Miracle-dz/UniFAR-FTUs huggingface dataset:
Association of fluid balance with mortality in sepsis is modified by admission hemoglobin levels: A large database study

Purpose Sepsis involves a dysregulated inflammatory response to infection that leads to organ dysfunction. Early fluid resuscitation has been advocated by the Surviving Sepsis Campaign guidelines. However, recent studies have shown that a positive fluid balance is associated with increased mortality in septic patients. We investigated if haemoglobin levels on admission to the intensive care unit (ICU) could modify the association of fluid balance with mortality in patients with sepsis. We hypothesized that with increasing fluid balance, patients with moderate anemia (hemoglobin 7-10g/dL) would have poorer outcomes compared to those without moderate anemia (hemoglobin >10g/dL). Materials and methods This retrospective study utilized the Medical Information Mart for Intensive Care-III (MIMIC-III) database. Patients with sepsis, as identified by the International Classification of Diseases, 9th, Clinical Modification codes, were studied. Patients were stratified into those with and without moderate anemia at ICU admission. We investigated the influence of fluid balance measured within 24 hours of ICU admission on 28-day mortality for both patient groups using multivariable logistic regression models. Subgroup and sensitivity analyses were conducted. Results 8,132 patients (median age 68.6 years, interquartile range 55.1–79.8 years; 52.8% female) were included. Increasing fluid balance (in L) was associated with a significantly decreased risk of 28-day mortality in patients without moderate anemia (OR 0.91, 95%CI 0.84–0.97, p = 0.005, at 6-hour). Conversely, increasing fluid balance was associated with a significantly increased risk of 28-day mortality in patients with moderate anemia (OR 1.05, 95% CI 1.01–1.1, p = 0.022, at 24-hour). Interaction analyses showed that mortality was highest when haemoglobin decreased in patients with moderate anemia who had the most positive fluid balance. Multiple subgroups and sensitivity analyses yielded consistent results. Conclusions In septic patients admitted to ICU, admission hemoglobin levels modified the association between fluid balance and mortality and are an important consideration for future fluid therapy trials.
The Use of Magnesium Sulfate and Peripheral Nerve Blocks

Supplemental Digital Content is available in the text. Objectives: With the popularization of ultrasound, nerve blocks have been widely implemented in current clinical practice. Although, they have seen limited success due to their shorter duration and suboptimal analgesia. Magnesium sulfate as a local anesthetic adjuvant for peripheral nerve blocks could enhance the effects of local anesthetics. However, previous investigations have not thoroughly investigated the analgesic efficacy of magnesium sulfate as an adjunct to local anesthetics for peripheral nerve blocks. Thus, we attempted to fill the gap in the existing literature by conducting a meta-analysis. Materials and Methods: We performed of a quantitative systematic review of randomized controlled trials published between May 30, 2011 and November 1, 2018. Inclusion criteria were: (1) magnesium sulfate used as adjuvant mixed with local anesthetic for nerve blockade, (2) complete articles and published abstracts of randomized controlled trials, (3) English language. Primary and Secondary Outcome Measures: The primary outcome measures were time of onset, total duration of the sensory blockade, and Visual Analog Scale pain scores. The secondary outcomes were postoperative oral and intravenous analgesics consumption and the incidence of nausea and vomiting. Results: The 21 trials analyzed in this study included 1323 patients. Magnesium sulfate effectively prolonged the total duration of sensory blockade (mean difference [MD]=114.59 min, 95% confidence interval [CI]: 89.31-139.88), reducing Visual Analog Scale pain scores at 6 hours (MD=1.36 points, 95% CI: −2.09 to −0.63) and 12 hours (MD=1.54 points, 95% CI: −2.56 to −0.53) postsurgery. Magnesium sulfate also effectively reduced postoperative analgesic use within 24 hours postsurgery (standard MD=−2.06, 95% CI: −2.67 to −1.35). Furthermore, adjuvant magnesium sulfate significantly reduced the incidence of nausea and vomiting after transversus abdominis plane blockade (odds ratio: 0.39, 95% CI: 0.18-0.81). Conclusion: Adjuvant magnesium sulfate enhanced the anesthetic effects of local anesthetics and improved postoperative analgesia following the perineural blockade.
Quality of Sex Life and Perceived Sexual Pleasure of PrEP Users in the Netherlands

ABSTRACT Next to its benefits for HIV prevention, PrEP may have psychosocial benefits relating to improved quality of sex life. The aim of the current study was to investigate the onset of changes in the quality of sex life and sexual pleasure of PrEP users in the first months of commencing PrEP use. Moreover, we investigated what factors were related to the quality of sex life of PrEP users. We recruited 145 participants via the Dutch PrEP-advocacy website PrEPnu.nl, and they received follow-up questionnaires after three and six months. We found that PrEP users reported an increase in the quality of their sex life, which was related to reduced fear of HIV since they started using PrEP but not to decreased condom use. PrEP users were more interested in experimenting with sex practices, but they did not always feel more desirable as a sex partner because of PrEP use. Health-care providers and health promotion campaigns could emphasize the positive effects of PrEP on the quality of sex life, in addition to the HIV-preventive effects of PrEP, to decrease PrEP stigma and increase PrEP uptake.
Concentration Dependence of Nonlinear Rheological Properties of Hydrophobically Modified Ethoxylated Urethane Aqueous Solutions

For aqueous solutions of a representative telechelic polymer, hydrophobically modified ethoxylated urethane (HEUR), a recent transient network model suggested that sparse and dense HEUR networks are formed at low and high HEUR concentrations c thereby exhibiting different rheological features [Uneyama, T. ; Suzuki, S. ; Watanabe, H. Phys. Rev. E2012, 86, 031802]. In this study, we examined those differences for nonlinear rheological behavior of HEUR solutions (with MHEUR = 4.6 × 104 and c = 1–10 wt %) under steady shear at 25 °C to test the model. For rather dilute solutions (c ≤ 3 wt %), the steady state viscosity η exhibited crossover from the linear (zero-shear) behavior to thickening and further to thinning with increasing the shear rate γ, whereas the first normal stress coefficient Ψ1 remained in the linear regime up to intermediate γ (where η exhibited the thickening) and then decreased with γ in the thinning regime of η. In contrast, for concentrated solutions (c ≥ 4 wt %), η exhibited no thicken.
Combined impact of HLA-allele matching and the CD34-positive cell dose on optimal unit selection for single-unit cord blood transplantation in adults

Abstract The combined effects of HLA-allele matching at six-loci (HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1) and CD34+ cell dose on clinical outcomes were analyzed in 1,226 adult cases with single-unit unrelated cord blood transplantation. In the six-loci analysis, low HLA-allele matches did not significantly increase the overall mortality compared to higher matches, whereas in the five-loci analysis excluding HLA-DPB1, they caused a higher overall mortality (HR 1.42, p = .002), possibly due to the graft-versus-leukemia effect of HLA-DPB1 mismatches. A lower CD34+ cell dose (<.50 × 105/kg) resulted in higher mortality and lower engraftment; these inferior outcomes were offset by high HLA-allele matches (7-10/10 match), while the inferior outcomes of low HLA-allele matches were improved by increasing the CD34+ cell dose. Consideration of the combined effects of the CD34+ cell dose and HLA matching may expand the options for transplantable units when HLA matching or the CD34+ cell dose is inadequate.
Non-Selective Thoracic Computed Tomography in Trauma Patients Results in Injury Severity Score Inflation

Introduction Extensive research relying on Injury Severity Scores (ISS) reports a mortality benefit from routine non-selective thoracic CTs (an integral part of pan-computed tomography (pan-CT)s). Recent research suggests this mortality benefit may be artifact. We hypothesized that the use of pan-CTs inflates ISS categorization in patients, artificially affecting admission rates and apparent mortality benefit. Methods Eight hundred and eleven patients were identified with an ISS >15 with significant findings in the chest area. Patient charts were reviewed and scores were adjusted to exclude only occult injuries that did not affect treatment plan. Pearson chi-square tests and multivariable logistic regression were used to compare adjusted cases vs non-adjusted cases. Results After adjusting for inflation, 388 (47.8%) patients remained in the same ISS category, 378 (46.6%) were reclassified into 1 lower ISS category, and 45 (5.6%) patients were reclassified into 2 lower ISS categories. Patients reclassified by 1 category had a lower rate of mortality (P < 0.001), lower median total hospital LOS (P < .001), ICU days (P < .001), and ventilator days (P = 0.008), compared to those that remained in the same ISS category. Conclusion Injury Severity Score inflation artificially increases survival rate, perpetuating the increased use of pan-CTs. This artifact has been propagated by outdated mortality prediction calculation methods. Thus, prospective evaluations of algorithms for more selective CT scanning are warranted.
Tetrahydroxanthohumol, a xanthohumol derivative, attenuates high-fat diet-induced hepatic steatosis by antagonizing PPARγ

We previously reported xanthohumol (XN), and its synthetic derivative tetrahydro-XN (TXN), attenuates high-fat diet (HFD)-induced obesity and metabolic syndrome in C57Bl/6J mice. The objective of the current study was to determine the effect of XN and TXN on lipid accumulation in the liver. Non-supplemented mice were unable to adapt their caloric intake to 60% HFD, resulting in obesity and hepatic steatosis; however, TXN reduced weight gain and decreased hepatic steatosis. Liver transcriptomics indicated that TXN might antagonize lipogenic PPARγ actions in vivo. XN and TXN inhibited rosiglitazone-induced 3T3-L1 cell differentiation concomitant with decreased expression of lipogenesis-related genes. A peroxisome proliferator activated receptor gamma (PPARγ) competitive binding assay showed that XN and TXN bind to PPARγ with an IC50 similar to pioglitazone and 8–10 times stronger than oleate. Molecular docking simulations demonstrated that XN and TXN bind in the PPARγ ligand-binding domain pocket. Our findings are consistent with XN and TXN acting as antagonists of PPARγ.
Association of Weight Loss With Type 2 Diabetes Remission Among Adults in Medically Underserved Areas: A Retrospective Cohort Study

Purpose: To examine the association between weight loss and type 2 diabetes remission among vulnerable populations living in medically underserved areas of the Mid-Southern United States. Design: Quantitative, retrospective cohort study. Setting: 114 ambulatory sites and 5 adults’ hospitals in the Mid-South participating in a regional diabetes registry. Participants: 9,900 adult patients with type 2 diabetes, stratified by remission status, with 1 year of baseline electronic medical record data, and 1 year of follow-up data for the 2015-2018 study period. Measures: The outcomes were diabetes remissions, categorized as any remission, partial remission, and complete remission based on the guidelines of the American Diabetes Association. The exposure was weight loss, calculated by the change in the Body Mass Index (BMI) as a proxy measure. Analysis: χ2 tests, Fisher’s exact tests, and the Mann-Whitney U-test were used to examine the differences in patient characteristics by remission status across the 3 remission categories, as appropriate. Multiple multivariable logistic regressions adjusting for confounders were performed to estimate the adjusted odds ratios (aORs) for the associations between weight loss and diabetes remission. Results: Among 9,900 patients identified, a reduction of 0.3 kg/m2 (standard deviation: 2.5) in the average BMI from the baseline to the follow-up was observed. 10.8% achieved any type of remission, with 9.8% for partial and 1.0% for complete remissions. Greater weight loss was significantly associated with an increased likelihood of any (aOR = 1.07, 95% confidence interval (CI), 1.06-1.08), partial (aOR 1.06, 95% CI, 1.04-1.07), and complete diabetes remission (aOR 1.10, 95% CI, 1.07-1.13). Conclusions: Weight loss is significantly associated with diabetes remission among patients living in medically underserved areas, but complete remission is rare.
Genetic architecture of 11 organ traits derived from abdominal MRI using deep learning

Cardiometabolic diseases are an increasing global health burden. While socioeconomic, environmental, behavioural, and genetic risk factors have been identified, a better understanding of the underlying mechanisms is required to develop more effective interventions. Magnetic resonance imaging (MRI) has been used to assess organ health, but biobank-scale studies are still in their infancy. Using over 38,000 abdominal MRI scans in the UK Biobank, we used deep learning to quantify volume, fat, and iron in seven organs and tissues, and demonstrate that imaging-derived phenotypes reflect health status. We show that these traits have a substantial heritable component (8–44%) and identify 93 independent genome-wide significant associations, including four associations with liver traits that have not previously been reported. Our work demonstrates the tractability of deep learning to systematically quantify health parameters from high-throughput MRI across a range of organs and tissues, and use the largest-ever study of its kind to generate new insights into the genetic architecture of these traits.
Semi-analytical modelling and evaluation of uniformly doped silicene nanotransistors for digital logic gates

Silicene has attracted remarkable attention in the semiconductor research community due to its silicon (Si) nature. It is predicted as one of the most promising candidates for the next generation nanoelectronic devices. In this paper, an efficient non-iterative technique is employed to create the SPICE models for p-type and n-type uniformly doped silicene field-effect transistors (FETs). The current-voltage characteristics show that the proposed silicene FET models exhibit high on-to-off current ratio under ballistic transport. In order to obtain practical digital logic timing diagrams, a parasitic load capacitance, which is dependent on the interconnect length, is attached at the output terminal of the logic circuits. Furthermore, the key circuit performance metrics, including the propagation delay, average power, power-delay product and energy-delay product of the proposed silicene-based logic gates are extracted and benchmarked with published results. The effects of the interconnect length to the propagation delay and average power are also investigated. The results of this work further envisage the uniformly doped silicene as a promising candidate for future nanoelectronic applications.
Identification of Novel Therapeutic Targets for Fibrolamellar Carcinoma Using Patient Derived Xenografts and Direct from Patient Screening.

To repurpose therapeutics for fibrolamellar carcinoma (FLC) we developed and validated patient-derived xenografts (PDX) from surgical resections. Most agents used clinically, and inhibitors of oncogenes overexpressed in FLC showed little efficacy on PDX. A high-throughput functional drug screen found primary and metastatic FLC were vulnerable to clinically available inhibitors of TOPO1 and HDAC, and to napabucasin. Napabucasin's efficacy was mediated through reactive oxygen species and inhibition of translation initiation, and specific inhibition of eIF4A was effective. The sensitivity of each PDX line inversely correlated with expression of the anti-apoptotic protein Bcl-xL, and inhibition of Bcl-xL synergized with other drugs. Screening directly on cells dissociated from patient resections validated these results. This demonstrates that a direct functional screen on patient tumors provides therapeutically informative data within a clinically useful time frame. Identifying these novel therapeutic targets and combination therapies is an urgent need, as effective therapeutics for FLC are currently unavailable.
Reconstructing Severe Lower Extremity Skin Necrosis in a Pediatric Patient

ABSTRACT Purpura fulminans can result in significant full-thickness wounds, posing a challenge in the pediatric population, given the paucity of donor sites for reconstruction. The authors present the case of an 11-month-old patient for whom a split-thickness skin allograft (TheraSkin) was successfully implemented as a temporizing measure for a large leg wound.
A prospective study to establish the minimal clinically important difference of the Mini-BESTest in individuals with stroke

Objective: To determine the minimal clinically important difference of the Mini-BESTest in individuals’ post-stroke. Design: Prospective cohort study. Setting: Outpatient stroke rehabilitation. Subjects: Fifty outpatients with stroke with a mean (SD) age of 60.8 (9.4). Intervention: Outpatients with stroke were assessed with the Mini-BESTest before and after a course of conventional rehabilitation. Rehabilitation sessions occurred one to two times/week for one hour and treatment duration was 1.3–42 weeks (mean (SD) = 17.4(10.6)). Main measures: We used a combination of anchor- and distribution-based approaches including a global rating of change in balance scale completed by physiotherapists and patients, the minimal detectable change with 95% confidence, and the optimal cut-point from receiver operating characteristic curves. Results: The average (SD) Mini-BESTest score at admission was 18.2 (6.5) and 22.4 (5.2) at discharge (effect size: 0.7) (P = 0.001). Mean change scores on the Mini-BESTest for patient and physiotherapist ratings of small change were 4.2 and 4.3 points, and 4.7 and 5.3 points for substantial change, respectively. The minimal detectable change with 95% confidence for the Mini-BESTest was 3.2 points. The minimally clinical importance difference was determined to be 4 points for detecting small changes and 5 points for detecting substantial changes. Conclusions: A change of 4–5 points on the Mini-BEST is required to be perceptible to clinicians and patients, and beyond measurement error. These values can be used to interpret changes in balance in stroke rehabilitation research and practice.
Heritable consequences of paternal nicotine exposure: from phenomena to mechanisms

Abstract Our understanding of the interactions between genetic and environmental factors in shaping behavioral phenotypes has expanded to include environment-induced epigenetic modifications and the intriguing possibility of their association with heritable behavioral phenotypes. The molecular basis of heritability of phenotypes arising from environment-induced epigenetic modifications is not well defined yet. However, phenomenological evidence in favor of it is accumulating rapidly. The resurgence of interest has led to focus on epigenetic modification of germ cells as a plausible mechanism of heritability. Perhaps partly because of practical reasons such as ease of access to male germ cells compared to female germ cells, attention has turned toward heritable effects of environmental influences on male founders. Public health implications of heritable effects of paternal exposures to addictive substances or to psycho-social factors may be enormous. Considering nicotine alone, over a billion people worldwide use nicotine-containing products, and the majority are men. Historically, the adverse effects of nicotine use by pregnant women received much attention by scientists and public policy experts alike. The implications of nicotine use by men for the physical and mental well-being of their children were not at the forefront of research until recently. Here, we review progress in the emerging field of heritable effects of paternal nicotine exposure and its implications for behavioral health of individuals in multiple generations. Summary sentence Nicotine exposure of male experimental animals produces adverse influences not only on somatic and germ cells of the exposed males but also on the brain and behavior of multiple generations descending from the males. Graphical Abstract
Assessment of P- to delta-wave interval and its relationship with accessory pathway properties in patients with pre-excitation.

BACKGROUND The first clinical manifestation of the Wolff-Parkinson-White syndrome in previously asymptomatic individuals may be sudden cardiac death. The options for non-invasive risk stratification are limited in the current era beyond ambulatory rhythm monitoring and an exercise stress test. In our study, we sought to investigate whether there was a relationship between the shortest measured P- to delta-wave time interval (PDI) on the conduction properties of surface electrocardiogram and accessory pathways expressed as antegrade effective refractory period (APERP). METHODS Demographic data, symptom status, electrocardiograms (ECG) and intra-cardiac recordings of invasive electrophysiology testing of 103 patients who underwent accessory pathway ablation procedures were collected. Exclusion criteria were: (1) intermittently occurring pre-excitation, which was detected in previous ECGs, (2) delta-wave resolution on treadmill test, (3) presence of multiple accessory pathways, and (4) accessory pathway locations other than the septum. The PDI was measured as the time interval from the beginning of the P wave to the earliest upstroke or downstroke of the delta wave on V1 and V2 derivations of the surface ECG, and the shortest measurement was recorded. RESULTS Patients were grouped into two groups: group I, if APERP was < 240 ms and group II if APERP was ≥ 240 ms. PDI was significantly shorter in group II. By correlation analysis, a positive and moderate correlation between PDI and APERP (r = 0.598, p < 0.001) and PDI and age (r = 0.800, p < 0.001) was found, and a negative and moderate correlation between PDI and inducible AF (r = -492, p < 0.001). The best cut-off value for PDI to predict APERP ≥ 240 was 90.5 ms with a sensitivity of 80% and a specificity of 83%. CONCLUSIONS Our results demonstrate that there was a strong correlation between the P- to delta-wave interval and universally accepted risk factors, such as low age, low APERP and atrial fibrillation inducibility. Further studies with larger patient groups and follow-up data are needed to appraise its predictive value.