Miracle-dz/UniFAR-FTUs huggingface dataset:
Enhancing inclusion of diverse populations in genomics: A competence framework

Genomic knowledge and technology have developed rapidly over the last decade and increased our capabilities to diagnose and manage rare diseases. However, current genomic datasets lack ethnic diversity as many genomic studies have focused on participants of white European ancestry. Studies, such as the Deciphering Developmental Disorders study, have been available to participants of any ancestry but have been unsuccessful in recruiting diverse populations. The inclusion of diverse populations in exome and genome sequencing is important to ensure that clinical benefits of genomics advances are equally shared among all populations and to advance scientific knowledge. Our clinical and research experience with the British Pakistani population (the largest ethnic minority in Yorkshire and Humber, accounting for 4.3% of the population) has fostered the development of an innovative cultural competence framework to enhance the inclusion of diverse populations in clinical genomic research and service provision. The application of this framework has the potential to guide healthcare professionals to develop a wide range of competences, so they are ready to embrace genomic advances in order to improve health outcomes for all patients. This practice model will inform precision medicine and improve access of diverse populations to genomic studies. Although based upon work with the Pakistani population in the UK, it is anticipated that the model would be broadly applicable to all underrepresented populations across the world.
Fertility decline in Bangladesh: an investigation of the major factors.

This study used data from the 1993-94 Bangladesh Demographic and Health Survey the Matlab Maternal and Child Health and Family Planning (MCH-FP) Project Recording System and Demographic Surveillance System and the Matlab MCH-FP Extension Project Sample Registration System. The aim was to examine the trends in fertility and contraceptive use and to identify the major factors that account for the fertility transition in Bangladesh. Positive factors that encouraged women to use contraception for spacing or limiting births included education female employment modernization access to media ideational changes and the decline in child mortality. Negative factors that compelled women to use contraception for spacing and/or limiting births included landlessness impoverishment and reduced employment opportunities which affect the economic value of children. Findings indicate that during 1975 to 1993/94 ever use of any methods of family planning increased about 5 times and the national contraceptive prevalence rate increased about 6 times. Fertility declined from over 7 children/woman in the mid-1970s to 4 children/woman in 1993-94. Contraceptive use was positively associated with education womens employment sanitation consumer durables water and energy supplies. Higher proportions of positively associated variables were associated with higher contraceptive use. Landholding was not clearly related to contraceptive use or the proportion of women with no births. The proportion of women with no births during the study period was higher among educated women working women households with sealed latrines women with access to tubewell water and households with radios and electricity. The probability of contraceptive use increased by varying proportions (13-37%) for a unit change in the composite score for the three data sets. Findings support government initiatives to strengthen family planning programs.
Unibody Endograft Using AFX 2 for Less Invasive and Faster Endovascular Aortic Repair: Protocol for a Multicenter Nonrandomized Study

Background Since the introduction of endovascular aortic repair (EVAR) for treatment of abdominal aortic aneurysms (AAAs), progressive improvements in results have been achieved. However, conventional bifurcated stent grafts have been proven to have a nonnegligible risk of failure and secondary intervention, principally due to the lack of adequate proximal sealing. The unique AFX 2 Endovascular AAA System (Endologix, Irvine, CA) unibody device, which provides different sealing and fixation features compared with conventional devices, seems to overcome these limitations. Objective The aim of this study is to evaluate intraoperative, perioperative, and postoperative results in patients treated with the AFX 2 Endovascular AAA System endografts for elective AAA repair in a large cohort of consecutive patients. Methods All eligible EVAR patients will be included in this observational, multicenter, prospective, nonrandomized study. The number of patients to be enrolled is 500. Results The primary endpoint of the study is to evaluate the technical and clinical success of EVAR with unibody endografts in short- (90-day), mid- (1-year), and long-term (5-year) follow-up periods. The following secondary endpoints will also be addressed: operative time, intraoperative radiation exposure, contrast medium usage, AAA sac shrinkage at 12-month and 5-year follow-up, and any potential role of patients’ baseline characteristics and device configuration on primary endpoint. The actual start date of the investigation was November 2019. The final patient is expected to be treated by the end of December 2020, and the estimated study completion date is December 2025. Conclusions This study will provide verified real-world data on AAAs treated by AFX 2 endografts and followed for a long-term interval. International Registered Report Identifier (IRRID) PRR1-10.2196/16959
Electrostatically gated nanofluidic membrane for ultra-low power controlled drug delivery†

Patient-centered therapeutic management for chronic medical conditions is a desired but unmet need, largely attributable to the lack of adequate technologies for tailored drug administration. While triggered devices that control the delivery of therapeutics exist, they often rely on impractical continuous external activation. As such, next generation continuously tunable drug delivery systems independent of sustained external activation remain an elusive goal. Here we present the development and demonstration of a silicon carbide (SiC)-coated nanofluidic membrane that achieves reproducible and tunable control of drug release via electrostatic gating. By applying a low-intensity voltage to a buried electrode, we showed repeatable and reproducible in vitro release modulation of three model analytes. A small fluorophore (Alexa Fluor 647), a large polymer poly(sodium 4-styrenesulfonate) and a medically relevant agent (DNA), were selected as representatives of small molecule therapeutics, polymeric drug carriers, and biological therapeutics, respectively. Unlike other drug delivery systems, our technology performed consistently over numerous cycles of voltage modulation, for over 11 days. Importantly, low power consumption and minimal leakage currents were achieved during the study. Further, the SiC coating maintained integrity and chemical inertness, shielding the membrane from degradation under simulated physiological and accelerated conditions for over 4 months. Through leveraging the flexibility offered by electrostatic gating control, our technology provides a valuable strategy for tunable delivery, setting the foundation for the next generation of drug delivery systems.
A case of MV2K subtype of sporadic Creutzfeldt–Jakob disease with florid‐like plaques: Similarities and differences to variant Creutzfeldt–Jakob disease

Variant Creutzfeldt–Jakob disease (vCJD) is traditionally regarded as having a distinct clinical course, imaging study findings and neuropathological features, which in combination should allow a clear distinction from the six currently well‐defined subtypes of sporadic Creutzfeldt‐Jakob disease (sCJD). This is of major importance, especially from the standpoint of epidemiology. As we would like to demonstrate through this case report, the MV2K subtype of sCJD, being rare and heterogeneous in both clinical and neuropathological presentations, might challenge this concept by virtue of partial overlapping, both clinically and neuropathologically, with the characteristic phenotype of vCJD. Chiefly, we observed prolonged isolated psychiatric prodrome, new onset limb pain and late cognitive decline clinically, while florid‐like plaques were present on routine histology, albeit in scarce and regionally restricted distribution when compared to vCJD. However, the issue is further complicated by the fact that a case of vCJD in a heterozygous (i.e. methionine – M and valine ‐ V) allelic state with regard to the polymorphic codon 129 of the prion protein gene (PRNP) has recently been described in the UK, which deviated from the otherwise well‐defined and constant clinicopathological phenotype that vCJD had thus far demonstrated. Taking both the facts into account, we would like to emphasize the use of complementary diagnostic methods to the established and otherwise reliable histological type‐based model, particularly when confronted with a rare or atypical phenotype such as ours.
Unravelling the menace: detection of antimicrobial resistance in aquaculture

One of the major problems to be addressed in aquaculture is the prominence of antimicrobial resistance (AMR). The occurrence of bacterial infections in cultured fishes promotes the continuous use of antibiotics in aquaculture, which results in the selection of proliferated antibiotic‐resistant bacteria and increases the possibility of transfer to the whole environment through horizontal gene transfer. Hence, the accurate cultivation‐dependent and cultivation‐independent detection methods are very much crucial for the immediate and proper management of this menace. Antimicrobial resistance determinants carrying mobile genetic transfer elements such as transposons, plasmids, integrons and gene cassettes need to be specifically analysed through molecular detection techniques. The susceptibility of microbes to antibiotics should be tested at regular intervals along with various biochemical assays and conjugation studies so as to determine the extent of spread of AMR. Advanced omic‐based and bioinformatic tools can also be incorporated for understanding of genetic diversity. The present review focuses on different detection methods to unearth the complexity of AMR in aquaculture. This monitoring helps the authorities to curb the use of antibiotics, commencement of appropriate management measures and adequate substitute strategies in aquaculture. The long battle of AMR could be overcome by the sincere implementation of One Health approach.
Repetitive mTBI is associated with age-related reductions in cerebral blood flow but not cortical thickness

Mild traumatic brain injury (mTBI) is a risk factor for Alzheimer’s disease (AD), and evidence suggests cerebrovascular dysregulation initiates deleterious neurodegenerative cascades. We examined whether mTBI history alters cerebral blood flow (CBF) and cortical thickness in regions vulnerable to early AD-related changes. Seventy-four young to middle-aged Veterans (mean age = 34, range = 23–48) underwent brain scans. Participants were divided into: (1) Veteran Controls (n = 27), (2) 1–2 mTBIs (n = 26), and (2) 3+ mTBIs (n = 21) groups. Resting CBF was measured using MP-PCASL. T1 structural scans were processed with FreeSurfer. CBF and cortical thickness estimates were extracted from nine AD-vulnerable regions. Regression analyses examined whether mTBI moderated the association between age, CBF, and cortical thickness. Regressions adjusting for sex and posttraumatic stress revealed mTBI moderated the association between age and CBF of the precuneus as well as superior and inferior parietal cortices (p’s < .05); increasing age was associated with lower CBF in the 3+ mTBIs group, but not in the VCs or 1–2 mTBIs groups. mTBI did not moderate associations between age and cortical thickness (p’s >.05). Repetitive mTBI is associated with cerebrovascular dysfunction in AD-vulnerable regions and may accelerate pathological aging trajectories.
Comprehensive single institute experience with melanoma TIL: Long term clinical results, toxicity profile, and prognostic factors of response

Adoptive cell transfer (ACT) of tumor‐infiltrating lymphocytes (TIL) mediates objective responses in 30% to 50% of patients with metastatic melanoma according to multiple, small phase 2 trials. Here we report the long‐term clinical results, intent‐to‐treat analysis, predictors of response and toxicity profile in a large patient cohort. A total of 179 refractory melanoma patients were enrolled in the ACT trial. TIL were administered in combination with high‐dose bolus interleukin‐2 following preconditioning with cyclophosphamide and fludarabine. Patients were followed‐up for a median of 7.2 years. A total of 107 (60%) of 179 enrolled patients were treated. The main reason for the drop out of the study was clinical deterioration. Of 103 evaluated patients, 29 patients (28%) achieved an objective response (OR), including complete remission (8%) or partial response (20%). Sixteen pateints exhibited stable disease. Predictors of response were performance status, time of TIL in culture and CD8 frequency in the infusion product. The absolute lymphocyte count 1 and 2 weeks after TIL infusion was the most predictive parameter of response. With a medium follow‐up time of 7.2 years, OR patients reached a median overall survival (OS) of 58.45 months and a median progression‐free survival (PFS) of 15.43 months, as compared with nonresponders, with 6.73 months OS and 2.60 months PFS. By 6 years, 50% of OR patients were alive and 43% had no documented progression. TIL ACT can yield durable objective responses, even as salvage therapy in highly advanced metastatic melanoma patients.
Glibenclamide nanosuspension inhaler: development, in vitro and in vivo assessment

Abstract Objective: The development of nanosuspension for targeted delivery of glibenclamide as hypoglycemic agent to the lung in an inhaler dosage form. Method: Glibenclamide nanosuspension formulations were prepared using Box–Behnken design to investigate the effect of independent factors on the dependent variables, Fourier-transform Infrared spectroscopy, Differential Scanning Calorimetry, evaluation of glibenclamide nanosuspension inhaler and in vivo hypoglycemic efficacy were performed to determine glibenclamide nanosuspension inhaler effect. Results: The results revealed that the mean particle sizes of the prepared nanosuspension ranged from 0.216 to 0.856 µm, zeta potential from +9 to +16 mV, the solubility ranged from 43% to 75%, the mass median aerodynamic diameter was 2.34 µm and the glucose level in rat was significantly reduced by about 60%. Conclusion: These results confirmed that glibenclamide nanosuspension inhaler enhance hypoglycemic effectiveness and reduce adverse effect of glibenclamide, opening up new dosage form in Diabetes mellitus treatment.
METABOLITES OF BACTERIAL-PHYTOPLANKTON INTERACTIONS IN THE SURFACE OCEAN by COURTNEY M. THOMAS

Marine dissolved organic matter (DOM) is a mixture of thousands of molecules that impact ocean life. Characterization of the most rapidly-cycling DOM, consisting of metabolites produced by marine microbes, has lagged behind that of other chemical compounds of this marine organic matter reservoir. However, identification of these compounds is important for understanding the flux of recently-fixed carbon and revealing interactions occurring between members of the ocean microbiome. Previous research identified transporter operons in the bacterium Ruegeria pomeroyi that had enriched expression levels when co-cultured with the diatom Thalassiosira pseudonana. The research presented here aims to identify the substrates that trigger expression of these operons and to quantify the abundance of these genes in the global ocean. Two of the targeted transporter operons increased in expression following the addition of acetate and taurine. Further, several of the operons could be associated with diverse groups of bacterial families in the surface ocean. INDEX WORDS: Metabolites, Transporter, Microbial Interactions METABOLITES OF BACTERIAL-PHYTOPLANKTON INTERACTIONS IN THE SURFACE OCEAN
A comparative-descriptive analysis of clinical characteristics in 2019-Coronavirus-infected children and adults.

Acute respiratory disease (ARD) caused by 2019 novel coronavirus (2019-nCoV) has rapidly spread throughout China. Children and adults show a different clinical course. The purpose of the current study is to comparatively analyze the clinical characteristics of 2019-nCoV infection in children and adults and to explore the possible causes for the discrepancies present. The medical records of 25 adults and 7 children confirmed cases of 2019-nCoV ARD were reviewed retrospectively. All children were family clusters. The total adult patients were differentiated into: the local residents of Wuhan, a history of travel to Wuhan and direct contact with people from Wuhan. The numbers were 14 (56%), 10 (40%) & 1 (4%), respectively. The median incubation period of children and adults was 5 days (range 3-12 days) and 4 days (range 2-12 days), respectively. Diarrhoea and/or vomiting (57.1%) were more common in children, whereas for adults it was myalgia or fatigue (52%). On admission, the percentage of children having pneumonia (5, 71.4%) was roughly the same as adults (20, 80%). 20% of adults had leucopoenia, but leukocytosis was more frequently in children (28.6%, P=0.014). A higher number of children had elevated creatine kinase isoenzyme (57.1% vs. 4%, P=0.004). Antiviral therapy was given to all adult patients but to none of the children. In summary, knowledge of these differences between children and adults will not only be helpful for the clinical diagnosis of 2019 novel coronavirus disease (COVID-19), but also for a future discussion on age-specific coronavirus infection. This article is protected by copyright. All rights reserved.
Allelopathic Effects of Castanea henryi Aqueous Extracts on the Growth and Physiology of Brassica pekinensis and Zea mays

The present study investigated the allelopathic effects of aqueous extracts of Castanea henryi litter on the growth and physiological responses of Brassica pekinensis and Zea mays. Treatment with high concentrations of leaf extract (0.05 g/ml for B. pekinensis and 0.10 g/ml for Z. mays) significantly increased malonaldehyde content and reduced seed germination, seedling growth, chlorophyll content, and the activity levels of antioxidant enzymes. These effects generally increased with increasing extract concentration. However, in Z. mays, low extract concentrations actually promoted seed germination, shoot growth, chlorophyll content, and antioxidant enzyme activity. The allelopathic effects of the various C. henryi extracts decreased as follows: leaf extract > twig extract > shell extract. Eleven potential allelochemicals including rutin, quercetin, luteolin, procyanidin A2, kaempferol, allantoin, propionic acid, salicylic acid, jasmonic acid, methylmalonic acid, and gentisic acid were identified in the leaves of C. henryi which were linked to the strongest allelopathic effects. These findings suggest that the allelopathic effects of C. henryi differ depending on receptor plant species, and that leaves are the most allelopathic litter in C. henryi.
Older Adults Who Meditate Regularly Perform Better on Neuropsychological Functioning and Visual Working Memory Tests: A Three-month Waitlist Control Design Study with a Cohort of Seniors in Assisted Living Facilities

ABSTRACT Background: Neuropsychological functioning and visual working memory are vulnerable to age-related decline. This investigation examines the impact of meditation on the said outcomes for older adults in assisted living facilities. Older adults (N = 136) from four assisted living facilities in Mumbai and Pretoria were randomized into intervention and waitlist control groups. Method: The Repeatable Battery for Assessment of Neuropsychological Status (RBANS) was used as a screening instrument for recruitment (cutoff total index score = 86 ± 4). RBANS, the Simple Object Span Test (SOST), and the Picture Span Test (PST) were used to assess the outcomes. The intervention group underwent a 90-day meditation training complemented with self-practice. Results: Posttest scores of the intervention group were higher. Older adult men, with college degree, middle class, widowed, in fair health, with no diagnosed psychiatric conditions, who attended at least 70 (out of 90) meditation lessons and who self-practiced at least 70 times, gained more from the meditation intervention. Intervention compliance had the strongest effect on posttest outcomes as well as sex and psychiatric morbidities. Conclusion: Meditation intervention needs some refinements for older adult women, with high school education, upper class, currently married, in poor health, with diagnosed anxiety/depression/drug dependence, who attended fewer meditation lessons and self-practiced infrequently.
Periodontal regeneration versus extraction and dental implant or prosthetic replacement of teeth severely compromised by attachment loss to the apex: A randomized controlled clinical trial reporting 10‐year outcomes, survival analysis and mean cumulative cost of recurrence

Abstract Background Periodontal regeneration can change tooth prognosis and represents an alternative to extraction in teeth compromised by severe intra‐bony defects. The aim of this study was to compare periodontal regeneration (PR) with tooth extraction and replacement (TER) in a population with attachment loss to or beyond the apex of the root in terms of professional, patient‐reported and economic outcomes. Methods This was a 10‐year randomized controlled clinical trial. 50 stage III or stage IV periodontitis subjects with a severely compromised tooth with attachment loss to or beyond the apex were randomized to PR or TER with either an implant‐ or a tooth‐supported fixed partial denture. Subjects were kept on a strict periodontal supportive care regimen every 3 months and examined yearly. Survival and recurrence analysis were performed. Results 88% and 100% survival rates were observed in the PR and TER groups. Complication‐free survival was not significantly different: 6.7–9.1 years for PR and 7.3–9.1 years for TER (p = .788). In PR, the observed 10‐year attachment gain was 7.3 ± 2.3 mm and the residual probing depths were 3.4 ± 0.8 mm. Recurrence analysis showed that the 95% confidence interval of the costs was significantly lower for PR compared with TER throughout the whole 10‐year period. Patient‐reported outcomes and oral health‐related quality‐of‐life measurements improved in both groups. Conclusions Periodontal regeneration can change the prognosis of hopeless teeth and is a less costly alternative to tooth extraction and replacement. The complexity of the treatment limits widespread application to the most complex cases but provides powerful proof of principle for the benefits of PR in deep intra‐bony defect.
The Scottish Women’s Hospitals: the first World War and the careers of early medical women

ABSTRACT The Scottish Women’s Hospitals for Foreign Service (SWH) was a women’s organization that equipped fourteen women’s hospital units across Europe during the First World War. About one hundred female doctors of different backgrounds served with the SWH. The aim of this study is to investigate how the experiences of women doctors during the First World War affected their later careers. This retrospective cohort study included the 92 women doctors who survived the War, as well as another 6 volunteers who qualified in medicine shortly after the War. By studying their publications, (auto)biographies, obituaries, genealogical databases and entries in the Medical Directory, their lives and careers are reconstructed. This study argues that, even though wartime service undoubtedly had an enormous impact on this group of brave and forward-thinking women, the beneficial effects on the position of women doctors, as a whole, were negligible.