Miracle-dz/UniFAR-FTUs huggingface dataset:
Novel Mutations of COL4A5 Identified in Chinese Families with X-Linked Alport Syndrome and Literature Review

Alport syndrome (AS) is an inherited kidney disease caused by defects in type IV collagen, which is characterized by hematuria, progressive nephritis or end-stage renal disease (ESRD), hearing loss, and occasionally ocular lesions. Approximately 80% of AS cases are caused by X-linked mutations in the COL4A5 gene. This study explored novel deletion and missense mutations in COL4A5 responsible for renal disorder in two Han Chinese families. In pedigree 1, the five male patients all had ESRD at a young age, while the affected female members only presented with microscopic hematuria. Whole exome sequencing and Sanger sequencing identified a novel frameshift deletion mutation (c.422_428del, p.Leu142Valfs∗11) in exon 7 of COL4A5. In pedigree 2, the 16-year-old male proband had elevated serum creatinine (309 μmol/L) without extrarenal manifestations, while his mother only manifested with hematuria. A missense mutation (c.476G>T, p.Gly159Val) was found in exon 9 of the COL4A5 gene. Neither of these mutations was present in the Exome Variant Server of the NHLBI-ESP database, nor was it found in the ExAC or 1000 Genomes databases. Through the literature review, it was found that male Chinese patients with X-linked AS carried COL4A5 deletion or missense mutations had a more severe phenotype than female patients, particularly in proteinuria and impaired renal function. Compared to male patients with missense mutations, patients in whom deletion mutations were found were more likely to progress to ESRD (15.4% vs. 36.0%, P = 0.041). This study identified two novel COL4A5 mutations in Chinese families with X-linked AS, expanded the mutational spectrum of the COL4A5 gene, and presented findings that are significant for the screening and genetic diagnosis of AS.
Optical coherence tomography-guided excimer laser coronary angioplasty in overlapping stents with severe under-expansion and underlying calcification

Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing Key Laboratory of Precision Medicine of Coronary Atherosclerotic Disease, Clinical Center for Coronary Heart Disease, Capital Medical University, Beijing, China The authors contributed equally to this manuscript ✉ Correspondence to: gqydyx3000@163.com ; azzyj12@163.com https://doi.org/10.11909/j.issn. 1671-5411.2021. 02.006
MLKL: Functions beyond serving as the Executioner of Necroptosis

Recently, necroptosis, as a programmed cell death pathway, has drawn much attention as it has been implicated in multiple pathologies, especially in the field of inflammatory diseases. Pseudokinase mixed lineage kinase domain-like protein (MLKL) serves as a terminal-known obligate effector in the process of necroptosis. To date, the majority of research on MLKL has focused on its role in necroptosis, and the prevailing view has been that the sole function of MLKL is to mediate necroptosis. However, increasing evidence indicates that MLKL can serve as a regulator of many diseases via its non-necroptotic functions. These functions of MLKL shed light on its functional complexity and diversity. In this review, we briefly introduce the current state of knowledge regarding the structure of MLKL, necroptosis signaling, as well as cross-linkages among necroptosis and other regulated cell death pathways, and we particularly highlight recent progress related to newly identified functions and inhibitors of MLKL. These discussions promote a better understanding of the role of MLKL in diseases, which will foster efforts to pharmacologically target this molecule in clinical treatments.
CHARACTERIZATION OF ANTIBACTERIAL SUBSTANCE PRODUCED BY Pseudomonas Fluorescens

Pseudomonas fluorescens isolate was isolated from soil. The antibacterial activity of crude extract of this isolate was determined against pathogenic bacteria (Klebsiella pneumonia, Staphylococcus aureus) which are isolated from patients with skin infections. The extraction of this substance was done and study it characterization after purified by silica gel chromatography, It was stable within range of pH (5-9) at 37 oC for 24 hr. and inactivated by serum at concentration > 50%. The substance was soluble in methylene chloride, chloroform, acetone, sodium hydroxide and hydrochloric acid and it was insoluble in water, methanol, ethyl acetate and hexane.
High-Pressure Vapor−Liquid Equilibria in the System Carbon Dioxide and 2-Propanol at Temperatures from 293.25 K to 323.15 K

Isothermal (P, T, x, y) data have been measured for the binary system carbon dioxide + 2-propanol at temperatures from (293 to 323) K. The pressure range under investigation was between (0.68 and 8.6) MPa. The new experimental data are correlated with the Soave−Redlich−Kwong (SRK) equation of state coupled with the HVID mixing rules. A correlation of the HVID parameters with temperature is proposed by using all reliable published data and those of this study.
Single-cell transcriptome dissection of the toxic impact of Di (2-ethylhexyl) phthalate on primordial follicle assembly

Rationale: Accumulated evidence indicates that environmental plasticizers are a threat to human and animal fertility. Di (2-ethylhexyl) phthalate (DEHP), a plasticizer to which humans are exposed daily, can trigger reproductive toxicity by acting as an endocrine-disrupting chemical. In mammals, the female primordial follicle pool forms the lifetime available ovarian reserve, which does not undergo regeneration once it is established during the fetal and neonatal period. It is therefore critical to examine the toxicity of DEHP regarding the establishment of the ovarian reserve as it has not been well investigated. Methods: The ovarian cells of postnatal pups, following maternal DEHP exposure, were prepared for single cell-RNA sequencing, and the effects of DEHP on primordial follicle formation were revealed using gene differential expression analysis and single-cell developmental trajectory. In addition, further biochemical experiments, including immunohistochemical staining, apoptosis detection, and Western blotting, were performed to verify the dataset results. Results: Using single-cell RNA sequencing, we revealed the gene expression dynamics of female germ cells and granulosa cells following exposure to DEHP in mice. Regarding germ cells: DEHP impeded the progression of follicle assembly and interfered with their developmental status, while key genes such as Lhx8, Figla, and others, strongly evidenced the reduction. As for granulosa cells: DEHP likely inhibited their proliferative activity, and activated the regulation of cell death. Furthermore, the interaction between ovarian cells mediated by transforming growth factor-beta signaling, was disrupted by DEHP exposure, since the expression of GDF9, BMPR1A, and SMAD3 was affected. In addition, DNA damage and apoptosis were elevated in germ cells and/or somatic cells. Conclusion: These findings offer substantial novel insights into the reproductive toxicity of DEHP exposure during murine germ cell cyst breakdown and primordial follicle formation. These results may enhance the understanding of DEHP exposure on reproductive health.
Lower Extremity Rehabilitation in Patients with Post-Stroke Sequelae through Virtual Reality Associated with Mirror Therapy

More innovative technologies are used worldwide in patient’s rehabilitation after stroke, as it represents a significant cause of disability. The majority of the studies use a single type of therapy in therapeutic protocols. We aimed to identify if the association of virtual reality (VR) therapy and mirror therapy (MT) exercises have better outcomes in lower extremity rehabilitation in post-stroke patients compared to standard physiotherapy. Fifty-nine inpatients from 76 initially identified were included in the research. One experimental group (n = 31) received VR therapy and MT, while the control group (n = 28) received standard physiotherapy. Each group performed seventy minutes of therapy per day for ten days. Statistical analysis was performed with nonparametric tests. Wilcoxon Signed-Rank test showed that both groups registered significant differences between pre-and post-therapy clinical status for the range of motion and muscle strength (p < 0.001 and Cohen’s d between 0.324 and 0.645). Motor Fugl Meyer Lower Extremity Assessment also suggested significant differences pre-and post-therapy for both groups (p < 0.05 and Cohen’s d 0.254 for the control group and 0.685 for the experimental group). Mann-Whitney results suggested that VR and MT as a therapeutic intervention have better outcomes than standard physiotherapy in range of motion (p < 0.05, Cohen’s d 0.693), muscle strength (p < 0.05, Cohen’s d 0.924), lower extremity functionality (p < 0.05, Cohen’s d 0.984) and postural balance (p < 0.05, Cohen’s d 0.936). Our research suggests that VR therapy associated with MT may successfully substitute classic physiotherapy in lower extremity rehabilitation after stroke.
Development of a Patient-Oriented Intervention to Support Patient-Provider Conversations about Unnecessary Lower Back Pain Imaging

Background: despite the efforts of multiple stakeholders to promote appropriate care throughout the healthcare system, studies show that two out of three lower back pain (LBP) patients expect to receive imaging. We used the Choosing Wisely Canada patient-oriented framework, prioritizing patient engagement, to develop an intervention that addresses lower back pain imaging overuse. Methods: to develop this intervention, we collaborated with a multidisciplinary advisory team, including two patient partners with lower back pain, researchers, clinicians, healthcare administrators, and the Choosing Wisely Canada lead for Saskatchewan. For this qualitative study, data were collected through two advisory team meetings, two individual interviews with lower back pain patient partners, and three focus groups with lower back pain patient participants. A lower back pain prescription pad was developed as an outcome of these consultations. Results: participants reported a lack of interactive and informative communication was a significant barrier to receiving appropriate care. The most cited content information for inclusion in this intervention was treatments known to work, including physical activity, useful equipment, and reliable sources of educational material. Participants also suggested it was important that benefits and risks of imaging were explained on the pad. Three key themes derived from the data were also used to guide development of the intervention: (a) the role of imaging in LBP diagnosis; (b) the impact of the patient-physician relationship on LBP diagnosis and treatment; and (c) the lack of patient awareness of Choosing Wisely Canada and their recommendations. Conclusions: the lower back pain patient-developed prescription pad may help patients and clinicians engage in informed conversations and shared decision making that could support reduce unnecessary lower back pain imaging.
320 Slice CT in Imaging of Congenital Heart Diseases in Infants: A Single-Center Experience

Objective The study was conducted to evaluate the best possible imaging technique for neonatal cardiac imaging including optimal injection techniques, intravenous line placement, expected radiation dose, and need for sedation while performing the study on a 320 slice Toshiba® Aquilion ONE® scanner. Study results can be used to optimize imaging parameters for maximum clinical yield. We provide representative images of our cases. Methodology Cardiac CTs performed on infants less than one year of age at the time of study were evaluated. Data collection included radiation dose, duration of the scan, heart rate, type and route of contrast injection, need for sedation or general anesthesia and quality of study including image contrast and motion artifacts. Results Average age of infants at the time of scan was approximately two months. Prospectively gated volumetric scans performed within one heartbeat with a single gantry turn formed the majority of studies. Average effective dose was below 1 mSv. Several patients were scanned without any sedation. Most studies were deemed diagnostic and of superior quality on a 4-point scale. Qualitative image analysis revealed an excellent intraclass correlation between two raters. Conclusion Parameters needed for successfully performing cardiac CTs with a high degree of diagnostic quality in neonates were identified. For infants below a year hand injection of Isovue 300 in a 24 G peripheral upper extremity IV line with real-time contrast bolus monitoring and manual start to scanning is adequate when being scanned on a 320 slice Volumetric scanner with prospective auto-target EKG gating. Sedation may not be necessary for infants when wrap and feed techniques and free breathing are employed. Radiation doses utilizing this technique were uniformly low.
Accurate in vivo tumor detection using plasmonic-enhanced shifted-excitation Raman difference spectroscopy (SERDS)

For the majority of cancer patients, surgery is the primary method of treatment. In these cases, accurately removing the entire tumor without harming surrounding tissue is critical; however, due to the lack of intraoperative imaging techniques, surgeons rely on visual and physical inspection to identify tumors. Surface-enhanced Raman scattering (SERS) is emerging as a non-invasive optical alternative for intraoperative tumor identification, with high accuracy and stability. However, Raman detection requires dark rooms to work, which is not consistent with surgical settings. Methods: Herein, we used SERS nanoprobes combined with shifted-excitation Raman difference spectroscopy (SERDS) detection, to accurately detect tumors in xenograft murine model. Results: We demonstrate for the first time the use of SERDS for in vivo tumor detection in a murine model under ambient light conditions. We compare traditional Raman detection with SERDS, showing that our method can improve sensitivity and accuracy for this task. Conclusion: Our results show that this method can be used to improve the accuracy and robustness of in vivo Raman/SERS biomedical application, aiding the process of clinical translation of these technologies.
Synthesis and Structural Characterization of Polyaniline/Mesoporous Carbon Nanocomposite

Abstract In this work, a new nanocomposite in which polyaniline (PANI) is encapsulated in ordered mesoporous carbon (CMK-3 type) has been synthesized. The aniline monomer was introduced into hosts from the vapor phase to avoid the formation of PANI layers on the outer surface. The structure and morphology of the nanocomposite were characterized by X-ray diffraction (XRD), N2 adsorption/desorption, FT-IR and Raman spectra, high-resolution transmission electron microscopy (HRTEM), and thermogravimetric analysis (TGA). The results show that PANI is almost formed in the channels of CMK-3 and the nanocomposite retains the ordered mesostructure. Encapsulated PANI exhibits better thermal stability than pure PANI because of confinement effect in the channel system. The conductivity of PANI/CMK-3 nanocomposite containing 8.4 wt% PANI is 0.78 S/cm at room temperature.
Room-Temperature Cu–Cu Bonding in Ambient Air Achieved by Using Cone Bump

We demonstrate room-temperature Cu–Cu bonding in ambient air by using a Cu cone bump in combination with a Cu electrode with a cross-shaped slit. By wedging the Cu cone bump into the cross-shaped slit, a bonded interface that is substantially free from contaminants can be formed. The cross-shaped slit gives lower connection resistance than a simple hole. The resistance per connection was approximately 83 mΩ.
The Healing after Gender-Based Violence Scale (GBV-Heal): An Instrument to Measure Recovery Progress in Women-Identifying Survivors

Current literature has primarily equated gender-based violence recovery with an improvement of physical or mental health symptoms, causing a gap in our understanding of the impact of interventions beyond the amelioration of adverse symptomology. The purpose of this research was to create an instrument to holistically measure gender-based violence recovery based on survivor healing goals. Ethnographic interviews were conducted in women-identifying gender-based violence survivors (ages 18–76) to determine healing domains and develop items using survivor language (n = 56). Focus groups with academic and community experts (n = 12) and cognitive interviews with gender-based violence survivors (n = 12) were conducted to ensure content and face validity, as well as to evaluate acceptability. This yielded a 31-item instrument to measure healing progress on a 5-point Likert scale. The Healing after Gender-based Violence Scale has the potential to highlight survivor strength and growth while more accurately measuring their recovery process based on survivor goals and desires.
ONE-DIMENSIONAL NONLINEAR MODEL FOR DETERMINING COMBUSTION INSTABILITY IN SOLID PROPELLANT ROCKET MOTORS

SUMMARY OF RESULTS A one-dimensional, nonlinear analysis of transverse mode instability in a solid pro- pellant rocket geometry indicated the relative combustion stability based on three para- metric groupings: burning rate, wall-loss, and viscous-dissipation parameters, of which only the burning rate parameter appeared to be significant in the one-dimensional model with a nonvibrating solid phase. The results of the analysis, presented as the minimum pressure amplitude required to incite instability as a function of the burning rate parameter, showed that erosive burning was an important factor in determining sta- bility. With only a 10-percent contribution to the burning rate due to erosion, the sta- bility boundary was significantly affected so as to reduce the stable region of operation. A two-fold increase in the pressure exponent in the burning rate law also showed a de- crease in the stable operating regime. This effect was not as pronounced as the erosive effect. Increasing the
Performance evaluation of anaerobic fluidized bed reactors using brick beads and porous ceramics as support materials for treating terephthalic acid wastewater

AbstractThis study evaluated two different porous support materials (brick beads and porous ceramics) used in rapid mass-transfer anaerobic fluidized bed reactors (AFBRs) for treating terephthalic acid wastewater. The AFBRs, denoted as R1 (containing brick beads) and R2 (containing porous ceramics), were inoculated with anaerobic sludge. Results showed that the system organic loading rate increased from 7.37 kg COD/(m3 d) to 18.52 kg COD/(m3 d) over a period of 73 d. During the steady period, R2 showed better performance than R1. The chemical oxygen demand removal efficiency and total alkalinity removal efficiency of R1 were 65–75% and 60–70%, whereas those of R2 were 75–88% and 72–84%, respectively.
ANO1 Expression Orchestrates p27Kip1/MCL1-Mediated Signaling in Head and Neck Squamous Cell Carcinoma

Simple Summary Our aim was to elucidate the molecular mechanisms of how ANO1 contributes to oncogenic processes in squamous cell carcinoma of the head and neck (HNSCC). We explored transcriptional programs influenced by ANO1 knockdown in patient-derived UT-SCC cell lines with 11q13 amplification and ANO1 overexpression. ANO1 depletion led to downregulation of broad pro-survival BCL2 family protein members, including MCL1, and simultaneously induced upregulation of the cell cycle inhibitor p27Kip1 and its redistribution from the cytoplasm into the nucleus in the studied HNSCC cells. Gene set enrichment analysis highlighted pathways associated with perturbed cell cycle and apoptosis in the ANO1-depleted samples. Silencing of ANO1 and application of an ANO1-targeting small-molecule inhibitor led to ANO1 degradation and reduction of cell viability. These findings suggest that ANO1 has drug target potential that deserves further evaluation in preclinical in vivo models. Abstract Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous group of tumors that derive from the mucosal epithelium of the upper aerodigestive tract and present high mortality rate. Lack of efficient targeted-therapies and biomarkers towards patients’ stratification are caveats in the disease treatment. Anoctamin 1 (ANO1) gene is amplified in 30% of HNSCC cases. Evidence suggests involvement of ANO1 in proliferation, migration, and evasion of apoptosis; however, the exact mechanisms remain elusive. Aim of this study was to unravel the ANO1-dependent transcriptional programs and expand the existing knowledge of ANO1 contribution to oncogenesis and drug response in HNSCC. We cultured two HNSCC cell lines established from primary tumors harboring amplification and high expression of ANO1 in three-dimensional collagen. Differential expression analysis of ANO1-depleted HNSCC cells demonstrated downregulation of MCL1 and simultaneous upregulation of p27Kip1 expression. Suppressing ANO1 expression led to redistribution of p27Kip1 from the cytoplasm to the nucleus and associated with a cell cycle arrested phenotype. ANO1 silencing or pharmacological inhibition resulted in reduction of cell viability and ANO1 protein levels, as well as suppression of pro-survival BCL2 family proteins. Collectively, these data provide insights of ANO1 involvement in HNSCC carcinogenesis and support the rationale that ANO1 is an actionable drug target.
Neuropathic Low Back Pain and Burnout among Hungarian Workers

Burnout is an increasingly prevalent syndrome mainly involving those working in human services. Although it is categorized as an occupational phenomenon and not as a medical condition, it seems to be strongly associated with several diseases such as pain syndromes. However, no studies examined the association between neuropathic low back pain and burnout. This questionnaire-based study was carried out between April 2019 and March 2020 in three main sites among teachers, social workers and healthcare workers. Demographic criteria included age, gender, marital status, number of children, type of work, years spent with work, work schedule, legal relation, secondary employment. Included diseases were diabetes, hypertension, ischemic heart disease, generalized pain (pain involving more than one area of the body) and depression. Low back pain was assessed by the painDETECT questionnaire, burnout was measured with the Maslach Burnout Inventory (MBI) and depression was measured by the Beck Depression Inventory. Dysfunctional attitudes were also recorded. Overall, 1500 questionnaires were successfully delivered and 1141 responses received (response rate of 76%). Three hundred social workers, 399 teachers, 339 paramedics, 35 doctors and 68 medical attendants have completed our survey. In a multivariate analysis including of all factors (demographic criteria, burnout, depression, dysfunctional attitudes, comorbidity etc.) neuropathic low back pain was associated with age > 62 (OR = 3.981, p = 0.01), number of children ≥ 2 (OR = 2.638, p = 0.003), job type (being a social worker) (OR = 6.654, p < 0.001), burnout (OR = 2.577, p < 0.001), current depression (OR = 2.397, p < 0.001), and suffering from generalized pain (OR= 4.076, p < 0.001). This is the first study showing the association of burnout and neuropathic low back pain, which is the most common cause of disability. Based on our results neuropathic low back pain and burnout have similar risk factors and consequences which raises the possibility of similar pathophysiology.