Miracle-dz/UniFAR-FTUs huggingface dataset:
MicroRNA-146a-5p enhances T helper 17 cell differentiation via decreasing a disintegrin and metalloprotease 17 level in primary sjögren’s syndrome

ABSTRACT In clinical practice, we found that microRNA (miR)-146a-5p is significantly up-regulated in peripheral blood mononuclear cells (PBMCs) of primary sjögren’s syndrome (pSS) patients. In vitro experiments confirmed that miR-146a-5p promotes T helper 17 (Th17) cell differentiation, but the specific mechanism is still unknown. To solve this problem, 20 pSS patients and 20 healthy subjects were enrolled in this study and PBMCs were isolated from their blood. The expression of the membrane IL-23 R (mIL-23 R) in PBMCs was determined. CD3+ T cells were also isolated and used to further analyze the relationship between the ectodomain shedding of mIL-23 R and a disintegrin and metalloprotease 17 (ADAM17). Finally, miR-146a-5p inhibitor and mimics were transfected into PBMCs to evaluate the relationship between ADAM17 and mIL-23 R, and explore the role of mIL-23 R and ADAM17 in Th17 cell differentiation. Our results revealed a significantly increased expression of miR-146a-5p in PBMCs from pSS patients and significantly increased percentage of Th17 cells compared to PBMCs from healthy controls. Under polarization culture conditions, pSS patient-derived PBMCs can more easily differentiate into Th17 cells, which was, to a great extent, attributable to the increased expression of mIL-23 R. Moreover, ADAM17, an ectodomain sheddase of mIL-23 R, was targeted and negatively regulated by miR-146a-5p, which reduced the ectodomain shedding of mIL-23 R. Overall, our results suggested that miR-146a-5p could promote Th17 cell differentiation through targeting and negatively regulating ADAM17. Thus, these results might offer a new approach in the treatment of pSS. Graphical abstract
Proximity Ligation Assay Detection of Protein–DNA Interactions—Is There a Link between Heme Oxygenase-1 and G-quadruplexes?

G-quadruplexes (G4) are stacked nucleic acid structures that are stabilized by heme. In cells, they affect DNA replication and gene transcription. They are unwound by several helicases but the composition of the repair complex and its heme sensitivity are unclear. We found that the accumulation of G-quadruplexes is affected by heme oxygenase-1 (Hmox1) expression, but in a cell-type-specific manner: hematopoietic stem cells (HSCs) from Hmox1−/− mice have upregulated expressions of G4-unwinding helicases (e.g., Brip1, Pif1) and show weaker staining for G-quadruplexes, whereas Hmox1-deficient murine induced pluripotent stem cells (iPSCs), despite the upregulation of helicases, have more G-quadruplexes, especially after exposure to exogenous heme. Using iPSCs expressing only nuclear or only cytoplasmic forms of Hmox1, we found that nuclear localization promotes G4 removal. We demonstrated that the proximity ligation assay (PLA) can detect cellular co-localization of G-quadruplexes with helicases, as well as with HMOX1, suggesting the potential role of HMOX1 in G4 modifications. However, this colocalization does not mean a direct interaction was detectable using the immunoprecipitation assay. Therefore, we concluded that HMOX1 influences G4 accumulation, but rather as one of the proteins regulating the heme availability, not as a rate-limiting factor. It is noteworthy that cellular G4–protein colocalizations can be quantitatively analyzed using PLA, even in rare cells.
Mimicking Tumor Hypoxia in Non-Small Cell Lung Cancer Employing Three-Dimensional In Vitro Models

Hypoxia is the most common microenvironment feature of lung cancer tumors, which affects cancer progression, metastasis and metabolism. Oxygen induces both proteomic and genomic changes within tumor cells, which cause many alternations in the tumor microenvironment (TME). This review defines current knowledge in the field of tumor hypoxia in non-small cell lung cancer (NSCLC), including biology, biomarkers, in vitro and in vivo studies and also hypoxia imaging and detection. While classic two-dimensional (2D) in vitro research models reveal some hypoxia dependent manifestations, three-dimensional (3D) cell culture models more accurately replicate the hypoxic TME. In this study, a systematic review of the current NSCLC 3D models that have been able to mimic the hypoxic TME is presented. The multicellular tumor spheroid, organoids, scaffolds, microfluidic devices and 3D bioprinting currently being utilized in NSCLC hypoxia studies are reviewed. Additionally, the utilization of 3D in vitro models for exploring biological and therapeutic parameters in the future is described.
Telehealth Role During the COVID-19 Pandemic: Lessons Learned from Health Care Providers in Saudi Arabia.

Background: Coronavirus disease 2019 (COVID-19) was originally recognized in December 2019 as a case of lung infection in Wuhan, China. COVID-19 has affected the capability of health care experts to treat patients face to face. One initiative to improve the efficacy and convenience of patient care despite the physical distancing limitations has been the application of "virtual clinics" (VCs) as a treatment modality. This study was aimed to investigate the use of VCs as a tool of telehealth during the COVID-19 pandemic in Saudi Arabia. Methods: This study was conducted in the ambulatory care setting at King Abdullah Specialized Children Hospital in Riyadh. Respondents were selected from different groups of health care providers. The study was a hospital-based cross-sectional design using an electronic survey. Results: In total, 277 surveys were collected. Principal findings showed the deployment of VCs by 67.2% (n = 186) of providers. Among these providers, 54.3% were female, and only 18.8% of providers were aged >54 years. 98.1% of the respondents have started running VCs since the COVID-19 outbreak, with 47.2% of respondents running between 51 and 100 VCs per month, and the majority (74%) were spending 6-15 min per patient visit. Chronically ill patients constituted 57.7% of the patient's population served. Almost 95% of respondents used electronic prescriptions during their VCs. Most providers (98.1%) used the telephone/mobile as a means of communication with the patient during these VCs. A total of 75.5% of VCs were integrated with electronic health records such as appointment scheduling (77.9%), and 88.3% of the providers were satisfied with their VCs. The major opportunity seen by providers was reducing appointment waiting times (73.4%). The major success metric seen in VCs was increased patient satisfaction as reported by providers (67.9%). In contrast, the major challenge seen was the lack of face-to-face interaction and physical examination (86.8%). Conclusion: VCs are one way of centering the health system around the patient, but careful attention is needed to integrate these services with the current health care delivery system in place and ensure quality care to the patients.
Water-Transmitted Fungi Are Involved in Degradation of Concrete Drinking Water Storage Tanks

Global warming, globalization, industrialization, and the rapidly growing population at present increasingly affect the production of safe drinking water. In combination with sustainable bio-based or recycled materials, used for water distribution systems, these factors promote emerging pathogens, including fungi. They can proliferate in oligotrophic water systems, affect the disinfection process, degrade building materials, and cause diseases in humans. In this study, we explored fungal-based degradation of modern concrete water storage tanks and the presence of fungi in chlorinated drinking water at the entrance and exit of the tanks. The degradation potential of isolated 52 fungal strains and their growth at different oligotrophic conditions was tested in vitro. Forty percent of strains grew at extremely oligotrophic conditions, and 50% classified as aerophilic. Two-thirds of tested strains produced acids, with Penicillium strains as the best producers. Only 29.7% of the strains were able to grow at 37 °C, and none of them was isolated from drinking water at consumers’ taps. Although not yet part of the guidelines for building materials in contact with drinking water, fungi should be taken into consideration in case of visible degradation. Their number of consumers’ endpoints should be checked to exclude possible health risks for consumers.
Using Mechanical Turk to Study Parents and Children: An Examination of Data Quality and Representativeness

ABSTRACT Objective Mechanical Turk (MTurk) is a popular data collection tool that is increasingly used to study parents and children. We examined the quality of data obtained via MTurk, the representativeness of parents on MTurk, and whether the wording of MTurk recruitment materials is related to sample characteristics. Method Participants were 650 parents with children aged 4 to 17 recruited for two separate studies (64.6% female, 83.8% Caucasian, mean age = 37.6 years). The Mental Health Survey (N = 322) recruitment materials described a study about mental health and the Health Survey (N = 328) materials only referenced health; both surveys restricted participation to parents in the United States (U.S.). Parents completed measures about demographics, mental health service seeking history, and parent and youth psychopathology. Results Participants provided reliable responses on study measures, with low rates of missing data. Participants were more female, less racially/ethnically diverse, and more educated than the U.S. population, and also had more children per household. Over 40% of parents and 30% of children had previously received mental health services and many scored in the clinical range on measures of psychopathology. Contrary to hypotheses, mental health help seeking was higher in the Health Survey than the Mental Health survey. Conclusions MTurk is a feasible method for child and adolescent clinical psychology research, although participants may not be fully demographically representative of the general population and could possibly be better considered an at-risk or clinical sample than a community sample.
Synthesis and Properties of New Polyamides Based on Bis[4-(4-aminophenoxy)phenyl]diphenylmethane

A new diamine, bis[4-(4-aminophenoxy)phenyl]diphenylmethane (BAPDM), bearing diphenylmethylene linkage was prepared starting from bis(4-hydroxyphenyl)diphenylmethane. The diamine was reacted with various aromatic dicarboxylic acids to obtain a series of new polyamides with moderate to high inherent viscosities of 0.65−0.97 dL g-1. Almost all of the polymers could be readily dissolved in NMP, N,N-dimethylacetamide, N,N-dimethylformamide, dimethyl sulfoxide, m-cresol, pyridine, tetrahydrofuran, and cyclohexanone. All of the polymers were amorphous, and the polyamide films had a tensile strength range of 85−108 MPa. These polyamides had glass transition temperatures between 237 and 272 °C and 10% weight loss temperatures in the range 500−524 °C in nitrogen.
Growth of crystal silicon by PMCZ method

In this paper, we present our research on the growth of CZSi in a ring permanent magnetic field (PMCZ). It was shown that in the ring permanent magnetic field thermal convection in melt and centrifugal pumping flows due to crystal rotation can be strongly suppressed so that the fluctuations of temperature and micro-growth rate at interface are restrained effectively. The oxygen concentration in as-grown crystal is lower and the dopant is more homogeneous. The mechanism of the effect of the permanent magnetic field on the growth of CZSi is also discussed.
A high resolution neutron powder diffraction study of D2O ice XI

The lattice parameters and diffraction peak profiles are presented for KOD‐doped D2O ice both in its low‐temperature ordered state (ice XI) and as a function of temperature through the transition to ice Ih at 76 K. They are compared with parallel measurements on pure D2O ice. We demonstrate that ice XI is orthorhombic, with lattice parameters a=4.465(3) A, b=7.859(4) A, and c=7.292(2) A at 5 K, as compared with a=4.4974(1) A and c=7.3236(1) A for pure ice. The detransformed phase measured at 5 K has a different c‐lattice parameter from that of pure ice, with a=4.4971(1) A and c=7.3182(1) A. The transformed sample is an intimate mixture of the orthorhombic transformed phase and hexagonal untransformed ice, giving rise to elastic strain effects such that the c‐lattice parameter of the untransformed phase is shifted, giving a=4.499(1) A and c=7.311(1) A. These strain effects also produce broadening of the diffraction peaks for the transformed phase relative to those of the detransformed and pure phases. We d.
Understanding arsenic metabolism through spectroscopic determination of arsenic in human urine

In this review we discuss a range of spectroscopic techniques that are currently used for analysis of arsenic in human urine for understanding arsenic metabolism and toxicity, especially in relation to genetics/ethnicity, ingestion studies and exposure to arsenic through drinking water and diet. Spectroscopic techniques used for analysis of arsenic in human urine include inductively coupled plasma mass spectrometry (ICP-MS), hydride generation atomic absorption spectrometry (HG-AAS), hydride generation atomic fluorescence spectrometry (HG-AFS), graphite furnace atomic absorption spectrometry (GF-AAS) and liquid chromatography mass spectrometry (LC-MS). Advantages and disadvantages of each of these techniques are highlighted in relation to analysis of total arsenic and speciation of arsenic compounds in human urine which would be of particular benefit to those new to the field of arsenic speciation of urine samples. The review summarises our current understanding of arsenic metabolism through the analysis of urine samples and provides a list of arsenic species that have been identified in urine samples. This is done by focusing on recent published reports on arsenic metabolism and toxicity in relation to most investigated issues, i.e. genetics/ethnicity, ingestion and exposure.
Clinical Proteomics of Metastatic Melanoma Reveals Profiles of Organ Specificity and Treatment Resistance

Purpose: Treatment of metastatic melanoma has dramatically improved in recent years, thanks to the development of immunotherapy and BRAF-MEK–targeted therapies. However, these developments revealed marked heterogeneity in patient response, which is yet to be fully understood. In this work, we aimed to associate the proteomic profiles of metastatic melanoma with the patient clinical information, to identify protein correlates with metastatic location and prior treatments. Experimental Design: We performed mass spectrometry–based proteomic analysis of 185 metastatic melanoma samples and followed with bioinformatics analysis to examine the association of metastatic location, BRAF status, survival, and immunotherapy response with the tumor molecular profiles. Results: Bioinformatics analysis showed a high degree of functional heterogeneity associated with the site of metastasis. Lung metastases presented higher immune-related proteins, and higher mitochondrial-related processes, which were shown previously to be associated with better immunotherapy response. In agreement, epidemiological analysis of data from the National Cancer Database showed improved response to anti-programmed death 1, mainly in patients with lung metastasis. Focus on lung metastases revealed prognostic and molecular heterogeneity and highlighted potential tissue-specific biomarkers. Analysis of the BRAF mutation status and prior treatments with MAPK inhibitors proposed the molecular basis of the effect on immunotherapy response and suggested coordinated combination of immunotherapy and targeted therapy may increase treatment efficacy. Conclusions: Altogether, the proteomic data provided novel molecular determinants of critical clinical features, including the effects of sequential treatments and metastatic locations. These results can be the basis for development of site-specific treatments toward treatment personalization.
Analysis of background parenchymal enhancement (BPE) on contrast enhanced spectral mammography compared with magnetic resonance imaging.

OBJECTIVES With the growing number of new breast cancer cases in women, new methods of imaging arise. Contrast enhanced spectral mammography (CESM) and magnetic resonance imaging (MRI) are comparable methods regarding sensitivity. The aim of this study is to check if analysis of background parenchymal enhancement on CESM can improve its usefulness. MATERIAL AND METHODS A total of 64 patients with breast lesions found previously on ultrasound or mammography underwent MRI and CESM within less than one month. On MRI the contrast enhancement kinetics and visual BPE were evaluated. On CESM the enhancement of lesions was noted as well as a quantitative level of BPH. The gathered data was analysed in terms of patterns and relations. RESULTS A total of 66 lesions were identified both on MRI and CESM, including 11 (17%) benign and 55 (83%) malignant lesions. Among malignant lesions 13 (20%) were assessed as intraductal and 42 (64%) as infiltrating carcinomas. The study showed correlation between the level of enhancement on CESM and the type of kinetic curve on MRI and lesion enhance-ment on CESM as well as confirmed the fact that the BPE is a destimulant in both methods of imaging. CONCLUSIONS Evaluation of BPE level on CESM can help reading radiologists to define a lesion as malignant with higher probability than based only on the qualitative lesion enhancement level.
Neurological Examination Techniques of Speech in Bahasa Malaysia for Adults: Simple Approach Practiced in Hospital Universiti Sains Malaysia

There are four classification levels for speech disorders namely dysphonia, dysarthria, dysprosody and dysphasia. In general, speech examination mainly focuses on three main components that are spontaneous speech, auditory comprehension, and oral motor examination. Quick bedside assessment on speech in Bahasa Malaysia is essential to assist the speech language therapist (SLT) and other physicians to determine the disorders. Speech therapy is also essential in monitoring and continuous assessment for patients with speech and language disorders such as dysphasia and dysarthria. Speech clinicians in Hospital Universiti Sains Malaysia (HUSM) have been adapting two most widely used batteries of speech assessment tools namely Western aphasia battery-revised (WAB-R) by Andrew Kertesz and Boston diagnostic aphasia examination (BDAE). These tools have been modified into simple and validated speech assessments in Bahasa Malaysia. This video manuscript will demonstrate the use of both tools in performing bedside speech assessment for patients with speech disorders. The Bahasa Malaysia speech examination should not be difficult when WAB-R and BDAE speech assessment tools are applied. The aim of this simple approach using the adapted version of BDAE and WAB-R is to assist the clinician to achieve quick and accurate diagnosis with a validated scoring system.
Psychological therapies for adolescents with borderline personality disorder (BPD) or BPD features—A systematic review of randomized clinical trials with meta-analysis and Trial Sequential Analysis

Objectives To review the effectiveness of psychological therapies for adolescents with borderline personality disorder (BPD) or BPD features. Methods We included randomized clinical trials on psychological therapies for adolescents with BPD and BPD features. Data were extracted and assessed for quality according to Cochrane guidelines, and summarized as mean difference (MD) with 95% confidence intervals (CI) for continuous data and as Odds ratios (OR) with 95% CI for dichotomous data. Risk of bias was assessed using Cochrane’s risk of bias tool for each domain. When possible, we pooled trials into meta-analyses, and used Trial Sequential Analysis (TSA) to control for random errors. Quality of the evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). Results 10 trials on adolescents with BPD or BPD features were included. All trials were considered at high risk of bias, and the quality of the evidence was rated as “very low”. We did TSA on the primary outcome and found that the required information size was reached. The risk of random error was thus discarded. Conclusion Only 10 trials have been conducted on adolescents with BPD or BPD features. Of these only few showed superior outcomes of the experimental intervention compared to the control intervention. No adverse effects of the interventions were mentioned. Attrition rates varied from 15–75% in experimental interventions. The overall quality was very low due to high risk of bias, imprecision and inconsistency, which limits the confidence in effect estimates. Due to the high risk of bias, high attrition rates and underpowered studies in this area, it is difficult to derive any conclusions on the efficacy of psychological therapies for BPD in adolescence. There is a need for more high quality trials with larger samples to identify effective psychological therapies for this specific age group with BPD or BPD features.
Continuous postoperative negative pressure irrigation assisted mammaplasty in treating chronic refractory plasma cell mastitis.

Background Chronic refractory plasma cell mastitis (CRPCM) is an aseptic inflammation of the breast with a chronic course of the disease, extended treatment cycle (months to years), with a high recurrence rate. The objective of this study was to evaluate the efficacy of continuous postoperative negative pressure irrigation assisted mammaplasty (CPNPIAM) in treating CRPCM. Methods Between 2016 and 2018, 36 CRPCM patients receiving CPNPIAM were enrolled in this study. CPNPIAM mainly involved complete lesion removal, immediate breast mammaplasty, and continuous postoperative negative pressure irrigation. The age of the patients, local symptoms, history of treatment, the duration of the disease before surgery, hospitalization period, related risk factors, the success rate, the recurrence rate and patients' overall satisfaction ratings were analyzed in the article. Results Patients were aged between 22 and 53 years (mean 34.64 years). All patients had a history of conservative treatment or simple drainage. Local symptoms included inflammatory mass (n=36, 100%), abscess (n=33, 92%), nipple discharge (n=7, 19%), inflammatory plaque (n=34, 94%), and sinus tract formation (n=19, 53%). The lesion sizes ranged from 3 to 10 cm (mean 5.13 cm) in diameter. The mean hospitalization period was 8.42 days. The success rate was 100% (36/36) and the recurrence rate was 0% (0/36) at a 3-month follow-up. The patients' overall satisfaction ratings were "very good" (n=22, 61%), "good" (n=12, 33%), and "moderate" (n=2, 6%) with no poor or unsatisfactory ratings. Conclusions CPNPIAM is an effective way of treating CRPCM, and showed a high success rate, a low recurrence rate, and high patient satisfaction.