Miracle-dz/UniFAR-FTUs huggingface dataset:
On the convergence of multi-scale free energy simulations

In this work, we employ simple model systems to evaluate the relative performance of two of the most important free energy methods: The Zwanzig equation (also known as ‘Free energy perturbation’) and Bennett’s acceptance ratio method (BAR). Although our examples should be transferable to other kinds of free energy simulations, we focus on applications of multi-scale free energy simulations. Such calculations are especially complex, since they connect two different levels of theory with very different requirements in terms of speed, accuracy, sampling and parallelisability. We try to reconcile all those different factors by developing some simple criteria to guide the early stages of the development of a free energy protocol. This is accomplished by quantifying how many intermediate steps and how many potential energy evaluations are necessary in order to reach a certain level of convergence.
Association of Rituximab Treatment With Disability Progression Among Patients With Secondary Progressive Multiple Sclerosis

Importance Therapeutic options for patients with secondary progressive multiple sclerosis (SPMS) are limited. Objective To analyze disability progression in patients with SPMS treated with rituximab compared with matched control patients never treated with rituximab. Design, Setting, and Participants This retrospective cohort study analyzed data obtained from patients with SPMS at 3 multiple sclerosis centers located in Basel and Lugano, Switzerland, and Amsterdam, the Netherlands, from 2004 to 2017. Patients were included for analysis if they had received a diagnosis of SPMS, were treated (57 eligible; 54 included) or never treated (504 eligible; 59 included) with rituximab, and had at least 1 follow-up visit. The variables used for propensity score matching were sex, age, Expanded Disability Status Scale (EDSS) score, and disease duration. Follow-up duration was up to 10 years, with a mean (SD) of 3.5 (2.6) years for rituximab-treated patients and 5.4 (2.4) years for controls in the total cohort and a mean (SD) of 3.5 (2.7) years for rituximab-treated patients and 4.8 (2.2) years for controls in the matched cohort. Exposures Comparing EDSS score progression in patients with SPMS (treated with rituximab vs not treated with rituximab) using propensity score matching. Main Outcomes and Measures The primary end point was progression of EDSS score after baseline, and the secondary end point was time to confirmed disability progression. Results After 1:1 propensity score matching, 44 matched pairs (88 patients) were included in the analysis. At baseline, patients treated with rituximab had a mean (SD) age of 49.7 (10.0) years, mean (SD) disease duration of 18.2 (9.4) years, and mean (SD) EDSS score of 5.9 (1.4), and 26 (59%) were women, whereas controls had a mean (SD) age of 51.3 (7.4) years, mean (SD) disease duration of 19.4 (8.7) years, and mean (SD) EDSS score of 5.70 (1.29), and 27 (61%) were women. In the covariate-adjusted analysis of the matched set, patients with SPMS who were treated with rituximab had a significantly lower EDSS score during a mean (SD) follow-up of 3.5 (2.7) years (mean difference, −0.52; 95% CI, −0.79 to −0.26; P < .001). Time to confirmed disability progression was significantly delayed in the rituximab-treated group (hazard ratio, 0.49; 95% CI, 0.26-0.93; P = .03). Conclusions and Relevance In this study, patients with SPMS treated with rituximab had a significantly lower EDSS score for up to 10 years of follow-up and a significantly delayed confirmed progression compared with matched controls, suggesting that B-cell depletion by rituximab may be therapeutically beneficial in these patients. A prospective randomized clinical trial with a better level of evidence is needed to confirm the efficacy of rituximab in such patients.
Improvement of a Cohesive Zone Model for Fatigue Delamination Rate Simulation

The cohesive zone model (CZM) has found wide acceptance as a tool for the simulation of delamination in composites and debonding in bonded joints and various implementations of the cohesive zone model dedicated to fatigue problems have been proposed in the past decade. In previous works, the authors have developed a model based on cohesive zone to simulate the propagation of fatigue defects where damage acts on cohesive stiffness, with an initial (undamaged) stiffness representative of that of the entire thickness of an adhesive layer. In the case of a stiffness that is order of magnitude higher than the previous one (for instance, in the simulation of the ply-to-ply interface in composites), the model prediction becomes inaccurate. In this work, a new formulation of the model that overcomes this limitation is developed. Finite element simulations have been conducted on a mode I, constant bending (constant G)-loaded double cantilever beam (DCB) joint to assess the response of the new model with respect to the original one for varying initial stiffness K0 and cohesive strength σ0. The results showed that the modified model is robust with respect to changes of two orders of magnitude in initial stiffness and of a factor of two in σ0.
The penetrating properties of the tumor homing peptide LyP‐1 in model lipid membranes

Cell‐penetrating peptides (CPPs) have the property to cross the plasma membrane and enhance its permeability. CPPs were successfully used to deliver numerous cargoes such as drugs, proteins, nucleic acids, imaging and radiotherapeutic agents, gold and magnetic nanoparticles, or liposomes inside cells. Although CPPs were intensively investigated over the past 20 years, the exact molecular mechanisms of translocation across membranes are still controversial and vary from passive to active mechanisms.
Neonatal vitamin A supplementation and immune responses to oral polio vaccine in Zimbabwean infants

Abstract Background Micronutrient deficiencies may contribute to reduced oral vaccine immunogenicity in developing countries. We hypothesised that neonatal vitamin A supplementation (NVAS) would improve oral vaccine responses. Methods We performed a cross-sectional study of infants recruited at birth to the Zimbabwe Vitamin A for Mothers and Babies (ZVITAMBO) trial, a randomised controlled trial of single, high-dose NVAS vs placebo conducted in Zimbabwe between 1997–2001. We measured poliovirus-specific IgA to type 1–3 polio strains by semiquantitative capture ELISA in cryopreserved plasma samples collected at 6 months of age. Results A total of 181 infants fulfilled inclusion criteria, of whom 80 were randomised to NVAS and 101 to placebo. There were no significant differences in baseline characteristics between groups. At 6 months of age, median (IQR) vaccine titres for infants randomised to NVAS vs placebo were 932 (421–3001) vs 1774 (711–5431) for Sabin-1 (p=0.04); 1361 (705–3402) vs 2309 (1081–4283) for Sabin-2 (p=0.15); and 1584 (796–4216) vs 2260 (996–5723) for Sabin-3 (p=0.14), respectively. After adjusting for breast feeding status, birth weight, season and infant sex in a linear regression model, there was only weak evidence of difference in log mean titres between vitamin A and placebo groups for Sabin-1 (p=0.08) and no evidence of difference in log mean titres for Sabin-2 and Sabin-3. Conclusions NVAS did not augment oral polio vaccine responses in Zimbabwean infants. Further research is required to understand the impact of NVAS on responses to other oral vaccines. The trial is registered with clinicaltrials.gov identifier: NCT00198718.
Patellar and Achilles Tendon Stiffness in Elite Soccer Players Assessed Using Myotonometric Measurements

Background: Tendon overuse injuries are an issue in elite footballers (soccer players) and may affect tendon function. Achilles and patellar tendinopathy are the most frequent pathologies. Tendon stiffness, the relationship between the force applied to a tendon and the displacement exerted, may help represent tendon function. Stiffness is affected by training and pathology. Nevertheless, information regarding this mechanical property is lacking for elite soccer athletes. Hypothesis: Achilles and patellar tendon stiffness assessed using myotonometric measurements will be greater in elite soccer athletes than in control participants. Study Design: Cross-sectional study. Level of Evidence: Level 4. Methods: Forty-nine elite soccer athletes and 49 control participants were evaluated during the 2017 preseason. A handheld device was used to measure Achilles and patellar tendon stiffness. Dominant and nondominant limbs were assessed for both groups. Results: A significantly stiffer patellar tendon was found for both the dominant and the nondominant limb in the elite soccer athletes compared with the control group. Nevertheless, no differences were found in Achilles tendon stiffness between groups. When comparing between playing positions in soccer athletes, no significant differences were found for both tendons. Conclusion: Greater patellar tendon stiffness may be related to an improvement in force transmission during muscle contraction. On the other hand, it seems that after years of professional training, Achilles tendon stiffness does not change, conserving the storing-releasing function of elastic energy. The nonsignificant differences between positions may be attributable to the years of homogeneous training that the players underwent. Clinical Relevance: The present study shows another technique for measuring mechanical properties of tendons in soccer athletes that could be used in clinical settings. In the future, this technique may help clinicians choose the best exercise protocol to address impairments in tendon stiffness.
Dual Mobility Cups: Effect on Risk of Revision of Primary Total Hip Arthroplasty Due to Osteoarthritis A Matched Population-Based Study Using the Nordic Arthroplasty Register Association Database

Background: The dual mobility acetabular cup (DMC) was designed to reduce prosthetic instability and has gained popularity for both primary and revision total hip arthroplasty (THA). We compared the risk of revision of primary THA for primary osteoarthritis between patients treated with a DMC and those who received a metal-on-polyethylene (MoP) or ceramic-on-polyethylene (CoP) bearing. Methods: A search of the Nordic Arthroplasty Register Association (NARA) database identified THAs performed with a DMC during 1995 to 2013. With use of propensity score matching, 2,277 of these patients were matched (1:1), with regard to sex, age, component fixation, and year of surgery, with patients with an MoP or CoP bearing. We estimated the cumulative incidence of revision taking death as a competing risk into consideration and performed competing risk regression with revision or death as end points. Results: There was no difference in the overall risk of revision between the DMC group and the propensity-score-matched MoP/CoP group (adjusted hazard ratio [HR] = 1.18; 95% confidence interval [95% CI] = 0.87 to 1.62). Patients with a DMC bearing had a lower risk of revision due to dislocation (adjusted HR = 0.09; 95% CI = 0.03 to 0.29) but a higher risk of revision caused by infection (adjusted HR = 3.20; 95% CI = 1.49 to 6.85). Conclusions: There was no difference in overall risk of revision between the DMC and MoP/CoP groups. The DMCs protected against revision due to dislocation but THAs performed with this bearing were more commonly revised because of infection. There may have been a selection bias toward placing DMC implants in patients with greater frailty as the mortality rates were higher in the DMC group than in the age and sex-matched MoP/CoP group. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
“I Walked into the Industry for Survival and Came Out of a Closet”

Background/Objectives: This article seeks to examine how gender and sexual identities shape sex work experiences among men, two spirit, and/or trans people in Vancouver. Methods: In-depth, semistructured interviews were conducted with men and trans people in Metro Vancouver from Community Health Assessment of Men Who Purchase and Sell Sex. An intersectional critical feminist perspective guided the thematic analysis of interview transcripts, and ATLAS.ti 7 was used to manage data analysis. Results: Three themes emerged from the data: (1) the diversity of sexual and gender identities among sex workers and clients, (2) the expression and exploration of sexual and gender identities through sex work, and (3) the migration of sexual and gender minorities to urban centers to escape discrimination in their places of origin. Discussion: These findings complicate existing narratives of sex work, demonstrating the need for policies and services that reflect the diversity of sex work experiences.
Association between thermal threshold abnormalities and peripheral artery disease in patients with type 2 diabetes

Abstract Both diabetic peripheral neuropathy and peripheral arterial disease (PAD) cause foot ulcers and often result in non-traumatic amputations in patients with type 2 diabetes. This study aimed to evaluate the association between clinical variables, PAD, and subclinical diabetic small fiber peripheral neuropathy detected by abnormal thermal thresholds of the lower extremities in patients with type 2 diabetes. We investigated 725 consecutive patients with type 2 diabetes (male/female: 372/353; mean age, 67 ± 11 years) who did not have apparent cardiovascular disease (including coronary artery disease, arrhythmia, and stroke) and who underwent the quantitative sensory test for thermal (warm and cold) thresholds of the lower limbs and ankle-brachial index (ABI)/toe-brachial index (TBI) examinations in 2015. The analyses included glycated hemoglobin, estimated glomerular filtration rate, and other characteristics. In total, 539 (74.3%) patients showed an abnormality of at least 1 thermal threshold in their feet. All patients with an abnormal ABI (<0.9) had concurrent impaired thermal thresholds, and 93% (87/94) of patients with an abnormal TBI experienced abnormal thermal thresholds in the lower limbs. Age- and sex-adjusted TBI and estimated glomerular filtration rate were significantly correlated to abnormal thermal thresholds. In the multivariate analysis, fasting plasma glucose, and glycated hemoglobin were independently associated with abnormal thermal thresholds in the lower extremities. Subclinical thermal threshold abnormalities of the feet are significantly associated with PAD and nephropathy in patients who have type 2 diabetes without cardiovascular disease.
Localization of distant metastases defines prognosis and treatment efficacy in patients with FIGO stage IV ovarian cancer

Background Patients with ovarian cancer who are diagnosed with Federation of Gynecology and Obstetrics (FIGO) stage IV disease are a highly heterogeneous group with possible survival differences. The FIGO staging system was therefore updated in 2014. Objective To evaluate the 2014 changes to FIGO stage IV ovarian cancer on overall survival. Methods We identified all patients diagnosed with FIGO stage IV disease between January 2008 and December 2015 from the Netherlands Cancer Registry. We analyzed the prognostic effect of FIGO IVa versus IVb. In addition, patients with extra-abdominal lymph node involvement as the only site of distant disease were analyzed separately. Overall survival was analyzed by Kaplan-Meier curves and multivariable Cox regression models. Results We identified 2436 FIGO IV patients, of whom 35% were diagnosed with FIGO IVa disease. Five-year overall survival of FIGO IVa and IVb patients (including those with no or limited therapy) was 8.9% and 13.0%, respectively (p=0.51). Patients with only extra-abdominal lymph node involvement had a significant better overall survival than all other FIGO IV patients (5-year overall survival 25.9%, hazard ratio 0.77 [95% CI 0.62 to 0.95]). Conclusion Our study shows that the FIGO IV sub-classification into FIGO IVa and IVB does not provide additional prognostic information. Patients with extra-abdominal lymph node metastases as the only site of FIGO IV disease, however, have a better prognosis than all other FIGO IV patients. These results warrant a critical appraisal of the current FIGO IV sub-classification.
The Relationship Between Networking, LinkedIn Use, and Retrieving Informational Benefits

Abstract Previous research has shown that users of social network sites designed for professional purposes, such as LinkedIn, report higher professional informational benefits than nonusers. However, this effect could only be partly explained by social media use as there was also a selection effect, such that people who have more informational benefits were more likely to use LinkedIn. The goal of this study was to explore whether differences in networking, defined as a set of behaviors with the aim of building, maintaining, and using internal and external contacts for instrumental purposes, can explain this selection effect. We used data from a panel study with a representative sample of Dutch Internet users (n = 685; 259 LinkedIn users) to examine the relationships between networking and LinkedIn use as well as professional informational benefits, that is, timely access to relevant information. The results showed that people scoring high on external networking (but not internal networking within their organization) are also more likely to use LinkedIn. External networking was also positively correlated with active and passive use as well as the number of strong and latent ties on LinkedIn. However, in a mediation model the direct effect of networking on informational benefits was not mediated by actual social media use and network composition; instead, the number of weak ties had a direct effect on informational benefits. The results thus indicate that networking is a major driver of informational benefits from LinkedIn use.
The value of syntax score to predict new‐onset atrial fibrillation in patients with acute coronary syndrome

New‐onset atrial fibrillation (NOAF) has been associated with poor outcome in patients with acute coronary syndromes (ACS). Also, Syntax score (SS) is a scoring system that is derived from angiographic images and is associated with long‐term mortality and major adverse cardiac events. In this study, we aimed to assess the relationship between SS and NOAF with known predictors of atrial fibrillation.
La variabilité morphologique en français langue seconde

Cet article examine la variabilite morphologique dans des donnees de production spontanee de deux enfants anglophones apprenant le francais langue seconde (FLS). Malgre la production de morphologie erronee, il est suggere que les categories fonctionnelles qui sous-tendent la morphologie inflexionnelle et le deplacement du verbe ne sont pas deficientes et font partie integrante des grammaires sous-jacentes developpees par les apprenants. Les resultats de l'etude sont similaires a ceux rapportes par Prevost & White (2000) concernant l'acquisition du FLS par des adultes.
Utility of Diffusion-weighted Imaging to Decrease Unnecessary Biopsies Prompted by Breast MRI: A Trial of the ECOG-ACRIN Cancer Research Group (A6702)

Purpose: Conventional breast MRI is highly sensitive for cancer detection but prompts some false positives. We performed a prospective, multicenter study to determine whether apparent diffusion coefficients (ADCs) from diffusion-weighted imaging (DWI) can decrease MRI false positives. Experimental Design: A total of 107 women with MRI-detected BI-RADS 3, 4, or 5 lesions were enrolled from March 2014 to April 2015. ADCs were measured both centrally and at participating sites. ROC analysis was employed to assess diagnostic performance of centrally measured ADCs and identify optimal ADC thresholds to reduce unnecessary biopsies. Lesion reference standard was based on either definitive biopsy result or at least 337 days of follow-up after the initial MRI procedure. Results: Of 107 women enrolled, 67 patients (median age 49, range 24–75 years) with 81 lesions with confirmed reference standard (28 malignant, 53 benign) and evaluable DWI were analyzed. Sixty-seven of 81 lesions were BI-RADS 4 (n = 63) or 5 (n = 4) and recommended for biopsy. Malignancies exhibited lower mean in centrally measured ADCs (mm2/s) than benign lesions [1.21 × 10−3 vs.1. 47 × 10−3; P < 0.0001; area under ROC curve = 0.75; 95% confidence interval (CI) 0.65–0.84]. In centralized analysis, application of an ADC threshold (1.53 × 10−3 mm2/s) lowered the biopsy rate by 20.9% (14/67; 95% CI, 11.2%–31.2%) without affecting sensitivity. Application of a more conservative threshold (1.68 × 10−3 mm2/s) to site-measured ADCs reduced the biopsy rate by 26.2% (16/61) but missed three cancers. Conclusions: DWI can reclassify a substantial fraction of suspicious breast MRI findings as benign and thereby decrease unnecessary biopsies. ADC thresholds identified in this trial should be validated in future phase III studies.
Hip-Muscle Activity in Men and Women During Resisted Side Stepping With Different Band Positions.

CONTEXT Weakness or decreased activation of the hip abductors and external rotators has been associated with lower extremity injury, especially in females. Resisted side stepping is commonly used to address hip weakness. Whereas multiple variations of this exercise are used clinically, few data exist regarding which variations to select. OBJECTIVE To investigate differences in muscle-activation and movement patterns and determine kinematic and limb-specific differences between men and women during resisted side stepping with 3 resistive-band positions. DESIGN Controlled laboratory study. SETTING Laboratory. PATIENTS OR OTHER PARTICIPANTS A total of 22 healthy adults (11 men, 11 women; age = 22.8 ± 3.0 years, height = 171.6 ± 10.7 cm, mass = 68.5 ± 11.8 kg). INTERVENTION(S) Participants side stepped with the resistive band at 3 locations (knees, ankles, feet). MAIN OUTCOME MEASURE(S) We collected surface electromyography of the gluteus maximus, gluteus medius, and tensor fascia lata (TFL) for the moving and stance limbs during the concentric and eccentric phases. We also measured trunk inclination, hip and knee flexion, and hip-abduction excursion. RESULTS Hip-abductor activity was higher in women than in men ( P ≤ .04). The pattern of TFL activity in the stance limb differed by sex. Women performed the exercise in greater forward trunk inclination ( P = .009) and had greater hip excursion ( P = .003). Gluteus maximus and medius activity increased when the band was moved from the knees to the ankles and from the ankles to the feet, whereas TFL activity increased only when the band was moved from the knees to the ankles. Findings were similar for both the stance and moving limbs, but the magnitudes of the changes differed. CONCLUSIONS Compared with placing the band around the ankles, placing the band around the feet for resisted side stepping elicited more activity in the gluteal muscles without increasing TFL activity. This band placement is most appropriate when the therapeutic goal is to activate the muscles that resist hip adduction and internal rotation.