Miracle-dz/UniFAR-FTUs huggingface dataset:
Randomized controlled trial of N-acetylcysteine therapy for RYR1-related myopathies

Objective To investigate the efficacy of N-acetylcysteine (NAC) for decreasing elevated oxidative stress and increasing physical endurance in individuals with ryanodine receptor 1-related myopathies (RYR1-RM). Methods In this 6-month natural history assessment (n = 37) followed by a randomized, double-blinded, placebo-controlled trial, 33 eligible participants were block-randomized (1:1) to receive NAC (n = 16) or placebo (n = 17), orally for 6 months (adult dose 2,700 mg/d; pediatric dose 30 mg/kg/d). The primary endpoint was urine 15-F2t isoprostane concentration and the clinically meaningful co-primary endpoint was 6-minute walk test (6MWT) distance. Results When compared to the general population, participants had elevated baseline 15-F2t isoprostane concentrations and most had a decreased 6MWT distance (mean ± SD 3.2 ± 1.5 vs 1.1 ± 1.7 ng/mg creatinine and 468 ± 134 vs 600 ± 58 m, respectively, both p < 0.001). 15-F2t isoprostane concentration and 6MWT distance did not change over the 6-month natural history assessment (p = 0.98 and p = 0.61, respectively). NAC treatment did not improve 15-F2t isoprostane concentration (least squares means difference 0.1 [95% confidence interval [CI] −1.4 to 1.6] ng/mg creatinine, p = 0.88) or 6MWT distance (least squares means difference 24 [95% CI −5.5 to 53.4] m, p = 0.11). NAC was safe and well-tolerated at the doses administered in this study. Conclusion In ambulatory RYR1-RM–affected individuals, we observed stable disease course, and corroborated preclinical reports of elevated oxidative stress and decreased physical endurance. NAC treatment did not decrease elevated oxidative stress, as measured by 15-F2t isoprostane. Classification of evidence This study provides Class I evidence that, for people with RYR1-RM, treatment with oral NAC does not decrease oxidative stress as measured by 15-F2t isoprostane. Clinicaltrials.gov identifier NCT02362425.
Efficacy of an m-Health Physical Activity and Sleep Intervention to Improve Sleep Quality in Middle-Aged Adults: The Refresh Study Randomized Controlled Trial.

BACKGROUND Poor sleep health is highly prevalent. Physical activity is known to improve sleep quality but not specifically targeted in sleep interventions. PURPOSE To compare the efficacy of a combined physical activity and sleep intervention with a sleep-only intervention and a wait-list control, for improving sleep quality in middle-aged adults without a diagnosed sleep disorder. METHODS Three-arm randomized controlled trial (Physical Activity and Sleep Health (PAS), Sleep Health Only (SO), Wait-list Control (CON) groups; 3-month primary time-point, 6-month follow-up) of 275 (PAS = 110, SO = 110, CON = 55) inactive adults (40-65 years) reporting poor sleep quality. The main intervention component was a smartphone/tablet "app" to aid goal setting and self-monitoring physical activity and/or sleep hygiene behaviors (including stress management), and a pedometer for PAS group. Primary outcome was Pittsburgh Sleep Quality Index (PSQI) global score. Secondary outcomes included several self-reported physical activity measures and PSQI subcomponents. Group differences were examined stepwise, first between pooled intervention (PI = PAS + SO) and CON groups, then between PAS and SO groups. RESULTS Compared with CON, PI groups significantly improved PSQI global and subcomponents scores at 3 and 6 months. There were no differences in sleep quality between PAS and SO groups. The PAS group reported significantly less daily sitting time at 3 months and was significantly more likely to report ≥2 days/week resistance training and meeting physical activity guidelines at 6 months than the SO group. CONCLUSIONS PIs had statistically significantly improved sleep quality among middle-aged adults with poor sleep quality without a diagnosed sleep disorder. The adjunctive physical activity intervention did not additionally improve sleep quality. CLINICAL TRIAL INFORMATION Australian New Zealand Clinical Trial Registry: ACTRN12617000680369; Universal Trial number: U1111-1194-2680; Human Research Ethics Committee, Blinded by request of journal: H-2016-0267.
Aldehyde dehydrogenase 2 inhibition potentiates 4‐hydroxy‐2‐nonenal induced decrease in angiogenesis of coronary endothelial cells

Coronary endothelial cell (EC) dysfunction including defective angiogenesis is reported in cardiac diseases. 4‐Hydroxynonenal (4HNE) is a lipid peroxidation product, which is increased in cardiac diseases and implicated in cellular toxicity. Aldehyde dehydrogenase (ALDH) 2 is a mitochondrial enzyme that metabolizes 4HNE and reduces 4HNE‐mediated cytotoxicity. Thus, we hypothesize that ALDH2 inhibition potentiates 4HNE‐mediated decrease in coronary EC angiogenesis in vitro. To test our hypothesis, first, we treated the cultured mouse coronary EC (MCEC) lines with 4HNE (25, 50, and 75 μM) for 2 and 4 hours. Next, we pharmacologically inhibited ALDH2 by disulfiram (DSF) (2.5 μM) before challenging the cells with 4HNE. In this study, we found that 4HNE attenuated tube formation which indicates decreased angiogenesis. Next, we found that 4HNE has significantly downregulated the expressions of vascular endothelial growth factor receptor (VEGFR) 2 (P < .05 for mRNA and P = .005 for protein), Sirtuin 1 (SIRT 1) (P < 0.0005 for mRNA), and Ets‐related gene (ERG) (P < 0.0001 for mRNA and P < 0.005 for protein) in MCECs compared with control. ALDH 2 inhibition by DSF potentiated 4HNE‐induced decrease in angiogenesis (P < 0.05 vs 4HNE at 2 h and P < 0.0005 vs 4HNE at 4 h) by decreasing the expressions of VEGFR2 (P < 0.005 for both mRNA and protein), SIRT 1 (P < 0.05), and ERG (P < 0.005) relative to 4HNE alone. Thus, we conclude that ALDH2 acts as a proangiogenic signaling molecule by alleviating the antiangiogenic effects of 4HNE in MCECs.
Influences of Ingredients and Bakers on the Bacteria and Fungi in Sourdough Starters and Bread

Sourdough starters are complex communities of yeast and bacteria which confer characteristic flavor and texture to sourdough bread. The microbes present in starters can be sourced from ingredients or the baking environment and are typically consistent over time. Herein, we show that even when the recipe and ingredients for starter and bread are identical, different bakers around the globe produce highly diverse starters which then alter bread acidity and flavor. Much of the starter microbial community comes from bread flour, but the diversity is also associated with differences in the microbial community on the hands of bakers. These results indicate that bakers may be a source for yeast and bacteria in their breads and/or that bakers’ jobs are reflected in their skin microbiome. ABSTRACT Sourdough starters are naturally occurring microbial communities in which the environment, ingredients, and bakers are potential sources of microorganisms. The relative importance of these pools remains unknown. Here, bakers from two continents used a standardized recipe and ingredients to make starters that were then baked into breads. We characterized the fungi and bacteria associated with the starters, bakers’ hands, and ingredients using 16S and internal transcribed spacer (ITS) rRNA gene amplicon sequencing and then measured dough acidity and bread flavor. Starter communities were much less uniform than expected, and this variation manifested in the flavor of the bread. Starter communities were most similar to those found in flour but shared some species with the bakers’ skin. While humans likely contribute microorganisms to the starters, the reverse also appears to be true. This bidirectional exchange of microorganisms between starters and bakers highlights the importance of microbial diversity on bodies and in our environments as it relates to foods. IMPORTANCE Sourdough starters are complex communities of yeast and bacteria which confer characteristic flavor and texture to sourdough bread. The microbes present in starters can be sourced from ingredients or the baking environment and are typically consistent over time. Herein, we show that even when the recipe and ingredients for starter and bread are identical, different bakers around the globe produce highly diverse starters which then alter bread acidity and flavor. Much of the starter microbial community comes from bread flour, but the diversity is also associated with differences in the microbial community on the hands of bakers. These results indicate that bakers may be a source for yeast and bacteria in their breads and/or that bakers’ jobs are reflected in their skin microbiome.
The Influence of Chronic Stress and Emotions on Eating Behavior Patterns and Weight among Young African American Women

This study examines the influence of chronic stress, varied positive and negative emotions on eating behaviors, and weight among 91 community-dwelling African American women 18–40 years old. Study measures include hair cortisol, Differential Emotional Scale IV, Eating Behavior Pattern Questionnaire, demographic form, waist circumference, and Body Mass Index (BMI). Analysis revealed positive emotions of interest (rs = .27, p = .011) and surprise (rs = .23, p = .029) were associated with low fat eating. Negative emotions of anger (rs = .23, p = .035), shyness (rs = .29, p = .006), and guilt (rs = .24, p = .022) were positively associated with emotional eating. Mediation analysis suggests that emotional eating mediates anger (indirect effect = 0.136), shyness (0.144), guilt (0.187), and BMI among young African American women. Chronic stress and positive and negative emotions impact eating behaviors and should be considered for successful weight management among African American women.
Bioorthogonal SERS Nanotags as a Precision Theranostic Platform for in vivo SERS Imaging and Cancer Photothermal Therapy.

Precise detection and effective treatment are crucial to prolong cancer patients' lives. Surface-enhanced Raman scattering (SERS) imaging coupled with photothermal therapy has been considered as a precise and effective strategy for cancer theranostics. Nevertheless, Raman reporters employed in literatures usually possessed multiple shift peaks in the fingerprint region which are overlapped with background signals from endogenous biological molecules. Herein, we fabricated a new kind of bioorthogonal Raman reporter and aptamer functionalized SERS nanotags. The SERS nanotags demonstrated a strong Raman signal at 2205 cm-1 in biologically Raman-silent region and recognized MCF-7 breast cancer cells for Raman imaging with high specificity. Laser irradiation induced serious toxicity of MCF-7 cells due to the excellent photothermal capability of the SERS nanotags. After intravenous administration of the SERS nanotags, tumor Raman spectral detection and mapping in living mice were successfully achieved. Further in vivo antitumor experiments manifested that the aptamer-modified SERS nanotags significantly restrained tumor growth after laser irradiation with 99% inhibition rate and good biocompatibility. These results clearly revealed that the SERS nanotags could serve as a novel and precise theranostic platform for in vivo cancer diagnosis and photothermal therapy.
Pre-collecting lymphatic vessels form detours following obstruction of lymphatic flow and function as collecting lymphatic vessels

Background Previously, we showed that lymphatic vessels (LVs) formed detours after lymphatic obstruction, contributing to preventing lymphedema. In this study, we developed detours using lymphatic ligation in mice and we identified the detours histologically. Methods and results Under anesthesia, both hindlimbs in mice were subcutaneously injected with Evans blue dye to detect LVs. We tied the right collecting LV on the abdomen that passes through the inguinal lymph node (LN) at two points. The right and left sides comprised the operation and sham operation sides, respectively. Lymphography was performed to investigate the lymph flow after lymphatic ligation until day 30, using a near-infrared fluorescence imaging system. Anti-podoplanin antibody and 5-ethynyl-2’-deoxyuridine (EdU) were used to detect LVs and lymphangiogenesis. Within 30 days, detours had developed in 62.5% of the mice. Detours observed between two ligation sites were enlarged and irregular in shape. Podoplanin+ LVs, which were located in the subcutaneous tissue of the upper panniculus carnosus muscle, connected to collecting LVs at the upper portion from the cranial ligation site and at the lower portion from the caudal ligation site. EdU+ cells were not observed in these detours. The sham operation side showed normal lymph flow and did not show enlarged pre-collecting LVs until day 30. Conclusions Detours after lymphatic ligation were formed not by lymphangiogenesis but through an enlargement of pre-collecting LVs that functioned as collecting LVs after lymphatic ligation. Further studies are required to explore the developmental mechanism of the lymphatic detour for treatment and effective care of lymphedema in humans.
A Systematic Review of Pediatric Phase I Trials in Oncology: Toxicity and Outcomes in the Era of Targeted Therapies.

BACKGROUND Pediatric phase I oncology trials have historically focused on safety and toxicity, with objective response rates (ORRs) <10%. Recently, with an emphasis on targeted approaches, response rates may have changed. We analyzed outcomes of recent phase I pediatric oncology trials. MATERIALS AND METHODS This was a systematic review of phase I pediatric oncology trials published in 2012-2017, identified through PubMed and EMBASE searches conducted on March 14, 2018. Selection criteria included full-text articles with a pediatric population, cancer diagnosis, and a dose escalation schema. Each publication was evaluated for patient characteristics, therapy type, trial design, toxicity, and response. RESULTS Of 3,431 citations, 109 studies (2,713 patients) met eligibility criteria. Of these, 78 (72%) trials incorporated targeted therapies. Median age at enrollment/trial was 11 years (range 3-21 years). There were 2,471 patients (91%) evaluable for toxicity, of whom 300 (12.1%) experienced dose-limiting toxicity (DLT). Of 2,143 patients evaluable for response, 327 (15.3%) demonstrated an objective response. Forty-three (39%) trials had no objective responses. Nineteen trials (17%) had an ORR >25%, of which 11 were targeted trials and 8 were combination cytotoxic trials. Targeted trials demonstrated a lower DLT rate compared with cytotoxic trials (10.6% vs. 14.7%; p = .003) with similar ORRs (15.0% vs. 15.9%; p = .58). CONCLUSION Pediatric oncology phase I trials in the current treatment era have an acceptable DLT rate and a pooled ORR of 15.3%. A subset of trials with target-specific enrollment or combination cytotoxic therapies showed high response rates, highlighting the importance of these strategies in early phase trials. IMPLICATIONS FOR PRACTICE Enrollment in phase I oncology trials is crucial for development of novel therapies. This systematic review of phase I pediatric oncology trials provides an assessment of outcomes of phase I trials in children, with a specific focus on the impact of targeted therapies. These data may aid in evaluating the landscape of current phase I options for patients and enable more informed communication regarding risk and benefit of phase I clinical trial participation. The results also suggest that, in the current treatment era, there is a rationale to increase earlier access to targeted therapy trials for this refractory patient population.
An Assessment of Surface Water Detection Methods for Water Resource Management in the Nigerien Sahel

Water is a scarce, but essential resource in the Sahel. Rainfed ephemeral ponds and lakes that dot the landscape are necessary to the livelihoods of smallholder farmers and pastoralists who rely on these resources to irrigate crops and hydrate cattle. The remote location and dispersed nature of these water bodies limits typical methods of monitoring, such as with gauges; fortunately, remote sensing offers a quick and cost-effective means of regularly measuring surface water extent in these isolated regions. Dozens of operational methods exist to use remote sensing to identify waterbodies, however, their performance when identifying surface water in the semi-arid Sahel has not been well-documented and the limitations of these methods for the region are not well understood. Here, we evaluate two global dynamic surface water datasets, fifteen spectral indices developed to classify surface water extent, and three simple decision tree methods created specifically to identify surface water in semi-arid environments. We find that the existing global surface water datasets effectively minimize false positives, but greatly underestimate the presence and extent of smaller, more turbid water bodies that are essential to local livelihoods, an important limitation in their use for monitoring water availability. Three of fifteen spectral indices exhibited both high accuracy and threshold stability when evaluated over different areas and seasons. The three simple decision tree methods had mixed performance, with only one having an overall accuracy that compared to the best performing spectral indices. We find that while global surface water datasets may be appropriate for analysis at the global scale, other methods calibrated to the local environment may provide improved performance for more localized water monitoring needs.
A Cost and Efficiency Analysis of the WALANT Technique for the Management of Trigger Finger in a Procedure Room of a Major City Hospital

Background: The “Wide Awake Local Anesthesia No Tourniquet” (WALANT) technique is gaining popularity in hand surgery owing to its benefits of reduced cost, shorter hospital stay, improved safety, and the ability to perform active intraoperative examinations. The aim of this study is to analyze the cost savings and efficiency of performing A1 pulley release for treatment of trigger finger using the WALANT technique in a major city hospital procedure room (PR) as compared with the standard tourniquet, operating room (OR) approach. Methods: Patients who underwent trigger finger release between 2012 and 2017 were identified. Demographic and procedural information were obtained. Patients were followed for an average of 82 and 242 days in the PR and OR groups, respectively. Results: Thirty-nine PR and 37 OR patients were identified. Case length and turnover time were shorter in the PR group [21.4 ± 7 versus 23.5 ± 14.3 min (P = 0.942) and 31.1 ± 11.1 and 65.3 ± 17.7 min (P < 0.001), respectively). The cost of the instrument tray utilized was calculated as $3,304.25 in the main OR and $993.79 in the PR. Cost per minute for all personal services in the OR was calculated to be $44/min, a cost that was virtually absent in the PR. Complication rates did not differ between both groups. Conclusion: Performing A1 pulley release for treatment of trigger finger using the WALANT technique is both cost effective and time efficient compared to performing the same procedure in the main OR of a major city public hospital.
Study of the Simultaneous Utilization of Mechanical Water Foaming and Zeolites and Their Effects on the Properties of Warm Mix Asphalt Concrete

The paper aimed at assessing the feasibility of using natural zeolites as a mineral filler substitute for asphalt mixtures produced at around 120 °C temperatures with a water foamed binder and compacted at 100 °C. The tests utilized the AC 16 asphalt concrete mixture intended for the binder and base course with the mineral filler fraction amounting to 4% by wt. comprising limestone dust and zeolites (when added). A reference hot mix and warm mix with foamed bitumen were compared to two mixes with zeolites, with one containing 0.4% of a water-modified (20% moisture content) zeolite and the second containing 1.0% of natural air-dried zeolite. The investigations included: assessment of campactability using a gyratory compactor, air void content, indirect tensile strength before and after conditioning with one freeze-thaw cycle, and the resulting resistance to moisture and frost damage. The mixtures with zeolites exhibited decreased compactability when compared to reference mixes, which the Marshall samples confirmed. The mechanical properties have also deteriorated in zeolite-bearing mixtures, which was partially accounted to the decreased compaction level. It was concluded that the temperature of the mixture production was too low for the zeolite water to significantly improve the compactablity of the asphalt mixture and its mechanical parameters.
Identifying playing talent in professional football using artificial neural networks

ABSTRACT The aim of the current study was to objectively identify position-specific key performance indicators in professional football that predict out-field players league status. The sample consisted of 966 out-field players who completed the full 90 minutes in a match during the 2008/09 or 2009/10 season in the Football League Championship. Players were assigned to one of three categories (0, 1 and 2) based on where they completed most of their match time in the following season, and then split based on five playing positions. 340 performance, biographical and esteem variables were analysed using a Stepwise Artificial Neural Network approach. The models correctly predicted between 72.7% and 100% of test cases (Mean prediction of models = 85.9%), the test error ranged from 1.0% to 9.8% (Mean test error of models = 6.3%). Variables related to passing, shooting, regaining possession and international appearances were key factors in the predictive models. This is highly significant as objective position-specific predictors of players league status have not previously been published. The method could be used to aid the identification and comparison of transfer targets as part of the due diligence process in professional football.
An international multi-center serum protein electrophoresis accuracy and M-protein isotyping study. Part II: limit of detection and follow-up of patients with small M-proteins

Abstract Background Electrophoretic methods to detect, characterize and quantify M-proteins play an important role in the management of patients with monoclonal gammopathies (MGs). Significant uncertainty in the quantification and limit of detection (LOD) is documented when M-proteins are <10 g/L. Using spiked sera, we aimed to assess the variability in intact M-protein quantification and LOD across 16 laboratories. Methods Sera with normal, hypo- or hyper-gammaglobulinemia were spiked with daratumumab or elotuzumab, with concentrations from 0.125 to 10 g/L (n = 62) along with a beta-migrating sample (n = 9). Laboratories blindly analyzed samples according to their serum protein electrophoresis (SPEP)/isotyping standard operating procedures. LOD and intra-laboratory percent coefficient of variation (%CV) were calculated and further specified with regard to the method (gel/capillary electrophoresis [CZE]), gating strategy (perpendicular drop [PD]/tangent skimming [TS]), isotyping (immunofixation/immunosubtraction [ISUB]) and manufacturer (Helena/Sebia). Results All M-proteins ≥1 g/L were detected by SPEP. With isotyping the LOD was moderately more sensitive than with SPEP. The intensity of polyclonal background had the biggest negative impact on LOD. Independent of the method used, the intra-laboratory imprecision of M-protein quantification was small (mean CV = 5.0%). Low M-protein concentration and high polyclonal background had the strongest negative impact on intra-laboratory precision. All laboratories were able to follow trend of M-protein concentrations down to 1 g/L. Conclusions In this study, we describe a large variation in the reported LOD for both SPEP and isotyping; overall LOD is most affected by the polyclonal immunoglobulin background. Satisfactory intra-laboratory precision was demonstrated. This indicates that the quantification of small M-proteins to monitor patients over time is appropriate, when subsequent testing is performed within the same laboratory.