Miracle-dz/UniFAR-FTUs huggingface dataset:
From Pancreatic β-Cell Gene Networks to Novel Therapies for Type 1 Diabetes

Completion of the Human Genome Project enabled a novel systems- and network-level understanding of biology, but this remains to be applied for understanding the pathogenesis of type 1 diabetes (T1D). We propose that defining the key gene regulatory networks that drive β-cell dysfunction and death in T1D might enable the design of therapies that target the core disease mechanism, namely, the progressive loss of pancreatic β-cells. Indeed, many successful drugs do not directly target individual disease genes but, rather, modulate the consequences of defective steps, targeting proteins located one or two steps downstream. If we transpose this to the T1D situation, it makes sense to target the pathways that modulate the β-cell responses to the immune assault—in relation to signals that may stimulate the immune response (e.g., HLA class I and chemokine overexpression and/or neoantigen expression) or inhibit the invading immune cells (e.g., PDL1 and HLA-E expression)—instead of targeting only the immune system, as it is usually proposed. Here we discuss the importance of a focus on β-cells in T1D, lessons learned from other autoimmune diseases, the “alternative splicing connection,” data mining, and drug repurposing to protect β-cells in T1D and then some of the initial candidates under testing for β-cell protection.
Seroepidemiology and associated risk factors of hepatitis B and C virus infections among pregnant women attending maternity wards at two hospitals in Swabi, Khyber Pakhtunkhwa, Pakistan

Background & aim Hepatitis B and C infections are global issues that are associated with a massive financial burden in developing countries where vertical transmission is the major mode and remains high. This cross-sectional study was designed to investigate the seroepidemiology and associated risk factors of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections among 375 pregnant women attending antenatal care health facilities at Bacha Khan Medical Complex (BKMC) Shahmansoor and District Head Quarter (DHQ) Hospital Swabi, Khyber Pakhtunkhwa, Pakistan. Methodology From a total of 375 pregnant women selected using systematic random sampling from both hospitals, 10 ml of blood samples were collected and alienated serum was examined for indicators identification through the Immuno-Chromatographic Test (ICT) and 3rd Generation Enzyme-Linked Immunosorbent Assay (ELISA). A pre-structured questionnaire was used to collect the socio-demographic data and possible risk factors. The data was analyzed via SPSS 23.0 statistical software. A chi-square analysis was performed to determine the association between variables. P-value < 0.05 was set statistically significant. Results The overall frequency of HBV and HCV among 375 pregnant women involved in the study was 3.7% and 2.1% respectively. None of the pregnant women were co-infected with HBV and HCV. Dental extraction (P = 0.001) and blood transfusion (P = 0.0005) were significantly allied with HBV infection while surgical procedure (P = 0.0001) was significantly associated with HCV infection. Moreover the sociodemographic characteristics: residential status (P = 0.017) and educational level (P = 0.048) were found significant risk factors of HBsAg and maternal age (P = 0.033) of anti-HCV, respectively. Conclusion & recommendation HBV and HCV infections are intermediary endemic in the study area. A higher prevalence of HBV was detected among pregnant mothers with a history of dental extraction, history of blood transfusion, resident to the urban area and low educational level. The age and surgical procedures were the potential risk factors found significantly associated with HCV positivity among pregnant mothers in our setup. Future negotiations to control vertical transmission should include routine antenatal screening for these infections early in pregnancy and the requirement of efficient preventive tools including the birth dose of the hepatitis B vaccine in combination with hepatitis B immune globulins to the neonate.
Traumatized Refugees in Psychotherapy

Abstract This pre- and posttreatment study of 22 severely traumatized adult refugees spanned a mean of 6.5 years. Changes in personality functioning, mental health, and well-being were examined using the Rorschach Performance Assessment System, Harvard Trauma Questionnaire, Hopkins Symptom Checklist–25, and the World Health Organization’s Quality of Life–BREF questionnaire. A paired samples t-test revealed significant improvement after psychotherapy in traumatic ideation and initial severe disruptions in thought processes, reality testing, perception, self and other representations, and relational capacity (Cohen’s d = 0.46–0.59). Symptoms of anxiety, depression, and posttraumatic stress were significantly reduced (d = 0.54–0.84), quality of life in the physical health and psychological health domains increased significantly (d = 0.87 and 0.97), and percentage of participants with exile language proficiency and work/study status increased significantly. The findings demonstrate the potential of psychotherapy to contribute to normalizing perceptual, cognitive, and relational capacities in severely traumatized refugees, paramount to well-being and functioning in exile.
Association of Epigenetic Age Acceleration with Incident Mild Cognitive Impairment and Dementia Among Older Women.

BACKGROUND Epigenetic age acceleration (AgeAccel), which indicates faster biological aging relative to chronological age, has been associated with lower cognitive function. However, the association of AgeAccel with mild cognitive impairment (MCI) or dementia is not well-understood. We examined associations of four AgeAccel measures with incident MCI and dementia. METHODS This prospective analysis included 578 older women from the Women's Health Initiative Memory Study selected for a case-cohort study of coronary heart disease (CHD). Women were free of CHD and cognitive impairment at baseline. Associations of AgeAccel measures (intrinsic AgeAccel [IEAA], extrinsic AgeAccel [EEAA], AgeAccelPheno, and AgeAccelGrim) with risks for incident adjudicated diagnoses of MCI and dementia overall and stratified by incident CHD status were evaluated. RESULTS IEAA was not significantly associated with MCI (HR 1.23; 95% CI 0.99-1.53), dementia (HR 1.10; 95% CI 0.88-1.38), or cognitive impairment (HR 1.18; 95% CI 0.99-1.40). In stratified analysis by incident CHD status, there was a 39% (HR 1.39; 95% CI 1.07-1.81) significantly higher risk of MCI for every 5-year increase in IEAA among women who developed CHD during follow-up. Other AgeAccel measures were not significantly associated with MCI or dementia. CONCLUSION IEAA was not significantly associated with cognitive impairment overall but was associated with impairment among women who developed CHD. Larger studies designed to examine associations of AgeAccel with cognitive impairment are needed, including exploration of whether associations are stronger in the setting of underlying vascular pathologies.
Recommendations on the Management of Interhospital Transport of Pediatric Patients With Mediastinal Mass

Purpose Children with mediastinal masses often present with insidious symptoms to nonspecialist centers and require interhospital transport to oncology centers for definitive care. We evaluated clinical characteristics and patient outcomes and proposed a management protocol. Materials and Methods This is a retrospective review of all children with mediastinal mass at the pediatric intensive care unit of the Hong Kong Children's Hospital between April 2019 and March 2020. Results Ten children with a median age of 14.5 years (interquartile range, 9.3–17.0 years) were included. Leukemia and lymphoma accounted for the majority of cases (n = 6, 60%). Nearly all patients (n = 9, 90%) required interhospital transport before definitive treatment could be instituted. There were no deaths, but 2 patients were transported with significant respiratory compromise. Among patients requiring more than 1 interhospital transport, there was a higher incidence of shortness of breath (100% vs 40%; odds ratio, 33; P = 0.048) and orthopnea (80% vs 0%; odds ratio, 33; P = 0.048), whereas none had a neck mass (0% vs 80%; odds ratio, 0.03; P = 0.048). Conclusions Children with mediastinal mass are at risk of life-threatening cardiorespiratory compromise. Pretransport assessment, planning, and stabilization along with clear management plans for deterioration during transport are crucial especially for patients who are symptomatic at time of presentation, to reduce risks associated with delays in arriving at the specialist point of care for definitive treatment.
Age, ATA risk group and response to therapy are prognostic factors in children with differentiated thyroid cancer.

BACKGROUND Against the background of increasing incidence, pediatric differentiated thyroid carcinoma (DTC) frequently presents with advanced disease and high recurrence rates while prognosis remains excellent. We investigated the use of a pediatric classification and an adult response to therapy risk stratification for pediatric DTC patients and their implications for adaptation of treatment and follow-up. METHODS Data from patients aged <18 years with a diagnosis of primary DTC, registered with the GPOH-MET registry since 1995 were analyzed. For risk prediction, patients were retrospectively assigned to the American Thyroid Association (ATA) risk groups and evaluated for response to therapy. RESULTS By October 2019, 354 patients with DTC had been reported (median age at diagnosis 13.7 years, range 3.6-17.9) with lymph node and distant metastases in 74.3% and 24.5%. Mean follow-up was 4.1 years (range 0-20.6). 10-years overall and event-free survival (EFS) rates were 98.9% and 78.1%. EFS was impaired for patients with lymph node and distant metastases (p<0.001), positive postoperative thyroglobulin (p=0.006), incomplete resection (p=0.002), sequential surgeries to achieve total thyroidectomy (p=0.042), invasion of capsule (p<0.001) and lymph vessels (p=0.005), infiltration of surrounding soft tissues (p<0.001), tumor multifocality (p<0.001), ATA intermediate- and high-risk group (p<0.001), and age <10 years (p<0.001). Multivariate analysis revealed age <10 years at diagnosis, ATA high-risk level, and poor response to therapy as significant negative prognostic factors for EFS. CONCLUSIONS Age, ATA risk group, and response to therapy emerged as significant prognostic factors for EFS in pediatric patients with DTC, requiring risk-adapted individualized therapy and follow-up.
The clinical and pathological effectiveness of microneedling and topical 5‐fluorouracil in vitiligo treatment: An association with matrix metalloproteinase 2 immunohistochemical expression

The current therapies for vitiligo require long duration with often disappointing outcomes. 5‐Fluorouracil (5‐FU) is a chemotherapeutic agent approved for topical use in the treatment of several dermatologic conditions. Matrix metalloproteinase 2 (MMP2) is synthesized by keratinocytes during the epidermal remodeling process and has been found to help in melanocyte migration.
Descriptive and Kinetic Analysis of Two Different Vertical Jump Tests Among Youth and Adolescent Male Basketball Athletes Using a Supervised Machine Learning Approach

Abstract Gillett, J, De Witt, J, Stahl, CA, Martinez, D, and Dawes, JJ. Descriptive and kinetic analysis of two different vertical jump tests among youth and adolescent male basketball athletes using a supervised machine learning approach. J Strength Cond Res 35(10): 2762–2768, 2021—The countermovement jump (CMJ) is a functional movement in basketball and is also frequently used as an assessment of lower-body power. The CMJ can be performed in a variety of manners, and multiple variables can be extracted, and calculated, from the ground reaction force (GRF) time curve. The purpose of this article is to present kinematic and kinetic data collected from adolescent male basketball players during performance of the CMJ with hands on hips (HOH) or with an arm swing while reaching overhead to a target (i.e., vertical jump reach [VJR]). This study also sought to determine the effectiveness of a machine learning algorithm to identify the most important features that relate to jump height. Bilateral GRF data were collected on 89 right-handed male basketball athletes (age: 13.19 ± 0.72 year old, mass: 60.44 ± 13.35 kg, standing reach height: 228.49 ± 16.79 cm) using force platforms (Forcedecks, Vald Performance, Newstead, Queensland, Australia) and their associated software. Fifty-six bilateral kinematic and kinetic variables from each condition were analyzed using supervised machine learning to identify the top 10 important features to predict jump height in each condition, and to predict VJR height using HOH data. Vertical center of mass flight height was greater during VJR trials than during HOH trials (38.9 ± 6.8 cm vs. 32.6 ± 5.5 cm, respectively). The only common predictor variables between the conditions were concentric impulse and peak power. HOH jump data were able to predict VJR height with a mean error of 7.13 cm. These data suggest that important force platform data relating to jump height differ depending on test condition, and that data from CMJ performed with HOH, particularly peak power, concentric impulse, and concentric rate of power development, can be used to predict jump height during functional performance.
Insect pest management in the age of synthetic biology

Summary Arthropod crop pests are responsible for 20% of global annual crop losses, a figure predicted to increase in a changing climate where the ranges of numerous species are projected to expand. At the same time, many insect species are beneficial, acting as pollinators and predators of pest species. For thousands of years, humans have used increasingly sophisticated chemical formulations to control insect pests but, as the scale of agriculture expanded to meet the needs of the global population, concerns about the negative impacts of agricultural practices on biodiversity have grown. While biological solutions, such as biological control agents and pheromones, have previously had relatively minor roles in pest management, biotechnology has opened the door to numerous new approaches for controlling insect pests. In this review, we look at how advances in synthetic biology and biotechnology are providing new options for pest control. We discuss emerging technologies for engineering resistant crops and insect populations and examine advances in biomanufacturing that are enabling the production of new products for pest control.
AOP Report: Uncoupling of Oxidative Phosphorylation Leading to Growth Inhibition via Decreased Cell Proliferation

This report describes a novel adverse outcome pathway (AOP) on uncoupling of oxidative phosphorylation (OXPHOS) leading to growth inhibition via decreased adenosine triphosphate (ATP) pool and cell proliferation (AOPWiki, AOP263). Oxidative phosphorylation is a major metabolic process that produces the primary form of energy (ATP) supporting various biological functions. Uncoupling of OXPHOS is a widely recognized mode of action of many chemicals and is known to affect growth via different biological processes. Capturing these events in an AOP can greatly facilitate mechanistic understanding and hazard assessment of OXPHOS uncouplers and growth regulators in eukaryotes. The four proposed key events in this AOP are intentionally generalized to cover a wide range of organisms and stressors. Three out of four events can be measured using in vitro high‐throughput bioassays, whereas for most organisms, growth inhibition can also be measured in a high‐throughput format using standard in vivo toxicity test protocols. The key events and key event relationships in this AOP are further assessed for weight of evidence using evolved Bradford‐Hill considerations. The overall confidence levels range from moderate to high with only a few uncertainties and inconsistencies. The chemical applicability domain of the AOP mainly contains protonophores uncouplers, which can be predicated using the quantitative structure‐activity relationship (QSAR) approach and validated using in vitro high‐throughput bioassays. The biological domain of the AOP basically covers all eukaryotes. The AOP described in this report is part of a larger AOP network linking uncoupling of OXPHOS to growth inhibition, and is considered highly relevant and applicable to both human health and ecological risk assessments.
Assessment of Axillary Lymph Nodes for Metastasis on Ultrasound Using Artificial Intelligence

The purpose of this study was to evaluate an artificial intelligence (AI) system for the classification of axillary lymph nodes on ultrasound compared to radiologists. Ultrasound images of 317 axillary lymph nodes from patients referred for ultrasound guided fine needle aspiration or core needle biopsy and corresponding pathology findings were collected. Lymph nodes were classified into benign and malignant groups with histopathological result serving as the reference. Google Cloud AutoML Vision (Mountain View, CA) was used for AI image classification. Three experienced radiologists also classified the images and gave a level of suspicion score (1–5). To test the accuracy of AI, an external testing dataset of 64 images from 64 independent patients was evaluated by three AI models and the three readers. The diagnostic performance of AI and the humans were then quantified using receiver operating characteristics curves. In the complete set of 317 images, AutoML achieved a sensitivity of 77.1%, positive predictive value (PPV) of 77.1%, and an area under the precision recall curve of 0.78, while the three radiologists showed a sensitivity of 87.8% ± 8.5%, specificity of 50.3% ± 16.4%, PPV of 61.1% ± 5.4%, negative predictive value (NPV) of 84.1% ± 6.6%, and accuracy of 67.7% ± 5.7%. In the three external independent test sets, AI and human readers achieved sensitivity of 74.0% ± 0.14% versus 89.9% ± 0.06% (p = .25), specificity of 64.4% ± 0.11% versus 50.1 ± 0.20% (p = .22), PPV of 68.3% ± 0.04% versus 65.4 ± 0.07% (p = .50), NPV of 72.6% ± 0.11% versus 82.1% ± 0.08% (p = .33), and accuracy of 69.5% ± 0.06% versus 70.1% ± 0.07% (p = .90), respectively. These preliminary results indicate AI has comparable performance to trained radiologists and could be used to predict the presence of metastasis in ultrasound images of axillary lymph nodes.
A Retrospective Evaluation on Demographic, Phenomenological, and Comorbidity Features of Pediatric Obsessive-Compulsive Disorder

Abstract The impacts of sex, age of onset, phenotype, and comorbidity on clinical features were explored in a large clinical sample with pediatric obsessive-compulsive disorder (p-OCD) (n = 457), along with concomitant specific features in the framework of different symptom dimensions/phenotypes, by a retrospective cross-sectional evaluation design. The most prevalent phenotype was obsession/checking (almost half), and the clinical features belonging to different phenotypes varied among sexes, age of onset, severity, and comorbidities. The contamination and aggressive obsessions, along with the compulsions such as cleaning and repeating routine activities, were the most prevalent symptoms, which were prevalently accompanied by generalized anxiety disorder, attention deficit hyperactivity disorder, and depression. Females with OCD were likely prone to exhibit comorbid internalizing disorders, whereas males were prone to externalizing. This recent study on a large Turkish clinical sample of p-OCD followed up within 5 years, highlighting separate evidence on subtyping of p-OCD in phenotype and comorbidity frame.
Qualitative study on mental health and well-being of Syrian refugees and their coping mechanisms towards integration in the UK

Objective This study aimed to explore the mental well-being of Syrian refugees and identify their coping mechanisms and pathways towards integration into new communities. Design Qualitative study using in-depth semi-structured interviews. Setting and participants Adult Syrian refugees (>18 years old) currently residing in South East of England. Results 12 participants (3 women and 9 men) took part in the study, all were born in Syria and the majority (n=9) were over 45 years of age. Our findings show that Syrian refugees face constant challenges as they try to integrate into a new society. Loss of and separation from loved ones as well as the nostalgia for the homeland were often cited as a source of psychological distress that created an overwhelming sense of sadness. Participants reported that they struggled for connectedness due to cultural difference and the problematic nature of rapidly formed migrant communities in their new setting. They believed in ‘being their own doctor’ and turning to faith, ritual and nature for healing and comfort. Taboo and stigma around mental health and language barriers were cited as barriers to accessing mental healthcare services. Conclusion Past experiences and present challenges frame Syrian refugees’ sense of well-being, impact use of healthcare and risk future mental health problems. It is hoped that this study will act as a catalyst for further research on this vulnerable group to promote integration, community support and culturally sensitive mental health services.
Insomnia, a new modifiable risk factor for heart failure?

Chronic insomnia is one of the most common sleep disorders, affecting 10–15% of the population. Furthermore, it is estimated that 30–40% of adults report symptoms of insomnia at some point in a given year. Insomnia symptoms commonly wax and wane over time, and chronic insomnia disorder is diagnosed when these symptoms are present on at least three nights per week for at least 3 months despite adequate opportunity to sleep. Insomnia symptoms • Early-morning awakening • Non-restora ve sleep • Difficulty ini a ng sleep • Difficulty maintaining sleep
Asphaltene precipitation and deposition from crude oil with CO2 and hydrocarbons: experimental investigation and numerical simulation

Asphaltenes are the heaviest and most complex components in crude oil. Their precipitation and deposition may cause severe problems during production, transportation and processing of crude oil, hence affecting efficiency and cost of production in both upstream and downstream operations. During crude oil production, asphaltenes can deposit in the pores of reservoir rocks resulting in formation damage. Despite significant research, asphaltene behaviour in different flow regimes remains elusive. This thesis presents an investigation into crude oil asphaltene precipitation and deposition at ambient and reservoir conditions, using different experimental techniques and multi-scale simulations. Asphaltene precipitation can be triggered by altering the crude oil composition, which has been studied here through filtration experiments; a useful method to determine the amount of asphaltene precipitation induced by any precipitant. The relationship between the mass of precipitated asphaltenes and the mass of a precipitant in a crude oil+hydrocarbon system was compared to a crude oil+CO2 mixture in high pressure-high temperature experiments under conditions where the assumption of full miscibility is not valid. The precipitation onset point for the heavy crude oil used throughout the study was precisely determined in terms of the Hildebrand solubility parameter, showing for the first time that CO2 follows the same behaviour as hydrocarbon precipitants. However, the solubility parameter was not suitable for