Miracle-dz/UniFAR-FTUs huggingface dataset:
High diagnostic rate of whole genome sequencing in primary ciliary dyskinesia

Aim: Primary ciliary dyskinesia (PCD) is a genetic disorder affecting motile cilia. Most cases are inherited recessively, due to variants in more than 50 genes that result in abnormal or absent motile cilia. This leads to chronic upper and lower airway disease, sub-fertility and laterality defects in some cases. Given overlapping clinical features and genetic heterogeneity, diagnosis can be difficult and often occurs late. Of those tested, an estimated 30% of genetically screened PCD patients still lack a molecular diagnosis. Here, we aimed to identify how readily a genetic diagnosis could be made in a clinically diagnosed population using whole genome sequencing (WGS) to facilitate identification of pathogenic variants in known genes as well as identify novel PCD candidate genes. Methods: WGS was used to screen for variants causing PCD in 8 clinically diagnosed PCD patients, sequenced as trios where parental samples were available. Results: Seven of the eight cases (87.5%) had homozygous or biallelic variants in DNAH5, DNAAF4 or DNAH11 that were classified as pathogenic or likely pathogenic. Three of the variants were deletions, ranging from 3kb to 13kb, for which WGS identified precise breakpoints, permitting confirmation by Sanger sequencing. WGS yielded a high genetic diagnostic rate from this clinically diagnosed population, in part through detection of structural variants as well as identification of a de novo variant in a novel PCD gene TUBB4B. Conclusion: A molecular diagnosis allows for appropriate clinical management for cases and their families, including prediction of phenotypic features correlated to genotype. Here, WGS uplifted genetic diagnosis in cases of clinically diagnosed PCD by identifying structural variants and novel modes of inheritance in new candidate genes. Our study suggests that WGS could be a powerful part of the PCD diagnostic toolkit to increase the current molecular diagnostic yield from 70%. It provides important new insight into our understanding of fundamental biology of motile cilia as well as of variation in the non-coding genome in PCD.
Pulmonary Hypertension and the Risk of 30-day Postoperative Pulmonary Complications after Gastrointestinal Surgical or Endoscopic Procedures: A Retrospective Propensity Score Weighted Cohort Analysis.

Background: Pulmonary hypertension (PH) patients are at higher risk of postoperative complications. We analyzed the association of PH with 30-day postoperative pulmonary complications (PPC). Methods: A single-center propensity score overlap weighting (OW) retrospective cohort study of 164 patients with mean pulmonary artery pressure (mPAP) of >20 mmHg within 24 months of procedure and a control cohort (N=1981), undergoing elective inpatient abdominal surgery or endoscopic procedures under general anesthesia. The primary outcome was PPC, and the secondary outcomes were PPC sub-composites; respiratory failure (RF), pneumonia (PNA), aspiration pneumonia/pneumonitis (ASP), pulmonary embolism (PE), length of stay (LOS), and 30-day mortality. Results: PPC was higher in the PH cohort (29.9% vs. 11.2%, p<0.001). When sub-composites were analyzed, higher rates of RF (19.3% vs. 6.6%, p<0.001) and PNA (11.2% vs. 5.7%, p=0.01) were observed. After OW, PH was still associated with higher PPC [RR 1.66, 95% CI (1.05 - 2.71), p=0.036] and increased LOS (median 8.0 days vs. 4.9 days) but not 30-day mortality. Sub-cohort analysis showed no difference in PPC between pre- and post-capillary PH patients. Conclusions: After covariate balancing, PH was associated with a higher risk for PPC and pro-longed LOS. This elevated PPC risk should be considered during preoperative risk assessment.
Long-term conditions in minoritised urban populations: Latin American community of London

Background Minoritised populations in the United Kingdom frequently identify in multiple ethnic groupings and therefore little is known of their health needs. There were 136,062 Latin American people recorded in the 2021 UK Census across six different ethnic groups. Aim Characterise the incidence of long-term conditions (LTCs) and multiple LTCs (mLTCs) amongst the Latin American community of London. Design and setting Retrospective cohort study using pseudonymised primary care data from 890,922 individuals in an urban, superdiverse area of London from 2005-2022. Method Latin American individuals were identified using country of birth, language and ethnicity codes, and validated against Census findings. Multivariable competing risks regression models estimated the effect of being Latin American, compared to the White British ethnic group, on incidence of 32 LTCs and risk factors relevant to urban populations. Results 28,617 Latin American people were identified in this cohort, 3.2% of total. In multivariable analysis, compared to the White British ethnic group, being Latin American was associated with twice the rate of HIV/AIDS (hazard ratio (HR) 2.00; 95% confidence interval (CI) 1.65-2.43), 60% increased rate of diabetes (HR 1.61; 95%CI 1.47-1.77) and almost twice the rate of systemic lupus erythematosus and rheumatoid arthritis (HRs 2.28; 95% CI 1.18-4.38 and 1.69; 95% CI 1.32-2.17 respectively). Conclusion Using commonly-recorded primary care codes accurately and reliably identifies markedly higher risks of HIV/AIDS, diabetes and joint disease among London's Latin American population. These data can be used to target inclusive and equitable health interventions.
The effect of prescription patterns on the performance of the pharmacy department of a Regional Referral Hospital, Uganda

ABSTRACT Background: Poor drug prescription patterns (PP) result in irrational medicine use, avoidable stock outs and drug expiries. Objective: This study primarily assessed the effects of PP on the performance of the pharmacy department (PD) of Mbarara Regional Referral Hospital (MRRH) Uganda. Methods: This was a mixed method cross-sectional study conducted in the outpatient department (OPD) of MRRH, questionnaires were administered to 86 prescribers and 300 patient prescriptions were reviewed. Ethical clearance was granted and informed consent of patients. Data were analysed, presented in the form of graphs, tables. Results: The overall prescription fill rate was 60.5%, being higher among dental officers and lower among those who did not adhere to generic prescribing and EML. Medical officers made most prescriptions at 69.3%. Prescriptions with four (47.1%) and six (17.5%) medicines respectively were made by clinical officers. Of the 300 prescriptions, 76% adhered to the Essential Medicines List (EML), 62% used generic name including 87.3% from dental officers and 52.9% by clinical officersThe overall prescription fill rate was 60.5%, being higher among dental officers and lower among those who did not adhere to generic prescribing and EML. Medical officers made most prescriptions at 69.3%. Prescriptions with four (47.1%) and six (17.5%) medicines respectively were made by clinical officers. Of the 300 prescriptions, 76% adhered to the Essential Medicines List (EML), 62% used generic name including 87.3% from dental officers and 52.9% by clinical officers. Conclusion: Prescription pattern affected the performance of the PD of MRRH, calling for its continued monitoring to ensure that guidelines are upheld, EML and UCG are availed and utilized.
Survival and safety after neoadjuvant chemotherapy or upfront surgery for locally advanced colon cancer: meta-analysis

Abstract Background Neoadjuvant chemotherapy is increasingly used to treat locally advanced (T3–4 Nx–2 M0) colon cancer due to its potential advantages over the standard approach of upfront surgery. The primary objective of this systematic review and meta-analysis was to analyse data from comparative studies to assess the impact of neoadjuvant chemotherapy on oncological outcomes. Methods A systematic review was conducted by searching the MEDLINE and Scopus databases. The search encompassed RCTs, propensity score-matched studies, and controlled prospective studies published up to 1 April 2023. As a primary objective, overall survival and disease-free survival were compared. As a secondary objective, perioperative morbidity, mortality, and complete resection were compared using the DerSimonian and Laird models. Results A total of seven studies comprising a total of 2120 patients were included. Neoadjuvant chemotherapy was associated with a reduction in the hazard of recurrence (HR 0.73, 95% c.i. 0.59 to 0.90; P = 0.003) and death (HR 0.67, 95% c.i. 0.54 to 0.83; P < 0.001) compared with upfront surgery. Additionally, neoadjuvant chemotherapy was significantly associated with higher 5-year overall survival (79.9% versus 72.6%; P < 0.001) and disease-free survival (73.1% versus 64.5%; P = 0.028) rates. No significant differences were observed in perioperative mortality (OR 0.97, 95% c.i. 0.28 to 3.33), overall complications (OR 0.95, 95% c.i. 0.77 to 1.16), or anastomotic leakage/intra-abdominal abscess (OR 0.88, 95% c.i. 0.60 to 1.29). However, neoadjuvant chemotherapy was associated with a lower risk of incomplete resection (OR 0.70, 95% c.i. 0.49 to 0.99). Conclusion Neoadjuvant chemotherapy is associated with a reduced hazard of recurrence and death, as well as improved overall survival and disease-free survival rates, compared with upfront surgery in patients with locally advanced colon cancer.
Digestive problems in rabbit production: moving in the wrong direction?

Digestive problems, both those with a clear pathogenic origin (e.g., Escherichia coli) and those without obvious pathogen involvement [e.g., syndromes like epizootic rabbit enteropathy (ERE)], are common in production rabbits and account for the majority of losses in meat rabbit production. A multitude of nutritional, genetic and housing factors have been found to play a role in the occurrence of digestive problems. However, the exact early pathophysiological mechanism, including the links between aforementioned risk factors and subsequent development and expression of gastrointestinal disease, is less clear, especially in non-specific enteropathies without obvious pathogen involvement. In this review, we aim to shed more light on the derailment of the normal gastrointestinal functioning in rabbits. We discuss a conceptual integrated view of this derailment, based on an “overload” pathway and a “chymus jam” pathway, which may occur simultaneously and interact. The “overload” pathway centers around exposure to excess amounts of easily fermentable substrate (e.g., starch and protein) that might be incompletely digested prior to entering the caecum. Once there, hyperfermentation may result in changes in caecal pH and inhibition of the normal microflora. The second pathway centers around a chymus jam resulting from a compromised passage rate. Here, reduced hindgut motility (e.g., resulting from stress or limited fiber supply) leads to reduced flow of digesta and increased caecal retention times, which might lead to the production of abnormal caecal fermentation products and subsequent inhibition of the normal microflora. A central role in the presumed mechanism is attributed to the fusus coli. We discuss the suggested mechanisms behind both pathways, as well as the empirical substantiation and alignment between theoretical concepts and observations in practice. The proposed hypotheses may explain the effect of time-based restriction to prevent ERE, which is widely applied in practice but to date not really understood, and suggest that the particle size of fiber may be a key point in the normal functioning of the colon and fusus coli. Further insight into the circumstances leading to the derailment of physiological processes in the rabbit hindgut could provide a meaningful starting point to help improve their gastrointestinal resilience.
Ochre-based compound adhesives at the Mousterian type-site document complex cognition and high investment

Ancient adhesives used in multicomponent tools may be among our best material evidences of cultural evolution and cognitive processes in early humans. African Homo sapiens is known to have made compound adhesives from naturally sticky substances and ochre, a technical behavior proposed to mark the advent of elaborate cognitive processes in our species. Foragers of the European Middle Paleolithic also used glues, but evidence of ochre-based compound adhesives is unknown. Here, we present evidence of this kind. Bitumen was mixed with high loads of goethite ochre to make compound adhesives at the type-site of the Mousterian, Le Moustier (France). Ochre loads were so high that they lowered the adhesive’s performance in classical hafting situations where stone implements are glued to handles. However, when used as handheld grips on cutting or scraping tools, a behavior known from Neanderthals, high-ochre adhesives present a real benefit, improving their solidity and rigidity. Our findings help understand the implications of Pleistocene adhesive making.
The TTN p. Tyr4418Ter mutation causes cardiomyopathy in human and mice

Objective To generate a mouse model carrying TTNtv Y4370* simulating the newly discovered human heterozygous nonsense TTNtv c.13254T>G (p.Tyr4418Ter) to supplement and improve the functional evidence of pathogenic mutation TTNtv c.13254T>G on the pathogenic type of dilated cardiomyopathy. Methods We generated 4 mice carrying TTNtv p. Y4370* through CRISPR/Cas-mediated genome engineering. Monthly serological detection, bimonthly echocardiography, and histology evaluation were carried out to observe and compare alterations of cardiac structure and function between 4 TTN+/- mice and 4 wild-type (WT) mice. Results For the two-month-old TTN+/- mice, serum glutamic-oxalacetic transaminase (AST), lactic dehydrogenase (LDH), and creatine kinase (CK) were significantly increased, the diastolic Left Ventricular Systolic Anterior Wall (LVAW), and the LV mass markedly rose, with the left ventricular volume displaying an increasing trend and Ejection Fraction (EF) and Fractional Shortening (FS) showing a decreasing trend. Besides, the histological evaluation showed that cardiac fibrosis level and positive rate of cardiac mast cell of TTN+/- mice were obviously increased compared with WT mice. Conclusions TTNtv Y4370* could lead to cardiac structure and function alterations in mice, supplementing the evidence of TTNtv c.13254T>G pathogenicity in human.
Microbial profile in bile from pancreatic and extra-pancreatic biliary tract cancer

Background Dysbiotic biliary bacterial profile is reported in cancer patients and is associated with survival and comorbidities, raising the question of its effect on the influence of anticancer drugs and, recently, the suggestion of perichemotherapy antibiotics in pancreatic cancer patients colonized by the Escherichia coli and Klebsiella pneumoniae. Objective In this study, we investigated the microbial communities that colonize tumours and which bacteria could aid in diagnosing pancreatic and biliary cancer and managing bile-colonized patients. Methods A retrospective study on positive bile cultures of 145 Italian patients who underwent cholangiopancreatography with PC and EPC cancer hospitalized from January 2006 to December 2020 in a QA-certified academic surgical unit were investigated for aerobic/facultative-anaerobic bacteria and fungal organisms. Results We found that among Gram-negative bacteria, Escherichia coli and Pseudomonas spp were the most frequent in the EPC group, while Escherichia coli, Klebsiella spp, and Pseudomonas spp were the most frequent in the PC group. Enterococcus spp was the most frequent Gram-positive bacteria in both groups. Comparing the EPC and PC, we found a significant presence of patients with greater age in the PC compared to the EPC group. Regarding Candida spp, we found no significant but greater rate in the PC group compared to the EPC group (11.7% vs 1.96%). We found that Alcaligenes faecalis was the most frequent bacteria in EPC than the PC group, among Gram-negative bacterial species. Conclusions Age differences in gut microbiota composition may affect biliary habitats in our cancer population, especially in patients with pancreatic cancer. Alcaligenes faecalis isolated in the culture of bile samples could represent potential microbial markers for a restricted follow-up to early diagnosis of extra-pancreatic cancer. Finally, the prevalence of Candida spp in pancreatic cancer seems to trigger new aspects about debate about the role of fungal microbiota into their relationship with pancreatic cancer.
Response to MHC‐based olfactory cues in a mate choice context in two species of darter (Percidae: Etheostoma)

Abstract Mate choice is hypothesized to play an important role in maintaining high diversity at major histocompatibility complex (MHC) genes in vertebrates. Many studies have revealed that females across taxa prefer the scent of males with MHC genotypes different to their own. In this study we tested the “opposites‐attract” hypothesis in two species of darter with known differences in female criteria used in mate choice: in the fantail darters (a paternal‐care species), females prefer males with visual traits related to nest guarding and egg tending, while in rainbow darters (not a paternal‐care species) female mate choice criteria are unknown. In dichotomous mate‐choice trials, we presented females of both species with the scents of conspecific males with MHC class IIb genotypes that were either similar or dissimilar to that of the focal female. We evaluated the proportion of time each female spent with each male and calculated the average strength of female preference for both species. Female fantail darters demonstrated a preference for the scent of males with similar (rather than dissimilar) MHC genotypes, but this result was not statistically significant. Rainbow darter females showed no preference for the scent of males with similar or dissimilar MHC genotypes. Our results do not support the “opposites‐attract” hypothesis in darters.
A randomized controlled pilot study of a cognitive–behavioral video game intervention for the promotion of active aging

Background Due to the accessibility barriers of in-person programs for active aging, the development of programs that use innovative technologies is needed. Video games can be an engaging tool for disseminating active aging interventions. Objective The objective of this pilot study was to analyze the feasibility of a cognitive–behavioral intervention to promote active aging administered through a video game. Methods Fifty-five participants (63.6% women, mean age = 53.0 years) were randomly assigned to a cognitive–behavioral intervention to promote active aging administered through an interactive multimedia online video game with a complementary app (CBI-V; n = 29) or to a control group that received nonspecific online information (CG; n = 26). Results Only 3.6% of the participants dropped out of the study (6.9% in CBI-V and 0.0% in CG; without significant differences between groups). The mean number of modules completed was 7.6 (SD = 0.9) out of 8 in the CBI-V and 7.9 (SD = 0.5) in the control group (CG), without significant between-group differences. In the CBI-V, the mean total time dedicated to the game was 516.8 min (SD = 94.3), including 143.2 min (SD = 31.6) of cognitive training tasks, and the mean of completed tasks was 206.2 (SD = 33.7) out of 259. Participants were highly engaged (M = 39.9, SD = 8.6) and satisfied (M = 25.8, SD = 4.5) with the intervention. After the intervention, the CBI-V group significantly improved on SF-36 dimensions of General Health (p = .0386), Vitality (p = .0283), Social Functioning (p = .0130), and Physical Summary Index (p = .0370) compared to the CG, with medium effect sizes (d = 0.56–0.75). Conclusions The results demonstrate the feasibility of the video game intervention to promote active aging and encourage conducting a large-scale randomized controlled trial.
Socio-Demographic Characteristics Associated with Waste Disposal Behaviour Among Residents in Selected Communities of South-western, Nigeria

The study examined socio-demographic characteristics (gender, age, level of education and place of location) associated with waste disposal behaviour. This was with a view to assessing the roles played by these variables on waste disposal practices among residents in Southwestern, Nigeria. The study used primary data collected through a cross-sectional survey design. The study population comprised residents in Ife Central, Ibadan Northwest and Lagos Mainland LGAs in Southwestern, Nigeria. This study sample consisted of 1200 residents comprising 687 males and 513 females selected using a multi-stage sampling procedure. Their age ranged between 15 to 76 years with a mean age of 24.49 years (SD = 8.51). Two standardized psychological scales were used to collect data in the study. The Personal Information Questionnaire (PIQ) was used to collect information on the socio- demographic background of the participants while the Waste Disposal Behaviour Scale (WDBS) was used to collect data on the participants’ solid waste disposal practices. Data collected were analyzed using frequency counts, mean, standard deviation and ANOVA. The result showed that there was no significant influence of gender on waste disposal behaviour (F = 0.028, p .05). The results also showed that there was no influence of education on waste disposal behaviour (F = 1.54 , p >.05). The results showed that residents from Ibadan Northwest LGA reported better waste disposal behaviour (M= 54.80 ; SD = 8.34) than those residents in Lagos Mainland LGA (M =53.55 ; SD = 8.07) and Ife Central LGA. The study however, recommended that effective waste management system could be achieved through urban renewal programme as reported from the findings.
The effect of urbanization and temperature on thermal tolerance, foraging performance, and competition in cavity‐dwelling ants

Abstract Human disturbance including rapid urbanization and increased temperatures can have profound effects on the ecology of local populations. Eusocial insects, such as ants, have adapted to stressors of increasing temperature and urbanization; however, these evolutionary responses are not consistent among populations across geographic space. Here we asked how urbanization and incubation temperature influence critical thermal maximum (CTmax) and various ecologically relevant behaviors in three ant species in urban and rural locations in Worcester, MA, USA. We did this by incubating colonies of three species of cavity dwelling ant (Aphaenogaster picea, Tapinoma sessile, and Temnothorax longispinosus) from 2 habitat types (Rural and Urban), for 60‐days at multiple temperatures. We found that incubation temperature, urbanization, and species of ant all significantly affected overall colony critical thermal maximum. We also found that recruitment time, colonization time, and defense response were significantly affected by incubation temperature and varied between species of ant, while recruitment and colonization time were additionally affected by urbanization. These variable changes in performance and competitive traits across species suggest that responses to urbanization and shifting temperatures are not universal across species. Changes in behavioral responses caused by urbanization may disrupt biodiversity, creating unusual competitive environments as a consequence of natural adaptations and cause both direct and indirect mechanisms for which human disturbance can lead to local species extinction.