Miracle-dz/UniFAR-FTUs huggingface dataset:
Kilohertz waveforms optimized to produce closed-state Na+ channel inactivation eliminate onset response in nerve conduction block

The delivery of kilohertz frequency alternating current (KHFAC) generates rapid, controlled, and reversible conduction block in motor, sensory, and autonomic nerves, but causes transient activation of action potentials at the onset of the blocking current. We implemented a novel engineering optimization approach to design blocking waveforms that eliminated the onset response by moving voltage-gated Na+ channels (VGSCs) to closed-state inactivation (CSI) without first opening. We used computational models and particle swarm optimization (PSO) to design a charge-balanced 10 kHz biphasic current waveform that produced conduction block without onset firing in peripheral axons at specific locations and with specific diameters. The results indicate that it is possible to achieve onset-free KHFAC nerve block by causing CSI of VGSCs. Our novel approach for designing blocking waveforms and the resulting waveform may have utility in clinical applications of conduction block of peripheral nerve hyperactivity, for example in pain and spasticity.
A comparison of frequency and magnitude of head impacts between Pee Wee And Bantam youth ice hockey

ABSTRACT The purpose of this research was to compare the frequency and magnitude of head impact events between Pee Wee and Bantam ice hockey players. Videos of Pee Wee and Bantam boys’ ice hockey were analysed to determine the frequency and type of head impact events. The head impact events were then reconstructed in the laboratory using physical and finite element models to determine the magnitude of strain in the brain tissues. The results showed that Pee Wee boys experienced more head impacts from elbows and boards, while Bantam players had more head impacts to the glass. Pee Wee and Bantam players experienced similar frequency and magnitudes of very low, low, and medium and above (med+) levels of strain to the brain. This research suggests to ice hockey leagues and coaches that to reduce the incidence of these levels of brain trauma, consideration must be given to either reducing the level of contact along the boards or the removal of body checking. In addition, companies who innovate in ice hockey should develop protective devices and equipment strategies that aim to reduce the risk of head injury from shoulder and glass impacts for Bantam players.
Progress in the correlation between PTPN12 gene expression and human tumors

Abstract Background: The global morbidity of cancer is rising rapidly. Despite advances in molecular biology, immunology, and cytotoxic and immune-anticancer therapies, cancer remains a major cause of death worldwide. Protein tyrosine phosphatase non-receptor type 12 (PTPN12) is a new member of the cytoplasmic protein tyrosine phosphatase family, isolated from a cDNA library of adult colon tissue. Thus far, no studies have reviewed the correlation between PTPN12 gene expression and human tumors. Methods: This article summarizes the latest domestic and international research developments on how the expression of PTPN12 relates to human tumors. The extensive search in Web of Science and PubMed with the keywords including PTPN12, tumor, renal cell carcinoma, proto-oncogenes, tumor suppressor genes was undertaken. Results: More and more studies have shown that a tumor is essentially a genetic disease, arising from a broken antagonistic function between proto-oncogenes and tumor suppressor genes. When their antagonistic effect is out of balance, it may cause uncontrolled growth of cells and lead to the occurrence of tumors. PTPN12 is a tumor suppressor gene, so inhibiting its activity will lead directly or indirectly to the occurrence of tumors. Conclusion: The etiology, prevention, and treatment of tumors have become the focus of research around the world. PTPN12 is a tumor suppressor gene. In the future, PTPN12 might serve as a novel molecular marker to benefit patients, and even the development of tumor suppressor gene activation agents can form a practical research direction.
Promotion of epithelial hyperplasia by interleukin‐8—CXCR axis in human prostate

The clinical manifestation of benign prostatic hyperplasia (BPH) is causally linked to the inflammatory microenvironment and proliferation of epithelial and stromal cells in the prostate transitional zone. The CXC‐chemokine interleukin‐8 (IL‐8) contributes to inflammation. We evaluated the expression of inflammatory cytokines in clinical specimens, primary cultures, and prostatic lineage cell lines. We investigated whether IL‐8 via its receptor system (IL‐8 axis) promotes BPH.
Pediatric Intentional Self-poisoning Evaluated in the Emergency Department

Supplemental digital content is available in the text. Background Suicide is a growing public health problem during late childhood and adolescence. The leading method of suicide attempts in this age group is intentional self-poisoning. A first self-poisoning episode is a strong predictor of subsequent suicide and premature death. The objective of this study was to analyze the presentation and management of children younger than 18 years with intentional self-poisonings admitted to an emergency department (ED) in a global research network of pediatric EDs. Methods We performed a secondary analysis of a large, international, multicenter, cross-sectional prospective registry of childhood poisoning presentations to 105 EDs in the Pediatric Emergency Research Networks (PERN) network. Data collection started at each ED between January and September 2013 and continued for 1 year. Results During the study period, we included 1688 poisoning exposures. Of these, 233 (13.8%) were intentional self-poisonings, with significant variation between regions. Female/male ratio was 4.7/1 and most occurred at home. The most common toxicants were therapeutic drugs, mainly psychotropics and analgesics. Ninety patients (38.6%) gave a history of a previous episode of intentional self-poisoning. Sixty-three children (27.0%) were not assessed by a psychiatric service nor transferred to a psychiatric inpatient facility. No patient died. There was significant variation in the involved toxicants and interventions among EDs in different global regions. Conclusions Most intentional self-poisoning presentations to pediatric EDs globally are related to intentional ingestions of therapeutic drugs at home by females. Best practices have to be translated into care to guarantee the best outcomes of these patients.
A Pathophysiological Perspective on COVID-19's Lethal Complication: From Viremia to Hypersensitivity Pneumonitis-like Immune Dysregulation

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the coronavirus responsible for our recent coronavirus disease 2019 pandemic, is driving a lung immunopathology that strongly resembles a severe form of hypersensitivity pneumonitis (HP). A review of recent Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and SARS-CoV-2 medical reports, as well as described characteristics of HP, lead us to postulate a theory for SARS-CoV-2 severe disease. We propose that the novel SARS-CoV-2 can act as a trigger and substrate of an HP-like severe immune reaction especially in genetically vulnerable individuals in addition to those with immune senescence and dysregulation. Accordingly, the purpose of our letter is to shift the emphasis of concern surrounding immune activity from viral infection to an HP-like severe immune reaction. We review similarities in disease presentation between infection and allergy, relevant immunopathology, and outline phases of SARS-CoV-2 disease with perspectives on therapy and critical care. Altogether, the favored course is to begin treatments that address the disease at the earliest phase before immune dysregulation leading to uncontrolled pulmonary inflammation.
Indigenous Australian women's experiences of participation in cervical screening

Aboriginal and Torres Strait Islander (collectively, Indigenous Australian) women experience a higher burden of cervical cancer than other women. The National Cervical Screening Program (NCSP) is failing to meet the needs of Indigenous Australian women, resulting in many women not regularly participating in cervical screening. However, one third of Indigenous Australian women do participate in cervical screening. The reasons that some women in this population commence and continue to screen remain unheard but could provide insights to support women who currently do not participate. We aimed to describe Indigenous Australian women’s experiences and views of participation in cervical screening by yarning (a culturally-appropriate interview technique) with 50 Indigenous Australian women aged 25–70 years who had completed cervical screening in the past five years, recruited via Primary Health Care Centres (PHCCs) from three jurisdictions. Aboriginal or Torres Strait Islander women researchers conducted the interviews. Thematic analysis identified six themes: screening as a means of staying strong and in control; overcoming fears, shame, and negative experiences of screening; needing to talk openly about screening; the value of trusting relationships with screening providers; logistical barriers; and overcoming privacy concerns for women employed at PHCCs. Despite describing screening as shameful, invasive, and uncomfortable, women perceived it as a way of staying healthy and exerting control over their health. This ultimately supported their participation and a sense of empowerment. Women valued open discussion about screening and strong relationships with health providers. We identified logistical barriers and specific barriers faced by women employed at PHCCs. This study is strengthened by a research approach that centred Indigenous Australian women’s voices. Understanding the experiences of Indigenous Australian women who participate in screening will help screening providers support women to start and continue to screen regularly. Recommendations for practice are provided.
Emerging treatments for bullous pemphigoid

Abstract Bullous pemphigoid (BP) is the most common autoimmune blistering disease. It is characterized by an immune response against the hemidesmosomal anchoring proteins BP180 and BP230. BP mainly affects elderly patients, with an increasing incidence over the past two decades. High potency topical and/or systemic corticosteroids as well as immunosuppressants are the current mainstay of treatment. However, long-term systemic immunosuppression may result in significant morbidity and mortality. Recent advances in the understanding of the pathogenesis of BP have enabled the investigation of newer therapies that specifically work against a variety of pro-inflammatory mediators associated with BP. These new treatments hold promise to be highly efficient and safer alternatives and are expected to be shortly available for the treatment of BP. This review discusses current evidence on the use of novel targeted therapeutic approaches in the treatment of BP.
Natural Orifice Transluminal Endoscopic Surgery: Long-Term Experience with Hybrid Transvaginal Cholecystectomies

Objective. To assess outcome and safety of 571 hybrid natural orifice transluminal endoscopic surgery (NOTES) cholecystectomies. Methods. We retrospectively analyzed all consecutive NOTES cholecystectomies performed at our center between June 2009 and January 2018. All procedures were performed using a hybrid transvaginal technique, including an umbilical small-size trocar. End points, calculated at discharge, 30 and up to 90 days postoperatively, included intra- and postoperative morbidity assessed by the validated Clavien–Dindo classification and the Comprehensive Complication Index (CCI). Special focus was held on outcome and necessity of pre- and postoperative gynecological examinations. Results. We performed 571 hybrid NOTES cholecystectomies within 9 years. The vast majority were elective, 9.6% were emergency cholecystectomies. 6.7% of patients developed at least one complication until discharge, most of them minor (≤grade II). 30- and 90-day complication rates were 10.7% and 11%, respectively. Mean CCI at discharge and postoperative days 30 and 90 was 1.45 (±6.4), 2.3 (±7.7), and 2.4 (±7.8), respectively. Major complications (≥grade IIIa) occurred in 1.6% of patients, and 4 patients required emergency reoperation. No mortality was observed. In 9.8%, an additional abdominal trocar was placed. All patients underwent routine gynecological examination, whereof only 5 were rejected for transvaginal access preoperatively. In no case transvaginal access was discontinued intraoperatively due to gynecological disease. Conclusion. Hybrid NOTES transvaginal cholecystectomy represents a safe and feasible alternative to standard laparoscopic cholecystectomy. Preoperative gynecological examination is no longer routinely necessary, as intraoperative assessment is adequate.
Patients With Acinar Cell Carcinoma of the Pancreas After 2005

Objectives Acinar cell carcinoma of the pancreas is a rare tumor with limited data. We aim to evaluate the characteristics, treatments, and outcomes of pancreatic acinar cell carcinoma after 2005. Methods We retrospectively reviewed patients with pancreatic acinar cell carcinoma treated in Peking University Cancer Hospital and Institute (2005–2018) and identified cases from Surveillance, Epidemiology, and End Results database (2005–2015). Results A total of 306 cases in our institute (n = 11) and Surveillance, Epidemiology, and End Results database (n = 295) were identified. The median age was 67 years, and 73.5% were male. The 5-year survival was 36.8% for all patients (median, 27 months). About 37% underwent surgical resection. The 5-year survival was 65.6% for resected patients as compared with 16.9% for unresected ones (P < 0.0001). Among locoregional and metastatic diseases, surgery significantly prolonged survival as well (P = 0.0003). Stage IV patients who received chemotherapy had a better survival than those without it (median, 16 vs 3 months; P = 0.0019). Aging, stage IV, and no surgery were independent predictors of poor overall survival. Conclusions For pancreatic acinar cell carcinoma, surgery is a potentially curative treatment contributing to long-term survival and suggested even in advanced diseases. Chemotherapy improved survival for metastatic patients.
PKD2/polycystin-2 induces autophagy by forming a complex with BECN1

ABSTRACT Macroautophagy/autophagy is an intracellular process involved in the breakdown of macromolecules and organelles. Recent studies have shown that PKD2/PC2/TRPP2 (polycystin 2, transient receptor potential cation channel), a nonselective cation channel permeable to Ca2+ that belongs to the family of transient receptor potential channels, is required for autophagy in multiple cell types by a mechanism that remains unclear. Here, we report that PKD2 forms a protein complex with BECN1 (beclin 1), a key protein required for the formation of autophagic vacuoles, by acting as a scaffold that interacts with several co-modulators via its coiled-coil domain (CCD). Our data identified a physical and functional interaction between PKD2 and BECN1, which depends on one out of two CCD domains (CC1), located in the carboxy-terminal tail of PKD2. In addition, depletion of intracellular Ca2+ with BAPTA-AM not only blunted starvation-induced autophagy but also disrupted the PKD2-BECN1 complex. Consistently, PKD2 overexpression triggered autophagy by increasing its interaction with BECN1, while overexpression of PKD2D509V, a Ca2+ channel activity-deficient mutant, did not induce autophagy and manifested diminished interaction with BECN1. Our findings show that the PKD2-BECN1 complex is required for the induction of autophagy, and its formation depends on the presence of the CC1 domain of PKD2 and on intracellular Ca2+ mobilization by PKD2. These results provide new insights regarding the molecular mechanisms by which PKD2 controls autophagy. Abbreviations: ADPKD: autosomal dominant polycystic kidney disease; ATG: autophagy-related; ATG14/ATG14L: autophagy related 14; Baf A1: bafilomycin A1; BCL2/Bcl-2: BCL2 apoptosis regulator; BCL2L1/BCL-XL: BCL2 like 1; BECN1: beclin 1; CCD: coiled-coil domain; EBSS: Earle’s balanced salt solution; ER: endoplasmic reticulum; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GFP: green fluorescent protein; GOLGA2/GM130: golgin A2; GST: glutathione s-transferase; LAMP1: lysosomal associated membrane protein 1; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MTORC1: mechanistic target of rapamycin kinase complex 1; NBR1: NBR1 autophagy cargo receptor; PIK3C3/VPS34: phosphatidylinositol 3-kinase catalytic subunit type 3; PKD2/PC2: polycystin 2, transient receptor potential cation channel; RTN4/NOGO: reticulon 4; RUBCN/RUBICON: rubicon autophagy regulator; SQSTM1/p62: sequestosome 1; UVRAG: UV radiation resistance associated; WIPI2: WD repeat domain, phosphoinositide interacting 2
COVID-19 Molecular Testing in Korea: Practical Essentials and Answers From Experts Based on Experiences of Emergency Use Authorization Assays

Coronavirus disease 2019 (COVID-19) is a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Early detection of COVID-19 and immediate isolation of infected patients from the naive population are important to prevent further pandemic spread of the infection. Real-time reverse transcription (RT)-PCR to detect SARS-CoV-2 RNA is currently the most reliable diagnostic method for confirming COVID-19 worldwide. Guidelines for clinical laboratories on the COVID-19 diagnosis have been recently published by Korean Society for Laboratory Medicine and the Korea Centers for Disease Control and Prevention. However, these formal guidelines do not address common practical laboratory issues related to COVID-19 real-time RT-PCR testing and their solutions. Therefore, this guideline is intended as a practical and technical supplement to the “Guidelines for Laboratory Diagnosis of COVID-19 in Korea”.
Can Epstein-Barr virus play a role in upper urinary tract urothelial carcinomas?

INTRODUCTION Upper urinary tract urothelial carcinomas are very rare tumours with different biological behaviours. The Epstein-Barr virus, which is the first known oncogenic virus, is being investigated for various malignant tumours. It is known that this virus is associated with nasopharyngeal carcinoma, as well as multiple haematological malignancies, head and neck and gastric cancers. We aimed to determine the presence of the Epstein-Barr virus in upper urinary tract urothelial carcinomas using chromogenic in situ hybridisation (CISH). MATERIALS AND METHODS A total of 44 upper urinary tract urothelial carcinomas from two different centres were included. Demographic data and survival rates were obtained from hospital records. One demonstrative paraffin block from each case was stained using Epstein-Barr encoded RNA (EBER) with an automated CISH procedure. The positivity of EBER was statistically analysed for prognostic factors. RESULTS Among all patients, 38 were male and 6 were female. The mean age of the patients was 65.93 years. At the time of the study, 15 patients had died and 29 were alive. EBER-CISH positivity was found in 13 patients. Four showed strong EBER-CISH expression and nine showed weak expression. EBER-CISH positivity was not statistically related to any of the prognostic factors or to overall survival. DISCUSSION Although EBER-CISH positivity showed no significant relation with prognostic factors, it was observed in one-third of all cases. Therefore, we think that the Epstein-Barr virus may have a role in the pathogenesis of upper urinary tract urothelial carcinomas. This finding needs to be supported by larger studies.
Effects of ankle pump exercise frequency on venous hemodynamics of the lower limb.

PURPOSE The purpose of this study was (1) to compare the effects of ankle pump exercise(APE) frequency on hemodynamics of the common femoral vein(CFV) and (2) to analyse the relationship between APE duration and lower limb fatigue. METHODS Twenty-seven males and thirty-three females performed APE. Among them, there were thirty participants with non-lower limb fracture (N-LLF) and thirty participants with lower limb fracture (LLF). The colour doppler ultrasound was used to record the time-averaged mean velocity (TAMV) of common femoral venous flow when the participants at rest and move at different frequencies of 6 times/min, 10 times/min, 30 times/min, 60 times/min. The ratings of perceived exertion (RPE) was used to assess the lower limb fatigue of the participants when performing APE at the frequency of 60 times/min after 1 min, 2 mins, 3 mins, 4 mins and 5 mins. RESULTS With the increase of frequency, TAMV increased significantly in both the participants with N-LLF and LLF (p < 0.01). The TAMV were 19.82±3.86, 33.78±8.76, 37.06±8.67, 43.82±10.40, 52.18±10.53, respectively in the participants with N-LLF and 16.98±3.01, 22.20±4.96, 24.01±5.78, 29.20±7.05, 35.75±9.28, respectively in the injured limb of patients with LLF when at rest and moving at the frequency of 6 times/min, 10 times/min, 30 times/min, 60 times/min. There was a positive correlation (p < 0.01) between lower limb fatigue and exercise duration.When the RPE was 16 points (the corresponding fatigue degree is "tired"), the exercise duration of the participants with N-LLF was 3 mins and that of the injured limb of patients with LLF was 2 mins. CONCLUSIONS Both fast and slow-frequency APE can promote venous blood return in the lower limb. Despite of the equivalent APE duration, fast-frequency APE can promote venous blood return more effectively. When the frequency of APE was 60 times/min, participants with N-LLF can exercise for 3 mins, and the injured limb of patients with LLF can exercise for 2 mins.
The Association Between Age of Onset of Type 2 Diabetes and the Long-term Risk of End-Stage Kidney Disease: A National Registry Study

OBJECTIVE The long-term risk of end-stage kidney disease (ESKD) in type 2 diabetes is poorly described, as is the effect that younger age of diabetes onset has on this risk. Therefore, we aimed to estimate the effect of age of onset on the cumulative incidence of ESKD from onset of type 2 diabetes. RESEARCH DESIGN AND METHODS This study included 1,113,201 people with type 2 diabetes registered on the Australian National Diabetes Services Scheme (NDSS) followed from 2002 until 2013. The NDSS was linked to the Australia and New Zealand Dialysis and Transplant Registry and the Australian National Death Index. RESULTS Between 2002 and 2013, there were 7,592 incident cases of ESKD during 7,839,075 person-years of follow-up. In the first 10–15 years following the onset of diabetes, the incidence of ESKD was highest in those with an older age of onset of diabetes, whereas over longer durations of diabetes, the incidence of ESKD became higher in those with younger-onset diabetes. After 40 years of diabetes, the cumulative incidence of ESKD was 11.8% and 9.3% in those diagnosed with diabetes at ages 10–29 and 30–39 years, respectively. When death from ESKD without renal replacement therapy was included, the incidence of ESKD remained higher in older-onset diabetes for the initial 20 years, with no clear effect of age thereafter. CONCLUSIONS The long-term risk of ESKD in type 2 diabetes is high, which disproportionately affects those with younger onset of diabetes because they are more likely to survive to longer diabetes durations.