Miracle-dz/UniFAR-FTUs huggingface dataset:
Folding landscape of a parallel G-quadruplex

Circular dichroism and stopped-flow UV spectroscopies were used to investigate the thermodynamic stability and the folding pathway of d[TGAG3TG3TAG3TG3TA2] at 25 °C in solutions containing 25 mM KCl. Under these conditions the oligonucleotide adopts a thermally stable, all-parallel G-quadruplex topography containing three stacked quartets. K+-induced folding shows three resolved relaxation times, each with distinctive spectral changes. Folding is complete within 200 s. These data indicate a folding pathway that involves at least two populated intermediates, one of which seems to be an antiparallel structure that rearranges to the final all-parallel conformation. Molecular dynamics reveals a stereochemically plausible folding pathway that does not involve complete unfolding of the intermediate. The rate of unfolding was determined using complementary DNA to trap transiently unfolded states to form a stable duplex. As assessed by 1D-1H NMR and fluorescence spectroscopy, unfolding is extremely slow with only one observable rate-limiting relaxation time. TOC GRAPHICS
Two Clostridium perfringens Type E Isolates in France

Clostridiumperfringens type E is a less frequently isolated C. perfringens type and has not previously been reported in France. We have characterized two recent type E isolates, C. perfringens 508.17 from the intestinal content of a calf that died of enterotoxemia, and 515.17 from the stool of a 60-year-old woman, subsequent to food poisoning, which contained the plasmid pCPPB-1 with variant iota toxin and C. perfringens enterotoxin genes.
Osteonecrosis in Children and Adolescents With Acute Lymphoblastic Leukemia: Early Diagnosis and New Treatment Strategies

Background/Aim: In the last few decades, treatment strategies for acute lymphoblastic leukemia (ALL) have been associated not only with improvement of prognosis, but also with an increasing rate of late complication as osteonecrosis (ON). Herein, the cumulative incidence, risk factors, new conservative therapeutic strategies as hyperbaric oxygen therapy (HBO), and outcome of symptomatic ON were studied in pediatric patients with ALL. Patients and Methods: Between 2000 and 2017, 495 children and young adolescents with a diagnosis of ALL were evaluated. All the symptomatic patients underwent magnetic resonance imaging (MRI) to detect bone vascularization and structure. Results: Twenty-three out of 495 patients presented ON (4.6%). ON was associated with an older age (p<0.0001) and a higher steroid dose (p=0.0013). All the patients underwent standard therapies and HBO was performed in 8 of 23 patients. During the follow-up, 15 patients were stable: 6 were totally asymptomatic, 5 complained of pain during activity, and 4 presented mild function limitation. Conclusion: Our data highlight the importance of early diagnosis of ON by screening MRI in asymptomatic patients, in order to start conservative treatment strategies. Moreover, HBO could have beneficial effects on ON patients.
DSS-induced damage to basement membranes is repaired by matrix replacement and crosslinking

ABSTRACT Basement membranes are an ancient form of animal extracellular matrix. As important structural and functional components of tissues, basement membranes are subject to environmental damage and must be repaired while maintaining functions. Little is known about how basement membranes get repaired. This paucity stems from a lack of suitable in vivo models for analyzing such repair. Here, we show that dextran sodium sulfate (DSS) directly damages the gut basement membrane when fed to adult Drosophila. DSS becomes incorporated into the basement membrane, promoting its expansion while decreasing its stiffness, which causes morphological changes to the underlying muscles. Remarkably, two days after withdrawal of DSS, the basement membrane is repaired by all measures of analysis. We used this new damage model to determine that repair requires collagen crosslinking and replacement of damaged components. Genetic and biochemical evidence indicates that crosslinking is required to stabilize the newly incorporated repaired Collagen IV rather than to stabilize the damaged Collagen IV. These results suggest that basement membranes are surprisingly dynamic. Highlighted Article: When fed to Drosophila, the irritant DSS reproducibly damages basement membranes around the midgut. We show that this damage is repaired by a mechanism that requires matrix replacement and crosslinking.
Evaluating the contact rate between companion dogs during dog walking and the practices towards potential cases of rabies among dog owners in Japan

This study aimed to examine the habits of dog walking in Japan using an internet survey of insured dog owners. About 96.4% of the respondents (n = 1,151) reported that they would take their dogs for a walk and they most frequently walk their dogs once or twice a day (75.9%) for 30 min to 1 hr (83.1%). The probability of a companion dog having contact with other dogs during dog walking was estimated to be 0.83 (95% confidence interval [CI]: 0.81–0.85), and the associated daily contact rate was estimated using log‐normal distribution with a mean of 2.73 (95% CI: 2.42–3.11) and a standard deviation (SD) of 6.39 (95% CI: 5.18–7.84). Multiple linear regression revealed that the contact rate is mainly influenced by the social behaviour of the owner and to a lesser degree by his/her demographic characteristics including the area of residence, the breed size of dog and the age of the owner. In addition, ten Likert items measured on a 5‐point scale were designed to assess the practices towards potential cases of rabies among dog owners. The respondents (n = 972) achieved a mean score of 2.99 (out of a full score of 4) with a SD of 0.90 in responding to situations related to dog bite incidents and injury from stray cat scratches during dog walking. They achieved a higher score in responding to situations related to sighting a stray or wild animal during dog walking and situations related to non‐specific clinical signs of rabies and bite injuries from stray dogs or wild animals during dog walking with a mean of 3.70 (SD = 0.58) and 3.84 (SD = 0.34), respectively. The level of best practice was also proved to be significantly associated with the demographic characteristics of the dog owner.
Subclinical Inflammation in Renal Transplantation.

The standardization of renal allograft pathology began in 1991 at the first Banff Conference held in Banff, Alberta, Canada. The first task of transplant pathologists, clinicians and surgeons was to establish diagnostic criteria for T cell-mediated rejection (TCMR). The histological threshold for this diagnosis was arbitrarily set at "i2t2": a mononuclear interstitial cell infiltrate present in at least 25% of normal parenchyma, and >4 mononuclear cells within the tubular basement membrane of non atrophic tubules. TCMR was usually found in dysfunctional grafts with an elevation in the serum creatinine; however our group and others found this extent of inflammation in "routine" or "protocol" biopsies of normally functioning grafts: "subclinical" TCMR. The prevalence of TCMR is higher in the early months post transplant and has decreased with the increased potency of current immunosuppressive agents. However, the pathogenicity of lesser degrees of inflammation under modern immunosuppression and the relation between ongoing inflammation and the development of donor-specific antibody (DSA) has renewed our interest in subclinical alloreactivity. Finally, the advances in our understanding of pre transplant risk assessment, and our increasing ability to monitor patients less invasively post transplant, promises to usher in the era of precision medicine.
Pulmonary Inflammatory Myofibroblastic Tumor Expressing a Novel Fusion, PPFIBP1–ALK: Reappraisal of Anti-ALK Immunohistochemistry as a Tool for Novel ALK Fusion Identification

Purpose: The anaplastic lymphoma kinase (ALK) inhibitor crizotinib has been used in patients with lung cancer or inflammatory myofibroblastic tumor (IMT), both types harboring ALK fusions. However, detection of some ALK fusions is problematic with conventional anti-ALK immunohistochemistry because of their low expression. By using sensitive immunohistochemistry, therefore, we reassessed “ALK-negative” IMT cases defined with conventional immunohistochemistry (approximately 50% of all examined cases). Experimental Design: Two cases of ALK-negative IMT defined with conventional anti-ALK immunohistochemistry were further analyzed with sensitive immunohistochemistry [the intercalated antibody-enhanced polymer (iAEP) method]. Results: The two “ALK-negative” IMTs were found positive for anti-ALK immunohistochemistry with the iAEP method. 5′-rapid amplification of cDNA ends identified a novel partner of ALK fusion, protein-tyrosine phosphatase, receptor-type, F polypeptide-interacting protein-binding protein 1 (PPFIBP1) in one case. The presence of PPFIBP1–ALK fusion was confirmed with reverse transcriptase PCR, genomic PCR, and FISH. We confirmed the transforming activities of PPFIBP1–ALK with a focus formation assay and an in vivo tumorigenicity assay by using 3T3 fibroblasts infected with a recombinant retrovirus encoding PPFIBP1–ALK. Surprisingly, the fusion was also detected by FISH in the other case. Conclusions: Sensitive immunohistochemical methods such as iAEP will broaden the potential value of immunohistochemistry. The current ALK positivity rate in IMT should be reassessed with a more highly sensitive method such as iAEP to accurately identify those patients who might benefit from ALK-inhibitor therapies. Novel ALK fusions are being identified in various tumors in addition to IMT, and thus a reassessment of other “ALK-negative” cancers may be required in the forthcoming era of ALK-inhibitor therapy. Clin Cancer Res; 17(10); 3341–8. ©2011 AACR.
Eukaryotic Translation Initiator Protein 1A Isoform, CCS-3, Enhances the Transcriptional Repression of p21CIP1 by Proto-oncogene FBI-1 (Pokemon/ZBTB7A)

FBI-1, a member of the POK (POZ and Krüppel) family of transcription factors, plays a role in differentiation, oncogenesis, and adipogenesis. eEF1A is a eukaryotic translation elongation factor involved in several cellular processes including embryogenesis, oncogenic transformation, cell proliferation, and cytoskeletal organization. CCS-3, a potential cervical cancer suppressor, is an isoform of eEF1A. We found that eEF1A forms a complex with FBI-1 by co-immunoprecipitation, SDS-PAGE, and MALDI-TOF Mass analysis of the immunoprecipitate. GST fusion protein pull-downs showed that FBI-1 directly interacts with eEF1A and CCS-3 via the zinc finger and POZ-domain of FBI-1. FBI-1 co-localizes with either eEF1A or CCS-3 at the nuclear periplasm. CCS-3 enhances transcriptional repression of the p21CIP1 gene (hereafter referred to as p21) by FBI-1. The POZ-domain of FBI-1 interacts with the co-repressors, SMRT and BCoR. We found that CCS-3 also interacts with the co-repressors independently. The molecular interaction between the co-repressors and CCS-3 at the POZ-domain of FBI-1 appears to enhance FBI-1 mediated transcriptional repression. Our data suggest that CCS-3 may be important in cell differentiation, tumorigenesis, and oncogenesis by interacting with the proto-oncogene FBI-1 and transcriptional co-repressors.
Analysis of Drivers of Disenrollment and Plan Switching Among Medicare Advantage Beneficiaries

Importance How often enrollees with complex care needs leave the Medicare Advantage (MA) program and what might drive their decisions remain unknown. Objective To characterize trends in switching to and from MA among high-need beneficiaries and to evaluate the drivers of disenrollment decisions. Design, Setting, and Participants This cross-sectional study of MA and traditional Medicare (TM) enrollees from January 1, 2014, through December 31, 2015, used a multinomial logit regression stratified by Medicare-Medicaid eligibility status. All 14 589 645 non–high-need MA enrollees and 1 302 470 high-need enrollees in the United States who survived until the end of 2014 were eligible for the analysis. Data were analyzed from November 1, 2017, through August 1, 2018. Exposures Enrollee dual eligibility and high-need status (based on complex chronic conditions, multiple morbidities, use of health care services, functional impairment, and frailty indicators), MA plan star rating, and cost sharing. Main Outcomes and Measures The proportion of enrollees who disenrolled into TM, remained in the same MA plan, or who switched plans within the MA program. Results A total of 13 901 816 enrollees were included in the analysis (56.2% women; mean [SD] age, 70.9 [9.9] years). Among the 1 302 470 high-need enrollees, an adjusted 4.6% (95% CI, 4.5%-4.6%) of Medicare-only and 14.8% (95% CI, 14.5%-15.0%) of Medicare-Medicaid members switched from MA to TM compared with 3.3% (95% CI, 3.3%-3.3%) and 4.6% (95% CI, 4.5%-4.7%), respectively, among non–high-need enrollees. Among enrollees in low-quality plans, 23.0% (95% CI, 22.3%-23.9%) of Medicare and 42.8% (95% CI, 40.5%-45.1%) of dual-eligible high-need enrollees left MA. Even in high-quality plans, high-need members disenrolled at higher rates than non–high-need members (4.9% [95% CI, 4.6%-5.2%] vs 1.8% [95% CI, 1.8%-1.9%] for Medicare-only enrollees and 11.3% vs 2.4% dual eligible enrollees). Enrollment in a 5.0-star rated plan was associated with a 30.1–percentage point reduction (95% CI, −31.7 to −28.4 percentage points) in the probability of disenrollment among high-need individuals. A $100 increase in monthly premiums was associated with a 33.9–percentage point increase (95% CI, −34.9 to −33.0 percentage points) in the likelihood of switching plans, and a small reduction in the likelihood of disenrolling (−2.7 percentage points; 95% CI, −3.2 to −2.2 percentage points). Among Medicare-Medicaid eligible participants, 14.1% (95% CI, 14.0%-14.2%) of high-need and 16.7% (95% CI, 16.6%-16.7%) of non–high-need enrollees switched from TM to MA. Conclusions and Relevance Results of this study suggest that substantially higher disenrollment from MA plans occurs among high-need and Medicare-Medicaid eligible enrollees. This study’s findings suggest that star ratings have the strongest association with disenrollment trends, whereas increases in monthly premiums are associated with greater likelihood of switching plans.
Metal binding to the dynamic cytoplasmic domain of the cation diffusion facilitator (CDF) protein MamM induces a ‘locked‐in’ configuration

Cation diffusion facilitator (CDF) proteins are a conserved family of transmembrane transporters that ensure cellular homeostasis of divalent transition metal cations. Metal cations bind to CDF protein's cytoplasmic C‐terminal domain (CTD), leading to closure from its apo open V‐shaped dimer to a tighter packed structure, followed by a conformational change of the transmembrane domain, thus enabling transport of the metal cation. By implementing a comprehensive range of biochemical and biophysical methods, we studied the molecular mechanism of metal binding to the magnetotactic bacterial CDF protein MamM CTD. Our results reveal that the CTD is rather dynamic in its apo form, and that two dependent metal‐binding sites, a single central binding site and two symmetrical, peripheral sites, are available for metal binding. However, only cation binding to the peripheral sites leads to conformational changes that lock the protein in a compact state. Thus, this work reveals how metal binding is regulating the sequential uptakes of metal cations by MamM, and extends our understanding of the complex regulation mechanism of CDF proteins.
Obesity Is Associated with Significant Morbidity after Multiligament Knee Surgery

Abstract The objective was to report the effect of obesity, utilizing a body mass index (BMI) threshold of 35 kg/m2, on outcomes and complications of multiple ligament knee injury (MLKI). It was hypothesized that obese patients would have longer intraoperative times and hospital length of stay, greater estimated blood loss, and higher rates of wound infection requiring irrigation and debridement (I&D) and revision ligament surgery. A retrospective review was performed on 143 individuals who underwent surgery for an MLKI between 2011 and 2018 at a single academic center. Patients were included if there was a plan for potential surgical repair/reconstruction of two or more ligaments. Patients with prior surgery to the affected knee or intra-articular fracture requiring reduction and fixation were excluded. Comparisons between obese and nonobese patients were made using two-sample t-test and either chi-square or Fisher's exact test for continuous and categorical variables, respectively. Significance was set at p < 0.05. Of 108 patients meeting inclusion criteria, 83 had BMI < 35 kg/m2 and 25 had BMI ≥ 35 kg/m2. Obese patients sustained higher rates of MLKI due to ultralow velocity mechanisms (28.0 vs. 1.2%; p = 0.0001) and higher rates of concomitant lateral meniscus injury (48.0 vs. 25.3%; p = 0.04). Among patients undergoing single-staged surgery, obese patients had significantly longer duration of surgery (219.8 vs. 178.6 minutes; p = 0.02) and more wound infections requiring I&D (20.0 vs. 4.8%; p = 0.03). In contrast, nonobese patients had higher rates of arthrofibrosis requiring manipulation under anesthesia and/or arthrolysis (25.3 vs. 0%; p = 0.003). Obese patients undergoing surgery of an MLKI have longer operative times, greater rates of wound infection requiring I&D, and lower rates of arthrofibrosis. Surgeons may consider these results when counseling patients on their postoperative course and risk for complications. Future research might focus on strategies to reduce complication rates in obese patients with MLKI. This is a Level III, retrospective comparative study.
Contrasting changes in space use induced by climate change in two Arctic marine mammal species

Global warming is inducing major environmental changes in the Arctic. These changes will differentially affect species owing to differences in climate sensitivity and behavioural plasticity. Arctic endemic marine mammals are expected to be impacted significantly by ongoing changes in their key habitats owing to their long life cycles and dependence on ice. Herein, unique biotelemetry datasets for ringed seals (RS; Pusa hispida) and white whales (WW; Delphinapterus leucas) from Svalbard, Norway, spanning two decades (1995–2016) are used to investigate how these species have responded to reduced sea-ice cover and increased Atlantic water influxes. Tidal glacier fronts were traditionally important foraging areas for both species. Following a period with dramatic environmental change, RS now spend significantly more time near tidal glaciers, where Arctic prey presumably still concentrate. Conversely, WW spend significantly less time near tidal glacier fronts and display spatial patterns that suggest that they are foraging on Atlantic fishes that are new to the region. Differences in levels of dietary specialization and overall behavioural plasticity are likely reasons for similar environmental pressures affecting these species differently. Climate change adjustments through behavioural plasticity will be vital for species survival in the Arctic, given the rapidity of change and limited dispersal options.
The effect of perceived organisational justice on job satisfaction and burnout levels of haemodialysis nurses.

BACKGROUND Organisational justice influences job satisfaction, the performance of individuals and the functioning of institutions. The lack of evidence-based studies investigating the relationship between hemodialysis nurses' perceptions of organisational justice, job satisfaction and burnout has created a research gap in this area. OBJECTIVE To investigate the effect of perceived organisational justice on professional satisfaction and burnout levels of haemodialysis nurses and to identify any relation ship with individual and organisational factors. MATERIAL AND METHODS The study was designed as a multi-centre descriptive study. The data were collected using the 'personal information form', the Organisational Justice Scale', the 'Maslach Burnout Inventory' and the 'Minnesota Satisfaction Questionnaire'. RESULTS The distributive justice scores decreased as the depersonalisation scores of the nurses increased. As the personal accomplishment scores of the nurses increased, the interactional justice scores also increased. It was observed that the job satisfaction scores increased as the sub-dimensional scores of the organisational justice scale increased and exhaustion decreased. CONCLUSION It was detected that there was a significant relationship between the organisational justice perception of nurses and their job satisfaction and level of burnout. Institutions are encouraged to adopt a fair policy towards nurses and promote personal development.
Influence of Chloroplast Defects on Formation of Jasmonic Acid and Characteristic Aroma Compounds in Tea (Camellia sinensis) Leaves Exposed to Postharvest Stresses

Characteristic aroma formation in tea (Camellia sinensis) leaves during the oolong tea manufacturing process might result from the defense responses of tea leaves against these various stresses, which involves upregulation of the upstream signal phytohormones related to leaf chloroplasts, such as jasmonic acid (JA). Whether chloroplast changes affect the formation of JA and characteristic aroma compounds in tea leaves exposed to stresses is unknown. In tea germplasms, albino-induced yellow tea leaves have defects in chloroplast ultrastructure and composition. Herein, we have compared the differential responses of phytohormone and characteristic aroma compound formation in normal green and albino-induced yellow tea leaves exposed to continuous wounding stress, which is the main stress in oolong tea manufacture. In contrast to single wounding stress (from picking, as a control), continuous wounding stress can upregulate the expression of CsMYC2, a key transcription factor of JA signaling, and activate the synthesis of JA and characteristic aroma compounds in both normal tea leaves (normal chloroplasts) and albino tea leaves (chloroplast defects). Chloroplast defects had no significant effect on the expression levels of CsMYC2 and JA synthesis-related genes in response to continuous wounding stress, but reduced the increase in JA content in response to continuous wounding stress. Furthermore, chloroplast defects reduced the increase in volatile fatty acid derivatives, including jasmine lactone and green leaf volatile contents, in response to continuous wounding stress. Overall, the formation of metabolites derived from fatty acids, such as JA, jasmine lactone, and green leaf volatiles in tea leaves, in response to continuous wounding stress, was affected by chloroplast defects. This information will improve understanding of the relationship of the stress responses of JA and aroma compound formation with chloroplast changes in tea.