Miracle-dz/UniFAR-FTUs huggingface dataset:
Early Local Therapy for the Primary Site in De Novo Stage IV Breast Cancer: Results of a Randomized Clinical Trial (EA2108)

PURPOSE Distant metastases are present in 6% or more of patients with newly diagnosed breast cancer. In this context, locoregional therapy for the intact primary tumor has been hypothesized to improve overall survival (OS), but clinical trials have reported conflicting results. METHODS Women presenting with metastatic breast cancer and an intact primary tumor received systemic therapy for 4-8 months; if no disease progression occurred, they were randomly assigned to locoregional therapy for the primary site (surgery and radiotherapy per standards for nonmetastatic disease) or continuing sysmetic therapy. The primary end point was OS; locoregional control and quality of life were secondary end points. The trial design provided 85% power to detect a 19.3% absolute difference in the 3-year OS rate in randomly assigned patients. The stratified log-rank test and Cox proportional hazards model were used to compare OS between arms. Cumulative incidence of locoregional progression was compared using Gray's test. Quality-of-life assessment used standard instruments. RESULTS Of 390 participants enrolled, 256 were randomly assigned: 131 to continued systemic therapy and 125 to early locoregional therapy. The 3-year OS was 67.9% without and 68.4% with early locoregional therapy (hazard ratio = 1.11; 90% CI, 0.82 to 1.52; P = .57). The median OS was 53.1 months (95% CI, 47.9 to not estimable) in the systemic therapy arm and 54.9 months (95% CI, 46.7 to not estimable) in the locoregional therapy arm. Locoregional progression was less frequent in those randomly assigned to locoregional therapy (3-year rate: 16.3% v 39.8%; P < .001). Quality-of-life measures were largely similar between arms. CONCLUSION Early locoregional therapy for the primary site did not improve survival in patients presenting with metastatic breast cancer. Although it was associated with improved locoregional control, this had no overall impact on quality of life. If breast cancer is diagnosed after distant spread has occurred, surgery and radiation for the breast tumor do not improve survival.
A Single Fasting Exhaled Methane Level Correlates With Fecal Methanogen Load, Clinical Symptoms and Accurately Detects Intestinal Methanogen Overgrowth

INTRODUCTION: A 2-hour breath test is the gold standard for diagnosing intestinal methanogen overgrowth (IMO). This method can be cumbersome especially if used repetitively to monitor treatment response. Therefore, we aimed to assess the reliability of a fasting single methane measurement (SMM) in diagnosing IMO and its utility as a biomarker to monitor treatment response in subjects with IMO. METHODS: First, we calculated the test characteristics of SMM compared with lactulose and glucose breath test in 2 large-scale retrospective cohorts. Second, the symptomology associated with SMM using various cutoffs was analyzed. Third, in a double-blind randomized control trial, the temporal stability of SMM levels in subjects taking placebo was analyzed. Fourth, stool Methanobrevibacter smithii loads were quantified using quantitative polymerase chain reaction and compared with SMM levels. Last, the change in SMM over time during antibiotic therapy was analyzed. RESULTS: Using the cutoff of SMM ≥10 ppm, SMM had a sensitivity of 86.4% and specificity of 100% for diagnosing IMO on the glucose and lactulose breath tests and was associated with constipation (5.65 ± 3.47 vs 4.32 ± 3.62, P = 0.008). SMM remained stable for 14 weeks without treatment (P = 0.45), and antibiotics lead to a decrease in SMM after 2 days (P < 0.0001). SMM was positively associate with stool M. smithii load (R = 0.65, P < 0.0001). DISCUSSION: Fasting SMM ≥10 ppm seems to accurately diagnose IMO, is associated with constipation, and correlates with stool M. smithii. SMM seems to be stable without treatment and decreases after antibiotics. SMM may be a useful test to diagnose IMO and monitor treatment response.
Drugs of Abuse and Sexual Function: What Is New?

ABSTRACT The association between drugs of abuse and sexual function is thought to be prehistoric. In our era, science has shed some light on the roles of different neurotransmitters on sexual function. Objective: This systematic review aims to summarize the role of drugs of abuse on human sexuality. Methods: A systematic review was undertaken, according to PRISMA guidelines, for PubMed indexed English articles between 2008 and 2020. Results: The use of addictive substances is associated with poorer relationship functioning. Additionally, they can be both a trigger and a maintaining factor for sexual dysfunction by affecting any or all phases of sexual response models. These substances include alcohol, tobacco, cannabis, opioids, cocaine, amphetamines, and party drugs. Failure to address drug-induced sexual problems and dysfunctions or their treatment may induce relapses or represent the loss of a precious therapeutic opportunity. Conclusion: Health care providers should be aware of the relationship between drugs of abuse and sexual function, and use the permission, limited information, specific suggestions, intensive therapy model. We believe addiction professionals should have skills on clinical sexology, and conversely, clinical sexologists should have training in addictions. L’association faite entre les drogues illicites et le fonctionnement sexuel est perçu comme étant archaïque. De nos jours, la science a apportée une certaine lumière sur les rôles des différents neurotransmetteurs dans le fonctionnement sexuel. Objectifs: Cette revue systématique vise à résumer le rôle des drogues illicites sur la sexualité humaine. Méthodes: Une revue systématique a été entreprise, conformément aux directives PRISMA, pour les articles en anglais indexés PubMed entre 2008 et 2020. Résultats: La consommation de substances addictives est associée à un fonctionnement relationnel inférieur. De plus, ils peuvent être à la fois un déclencheur et un facteur de maintien de la dysfonction sexuelle en affectant une ou toutes les phases des modèles de réponse sexuelle. Ces substances comprennent l’alcool, le tabac, le cannabis, les opioïdes, la cocaïne, les amphétamines et les drogues festives (party drugs). Ne pas s’attaquer aux problèmes et dysfonctionnements sexuels induits par ces drogues ou à leur traitement peut provoquer des rechutes ou représenter la perte d’une précieuse opportunité thérapeutique. Conclusions: Les pourvoyeurs de soins de santé devraient être conscients de la relation entre les drogues et le fonctionnement sexuel, et utiliser le modèle PLISSIT. Nous pensons que les professionnels de l’addiction devraient avoir des compétences en sexologie clinique et, à l’inverse, les sexologues cliniciens devraient avoir une formation en addiction.
Blame the Player and The Game

How do people assign credit for others’ actions? The Correspondence Bias — a classic bias in social psychology — purports that people are predisposed to attribute behaviors to dispositional, rather than situational, factors. However, recent work suggests that the pattern of data cited as evidence of a bias may be a natural consequence of attribution under uncertainty. Here we devise a novel “Bucket-Toss” task in which we can independently and parametrically manipulate and measure situation and disposition pressures to evaluate whether attribution to dispositions and situations are consistent with probabilistic inference. We find that as the strength of the situation or disposition is varied, attributions to the other (unobserved) cause follow roughly symmetric patterns of graded attribution. Together, these results confirm that social attribution appears to be largely consistent with unbiased inference under uncertainty.
Rheumatoid Arthritis Patients Have Better Outcomes Than Non-Rheumatoid Arthritis Patients When Hospitalized for Ischemic Stroke

Supplemental digital content is available in the text. Objectives The aims of this study were to compare the outcomes of patients primarily admitted for ischemic stroke with and without a secondary diagnosis of RA. Methods Data were abstracted from the National Inpatient Sample (NIS) 2016 and 2017 database. The NIS was searched for hospitalizations for adult patients with ischemic stroke as principal diagnosis with and without RA as secondary diagnosis using International Classification of Diseases, 10th Revision codes. The primary outcome was inpatient mortality. Hospital length of stay (LOS), total hospital charges, odds of receiving tissue plasminogen activator, and mechanical thrombectomy were secondary outcomes of interest. Multivariate logistic and linear regression analyses were used accordingly to adjust for confounders. Results There were more than 71 million discharges included in the combined 2016 and 2017 NIS database. Of 525,570 patients with ischemic stroke, 8670 (1.7%) had RA. Hospitalizations for ischemic stroke with RA had less inpatient mortality (4.7% vs. 5.5%; adjusted odds ratio, 0.66; 95% confidence interval, 0.52–0.85; p = 0.001), shorter LOS (5.1 vs 5.7 days, p < 0.0001), lower mean total hospital charges ($61,626 vs. $70,345, p < 0.0001), and less odds of undergoing mechanical thrombectomy (3.9% vs. 5.1%; adjusted odds ratio, 0.55; 95% confidence interval, 0.42–0.72; p < 0.0001) compared with those without RA. Conclusions Hospitalizations for ischemic stroke with RA had less inpatient mortality, shorter LOS, lower total hospital charges, and less likelihood of undergoing mechanical thrombectomy compared with those without RA. However, the odds of receiving tissue plasminogen activator were similar between both groups. Further studies to understand its mechanism would be helpful.
IBI-CCS: a regional high-resolution model to evaluate western Europe simulate sea level changesin Western Europe

Projections of coastal sea level (SL) changes are of great interest for coastal risk assessment and decisionmaking. SL projections are typically produced using global climate models (GCMs)), which cannot fully resolve SL changes at the 10 coast due to their coarse resolution and lack of representation of some relevant processes. (tides, atmospheric surface pressure forcing, waves). To overcome these limitations and refine projections at regional scales, GCMs can be dynamically downscaled through the implementation of a high-resolution regional climate model (RCM). In this study, we developed the IBI-CCS (Iberian-Biscay-Ireland Climate Change Scenarios) regional ocean model based on a 1/12 ° north-easternnortheastern Atlantic NEMO ocean model configuration to dynamically downscale CNRM-CM6-1-HR, a GCM with a 1⁄4 ° resolution ocean model 15 component developed forparticipating in the Coupled Model Intercomparison Project 6th Phase (CMIP6) by the Centre National de Recherches Météorologiques (CNRM). For a more complete representation of the processes driving coastal SL changes, tides and atmospheric surface pressure forcing are explicitly resolved in IBI-CCS in addition to the ocean general circulation. To limit the propagation of climate drifts and biases from the GCM into the regional simulations, several corrections are applied to the GCM fields used to force the RCM. The regional simulations are performed over the 1950 to 2
A Community Emergency Department Rotation for Pediatric Emergency Medicine Fellows

Objective There have been increasing job opportunities for pediatric emergency medicine (PEM) specialists within community emergency departments (CEDs), where 90% of children receive emergency care. The majority of training for PEM fellows occurs in academic children's hospitals, which may expose fellows to different resources than CEDs. Our goals were to develop and to evaluate a CED rotation aimed at improving exposure to this care environment for PEM fellows. Methods Kern's 6 steps of curriculum development served as our framework to identify the problem, conduct a needs assessment, develop goals and objectives, formulate an educational strategy, and then plan the implementation and evaluation. Discussion and buy-in among trainees and hospital leadership took place during rotation development. Informal and web-based surveys of PEM fellows and CED attendings evaluated the rotation and assessed participants' reactions, changes in knowledge, and changes in behavior. Results The CED rotation was piloted at 1 PEM fellowship program over 2 years. Nine PEM fellows participated in the month-long rotation. The majority of participants reported that the rotation goals and objectives were met and that they acquired new skills and rated the CED rotation as good or excellent. Challenges to the CED rotation included lower patient acuity and distance to the CED. Conclusions A new CED rotation was developed, piloted, and well received by participants. Given the potential differences in practice between tertiary care children's emergency departments and CEDs, as well as increasing job opportunities in CEDs, program directors should consider incorporating a CED rotation for their PEM fellows.
Combating multidrug resistance and metastasis of breast cancer by endoplasmic reticulum stress and cell-nucleus penetration enhanced immunochemotherapy

Rationale: Multidrug resistance (MDR) and metastasis of breast cancer remain major hurdles in clinical anticancer therapy. The unsatisfactory outcome is largely due to insufficient cytotoxicity of chemotherapeutic agents and limited immunogenic cell death (ICD). On the other hand, efflux proteins, especially P-glycoprotein (P-gp), can recognize and promote the efflux of drugs from tumor cells. Methods: In this study, silver nanoparticles (Ag NPs) and peptide- functionalized doxorubicin (PDOX) were used to prepare a theranostic nanocomposite (Ag-TF@PDOX), which induced organelle-mediated immunochemotherapy and drug efflux protein inhibition in drug-resistant breast cancer cells (MCF-7/ADR) via a strategy based on endoplasmic reticulum (ER) stress and cell-nucleus penetration. Results: The silver nanoparticle-triggered persistent activation of ER stress synergizes with chemotherapy to enhance cytotoxicity and stimulate the ICD effect. It has the potential to enhance chemosensitivity by downregulating of P-gp expression due to the increased production of ATP-consuming chaperones. In addition, the novel peptide (CB5005), which not only penetrates the cell membrane but also has a nuclear localization sequence, is conjugated to DOX to improve both cellular internalization and intranuclear accumulation. Moreover, surface TA-Fe3+ engineering endows the nanocomposite with ATP-responsive disassembly and ATP depletion properties to improve biocompatibility and decrease ATP-dependent drug efflux. Ag-TF@PDOX has potential as a dual-mode (PAI/MRI) contrast-enhanced agent for realizing theranostic guidance. Conclusion: This theranostic nanocomposite greatly restricts the growth of drug-resistant breast tumors and activates a strong immune response as well, providing an opportunity for the development of therapeutics that reverse tumor MDR and metastasis at the subcellular level.
The Seasonal-to-Multiyear Large Ensemble (SMYLE) prediction system using the Community Earth System Model version 2

Abstract. The potential for multiyear prediction of impactful Earth system change remains relatively underexplored compared to shorter (subseasonal to seasonal) and longer (decadal) timescales. In this study, we introduce a new initialized prediction system using the Community Earth System Model version 2 (CESM2) that is specifically designed to probe potential and actual prediction skill at lead times ranging from 1 month out to 2 years. The Seasonal-to-Multiyear Large Ensemble (SMYLE) consists of a collection of 2-year-long hindcast simulations, with four initializations per year from 1970 to 2019 and an ensemble size of 20. A full suite of output is available for exploring near-term predictability of all Earth system components represented in CESM2. We show that SMYLE skill for El Niño–Southern Oscillation is competitive with other prominent seasonal prediction systems, with correlations exceeding 0.5 beyond a lead time of 12 months. A broad overview of prediction skill reveals varying degrees of potential for useful multiyear predictions of seasonal anomalies in the atmosphere, ocean, land, and sea ice. The SMYLE dataset, experimental design, model, initial conditions, and associated analysis tools are all publicly available, providing a foundation for research on multiyear prediction of environmental change by the wider community.
Linear Contextual Bandits”

Linear contextual bandits. The reward model considered in this work is similar to that of linear contextual bandits in the literature. The single-agent setting is first introduced in Auer (2003) through the LinRel algorithm and is subsequently improved through the OFUL algorithm in Dani et al. (2008) and the LinUCB algorithm in Li et al. (2010). Rusmevichientong and Tsitsiklis (2010) extend the work of Dani et al. (2008) by considering both optimistic and explore-then-commit strategies. A modified version of LinUCB, named SupLinUCB, is considered in Chu et al. (2011), which is further improved by Valko et al. (2013). This line of literature typically allows for sequential stochastic (Goldenshluger and Zeevi, 2013; Bastani and Bayati, 2015) or adversarial (Raghavan et al., 2018; Kannan et al., 2018) context arrivals, which is different from the fixed context setting and distributed nature of the federated linear contextual bandits considered in this work.
Treatment of Recurrent Axillary Osmidrosis

Objective The aim of this study was to explore the clinical effect of treatment for recurrent axillary osmidrosis (AO) after small-incision minimally invasive surgery by trimming and electrocoagulation of apocrine glands under direct vision through double incisions parallel to axillary creases. Methods This was a retrospective study. From September 2012 to January 2019, 75 axillae in 48 cases of recurrent AO after small-incision minimally invasive surgery were treated using trimming and electrocoagulation of apocrine glands under direct vision through double incisions parallel to axillary creases. Patient data, such as sex, age, original surgery method, the severity of underarm malodor before and after the operation, and occurrence of complications, were collected and analyzed. Results For the follow-up of at least 12 months after the surgery, all patients' underarm malodor disappeared or was significantly reduced. Patients with preoperative severity of grade I did not show a recurring AO, whereas the recurrence rate of grade II and grade III AO was 7.9% and 14.3%, respectively. Furthermore, the AO recurrence rate was 9.1% for those younger than 18 years and 6.2% in those 18 years or older. Subcutaneous hematomas appeared on 3 axillae (4.0%), and the contraction of subdermal fibrotic bands appeared on 5 axillae (6.7%). Conclusions Patients with recurring AO after small-incision minimally invasive surgery achieved good treatment results by trimming and electrocoagulation of apocrine glands under direct vision through double incisions parallel to axillary creases.
Gliflozins for the preventi on of stroke in diabetes and cardiorenal diseases A meta-analysis of cardiovascular outcome trials

Background: Individual randomized trials are not powered to assess the relationship between use of sodium–glucose transporter 2 inhibitors and risk of stroke. We sought to explore this issue by a meta-analysis incorporating relevant trials including several latest trials. Methods: Cardiovascular outcome trials of gliflozins were included. Primary outcome was stroke, while secondary outcome was major adverse cardiovascular events (MACE), which was a composite of stroke, myocardial infarction, or cardiovascular death. Metaanalysis was conducted stratified by with/without chronic kidney disease (CKD), with/without heart failure (HF), and with/without atherosclerotic cardiovascular disease (ASCVD), and stratified by different gliflozins. Results:We included 9 trials in this meta-analysis. Compared with placebo, gliflozins significantly lowered stroke (hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.55–0.84) and MACE (HR 0.77, 95% CI 0.69–0.86) in type 2 diabetes (T2D) patients with CKD, but did not significantly affect stroke (HR 1.00, 95% CI 0.86–1.16) and MACE (HR 0.94, 95% CI 0.86–1.02) in T2D patients without CKD. Gliflozins had no significant effects on the stroke risk (HR 0.94, 95% CI 0.82–1.07) in T2D patients regardless of HF status (Psubgroup= .684) and ASCVD status (Psubgroup= .915), but significantly lowered MACE (HR 0.89, 95% CI 0.83–0.96) in T2D patients regardless of HF status (Psubgroup= .428) and ASCVD status (Psubgroup= .423). Canagliflozin (HR 0.84, 95% CI 0.69–1.01) showed the trend of a reduction in the stroke risk versus placebo, and sotagliflozin (HR 0.73, 95% CI 0.54–0.98) significantly lowered the stroke risk; whereas the other 3 gliflozins did not significantly affect that risk. Ertugliflozin (HR 0.97, 95% CI 0.85–1.11) had no significant effects on the MACE risk, whereas the other 4 gliflozins significantly lowered that risk. Conclusions: Gliflozins, especially canagliflozin and sotagliflozin, should be recommended in T2D patients with CKD to prevent stroke. Most gliflozins lower the risk of MACE in T2D patients regardless of HF status and ASCVD status, whereas ertugliflozin is not observed to lower that risk. Abbreviations: ASCVD = atherosclerotic cardiovascular disease, CI = confidence interval, CKD = chronic kidney disease, HF = heart failure, HR= hazard ratio, MACE=major adverse cardiovascular events, SGLT2= sodium–glucose transporter 2, T2D= type 2 diabetes.
How can instructions and feedback with external focus be shaped to enhance motor learning in children? A systematic review

Aim This systematic review investigates the effectiveness of instructions and feedback with external focus applied with reduced frequency, self-controlled timing and/or in visual or auditory form, on the performance of functional gross motor tasks in children aged 2 to 18 with typical or atypical development. Methods Four databases (PubMed, Web of Science, Scopus, Embase) were systematically searched (last updated May 31st 2021). Inclusion criteria were: 1. children aged 2 to 18 years old; 2. Instructions/feedback with external focus applied with reduced frequency, self-controlled timing, and/or visual or auditory form as intervention, to learn functional gross motor tasks; 3. Instructions/feedback with external focus applied with continuous frequency, instructor-controlled timing, and/or verbal form as control; 4. performance measure as outcome; 5. (randomized) controlled studies. Article selection and risk of bias assessment (with the Cochrane risk of bias tools) was conducted by two reviewers independently. Due to heterogeneity in study characteristics and incompleteness of the reported data, a best-evidence synthesis was performed. Results Thirteen studies of low methodological quality were included, investigating effectiveness of reduced frequencies (n = 8), self-controlled timing (n = 5) and visual form (n = 1) on motor performance of inexperienced typically (n = 348) and atypically (n = 195) developing children, for acquisition, retention and/or transfer. For accuracy, conflicting or no evidence was found for most comparisons, at most time points. However, there was moderate evidence that self-controlled feedback was most effective for retention, and limited evidence that visual analogy was most effective for retention and transfer. To improve quality of movement, there was limited evidence that continuous frequency was most effective for retention and transfer. Conclusion More methodologically sound studies are needed to draw conclusions about the preferred frequency, timing or form. However, we cautiously advise considering self-controlled feedback, visual instructions, and continuous frequency. Registration Prospero CRD42021225723