Miracle-dz/UniFAR-FTUs huggingface dataset:
Sleep architecture based on sleep depth and propensity: patterns in different demographics and sleep disorders and association with health outcomes

Abstract Study Objectives Conventional metrics of sleep quantity/depth have serious shortcomings. Odds-Ratio-Product (ORP) is a continuous metric of sleep depth ranging from 0 (very deep sleep) to 2.5 (full-wakefulness). We describe an ORP-based approach that provides information on sleep disorders not apparent from traditional metrics. Methods We analyzed records from the Sleep-Heart-Health-Study and a study of performance deficit following sleep deprivation. ORP of all 30-second epochs in each PSG and percent of epochs in each decile of ORPs range were calculated. Percentage of epochs in deep sleep (ORP < 0.50) and in full-wakefulness (ORP > 2.25) were each assigned a rank, 1–3, representing first and second digits, respectively, of nine distinct types (“1,1”, “1,2” … ”3,3”). Prevalence of each type in clinical groups and their associations with demographics, sleepiness (Epworth-Sleepiness-Scale, ESS) and quality of life (QOL; Short-Form-Health-Survey-36) were determined. Results Three types (“1,1”, “1,2”, “1,3”) were prevalent in OSA and were associated with reduced QOL. Two (“1,3” and “2,3”) were prevalent in insomnia with short-sleep-duration (insomnia-SSD), but only “1,3” was associated with poor sleep depth and reduced QOL, suggesting two phenotypes in insomnia-SSD. ESS was high in types “1,1” and “1,2”, and low in “1,3” and “2,3”. Prevalence of some types increased with age while in others it decreased. Other types were either rare (“1,1” and “3,3”) or high (“2,2”) at all ages. Conclusions The proposed ORP histogram offers specific and unique information on the underlying neurophysiological characteristics of sleep disorders not captured by routine metrics, with potential of advancing diagnosis and management of these disorders.
NT-proBNP and sRAGE levels in early rheumatoid arthritis

Objective Several biomarkers of cardiovascular function are found to be increased in rheumatoid arthritis (RA), with some suggesting a relationship with disease activity and improvement with adequate anti-rheumatic treatment. Promising biomarkers include N-terminal pro-brain natriuretic peptide (NT-proBNP) and the soluble receptor form of advanced glycation end-products (sRAGE). The objective of this study was to investigate associations between NT-proBNP and sRAGE levels and markers of inflammation and disease activity in early RA patients and their changes during (effective) anti-rheumatic treatment. Method Data from 342 consecutive early RA patients participating in the ‘Parelsnoer’ cohort were used. At baseline and after 6 months’ disease activity, NT-proBNP and sRAGE levels were assessed. Results After 6 months, NT-proBNP decreased from 83 pmol/L (mean) at baseline to 69 pmol/L at follow-up (p < 0.001), while sRAGE increased from 997 pg/mL to 1125 pg/mL (p < 0.001). A larger decrease in erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) was associated with larger changes in NT-proBNP and sRAGE. For every point decrease in ESR, there was a 1.7-point decrease in NT-proBNP and a 2.2-point increase in sRAGE. For CRP, these values were 1.7 and 2.7, respectively (p < 0.001). Conclusion Suppressing inflammation, independently of achieving remission, increases sRAGE levels and decreases NT-proBNP levels significantly. Whether this translates into a decrease in incident cardiovascular disease remains to be elucidated.
Development of Various Diabetes Prediction Models Using Machine Learning Techniques

Background There are many models for predicting diabetes mellitus (DM), but their clinical implication remains vague. Therefore, we aimed to create various DM prediction models using easily accessible health screening test parameters. Methods Two sets of variables were used to develop eight DM prediction models. One set comprised 62 easily accessible examination results of commonly used variables from a tertiary university hospital. The second set comprised 27 of the 62 variables included in the national routine health checkups. Gradient boosting and random forest algorithms were used to develop the models. Internal validation was performed using the stratified 10-fold cross-validation method. Results The area under the receiver operating characteristic curve (ROC-AUC) for the 62-variable DM model making 12-month predictions for subjects without diabetes was the largest (0.928) among those of the eight DM prediction models. The ROC-AUC dropped by more than 0.04 when training with the simplified 27-variable set but still showed fairly good performance with ROC-AUCs between 0.842 and 0.880. The accuracy was up to 11.5% higher (from 0.807 to 0.714) when fasting glucose was included. Conclusion We created easily applicable diabetes prediction models that deliver good performance using parameters commonly assessed during tertiary university hospital and national routine health checkups. We plan to perform prospective external validation, hoping that the developed DM prediction models will be widely used in clinical practice.
Clemastine protects against sepsis-induced myocardial injury in vivo and in vitro

ABSTRACT Sepsis-induced myocardial dysfunction (SIMD) is associated with high morbidity and mortality rates; however, it lacks targeted therapies. Modulating cardiomyocyte autophagy maintains intracellular homeostasis during SIMD. Clemastine, a histamine receptor inhibitor, promotes autophagy and other effective biological functions. Nevertheless, the effect of clemastine on SIMD remains unclear. This study aimed to explore the underlying mechanism of clemastine in cardiomyocyte injury in cecum ligation and perforation (CLP)-induced rats and lipopolysaccharide (LPS)-stimulated H9c2 cells. Clemastine (10 mg/kg, 30 mg/kg, and 50 mg/kg) was intraperitoneally injected after 30 min of CLP surgery. Serum cTnI levels and the 7-day survival rate were evaluated. Echocardiograms and H&E staining were used to evaluate cardiac function and structure. TEM was used to detect the mitochondrial ultrastructure and autophagosomes. Clemastine significantly improved the survival rate and reduced cTnI production in serum. Clemastine ameliorated cellular apoptosis, improved mitochondrial ultrastructure both in vivo and in vitro, increased ATP content, decreased dynamin-related protein 1 (DRP1) expression, and decreased mitochondrial ROS levels. Additionally, clemastine treatment increased autophagosome concentration, LC3II/LC3I rate, and Beclin 1 expression. However, 3-methyladenine (3-MA), an autophagy inhibitor, could abolish the effect of clemastine on alleviating myocardial apoptosis. In conclusion, clemastine protected against cardiac structure destruction and function dysfunction, mitochondrial damage, apoptosis, and autophagy in vivo and in vitro. Moreover, clemastine attenuated myocardial apoptosis by promoting autophagy. This study provides a novel favorable perspective for SIMD therapy. Graphical Abstract
Spectrum of DNA mismatch repair failures viewed through the lens of cancer genomics and implications for therapy

Abstract Genome sequencing can be used to detect DNA repair failures in tumors and learn about underlying mechanisms. Here, we synthesize findings from genomic studies that examined deficiencies of the DNA mismatch repair (MMR) pathway. The impairment of MMR results in genome-wide hypermutation and in the ‘microsatellite instability’ (MSI) phenotype—occurrence of indel mutations at short tandem repeat (microsatellite) loci. The MSI status of tumors was traditionally assessed by molecular testing of a selected set of MS loci or by measuring MMR protein expression levels. Today, genomic data can provide a more complete picture of the consequences on genomic instability. Multiple computational studies examined somatic mutation distributions that result from failed DNA repair pathways in tumors. These include analyzing the commonly studied trinucleotide mutational spectra of single-nucleotide variants (SNVs), as well as of other features such as indels, structural variants, mutation clusters and regional mutation rate redistribution. The identified mutation patterns can be used to rigorously measure prevalence of MMR failures across cancer types, and potentially to subcategorize the MMR deficiencies. Diverse data sources, genomic and pre-genomic, from human and from experimental models, suggest there are different ways in which MMR can fail, and/or that the cell-type or genetic background may result in different types of MMR mutational patterns. The spectrum of MMR failures may direct cancer evolution, generating particular sets of driver mutations. Moreover, MMR affects outcomes of therapy by DNA damaging drugs, antimetabolites, nonsense-mediated mRNA decay (NMD) inhibitors, and immunotherapy by promoting either resistance or sensitivity, depending on the type of therapy.
Ultrasound-guided thermal ablation for hyperparathyroidism: current status and prospects

Abstract Background Hyperparathyroidism (HPT) is classified into primary HPT (PHPT), secondary HPT (SHPT), tertiary HPT (THPT), and pseudohyperparathyroidism. Parathyroid surgery is generally reserved for patients with symptomatic PHPT and asymptomatic patients who meet the surgical guideline criteria. However, the risk of complications and mortality after parathyroid gland surgery increases with increasing patient age. Aim This study aimed to review existing research on laser ablation, radiofrequency ablation, microwave ablation, and high-intensity focused ultrasound in the treatment of HPT and analyze its application prospects. Conclusions Thermal ablation is a good alternative treatment for patients with parathyroid hyperplasia who do not meet the criteria or decline surgery. Being a type of minimally invasive treatment, ultrasound-guided thermal ablation has the advantages of easy operation, rapid recovery, and reusability and is used widely.
Efficacy of Metacognitive Training for Depression as Add-on Intervention for Patients with Depression in Acute Intensive Psychiatric Inpatient Care: A Randomized Controlled Trial.

BACKGROUND Metacognitive Training for Depression (D-MCT) is a novel low-intensity group training for economic treatment of depression. Previous studies demonstrate its efficacy in moderately depressed outpatients. The present study evaluated efficacy and patient's perspective of the D-MCT in severely depressed psychiatric inpatients. METHODS In a randomized-controlled trial, 75 individuals with a major depressive disorder (MDD) were allocated to D-MCT versus Euthymic therapy as add-on (twice a week) to cognitive-behavioural-based (CBT) inpatient-care. Depressive symptoms (HDRS, BDI), dysfunctional (meta)cognition (DAS, MCQ-30), and subjective appraisal were assessed at baseline, 4 weeks (post) and 3 months (follow-up). RESULTS Participants in both conditions showed a large decline in depression at post and follow-up-assessment. No superior add-effect of D-MCT versus active control emerged for depression severity on top of the inpatient care. However, among patients with a diagnosis of MDD with no (vs. at least one) comorbidity, D-MCT participants showed a larger decline in depressive (meta-)cognition at follow-up with medium-to-large effect sizes. D-MCT was evaluated as superior in overall appraisal, treatment preference, motivation, and satisfaction. LIMITATIONS The follow-up time interval of 3 months may have been too short to detect long-term effects. There is emerging evidence that modification of (meta)cognition unfolds its full effects only with time. Effects of CBT inpatient-care on outcome parameters cannot be differentiated. CONCLUSIONS Although D-MCT as an add-on was not superior in complete case analyses, results suggest greater benefit for patients with MDD and no comorbidity. D-MCT proved feasible in acute-psychiatric inpatient-care and was highly accepted by patients. Future studies should investigate the role of modified (meta)cognition on long-term treatment outcome, including dropout and relapse rates.
Qualitative evidence syntheses of attitudes and preferences to inform guidelines on infant feeding in the context of Ebola Virus Disease (EVD) transmission risk

Background Breast-feeding holds considerable potential to reduce infant mortality. Feeding choices, already complex, take on additional complexity against a backdrop of the risk of transmissible Ebola Virus. This review describes the factors that influence infant feeding and attitudes of pregnant women, mothers, family members and health practitioners, policy makers and providers (midwives) concerning infant feeding when there is a risk of Mother-to-Child (MTC) transmission of Ebola Virus Disease (EVD). Methodology A systematic review of qualitative studies identified through rigorous searches of thirteen online databases and additional citation searches of included studies was undertaken. Search terms included breast-feeding, breast-feeding, infant feeding; Ebola; and qualitative, interview(s) and findings. Independent extraction of data by two reviewers using predefined extraction forms. Studies were assessed using the CASP Qualitative checklist. Principal findings 5219 references were screened. 38 references related specifically to Ebola, and five papers met the inclusion criteria with data gathered from two settings: Guinea and Sierra Leone. The EVD outbreak had a significant impact on beliefs, attitudes, and resources to support infant feeding practices negatively affecting the nutritional status of children. The evidence from these studies highlight the need for guidance and appropriate psychosocial support need to be available to mothers who display symptoms and become infected and to front-line staff who are giving advice. Communities need to be engaged because stigma and fear may hinder uptake of appropriate interventions. The EVD outbreak caused multi-level system disruption akin to that seen following a natural disaster, meaning that logistics and coordination are critical and need adequate resourcing. Food production and distribution, and malnutrition screening are also disrupted and thereby compounding compromised nutritional status. The limited number of relevant studies highlights the need for further primary research, particularly in translation of messages to local settings. Conclusions An EVD outbreak causes multi-level disruption that negatively impacts infant feeding and child care practices. Negative impacts have multiple causes and successful planning for Ebola outbreaks requires that nutrition of infants and young children is a priority. Lessons from the Ebola pandemic have wider applicability to other pandemic contexts including Covid-19.
Phase I Study Evaluating Dose De-escalation of Sorafenib with Metformin and Atorvastatin in Hepatocellular Carcinoma (SMASH)

Abstract Background This phase I dose de-escalation study aimed to assess the tolerability, safety, pharmacokinetics (PK), and efficacy of sequentially decreasing doses of sorafenib in combination (SAM) with atorvastatin (A, 10 mg) and metformin (M, 500 mg BD) in patients with advanced hepatocellular carcinoma (HCC). Methods Patients were enrolled in 1 of 4 sequential cohorts (10 patients each) of sorafenib doses (800 mg, 600 mg. 400 mg, and 200 mg) with A and M. Progression from one level to the next was based on prespecified minimum disease stabilization (at least 4/10) and upper limits of specific grade 3-5 treatment-related adverse events (TRAE). Results The study was able to progress through all 4 dosing levels of sorafenib by the accrual of 40 patients. Thirty-eight (95%) patients had either main portal vein thrombosis or/and extra-hepatic disease. The most common grade 3-5 TRAEs were hand-foot-syndrome (grade 2 and grade 3) in 3 (8%) and transaminitis in 2 (5%) patients, respectively. The plasma concentrations of sorafenib peaked at 600 mg dose, and the concentration threshold of 2400 ng/mL was associated with higher odds of achieving time to exposure (TTE) concentrations >75% centile (odds ratio [OR] = 10.0 [1.67-44.93]; P = .01). The median overall survival for patients without early hepatic decompensation (n = 31) was 8.9 months (95% confidence interval [CI]: 3.2-14.5 months). Conclusion The SAM combination in HCC patients with predominantly unfavorable baseline disease characteristics showed a marked reduction in sorafenib-related side effects. Studies using sorafenib 600 mg per day in this combination along with sorafenib drug level monitoring can be evaluated in further trials. (Trial ID: CTRI/2018/07/014865).
Association between magnetic resonance imaging characteristics and pathological findings in entire posterior cruciate ligament with mucoid degeneration

Magnetic resonance imaging (MRI) findings of a tram-track appearance and celery stalk appearance in mucoid degeneration of the cruciate ligament are valuable; however, their pathological basis is unclear. Because these appearances are generally seen throughout the entire ligament, the association between MRI findings and pathological findings must be verified in specimens of the whole degenerated ligament, including the ligamentous attachments to bone. We herein report two cases of mucoid degeneration of the posterior cruciate ligament with osteoarthritis of the knee requiring total knee arthroplasty. The entire degenerated ligament, including the ligamentous attachments to bone, was removed and pathologically evaluated. On pathological examination, the central portion of the lesion showed typical mucoid degeneration, whereas the marginal and adherent portions showed normal ligament tissue, consistent with a tram-track appearance on T2-weighted MRI. The fibrous normal ligament tissues in the longitudinal direction in regions of mucoid degeneration were consistent with a celery stalk appearance on T2-weighted MRI. No mucoid degeneration was found in the attachment area. The tram-track appearance and celery stalk appearance of mucoid degeneration on MRI can be explained by the pathological findings.
How Involved Do Patients Want to Be in the Medical Decision-Making at the Initial Urogynecology Clinic Visit?

Objective The aim of this study was to compare patients' preferred role in medical decision-making before the initial urogynecology visit to their perceived role after the visit. Methods This prospective cohort study enrolled women presenting for their initial urogynecology visit. Before and after the visit, patients completed the Control Preference Scale (CPS), which categorizes the role that patients want to have in medical decision-making: active, collaborative, or passive. Patients also completed the Pelvic Floor Distress Inventory, CollaboRATE, Patient Global Impression of Improvement, patient satisfaction, and Short Test of Functional Health Literacy in Adults questionnaires. Univariable and multivariable generalized estimating equations were used. Results Women (n = 100) with a mean age of 59.1 years (SD = 15.5) participated in the study. Based on CPS before the visit, 50% of the women preferred active involvement, whereas 45% preferred collaborative and 5% preferred passive involvement. After the visit, these rates change to 40%, 48%, and 11%, respectively. On univariable analysis, women were 1.56 times more likely to report a collaborative or passive CPS response after the visit (P = 0.02). This remained true on multivariable analysis (odds ratio, 1.57; P = 0.04). Patients' CPS responses were not associated with their responses on CollaboRATE, Patient Global Impression of Improvement, patient satisfaction, or Short Test of Functional Health Literacy in Adults. Eighty-eight percent of women reported a fully collaborative visit based on CollaboRATE, and 87% reported being “completely satisfied” with the visit. Conclusions Despite a change in women's reported involvement in decision-making after their first urogynecology visit compared with their preferences before the visit, most women perceived collaboration during their visit and were completely satisfied.
How Do Clinicians Judge Fluency in Aphasia?

PURPOSE Aphasia fluency is multiply determined by underlying impairments in lexical retrieval, grammatical formulation, and speech production. This poses challenges for establishing a reliable and feasible tool to measure fluency in the clinic. We examine the reliability and validity of perceptual ratings and clinical perspectives on the utility and relevance of methods used to assess fluency. METHOD In an online survey, 112 speech-language pathologists rated spontaneous speech samples from 181 people with aphasia (PwA) on eight perceptual rating scales (overall fluency, speech rate, pausing, effort, melody, phrase length, grammaticality, and lexical retrieval) and answered questions about their current practices for assessing fluency in the clinic. RESULTS Interrater reliability for the eight perceptual rating scales ranged from fair to good. The most reliable scales were speech rate, pausing, and phrase length. Similarly, clinicians' perceived fluency ratings were most strongly correlated to objective measures of speech rate and utterance length but were also related to grammatical complexity, lexical diversity, and phonological errors. Clinicians' ratings reflected expected aphasia subtype patterns: Individuals with Broca's and transcortical motor aphasia were rated below average on fluency, whereas those with anomic, conduction, and Wernicke's aphasia were rated above average. Most respondents reported using multiple methods in the clinic to measure fluency but relying most frequently on subjective judgments. CONCLUSIONS This study lends support for the use of perceptual rating scales as valid assessments of speech-language production but highlights the need for a more reliable method for clinical use. We describe next steps for developing such a tool that is clinically feasible and helps to identify the underlying deficits disrupting fluency to inform treatment targets. SUPPLEMENTAL MATERIAL https://doi.org/10.23641/asha.19326419.
Synonymous mutation in adenosine triphosphatase copper‐transporting beta causes enhanced exon skipping in Wilson disease

Wilson disease (WD) is caused by biallelic pathogenic variants in adenosine triphosphatase copper‐transporting beta (ATP7B); however, genetic testing identifies only one or no pathogenic ATP7B variant in a number of patients with WD. Synonymous single‐nucleotide sequence variants have been recognized as pathogenic in individual families. The aim of the present study was to evaluate the prevalence and disease mechanism of the synonymous variant c.2292C>T (p.Phe764=) in WD. A cohort of 280 patients with WD heterozygous for a single ATP7B variant was investigated for the presence of c.2292C>T (p.Phe764=). In this cohort of otherwise genetically unexplained WD, the allele frequency of c.2292C>T (p.Phe764=) was 2.5% (14 of 560) compared to 7.1 × 10−6 in the general population (2 of 280,964 in the Genome Aggregation Database; p < 10−5; Fisher exact test). In an independent United Kingdom (UK) cohort, 2 patients with WD homozygous for p.Phe764= were identified. RNA analysis of ATP7B transcripts from patients homozygous or heterozygous for c.2292C>T and control fibroblasts showed that this variant caused high expression of an ATP7B transcript variant lacking exon 8. Conclusion: The synonymous ATP7B variant c.2292C>T (p.Phe764=) causes abnormal messenger RNA processing of ATP7B transcripts and is associated with WD in compound heterozygotes and homozygotes.