Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of acute sprint interval exercise on follistatin-like 1 and apelin secretions

Abstract Context Insulin resistance is the main triggering factor for type 2 diabetes. Recently, it has been reported that high-intensity sprint interval training (SIT) was effective for improving glucose metabolism and insulin sensitivity despite lower training volume. However, the mechanisms underlying the SIT-induced increases in glucose metabolism and insulin sensitivity have not been well-understood. Follistatin-like 1 (FSTL1) and apelin, which are novel myokines, have a favourable effect on glucose metabolism. Objective We examined the impact of acute SIT on FSTL1 and apelin secretions. Methods Eight healthy men were enrolled in this study. The subjects performed acute SIT consisting of four 30-s all-out cycling efforts with 4-min rest periods. Blood samples were obtained before and after the acute SIT to measure FSTL1 and apelin concentrations. Results FSTL1 and apelin both significantly increased following acute SIT. Conclusion Acute SIT may be an effective stimulus for increasing of FSTL1 and apelin secretions.
Cell cycle and protein complex dynamics in discovering signaling pathways

Signaling pathways are responsible for the regulation of cell processes, such as monitoring the external environment, transmitting information across membranes, and making cell fate decisions. Given the increasing amount of biological data available and the recent discoveries showing that many diseases are related to the disruption of cellular signal transduction cascades, in silico discovery of signaling pathways in cell biology has become an active research topic in past years. However, reconstruction of signaling pathways remains a challenge mainly because of the need for systematic approaches for predicting causal relationships, like edge direction and activation/inhibition among interacting proteins in the signal flow. We propose an approach for predicting signaling pathways that integrates protein interactions, gene expression, phenotypes, and protein complex information. Our method first finds candidate pathways using a directed-edge-based algorithm and then defines a graph model to include causal activation relationships among proteins, in candidate pathways using cell cycle gene expression and phenotypes to infer consistent pathways in yeast. Then, we incorporate protein complex coverage information for deciding on the final predicted signaling pathways. We show that our approach improves the predictive results of the state of the art using different ranking metrics.
Amyloidogenicity of naturally occurring full‐length animal IAPP variants

The aggregation of the 37‐amino acid polypeptide human islet amyloid polypeptide (hIAPP), as either insoluble amyloid or as small oligomers, appears to play a direct role in the death of human pancreatic β‐islet cells in type 2 diabetes. hIAPP is considered to be one of the most amyloidogenic proteins known. The quick aggregation of hIAPP leads to the formation of toxic species, such as oligomers and fibers, that damage mammalian cells (both human and rat pancreatic cells). Whether this toxicity is necessary for the progression of type 2 diabetes or merely a side effect of the disease remains unclear. If hIAPP aggregation into toxic amyloid is on‐path for developing type 2 diabetes in humans, islet amyloid polypeptide (IAPP) aggregation would likely need to play a similar role within other organisms known to develop the disease. In this work, we compared the aggregation potential and cellular toxicity of full‐length IAPP from several diabetic and nondiabetic organisms whose aggregation propensities had not yet been determined for full‐length IAPP.
Factors associated with HPV and other self-reported STI coinfections among sexually active Brazilian young adults: cross-sectional nationwide study

Objectives To analyse factors associated with genital human papillomavirus (HPV) and other self-reported sexually transmitted infection (STI) coinfections among women and men aged 16–25 years from Brazil. Design A cross-sectional, nationwide, multicentre study. Setting 119 primary healthcare centres between September 2016 and November 2017. Participants 6388 sexually active young adults were enrolled by trained health professionals. Primary outcome measure Genital HPV and other self-reported STI coinfections. Results Of 3512 participants with valid data for genital HPV and (STI)-positive status, 276 (9.60%, 95% CI 7.82% to 11.36%) had HPV/STI coinfection. Among men, HPV/STI coinfection was more prevalent than HPV infection alone. Among HPV-positive participants, the percentage of subjects who reported having another STI was highest for gonorrhoea at 4.24% (95% CI 2.67% to 5.81%), followed by syphilis, herpes and HIV. Smoking, drug use and ever having a same-sex sexual experience were risk factors that were uniquely associated with HPV/STI coinfection compared with HPV infection alone. Conclusions The results identified a low prevalence of self-reported STIs, but in participants with at least one STI, the prevalence of HPV was high. These results reinforce the importance of implementing strategies to prevent risky behaviours among Brazilian young adults.
New graduate nurses' clinical safety knowledge by the numbers.

AIM To explore new graduate registered nurses' knowledge and attitudes concerning medical error and patient safety, during their first six months of professional practice BACKGROUND: New graduate registered nurses demonstrate basic skills and levels of performance due to limited exposure and experience in actual situations. There is a concern held for their clinical reasoning skills required to recognise patient deterioration, posing a threat to patient safety. METHODS An online questionnaire was used to survey New graduate registered nurses at three time points during graduate nurse programs between August 2016 and February 2018. RESULTS A decrease in self-reported knowledge and attitudes regarding medical errors was noted over the three time points. These results indicate initial confidence in theoretical knowledge and attitudes upon completion of undergraduate education, and prior to commencing professional practice. CONCLUSION Results suggest that a theory practice gap persists with respect to medical error for transitioning new nurses. IMPACT FOR NURSING MANAGEMENT New nurses lack confidence around compromised patient safety situations and a knowledge gap around actions related to medical error. Nurse managers and educators should be made aware of this gap to implement strategies to decrease risk during novice nurse transition. This article is protected by copyright. All rights reserved.
Trends in Blood Pressure and High-Sensitivity Cardiac Troponin-T with Cardiovascular Disease: The Cardiovascular Health Study.

BACKGROUND High-sensitivity cardiac troponin T (hs-cTnT) is individually associated with incident hypertension (HTN) and cardiovascular disease (CVD) events. We hypothesize that the increases in hs-cTnT with increases in blood pressure will be related to higher incidence of CVD. METHODS The Cardiovascular Health Study is a longitudinal cohort of older adults. Those with hs-cTnT data and CVD risk factors at baseline and follow-up (2-3 years later) were stratified based on systolic blood pressure (SBP) (optimal: <120 mmHg, intermediate: 120-139 mmHg, elevated: ≥140 mmHg) and hs-cTnT (undetectable: <5 ng/L, detectable: 5-13 ng/L, elevated: ≥14 ng/L) categories. SBP and hs-cTnT were classified as increased or decreased if they changed categories between exams, and stable if they did not. Cox regression evaluated incident CVD events over an average 9 year follow-up. RESULTS Among 2219 adults, 510 (23.0 %) had decreased hs-cTnT, 1,279 (57.6 %) had stable hs-cTnT, and 430 (19.4 %) had increased hs-cTnT. Those with increased hs-cTnT had a higher CVD risk with stable SBP (HR: 1.28 [1.04-1.57], p=0.02) or decreased SBP (HR: 1.57 [1.08-2.28], p=0.02) compared to those within the same SBP group but a stable hs-cTnT. In those with lower SBP at follow-up, there was an inverse relation between DBP and risk of CVD events in those with increased hs-cTnT (HR: 0.44 per 10 mmHg increase, p<0.01). CONCLUSION An increase in hs-cTnT over time is associated with a higher risk of CVD even when the blood pressure is stable or decreases over time.
Suboptimal outcomes after internal fixation for displaced intracapsular femoral neck fractures in 50- to 60-year-old patients

Purpose: The aim of this study was to evaluate outcomes of internal fixation for displaced femoral neck fracture (FNF) between 50 and 60 years old. The patient and surgical factors for the failure were identified. Methods: We retrospectively reviewed the records of 102 displaced FNF patients between 50 and 60 years old (mean age 54.9 years) who had undergone internal fixation between 2005 and 2016. The minimum follow-up was 12 months. Primary end points included loss of reduction, non-union, and osteonecrosis of the femoral head (ONFH). Preoperative Pauwel’s angle, fixation timing and methods, reduction quality, removal of implant and medical comorbidities were analysed. Results: The overall failure rate was 44.1%. In multivariate logistic regression analysis, poor reduction quality (adjusted odds ratio [aOR] 4.38; 95% confidence interval [CI], 1.54–12.46) and internal fixation delayed more than 6 hours (aOR 3.24; 95% CI, 1.08–9.69) were risk factors for all causes of failure. In a stratified analysis, poor reduction quality (aOR 3.81; 95% CI, 1.11–13.04) and a history of alcohol dependency (aOR 4.91; 95% CI, 1.09–22.13) were risk factors for loss of reduction. Internal fixation delayed >6 hours (aOR 3.67; 95% CI, 1.05–12.77) and removal of implant (aOR 3.32; 95% CI, 1.02–10.77) were risk factors for ONFH. Conclusions: The outcome of internal fixation of displaced FNF in patients between 50 and 60 years old is suboptimal. The patient selection is important. Non-alcohol dependency lowered early failure. Implant retention reduced ONFH. Surgery within 6 hours and good quality of reduction yield better results.
Catastrophic femoral head trunnion dissociation: a case series with surface wear analysis

Introduction: Modular designs enhance accuracy of limb length and offset during total hip arthroplasty. However, such interfaces can be the site of corrosion and implant failure. The purpose of this study was to review 5 cases of catastrophic femoral head trunnion dissociation to better understand clinical and implant related risk factors for this complication. Methods: We describe 5 cases of femoral head dissociation following significant trunnion wear. Patient and implant related factors are reviewed. Surface wear patterns were assessed using electron microscopy and wear patterns were described qualitatively. Results: Commonalties among 5 presented cases include male, age over 65 and increased BMI. All femoral heads were cobalt chromium with a head size of at least 36 mm or greater. 4 out of 5 had high offset. All stems were the same design. Surface wear analysis showed material removed initially on the inferomedial aspect of the trunnion where the femoral head contacted the stem. Conclusions: Femoral head dissociation secondary to failure of the trunnion is a rare complication. We show associations with older age, increased BMI and male patients with increased femoral head size and offset. Material is removed initially inferomedially and progresses to fracturing the superior aspect of the trunnion.
Expression of toll‐like receptors and their regulatory roles in murine cardiac telocytes

Telocytes, newly discovered in the last decade, are interstitial cells found in numerous organs, with multiple proposed potential biological functions. Toll‐like receptors (TLRs) play an important role in innate and adaptive immunity by recognizing pathogen‐associated molecular patterns (PAMPs). However, it is still unknown whether telocytes express these innate receptors. We sought to determine the expression and role of TLRs in telocytes. In our study, we primarily detected TLR1‐9 expression in telocytes. The proliferation, apoptosis and immunoregulatory activity of telocytes activated with or without TLR ligands were determined. Our results showed that purified telocytes expressed TLR2, TLR3 and TLR5. In particular, telocytes expressed high levels of TLR2 as observed using flow cytometry. When we stimulated telocytes with TLR2 or TLR3 agonists (Pam3CSK4, PolyI:C), iNOS expression was greatly increased after Pam3CSK4 treatment. Additionally, telocyte proliferation was reduced and cell apoptosis was increased after TLR agonist stimulation. A co‐culture experiment showed that supernatant from telocytes pretreated with Pam3CSK4 inhibited T cell activation much more than that from untreated telocytes and this effect was mediated by iNOS. Overall, our results demonstrated TLR expression on telocytes for the first time and provided evidence of an immunoregulatory role of telocytes, indicating their clinical potential.
Effect on osseointegration of two implant macro-designs:A histomorphometric analysis of bicortically installed implants in different topographic sites of rabbit’s tibiae

Background To evaluate the effect of two different implant macro-designs on the sequential osseointegration at bicortically installed implants in the rabbit tibia. A further aim is to compare the osseointegration at different topographic zones. Material and Methods 27 New Zealand rabbits were implemented. Two implants, one for each macro-design (Ticare Inhex® or Ticare Quattro®, Mozo-Grau, Valladolid, Spain), were randomly implanted in the diaphysis or metaphysis of each tibia. The flaps were sutured to allow a submerged healing. The animals were sacrificed after 2, 4 or 8 weeks. Ground sections were prepared and analyzed. Results No statistically significant differences were found between the two groups for newly formed bone in contact with the implant surface, being about 16%, 19% and 33% in both groups, after 2, 4, and 8 weeks of healing. Bone apposition was slightly higher in the diaphysis, reaching values of 36.4% in the diaphysis, and 29.3% in the metaphysis at 8 weeks of healing. It was observed that the implant position showed a statistical significance regarding BIC values at 4 and 8 weeks (p<0.05). Multivariate analysis fails to detect statistical significant differences for the interaction between implant designs and topographic site. Ticare Quattro® design had a slight better BIC values at diaphysis sites across healing stages, but without reaching a statistical significance. Conclusions The both implant macro-designs provided similar degrees of osseointegration. Bone morphometry and density may affect bone apposition onto the implant surface. The apposition rates were slightly better in diaphysis compared to metaphysis. Key words:Animal study, bicortical stabilization, implant macro-design, osseointegration, dental implant, submerged healing.
Effectiveness of 12 week ledipasvir/sofosbuvir and predictors of treatment failure in patients with hepatitis C

SUMMARY Introduction The efficacy of ledipasvir/sofosbuvir (LDV/SOF) have been demonstrated in randomized controlled trials, however, there is an unmet need for real-world effectiveness data. It is important to gather data regarding potential predictors of treatment failure with (LDV/SOF). Predictors of sustained virologic response (SVR) to all-oral HCV regimens can inform nuanced treatment decisions. The objectives of this study were to evaluate the effectiveness of LDV/SOF, SVR12 as main endpoint and SVR24 as second endpoint, and identify predictors of treatment failure. Material and methods Retrospective and observational study carried out from April 2015 to January 2016. Inclusion criteria: patients with HCV infection treated with LDV/SOF for 12 weeks during study period. The patients that were treated during 24 weeks were excluded as well as those treated with peg-interferon. Binary logistic regression was used to predict what variable was associated with treatment failure. Results A total of 122 patients were analyzed achieving SVR12 91.80% (112/122) of them. The patients with HCV genotype (GT) 1a or GT1b or GT4 achieved SVR12. Only one pre-treated non-cirrhotic HCV GT1 patients relapsed to treatment. The lowest SVR12 were obtained for GT3, 43.75%, (7/16). Everybody that got SVR12 achieved SVR24. None of the variables analyzed significantly influenced the SVR12, except GT (p=0.001). Almost all the relapses occurred in GT3. Conclusion LDV/SOF combination has been very effective to treat GT1 and GT4 infected patients, however, has constituted a suboptimal therapeutic option for those patients infected with GT3, regardless of the rest of the variables analyzed.
Multicentre randomized clinical trial of colonic J pouch or straight stapled colorectal reconstruction after low anterior resection for rectal cancer

Colonic J pouch reconstruction has been found to be associated with a lower incidence of anastomotic leakage than straight anastomosis. However, studies on this topic are underpowered and retrospective. This randomized trial evaluated whether the incidence of anastomotic leakage was reduced after colonic J pouch reconstruction compared with straight colorectal anastomosis following anterior resection for rectal cancer.
Prokaryotic SPHINX replication sequences are conserved in mammalian brain and participate in neurodegeneration

A new class of viral mammalian Slow Progressive Hidden INfections of variable (X) latency (“SPHINX”) DNAs, represented by the 1.8 and 2.4 kb nuclease‐protected circular elements, were discovered in highly infectious cytoplasmic particles isolated from Creutzfeldt‐Jakob Disease (CJD) and scrapie samples. These DNAs contained replication initiation sequences (REPs) with approximately 70% homology to those of environmental Acinetobacter phage. Antibodies against REP peptides from the 1.8 kb DNA highlighted a 41 kDa protein (spx) on Western blots, and in situ studies previously revealed its peripheral tissue expression, for example, in pancreatic islet cells, keratinocytes, kidney tubules, and oocytes but not pancreatic exocrine cells, alveoli, and striated muscle. To determine if spx concentrated in specific neurons and synapses, and also maintained a conserved pattern of architectural organization in mammalian brains, we evaluated mouse, rat, hamster, guinea pig (GP), and human samples. Most outstanding was the cross‐species concentration of spx in huge excitatory synapses of mossy fibers and small internal granule neuron synapses, the only excitatory neuron within the cerebellum. Spx also localized to excitatory glutamate type synapses in the hippocampus, and both cerebellar and hippocampal synaptic spx was demonstrable ultrastructurally. Studies of two well‐characterized models of sporadic CJD (sCJD) revealed novel spx pathology. Vacuolar loss of cerebellar synaptic complexes, thinning of the internal granule cell layer, and fibrillar spx accumulations within Purkinje neurons were prominent in sCJD GP brains. In rats, comparable spx fibrillar changes appeared in hippocampal pyramidal neurons, and they preceded prion protein misfolding. Hence, spx is an integral player in progressive neurodegeneration. The evolutionary origin, spread, and neuropathology of SPHINX 1.8 REP sequences opens another unanticipated chapter for mammalian symbiotic interactions with environmental microbes.
Bartonella gene transfer agent: Evolution, function, and proposed role in host adaptation

The processes underlying host adaptation by bacterial pathogens remain a fundamental question with relevant clinical, ecological, and evolutionary implications. Zoonotic pathogens of the genus Bartonella constitute an exceptional model to study these aspects. Bartonellae have undergone a spectacular diversification into multiple species resulting from adaptive radiation. Specific adaptations of a complex facultative intracellular lifestyle have enabled the colonisation of distinct mammalian reservoir hosts. This remarkable host adaptability has a multifactorial basis and is thought to be driven by horizontal gene transfer (HGT) and recombination among a limited genus‐specific pan genome. Recent functional and evolutionary studies revealed that the conserved Bartonella gene transfer agent (BaGTA) mediates highly efficient HGT and could thus drive this evolution. Here, we review the recent progress made towards understanding BaGTA evolution, function, and its role in the evolution and pathogenesis of Bartonella spp. We notably discuss how BaGTA could have contributed to genome diversification through recombination of beneficial traits that underlie host adaptability. We further address how BaGTA may counter the accumulation of deleterious mutations in clonal populations (Muller's ratchet), which are expected to occur through the recurrent transmission bottlenecks during the complex infection cycle of these pathogens in their mammalian reservoir hosts and arthropod vectors.
Clinical application of RNA sequencing in sarcoma diagnosis

Abstract Accurate diagnoses of sarcoma are sometimes challenging on conventional histomorphology and immunophenotype. Many specific genetic aberrations including chromosomal translocations have been identified in various sarcomas, which can be detected by fluorescence in situ hybridization and polymerase chain reaction analysis. Next-generation sequencing-based RNA sequencing can screen multiple sarcoma-specific chromosome translocations/fusion genes in 1 test, which is especially useful for sarcoma without obvious differentiation. In this report, we utilized RNA sequencing on formalin-fixed paraffin-embedded (FFPE) specimens to investigate the possibility of diagnosing sarcomas by identifying disease-specific fusion genes. Targeted RNA sequencing was performed on 6 sarcoma cases. The expected genetic alterations (clear cell sarcoma/EWSR1-ATF1, Ewing sarcoma/EWSR1-FLI1, myxoid liposarcoma/DDIT3-FUS) in four cases were detected and confirmed by secondary tests. Interestingly, three SS18 fusion genes (SS18-SSX2B, SS18-SSX2, and SS18-SSX4) were identified in a synovial sarcoma case. A rare fusion gene (EWSR1-PATZ1) was identified in a morphologically challenging case; which enabled us to establish the diagnosis of low grade glioneural tumor. In conclusion, RNA sequencing on FFPE specimen is a reliable method in establishing the diagnosis of sarcoma in daily practice.
Recent developments in the management of acute and chronic hyponatremia.

PURPOSE OF REVIEW The aim of the study is to review recent studies on the management of acute and chronic hyponatremia. RECENT FINDINGS In acute symptomatic hyponatremia, bolus infusion of hypertonic saline improves hyponatremia and neurological status more quickly than continuous infusion. In chronic hyponatremia, newly identified predictors of nonresponse to fluid restriction include a high urine osmolality (>500 mOsm/kg) and high urine sodium (>133 mmol/l). Vasopressin-receptor antagonists effectively raise the serum sodium concentration in patients with euvolemic or hypervolemic hyponatremia but have a risk of overcorrection, even at low doses. Several observational studies now support the use of urea for a more gradual correction of hyponatremia without a risk of overcorrection. Recently identified risk factors for overcorrection include lower serum sodium at presentation, polydipsia, hypovolemia, and early urine output during treatment. Specific treatments with potential efficacy are the use of intravenous albumin for hyponatremia because of liver cirrhosis, and fludrocortisone for hyponatremia in tuberculous meningitis. SUMMARY The recent data will help to further optimize and personalize the management of patients with acute and chronic hyponatremia. However, most data are still observational and retrospective. Therefore, the field is in need of prospective studies comparing interventions for chronic hyponatremia and focusing on patient-relevant outcomes.