bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variation in prescription duration for long term conditions: a cohort study in English NHS primary care using OpenPrescribing
Authors: MacKenna Brian , Brown Andrew D , Croker Rich , Walker Alex J , Tsiachristas Apostolos , Evans Dave , Inglesby Peter , Goldacre Ben , Bacon Seb , Curtis Helen J 
Published: May 2024

AbstractBackgroundMany patients receive routine medications for long-term conditions (LTCs). Doctors typically issue repeat prescriptions in one to three month durations, but England currently has no national guidance on the optimal duration.MethodsWe calculated the duration of prescriptions for common LTCs in England over a 12-month period (December 2018-November 2019). We assessed the level of variation between regional clinical commissioning groups (CCGs) and determine practice factors associated with different durations.ResultsOf the common medications included, 28-day (one-monthly) prescriptions accounted for 48.5% (2.5 billion) tablets/capsules issued. There was very wide regional variation in the proportion of 28-day prescriptions (7.2% to 95.0%). Practice dispensing status was the most likely predictor of prescription duration. The proportion of patients with LTCs and the electronic health record software used by a practice were also associated with prescription duration.ConclusionsOne month prescription durations are common for patients taking medicines routinely for long term conditions, particularly in dispensing practices. Electronic health record configurations offer an opportunity to implement and evaluate new policies on repeat prescription duration in England.
The effect of mentorship as a means of strengthening leadership in the health system at the operational level: a case study of the Walungu rural health zone in the eastern Democratic Republic of Congo
Authors: Bigirinama Rosine , Bisimwa Ghislain , Makali Samuel , Cikomola Aimé , Barhobagayana Janvier , Lembebu Jean-Corneille , Chiribagula Christian , Mwene-Batu Pacifique , Mukalay Abdon , Porignon Denis , Tambwe Albert 
Published: May 2024

AbstractContextIn the rural Health Zone (HZ) of Walungu, eastern Democratic Republic of Congo, major constraints impede health outcomes. From 2015 to 2019, the “RIPSEC” program transformed Walungu into a Learning and Research Zone (LRZ) under the mentorship of a local university to enhance the leadership capabilities of HZ managers, focusing on managing challenges including the proliferation of Informal Healthcare Facilities (IHFs).ObjectiveThis study evaluates the impact of RIPSEC mentorship on leadership development and the performance of the Walungu LRZ, particularly concerning the utilization of integrated curative health services in competition with IHFs.MethodsWe used a mixed method approach, combining retrospective analysis of some key health indicators before (2014) and during RIPSEC program (2015-2019), and in-depth qualitative interviews with members of the HZ management team. Quantitative data were presented as frequencies and proportions. Simple linear regression (p<0.05) measured the influence of IHFs on service use. The functionality and performance of the HZ were assessed using an internal benchmarking approach, with results presented as trend curves. Deductive analysis of interviews allowed for a deeper exploration of quantitative trends.ResultsDespite efforts to manage them, IHFs negatively influenced the use of curative services. RIPSEC mentorship notably enhanced the leadership skills of managers, leading to improved management effectiveness. While the use of curative health services slightly increased during the program, rates remained below 50%, and gains were not sustained post-program.ConclusionRIPSEC mentorship has positively impacted leadership and performance in Walungu. However, challenges related to sustainability and financing persist, necessitating comprehensive interventions beyond enhancing managerial leadership solely.
Antibiotic Resistance related Mortality, Length of Hospital Stay, and Disability-Adjusted Life Years at select Tertiary Hospitals in Uganda:A retrospective study
Authors: Mayito Jonathan , Dhikusooka Flavia , Kibombo Daniel , Busuge Andrew , Andema Alex , Yayi Alfred , Obbo Stephen , Walwema Richard , Kakooza Francis 
Published: May 2024

AbstractBackgroundAntimicrobial Resistance (AMR) is a major global health threat but its burden has not been extensively described in Uganda. We aimed to investigate the antibiotic resistance related mortality, length of hospital stays (LOS) and Disability Adjusted Life Years (DALYs).MethodsThis was a retrospective study of clinical records of patients with infectious syndromes admitted at Arua, Jinja and Mbale regional referral hospitals between October 2022 and September 2023. Data was abstracted from clinical records and analyzed to derive the mortality, LOS, DALYs, and factors associated with AMR and mortality using the modified Poisson regression model.ResultsOf the 291 participants included in the analysis, 56.6% were males, 10% were living with HIV, and their median age was 35 years (IQR: 21-56). The most common infectious syndromes were sepsis (43.6%) and diarrhea (9.6%). The prevalence of antibiotic-resistant infections (ARI) was 29.6%, while that for multi-drug resistant infections (MDRI) was 17.9%. Patients at Jinja and Mbale RRHs exhibited a 2.42 and 2.65 higher risk of ARI respectively compared to those at Arua RRH. Overall, mortality due to an infectious syndrome was 44.7%, of which 34.9% was due to ARI while 30.8% of the ARI related mortality was due to MDR infections. Most deaths were due to sepsis (42.3%), followed by pneumonia (15.4%) and meningitis (6.2%). Participants with comorbidities had higher risk of mortality due to ARI (45% vs. 31% for those without comorbidities). Among Gram-negative bacteria,Escherichia coliandKlebsiellaspp contributed most to mortality, while among Gram-positives,Staphylococcus aureusandEnterobacterspp contributed equally. Patients with ARI’s LOS was 1.2 times higher than that for those without ARI while a longer LOS was associated with a 21% higher ARI risk but a 24% decline in risk of death. ARI was associated with higher DALYs, 235.4, compared to 147.0 for non-ARI.ConclusionThe study revealed a high burden of AMR in Uganda, including a high prevalence of MDR and associated mortality, particularly among patients with comorbidities. This indicates an urgent need for stewardship and infection prevention strategies to control the AMR burden.
New WHO guideline on the definition of anemia: implications for 6-35 months old children in Peru 2009-2023
Authors: Campos-Sánchez Miguel , Cordero Muñoz Luis , Velásquez Hurtado Enrique , Baiocchi Ureta Nelly , Miranda-Cuadros Marianella , Sánchez-Griñán María Inés , Valdivia Miranda Walter 
Published: May 2024

AbstractIntroductionThe World Health Organization recently published a guideline updating the cut-off points defining anemia, modifying the age and altitude adjustments and recommending auto-analyzers. We compute in a national sample the magnitude of anemia prevalence with the previous and current guidelines between 6 and 35 months old and discuss the implications.MethodsSecondary analysis of the Peruvian Demographic and Health Survey 2009-2023, a repeated cross-sectional design upon a national stratified and cluster random sample.Results117995 children were included. With the new guideline, the national prevalence is reduced and the regional prevalences are generally reduced (some increased) in variable amounts.Conclusions and RecommendationsThe comparison confirms that the new guideline modifies, mostly reducing, the prevalence in an important and heterogeneous magnitude. Literature supports the direction, but not the magnitude of the correction. We recommend the quick, but cautious and gradual adoption of the new guideline. For analytic calculations, age and altitude formulas (not categories) should be used. Surveillance must be reinforced and control strategies must be reviewed. Case management guidelines must be updated.
High burden of non-adherence to blood pressure-lowering medications: meta-analysis of data from over 34,000 adults with hypertension in Sub-Saharan Africa
Authors: Aminde Leopold Ndemnge , Agbor Valirie Ndip , Fongwen Noah Takah , Ngwasiri Calypse , Nkoke Clovis , Nji Miriam , Dzudie Anastase , Schutte Aletta E. 
Published: May 2024

AbstractIntroductionNon-adherence to blood pressure (BP)-lowering medication is a strong predictor of poor BP control. Sub-Saharan Africa (SSA) has extremely low BP control rates (∼10%), but it is unclear what the burden of medication non-adherence among Africans with hypertension is. This systematic review estimated the prevalence and determinants of non-adherence to BP-lowering medications in SSA.MethodsMultiple databases were searched from inception to 6 December 2023. Two reviewers performed independent screening, extraction, and quality assessment of studies. We pooled the prevalence estimates using random effects meta-analyses and summarized the determinants using a narrative synthesis.ResultsFrom the 1,307 records identified, we included 95 studies published between 1995 and 2023. The overall prevalence of non-adherence to BP-lowering medication among 34,102 people treated for hypertension in 27 countries was 43.5% (95% confidence interval 39.4 to 47.6; I2= 98.3%). There was no change in the prevalence of non-adherence over time. The burden of non-adherence varied by measurement method (p = 0.028) and by median age (38.8%, > 57 years vs. 47.9%, ≤ 57 years; p = 0.015). Socioeconomic and patient-related factors were the most frequent factors that influenced medication adherence. Active patient participation in management, accurate perceptions, and knowledge of hypertension and its treatment predicted good medication adherence, whereas high pill burden, medication cost, side effects, and comorbidities predicted poor adherence.ConclusionsWith the African population projected to increase from 1.4 to ∼2.5 billion by 2050, targeted strategies are urgently needed to optimise medication adherence in people with hypertension in SSA.
Post-stroke delirium and associations with neuroimaging biomarkers on routine Computed Tomography (CT): a cohort study
Authors: Barugh Amanda , Farrall Andrew , Ferguson Karen , Shenkin Susan , MacLullich Alasdair , Mead Gillian 
Published: May 2024

AbstractBackgroundDelirium affects a quarter of patients after acute stroke and predicts poorer outcomes. Our aim was to determine whether either qualitative assessment or quantitative assessments of the regional atrophy obtained from routinely performed computed tomography (CT) brain imaging could identify those most at risk of developing delirium.MethodsWe recruited 95 patients with acute stroke (age ≥65) over one year. Follow-up for delirium and cognition was performed at 1, 3, 5, 7, 14, 21, 28 days, 4 months and 12 months. All participants underwent routine CT brain (Toshiba 64-slice or 128-slice scanner). White matter disease and atrophy were rated qualitatively (mild, moderate, severe). Atrophy in multiple specific areas was measured quantitatively.ResultsTwenty-six (27%) developed delirium during the 12 months of follow-up. On univariable analysis, delirium was associated with increasing age, being female, less independent in pre-stroke activities of daily living, pre-existing cognitive impairment, increasing stroke severity, having had a total anterior circulation stroke and global cerebral atrophy on brain CT. Multivariable analysis demonstrated that only global cerebral atrophy, being female and having a more severe stroke predicted delirium. This model accounted for between 38% and 55% of the variance in delirium.For quantitative CT analysis, on univariable analysis, delirium was associated with atrophy in several specific brain areas. On multivariable analysis, only NIHSS (for every one point increase OR 1.23, 95% CI 1.06-1.43; p=0.006)) and cistern ambiens ratio (OR 1.41, 95% CI 1.48-4.96; p=0.028) were significantly associated. This model accounted for between 35.1% and 51.2% of delirium variance.ConclusionClinical variables together with either qualitative atrophy assessment or cistern ambiens ratio on routine CT brain could identify stroke patients most at risk of delirium and to stratify patients in clinical trials of delirium prevention and treatment.
Personalised interactive music systems for physical activity and exercise: A systematic review and exploratory meta-analysis
Authors: Danso Andrew , Kekäläinen Tiia , Koehler Friederike , Knittle Keegan , Nijhuis Patti , Burunat Iballa , Neto Pedro , Mavrolampados Anastasios , Randall William M. , Hansen Niels Chr. , Ansani Alessandro , Rantalainen Timo , Alluri Vinoo , Hartmann Martin , Schaefer Rebecca S. , Ihalainen Johanna , Rousi Rebekah , Agres Kat , MacRitchie Jennifer , Toiviainen Petri , Saarikallio Suvi , Chastin Sebastien , Luck Geoff 
Published: May 2024

AbstractPersonalised Interactive Music Systems (PIMS) are emerging as promising devices for enhancing physical activity and exercise outcomes. By leveraging real-time data and adaptive technologies, PIMS align musical features, such as tempo and genre with users’ physical activity patterns, including frequency and intensity, enhancing their overall experience. This systematic review and exploratory meta-analysis evaluates the effectiveness of PIMS across physical, psychophysical, and affective domains. Searches across nine databases identified 18 eligible studies, of which six (comprising 17 intervention arms) contained sufficient data for meta-analysis. Random-effects meta-analyses and meta-regression were performed to assess outcomes for physical activity levels, physical exertion, ratings of perceived exertion (RPE), and affective valence. Results showed significant improvements in physical activity levels (g= 0.49, CI [0.07, 0.91],p= .02,k= 4) and affective valence (g= 1.68, CI [0.15, 3.20],p= .03,k= 4), with faster music tempo identified as a significant moderator (p= 0.04). No significant effects were observed for RPE (g= 0.72, CI [-0.14, 1.59],p= .10,k= 3) or physical exertion (g= 0.79, CI [-0.64, 2.10],p= .28,k= 5). Substantial heterogeneity and limited study quality indicate the need for more robust, randomised controlled trials to establish the efficacy of PIMS in diverse populations.
SARS-CoV-2 correlates of protection from infection against variants of concern
Authors: Sun Kaiyuan , Bhiman Jinal N. , Tempia Stefano , Kleynhans Jackie , Madzorera Vimbai Sharon , Mkhize Qiniso , Kaldine Haajira , McMorrow Meredith L , Wolter Nicole , Moyes Jocelyn , Carrim Maimuna , Martinson Neil A , Kahn Kathleen , Lebina Limakatso , du Toit Jacques D. , Mkhencele Thulisa , von Gottberg Anne , Viboud Cécile , Moore Penny L. , Cohen Cheryl ,   PHIRST-C group
Published: May 2024

AbstractSerum neutralizing antibodies (nAbs) induced by vaccination have been linked to protection against symptomatic COVID-19 and severe disease. However, much less is known about the efficacy of nAbs in preventing the acquisition of infection, especially in the context of natural immunity and against SARS-CoV-2 immune-escape variants. In this study, we conducted mediation analysis to assess serum nAbs induced by prior SARS-CoV-2 infections as potential correlates of protection (CoPs) against Delta and Omicron BA.1/2 wave infections, in rural and urban household cohorts in South Africa. We find that, in the Delta wave, anti-D614G nAbs mediate 37% (95%CI 34% – 40%) of the total protection against infection conferred by prior exposure to SARS-CoV-2, and that protection decreases with waning immunity. In contrast, anti-Omicron BA.1 nAbs mediate 11% (95%CI 9 – 12%) of the total protection against Omicron BA.1/2 wave infections, due to Omicron’s neutralization escape. These findings underscore that CoPs mediated through nAbs are variant-specific, and that boosting of nAbs against circulating variants might restore or confer immune protection lost due to nAb waning and/or immune escape. However, the majority of immune protection against SARS-CoV-2 conferred by natural infection cannot be fully explained by serum nAbs alone. Measuring these and other immune markers including T-cell responses, both in the serum and in other compartments such as the nasal mucosa, may be required to comprehensively understand and predict immune protection against SARS-CoV-2.
Autism gene variants disrupt enteric neuron migration and cause gastrointestinal dysmotility
Authors: McCluskey Kate E. , Stovell Katherine M. , Law Karen , Kostyanovskaya Elina , Schmidt James , Exner Cameron R. T. , Dea Jeanselle , Brimble Elise , State Matthew W. , Willsey A. Jeremy , Willsey Helen Rankin 
Published: May 2024

ABSTRACTThe comorbidity of autism spectrum disorders and severe gastrointestinal symptoms is well-established, yet the molecular underpinnings remain unknown. The identification of high-confidence large-effect autism risk genes offers the opportunity to identify convergent, underlying biology by studying these genes in the context of the gastrointestinal system. Here we show that the expression of these genes is enriched in human prenatal gut neurons as well as their migratory progenitors, suggesting that the development and/or function of these neurons may be disrupted by autism-associated pathogenic variants, leading to gastrointestinal dysfunction. Here we document the prevalence of gastrointestinal issues in patients with large-effect variants in sixteen of these genes, highlighting dysmotility, consistent with potential enteric neuron dysfunction. Using the high-throughput diploid frogXenopus tropicalis, we individually target five of these genes (SYNGAP1, CHD8, SCN2A, CHD2, andDYRK1A) and observe disrupted enteric neuronal progenitor migration for each. More extensive analysis ofDYRK1Areveals that perturbation causes gut dysmotilityin vivo, which can be ameliorated by treatment with a selective serotonin reuptake inhibitor (escitalopram) or a serotonin receptor 6 agonist, identified byin vivodrug screening. This work suggests that atypical development of enteric neurons contributes to the gastrointestinal distress commonly seen in individuals with autism and that increasing serotonin signaling may be a productive therapeutic avenue.
Cotranslational membrane insertion of the voltage-sensitive K+channel KvAP
Authors: Westerfield Justin M. , Kozojedová Petra , Juli Cara , Metola Ane , von Heijne Gunnar 
Published: May 2024

AbstractVoltage-sensor domains (VSDs), found in many voltage-sensitive ion channels and enzymes, are composed of four transmembrane helices (TMHs), including the atypical, highly positively charged S4 helix. VSDs are cotranslationally inserted into the membrane, raising the question of how the highly charged S4 helix is integrated into the lipid bilayer as it exits the ribosome. Here, we have used Force Profile Analysis to follow the cotranslational insertion of the six-TMH KvAP voltage-sensitive ion channel into theE. coliinner membrane. We find that the insertion process proceeds through three semi-independent steps: (i) insertion of the S1-S2 helix hairpin, (ii) insertion of the S3-S5 helices, and (iii) insertion of the Pore and S6 helices. Our analysis highlights the importance of the concerted insertion of helical hairpins, the dramatic influence of the positively charged residues in S4, and the unexpectedly strong forces and effects on downstream TMHs elicited by amphipathic and re-entrant helices.
Comparative genomics studies provide insights into the taxonomic classification and secondary metabolic potential of five bioactiveStreptomycesspecies isolated from the North-Western Himalaya
Authors: Bhat Aasif Majeed , Haneen Mariam Azeezuddin , Hussain Aehtesham , Sharma Gaurav , Hassan Qazi Parvaiz 
Published: May 2024

AbstractThe linear genome of genusStreptomycesmembers has the potential to encode diverse and novel biosynthetic gene clusters of invaluable antimicrobial and therapeutic significance. The use of limited taxonomic markers makes the precise identification of these miracle microbes very challenging. In the ongoing omics era, genome sequencing andin-silicoanalysis of these potential antibiotic producers provide deeper insights into their taxonomy, functional capabilities, and potential for antibiotic production. Here this study presents a multifaceted approach for proper taxonomic identification and genomic and bioinformatic analysis of five bioactiveStreptomycesspecies collected from different sampling sites in the high-altitude oligotrophic North-Western Himalaya, Kashmir, India. We used polyphasic taxonomic classification approaches, such as phylogenetic markers (16S rDNA and gyrase B), average nucleotide identity (ANI) estimation, and digital DNA-DNA hybridization (dDDH), which revealed accurate taxonomic placement of fiveStreptomycesspecies, named as,Streptomyces violarusASQP_29,S. rhizosphaerihabitansASQP_78,S. fulvoviolaceusASQP_80,S. mirabilisASQP_98, andS. thajiwasiensisASQP_92. Amongst these, one notable finding is the discovery of a novel species proposed asStreptomyces thajiwasiensissp. nov. ASQP_92. In addition, our study presents the first genome announcement report and analysis forS. rhizosphaerihabitansASQP_78. Genomic annotation highlighted the presence of an exceptionally high number of poorly characterized genes and hypothetical proteins, indicating their potential for undiscovered biotechnological applications. Clusters of orthologous groups (COG) and gene ontology (GO) analysis provided insights into their varied functional roles in metabolism, signaling, information storage and secondary metabolite biosynthesis. Domain-based functional characterization further detailed their involvement in various biological processes particularly in antibiotic biosynthesis, transport, and resistance. Biosynthetic gene clusters (BGC) analysis demonstrated their diverse metabolite biosynthetic capabilities and identified both unique and conserved BGCs emphasizing the species-specific roles in bioactive metabolite production and the potential of orphan BGCs in novel drug discovery.Graphical abstract:Genomic analysis and taxonomic affiliations of five bioactiveStreptomycesspecies isolated from high altitudes of the North Western Himalaya
WITHDRAWN: Progressive neural engagement within the IFG-pMTG circuit as gesture and speech entropy and MI advances
Authors: Zhao Wanying , Li Zhouyi , Li Xiang , Du Yi 
Published: May 2024

Withdrawal StatementThe authors have withdrawn this manuscript due to a duplicate posting of manuscript number BIORXIV/2022/517759. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author. The correct preprint can be found at doi: 10.1101/2022.11.23.517759