Miracle-dz/UniFAR-FTUs huggingface dataset:
Further psychometric validation and test–retest reproducibility of the WOUND‐Q

Abstract WOUND‐Q is a condition‐specific patient‐reported outcome measure developed for all types of chronic wounds, located anywhere on the body. To establish reliability and validity of a patient‐reported outcome measure, multiple pieces of evidence are required. The purpose of this study was to examine the measurement properties of 9 of the 13 WOUND‐Q scales and perform a test–retest reproducibility study in an international sample. In August 2022, we invited members of an international online community (Prolific.com) with any type of chronic wound to complete a survey containing the WOUND‐Q scales, the Wound‐QoL and EQ‐5D. A test–retest survey was performed 7 days after the first survey. It was possible to examine the reliability and validity of eight of the nine WOUND‐Q scales by Rasch Measurement Theory (RMT). To examine test–retest reproducibility intraclass correlation coefficients (ICCs), the standard error of the measurement and the smallest detectable change were calculated. In total, 421 patients from 22 different countries with 11 different types of chronic wounds took part in this study. Our analyses provided further evidence of the reliability and validity of the scales measuring wound characteristics (assessment, drainage, smell), health‐related quality of life (life impact, psychological, sleep, social) and wound treatment (dressing).
Low‐intensity pulsed ultrasound at ST36 improves the gastric motility by TNF‐α/IKKβ/NF‐κB signaling pathway in diabetic rats

Low‐intensity pulsed ultrasound (LIPUS) can effectively regulate the central and peripheral nervous system. However, whether LIPUS could act on acupuncture points to modulate the activity of peripheral nervous has rarely been studied. Our study aimed to investigate whether LIPUS at ST36 could improve gastric emptying in diabetic gastroparesis rats.
Salivary cortisol and perceived psychological stress in patients with chronic contact hand dermatitis

REFERENCES 1. Knapik JJ, Farina EK, Ramirez CB, Pasiakos SM, McClung JP, Lieberman HR. Medical encounters during the United States Army special forces assessment and selection course.Mil Med. 2019;184:e0337-e0343. 2. Reynolds K, Miller C, Mathis A, Dettori J. Injuries and risk factors in an 18-day marine winter mountain training exercise.Mil Med. 2000;165:905-910. 3. Bruze M, Trulsson L, Bendsöe N. Patch testing with ultrasonic bath extracts. Am J Contact Dermat. 1992;3:133-137. 4. Fregert S. Manual of Contact Dermatitis. 2nd ed. Munksgaard; 1981. 5. Johansen JD, Aalto-Korte K, Agner T, et al. European Society of Contact Dermatitis guideline for diagnostic patch testing—recommendations on best practice. Contact Dermatitis. 2015;73(4):195-221. 6. Bruze M. Simultaneous reactions to phenol-formaldehyde resins colophony/hydroabietyl alcohol and balsam of Peru/perfume mixture. Contact Dermatitis. 1986;14(2):119-120. 7. Hamnerius N, Dahlin J, Bruze M, et al. Medical device product used for prevention causes colophonium-related allergic contact dermatitis in soldiers. Submitted for publication. 8. Dendooven E, Foubert K, Naessens T, et al. Allergic contact dermatitis from (“hypoallergenic”) adhesives containing D-limonene. Contact Dermatitis. 2022;86(2):113-119. doi:10.1111/cod.14008 Epub 2021 Dec 5. PMID: 34786729.
Magic bubbles: utilizing histotripsy to modulate the tumor microenvironment and improve systemic anti-tumor immune responses

Abstract Focused Ultrasound (FUS) is emerging as a promising primary and adjunct therapy for the treatment of cancer. This includes histotripsy, which is a noninvasive, non-ionizing, non-thermal ultrasound guided ablation modality. As histotripsy has progressed from bench-to-bedside, it has become evident that this therapy has benefits beyond local tumor ablation. Specifically, histotripsy has the potential to shift the local tumor microenvironment from immunologically ‘cold’ to ‘hot’. This is associated with the production of damage associated molecular patterns, the release of a selection of proinflammatory mediators, and the induction of inflammatory forms of cell death in cells just outside of the treatment zone. In addition to the induction of this innate immune response, histotripsy can also improve engagement of the adaptive immune system and promote systemic anti-tumor immunity targeting distal tumors and metastatic lesions. These tantalizing observations suggest that, in settings of widely metastatic disease burden, selective histotripsy of a limited number of accessible tumors could be a means of maximizing responsiveness to systemic immunotherapy. More work is certainly needed to optimize treatment strategies that best synergize histotripsy parameters with innate and adaptive immune responses. Likewise, rigorous clinical studies are still necessary to verify the presence and repeatability of these phenomena in human patients. As this technology nears regulatory approval for clinical use, it is our expectation that the insights and immunomodulatory mechanisms summarized in this review will serve as directional guides for rational clinical studies to validate and optimize the potential immunotherapeutic role of histotripsy tumor ablation.
Novel Practical Stability Conditions for Discrete-Time Switched Affine Systems

This technical note proposes novel state feedback stability conditions based on the so called Lyapunov–Metzler inequalities for discrete-time switched affine systems, assuring practical stability of a desired equilibrium point. These conditions are obtained taking into account the volume minimization of an ellipsoidal set containing the nonconvex set of attraction to where the state trajectories are globally attracted. Compared with other recent results, the present ones are based on less conservative conditions for the existence of an attraction set. Moreover, it is not required that the equilibrium point be inside a predetermined set of attainable ones, which enlarges the range of applicability of the present technique. To the best of the authors’ knowledge, it is the first time that the Lyapunov–Metzler inequalities are adopted in the context of switched affine systems. As a second step, the associated nonconvex invariant set is provided. Academical examples illustrate the method and compare the theoretical results with recent ones available in the literature.
Discrepancies in Vessel Density and Blood Flow Distribution in Different Areas of the Iris among Pediatric Type 1 Diabetes Mellitus and Adult Type 2 Diabetes Mellitus Patients

Introduction: Diabetes mellitus may compromise the vasculature of the iris, thereby leading to severe vision-threatening complications. This study aimed to investigate differences in iris blood flow indices between pediatric type 1 diabetes mellitus (T1DM) patients and adult type 2 diabetes mellitus (T2DM) patients. Methods: This was a cross-sectional study. Pediatric T1DM patients and healthy children were members of the Shanghai Children and Adolescent Diabetes Eye (SCADE) cohort who visited Shanghai Eye Hospital in February 2022. The adult T2DM patients and healthy adults were patients who visited Shanghai General Hospital from October 2021 to January 2022. Iris OCTA was acquired through a Cirrus HD-OCT 5000 angiography system (Carl Zeiss Meditec, Inc.). A unique iris OCTA quantification method was used, and the vessel area density (VAD) and vessel skeleton density (VSD) were obtained. The area from the pupillary margin to the corneoscleral limbus was taken as the whole iris blood flow index, and the inner third near the pupillary margin of the whole iris was taken as the pupillary margin blood flow index. Results: This study enrolled 34 pediatric T1DM patients, 34 age-matched healthy children, 34 adult T2DM patients, and 34 age-matched healthy adults. The whole iris and pupillary margin VAD and VSD of the pediatric T1DM patients were not different from those of healthy children. The whole iris VAD and VSD of the adult T2DM patients were lower than those of healthy adults, and the pupillary margin VAD and VSD were the same in these two groups. Compared with adult T2DM patients, pediatric T1DM patients had higher whole iris VAD and VSD and lower pupillary margin VAD and VSD values, all with statistical significance. Among diabetic patients, age, BMI, and glycated hemoglobin level were negative independent influencing factors for whole iris VAD and VSD, and age was a positive influencing factor for pupillary margin VAD and VSD. Conclusion: There are diverse alterations in iris vessel density and blood flow distribution between pediatric T1DM patients and adult T2DM patients.
Racial disparities in early pregnancy: a narrative review

Purpose of review This review introduces the recognized body of evidence on social determinants of health, which continue to show that a person's health is determined by their broader environmental and social context and that societal inequities harm health and healthcare outcomes. An area of inequity is race, which, although a social construct, has a significant impact on a person's morbidity and mortality as well as their access and experience of healthcare. Racial disparities in maternal and perinatal outcomes are widely recognized. Therefore, this review focuses on the less commonly addressed early pregnancy setting. Recent findings Health inequities are present in the early pregnancy setting, as racial disparities exist in early pregnancy presentations and outcomes. Black women have a higher incidence of miscarriage, ectopic pregnancy and poorer survival rates from gestational trophoblastic neoplasms. Asian women have a statistically significantly higher incidence of gestational trophoblastic disease. Summary The findings support the need for more consistent and detailed research on the impact of race on early pregnancy outcomes and increasing ethnic diversity among study populations for trials to ensure meaningful and applicable data. Raising awareness of this racial health inequity in early pregnancy is the first step clinicians can take to tackle this issue.
Exploring the Boundaries for In Vitro–In Vivo Extrapolation: Use of Isolated Rat Hepatocytes in Co-culture and Impact of Albumin Binding Properties in the Prediction of Clearance of Various Drug Types

Prediction of hepatic clearance of drugs (via uptake or metabolism) from in vitro systems continues to be problematic, particularly when plasma protein binding is high. The following work explores simultaneous assessment of both clearance processes, focusing on a commercial hepatocyte-fibroblast co-culture system (HμREL) over a 24-hour period using six probe drugs (ranging in metabolic and transporter clearance and low-to-high plasma protein binding). A rat hepatocyte co-culture assay was established using drug depletion (measuring both medium and total concentrations) and cell uptake kinetic analysis, both in the presence and absence of plasma protein (1% bovine serum albumin). Secretion of endogenous albumin was monitored as a marker of viability, and this reached 0.004% in incubations (at a rate similar to in vivo synthesis). Binding to stromal cells was substantial and required appropriate correction factors. Drug concentration-time courses were analyzed both by conventional methods and a mechanistic cell model prior to in vivo extrapolation. Clearance assayed by drug depletion in conventional suspended rat hepatocytes provided a benchmark to evaluate co-culture value. Addition of albumin appeared to improve predictions for some compounds (where fraction unbound in the medium is less than 0.1); however, for high-binding drugs, albumin significantly limited quantification and thus predictions. Overall, these results highlight ongoing challenges concerning in vitro hepatocyte system complexity and limitations of practical expediency. Considering this, more reliable measurement of hepatically cleared compounds seems possible through judicious use of available hepatocyte systems, including co-culture systems, as described herein; this would include those compounds with low metabolic turnover but high active uptake clearance. SIGNIFICANCE STATEMENT Co-culture systems offer a more advanced tool than standard hepatocytes, with the ability to be cultured for longer periods of time, yet their potential as an in vitro tool has not been extensively assessed. We evaluate the strengths and limitations of the HμREL system using six drugs representing various metabolic and transporter-mediated clearance pathways with various degrees of albumin binding. Studies in the presence/absence of albumin allow in vitro–in vivo extrapolation and a framework to maximize their utility.
The advances in the early and accurate diagnosis of Creutzfeldt–Jakob disease and other prion diseases: where are we today?

ABSTRACT Introduction Before the introduction of MRI diffusion-weighted images (DWI), the diagnosis of Creutzfeldt–Jakob disease (CJD) relied upon nonspecific findings including clinical symptoms, EEG abnormalities, and elevated levels of cerebrospinal fluid 14-3-3 protein. Subsequently, the use of DWI has improved diagnostic accuracy, but it sometimes remains difficult to differentiate CJD from encephalitis, epilepsy, and other dementing disorders. The revised diagnostic criteria include real-time quaking-induced conversion (RT-QuIC), detecting small amounts of CJD-specific prion protein, and clinically sensitive DWI. Combining these techniques has further improved diagnostic accuracy, enabling earlier diagnosis. Areas covered Herein, the authors review the recent advances in diagnostic methods and revised diagnostic criteria for sporadic CJD. They also discuss other prion diseases, such as variant CJD and chronic wasting disease, where the emergence of new types is a concern. Expert opinion Despite improvements in diagnostic methods and criteria, some subtypes of prion disease are still difficult to diagnose, and even the diagnosis using the most innovative RT-QuIC test remains a challenge in terms of accuracy and standardization. However, these revised criteria can be adapted to the emergence of new types of prion diseases. It is essential to continue careful surveillance and update information on the latest prion disease phenotypes.
Molecular Results and Potential Biomarkers Identified from the Phase 3 MILO/ENGOT-ov11 Study of Binimetinib versus Physician Choice of Chemotherapy in Recurrent Low-Grade Serous Ovarian Cancer

Abstract Purpose: We present the results of a post hoc tumor tissue analysis from the phase 3 MILO/ENGOT-ov11 study (NCT01849874). Patients and Methods: Mutation/copy-number analysis was performed on tissue obtained pre-randomization. The Kaplan–Meier method was used to estimate progression-free survival (PFS). Unbiased univariate analysis, Cox regression, and binary logistic regression were used to test associations between mutation status and outcomes, including PFS and binary response by local RECIST 1.1. Results: MILO/ENGOT-ov11 enrolled 341 patients, ranging in age from 22 to 79, from June, 2013 to April, 2016. Patients were randomized 2:1 to binimetinib or physician's choice of chemotherapy (PCC). The most commonly altered gene was KRAS (33%). In 135 patients treated with binimetinib with response rate (RR) data, other detected MAPK pathway alterations included: NRAS (n = 11, 8.1%), BRAF V600E (n = 8, 5.9%), RAF1 (n = 2, 1.5%), and NF1 (n = 7, 5.2%). In those with and without MAPK pathway alterations, the RRs with binimetinib were 41% and 13%, respectively. PFS was significantly longer in patients with, compared with those without, MAPK pathway alterations treated with binimetinib [HR, 0.5; 95% confidence interval (CI) 0.31–0.79]. There was a nonsignificant trend toward PFS improvement in PCC-treated patients with MAPK pathway alterations compared with those without (HR, 0.82; 95% CI, 0.43–1.59). Conclusions: Although this hypothesis-generating analysis is limited by multiple testing, higher RRs and longer PFS were seen in patients with low-grade serous ovarian cancer (LGSOC) treated with binimetinib, and to a lesser extent in those treated with PCC, who harbored MAPK pathway alterations. Somatic tumor testing should be routinely considered in patients with LGSOC and used as a future stratification factor.
Tumor necrosis factor–like cytokine 1A plays a role in inflammatory bowel disease pathogenesis

Significance We utilized various mouse models of IBD to demonstrate that TL1A expression on the surface of DCs is increased in inflamed intestines. Moreover, Tl1a−/− naive CD4+ T cells exhibited impaired ability for Th1 or Th17 differentiation ex vivo, and we used Tl1a−/−Rag1−/− and Rag1−/− mice to explore how TL1A influences T cell differentiation in vivo. Our findings indicate that TL1A plays a crucial role in the interaction between T-T cells and APC-T cells and contributes to the development of intestinal inflammation by binding to DR3. Additionally, we observed that TL1A was located in the cytoplasm and nucleus of DCs, where it bound to RAF1 and positively regulated the RAF1/p65 signaling pathway, enhancing the antigen uptake ability of BMDCs in vitro.
A synergy between site-specific and transient interactions drives the phase separation of a disordered, low-complexity domain

Significance The RNA-binding protein TDP-43 is a component of neuronal inclusions associated with diseases such as amyotrophic lateral sclerosis, frontotemporal dementia, and Alzheimer’s disease. The C-terminal domain (CTD) of TDP-43 is a disordered, low-complexity domain which is aggregation-prone and undergoes liquid–liquid phase separation (LLPS). CTD contains a hydrophobic, conserved region (CR, aa:319-341) which is α-helical and critical for oligomerization and LLPS. Using multiscale simulations and experiments, we report a noncanonical mechanism of biomolecular recognition wherein transient interactions involving hydrophobic residues in CR flanking regions drive the phase separation of CTD through direct enhancement of site-specific, CR-mediated interactions. Our study uncovers rich, mechanistic insights into CTD phase separation which is essential for understanding TDP-43 function and pathology.
Bibliometric Insights in Advances of Chordoma: Global Trends and Research Development in the Last Decade

Chordoma is a rare tumor, but has a serious effect on the quality of life of patients. This study aims to assess the overall knowledge structure and trends in the development of chordoma research using a bibliometric analysis and visualization tool. Research datasets were acquired from the Web of Science. VOS viewer and CiteSpace visualization software were used to demonstrate collaborations and correlations. Annual trends in publications, distribution, H‐index status, co‐authorship status, and research hotspots were analyzed. A total of 1844 publications from 2012 to 2022 were included. The number of chordoma‐related publications increased year by year. The United States contributed the most publications (717) and had the highest total citations (10130) and H‐index (50), followed by China. The United States was also the country most frequently involved in international cooperation. The most productive organization involved in chordoma research was Massachusetts General Hospital. World Neurosurgery (114) published the most papers on chordoma. Hornicek FJ was the most productive author over the last decade (41). Initially, diagnosis and the location of onset captured the attention of the research society. Quality of life, risk factors, disability, minimally invasive surgical techniques, molecular targeted therapy, and radiotherapy technology are the research hotspots in recent years. Indeed, this study provides important insights into the overall landscape of chordoma research and also contributes to the further investigation of the international frontier of chordoma.
Gender Affirmation–Related Information-Seeking Behaviors in a Diverse Sample of Transgender and Gender-Diverse Young Adults: Survey Study

Background Of the 1.6 million transgender and gender-diverse (TGD) people in the United States, approximately 700,000 are youth aged 13-24 years. Many factors make it difficult for TGD young people to identify resources for support and information related to gender identity and medical transition. These range from lack of knowledge to concerns about personal safety in the setting of increased antitransgender violence and legislative limitations on transgender rights. Web-based resources may be able to address some of the barriers to finding information and support, but youth may have difficulty finding relevant content or have concerns about the quality and content of information they find on the internet. Objective We aim to understand ways TGD young adults look for web-based information about gender and health. Methods In August 2022, 102 young adults completed a 1-time survey including closed- and open-ended responses. Individuals were recruited through the Prolific platform. Eligibility was restricted to people between the ages of 18-25 years who identified as transgender and were residents of the United States. The initial goal was to recruit 50 White individuals and 50 individuals who identified as Black, indigenous, or people of color. In total, 102 people were eventually enrolled. Results Young adults reported looking on the internet for information about a broad range of topics related to both medical- and social-gender affirmation. Most participants preferred to obtain information via personal stories. Participants expressed a strong preference for obtaining information from other trans people. Conclusions There is a need for accessible, expert-informed information for TGD youth, particularly more information generated for the transgender community by members of the community.
Cognitive status and sleep quality can explain the fear of falling and fall history in people with Parkinson’s disease

Fear of falling (FOF) is highly prevalent in people with Parkinson’s disease (PwPD) and contributes to high fall risk. Studies reporting on the relationship between falls, FOF, and non-motor factors such as cognitive function and sleep quality in Parkinson’s disease are limited. This study aimed to investigate (1) the relationship of cognitive function and sleep quality with FOF, and history of falls in PwPD; (2) differences in cognitive function and sleep quality between Parkinson’s disease fallers and non-fallers; and (3) a cut-off score for cognitive function and sleep quality to discriminate Parkinson’s disease fallers from non-fallers. Fifty PwPD were assessed for FOF [Falls Efficacy Scale-International (FES-I)], cognition [Montréal Cognitive Assessment (MOCA)], sleep quality [Pittsburgh Sleep Quality Index (PSQI)], and falls history. The MOCA is significantly associated with FES-I scores (R2 = 0.429, P < 0.0001). Both MOCA (P = 0.012) and PSQI (P = 0.027) were associated with falls history even after adjusting for confounding factors (age, sex, L-dopa use, Parkinson’s disease severity). Both MOCA and PSQI scores were able to distinguish fallers from non-fallers with cut-off scores of 15.5 and 7.5, respectively. Although our findings revealed that both cognitive function and sleep quality are important factors influencing falls and FOF in PwPD, it remains to be determined if addressing cognitive impairments and poor sleep quality may favorably impact balance before integrating such screenings into fall prevention programs.