Miracle-dz/UniFAR-FTUs huggingface dataset:
Human Respiratory Syncytial Virus Subgroup A and B Infections in Nasal, Bronchial, Small-Airway, and Organoid-Derived Respiratory Cultures

Human respiratory syncytial virus (HRSV) is the major cause of bronchiolitis and pneumonia in young infants and causes almost 200,000 deaths per year. Currently, there is no vaccine or treatment available, only a prophylactic monoclonal antibody (palivizumab). ABSTRACT Human respiratory syncytial virus (HRSV) is the leading cause of bronchiolitis in infants. Two subgroups of HRSV (A and B) routinely cocirculate. Most research has been performed with HRSV-A strains because these are easier to culture than HRSV-B strains. In this study, we aimed to compare the replicative fitness and HRSV-induced innate cytokine responses of HRSV-A and HRSV-B strains in disease-relevant cell culture models. We used two recombinant (r) clinical isolate-based HRSV strains (A11 and B05) and one recombinant laboratory-adapted HRSV strain (A2) to infect commercially available nasal, bronchial, and small-airway cultures. Epithelial cells from all anatomical locations were susceptible to HRSV infection despite the induction of a dominant type III interferon response. Subgroup A viruses disseminated and replicated faster than the subgroup B virus. Additionally, we studied HRSV infection and innate responses in airway organoids (AOs) cultured at air-liquid interface (ALI). Results were similar to the commercially obtained bronchial cells. In summary, we show that HRSV replicates well in cells from both the upper and the lower airways, with a slight replicative advantage for subgroup A viruses. Lastly, we showed that AOs cultured at ALI are a valuable model for studying HRSV ex vivo and that they can be used in the future to study factors that influence HRSV disease severity. IMPORTANCE Human respiratory syncytial virus (HRSV) is the major cause of bronchiolitis and pneumonia in young infants and causes almost 200,000 deaths per year. Currently, there is no vaccine or treatment available, only a prophylactic monoclonal antibody (palivizumab). An important question in HRSV pathogenesis research is why only a fraction (1 to 3%) of infants develop severe disease. Model systems comprising disease-relevant HRSV isolates and accurate and reproducible cell culture models are indispensable to study infection, replication, and innate immune responses. Here, we used differentiated AOs cultured at ALI to model the human airways. Subgroup A viruses replicated better than subgroup B viruses, which we speculate fits with epidemiological findings that subgroup A viruses cause more severe disease in infants. By using AOs cultured at ALI, we present a highly relevant, robust, and reproducible model that allows for future studies into what drives severe HRSV disease.
Quality of life assessment in amyloid transthyretin (ATTR) amyloidosis

Amyloid transthyretin (ATTR) amyloidosis is caused by the systemic deposition of transthyretin molecules, either normal (wild‐type ATTR, ATTRwt) or mutated (variant ATTR, ATTRv). ATTR amyloidosis is a disease with a severe impact on patients’ quality of life (QoL). Nonetheless, limited attention has been paid to QoL so far, and no specific tools for QoL assessment in ATTR amyloidosis currently exist. QoL can be evaluated through patient‐reported outcome measures (PROMs), which are completed by patients, or through scales, which are compiled by clinicians. The scales investigate QoL either directly or indirectly, i.e., by assessing the degree of functional impairment and limitations imposed by the disease.
Predicting patients with false negative SARS-CoV-2 testing at hospital admission: A retrospective multi-center study

Importance False negative SARS-CoV-2 tests can lead to spread of infection in the inpatient setting to other patients and healthcare workers. However, the population of patients with COVID who are admitted with false negative testing is unstudied. Objective To characterize and develop a model to predict true SARS-CoV-2 infection among patients who initially test negative for COVID by PCR. Design Retrospective cohort study. Setting Five hospitals within the Yale New Haven Health System between 3/10/2020 and 9/1/2020. Participants Adult patients who received diagnostic testing for SARS-CoV-2 virus within the first 96 hours of hospitalization. Exposure We developed a logistic regression model from readily available electronic health record data to predict SARS-CoV-2 positivity in patients who were positive for COVID and those who were negative and never retested. Main outcomes and measures This model was applied to patients testing negative for SARS-CoV-2 who were retested within the first 96 hours of hospitalization. We evaluated the ability of the model to discriminate between patients who would subsequently retest negative and those who would subsequently retest positive. Results We included 31,459 hospitalized adult patients; 2,666 of these patients tested positive for COVID and 3,511 initially tested negative for COVID and were retested. Of the patients who were retested, 61 (1.7%) had a subsequent positive COVID test. The model showed that higher age, vital sign abnormalities, and lower white blood cell count served as strong predictors for COVID positivity in these patients. The model had moderate performance to predict which patients would retest positive with a test set area under the receiver-operator characteristic (ROC) of 0.76 (95% CI 0.70–0.83). Using a cutpoint for our risk prediction model at the 90th percentile for probability, we were able to capture 35/61 (57%) of the patients who would retest positive. This cutpoint amounts to a number-needed-to-retest range between 15 and 77 patients. Conclusion and relevance We show that a pragmatic model can predict which patients should be retested for COVID. Further research is required to determine if this risk model can be applied prospectively in hospitalized patients to prevent the spread of SARS-CoV-2 infections.
Perceptions of Mobile Health Apps and Features to Support Psychosocial Well-being Among Frontline Health Care Workers Involved in the COVID-19 Pandemic Response: Qualitative Study

Background Frontline health care workers are experiencing a myriad of physical and psychosocial challenges amid the COVID-19 pandemic. There is growing recognition that digital technologies have the potential to improve the well-being of frontline workers. However, there has been limited development of wellness interventions using mobile health (mHealth) technology. More importantly, little research has been conducted on how frontline workers perceive mHealth-based support to promote their well-being. Objective This study aimed to explore frontline workers’ experience of conventional psychological wellness programs and their perceptions of the usefulness of mHealth apps and features for promoting well-being. It also sought to identify factors that could potentially influence uptake and retention of an mHealth-based wellness program. Methods We conducted semistructured interviews using purposive sampling with frontline workers involved in the COVID-19 response. Various visual materials, collated from existing mHealth app features, were presented to facilitate discussion. Interviews were audio-recorded and transcribed verbatim. Thematic analysis based on grounded theory was undertaken. Themes were subsequently mapped to key nudge strategies—those commonly used for mHealth development—to assess participants’ preferences for particular features and their reasoning. Results A total of 42 frontline workers participated in 12 one-on-one interviews or focus group discussions. Frontline workers generally had a limited ability to identify their own psychological problems and liked the reminders functionality of the app to track their mood over time. A personalized goal-setting feature (ie, tailoring) and in-app resources were generally valued, while frequent coaching and messages (ie, framing) were seen as a distraction. The majority of participants desired a built-in chat function with a counselor (ie, guidance) for reasons of accessibility and protection of privacy. Very few participants appreciated a gamification function. Frontline workers commonly reported the need for ongoing social support and desired access to an in-app peer support community (ie, social influence). There were, however, concerns regarding potential risks from virtual peer interactions. Intrinsic motivational factors, mHealth app technicality, and tangible rewards were identified as critical for uptake and retention. Conclusions Our study highlights the potential of mHealth apps with relevant features to be used as wellness tools by frontline health care workers. Future work should focus on developing a nonintrusive and personalized mHealth app with in-app counseling, peer support to improve well-being, and tangible and extrinsic rewards to foster continued use.
Infobuttons for Genomic Medicine: Requirements and Barriers

Abstract Objectives The study aimed to understand potential barriers to the adoption of health information technology projects that are released as free and open source software (FOSS). Methods We conducted a survey of research consortia participants engaged in genomic medicine implementation to assess perceived institutional barriers to the adoption of three systems: ClinGen electronic health record (EHR) Toolkit, DocUBuild, and MyResults.org. The survey included eight barriers from the Consolidated Framework for Implementation Research (CFIR), with additional barriers identified from a qualitative analysis of open-ended responses. Results We analyzed responses from 24 research consortia participants from 18 institutions. In total, 14 categories of perceived barriers were evaluated, which were consistent with other observed barriers to FOSS adoption. The most frequent perceived barriers included lack of adaptability of the system, lack of institutional priority to implement, lack of trialability, lack of advantage of alternative systems, and complexity. Conclusion In addition to understanding potential barriers, we recommend some strategies to address them (where possible), including considerations for genomic medicine. Overall, FOSS developers need to ensure systems are easy to trial and implement and need to clearly articulate benefits of their systems, especially when alternatives exist. Institutional champions will remain a critical component to prioritizing genomic medicine projects.
Depressive symptoms in early alcohol or opioid abstinence: course & correlates

Abstract Background Depressive symptoms are common during abstinence from psychoactive substances. Research caveats limit the study of persistence of significant depressive symptoms beyond four weeks of abstinence. This prospective study examined the course and correlates of depressive symptoms in patients with alcohol or opioid use disorder over 5-8 weeks. Methods Sample consisted of 100 men randomly selected out of 307 inpatient men with either alcohol or opioid use disorder. Weekly assessments focused on depressive symptoms (HDRS, BDI), and their correlates (HAM-A for anxiety symptoms, CIWA-Ar and COWS for withdrawal symptoms, OCDS and OCDUS for craving for alcohol and opioids respectively). Other correlates assessed were severity of dependence and family support. PRISM (Psychiatric Research Interview for Substance and Mental disorders) was used for diagnosis of substance-induced depression and major depressive episode. Repeated measures ANOVA was used for weekly comparison of depressive symptoms. Results Participants were dependent on opioids (56%), or alcohol (41%), or both (3%). Mean age was 33.5 years. Eighty-eight participants completed the study. Substance-induced depressive episode was diagnosed by PRISM in 59% participants. Weekly assessments of depressive symptoms recorded significant reductions (p < 0.0001; Wilk’s Lambda for HDRS and BDI 137.01 and 105.4 respectively). Baseline depressive symptoms correlated significantly with anxiety, withdrawal symptoms, and negatively with social support. No participant was diagnosed with a major depressive episode at 6-8 weeks. Conclusion Depressive symptoms in early alcohol or opioid abstinence resolve significantly over a month; therefore, clinicians should exercise watchful waiting before starting antidepressant therapy.
Improved development of mouse somatic cell nuclear transfer embryos by chlamydocin analogues, class I and IIa histone deacetylase inhibitors†

Abstract In mammalian cloning by somatic cell nuclear transfer (SCNT), the treatment of reconstructed embryos with histone deacetylase (HDAC) inhibitors improves efficiency. So far, most of those used for SCNT are hydroxamic acid derivatives—such as trichostatin A—characterized by their broad inhibitory spectrum. Here, we examined whether mouse SCNT efficiency could be improved using chlamydocin analogues, a family of newly designed agents that specifically inhibit class I and IIa HDACs. Development of SCNT-derived embryos in vitro and in vivo revealed that four out of five chlamydocin analogues tested could promote the development of cloned embryos. The highest pup rates (7.1–7.2%) were obtained with Ky-9, similar to those achieved with trichostatin A (7.2–7.3%). Thus, inhibition of class I and/or IIa HDACs in SCNT-derived embryos is enough for significant improvements in full-term development. In mouse SCNT, the exposure of reconstructed oocytes to HDAC inhibitors is limited to 8–10 h because longer inhibition with class I inhibitors causes a two-cell developmental block. Therefore, we used Ky-29, with higher selectivity for class IIa than class I HDACs for longer treatment of SCNT-derived embryos. As expected, 24-h treatment with Ky-29 up to the two-cell stage did not induce a developmental block, but the pup rate was not improved. This suggests that the one-cell stage is a critical period for improving SCNT cloning using HDAC inhibitors. Thus, chlamydocin analogues appear promising for understanding and improving the epigenetic status of mammalian SCNT-derived embryos through their specific inhibitory effects on HDACs. Summary sentence Chlamydocin analogues, a novel family of inhibitors specific for class I and IIb HDACs, significantly improved the ability of mouse SCNT-derived embryos to produce offspring.
Laughter and smiling facial expression modelling for the generation of virtual affective behavior

Laughter and smiling are significant facial expressions used in human to human communication. We present a computational model for the generation of facial expressions associated with laughter and smiling in order to facilitate the synthesis of such facial expressions in virtual characters. In addition, a new method to reproduce these types of laughter is proposed and validated using databases of generic and specific facial smile expressions. In particular, a proprietary database of laugh and smile expressions is also presented. This database lists the different types of classified and generated laughs presented in this work. The generated expressions are validated through a user study with 71 subjects, which concluded that the virtual character expressions built using the presented model are perceptually acceptable in quality and facial expression fidelity. Finally, for generalization purposes, an additional analysis shows that the results are independent of the type of virtual character’s appearance.
Renal Normothermic Machine Perfusion: The Road Toward Clinical Implementation of a Promising Pretransplant Organ Assessment Tool

Supplemental Digital Content is available in the text. The increased utilization of high-risk renal grafts for transplantation requires optimization of pretransplant organ assessment strategies. Current decision-making methods to accept an organ for transplantation lack overall predictive power and always contain an element of subjectivity. Normothermic machine perfusion (NMP) creates near-physiological conditions, which might facilitate a more objective assessment of organ quality before transplantation. NMP is rapidly gaining popularity, with various transplant centers developing their own NMP protocols and renal viability criteria. However, to date, no validated sets of on-pump viability markers exist nor are there unified NMP protocols. This review provides a critical overview of the fundamentals of current renal NMP protocols and proposes a framework to approach further development of ex vivo organ evaluation. We also comment on the potential logistical implications of routine clinical use of NMP, which is a more complex procedure compared with static cold storage or even hypothermic machine perfusion.
Dissecting pain processing in adolescents with Non‐Suicidal Self Injury: Could suicide risk lurk among the electrodes?

Although non‐suicidal self‐injury (NSSI) disorder is highly prevalent in adolescents, its relationship with pain system function and suicidality is still controversial. The present study was designed to assess the function of the nociceptive afferent pathways and the endogenous pain modulation in adolescent patients with NSSI and to longitudinally register any suicide attempt, describe its frequency and find a possible association between suicide, neurophysiological measures and psychological measures.
“This ‘Family Setting’ Is Not that Anymore”: Rewards and Challenges of Adult Foster Home Owners

ABSTRACT Small residential care settings for older adults and people with disabilities are found throughout the United States. Those with fewer than 25 residents account for half of residential care settings. Adult foster homes (AFH) are under-studied although they provide personal and health-related services to residents, including people with Alzheimer’s disease. This qualitative study collected data from 726 AFH owners over four years. Results provide a contemporary perspective on owners’ experience of the rewards and challenges of operating a small home. These results are relevant since many residents prefer small settings, and because federal regulatory changes affect AFH policies and practices.
A Systematic IoU-Related Method: Beyond Simplified Regression for Better Localization

Four-variable-independent-regression localization losses, such as Smooth-<inline-formula> <tex-math notation="LaTeX">$\ell _{1}$ </tex-math></inline-formula> Loss, are used by default in modern detectors. Nevertheless, this kind of loss is oversimplified so that it is inconsistent with the final evaluation metric, intersection over union (IoU). Directly employing the standard IoU is also not infeasible, since the constant-zero plateau in the case of non-overlapping boxes and the non-zero gradient at the minimum may make it not trainable. Accordingly, we propose a systematic method to address these problems. Firstly, we propose a new metric, the extended IoU (EIoU), which is well-defined when two boxes are not overlapping and reduced to the standard IoU when overlapping. Secondly, we present the convexification technique (CT) to construct a loss on the basis of EIoU, which can guarantee the gradient at the minimum to be zero. Thirdly, we propose a steady optimization technique (SOT) to make the fractional EIoU loss approaching the minimum more steadily and smoothly. Fourthly, to fully exploit the capability of the EIoU based loss, we introduce an interrelated IoU-predicting head to further boost localization accuracy. With the proposed contributions, the new method incorporated into Faster R-CNN with ResNet50+FPN as the backbone yields 4.2 mAP gain on VOC2007 and 2.3 mAP gain on COCO2017 over the baseline Smooth-<inline-formula> <tex-math notation="LaTeX">$\ell _{1}$ </tex-math></inline-formula> Loss, at almost no training and inferencing computational cost. Specifically, the stricter the metric is, the more notable the gain is, improving 8.2 mAP on VOC2007 and 5.4 mAP on COCO2017 at metric <inline-formula> <tex-math notation="LaTeX">$AP_{90}$ </tex-math></inline-formula>.
Clinical Psychology and Mental Disorder SKILLS – A psychoeducational group programme for children with ADHD

SKILLS – A psychoeducational group programme for children with ADHD. Psychology, 62, – Psychoeducation is regarded as a ﬁ rst line of intervention for attention-de ﬁ cit/hyperactivity disorder (ADHD). Previous studies have been limited to psychoeducation for adult patients or parents of children with ADHD. Therefore, the aim of the present study was to investigate the acceptability and effectiveness of a psychoeducational group intervention for children with ADHD. The two-session psychoeducational intervention, SKILLS, was completed by 125 children (6 – 12 years) with ADHD and their parents. Self-ratings and parental ratings of ADHD symptoms, functional impairment and attitudes to diagnosis and treatment were collected before and after treatment. Post-treatment client satisfaction and parental responses to an open question about SKILLS were assessed. The data were analyzed using a combination of quantitative and qualitative (content analysis) methods. A majority of the participants expressed satisfaction with the group intervention. The intervention had no effect on symptoms and level of function, although the parents were more positive to their child ’ s diagnosis after the intervention. The parents were positive to the group format and to the opportunity for their children to meet other children with similar symptoms. Parents wished for more interactive elements and more opportunities for children to share experiences. We concluded that the group intervention was accepted by most participants, although more activating exercises and opportunities for interaction between participants should be included. Since the intervention group was not compared with a control group, the results should be interpreted with caution. Future studies should use a randomized control treatment design and investigate the effect on adherence to later treatment.
Inhibition of Antiviral Innate Immunity by Foot-and-Mouth Disease Virus Lpro through Interaction with the N-Terminal Domain of Swine RNase L

FMDV is a picornavirus that causes a significant disease in agricultural animals. FMDV has developed diverse strategies to escape the host interferon response. ABSTRACT Foot-and-mouth disease virus (FMDV) is the pathogen of foot-and-mouth disease (FMD), which is a highly contagious disease in cloven-hoofed animals. To survive in the host, FMDV has evolved multiple strategies to antagonize host innate immune responses. In this study, we showed that the leader protease (Lpro) of FMDV, a papain-like proteinase, promoted viral replication by evading the antiviral interferon response through counteracting the 2′,5′-oligoadenylate synthetase (OAS)/RNase L system. Specifically, we observed that the titers of Lpro deletion virus were significantly lower than those of wild-type FMDV (FMDV-WT) in cultured cells. Our mechanistic studies demonstrated that Lpro interfered with the OAS/RNase L pathway by interacting with the N-terminal domain of swine RNase L (sRNase L). Remarkably, Lpro of FMDV exhibited species-specific binding to RNase L in that the interaction was observed only in swine cells, not human, monkey, or canine cells. Lastly, we presented evidence that by interacting with sRNase L, FMDV Lpro inhibited cellular apoptosis. Taken together, these results demonstrate a novel mechanism that Lpro utilizes to escape the OAS/RNase L-mediated antiviral defense pathway. IMPORTANCE FMDV is a picornavirus that causes a significant disease in agricultural animals. FMDV has developed diverse strategies to escape the host interferon response. Here, we show that Lpro of FMDV antagonizes the OAS/RNase L pathway, an important interferon effector pathway, by interacting with the N-terminal domain of sRNase L. Interestingly, such a virus-host interaction is species-specific because the interaction is detected only in swine cells, not in human, monkey, or canine cells. Furthermore, Lpro inhibits apoptosis through interacting with sRNase L. This study demonstrates a novel mechanism by which FMDV has evolved to inhibit host innate immune responses.