Miracle-dz/UniFAR-FTUs huggingface dataset:
The immunopeptidomes of two transmissible cancers and their host have a common, dominant peptide motif

Transmissible cancers are malignant cells that can spread between individuals of a population, akin to both a parasite and a mobile graft. The survival of the Tasmanian devil, the largest remaining marsupial carnivore, is threatened by the remarkable emergence of two independent lineages of transmissible cancer, devil facial tumour (DFT) 1 and devil facial tumour 2 (DFT2). To aid the development of a vaccine and to interrogate how histocompatibility barriers can be overcome, we analysed the peptides bound to major histocompatibility complex class I (MHC‐I) molecules from Tasmanian devil cells and representative cell lines of each transmissible cancer. Here, we show that DFT1 + IFN‐γ and DFT2 cell lines express a restricted repertoire of MHC‐I allotypes compared with fibroblast cells, potentially reducing the breadth of peptide presentation. Comparison of the peptidomes from DFT1 + IFNγ, DFT2 and host fibroblast cells demonstrates a dominant motif, despite differences in MHC‐I allotypes between the cell lines, with preference for a hydrophobic leucine residue at position 3 and position Ω of peptides. DFT1 and DFT2 both present peptides derived from neural proteins, which reflects a shared cellular origin that could be exploited for vaccine design. These results suggest that polymorphisms in MHC‐I molecules between tumours and host can be ‘hidden’ by a common peptide motif, providing the potential for permissive passage of infectious cells and demonstrating complexity in mammalian histocompatibility barriers.
Effect of Discontinuing vs Continuing Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers on Days Alive and Out of the Hospital in Patients Admitted With COVID-19: A Randomized Clinical Trial.

Importance It is unknown whether angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) have a positive, neutral, or negative effect on clinical outcomes in patients with coronavirus disease 2019 (COVID-19). Objective To determine whether discontinuation compared with continuation of ACEIs or ARBs changed the number of days alive and out of the hospital through 30 days. Design, Setting, and Participants A randomized clinical trial of 659 patients hospitalized in Brazil with mild to moderate COVID-19 who were taking ACEIs or ARBs prior to hospitalization (enrolled: April 9-June 26, 2020; final follow-up: July 26, 2020). Interventions Discontinuation (n = 334) or continuation (n = 325) of ACEIs or ARBs. Main Outcomes and Measures The primary outcome was the number of days alive and out of the hospital through 30 days. Secondary outcomes included death, cardiovascular death, and COVID-19 progression. Results Among 659 patients, the median age was 55.1 years (interquartile range [IQR], 46.1-65.0 years), 14.7% were aged 70 years or older, 40.4% were women, and 100% completed the trial. The median time from symptom onset to hospital admission was 6 days (IQR, 4-9 days) and 27.2% of patients had an oxygen saturation of less than 94% of room air at baseline. In terms of clinical severity, 57.1% of patients were considered mild at hospital admission and 42.9% were considered moderate. There was no significant difference in the number of days alive and out of the hospital in patients in the discontinuation group (mean, 21.9 days [SD, 8 days]) vs patients in the continuation group (mean, 22.9 days [SD, 7.1 days]) and the mean ratio was 0.95 (95% CI, 0.90-1.01). There also was no statistically significant difference in death (2.7% for the discontinuation group vs 2.8% for the continuation group; odds ratio [OR], 0.97 [95% CI, 0.38-2.52]), cardiovascular death (0.6% vs 0.3%, respectively; OR, 1.95 [95% CI, 0.19-42.12]), or COVID-19 progression (38.3% vs 32.3%; OR, 1.30 [95% CI, 0.95-1.80]). The most common adverse events were respiratory failure requiring invasive mechanical ventilation (9.6% in the discontinuation group vs 7.7% in the continuation group), shock requiring vasopressors (8.4% vs 7.1%, respectively), acute myocardial infarction (7.5% vs 4.6%), new or worsening heart failure (4.2% vs 4.9%), and acute kidney failure requiring hemodialysis (3.3% vs 2.8%). Conclusions and Relevance Among patients hospitalized with mild to moderate COVID-19 and who were taking ACEIs or ARBs before hospital admission, there was no significant difference in the mean number of days alive and out of the hospital for those assigned to discontinue vs continue these medications. These findings do not support routinely discontinuing ACEIs or ARBs among patients hospitalized with mild to moderate COVID-19 if there is an indication for treatment. Trial Registration ClinicalTrials.gov Identifier: NCT04364893.
Divergence of dose–response with asenapine: a cluster analysis of randomized, double-blind, and placebo control study

Abstract Background Differences in psychiatric background and dose–response to asenapine in patients with schizophrenia were examined based on efficacy and safety, using data obtained in a double-blind, placebo-controlled trial. Methods Patients with schizophrenia were classified into three clusters by a cluster analysis based on the Positive and Negative Symptom Scale (PANSS) subscores at baseline, using the data from a 6-week, double-blind, placebo-controlled trial. PANSS Marder factor scores were calculated for each cluster. The efficacy of 10 or 20 mg/day of asenapine on PANSS score was used as the primary endpoint, with the incidence of adverse events evaluated as the secondary endpoint. Results A total of 529 asenapine-treated patients were classified into 3 clusters: Cluster-P with the higher scores in positive symptoms, disorganized thoughts, and hostility/excitement, Cluster-N with higher scores in negative symptoms, and Cluster-L with overall lower scores. In Cluster-N and Cluster-L, both 10 and 20 mg/day groups showed significant improvement in PANSS scores, while only the 20 mg/day group showed a significant difference in Cluster-P. Cluster-N and Cluster-L had differences in the incidence of adverse events, but this was not seen in Cluster-P. Conclusions The efficacy and safety of asenapine 10 and 20 mg/day differed between the 3 clusters of patients. This suggests that background information regarding baseline psychiatric symptoms may affect the therapeutic response in patients with schizophrenia.
Clinicopathologic Features of COVID-19: A Case Report and Value of Forensic Autopsy in Studying SARS-CoV-2 Infection

Abstract As of August 23, 2020, the 2019 novel coronavirus disease (COVID-19) has infected more than 23,518,340 people and caused more than 810,492 deaths worldwide including 4,717 deaths in China. We present a case of a 53-year-old woman who was admitted to the hospital because of dry coughs and high fever on January 26, 2020, in Wuhan, China. She was not tested for SARS-CoV-2 RNA until on hospital day 11 (illness day 21) because of a significant shortage of test kits at the local hospital. Then, her test was positive for COVID-19 on hospital day 20. Despite intensive medical treatments, she developed respiratory failure with secondary bacterial infection and expired on hospital day 23 (3 days after she was tested positive for SARS-CoV-2 RNA). A systemic autopsy examination, including immunohistochemistry and ultrastructural studies, demonstrates that SARS-CoV-2 can infect multiple organs with profound adverse effect on the immune system, and the lung pathology is characterized by diffuse alveolar damage. Extrapulmonary SARS-CoV-2 RNA was detected in several organs postmortem. The detailed pathological features are described. In addition, this report highlights the value of forensic autopsy in studying SARS-CoV-2 infection and the importance of clinicopathological correlation in better understanding the pathogenesis of COVID-19.
DNA damage promotes ER stress resistance through elevation of unsaturated phosphatidylcholine in Caenorhabditis elegans.

DNA damage triggers the cellular adaptive response to arrest proliferation and repair DNA damage; when damage is too severe to be repaired, apoptosis is initiated to prevent the spread of genomic insults. However, how cells endure DNA damage to maintain cell function remains largely unexplored. By using Caenorhabditis elegans as a model, we report that DNA damage elicits cell maintenance programs, including the unfolded protein response of the endoplasmic reticulum (UPRER). Mechanistically, sublethal DNA damage unexpectedly suppresses apoptotic genes in C. elegans, which in turn increases the activity of the inositol-requiring enzyme 1/X-box binding protein 1 (IRE-1/XBP-1) branch of the UPRER by elevating unsaturated phosphatidylcholine. In addition, UPRER activation requires silencing of the lipid regulator skinhead-1 (SKN-1). DNA damage suppresses SKN-1 activity to increase unsaturated phosphatidylcholine and activate UPRER. These findings reveal the UPRER activation as an organismal adaptive response that is important to maintain cell function during DNA damage.
Ultrasound as a Valuable Imaging Modality in Sclerosing Lymphocytic Lobulitis: Imaging Features Based on a Retrospective Cohort Analysis of 51 Cases

Purpose: Sclerosing lymphocytic lobulitis (SLL) is a rare benign breast condition usually associated with diabetes mellitus and whose imaging features have been assessed in few studies, limiting the adoption of diagnostic guidelines. We aimed to identify the main morphological features associated with SLL on imaging examinations (mainly ultrasound and mammography) and to retrospectively evaluate the role that each method played in the diagnostic workup (detection and indication for biopsy). Methods: A retrospective study was conducted in a high-volume single center, encompassing 51 consecutive patients (100% female; 26-78 y; 43.7 ± 15.5 y) with histopathologically proven SLL (59 lesions; 0.5-6.1 cm). Results: Most lesions (31/59; 53%) were found in asymptomatic individuals. Ultrasound detected 91.1% (51 out of 56 lesions assessed by this modality), of which 94.1% were non-circumscribed masses (BI-RADS® 4). Mammography detected 41.6% (15 out of 36 lesions assessed by this modality), with a predominance (80%) of non-calcified ones (masses, asymmetries and distortion). Two-year follow-up was achieved in 29 lesions (49%), showing complete remission (45%) or stability (41%) in most cases. Conclusions: Most lesions in this retrospective sample have been detected by means of ultrasound and had their need for biopsy indicated by this modality. Female diabetic patients younger than 40 years presenting with a palpable lesion and a non-circumscribed mass on ultrasound could be submitted to core biopsy; histopathologic findings suggestive of SLL should be considered concordant in this scenario, with subsequent conservative treatment.
Developing self-care in an interdependent therapeutic relationship: patients’ experiences from Norwegian psychomotor physiotherapy

ABSTRACT Factors causing and sustaining long-lasting musculoskeletal pain differ between patients, but must be identified in order to target treatment. During physiotherapy, there are multiple factors influencing the treatment outcome. The focus in the present study was to grasp patients’ experiences of how social burdens influence the development and persistence of symptoms of muscle pain, and how the relationship with the physiotherapist influences the process of change during Norwegian Psychomotor Physiotherapy. A phenomenological, descriptive, and retrospective design was chosen. Data were collected through focus-group interviews. Eleven patients participated. They ranged in age from 34 to 67 years. The analysis was inspired by Giorgi’s phenomenological method. The results identified a general, overarching structure; “Caring for others and developing self-care” and the two interwoven themes “Emerging awareness of overload” and “Receiving care from the physiotherapist. ” These themes describe the essence of the experiences from the treatment process. To be recognized by the physiotherapist, both through the hands-on treatment and verbal communication, appears to be crucial for patients to develop an awareness of the factors causing and sustaining their pain problems. This awareness seemed necessary for the process of change to take place and for the patients to take more responsibility for their own care.
Pharmacological therapy in gestational diabetes – a comparison between insulin and oral therapy

Abstract Background The appropriate medical treatment for gestational diabetes mellitus (GDM) is controversial and recommendations vary between different organizations. Objective To compare the safety and efficacy of glyburide and insulin as treatments for GDM. Methods Retrospective analysis of all pregnant women diagnosed with GDM and treated with either glyburide or insulin. Demographic features, clinical characteristics, maternal and neonatal outcomes were compared according to type of pharmacological treatment. Results Included in the study were 323 women, of whom 269 (83.28%) were treated with glyburide and 54 (16.72%) with insulin. There were no significant differences between the groups, apart from a higher one-hour oral glucose tolerance test (OGTT) value (191.80 mg/dl in the glyburide group, 204.33 in the insulin group, p = .01). Optimal glucose control was achieved in 130 women in the glyburide group (48.32%) and 15 in the insulin group (27.77%), p = . 007. This difference remained significant after adjustment for age, BMI, and fasting glucose during OGTT (aOR = 2.22). Mean gestational weight gain was lower in the glyburide group vs. insulin group (10.01 vs. 11.99 kg, p = .048). Apart from higher maternal hypoglycemia rate (12.64% in glyburide group vs. 1.85% in insulin group, p = .016), there were no other differences in maternal and neonatal outcomes between the groups. Glyburide failure rate was 13.38%, and associated with higher fasting OGTT value (100.70 mg/dl in glyburide failure group vs. 94.67 mg/dl in the glyburide treatment until delivery group, p = .041). Conclusions Glyburide is at least as safe and effective as insulin except for higher rates of maternal hypoglycemia. Considering its advantages compared to insulin (ease of use and storage, increased patient responsiveness, and lower cost), it may be considered as first line treatment in GDM, especially when fasting OGTT value is not high.
Research progress on radioprotective effects of bee products

Abstract Radiation exposure is an on going and serious threat in military and public health concern. There is an unmet need for effective preventative or mitigative treatments against radiation-induced injuries. The handful of Food and Drug Administration in the US approved radiation protection agents cannot be widely used due to their side effects. Some natural nontoxic compounds such as bee products have been reported to prevent and treat radiation-induced injuries (e.g. scavenging free radicals, inhibiting cell apoptosis and reducing DNA damage), indicating that they may be a potential option as a safe radioprotective agent. Bee products are nontoxic and have no known side effects on the human body, and are effective in the field of radiation protection. They are expected to be interesting drug candidates for preventing and treating radiation-induced injuries. This article reviews the prevention and treatment of bee products on radiation-induced injuries.
Urinary Alpha1-Microglobulin: A New Predictor for In-Hospital Mortality in Patients with ST-Segment Elevation Myocardial Infarction

Background Alpha1-microglobulin (A1MG) is a small molecular protein related to oxidation and inflammation. It exists in diverse body fluids, including urine. Results from urine tests are sometimes neglected when predicting in-hospital prognosis. It remains unclear whether urinary A1MG (UA1MG) can predict short-term prognosis of ST-elevated myocardial infarction (STEMI). Material/Methods A total of 1854 hospitalized patients with acute STEMI were retrospectively enrolled in our study. Medical records were used to obtain patient demographic and clinical information, UA1MG values (which were used to divide patients into groups of low, medium, or high), and other laboratory parameters. Principal clinical outcomes of interest were all-cause in-hospital deaths, cardiac deaths, and major adverse cardiac events (MACEs). Results Among the 1854 enrolled patients, 43 (2.3%) died in the hospital, of which 33 (1.8%) were cardiac deaths. MACEs were noted in 113 patients (6.1%) during hospitalization. The group with the highest UA1MG value showed a significantly higher frequency of in-hospital deaths, cardiac deaths, and MACEs, compared to those of the lowest UA1MG value group (4.4% vs. 1.0%, P<0.001; 3.1% vs. 0.6%, P<0.005; and 8.6% vs. 4.7%, P=0.007, respectively). Multivariate regression analysis revealed that UA1MG levels (odds ratio 1.109, 95% confidence interval (CI) 1.027–1.197, P=0.008) independently predicted all-cause in-hospital mortality. A UA1MG value of 3.23 mg/dL was considered as an optimal cutoff point in STEMI to predict all-cause mortality after receiver operating characteristic curve analysis (area under the curve 0.73, 95% CI 0.65–0.80, P<0.001). Conclusions The UA1MG value at hospital admission could be an independent prognostic factor of all-cause in-hospital mortality in patients with STEMI.
Gender Norms, Beliefs and Academic Achievement of Orphaned Adolescent Boys and Girls in Uganda

Abstract This study examined the traditional gender norms and beliefs held by orphaned adolescent boys and girls, and the role of such norms and beliefs on their academic performance. Data from a NIMH-funded study known as Suubi-Maka in Uganda were analyzed. Results indicate that overall, adolescents held strong gendered norms and beliefs that favor males over females. Compared to boys, girls were more likely to report more egalitarian gender norms and beliefs that give equal consideration to both girls and boys. In addition, more egalitarian gender norms and beliefs were associated with better school grades. Study findings point to the need to integrate targeted components that address harmful gender norms and beliefs in programs that support vulnerable adolescents, including education policy, if we are to address inequalities in education access and achievement, as well promote and strengthen education for all in sub-Saharan Africa.
Stress and its contribution to the development of depression symptoms are reduced in caregivers of elderly with higher educational level

Abstract Caregivers of elderly people with neurodegenerative diseases are highly vulnerable to stressful situations and mood disorders due to their work conditions. Stress has been associated with an increased risk of developing depression, and studies have supported that caffeine consumption can act as an independent protective factor for disorder. This study investigated indexes of stress and depression symptoms in caregivers of the elderly with neurodegenerative diseases, their caffeine intake and the association between stress and depressive symptoms with the salivary biomarkers cortisol, nitric oxide and DNA damage. Participants (n = 81) were recruited from the community between July 2018 and April 2019. Stress was assessed using Lipp’s Inventory of Stress Symptoms, and depressive symptoms were measured using the Hamilton Depressive Rating Scale. Participants provided a 72-hour recall of their diet to measure caffeine intake. Saliva samples were used to measure cortisol and nitric oxide. DNA damage was measured through micronuclei frequency after swabbing on the buccal mucosa. The majority of caregivers displayed stress and depressive symptoms. Stress was associated with educational level, tobacco use and total DNA damage. The indexes found in this population were not associated with caffeine intake or other salivary biomarkers, indicating that only some salivary molecules could be used as biomarkers for stress-related disorders. Caregivers of the elderly are exposed to stressful situations daily, however, we observed that educational level can reduce the psychological symptoms of stress and thus reduce the negative impact on quality of life.
Early appearance of developmental alterations in the dendritic tree of the hippocampal granule cells in the Ts65Dn model of Down syndrome

Down syndrome (DS), a genetic condition caused by triplication of chromosome 21, is characterized by alterations in various cognitive domains, including hippocampus‐dependent memory functions, starting from early life stages. The major causes of intellectual disability in DS are prenatal neurogenesis alterations followed by impairment of dendritic development in early infancy. While there is evidence that the Ts65Dn mouse, the most widely used model of DS, exhibits dendritic alterations in adulthood, no studies are available regarding the onset of dendritic pathology. The goal of the current study was to establish whether this model exhibits early dendritic alterations in the hippocampus, a region whose function is severely damaged in DS. To this purpose, in Golgi‐stained brains, we evaluated the dendritic arborization and dendritic spines of the granule cells of the hippocampal dentate gyrus in Ts65Dn mice aged 8 (P8) and 15 (P15) days. While P15 Ts65Dn mice exhibited a notably hypotrophic dendritic arbor and a reduced spine density, P8 mice exhibited a moderate reduction in the number of dendritic ramifications and no differences in spine density in comparison with their euploid counterparts. Both in P8 and P15 mice, spines were longer and had a longer neck, suggesting possible alterations in synaptic function. Moreover, P8 and P15 Ts65Dn mice had more thin spines and fewer stubby spines in comparison with euploid mice. Our study provides novel evidence on the onset of dendritic pathology, one of the causes of intellectual disability in DS, showing that it is already detectable in the dentate gyrus of Ts65Dn pups. This evidence strengthens the suitability of this model of DS as a tool to study dendritic pathology in DS and to test the efficacy of early therapeutic interventions aimed at ameliorating hippocampal development and, therefore, memory functions in children with DS.
Factors Increasing Risk of Suicide after Traumatic Brain Injury: A State-of-the-Science Review of Military and Civilian Studies

ABSTRACT Primary Objective: Survey TBI literature to identify evidence of risk for post-injury suicide. Literature Selection: Search terms ((traumatic brain injury OR TBI) AND (suicidality OR suicidal behaviour OR suicidal ideation)) entered in PubMed, OVID Medline, PsychInfo, and Web of Science for papers published in print 01/01/1997 to 06/30/2019. Analysis of Literature: Authors screened abstracts, excluding duplicates and articles not meeting inclusion/exclusion criteria. Full papers were reviewed to make final exclusions. Data were extracted from 40 papers included co- and premorbid disorders, demographics, injury-related and psychological factors. Results: Persons with TBI have a higher risk for suicide than the general population. Reviewed articles reported comorbid depression and/or PTSD as risk factors for post-TBI suicide. Co- or premorbid substance misuse, sex, and sleep disturbance moderate risk. Quality of the literature was limited by sample size, the predominance of male participants, and inconsistency in reporting of findings. Conclusions: Comorbid depression and PTSD are significant post-TBI risk factors for suicide. Several variables combine to moderate or mediate TBI’s connection with suicide. Civilian and military clinician cross-talk and consistent reporting of results from reproducible studies of post-TBI suicide risk factors could improve prevention and treatment efforts in veterans and civilians.