Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of the Effects of Developmental Trauma on Neurotransmitter Systems Using Functional Molecular Imaging

Early life stress (ELS) is strongly associated with psychiatric disorders such as anxiety, depression, and schizophrenia in adulthood. To date, biological, behavioral, and structural aspects of ELS have been studied extensively, but their functional effects remain unclear. Here, we examined NeuroPET studies of dopaminergic, glutamatergic, and serotonergic systems in ELS animal models. Maternal separation and restraint stress were used to generate single or complex developmental trauma. Body weights of animals exposed to single trauma were similar to those of control animals; however, animals exposed to complex trauma exhibited loss of body weight when compared to controls. In behavioral tests, the complex developmental trauma group exhibited a decrease in time spent in the open arm of the elevated plus-maze and an increase in immobility time in the forced swim test when compared to control animals. In NeuroPET studies, the complex trauma group displayed a reduction in brain uptake values when compared to single trauma and control groups. Of neurotransmitter systems analyzed, the rate of decrease in brain uptake was the highest in the serotonergic group. Collectively, our results indicate that developmental trauma events induce behavioral deficits, including anxiety- and depressive-like phenotypes and dysfunction in neurotransmitter systems.
Kidney involvement in coronavirus-associated diseases (Review)

Since 2003, coronaviruses have caused multiple global pandemic diseases, including severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and coronavirus disease 2019 (COVID-19). Clinical and autopsy findings suggest that the occurrence of kidney injury during infection may negatively affect the clinical outcomes of infected patients. The authoritative model predicts that outbreaks of other novel coronavirus pneumonias will continue to threaten human health in the future. The aim of the present systematic review was to summarize the basic knowledge of coronavirus, coronavirus infection-associated kidney injury and the corresponding therapies, in order to provide new insights for clinicians to better understand the kidney involvement of coronavirus so that more effective therapeutic strategies can be employed against coronavirus infection in the future.
A Study on Digit Sucking Among Children Presented to a Tertiary Care Paediatric Clinic in Sri Lanka

Background Sucking habits are common among children, especially in early childhood. There is, however, controversy about its prevalence probably due to under-reporting. The objective of this study is to analyze the demographic factors, reasons for clinic attendance, and treatment options chosen by parents and health care providers to control digit sucking. Material and methods A retrospective cross-sectional study was conducted including 82 children presented to the paediatric clinic, Teaching Hospital, Batticaloa, with digit sucking over a period of three years from November 2017 to October 2020. The data was analyzed using SPSS version 19.0 (IBM Corp., Armonk, NY, USA). Results Eighty-two children were enrolled in this study. The majority (n=29, 35.4%) of them presented between seven months to two years, and very few (n=3, 3.6%) presented after five years. Female children outnumbered males (50: 32). Only 24 (29.3%) mothers had been working and away from home during the daytime whilst the rest were housewives and were available to their children most of the time of the day. About 70 (85.4%) children had been given exclusive breastfeeding while the rest had either formula alone or formula with breastfeeding during the first six months of their age. Around 62 (75.6%) children had used their right hand for sucking. Sixty-six children (80.5%) had been using the thumb. Most children (n=56, 68.3%) were sucking since birth. The most common reason (n=68, 82.9%) for clinic attendance was that parents were scared about the future occurrence of mal-alignment or malocclusion of teeth. Thirty-one parents (37.8%) did nothing to stop digit sucking while 25 (30.5%) applied bitter oil and the majority tried pacifier without success. All children were referred to the dental surgeon for further management of digit sucking and amongst them, 78 children (95.1%) attended the appointment. All 78 children had been reassured that the habit eventually disappears before permanent teeth will appear and explained that digit fixing therapy would be offered for persisting habitual digit sucking. Four children did not visit the dental department. Conclusions The majority of children presented to the clinic were below three years and females outnumbered males in all age groups. A greater number of children had been using their right hand and thumb. Most of them had the habit of sucking since birth and most of the parents anticipated mal-alignment of teeth due to consequences of sucking. None of them succeeded in stopping the habit of digital sucking with various remedies performed at home by their parents.
Cortical Bone Mass is Low in Boys with Klinefelter Syndrome and Improves with Oxandrolone

Abstract Context Klinefelter syndrome (KS) is the most common sex aneuploidy in men. Affected males have hypogonadism, and, as a result, face an increased risk for osteoporosis and fractures. Androgen therapy is standard in adolescents and adults with KS but has not been used earlier in childhood. Objective To determine the effects of androgen treatment on bone mass in children with KS. Methods Randomized, double-blind, placebo-controlled clinical trial of oxandrolone (OX; 0.06 mg/kg daily; n = 38) versus placebo (PL; n = 40) for 2 years in boys with KS (ages 4-12 years). Changes in bone mass were examined by digital x-ray radiogrammetry, which determines the Bone Health Index (BHI) and standard deviation score (SDS). Results BHI SDS was similar between groups at baseline (–0.46 ± 1.1 vs –0.34 ± 1.0 OX vs PL, P > .05) and higher in the OX group at 2 years (–0.1 ± 1.3 vs –0.53 ± 0.9, OX vs PL, P < .01). At baseline, BHI SDS values of all subjects were not normally distributed with 25.7% of subjects plotted below –1 SDS (P < .001), suggesting a deficit in bone mass. In total, 13.5% of subjects had sustained a fracture and their BHI SDS was lower than those with no fractures (–1.6 ± 1.3 vs –0.3 ± 1.0, P = .004). Conclusion Bone mass using BHI SDS is reduced in some children with KS and improves with OX. Since these individuals are at risk for osteoporosis, age-appropriate androgen replacement and future studies on bone health in children with KS should be further explored.
Time density curve of dynamic contrast-enhanced computed tomography correlates with histological characteristics of pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is characterized by an infiltrative growth pattern with intense desmoplastic stroma comprised of cancer-associated fibroblasts (CAFs). Additionally, the histological characteristics are considered to play a vital role in the poor prognosis of PDAC. However, the density of cancer cells, degree of desmoplasia and vascular proliferation varies in individual cases. We hypothesized that preoperative radiological images would reflect histological characteristics, such as cancer cell density, CAF density and microvessel density. To clarify the association between the histological characteristics and radiological images of PDAC, the cancer cell density, CAF density and microvessel density from surgical specimens were measured with immunostaining, and the time density curve of dynamic contrast-enhanced computed tomography (CECT) was analyzed. Overall, the initial slope between non-enhanced and arterial phases was correlated with microvessel density, and the second slope between arterial and portal phases was correlated with CAF and cancer cell densities. In conclusion, the present study suggested the possibility of estimating cancer cell, CAF and microvessel densities using the TDC of dynamic CECT.
Clinical Impact of Liraglutide as a Treatment of Obesity

Abstract Obesity is defined as a chronic, complex, relapsing disease characterized by excessive adipose tissue. Obesity impacts an individual’s health by increasing complications such as prediabetes, type 2 diabetes mellitus (T2DM), hypertension, dyslipidemia, metabolic syndrome, cardiovascular disease, nonalcoholic fatty liver disease (NAFLD), cancers (eg endometrial), and obstructive sleep apnea (OSA). With the increase of obesity prevalence and its negative influences on individuals’ quality of life, there is a great need for therapy with a purpose to produce sustainable weight loss of more than 10% in order to improve or even reverse the progress of obesity related complications. The GLP-1 analogue, liraglutide reduce food consumption, promote weight reduction and improve metabolic functions. The primary mechanism of GLP-1 effect on food intake, metabolism, and weight reduction is mainly due to its actions on peripheral (vagal) and central pathways and activation of hindbrain and hypothalamus. The average weight reduction induced by liraglutide was significant and the weight loss was maintained as long as the patients on therapy. Liraglutide has advantages on weight loss maintenance and promoting cardiovascular disease (CVD) risk reduction, by decreasing systolic blood pressure and glycemic index. In this review, we aim to explain the mechanism of action of Liraglutide, its pharmacokinetic properties, its clinical impact on obesity and its safety and tolerability.
Biomechanical Analysis in Five Bar Linkage Prototype Machine of Gait Training and Rehabilitation by IMU Sensor and Electromyography

The prototype machine of gait training and rehabilitation (MGTR) with a five-bar linkage structure was designed to improve the common end-effector type. Additionally, the study was conducted to evaluate the joint angle and muscle activity during walking for the evaluation of prototype: (1) Background: The gait rehabilitation systems are largely divided into exoskeletal type and end-effector type. The end-effector type can be improved a gait trajectory similar to normal gait according to this prototype. Therefore, a new design of prototype MGTR is proposed in this study. (2) Methods: The gait experience was conducted with thirteen healthy male subjects using an inertial measurement unit (IMU) sensor and electromyography (EMG). It was compared that the hip and knee joints and the muscle activity between the normal gait and MGTR. (3) Results: The results showed that there was a high correlation between the knee joint angle for normal gait and MGTR. The range of motion (RoM) was small for the MGTR. The EMG results showed that the activation of the rectus femoris muscle was most similar to the normal gait and MGTR. (4) Conclusions: The characteristics of the kinematic variables of the subjects varied widely. It is necessary to modify the machine so that the link length can be adjusted in consideration of various segment lengths of patients.
Practice and Attitude Towards COVID-19 Prevention and Divine Belief Among Residents in Ethiopia: Cross-Sectional Survey

Purpose Coronavirus disease-2019 is an emerging disease that threatens the world. With the absence of successful treatment precipitated by the lack of health infrastructures in developing countries including Ethiopia, efforts to enhance the attitudes and practice of people are critical for managing the pandemic. Hence, this study aimed to assess the practice, attitude towards COVID-19, and divine belief among residents in Ethiopia. Patients and Methods A community-based cross-sectional study combining qualitative design was conducted in August 2020. The qualitative design was employed to explore the respondents’ divine belief towards the COVID-19 pandemic. Chi-square analysis was computed to identify factors associated with practice against COVID-19 prevention measures. The calculated chi-square greater than the tabulated value at a degree of freedom ((row total-1) * (column total)) and P-value <0.05 were considered statistically significant. Results In this study, a total of 508 respondents participated. The mean age of the participants was 38.4 ± 11.2 (SD) years. The overall practice of prevention measures and attitude towards COVID-19 was 53.3% (95% CI: 49.0–57.6%) and 49.6% (95% CI: 45.3–53.9%), respectively. Age, residency, educational status, monthly income of the household, having a child, and attitude towards COVID-19 were statistically significant predictors of COVID-19 prevention measures (P< 0.05). Conclusion As the global threat of COVID-19 continues, it is critical to improving the respondents’ practice and attitude towards the precautionary measures, especially some religious followers.
Profiles of Accelerometry-Derived Physical Activity Are Related to Perceived Physical Fatigability in Older Adults

Physical activity (PA) is associated with greater fatigability in older adults; little is known about magnitude, shape, timing and variability of the entire 24-h rest–activity rhythm (RAR) associated with fatigability. We identified which features of the 24-h RAR pattern were independently and jointly associated with greater perceived physical fatigability (Pittsburgh Fatigability Scale, PFS, 0–50) in older adults (n = 181, 71.3 ± 6.7 years). RARs were characterized using anti-logistic extended cosine models and 4-h intervals of PA means and standard deviations across days. A K-means clustering algorithm approach identified four profiles of RAR features: “Less Active/Robust”, “Earlier Risers”, “More Active/Robust” and “Later RAR”. Quantile regression tested associations of each RAR feature/profile on median PFS adjusted for age, sex, race, body mass index and depression symptomatology. Later rise times (up mesor; β = 1.38, p = 0.01) and timing of midpoint of activity (acrophase; β = 1.29, p = 0.01) were associated with higher PFS scores. Lower PA between 4 a.m. and 8 a.m. was associated with higher PFS scores (β = −4.50, p = 0.03). “Less Active/Robust” (β = 6.14, p = 0.01) and “Later RAR” (β = 3.53, p = 0.01) patterns were associated with higher PFS scores compared to “Earlier Risers”. Greater physical fatigability in older adults was associated with dampened, more variable, and later RARs. This work can guide development of interventions aimed at modifying RARs to reduce fatigability in older adults.
Sex Differences of Combined Effects Between Hypertension and General or Central Obesity on Ischemic Stroke in a Middle-Aged and Elderly Population

Background Hypertension and obesity are recognized as modifiable risk factors for stroke, but their combined effects are unknown. This study aimed to explore the combined effects of hypertension and general or central obesity on the risk of ischemic stroke in a middle-aged and elderly population. Methods The data of 11,731 participants (53.5 ± 10.5 years old) were analyzed from the Northeast China Rural Cardiovascular Health Study, 2012–2013. General obesity (GO) was defined by body mass index (BMI); central obesity (CO) was measured by waist circumference (WC), waist-to-height ratio (WHtR) and waist-to-hip ratio (WHpR). Results The overall prevalence of ischemic stroke was 3.1%. After adjusting for age and sex, the odds ratios for having ischemic stroke were 4.31 (3.14–5.91) among subjects with hypertension, 1.79 (1.40–2.30) with GO, 1.94 (1.54–2.43), 1.98 (1.54–2.53), and 1.65 (1.33–2.06) with CO measured by WC, WHtR and WHpR, respectively. After full adjustment for potential confounders, the combinations of hypertension and obesity indices (including BMI, WC, WHtR and WHpR) were associated with the highest risk of ischemic stroke, especially in women, which were respectively 7.3-fold, 9.3-fold, 9.9-fold and 7.6-fold higher than that of individuals without both conditions. Conclusion Our study results suggest that women with both hypertension and obesity, no matter defined by BMI, WC, WHtR or WHpR, were more likely to have ischemic stroke. A better understanding of the combined effects of these risk factors can help promote primary prevention in susceptible subgroups.
Applications of Biomaterials in 3D Cell Culture and Contributions of 3D Cell Culture to Drug Development and Basic Biomedical Research

The process of evaluating the efficacy and toxicity of drugs is important in the production of new drugs to treat diseases. Testing in humans is the most accurate method, but there are technical and ethical limitations. To overcome these limitations, various models have been developed in which responses to various external stimuli can be observed to help guide future trials. In particular, three-dimensional (3D) cell culture has a great advantage in simulating the physical and biological functions of tissues in the human body. This article reviews the biomaterials currently used to improve cellular functions in 3D culture and the contributions of 3D culture to cancer research, stem cell culture and drug and toxicity screening.
Fitness consequences of longer breeding seasons of a migratory passerine under changing climatic conditions

Abstract Numerous studies have shown that climate change affects the timing of migration and bird laying dates, but the resulting changes in the duration of breeding seasons and their fitness consequences remain largely unknown. We compared breeding parameters of 343 individually marked female Eurasian reed warblers, a multi‐brooded migratory passerine, studied in the same area in 1980–1983 and 2005–2012. The latter period was warmer, with mean temperatures during the breeding season higher by 1.5°C on average. As, in recent years, birds arrive earlier from wintering areas and the breeding season of the population is longer, we hypothesized it should result in the increased re‐nesting opportunities of individual females. We found that breeding periods of individual females (from building of the first nest till the end of caring for last fledglings/last nest failure) in the current century have extended by 2 weeks compared to the 1980s. In the 2000s, females produced 75% more fledglings annually than females in the 1980s (2.8 vs. 1.6, respectively). The proportion of females raising second broods increased from 2.7% to 23.6% between the first and the second study period while the share of females that did not produce any young annually decreased from 48.1% to 15.5%. The higher offspring production in recent years was related to more successfully fledged broods and an earlier start of breeding, which secured more time to re‐nest. Higher female parental effort in recent years was not manifested in the reduction of the female apparent survival: it was almost identical in the two study periods (0.30 vs. 0.31). We conclude that prolonged reproductive seasons might be beneficial for some species. Identifying causes and consequences of changes in the duration of breeding seasons may be essential to predict demography of populations under changing climatic conditions.
Fezolinetant in the treatment of vasomotor symptoms associated with menopause

ABSTRACT Introduction: Although international clinical practice guidelines recognize a continued role for menopausal hormone therapy (HT), particularly for symptomatic women <60 years of age or within 10 years of menopause, safety and tolerability concerns have discouraged HT use due to potential links with a perceived increased risk of hormone-dependent cancers, and an established risk of stroke and venous thromboembolism. There is therefore a need for safe, effective non-hormonal therapy for relief of menopausal vasomotor symptoms (VMS). Areas covered: This narrative review summarizes the dataset accrued for fezolinetant, a neurokinin-3 receptor (NK3R) antagonist in clinical development for menopause-associated VMS. Expert opinion: Altered signaling in neuroendocrine circuits at menopause leads to VMS wherein NK3R activity plays a key role to modulate the thermoregulatory center in a manner conducive to triggering the ‘hot flash’ response. Thus, a new generation of NK3R antagonists has entered clinical development to specifically target the mechanistic basis of VMS. Fezolinetant is the most advanced NK3R antagonist in terms of stage of clinical development. Results to date have demonstrated rapid and substantial reduction in VMS frequency and severity and associated improvements in health-related quality of life. NK3R antagonists offer a non-hormonal alternative to HT for the treatment of menopause-related VMS.
Interindividual immunogenic variants: Susceptibility to coronavirus, respiratory syncytial virus and influenza virus

The coronavirus disease (Covid‐19) pandemic is the most serious event of the year 2020, causing considerable global morbidity and mortality. The goal of this review is to provide a comprehensive summary of reported associations between inter‐individual immunogenic variants and disease susceptibility or symptoms caused by the coronavirus strains severe acute respiratory syndrome‐associated coronavirus, severe acute respiratory syndrome‐associated coronavirus‐2, and two of the main respiratory viruses, respiratory syncytial virus and influenza virus. The results suggest that the genetic background of the host could affect the levels of proinflammatory and anti‐inflammatory cytokines and might modulate the progression of Covid‐19 in affected patients. Notably, genetic variations in innate immune components such as toll‐like receptors and mannose‐binding lectin 2 play critical roles in the ability of the immune system to recognize coronavirus and initiate an early immune response to clear the virus and prevent the development of severe symptoms. This review provides promising clues related to the potential benefits of using immunotherapy and immune modulation for respiratory infectious disease treatment in a personalized manner.
Endoscopic treatment of Crohn-related strictures with a self-expandable stent compared with balloon dilation: a prospective, randomised, controlled study

Objective Fibrotic strictures in the gastrointestinal tract are frequent in Crohn’s disease. Endoscopic dilation is a standard treatment. However, recurrence is common after dilation and there are complications such as bleeding or perforation. Endoscopic treatment using self-expandable metal stents has shown diverging results. The aim of this study was to evaluate the outcome of endoscopic treatment with a self-expandable stent in ileocecal Crohn’s disease. Design/method Patients with Crohn’s disease and a symptomatic ileocecal stricture were eligible for prospective, consecutive inclusion in a single-centre setting. Patients were randomised to treatment with either 18 mm balloon dilatation (GroupDIL) or stenting (GroupSTENT) using a 20 mm diameter, partially covered Hanarostent NCN. Patients were followed for a minimum of 24 months postendoscopy. Outcomes were technical success, adverse events and clinical success (defined as no need for repeated interventions). Results Thirteen patients (GroupDIL n=6; GroupSTENT=7) were included with twelve patients (GroupDIL n=5; GroupSTENT=7) being eligible for complete follow-up. Technical success was achieved in all cases. Adverse events were border-line significantly more common in the GroupSTENT: 4/7 (57%) (pain: n=3; pain and rectal bleeding: n=1) compared with the GroupDIL: 0/5 (0%), p=0.08, which resulted in preterm termination of the study. The clinical success rate was GroupSTENT: 6/7 (86%) vs GroupDIL: 1/5 (20%), p=0.07. Conclusion Patients with strictures related to Crohn’s disease may benefit from treatment with self-expandable metal stents rather than dilatation. However, there seems to be an increased risk for patient pain after stenting, which has to be considered and handled. Trail registration number The study was registered at Clinical Trials (NCT04718493).