and related information and communication technologies (ICTs) in developing countries has focused on social networking and economic benefits in primarily urban or agricultural settings. Few studies, however, have examined the implications of mobile technologies on pastoralist livelihoods and biodiversity conservation. To build on this opportunity, this study examines the impact of mobile phone technology on four Maasai communities near Tarangire National Park in northern Tanzania. I asked the questions: (1) How do phones affect human-wildlife interactions? ; and (2) What are the effects of mobile phone use on measures of human-wildlife conflict (HWC)? This research uses a mixed methods approach to address these two questions and test the hypothesis that mobile phone use reduces HWC. Qualitative group interviews revealed that households use phones to manage wildlife interactions in every aspect of their lives especially when the interactions relate to pastoralism and cropbased agriculture. Maasai use mobile phones as tools of information distribution to mitigate and reduce the severity of effects of HWC. Multivariate analyses of survey measures of phone use and exposure to conflict (i.e., crop and livestock predation and human attacks) offer mixed evidence that mobile phone use is correlated with a perception of less recent HWC events. These findings provide an indication that the expansion of mobile digital technologies may be able to support livelihoods and biodiversity simultaneously.
Prediction of Flood Levels Along a Stretch of the Langat River with Insufficient Hydrological Data

Malaysia is a tropical country and it is subjected to flooding in both the urban and rural areas. Flood modelling can help to reduce the impacts of flood hazard by taking extra precautions. HEC-RAS model was used to predict the flood levels at selected reach of the Langat River with a total length of 34.4 km. The Langat River is located in the state of Selangor, Malaysia and it is subjected to regular flooding. The selected reach of the Langat River has insufficient data and a methodology was proposed to overcome this particular problem. Since complete floodplain data for the area are not available, the modelling therefore assumed vertical walls at the left and right banks of the Langat River and all the predicted flood levels above the banks were based on this assumption. The HEC-RAS model was calibrated and the values of Manning's coefficients of roughness for the Langat River were found to range from 0.04 to 0.10. The discharge values were calculated for 5, 10, 25, 50, and 100 year return periods and the maximum predicted flood depth ranged from 2.1m to 7.8m. Meanwhile, the model output was verified using the historical record and the error between the recorded and predicted water levels was found to range from 3% to 15%.
Sharp Detection of Event’s Onset in Seismic Signals With Asymmetrical Kaiser Window-Based S-Transform

The S-transform (ST) is a commonly used tool for time–frequency (TF) localization. It uses scalable Gaussian kernel for multiresolution analysis. It is widely used for the analysis of seismic signals. However, the long taper of the Gaussian window results in the degradation of the time resolution at lower frequencies and, hence, lowers its effectiveness in reliable detection of onset of events. This letter proposes an asymmetrical Kaiser window-based ST that provides better time resolution in the forward direction which facilitates sharp detection of events in seismic signals. The inherent optimal energy concentration characteristics of the Kaiser window provide better TF localization compared to existing approaches. The window parameters are also generalized to provide frequency-dependent asymmetry while avoiding unwanted degradation of frequency resolution at higher frequencies. The efficacy of the proposed approach is illustrated by testing it with a synthetic seismic trace and a real noisy seismograph. Simulation results illustrate the improvement in time resolution with the proposed approach as compared to other asymmetrical window-based STs for the detection of event’s onset.
Neoproterozoic alkaline intrusive complex in the northwestern Yangtze Block, Micang Mountains region, South China: petrogenesis and tectonic significance

ABSTRACT Voluminous Neoproterozoic mafic–ultramafic, felsic, and alkaline intrusions are found in the northern Yangtze Block, South China. Here, we present whole-rock major and trace element, and Sr–Nd isotopic compositions, together with zircon U–Pb ages, for syenite and gabbro samples from the Shuimo–Zhongziyuan alkaline intrusive complex in the Micang Mountains region at the northwestern margin of the Yangtze Block. Zircon U–Pb dating yields crystallization ages for the Na- and K-rich Shuimo syenites of 869 ± 4 (MSWD = 0.85, 2σ) and 860 ± 5 Ma (MSWD = 0.47, 2σ), respectively, and for the Zhongziyuan gabbros of 753 ± 4 Ma (MSWD = 0.23, 2σ), indicating that the syenites and gabbros represent different stages of magmatism. The syenites include both Na- and K-rich types and have high values of the Rittman index (σ), and high SiO2 and Na2O + K2O contents. These syenites are enriched in light rare earth elements (LREE) and large-ion lithophile elements (LILE), but depleted in high-field-strength elements (HFSE), with high (La/Yb)N values and small negative and positive Eu anomalies (Eu/Eu* = 0.74–1.17). In contrast, the gabbros have lower SiO2 and Na2O + K2O contents, are only slightly enriched in LREEs, are enriched in LILE but depleted in HFSEs, and have small negative and positive Eu anomalies (Eu/Eu* = 0.86–1.37). The syenites have low initial 87Sr/86Sr (0.703340) and ɛNd(t) values (+1.9 to +7.7). The gabbros have relatively high initial 87Sr/86Sr (0.703562–0.704933) and positive ɛNd(t) values (+1.6 to +4.5). These data suggest that the syenites and gabbros are isotopically similar and were largely derived from melts of depleted mantle. The syenites underwent significant fractional crystallization and small amounts of crustal contamination during magma evolution. In contrast, the gabbros were formed by partial melting (>15%) of a garnet lherzolite source and might also have experienced crustal assimilation. Taking into account the geochemical signatures and magmatic events, we propose that the Shuimo syenites formed in an intra-arc rifting setting, however, the Zhongziyuan gabbros were most likely produced in a subduction-related, continental margin arc setting during the Neoproterozoic, thus suggesting that the alkaline intrusive complex were formed by the arc-related magmatism in the Micang Mountains.
Viscous Loading Regulates the Flagellar Energetics of Human and Bull Sperm.

The viscoelastic properties of the female reproductive tract influence sperm swimming behavior, but the exact role of these rheological changes in regulating sperm energetics remains unknown. Using high-speed dark-field microscopy, the flagellar dynamics of free-swimming sperm across a physiologically relevant range of viscosities is resolved. A transition from 3D to 2D slither swimming under an increased viscous loading is revealed, in the absence of any geometrical or chemical stimuli. This transition is species-specific, aligning with viscosity variations within each species' reproductive tract. Despite substantial drag increase, 2D slithering sperm maintain a steady swimming speed across a wide viscosity range (20-250 and 75-1000 mPa s for bull and human sperm) by dissipating over sixfold more energy into the fluid without elevating metabolic activity, potentially by altering the mechanisms of dynein motor activity. This energy-efficient motility mode is ideally suited for the viscous environment of the female reproductive tract.
Behavioral Validation of Individualized Low-Intensity Transcranial Electrical Stimulation (tES) Protocols

Abstract Large interindividual variability in the effects of low-intensity transcranial electrical stimulation (tES) considerably limits its potential for clinical applications. It has been recently proposed that individualizing stimulation dose by accounting for interindividual anatomic differences would reduce the variability in electric fields (E-fields) over the targeted cortical site and therefore produce more consistent behavioral outcomes. However, improvement in behavioral outcomes following individualized dose tES has never been compared with that of conventional fixed dose tES. In this study, we aimed to empirically evaluate the effect of individualized dose tES on behavior and further compare it with the effects of sham and fixed dose stimulations. We conducted a single-blinded, sham-controlled, repeated-measures study to examine the impact of transcranial direct current stimulation on motor learning and that of transcranial alternating current stimulation on the working memory of 42 healthy adult individuals. Each participant underwent three sessions of tES, receiving fixed dose, individualized dose, or sham stimulation over the targeted brain region for the entire behavioral task. Our results showed that the individualized dose reduced the variability in E-fields at the targeted cortical surfaces. However, there was no significant effect of tES on behavioral outcomes. We argue that although the stimulation dose and E-field intensity at the targeted cortical site are linearly correlated, the effect of E-fields on behavior seems to be more complex. Effective optimization of tES protocols warrants further research considering both neuroanatomical and functional aspects of behavior.
Cross‐sectional associations between sedentary time with cognitive engagement and brain volume among community‐dwelling vulnerable older adults

Vulnerable older adults tend to decrease physical activity (PA) and increase sedentary time (ST). Previous research on the associations between ST and brain volume have yielded inconsistent findings, without considering the impact of cognitive engagement (CE) on cognitive function. We aimed to examine the association between ST with CE and brain volume.
Analysis of maternal and child health spillover effects in PEPFAR countries

Objectives This study examined whether the US President’s Emergency Plan for AIDS Relief (PEPFAR) funding had effects beyond HIV, specifically on several measures of maternal and child health in low-income and middle-income countries (LMICs). The results of previous research on the question of PEPFAR health spillovers have been inconsistent. This study, using a large, multicountry panel data set of 157 LMICs including 90 recipient countries, adds to the literature. Design Seven indicators including child and maternal mortality, several child vaccination rates and anaemia among childbearing-age women are important population health indicators. Panel data and difference-in-differences estimators (DID) were used to estimate the impact of the PEPFAR programme from inception in 2004 to 2018 using a comparison group of 67 LMICs. Several different models of baseline (2004) covariates were used to help balance the comparison and treatment groups. Staggered DID was used to estimate impacts since all countries did not start receiving aid at PEPFAR’s inception. Setting All 157 LMICs from 1990 to 2018. Participants 90 LMICs receiving PEPFAR aid and cohorts of those countries, including those required to submit annual country operational plans (COP), other recipient countries (non-COP), and three groupings of countries based on cumulative amount of per capita aid received (high, medium, low). Interventions PEPFAR aid to combat the HIV epidemic. Primary outcome measures Maternal mortality and child mortality rates, vaccination rates to protect children for diphtheria, whooping cough and tetanus, measles, HepB3, and tetanus, and prevalence of anaemia in women of childbearing age. Results Across PEPFAR recipient countries, large, favourable PEPFAR health effects were found for rates of childhood immunisation, child mortality and maternal mortality. These beneficial health effects were large and significant in all segments of PEPFAR recipient countries studied. We also found significant and favourable programme effects on the prevalence of anaemia in women of childbearing age in PEPFAR recipient countries receiving the most intensive financial support from the PEPFAR programme. Other recipient countries did not demonstrate significant effects on anaemia. Conclusions This study demonstrated that important health indicators, beyond HIV, have been consistently and favourably influenced by PEPFAR presence. Child and maternal mortality have been substantially reduced, and childhood immunisation rates increased. We also found no evidence of ‘crowding out’ or negative spillovers in these resource-poor countries. These findings add to the body of evidence that PEPFAR has had favourable health effects beyond HIV. The implications of these findings are that foreign aid for health in one area may have favourable health effects in other areas in recipient countries. More research is needed on the influence of the mechanisms at work that create these spillover health effects of PEPFAR.
Natural Products Inhibition of CYP2B6 Activity and Methadone Metabolism.

Methadone is cleared predominately by hepatic CYP2B6-catalyzed metabolism to inactive metabolites. CYP2B6 also catalyzes the metabolism of several other drugs. Methadone and CYP2B6 are susceptible to pharmacokinetic drug-drug interactions. Use of natural products such as herbals and other botanicals is substantial and growing, concomitant use of prescription medicines and non-prescription herbals is common and may result in interactions, often precipitated by CYP inhibition. Little is known about herbal product effects on CYP2B6 activity, and CYP2B6-catalyzed methadone metabolism. We screened a family of natural product compounds used in traditional medicines, herbal teas, and synthetic analogs of compounds found in plants, including kavalactones, flavokavains, chalcones and gambogic acid, for inhibition of expressed CYP2B6 activity and specifically inhibition of CYP2B6-mediated methadone metabolism. An initial screen evaluated inhibition of CYP2B6-catalyzed 7-ethoxy-4-(trifluoromethyl) coumarin O-deethylation. Hits were further evaluated for inhibition of racemic methadone metabolism, including mechanism of inhibition and kinetic constants. In order of decreasing potency, the most effective inhibitors of methadone metabolism were dihydromethysticin (competitive, K i 0.074 µM), gambogic acid (noncompetitive, K i 6 µM), and 2,2'-dihydroxychalcone (noncompetitive, K i 16 µM). Molecular modeling of CYP2B6-methadone and inhibitor binding showed substrate and inhibitor binding position and orientation and their interactions with CYP2B6 residues. These results show that CYP2B6 and CYP2B6-catalyzed methadone metabolism are inhibited by certain natural products, at concentrations which may be clinically relevant. Significance Statement This investigation identified several natural product constituents which inhibit in vitro human recombinant CYP2B6 and CYP2B6-catalyzed N-demethylation of the opioid methadone. The most potent inhibitors (K i) were dihydromethysticin (0.074 µM), gambogic acid (6 µM) and 2,2'-dihydroxychalcone (16 µM). Molecular modeling of ligand interactions with CYP2B6 found that dihydromethysticin and 2,2'-dihydroxychalcone bound at the active site, while gambogic acid interacted with an allosteric site on the CYP2B6 surface. Natural product constituents may inhibit CYP2B6 and methadone metabolism at clinically relevant concentrations.