A compendium of observational studies of adults that collected accelerometry to assess physical activity and sedentary behavior (i.e., physical behaviors) could facilitate cross-study comparisons, meta-analyses, and future research collaborations. Therefore, we performed a systematic search to identify observational studies, including surveillance systems, that collected accelerometry-measured physical activity and sedentary behavior among adults. We performed a search using PubMed, Web of Science, and SPORTDiscus for studies published on or before June 1, 2021. After screening 5686 abstracts and 1027 full text articles, we included 155 unique studies that collected accelerometry on at least 500 adults 18 years or older. Most studies used one accelerometer (n=146), although eight studies used two accelerometers and one study used four accelerometers. The country of data collection, age range, and accelerometer characteristics were abstracted and checked by a second reviewer. These datasets summarizing relevant observational studies of adults can be a resource to researchers seeking to identify data sources for accelerometer-measured physical activity and sedentary behavior from around the world.

UNASSIGNED: The case-based learning with situated cognition theory (CBL-SCT) approach focuses on teaching over learning, making it suited to student nurse education. However, it is rare in student nurse training in pediatric surgery, and some subjective evaluations of the learning effect are still affected by the assessor. This study investigated the effect of the CBL-SCT approach on improving the nursing quality/safety and comprehensive performance of student nurses, and explored a method for analyzing the reliability of subjective evaluations.
UNASSIGNED: Thirty-six student nurses were divided into a control group and an experimental group and received seven days of orientation via conventional and CBL-SCT training, respectively. The learning effect was evaluated via examining their implementation of nursing quality criteria within the following month and their comprehensive clinical performance after six months. Among the evaluation indicators, professional skills, job competency, and professional quality were evaluated by assessors, whose scores were tested for consistency using Cronbach\'s alpha.
UNASSIGNED: Among the 11 nursing quality criteria, the correct implementation of patient identification and communication (t = 2.257, P = 0.031), medication-checking (t = 5.444, P < 0.001), tumbles/bed-falling prevention (t = 3.609, P = 0.001), pressure injury prevention (t = 3.834, P = 0.001), catheter management (t = 3.409, P = 0.002), and nursing record writing (t = 2.911, P = 0.006) in the experimental group were all higher than in the control group. Six months after training, the experimental group was also higher in professional theory (t = 4.889, P < 0.001), professional skills (t = 2.736, P = 0.010), job competency (t = 5.166, P < 0.001), and professional quality (t = 16.809, P < 0.001). Cronbach\'s alpha test verified that the assessors\' evaluations had good internal consistency and reliability for job competency (alpha = 0.847, 95% CI lower limit = 0.769), professional quality (alpha = 0.840, 95% CI lower limit = 0.759), and professional skills (alpha = 0.888, 95% CI lower limit = 0.822).
UNASSIGNED: The CBL-SCT method can help student nurses quickly change their nursing role, and Cronbach\'s alpha test can verify the reliability of subjective evaluations, thus indirectly reflecting the training effect equitably and objectively.

UNASSIGNED: The majority of patients with autoimmune hepatitis (AIH) achieve complete remission with established treatment regiments. In patients with intolerance or insufficient response to these drugs, the remaining options are limited and novel treatment approaches necessary. In primary biliary cholangitis (PBC), ursodeoxycholic acid (UDCA) and fibrates have improved prognosis dramatically, but there remains a proportion of patients with refractory disease.In patients with refractory AIH and/or PBC, we used a novel treatment strategy with the anti-B cell activating factor, belimumab. The first three patients had concomitant Sjögren\'s disease. The connecting element between all three diseases is B cell activation, including elevated levels of the B cell activating factor (BAFF). Furthermore, belimumab has been shown to be beneficial in Sjögren\'s disease.
UNASSIGNED: To retrospectively investigate treatment response in six patients with AIH or PBC with or without concomitant Sjögren\'s disease treated with the anti-BAFF therapy belimumab at the University Hospital in Bern, Switzerland.
UNASSIGNED: In all three patients with AIH, belimumab improved disease control and helped by-pass or reduce problematic side effects from corticosteroids and calcineurin inhibitors. In PBC patients (n = 3), there was no clear improvement of liver function tests, despite reduction or normalization of IgM. All patients with concomitant Sjögren\'s disease (n = 3) had an improvement of sicca symptoms and two out of three patients experienced an initially marked reduction in fatigue, which lessened over time.
UNASSIGNED: Belimumab may be a promising treatment option for patients with AIH and further investigations are needed. In PBC however, response was not convincing. The effects on sicca symptoms and fatigue were encouraging.

While analysis of the bacterial microbiome has become routine, that of the fungal microbiome is still hampered by the lack of robust databases and bioinformatic pipelines. Here, we present FunOMIC, a pipeline with built-in taxonomic (1.6 million marker genes) and functional (3.4 million non-redundant fungal proteins) databases for the identification of fungi. Applied to more than 2,600 human metagenomic samples, the tool revealed fungal species associated with geography, body sites, and diseases. Correlation network analysis provided new insights into inter-kingdom interactions. With this pipeline and two of the most comprehensive fungal databases, we foresee a fast-growing resource for mycobiome studies.

Effectiveness and tolerability of adjunctive cenobamate for uncontrolled focal seizures in adults living with a developmental disability are not defined. Retrospective medical record review included adults ≥18 years old living with a developmental disability, either in a group home or with parents, and experiencing uncontrolled focal seizures despite stable doses of ≥1 antiseizure medication (ASM). Effectiveness was examined as percentage change in focal seizure frequency per month from the 2-month average before cenobamate to the average of months 5 and 6 while receiving cenobamate. Percentages of patients achieving responder rates in focal seizure frequency at 6 months of cenobamate treatment were examined. Adverse effects and concomitant ASM dosage adjustments were assessed. Of the 28 included patients, 26 (92.9%) continued cenobamate beyond 6 months. The responder rate of 100% seizure reduction (seizure-free) occurred in 48.2% of the patients who continued cenobamate for 6 months. Ten adverse effects were reported in 9 patients (32.1%), and 80% (8/10) were resolved by reducing concomitant ASM dosages. Two patients (7.1%) discontinued cenobamate due to adverse effects. Cenobamate resulted in substantial reduction in focal seizure frequency and was well tolerated.

OBJECTIVE: To estimate the potential risk for a future postmarket black box warning (BBW) of US Food and Drug Administration (FDA)-approved monoclonal antibodies (mAbs) because of the importance for medical clinicians to understand mAb risks and benefits, including unknown future risks, especially for recently approved mAbs.
METHODS: The complete dates of the study were March 16, 2020, through May 12, 2021. We searched the FDALabel database online and reviewed the scientific literature to determine current and previous FDA-approved mAbs as of March 2020. The BBWs and initial FDA-issued safety warnings were identified. The BBWs were categorized as premarket or postmarket. For mAbs with specific postmarket BBWs, previous FDA labels were evaluated to identify the presence or absence of an initial corresponding specific FDA warning.
RESULTS: In March 2020, a total of 83 mAbs had FDA approval; 33 had BBWs (27 premarket and 13 postmarket BBWs). Of these 33 mAbs, 55 individual specific BBWs existed (36 premarket and 19 postmarket specific warnings). On average, the specific BBWs occurred in the postmarket period at a rate of 3.4% (19/562) per year. Most (73.7%; 14/19) specific postmarket BBWs were preceded by an FDA warning in a median time of 3.61 (interquartile range, 1.36-5.78) years. Specific postmarket BBWs not preceded by a specific FDA product label warning occurred at an average rate of 0.9% (5/562) per year.
CONCLUSIONS: Specific postmarket BBWs occurred in FDA-approved mAbs at a rate of 3.4% per year. Specific postmarket BBWs not preceded by a specific FDA product label warning had a rate of 0.9% per year.

BACKGROUND: Indigenous peoples are vulnerable to pandemics, including to the coronavirus disease (COVID)-19, since it causes high mortality and specially, the loss of elderly Indigenous individuals.
METHODS: The epidemiological data of severe acute respiratory syndrome (SARS) by SARS-CoV-2 infection or other etiologic agents (OEA) among Brazilian Indigenous peoples during the first year of COVID-19 pandemic was obtained from a Brazilian Ministry of Health open-access database to perform an observational study. Considering only Indigenous individuals diagnosed with SARS by COVID-19, the epidemiology data were also evaluated as risk of death. The type of sample collection for virus screening, demographic profile, clinical symptoms, comorbidities, and clinical evolution were evaluated. The primary outcome was considered the death in the Brazilian Indigenous individuals and the secondary outcome, the characteristics of Brazilian Indigenous infected by SARS-CoV-2 or OEA, as the need for intensive care unit admission or the need for mechanical ventilation support. The statistical analysis was done using Logistic Regression Model. Alpha of 0.05.
RESULTS: A total of 3,122 cases of Indigenous individuals with SARS in Brazil were reported during the first year of the COVID-19 pandemic. Of these, 1,994 were diagnosed with COVID-19 and 730/1,816 (40.2%) of them died. The death rate among individuals with SARS-CoV-2 was three-fold increased when compared to the group of individuals with OEA. Several symptoms (myalgia, loss of smell, and sore throat) and comorbidities (cardiopathy, systemic arterial hypertension, and diabetes mellitus) were more prevalent in the COVID-19 group when compared to Indigenous individuals with OEA. Similar profile was observed considering the risk of death among the Indigenous individuals with COVID-19 who presented several symptoms (oxygen saturation <95%, dyspnea, and respiratory distress) and comorbidities (renal disorders, cardiopathy, and diabetes mellitus). The multivariate analysis was significant in differentiating between the COVID-19-positive and non-COVID-19 patients [X2 (7)=65.187; P-value<0.001]. Among the patients\' features, the following contributed in relation to the diagnosis of COVID-19: age [≥43 years-old [y.o.]; OR=1.984 (95%CI=1.480-2.658)]; loss of smell [OR=2.373 (95%CI=1.461-3.854)]; presence of previous respiratory disorders [OR=0.487; 95%CI=0.287-0.824)]; and fever [OR=1.445 (95%CI=1.082-1.929)]. Also, the multivariate analysis was able to predict the risk of death [X2 (9)=293.694; P-value<0.001]. Among the patients\' features, the following contributed in relation to the risk of death: male gender [OR=1.507 (95%CI=1.010-2.250)]; age [≥60 y.o.; OR=3.377 (95%CI=2.292-4.974)]; the need for ventilatory support [invasive mechanical ventilation; OR=24.050 (95%CI=12.584-45.962) and non-invasive mechanical ventilation; OR=2.249 (95%CI=1.378-3.671)]; dyspnea [OR=2.053 (95%CI=1.196-3.522)]; oxygen saturation <95% [OR=1.691 (95%CI=1.050-2.723)]; myalgia [OR=0.423 (95%CI=0.191-0.937)]; and the presence of kidney disorders [OR=3.135 (95%CI=1.144-8.539)].
CONCLUSIONS: The Brazilian Indigenous peoples are in a vulnerable situation during the COVID-19 pandemic and presented an increased risk of death due to COVID-19. Several factors were associated with enhanced risk of death, as male sex, older age (≥60 y.o.), and need for ventilatory support; also, other factors might help to differentiate SARS by COVID-19 or by OEA, as older age (≥43 y.o.), loss of smell, and fever.
BACKGROUND: Fundação de Amparo à Pesquisa do Estado de São Paulo (Foundation for Research Support of the State of São Paulo; #2021/05810-7).

The present study explored vacuum drum drying (VDD) as an alternative technology for amorphous solid dispersions (ASDs) manufacture compared to hot-melt extrusion (HME) and spray drying (SD) focusing on downstream processability (powder properties, compression behavior and tablet performance). Ritonavir (15% w/w) in a copovidone/sorbitan monolaurate matrix was used as ASD model system. The pure ASDs and respective tablet blends (TB) (addition of filler, glidant, lubricant) were investigated. Milled extrudate showed superior powder properties (e.g., flowability, bulk density) compared to VDD and SD, which could be compensated by the addition of 12.9% outer phase. Advantageously, the VDD intermediate was directly compressible, whereas the SD material was not, resulting in tablets with defects based on a high degree of elastic recovery. Compared to HME, the VDD material showed superior tabletability when formulated as TB, resulting in stronger compacts at even lower solid fraction values. Despite the differences in tablet processing, tablets showed similar tablet performance in terms of disintegration and dissolution independent of the ASD origin. In conclusion, VDD is a valid alternative to manufacture ASDs. VDD offered advantageous downstream processability compared to SD: less solvents and process steps required (no second drying), improved powder properties and suitable for direct compression.

Biliary tract cancers (BTCs) are aggressive epithelial malignancies that can arise at any point of the biliary tree. Albeit rare, their incidence and mortality rates have been rising steadily over the past 40 years, highlighting the need to improve current diagnostic and therapeutic strategies. BTCs show high inter- and intra-tumour heterogeneity both at the morphological and molecular level. Such complex heterogeneity poses a substantial obstacle to effective interventions. It is widely accepted that the observed heterogeneity may be the result of a complex interplay of different elements, including risk factors, distinct molecular alterations and multiple potential cells of origin. The use of genetic lineage tracing systems in experimental models has identified cholangiocytes, hepatocytes and/or progenitor-like cells as the cells of origin of BTCs. Genomic evidence in support of the distinct cell of origin hypotheses is growing. In this review, we focus on recent advances in the histopathological subtyping of BTCs, discuss current genomic evidence and outline lineage tracing studies that have contributed to the current knowledge surrounding the cell of origin of these tumours.

BACKGROUND: Many parents develop stress-related symptoms and depression when their preterm infant is hospitalised in the neonatal intensive care unit (NICU) after birth. We reviewed the evidence of parent well-being with preterm infants hospitalised in single family rooms (SFRs) or in open bay neonatal units (OBUs).
METHODS: For this systematic review and meta-analysis, we searched MEDLINE, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Clinicaltrials.gov, and International Clinical Trials Registry Platform (ICTRP) databases from inception through 22 November 2019 using controlled terms and text words related to prematurity and NICU-design. We included randomised and non-randomised studies comparing outcomes in parents with preterm infants admitted to SFRs or OBUs. Methodological quality was assessed using Cochrane Collaboration\'s Risk of Bias Tool for randomised controlled trials and the Risk of Bias Tool for Non-Randomised Studies of Interventions (ROBINS-I). Outcomes included: parental stress, satisfaction, participation (presence/involvement/skin-to-skin care), self-efficacy, parent-infant-bonding, depression, anxiety, post-traumatic stress, empowerment, and degree of family-centred care. Summary estimates were calculated using random effects models with standardised mean differences (SMDs). PROSPERO registration: CRD42016050643.
RESULTS: We identified 614 unique publications. Eleven study populations (1, 850 preterm infants, 1, 549 mothers and 379 fathers) were included. All but one study were at serious to critical risk of bias. SFRs were associated with higher levels of parental presence, involvement, and skin-to-skin care. Upon discharge, SFRs were associated with lower stress levels (n = 828 parents, SMD-0·30,95%CI -0·50;-0·09, p<0·004, I2=46%), specifically NICU-related stress (n = 573, SMD-0·42,95%CI -0·61;-0·23, p<0·0001, I2=0%). In majority of studies higher levels of empowerment, family-centred care, and satisfaction was present with SFRs. No differences were found for anxiety, parent-infant bonding, or self-efficacy. Depression was high (up to 29%) but not different between settings. No studies described post-traumatic stress.
CONCLUSIONS: Single family rooms seem to facilitate parental presence, involvement, skin-to-skin care, and reduce NICU-related parental stress.