Miracle-dz/UniFAR-FTUs huggingface dataset:
Weakly electric fish distinguish between envelope stimuli arising from different behavioral contexts

ABSTRACT Understanding how sensory information is processed by the brain in order to give rise to behavior remains poorly understood in general. Here, we investigated the behavioral responses of the weakly electric fish Apteronotus albifrons to stimuli arising from different contexts, by measuring changes in the electric organ discharge (EOD) frequency. Specifically, we focused on envelopes, which can arise either because of movement (i.e. motion envelopes) or because of interactions between the electric fields of three of more fish (i.e. social envelopes). Overall, we found that the animal's EOD frequency effectively tracked the detailed time course of both motion and social envelopes. In general, behavioral sensitivity (i.e. gain) decreased while phase lag increased with increasing envelope and carrier frequency. However, changes in gain and phase lag as a function of changes in carrier frequency were more prominent for motion than for social envelopes in general. Importantly, we compared behavioral responses to motion and social envelopes with similar characteristics. Although behavioral sensitivities were similar, we observed an increased response lag for social envelopes, primarily for low carrier frequencies. Thus, our results imply that the organism can, based on behavioral responses, distinguish envelope stimuli resulting from movement from those that instead result from social interactions. We discuss the implications of our results for neural coding of envelopes and propose that behavioral responses to motion and social envelopes are mediated by different neural circuits in the brain. Summary: Weakly electric fish can experience stimuli arising from different behavioral contexts; we provide the first evidence that they can distinguish envelopes arising from movement from those that occur during social interactions.
Risk factors for increased sagittal pelvic motion causing unfavourable orientation of the acetabular component in patients undergoing total hip arthroplasty

Aims It is important to consider sagittal pelvic rotation when introducing the acetabular component at total hip arthroplasty (THA). The purpose of this study was to identify patients who are at risk of unfavourable pelvic mobility, which could result in poor outcomes after THA. Patients and Methods A consecutive series of 4042 patients undergoing THA had lateral functional radiographs and a low‐dose CT scan to measure supine pelvic tilt, pelvic incidence, standing pelvic tilt, flexedseated pelvic tilt, standing lumbar lordotic angle, flexed‐seated lumbar lordotic angle, and lumbar flexion. Changes in pelvic tilt from supine‐to‐standing positions and supine‐to‐flexedseated positions were determined. A change in pelvic tilt of 13° between positions was deemed unfavourable as it alters functional anteversion by 10° and effectively places the acetabular component outside the safe zone of orientation. Results For both men and women, the degree of lumbar flexion was a significant predictor of risk in hip flexion (p < 0.0001) with increased odds of unfavourable pelvic mobility in those with lumbar flexion of < 20° (men, odds ratio (OR) 6.74, 95% confidence interval (CI) 3.83 to 11.89; women, OR 2.97, 95% CI 1.87 to 4.71). In women, age and standing pelvic tilt were significant predictors of risk in hip extension (p = 0.0082 and p < 0.0001, respectively). The risk of unfavourable pelvic mobility was higher in those aged > 75 years (OR 2.28, 95% CI 1.56 to 3.32) and those with standing pelvic tilt of <‐10° for extension risk (OR 7.10, 95% CI 4.10 to 10.29). In men, only standing pelvic tilt was significant (p < 0.0001) for hip extension with an increased risk of unfavourable pelvic mobility (OR 8.68, 95% CI 5.19 to 14.51). Conclusion Patients found to have unfavourable pelvic mobility had limited lumbar flexion and more posterior standing pelvic tilt in both men and women, as well as increasing age in women. We recommend that patients undergo preoperative functional radiographic screening to determine specific parameters that can affect the functional orientation of the acetabular component.
Microcirculatory Impairment Is Associated With Multiple Organ Dysfunction Following Traumatic Hemorrhagic Shock: The MICROSHOCK Study

Objectives: To assess the relationship between microcirculatory perfusion and multiple organ dysfunction syndrome in patients following traumatic hemorrhagic shock. Design: Multicenter prospective longitudinal observational study. Setting: Three U.K. major trauma centers. Patients: Fifty-eight intubated and ventilated patients with traumatic hemorrhagic shock. Interventions: Sublingual incident dark field microscopy was performed within 12 hours of ICU admission (D0) and repeated 24 and 48 hours later. Cardiac output was assessed using oesophageal Doppler. Multiple organ dysfunction syndrome was defined as Serial Organ Failure Assessment score greater than or equal to 6 at day 7 post injury. Measurements and Main Results: Data from 58 patients were analyzed. Patients had a mean age of 43 ± 19 years, Injury Severity Score of 29 ± 14, and initial lactate of 7.3 ± 6.1 mmol/L and received 6 U (interquartile range, 4–11 U) of packed RBCs during initial resuscitation. Compared with patients without multiple organ dysfunction syndrome at day 7, patients with multiple organ dysfunction syndrome had lower D0 perfused vessel density (11.2 ± 1.8 and 8.6 ± 1.8 mm/mm2; p < 0.01) and microcirculatory flow index (2.8 [2.6–2.9] and 2.6 [2.2–2.8]; p < 0.01) but similar cardiac index (2.5 [± 0.6] and 2.1 [± 0.7] L/min//m2; p = 0.11). Perfused vessel density demonstrated the best discrimination for predicting subsequent multiple organ dysfunction syndrome (area under curve 0.87 [0.76–0.99]) compared with highest recorded lactate (area under curve 0.69 [0.53–0.84]), cardiac index (area under curve 0.66 [0.49–0.83]) and lowest recorded systolic blood pressure (area under curve 0.54 [0.39–0.70]). Conclusions: Microcirculatory hypoperfusion immediately following traumatic hemorrhagic shock and resuscitation is associated with increased multiple organ dysfunction syndrome. Microcirculatory variables are better prognostic indicators for the development of multiple organ dysfunction syndrome than more traditional indices. Microcirculatory perfusion is a potential endpoint of resuscitation following traumatic hemorrhagic shock.
Immunogenetic and structural analysis of a class of HCV broadly neutralizing antibodies and their precursors

Significance Hepatitis C virus (HCV) infects 1–2% of the world’s population, but a vaccine to limit spreading of this silent killer is unavailable. A leading strategy in vaccine design to counter the genetic variability of HCV is to elicit broadly neutralizing antibodies (bnAbs) targeting conserved viral epitopes. The HCV antigenic site 412–423 (AS412) is highly conserved and a prime vaccine target. In this study, the genetic and structural properties of murine bnAbs targeting AS412 were determined. Using specific molecular interactions encoded in the antibody germline genes and those acquired by somatic hypermutation, two distinct antibody lineages recognize AS412 in near identical conformations. The results provide key insights in the development of HCV bnAbs for rational vaccine design. Elicitation of broadly neutralizing antibodies (bnAbs) is a leading strategy in rational vaccine design against antigenically diverse pathogens. Here, we studied a panel of monoclonal antibodies (mAbs) from mice immunized with the hepatitis C virus (HCV) envelope glycoproteins E1E2. Six of the mAbs recognize the conserved E2 antigenic site 412–423 (AS412) and cross-neutralize diverse HCV genotypes. Immunogenetic and structural analysis revealed that the antibodies originated from two different germline (GL) precursors and bind AS412 in a β-hairpin conformation. Intriguingly, the anti-HCV activity of one antibody lineage is associated with maturation of the light chain (LC), whereas the other lineage is dependent on heavy-chain (HC) maturation. Crystal structures of GL precursors of the LC-dependent lineage in complex with AS412 offer critical insights into the maturation process of bnAbs to HCV, providing a scientific foundation for utilizing the mouse model to study AS412-targeting vaccine candidates.
Amyloid seeding of transthyretin by ex vivo cardiac fibrils and its inhibition

Significance Transthyretin (TTR) cardiac amyloidosis is characterized by the deposition of TTR amyloid fibrils in the heart. No therapy is currently available for wild-type cardiac amyloidosis. Hereditary cases are treated by liver transplantation, a crude form of gene therapy which replaces amyloidogenic mutant TTR by the more stable wild-type form, with the goal of halting further deposition and disease progression. However, wild-type TTR continues to deposit in the heart of many patients after the procedure. Until now, seeding of TTR fibril formation has not been demonstrated in vitro. We show that patient-extracted cardiac fibrils can seed both wild-type and mutant TTR fibril formation in vitro. This process can be inhibited by structure-based peptide inhibitors, thereby providing an alternative approach to therapy. Each of the 30 human amyloid diseases is associated with the aggregation of a particular precursor protein into amyloid fibrils. In transthyretin amyloidosis (ATTR), mutant or wild-type forms of the serum carrier protein transthyretin (TTR), synthesized and secreted by the liver, convert to amyloid fibrils deposited in the heart and other organs. The current standard of care for hereditary ATTR is liver transplantation, which replaces the mutant TTR gene with the wild-type gene. However, the procedure is often followed by cardiac deposition of wild-type TTR secreted by the new liver. Here we find that amyloid fibrils extracted from autopsied and explanted hearts of ATTR patients robustly seed wild-type TTR into amyloid fibrils in vitro. Cardiac-derived ATTR seeds can accelerate fibril formation of wild-type and monomeric TTR at acidic pH and under physiological conditions, respectively. We show that this seeding is inhibited by peptides designed to complement structures of TTR fibrils. These inhibitors cap fibril growth, suggesting an approach for halting progression of ATTR.
Frequency of Cardiac Rhythm Abnormalities in a Half Million Adults

Background: The frequency of cardiac rhythm abnormalities and their risk factors in community-dwelling adults are not well characterized. Methods: We determined the frequency of rhythm abnormalities in the UK Biobank, a national prospective cohort. We tested associations between risk factors and incident rhythm abnormalities using multivariable proportional hazards regression. Results: Of 502 627 adults (median age, 58 years [interquartile range, 13]; 54.4% women), 2.35% had a baseline rhythm abnormality. The prevalence increased with age with 4.84% of individuals aged 65 to 73 years affected. During 3 368 332 person-years of follow-up, 15 906 new rhythm abnormalities were detected (4.72 per 1000 person-years; 95% confidence interval [CI]: 4.65–4.80). Atrial fibrillation (3.11 per 1000 person-years; 95% CI: 3.05–3.17), bradyarrhythmias (0.89 per 1000 person-years; 95% CI: 0.86–0.92), and conduction system diseases (1.06 per 1000 person-years; 95% CI: 1.02–1.09) were more common than supraventricular (0.51 per 1000 person-years; 95% CI: 0.48–0.53) and ventricular arrhythmias (0.57 per 1000 person-years; 95% CI: 0.55–0.60). Older age (hazard ratio [HR]: 2.35 per 10-year increase; 95% CI: 2.29–2.41; P<0.01), male sex (HR: 1.83; 95% CI: 1.76–1.89; P<0.01), hypertension (HR: 1.49; 95% CI: 1.44–1.54; P<0.01), chronic kidney disease (HR: 1.95; 95% CI: 1.67–2.27; P<0.01), and heart failure (HR: 1.99; 95% CI: 1.76–2.26; P<0.01) were associated with new rhythm abnormalities. Conclusions: The frequency of rhythm abnormalities in middle-aged to older community-dwelling adults is substantial. Atrial fibrillation, bradyarrhythmias, and conduction system diseases account for most rhythm conditions.
Scrambler therapy in the management of somatosensory signs and symptoms related to neuropathic pain: an exploratory and prospective analysis

Objectives: Neuropathic pain is a severe and disabling health problem, often difficult to treat and characterized by specific somatosensory signs and symptoms. The goal of this study is to detect the effect of Scrambler therapy (ST) on the reset of Neuropathic Pain Diagnostic Questionnaire (DN4), in a cohort of patients affected by intense drug-resistant neuropathic pain. Methods: Patients with chronic neuropathic pain were consecutively enrolled to receive 45-minute daily ST for an average of 10 consecutive days. Evaluation of pain intensity by Numerical Rating Scale (NRS) score and DN4 questionnaire was performed at the beginning and at the end of the treatment. Primary endpoint was to achieve a significant negativization of DN4 (DN4 <4) in the study population after 10 ST sessions. Secondary endpoints were to detect a correlation between DN4 negativization and pain intensity reduction ≥50% (patient responders), finally to analyse the impact of ST on each item of DN4 survey. Results: We prospectively treated 45 patients. Mean baseline DN4 score was 5.67 [±1.43] and fell by 50.3%, with a mean DN4 score of 2.82 [±2.18] at the end of treatment (OR 2.84; 95%CI: 2.07-3.62; p<0.0001). In 28 out of 45 (62.2%) patients we reported a negativisation of DN4 (p<0.0001). Correlation between the percentage of patient responders and patients with negativization of DN4 was statistically significant (p<0.0062). Analysing each DN4 item pre- and post-ST, we reported a significant negativization in 6 out of 10 DN4 items. Discussion: Our prospective exploratory analysis met the primary endpoint and ST seems to resolve relevant somatosensory signs and symptoms related to neuropathic pain. Based on these encouraging results, the next step will be to evaluate these neuropathic pain features with dedicated tools. (www.actabiomedica.it)
HİZMET İÇİ EĞİTİMİN ÖĞRETMENLERİN ÖĞRETİM YÖNTEM VE TEKNİKLERİNE İLİŞKİN BİLGİLERİNE ETKİSİ: ÖPYEP ÖRNEĞİ

Arastirmanin amaci; hizmet ici egitime katilan Anadolu Ogretmen Lisesi ogretmenlerinin, yontem-tekniklerle ilgili bilgilerinde HIE oncesi ve sonrasinda, farklilik olup olmadiginin ortaya konmasidir. Arastirmaya farkli illerden 120 ogretmen katilmis, ancak degerlendirmeye 104 ogretmen alinmistir. Calismaya katilan ogretmenler 6 farkli alandandir. Arastirtma tek gruplu on test son test calismasidir. Calismada elde edilen veriler nitel arastirma veri analiz yontemlerine gore degerlendirilmistir. Calismada ogretmenlere 11 acik uclu soru sorularak, bilgilerinde kidemlerine ve alanlarina gore degisiklik olup olmadigi arastirilmistir. Verilerin degerlendirilmesi sonucunda; egitimden once ogretmenlerin siniflarinda en cok soru-cevap, duz anlatim ve deney yontemlerini kullandiklari belirlenmis; kidemlerine ve alanlarina bagli olarak her hangi bir farklilik bulunmamistir. Ancak, egitimden sonra ogretmenlerin ogretim yontem-tekniklerine ve yapilandirmaci yaklasima iliskin bilgilerinde onemli artislar oldugu saptanmistir
Is Male Unpredictability a Paternity Assurance Strategy

In socially monogamous birds, levels of extra-pair paternity vary widely across species. A possible explanation for this variation is that the costs to both sexes of pursuing extra-pair copulations (EPCs) varies widely, which may substantially depend upon the effectiveness of the paternity assurance tactics employed by pair males. Given the prevalence of extra-pair paternity, an enigma exists in non-mate-guarding species in which males have no apparent means of assuring their paternity and yet rarely or never lose paternity. We propose that males in some species may pursue a subtle but effective paternity assurance tactic consisting of unpredictable behaviour. By departing and returning to and from their mates at unpredictable intervals males may be able to deter other males and their mates from attempting EPCs. Consistent with this idea, we found in the monogamous kittiwake Rissa tridactyla that the absences of males became decreasingly predictable in duration as their mates' fertile periods approached. Moreover, the durations of 80% of male absences were shorter than the minimum duration of copulations, creating a high probability of pair males returning in time to prevent EPCs. Factors other than male unredictability may explain the lack of extra-pair paternity in kittiwakes. Nevertheless, the unpredictable male hypothesis is testable in the many species with variable levels of EPP. Furthermore, we suggest that unpredictability may comprise a general strategy by which animals of both sexes protect various reproductive assets such as food, mates and territories.
Contribution of Epstein–Barr Virus Latent Proteins to the Pathogenesis of Classical Hodgkin Lymphoma

Pathogenic viruses have evolved to manipulate the host cell utilising a variety of strategies including expression of viral proteins to hijack or mimic the activity of cellular functions. DNA tumour viruses often establish latent infection in which no new virions are produced, characterized by the expression of a restricted repertoire of so-called latent viral genes. These latent genes serve to remodel cellular functions to ensure survival of the virus within host cells, often for the lifetime of the infected individual. However, under certain circumstances, virus infection may contribute to transformation of the host cell; this event is not a usual outcome of infection. Here, we review how the Epstein–Barr virus (EBV), the prototypic oncogenic human virus, modulates host cell functions, with a focus on the role of the EBV latent genes in classical Hodgkin lymphoma.
Ten‐year survivorship of primary total hip arthroplasty in patients 30 years of age or younger

Aims For this retrospective cohort study, patients aged ≤ 30 years (very young) who underwent total hip arthroplasty (THA) were compared with patients aged ≥ 60 years (elderly) to evaluate the rate of revision arthroplasty, implant survival, the indications for revision, the complications, and the patient‐reported outcomes. Patients and Methods We retrospectively reviewed all patients who underwent primary THA between January 2000 and May 2015 from our institutional database. A total of 145 very young and 1359 elderly patients were reviewed. The mean follow‐up was 5.3 years (1 to 18). Logistic generalized estimating equations were used to compare characteristics and the revision rate. Survival was evaluated using Kaplan‐Meier curves and hazard rates were created using Cox regression. Results The overall revision rate was 11% (16/145) in the very young and 3.83% (52/1359) in the elderly groups (odds ratio (OR) 2.58, 95% confidence interval (CI) 1.43 to 4.63). After adjusting for the American Society of Anesthesiologists (ASA) score, gender, and a history of previous surgery in a time‐to‐event model, the risk of revision remained greater in the very young (adjusted hazard ratio (HR) 2.48, 95% CI 1.34 to 4.58). Survival at ten years was 82% (95% CI, 71 to 89) in the very young and 96% (95% CI, 94 to 97) in the elderly group (p < 0.001). The very young had a higher rate of revision for complications related to metalonmetal (MoM) bearing surfaces (p < 0.001). At last follow‐up, the very young group had higher levels of physical function (p = 0.002), lower levels of mental health (p = 0.001), and similar levels of pain (p = 0.670) compared with their elderly counterparts. Conclusion The overall revision rate was greater in very young THA patients. This was largely explained by the use of MoM bearings. Young patients with non‐MoM bearings had high survivorship with similar complication profiles to patients aged ≥ 60 years.
A novel formulation of zolpidem for direct nose‐to‐brain delivery: synthesis, encapsulation and intranasal administration to mice

Anxiolytic drug zolpidem was incorporated into the microcontainers based on mesoporous calcium carbonate particles modified by diethylaminoethyl‐dextran/hyaluronic acid shell. The release of zolpidem in saline solution and in polymer film modelling nasal mucosa was investigated. The anxiolytic effect of zolpidem upon intranasal administration of microcontainers and free medicine was determined by in vivo experiments on mice.
Cost-effectiveness analysis of 13-valent pneumococcal conjugate vaccine versus 23-valent pneumococcal polysaccharide vaccine in an adult population in South Korea

ABSTRACT In South Korea, the National Immunization Program offers a 23-valent pneumococcal polysaccharide vaccine (PPSV23) for the elderly; however, the 13-valent pneumococcal conjugate vaccine (PCV13) is not included, and vaccination is not offered to younger, at-risk populations. This study offers a comparative analysis of PCV13 and PPSV23 in Korea's adults, stratified by age and risk group. A Markov model with a lifetime horizon was developed from the healthcare perspective. Data sources included the Health Insurance Review & Assessment Service, Korea Centre for Disease Control & Prevention and Korean medical institutions. An expert panel tested data validity. The CAPiTA trial and Cochrane meta-analysis were used to obtain vaccine effectiveness data. Regardless of co-morbidity, when the sequential PCV13-PPSV23 strategy was compared to that using PPSV23-only, in elderly populations, the incremental cost-effectiveness ratio (ICER) was 3,300 USD per quality-adjusted life years (QALY). For the risk group aged ≥65 years, the ICER of the addition of PCV13 over the existing PPSV23-only strategy was 3,404 USD/QALY. However, on replacing PPSV23 with PCV13, for all elderly populations, an ICER of 1,421 USD/QALY resulted; for the risk group aged ≥65 years, the ICER was 1,736 USD/QALY. For the 18–64 year-old risk group, the sequential PCV13-PPSV23 strategy yielded an ICER of 3,629 USD/QALY over the PPSV23-only strategy, and 6,643 USD/QALY compared to no vaccination. Thus, the PCV13→PPSV23 combination strategy for elderly populations was found to be a cost-effective alternative to the current National Immunization Program regardless of co-morbidity. This finding was the same as that for younger, at-risk populations.
Proposal of Decision-making Model Using the DeLone and McLean's Information System Success Model Together with the AHP

The focus of the paper is to present an evaluation of a proposed decision-making model concept. The concept takes into account the quality of a currently used information system’s subsystem (the Business Intelligence subsystem in our case), as it is perceived by its current users. The Analytic Hierarchy Process (AHP) multi-criteria decision making method is used to support the concept with a hierarchical decision criteria structuring framework. A selected part of the DeLone and McLean’s (D&M) information system success assessment model is used for the determination of appropriate criteria (success factors). The D&M model is composed of information system quality assessment dimensions. These dimensions represent a solid base for surveying information system’s users according to their perception of key information system performance aspects. The presented model helps to combine opinions of the management and users successfully when carrying out important information system related decision. The results also illustrate the possibility of using the D&M model in a novel application together with the AHP method.