Miracle-dz/UniFAR-FTUs huggingface dataset:
Follow-up care for premature children: the repercussions of the COVID-19 pandemic*

Objective: to analyze elements of the follow-up care provided to premature children amidst the COVID-19 pandemic. Method: qualitative study from the perspective of philosophical hermeneutics, interpreting experiences with childcare provided at home. Twelve mothers and 14 children aged two years old were interviewed online via a text messaging application. Data were analyzed by interpreting meanings. Results: weaknesses stood out in the follow-up care provided to children such as gaps of communication, lack of guidance and delayed immunizations, while care intended to meet health demands was interrupted. Vulnerability aspects affecting child development included: social isolation measures that impeded the children from socializing with their peers, increased screen time, the manifestation of demanding behaviors and irritation and the mothers experiencing an overload of responsibilities. The elements that strengthened maternal care included the mothers being attentive to contagion, enjoying greater experience and satisfaction with the maternal role, spending more time with their children, and recognizing respiratory signs and symptoms, especially fever. Conclusion: follow-up care provided to children in stressful situations implies implementing practices that support the wellbeing of children and families, decreasing the likelihood of children being exposed to development deficits, and detecting signs and symptoms timely. The use of nursing call centers can break the invisibility of longitudinal needs and promote health education actions at home.
Usability of Electronic Health Record–Generated Discharge Summaries: Heuristic Evaluation

Background Obtaining accurate clinical information about recent acute care visits is extremely important for outpatient providers. However, documents used to communicate this information are often difficult to use. This puts patients at risk of adverse events. Elderly patients who are seen by more providers and have more care transitions are especially vulnerable. Objective This study aimed to (1) identify the information about elderly patients’ recent acute care visits needed to coordinate their care, (2) use this information to assess discharge summaries, and (3) provide recommendations to help improve the quality of electronic health record (EHR)–generated discharge summaries, thereby increasing patient safety. Methods A literature review, clinician interviews, and a survey of outpatient providers were used to identify and categorize data needed to coordinate care for recently discharged elderly patients. Based upon those data, 2 guidelines for creating useful discharge summaries were created. The new guidelines, along with 17 previously developed medical documentation usability heuristics, were applied to assess 4 simulated elderly patient discharge summaries. Results The initial research effort yielded a list of 29 items that should always be included in elderly patient discharge summaries and a list of 7 “helpful, but not always necessary” items. Evaluation of 4 deidentified elderly patient discharge summaries revealed that none of the documents contained all 36 necessary items; between 14 and 18 were missing. The documents each had several other issues, and they differed significantly in organization, layout, and formatting. Conclusions Variations in content and structure of discharge summaries in the United States make them unnecessarily difficult to use. Standardization would benefit both patients, by lowering the risk of care transition–related adverse events, and outpatient providers, by helping reduce frustration that can contribute to burnout. In the short term, acute care providers can help improve the quality of their discharge summaries by working with EHR vendors to follow recommendations based upon this study. Meanwhile, additional human factors work should determine the most effective way to organize and present information in discharge summaries, to facilitate effective standardization.
SARS-CoV-2 one year on: evidence for ongoing viral adaptation

SARS-CoV-2 is thought to have originated in the human population from a zoonotic spillover event. Infection in humans results in a variety of outcomes ranging from asymptomatic cases to the disease COVID-19, which can have significant morbidity and mortality, with over two million confirmed deaths worldwide as of January 2021. Over a year into the pandemic, sequencing analysis has shown that variants of SARS-CoV-2 are being selected as the virus continues to circulate widely within the human population. The predominant drivers of genetic variation within SARS-CoV-2 are single nucleotide polymorphisms (SNPs) caused by polymerase error, potential host factor driven RNA modification, and insertion/deletions (indels) resulting from the discontinuous nature of viral RNA synthesis. While many mutations represent neutral ‘genetic drift’ or have quickly died out, a subset may be affecting viral traits such as transmissibility, pathogenicity, host range, and antigenicity of the virus. In this review, we summarise the current extent of genetic change in SARS-CoV-2, particularly recently emerging variants of concern, and consider the phenotypic consequences of this viral evolution that may impact the future trajectory of the pandemic.
Association of Hemoglobin A1C With TDP-43 Pathology in Community-Based Elders

Objective To test the hypothesis that an inverse association exists between diabetes mellitus (DM) and hemoglobin A1C (A1C) with transactive response DNA binding protein 43 (TDP-43) levels in older adults. Methods We leveraged antemortem and postmortem data of decedents from 3 community-based clinical–pathologic studies. DM status, A1C levels, and medications for DM were documented annually. TDP-43 cytoplasmic inclusions, evaluated in 6 brain regions using immunohistochemistry, were used to obtain a semiquantitative TDP-43 score (0–5) in each region, and scores were averaged across regions to obtain a TDP-43 severity score. We used linear regressions to test the association of DM and A1C with the TDP-43 severity score. Results On average, participants (n = 817) were 90 years old at the time of death, three-fourths were women, and one-fourth had DM. The mean A1C was 6.0% (SD 0.6). TDP-43 was observed in 54% of participants, and the mean TDP-43 score was 0.7 (range 0–4.5). A higher level of A1C was associated with a lower TDP-43 score (estimate −0.156, SE 0.060, p = 0.009), while DM had a borderline inverse association with the TDP-43 score (estimate −0.163, SE 0.087, p = 0.060). The association of higher levels of A1C with lower TDP-43 scores persisted after further adjustment by APOE ε4, vascular risk factors, stroke, and hypoglycemic medications. Exclusion of the oldest old participants did not change the results. Conclusion Overall, the results suggest that a high level of A1C is associated with less TDP-43 proteinopathy in older persons while the relationship of DM with TDP-43 needs further study.
Risk of COVID-19 hospitalization and mortality in rheumatic patients treated with hydroxychloroquine or other conventional DMARDs in Italy

Abstract Objectives To ascertain if hydroxychloroquine (HCQ)/chloroquine (CLQ) and other conventional disease-modifying anti-rheumatic drugs (cDMARDs) use, and rheumatic diseases per se, may be associated with COVID-19-related risk of hospitalization and mortality. Methods This case-control study nested within a cohort of cDMARD users was conducted in the Lombardy, Veneto, Tuscany and Lazio regions and Reggio Emilia province. Claims databases were linked to COVID-19 surveillance registries. Risk of COVID-19-related outcomes was estimated using a multivariate conditional logistic regression analysis, comparing HCQ/CLQ vs methotrexate, vs other cDMARDs and vs non-use of these drugs. Presence of rheumatic diseases vs their absence in a non-nested population was investigated. Results 1275 cases hospitalized due to COVID-19 were matched to 12 734 controls. Compared with recent use of methotrexate, no association between HCQ/CLQ monotherapy and COVID-19 hospitalization (OR 0.83 [95%CI, 0.69–1.00]) or mortality (OR 1.19 [95%CI, 0.85–1.67]) was observed. A lower risk was found when comparing HCQ/CLQ use to the concomitant use of other cDMARDs and glucocorticoids. HCQ/CLQ was not associated with COVID-19 hospitalization as compared with non-use. An increased risk for recent use of either methotrexate monotherapy (OR 1.19 [95% CI, 1.05–1.34]) or other cDMARDs (OR 1.21 [95% CI, 1.08–1.36]) vs non-use was found. Rheumatic diseases were not associated with COVID-19-related outcomes. Conclusion HCQ/CLQ use in rheumatic patients was not associated with a protective effect against COVID-19-related outcomes. Use of other cDMARDs was associated with an increased risk when compared with non-use, and, if concomitantly used with glucocorticoids, also vs HCQ/CLQ, probably to be ascribed to immunosuppressive action.
Describing nurses’ awareness of biological risk in delivering care for renal-dialysis patients: an italian pilot survey

Background and aim of work. Despite national descriptions of awareness, knowledge, and perceptions about the exposure to the biological risk among nurses employed in renal-dialysis care are pivotal to increase work safety, there is a paucity of data on these descriptions in the Italian context. This study aimed at describing Italian nurses’ awareness and knowledge about biological risk in delivering care for renal-dialysis patients, and their experiences of biological accidents. Methods. A pilot survey using cross-sectional data collection and convenience sampling procedure. 124 nurses were enrolled receiving a 7-item questionnaire: Questions 1, 2, and 7 were referred to the awareness about educational learning needs, questions 3 and 4 explored nurses’ knowledge about biological risk, questions 5 and 6 collected accident-related information. Results. Overall, nurses’ awareness and knowledge about biological risk appeared almost limited. Surprisingly, 52% of the enrolled nurses experienced a biological accident, and 29.5% reported to know colleagues who developed work-related disease after a biological accident. We found positive significant associations between awareness and knowledge. Conclusions. This pilot study highlighted the need to further describe Italian nurses’ awareness and knowledge about biological risk in delivering care for renal-dialysis patients, as well as the need of up-to-date epidemiological description about biological accidents. Accordingly, future studies are highly recommended to provide robust evidence aimed at supporting policy makers, educators, clinicians, regulators, and managers.
The type 2 diabetes mellitus susceptibility gene CDKAL1 polymorphism is associated with depressive symptom in first‐episode drug‐naive schizophrenic patients

Patients with schizophrenia have an increased prevalence of type 2 diabetes mellitus that has shown a significant association with the rs7754840 polymorphism in the gene encoding the cyclin‐dependent kinase 5 (CDK5) regulatory subunit‐associated protein 1‐like 1 (CDKAL1).
Recruitment of KMT2C/MLL3 to DNA Damage Sites Mediates DNA Damage Responses and Regulates PARP Inhibitor Sensitivity in Cancer

This study uncovers a critical role for KMT2C in DDR via direct recruitment to DNA damage sites, identifying high-frequency KMT2C/D mutations as biomarkers for response to PARP inhibition in cancer. When recruited to promoters, histone 3 lysine 4 (H3K4) methyltransferases KMT2 (KMT2A-D) activate transcription by opening chromatin through H3K4 methylation. Here, we report that KMT2 mutations occur frequently in non–small cell lung cancer (NSCLC) and are associated with high mutation loads and poor survival. KMT2C regulated DNA damage responses (DDR) through direct recruitment to DNA damage sites by Ago2 and small noncoding DNA damage response RNA, where it mediates H3K4 methylation, chromatin relaxation, secondary recruitment of DDR factors, and amplification of DDR signals along chromatin. Furthermore, by disrupting homologous recombination (HR)–mediated DNA repair, KMT2C/D mutations sensitized NSCLC to Poly(ADP-ribose) polymerase inhibitors (PARPi), whose efficacy is unclear in NSCLC due to low BRCA1/2 mutation rates. These results demonstrate a novel, transcription-independent role of KMT2C in DDR and identify high-frequency KMT2C/D mutations as much-needed biomarkers for PARPi therapies in NSCLC and other cancers with infrequent BRCA1/2 mutations. Significance: This study uncovers a critical role for KMT2C in DDR via direct recruitment to DNA damage sites, identifying high-frequency KMT2C/D mutations as biomarkers for response to PARP inhibition in cancer.
Teaching well-being at scale: An intervention study

Courses that teach evidence-based interventions to enhance well-being are a public health tool that could be used to improve mental health in the population. We compared the well-being of six cohorts of adult students before and after they completed one of two massive open online courses: The Science of Well-Being (N = 581; 441; 1,228) and a control course, Introduction to Psychology (N = 677; 480; 1,480). Baseline well-being levels were equivalent across all six samples. Students in both courses increased in their well-being from baseline to follow-up in all three samples (p < .001); however, at follow-up, students in The Science of Well-Being course had higher subjective well-being than the control course (sample 1: r = .18, d = .37, p < .001; sample 2: r = .21, d = .43, p < .001; sample 3: r = .19, d = .38, p < .001). Overall, across three samples, we found that students who completed either of these online psychology courses increased in their well-being––but that students in The Science of Well-Being course showed greater improvement. These findings suggest that large free online courses that teach evidence-based approaches to well-being could positively impact mental health at large scales.
RSU-1 interaction with prohibitin-2 links cell–extracellular matrix detachment to downregulation of ERK signaling

Cell–extracellular matrix (ECM) detachment is known to decrease extracellular signal–regulated kinase (ERK) signaling, an intracellular pathway that is central for control of cell behavior. How cell–ECM detachment is linked to downregulation of ERK signaling, however, is incompletely understood. We show here that focal adhesion protein Ras Suppressor 1 (RSU1) plays a critical role in cell–ECM detachment induced suppression of ERK signaling. We have identified prohibitin 2 (PHB2), a component of membrane lipid rafts, as a novel binding protein of RSU1, and mapped a major RSU1-binding site to PHB2 amino acids 150 to 206 in the C-terminal region of the PHB/SPFH (stomatin/prohibitin/flotillin/HflKC) domain. The PHB2 binding is mediated by multiple sites located in the N-terminal leucine-rich repeat region of RSU1. Depletion of PHB2 suppressed cell–ECM adhesion–induced ERK activation. Furthermore, cell–ECM detachment increased RSU1 association with membrane lipid rafts and interaction with PHB2. Finally, knockout of RSU1 or inhibition of RSU1 interaction with PHB2 by overexpression of the major RSU1-binding PHB2 fragment (amino acids 150–206) effectively suppressed the cell–ECM detachment induced downregulation of ERK signaling. Additionally, expression of venus-tagged wild-type RSU1 restored ERK signaling, while expression of venus-tagged PHB2-binding defective RSU1 mutant in which the N-terminal leucine-rich repeat region is deleted did not. Taken together, Our findings identify a novel RSU1-PHB2 signaling axis that senses cell–ECM detachment and links it to decreased ERK signaling.
The Perceptions of Patients, Families, Doctors, and Nurses Regarding Malignant Bone Tumor Disclosure in China: A Qualitative Study

Introduction Withholding the malignant bone tumors disclosure from patients is common in China. The purpose of the study was to explore the perceptions of patients, families, doctors, and nurses regarding the disclosure of malignant bone tumors in China. Method Semistructured interviews were conducted with 25 cases, consisting of 69 participants (14 patients, 25 family members, 17 doctors, and 13 nurses), and the transcripts were analysed using Colaizzi’s (1978) descriptive phenomenological analysis process. Results Five themes were identified: (1) doctors preferred to inform the family members first, (2) family members’ decisions depended on different situations, (3) the patients agreed that disclosure should be different for each person/personally, (4) care from nurses reduced the overreaction of patients, and (5) key points improve the informing quality. Discussion Family participatory cancer disclosure and multidisciplinary teams could improve the quality of cancer disclosure. Culturally congruent health care and culturally sensitive interventions in cancer disclosure are suggested.
Long-term Mortality among Patients with Chronic Ulcers

Chronic ulcers cause a significant burden to patients and society. This study evaluated long-term mortality among patients with chronic ulcers diagnosed at a dermatology clinic between 1980 and 2010. The mortality risk and causes of death of 3,489 patients with ulcers were compared with a matched reference group of 10,399 individuals, and factors associated with increased mortality risk were examined. Long-term mortality was increased in patients with chronic ulcers (hazard ratio (HR) 1.74) and in both males and females (HR 1.99 and 1.62, respectively). Diabetes was the most relevant underlying cause of death (HR 8.98), and of the immediate causes of death, sepsis was strongly associated with mortality (HR 5.86). The mortality risk was highest among those with arterial ulcers (HR 2.85), but also increased in patients with atypical, mixed and venous leg ulcers. In conclusion, patients with chronic ulcers are at an increased mortality risk irrespective of age, sex and ulcer aetiology.
Interacting impact of maternal inflammatory response and stress on the amygdala transcriptome of pigs

Abstract Changes at the molecular level capacitate the plasticity displayed by the brain in response to stress stimuli. Weaning stress can trigger molecular changes that influence the physiology of the offspring. Likewise, maternal immune activation (MIA) during gestation has been associated with behavior disorders and molecular changes in the amygdala of the offspring. This study advances the understanding of the effects of pre- and postnatal stressors in amygdala gene networks. The amygdala transcriptome was profiled on female and male pigs that were either exposed to viral-elicited MIA or not and were weaned or nursed. Overall, 111 genes presented interacting or independent effects of weaning, MIA, or sex (FDR-adjusted P-value <0.05). PIGY upstream reading frame and orthodenticle homeobox 2 are genes associated with MIA-related neurological disorders, and presented significant under-expression in weaned relative to nursed pigs exposed to MIA, with a moderate pattern observed in non-MIA pigs. Enriched among the genes presenting highly over- or under-expression profiles were 24 Kyoto Encyclopedia of Genes and Genomes pathways including inflammation, and neurological disorders. Our results indicate that MIA and sex can modulate the effect of weaning stress on the molecular mechanisms in the developing brain. Our findings can help identify molecular targets to ameliorate the effects of pre- and postnatal stressors on behaviors regulated by the amygdala such as aggression and feeding.
Intraoperative Celiac Plexus Block With Preperitoneal Infusion Reduces Opioid Usage in Major Hepato-pancreato-biliary Surgery

Objective: Given the role of celiac plexus block (CPB) in the management of chronic pain, we sought to investigate the utility of CPB in the control of postoperative pain in major hepato-pancreato-biliary surgeries. Summary Background Data: CPB has been in practice for decades for the management of upper abdominal visceral pain, especially in cancer patients. Typically, in this group of patients with chronic pain, a neurolytic agent is injected to cause irreversible neural damage to achieve pain control. We apply this concept to postoperative pain control by injecting bupivacaine to the celiac plexus instead of a neurolytic agent. We aim to investigate if this novel technique decreases postoperative opioid usage, offers better pain relief and leads to earlier ambulation Methods: A retrospective, single institution study comparing consecutive patients who received intraoperative CPB and preperitoneal infusion with patients who received only preperitoneal infusion in open hepato-pancreato-biliary surgery between the years 2016 and 2019 by a single surgeon. Patients with incomplete data on patient-controlled analgesia usage and postoperative ambulation information were excluded. Results: Patients with CPB used 31% less morphine on postoperative day 1 compared to patient without CPB and 42% less morphine on postoperative day 2. Overall average morphine usage was significantly lower in patients with CPB. Duration of patient-controlled analgesia was shorter for patient with CPB compared with patient without CPB. The dynamic visual analogue score was marginally better in patients with CPB. Time to ambulation was similar in both groups. Conclusions: CPB can be considered as part of a multimodal approach for postoperative pain management in open hepato-pancreato-biliary surgeries.
MiR-30a and miR-200c differentiate cholangiocarcinomas from gastrointestinal cancer liver metastases

Prior studies have demonstrated the utility of microRNA assays for predicting some cancer tissue origins, but these assays need to be further optimized for predicting the tissue origins of adenocarcinomas of the liver. We performed microRNA profiling on 195 frozen primary tumor samples using 14 types of tumors that were either adenocarcinomas or differentiated from adenocarcinomas. The 1-nearest neighbor method predicted tissue-of-origin in 33 samples of a test set, with an accuracy of 93.9% at feature selection p values ranging from 10−4 to 10−10. According to binary decision tree analyses, the overexpression of miR-30a and the underexpression of miR-200 family members (miR-200c and miR-141) differentiated intrahepatic cholangiocarcinomas from extrahepatic adenocarcinomas. When binary decision tree analyses were performed using the test set, the prediction accuracy was 84.8%. The overexpression of miR-30a and the reduced expressions of miR-200c, miR-141, and miR-425 could distinguish intrahepatic cholangiocarcinomas from liver metastases from the gastrointestinal tract.
A Preliminary Test of the Efficacy of Brief Self-Administered Behavioral Interventions for Rumination

Rumination is theorized to be a cognitive avoidance process that is implicated in several manifestations of psychopathology. Few interventions directly target rumination as a core process maintaining emotional disorder symptoms. This pilot study compared the feasibility and preliminary efficacy of self-directed behavioral approaches for reducing rumination. Participants (N = 60) with elevations in rumination were randomized to 3 weeks of self-directed interventions: (a) scheduled rumination time; (b) a strategy combining mindfulness, shaping, and disengagement strategies; or (c) self-monitoring control. Both active treatment conditions outperformed self-monitoring control on post-treatment depression scores. Scheduled rumination time significantly outperformed the other two conditions on measures of rumination and worry. No between-group differences emerged on the secondary outcome (i.e., anxiety symptoms). Brief, self-directed, behavioral interventions targeting rumination are feasible and demonstrate preliminary efficacy. Scheduled rumination time shows moderate to large effects. The use of a small, non-treatment seeking sample was the primary limitation.