Miracle-dz/UniFAR-FTUs huggingface dataset:
Family Perspectives on Clinical Research for Pediatric Multiple Sclerosis: Enhancing Equity

Pediatric new drug trials are federally mandated, but family perspectives in multiple sclerosis (MS) research are limited. Due to MS chronicity and long-term medical system involvement, we obtained family views on research priorities and optimized methods for future studies. Focus groups were convened with families impacted by pediatric-onset MS. Recruitment included those followed by the Network of Pediatric MS Centers, geographically disparate locations, and centers’ voluntary election. Study questions included: healthcare experiences, clinical trials perspectives, cognitive/psychosocial/educational outcomes, disease course and disability accrual. All subjects supported future clinical studies. Patients highlighted contribution to knowledge base but were wary of experimental medication and disease-course impeding activities. Parents underscored medication delivery modalities, side-effects, and limiting children’s discomfort. All wanted study relevance made explicit. Suggested future study design elements included: providing compensation, limiting assumptions regarding outcome linkages, understanding study-related psychological impacts, and reducing participation burdens. Rare disease research can assist general medicine diagnosis and referral. Variable study designs and explicit rationale may augment participation. Closing the pediatric research gap requires family engagement in the research process.
SSMFN: a fused spatial and sequential deep learning model for methylation site prediction

Background Conventional in vivo methods for post-translational modification site prediction such as spectrophotometry, Western blotting, and chromatin immune precipitation can be very expensive and time-consuming. Neural networks (NN) are one of the computational approaches that can predict effectively the post-translational modification site. We developed a neural network model, namely the Sequential and Spatial Methylation Fusion Network (SSMFN), to predict possible methylation sites on protein sequences. Method We designed our model to be able to extract spatial and sequential information from amino acid sequences. Convolutional neural networks (CNN) is applied to harness spatial information, while long short-term memory (LSTM) is applied for sequential data. The latent representation of the CNN and LSTM branch are then fused. Afterwards, we compared the performance of our proposed model to the state-of-the-art methylation site prediction models on the balanced and imbalanced dataset. Results Our model appeared to be better in almost all measurement when trained on the balanced training dataset. On the imbalanced training dataset, all of the models gave better performance since they are trained on more data. In several metrics, our model also surpasses the PRMePred model, which requires a laborious effort for feature extraction and selection. Conclusion Our models achieved the best performance across different environments in almost all measurements. Also, our result suggests that the NN model trained on a balanced training dataset and tested on an imbalanced dataset will offer high specificity and low sensitivity. Thus, the NN model for methylation site prediction should be trained on an imbalanced dataset. Since in the actual application, there are far more negative samples than positive samples.
Sensitive timing of undifferentiation in oligodendrocyte progenitor cells and their enhanced maturation in primary visual cortex of binocularly enucleated mice

Sensory experience modulates proliferation, differentiation, and migration of oligodendrocyte progenitor cells (OPCs). In the mouse primary visual cortex (V1), visual deprivation-dependent modulation of OPCs has not been demonstrated. Here, we demonstrate that undifferentiated OPCs developmentally peaked around postnatal day (P) 25, and binocular enucleation (BE) from the time of eye opening (P14-15) elevated symmetrically-divided undifferentiated OPCs in a reversible G0/G1 state even more at the bottom lamina of the cortex by reducing maturing oligodendrocyte (OL) lineage cells. Experiments using the sonic hedgehog (Shh) signaling inhibitor cyclopamine in vivo suggested that Shh signaling pathway was involved in the BE-induced undifferentiation process. The undifferentiated OPCs then differentiated within 5 days, independent of the experience, becoming mostly quiescent cells in control mice, while altering the mode of sister cell symmetry and forming quiescent as well as maturing cells in the enucleated mice. At P50, BE increased mature OLs via symmetric and asymmetric modes of cell segregation, resulting in more populated mature OLs at the bottom layer of the cortex. These data suggest that fourth postnatal week, corresponding to the early critical period of ocular dominance plasticity, is a developmentally sensitive period for OPC state changes. Overall, the visual loss promoted undifferentiation at the early period, but later increased the formation of mature OLs via a change in the mode of cell type symmetry at the bottom layer of mouse V1.
Stem Cell Therapy and Its Significance in Pain Management

Pain management has always been a challenging issue, which is why it has been a major focus of many rigorous studies. Chronic pain which typically lasts for more than three months is prevalent at an astounding rate of 11% to 19% of the adult population. Pain management techniques have gone through major advances in the last decade with no major improvement in the quality of life in affected populations. Recently there has been growing interest in the utilization of stem cells for pain management. Advancement of stem cell therapy has been noted for the past few years and is now being used in human clinical trials. Stem cell therapy has shown promising results in the management of neuropathic, discogenic back, osteoarthritis, and musculoskeletal pain. In this article, we will discuss the role of stem cells in the pain management of the aforementioned conditions, along with the mechanism, adverse effects, and risks of stem cell therapy.
Anthropometrics of Estonian children in relation to family disruption

Abstract Background and objectives The thrifty phenotype hypothesis proposes that at resource limitation, the growth of some organs/tissues is selectively spared to preserve more critical ones, such as the brain or lungs. The Trivers–Willard hypothesis (TWH) predicts that boys are more vulnerable in the case of resource limitation than girls. Both hypotheses were tested in children from disrupted families, differing in the extent of deprivation/adversities imposed on them. Methodology In a retrospective cohort study in the mid-20th century Estonia (Juhan Aul’s database), different types of orphans and children of divorced parents (treatment groups; n = 106–1401) were compared with children from bi-parental families (control groups; n = 2548–8648) so that children from treatment groups were matched with control children on the basis of sex, age, year of birth, urban versus rural origin and socioeconomic position. Results Children in orphanages suffered strong growth suppression, best explained by psychosocial deprivation. Their feet were on average 0.5 SD shorter than the feet of the controls, followed by height, leg/torso ratio and cranial volume that differed from controls by ca 0.4 SD. Weight difference was 0.2 SD units, while body mass index did not differ from controls. The growth of boys and girls in orphanages was suppressed to the same extent. Boys whose mothers were dead were relatively smaller and less masculine than girls from such families. Fathers’ absence was unrelated to growth suppression. Sons of divorced parents had broader shoulders than boys whose fathers were dead. Conclusions and implications Prediction of TWH about the greater vulnerability of male growth may hold under some conditions but not universally. Predictions of the thrifty phenotype hypothesis were partly supported: trunk growth was spared at the expense of leg growth; however, no evidence for brain sparing was found. Comparison of children of divorced versus dead fathers may appear useful for indirect assessment of sexual selection on offspring quality. Lay Summary: Boys and girls in orphanages suffered similarly strong growth suppression, best explained by psychosocial deprivation. Boys whose mothers were dead were relatively smaller and less masculine than girls from such families. The occurrence of sex-specific associations between family structure and children’s growth depends on the type of family disruption.
Followership at a distance: Follower adjustment to distal leadership during COVID‐19

Abstract Leader distance theory has received scant empirical attention in the extant literature; however, the “work from home” orders associated with COVID‐19 have made this theory and its empirical findings highly relevant for organizations. Our study integrates leader distance theory and followership theory to understand how follower role beliefs affect follower effort, performance, and withdrawal under physical leader distance and varying conditions of leader interaction frequency. Using a three‐wave survey methodology with 260 adults working remotely, our study finds that followers' levels of effort, performance, and withdrawal were contingent on leader interaction frequency. Specifically, followers with a coproduction role orientation, who see their role as more collaborative, reported higher levels of effort under conditions of high leader interaction. Furthermore, the indirect effect of coproduction on follower performance and withdrawal via effort was moderated by leader interaction frequency. The results for followers with passive role orientations, however, were in the opposite direction. These followers reported less effort when leader interaction was high, and the mediational chain predicting performance and withdrawal was contingent on leader interaction frequency. Our study contributes to the ongoing conversation about the positive and negative effects of leader distance and positions followership characteristics as important boundary conditions of distal leadership.
Butorphanol alleviates lipopolysaccharide-induced inflammation and apoptosis of cardiomyocytes via activation of the κ-opioid receptor

Sepsis-induced myocardial dysfunction is a leading cause of the high mortality rates associated with sepsis. The aim of the present study was to investigate the effect of butorphanol on sepsis-induced cardiomyocyte dysfunction. Lipopolysaccharide (LPS) was used to induce H9C2 cardiomyocytes to establish an in vitro sepsis model. The effect of butorphanol on the viability of LPS-induced H9C2 cells was analyzed using a Cell Counting Kit-8 assay. The levels of tumor necrosis factor-α, interleukin (IL)-1β and IL-6 were detected using ELISA. Western blotting was used to analyze the expression levels of inflammation-and apoptosis-related proteins. Cell apoptosis was measured using a TUNEL assay. The expression levels of κ-opioid receptor (KOR) were analyzed using reverse transcription-quantitative PCR analysis and western blotting. Following LPS induction, the levels of inflammatory cytokines and proapoptotic proteins were found to be upregulated in H9C2 cells, while butorphanol treatment downregulated these levels. The expression levels of KOR were also upregulated following butorphanol treatment in LPS-induced H9C2 cells. Addition of the KOR inhibitor, nor-binaltorphimine, alleviated the inhibitory effects of butorphanol on inflammation and apoptosis in LPS-induced H9C2 cells. In conclusion, the findings of the present study provided evidence indicating that butorphanol may alleviate LPS-induced inflammation and apoptosis in cardiomyocytes by upregulating KOR expression, which may provide a novel insight into the potential therapeutic effects of butorphanol and its underlying mechanism of action.
Germline mutation analyses of malignant ground glass opacity nodules in non-smoking lung adenocarcinoma patients

Background Germline mutations play an important role in the pathogenesis of lung cancer. Nonetheless, research on malignant ground glass opacity (GGO) nodules is limited. Methods A total of 13 participants with malignant GGO nodules were recruited in this study. Peripheral blood was used for exome sequencing, and germline mutations were analyzed using InterVar. The whole exome sequencing dataset was analyzed using a filtering strategy. KOBAS 3.0 was used to analyze KEGG pathway to further identify possible deleterious mutations. Results There were seven potentially deleterious germline mutations. NM_001184790:exon8: c.C1070T in PARD3, NM_001170721:exon4:c.C392T in BCAR1 and NM_001127221:exon46: c.G6587A in CACNA1A were present in three cases each; rs756875895 frameshift in MAX, NM_005732: exon13:c. 2165_2166insT in RAD50 and NM_001142316:exon2:c.G203C in LMO2, were present in two cases each; one variant was present in NOTCH3. Conclusions Our results expand the germline mutation spectrum in malignant GGO nodules. Importantly, these findings will potentially help screen the high-risk population, guide their health management, and contribute to their clinical treatment and determination of prognosis.
An autoethnography of pregnancy and birth during Covid times: Transcending the illusio of overwork in academia?

Abstract Under the pressure of always increasing demands of publication, excessive working hours are widespread in academia. Based on an autoethnography of myself as a pregnant woman under Covid, I explore the extent of my being caught by the illusio–“being taken in and by the game” (Bourdieu & Wacquant, 1992), that prompted me to remain absorbed by the publishing game and to overwork until the very last day before giving birth to my son. I also explore how the forced deceleration induced by the maternity leave as well as the Covid confinement contributed to increased awareness and reflection thus helping me to transcend the illusio that prompted me to overwork. I also reflect to the extent of this conversion being reversible given the continued pressures of the academic context.
Examining performance and likelihood ratios for two likelihood ratio systems using the PROVEDIt dataset

A likelihood ratio (LR) system is defined as the entire pipeline of the measurement and interpretation processes where probabilistic genotyping software (PGS) is a piece of the whole LR system. To gain understanding on how two LR systems perform, a total of 154 two-person, 147 three-person, and 127 four-person mixture profiles of varying DNA quality, DNA quantity, and mixture ratios were obtained from the filtered (.CSV) files of the GlobalFiler 29 cycles 15s PROVEDIt dataset and deconvolved in two independently developed fully continuous programs, STRmix v2.6 and EuroForMix v2.1. 0. Various parameters were set in each software and LR computations obtained from the two software were based on same/fixed EPG features, same pair of propositions, number of contributors, theta, and population allele frequencies. The ability of each LR system to discriminate between contributor (H1-true) and non-contributor (H2-true) scenarios was evaluated qualitatively and quantitatively. Differences in the numeric LR values and their corresponding verbal classifications between the two LR systems were compared. The magnitude of the differences in the assigned LRs and the potential explanations for the observed differences greater than or equal to 3 on the log10 scale were described. Cases of LR < 1 for H1-true tests and LR > 1 for H2-true tests were also discussed. Our intent is to demonstrate the value of using a publicly available ground truth known mixture dataset to assess discrimination performance of any LR system and show the steps used to understand similarities and differences between different LR systems. We share our observations with the forensic community and describe how examining more than one PGS with similar discrimination power can be beneficial, help analysts compare interpretation especially with low-template profiles or minor contributor cases, and be a potential additional diagnostic check even if software in use does contain certain diagnostic statistics as part of the output.
Risk and protective factors associated with grandparent kinship caregivers' psychological distress in COVID‐19: Kinship license status as a moderator

Abstract COVID‐19 and its related policy measures have increased the psychological distress of individuals, including grandparent kinship caregivers. Guided by the Resilience Model of Family Stress, Adjustment, and Adaptation, this study examines relationships between material hardship, parenting stress, social support, resilience and psychological distress of grandparent kinship caregivers during the COVID‐19 pandemic, as well as the moderating role of kinship license status on these relationships. Kinship care licensing is a prerequisite to receiving financial assistance and other supporting services from the government. We administered a cross‐sectional survey of grandparent kinship caregivers (N = 362) in the United States. Logistic regression results indicated that material hardship was associated with higher odds of experiencing psychological distress, whereas resilience and social support were associated with lower odds. Kinship license status moderated the relationships of social support and resilience with psychological distress. Results suggest that additional emergency funds and more tailored financial services should be provided to meet material needs, and interventions with a focus on resilience and social support are particularly needed. The moderating effects of license status indicate that some interventions should be specifically implemented among licensed kinship caregivers, whereas parallel services should be provided to kinship caregivers regardless of their license status.
Comparison of Epidural Dexmedetomidine Versus Ropivacaine Infusion Effectiveness in Preventing Erection Following Reconstructive Urethral Surgery: A Randomized Clinical Trial

Background One of the most common devastating problems that occur after urethroplasty is erection, which causes surgical complications (fistula, wound dehiscence, and surgical graft failure) and the need for repairing the complications. We attempted to compare the effect of continuous epidural infusion of dexmedetomidine and ropivacaine as a post-surgical erection prevention strategy. Objectives In this study, we aimed to compare the effect of dexmedetomidine and ropivacaine epidural infusion on the incidence of erection after reconstructive urethral surgery. Methods An RCT was conducted on 45 patients who were scheduled for reconstructive urethral surgery. They were randomly divided into three groups: (1) control (n = 15), (2) epidural dexmedetomidine (n = 15), (3) and epidural ropivacaine (n = 15). The control group received oral medication after surgery according to the conventional method (cyproterone compound tablets 50 mg BD and diazepam tablets 2 mg TDS for a week) to prevent erection. The DEX group received dexmedetomidine as continuous epidural infusion, and the ROP group received ropivacaine in addition to the conventional method. The occurrence of erection during day and night was recorded separately until the seventh day after surgery. Due to the long-time interval between case selection, participants from different groups were not matched with each other. Results The incidence of erection in the dexmedetomidine group was lower than that in the ropivacaine group per person (0.87) and significantly lower than in the control group (2.8 per person). Also, there was significantly less erection in the ropivacaine group (1.2 per person) than in the control group. Our study showed that erection after surgery significantly decreased with the continuous epidural infusion of dexmedetomidine and ropivacaine. Conclusions Dexmedetomidine seems to have a significant preventive effect on erection after reconstructive urethral surgery.
When, why, and how do People Deviate from Physical Distancing Measures During the COVID-19 Pandemic: A Mixed-Methods Study

Introduction: To limit the spread of COVID-19, many countries, including Belgium, have installed physical distancing measures. Yet, adherence to these newly installed behavioral measures has been described as challenging and effortful. Based on the Health Action Process Approach (HAPA) model, this study performed an in-depth evaluation of when, why, and how people deviated from the physical distancing measures. Methods: An online mixed-method study was conducted among Belgian adults (N = 2055) in the beginning of May 2020. Participants were recruited via an open call through email and social media platforms, using snowball sampling. Conditions wherein people deviated from the physical distancing measures were assessed by means of an open-ended question. HAPA determinants were assessed in a quantitative way. Results: Half of the sample reported to deviate from the measures. Further, deviation from the measures was associated with each determinant outlined by the HAPA. Findings highlight that many people deviated from the measures because of their need for social contact. The majority of the people who deviated from the measures stated that they carefully weighed the risks of their behavior. Conclusions: Need for social contact pushed people to deviate from physical distancing measures in a deliberate manner. Potential areas for future interventions aimed at promoting adherence to physical distancing measures and enhancing psychosocial well-being are discussed.
Ipsilateral internal carotid artery web and acute ischemic stroke: A cohort study, systematic review and meta-analysis

Introduction The carotid web is a compelling potential mechanism of embolic ischemic stroke. In this study, we aim to determine the prevalence of ipsilateral carotid web in a cohort of ischemic stroke patients and to perform a systematic review and meta-analysis of similar cohorts. Patients & methods We performed a retrospective, observational, cohort study of acute ischemic stroke patients admitted to a comprehensive stroke center from June 2012 to September 2017. Carotid web was defined on computed tomography angiography (CTA) as a thin shelf of non-calcified tissue immediately distal to the carotid bifurcation. We described the prevalence of carotid artery webs in our cohort, then performed a systematic review and meta-analysis of similar cohorts in the published literature. Results We identified 1,435 potentially eligible patients of whom 879 met criteria for inclusion in our analysis. An ipsilateral carotid web was detected in 4 out of 879 (0.45%) patients, of which 4/4 (1.6%) were in 244 patients with cryptogenic stroke and 3/4 were in 66 (4.5%) patients <60 years old with cryptogenic stroke. Our systematic review yielded 3,192 patients. On meta-analysis, the pooled prevalence of ipsilateral carotid web in cryptogenic stroke patients <60 was 13% (95% CI: 7%-22%; I2 = 66.1%). The relative risk (RR) of ipsilateral versus contralateral carotid web in all patients was 2.5 (95% CI 1.5–4.2, p = 0.0009) whereas in patients less than 60 with cryptogenic stroke it was 3.0 (95% CI 1.6–5.8, p = 0.0011). Discussion Carotid webs are more common in young patients with cryptogenic stroke than in other stroke subtypes. Future studies concerning the diagnosis and secondary prevention of stroke associated with carotid web should focus on this population.