Miracle-dz/UniFAR-FTUs huggingface dataset:
Factors associated with resilience among children and youths with disability during the COVID-19 pandemic

There is evidence of negative impact of social distancing and confinement measures to manage the COVID-19 pandemic on children, including increased anxiety and depression and behaviour difficulties. Paradoxically, positive impacts like increased support and more self-care activities have also been documented. Little is known about the impact of the COVID-19 pandemic on the children with disability and the potential role of familial, environmental, and biological factors on mitigating this impact. The aims of the study were 1) identifying profiles of functioning across multiple domains during the COVID-19 pandemic and 2) examining the extent to which parenting self-efficacy, support in accessing schooling, and type of diagnosis predict the likelihood of resilience among children with disability, after controlling for household income and single-parent status. An online survey developed from COVID-19 guidance recommendations, was available from June 11- July 21, 2020, and resulted in a convenience sample of caregivers across Canada (n = 883) of children with disability (mean age of 9.4 years old, SDage = 5.7, 58% male). We conducted latent class analysis to examine the number of latent profiles on caregiver-reported changes of 12 functioning domains, as either ‘worsening’, ‘no change’, or ‘improving’. Most participants belonged to ‘stable’ or ‘worsening’ profiles. However, we identified a small subgroup with improvements in child functioning, a pattern indicative of a ‘resilient’ profile. Using a multinomial logistic regression, we found that diagnosis type, parenting self-efficacy and support in accessing schooling were associated with membership in the Resilient or Stable profiles compared to the Worsening profile, after controlling for single-parent status and income. Taken together, our findings identified variability in responses to adversity that is dependent on the child’s diagnosis type, parenting self-efficacy, and support in accessing schooling. By identifying potentially modifiable predictors of resilience, namely parenting self-efficacy and support in accessing schooling, we signal the potential for tailored supports for different diagnoses, through interventions that enhance caregiver empowerment, access to schooling, access to health and social services, and/or mitigate disparities resulting from social disadvantage.
Tuning Lasso for sup-norm optimality

We introduce novel schemes for tuning parameter calibration in high-dimensional linear regression with Lasso. These calibration schemes are inspired by Lepski's method for bandwidth adaptation in non-parametric regression and are the first calibration schemes that are equipped with both theoretical guarantees and fast algorithms. In particular, we develop optimal finite sample guarantees for sup-norm performance and give algorithms that consist of simple tests along a single Lasso path. Moreover, we show that false positives can be safely reduced without increasing the number of false negatives. Applying Lasso to synthetic data and to real data, we finally demonstrate that the novel schemes can rival standard schemes such as Cross-Validation in speed as well as in sup-norm and variable selection performance.
Oxygen gradients dictate angiogenesis but not barriergenesis in a 3D brain microvascular model

A variety of biophysical properties are known to regulate angiogenic sprouting, and in vitro systems can parse the individual effects of these factors in a controlled setting. Here, a three‐dimensional brain microvascular model interrogates how variables including extracellular matrix composition, fluid shear stress, and radius of curvature affect angiogenic sprouting of cerebral endothelial cells. Tracking endothelial migration over several days reveals that application of fluid shear stress and enlarged vessel radius of curvature both attenuate sprouting. Computational modeling informed by oxygen consumption assays suggests that sprouting correlates to reduced oxygen concentration: both fluid shear stress and vessel geometry alter the local oxygen levels dictated by both ambient conditions and cellular respiration. Moreover, increasing cell density and consequently lowering the local oxygen levels yields significantly more sprouting. Further analysis reveals that the magnitude of oxygen concentration is not as important as its spatial concentration gradient: decreasing ambient oxygen concentration causes significantly less sprouting than applying an external oxygen gradient to the vessels. In contrast, barriergenesis is dictated by shear stress independent of local oxygen concentrations, suggesting that different mechanisms mediate angiogenesis and barrier formation and that angiogenic sprouting can occur without compromising the barrier. Overall, these results improve our understanding of how specific biophysical variables regulate the function and activation of cerebral vasculature, and identify spatial oxygen gradients as the driving factor of angiogenesis in the brain.
Combined Blockade Of PD-1 and TIGIT is not Sufficient to Improve the Function Of CD8+ T-Cells in Chronic Lymphocytic Leukemia

Background and Objective: Blockade of immune checkpoint receptors in the treatment of cancers has been mentioned in several studies. Here, we investigated the efficacy of combined blockade of two inhibitory receptors, PD-1 and TIGIT, in restoring functional features of CD8+ T-cells in CLL. Methods: CD8+ T-cells were separated from the peripheral blood of 11 CLL patients and targeted with malignant B-cells isolated from the same patients. Cells were then stimulated with anti-CD3/CD28 and PMA/ionomycin to assess their proliferative response and cytotoxic activity using MTT and CD107a degranulation assays, respectively. Cytokine production of isolated CD8+ T-cells was also determined using ELISA. Results: There were no significant differences in proliferation and cytotoxic activity of CD8+ T-cells co-blocked with anti-PD-1/TIGIT compared to those single blocked with anti-PD-1, anti-TIGIT, or the control antibody. There was no significant difference in cytokine production of mentioned groups, either. Conclusions: Collectively, combined blockade of PD-1 and TIGIT failed to restore the proliferation and function of CD8+ T-cells isolated from CLL patients.
Duodenal eosinophilia is associated with symptomatic erosive gastro-oesophageal reflux disease, presence of co-morbidities, and ethnicity but not undifferentiated functional dyspepsia: A retrospective Malaysian study.

BACKGROUND Duodenal eosinophilia is postulated to play a key role in the pathogenesis of functional dyspepsia, a common condition responsible for considerable impairment of quality of life. Our objective was to evaluate the relative strength of the associations between duodenal eosinophilia, functional dyspepsia, symptomatic erosive gastroesophageal reflux disease (GERD), the presence of co-morbidities, and a number of other variables. METHODS Eosinophil counts of archived endoscopic duodenal biopsies of 289 subjects were determined by a pathologist blinded to the clinical data. Duodenal eosinophilia was defined by a count of more than 15 per 5 high power fields. Clinical charts were reviewed by a gastroenterologist blinded to the histology review. RESULTS In the study sample, the primary diagnosis was functional dyspepsia (undifferentiated by subtypes) in 45, symptomatic erosive GERD in 29, gall stone disease in 17, irritable bowel syndrome in 23, and an alternative or undetermined diagnosis in 175 subjects, respectively. On logistic regression analyses, eosinophil counts were positively associated with symptomatic erosive GERD (Odds Ratio, OR 1.03, 95% Confidence Interval, 95%CI: 1.00, 1.05; p=0.035) but not functional dyspepsia. Pre-defined duodenal eosinophilia was associated with symptomatic erosive gastro-oesophageal reflux disease (OR 3.36, 95%CI 1.18,-9.60; p=0.023), the presence of co-morbidities (OR 2.00, 95%CI 1.10, 3.62; p=0.022), and Chinese (as compared to Malay and Indian) ethnicity but not with either functional dyspepsia, irritable bowel syndrome, gallstone disease, Helicobacter pylori infection, or gender. CONCLUSION Duodenal eosinophilia was associated with symptomatic erosive GERD, the presence of co-morbidities, and Chinese ethnicity but not with undifferentiated functional dyspepsia.
Beyond arboviruses: A multicenter study to evaluate differential diagnosis of rash diseases and acute febrile illness cases in Rio de Janeiro, Brazil

Introduction A wide variety of viruses can cause rash diseases (RDs) or acute febrile illness (AFIs) in children, adolescents and adults; however, approximately 19% of RD cases and 40% of AFI cases remain without a defined etiology. Parvovirus B19 (B19V) and herpesvirus infection can also cause RD and/or AFI, and in some risk groups, these infections can become persistent (or latent) and may require hospital treatment. Since these infections do not have mandatory reporting, they can be hidden by other diseases, such as those caused by arboviruses (e.g., dengue virus). In this context, the aim of this study was to pursue the differential laboratory diagnoses of B19V and herpesvirus infections in patients with RD and AFI, without a defined etiology, seen in hospitals and/or reference centers for infectious diseases in Rio de Janeiro. Methods A total of 114 participants were enrolled in the study, including 54 children and 60 adults. B19V infection was assessed by real-time PCR (qPCR) and ELISA (anti-B19V IgM and IgG). EBV was assessed through qPCR, and betaherpesviruses (HCMV, HHV-6 and HHV-7) were assessed through multiplex qPCR. Sociodemographic and clinical data were obtained from the medical record data of these participants. Results The median age of children with RD was 2 years (interquartile range (IQR): 5), and 55.6% were male. Among adults with AFI, the median age was 38 years (IQR: 21), and 56.7% were female. Regarding RD patients, viral prevalence (and load) were 5.5%(104IU/mL), 3.4%(104IU/mL), 5.5%(104IU/mL) and 11.1%(105IU/mL) for B19V, EBV, HCMV and HHV-6 infection, respectively, and in AFI patients they were 6.6%(105IU/mL), 1.6%(103IU/mL), 3.3%(104IU/mL) for B19V, HCMV and HHV-6, respectively. HHV-7 was not detected in RD or AFI patients. Conclusion These results suggest the importance of including B19V and herpesviruses in the differential laboratory diagnoses for patients with RD and AFI, not only for epidemiological purposes but also for the proper management of the patient.
The HDAC7–TET2 epigenetic axis is essential during early B lymphocyte development

Abstract Correct B cell identity at each stage of cellular differentiation during B lymphocyte development is critically dependent on a tightly controlled epigenomic landscape. We previously identified HDAC7 as an essential regulator of early B cell development and its absence leads to a drastic block at the pro-B to pre-B cell transition. More recently, we demonstrated that HDAC7 loss in pro-B-ALL in infants associates with a worse prognosis. Here we delineate the molecular mechanisms by which HDAC7 modulates early B cell development. We find that HDAC7 deficiency drives global chromatin de-condensation, histone marks deposition and deregulates other epigenetic regulators and mobile elements. Specifically, the absence of HDAC7 induces TET2 expression, which promotes DNA 5-hydroxymethylation and chromatin de-condensation. HDAC7 deficiency also results in the aberrant expression of microRNAs and LINE-1 transposable elements. These findings shed light on the mechanisms by which HDAC7 loss or misregulation may lead to B cell–based hematological malignancies.
Disability Pension Did Not Reduce Opioid Use Among Patients With Failed Back Surgery Syndrome Who Were Trialed and Implanted for Spinal Cord Stimulation.

BACKGROUND Spinal cord stimulation (SCS) is an effective treatment for failed back surgery syndrome (FBSS). In patients with FBSS, opioids have often been initiated, even before SCS is trialed. OBJECTIVE We studied the effect of retirement on opioid use in patients with chronic pain after failed back surgery. STUDY DESIGN A retrospective study design. SETTING The study was conducted at Kuopio University Hospital. METHODS The study group consisted of all 230 patients with SCS trialed or implanted for FBSS at Kuopio University Hospital Neurosurgery from January 1, 1996 through December 31, 2014. All purchases of prescribed opioids and their daily defined doses, as well as data on working ability, were obtained from the Social Insurance Institution. Patients were divided into 3 groups: SCS trial only, SCS implanted permanently, and SCS implanted but later explanted. We analyzed the differences in opioid use among these groups 2 years before and 2 years after the start of their disability pension (DP). RESULTS During the follow-up period, a total of 60 patients received a DP. One year before DP, the majority of patients used opioids (n = 43, 72%), and throughout the one-year follow-up after retirement, the number of users increased slightly (n = 46, 77%). In the permanently implanted SCS group, the number of strong opioid users decreased after retirement. Most patients used a moderate dose (0.1-10.5 morphine milligram equivalent/d). Retirement appeared to interrupt dose escalation in all groups, but doses increased further as the follow-up continued. LIMITATIONS No structured questionnaires were used in this study. Also, many underlying factors contributing to chronic pain were missing. CONCLUSIONS DP did not reduce the use of opioids in patients with FBSS. Opioid doses were lower and dose escalation less steep with continuous SCS therapy.
Current status of reimbursement practices for remote monitoring of cardiac implantable electrical devices across Europe

Abstract Remote monitoring (RM) of cardiac implantable electrical devices (CIEDs) is currently proposed as a standard of care for CIEDs follow-up, as recommended by major cardiology societies worldwide. By detecting a series of relevant device and patient-related parameters, RM is a valuable option for early detection of CIEDs' technical issues, as well as changes in parameters related to cardio-respiratory functions. Moreover, RM may allow longer spacing between in-office follow-ups and better organization of in-hospital resources. Despite these potential advantages, resulting in improved patient safety, we are still far from a widespread diffusion of RM across Europe. Reimbursement policies across Europe still show an important heterogeneity and have been considered as an important barrier to full implementation of RM as a standard for the follow-up of all the patients with pacemakers, defibrillators, devices for cardiac resynchronization, or implantable loop recorders. Indeed, in many countries, there are still inertia and unresponsiveness to the request for widespread implementation of RM for CIEDs, although an improvement was found in some countries as compared to years ago, related to the provision of some form of reimbursement. As a matter of fact, the COVID-19 pandemic has promoted an increased use of digital health for connecting physicians to patients, even if digital literacy may be a limit for the widespread implementation of telemedicine. CIEDs have the advantage of making possible RM with an already defined organization and reliable systems for data transmissions that can be easily implemented as a standard of care for present and future cardiology practice.
Correlation of Moraxella catarrhalis macrolide susceptibility with the ability to adhere and invade human respiratory epithelial cells

ABSTRACT Recently, the prevalence of macrolide-resistant Moraxella catarrhalis has been reported, especially among Chinese children. The fitness cost of resistance is reported to render the resistant bacteria less virulent. To investigate the correlation between macrolide susceptibility of M. catarrhalis and pathogenicity, the whole genome of 70 M. catarrhalis isolates belonging to four clonal complexes with different macrolide susceptibilities was sequenced. The gene products were annotated with the Gene Ontology terms. Based on 46 extracted essential virulence genes, 19 representative isolates were selected to infect type II alveolar cells (A549 cells). The ability of these isolates to adhere and invade human epithelial cells and to produce cytokines was comparatively analysed. Furthermore, mice were infected with a pair of M. catarrhalis isolates with different pathogenic behaviours and macrolide susceptibilities to examine pulmonary clearance, histological findings, and the production of cytokines. The percentages of annotations for binding, metabolic process, cellular process, and cell were non-significantly different between the macrolide-resistant and macrolide-susceptible groups. The presence of uspA2, uspA2H, pilO, lbpB, lex1, modM, mboIA, and mboIB significantly differed among the four clonal complexes and macrolide susceptibility groups. Furthermore, compared with those in macrolide-susceptible isolates, the adhesion ability was stronger (P = 0.0019) and the invasion ability was weaker (P < 0.0001) in the macrolide-resistant isolates. Mouse experiments revealed that pulmonary macrophages elicit immune responses against M. catarrhalis infection by significantly upregulating the Csf2, Il4, Il13, Il1b, Il6, Tnf, and Il18. Therefore, M. catarrhalis populations exhibited diverse pathogenicity in vitro and in vivo.
Noninvasive Brain Stimulation: Multiple Effects on Cognition

Noninvasive brain stimulation (NIBS) techniques are widely used tools for the study and rehabilitation of cognitive functions. Different NIBS approaches aim to enhance or impair different cognitive processes. The methodological focus for achieving this has been on stimulation protocols that are considered either inhibitory or facilitatory. However, despite more than three decades of use, their application is based on incomplete and overly simplistic conceptualizations of mechanisms of action. Such misconception limits the usefulness of these approaches in the basic science and clinical domains. In this review, we challenge this view by arguing that stimulation protocols themselves are neither inhibitory nor facilitatory. Instead, we suggest that all induced effects reflect complex interactions of internal and external factors. Given these considerations, we present a novel model in which we conceptualize NIBS effects as an interaction between brain activity and the characteristics of the external stimulus. This interactive model can explain various phenomena in the brain stimulation literature that have been considered unexpected or paradoxical. We argue that these effects no longer seem paradoxical when considered from the viewpoint of state dependency.
In vitro antifungal activity of Morinda citrifolia (noni) extract against Candida albicans.

INTRODUCTION Candida albicans is the main agent of the most common fungal infection, Candidiasis. It is an opportunistic and dangerous pathogen, especially in immunosuppressed patients. The biological properties of Morinda citrifolia (noni) make it a potent antifungal. In this study, antifungal effect of M. citrifolia was evaluated to verify its effect on human cells. METHODOLOGY Extract of M. citrifolia was used against strains of C. albicans (cEC 1291). Glucose consumption in C. albicans biofilm was determined at different concentrations of M. citrifolia, and germ tube formation was evaluated in the presence and absence of M. citrifolia. Fungicidal activity was determined by the kinetics of fungal cell death. THP-1 and HeLa cells were used for cell viability and apoptosis, and cell proliferation assays, respectively. RESULTS Cells treated with M. citrifolia maintained higher concentration of glucose than the control group (p < 0.05). Germ tube formation was inhibited in cells treated with M. citrifolia (p < 0.05). M. citrifolia exerted a cytotoxic effect on C. albicans cells with 99.99% lethality after 6.82 h (1:1 and 1:2), and reduced the viability of THP-1 cells by 25% and 67% after 12 and 36 h, respectively. Annexin V expression in THP-1 increased in groups that received higher concentrations of M. citrifolia (p < 0.05), reducing the proliferation of THP-1 and HeLa cells (2.8-fold). A greater cytotoxic effect was observed in fungal cells. CONCLUSIONS These results indicate that M. citrifolia exerts biological activity against C. albicans and reduces the viability and proliferation of human cells.
Early Drug Prescription Patterns as Predictors of Final Workers Compensation Claim Costs and Closure

This study evaluated the early drug prescription patterns as predictors of final workers compensation claim costs and closure based on an updated analysis on a large cohort. The result would provide claim management with tools to estimate final claims outcomes in the first 3- or 6-months post-injury. Objective The aim of the study is to determine the associations of workers’ compensation claim costs and return to work with drugs prescribed for early symptom management. Methods Claims filed from 1998 to 2007 were followed for 10 years from the injury date. Drugs analyzed included gabapentin, pregabalin, antipsychotics, antidepressants, sedatives, benzodiazepines, carisoprodol, and opioids, controlling for initial reserve, sex, age, physical therapy, attorney involvement, and surgery. Results Gabapentin, antipsychotics, antidepressants, and sedatives used in the first 3 months after injury were significantly associated with higher claim cost (≥$100,000). All opioid morphine equivalent doses greater than or equal to 5 mg/d for the first 6 months was significantly associated with higher cost (≥$100,000) and not being released to work at end of third year after injury with dose-response relationships. Conclusions Prescription patterns in the first 3 months or first 6 months of workers’ compensation claim development may be used as predictors of claim outcomes.
Next‐generation sequencing and analysis of consecutive patients referred for connective tissue disorders

Heritable connective tissue disorders (HCTDs) consist of a wide array of genetic disorders such as Ehlers–Danlos syndrome, Marfan syndrome, and osteogenesis imperfecta. The diagnosis relies on clinical presentation and family history to guide genetic testing with next‐generation sequencing (NGS) for identification of gene variants in HCTDs. NGS was performed on a cohort of 100 consecutive, unrelated patients referred for a connective tissue disorder at Fulgent Genetics, an accredited commercial laboratory. One hundred seventeen gene variants were found in 76 patients with 10 recognized pathogenic or likely pathogenic variants seen in nine patients. The remaining variants were grouped as unknown clinical significance with 36 meeting three out of four pathogenicity criteria, or potentially pathogenic, as defined in our study in 33 patients. They were judged as potentially pathogenic for clinical care and management with disease surveillance based on the specific gene and phenotypic presentation. Gene variants in collagen‐related proteins were the most frequent with ZNF469 and ADAMTSL2 variants most often identified. Joint hypermobility was the most frequent clinical finding. Variants were found in 76% of patients who had distinct clinical features of a HCTD. The data were stratified to provide insight into frequency and types of variants, their classification, and clinical manifestations.