Miracle-dz/UniFAR-FTUs huggingface dataset:
Endocarditis and the impact of intravenous drug use: a cohort study

Abstract Objectives This cohort study is a comparison of infective endocarditis in intravenous drug users (IDUs) and non-IDUs within a single tertiary centre. We aim to quantify and describe the factors that influence prognosis and microbiological characteristics. Method All consecutive admissions to a tertiary referral hospital in the north of England with a diagnosis of endocarditis from April 2013 to January 2020 were identified. Outcomes were all-cause mortality at 30 days, 12 months and 3 years, length of stay and progression to surgery. Results A total of 303 cases were identified via clinical coding of which 287 cases of endocarditis were confirmed. First episode endocarditis was then confirmed in 263 episodes, 44 in IDUs and 219 in non-IDUs. Methicillin sensitive Staphylococcus aureus (MSSA) was the most common organism seen overall, significantly more so in IDU than non-IDU cases (29/44 [65.9%] vs. 51/219 [23.3%], p < .001). Overall progression to valve surgery was similar between the two groups (92/219 [42.0%] vs. 19/44[43.2%], p = .886). In IDUs 30-d survival was 93% (80–98) and 3-year survival 47% (30–63%). In non-IDU 30-d survival was 88% (83–92%) and 60% (53–67%) at 3 years. Of the 19 IDUs who underwent valve surgery 7 (37%) survived to study completion without reinfection and 8 (42%) died following recurrent endocarditis. Conclusions We demonstrate that prognosis in IDUs is worse than previously described, particularly in those undergoing valve surgery. This is despite comparable receipt of inpatient treatment to non-IDUs as demonstrated by equal length of stay and rates of surgery. Clinicians should consider the role of addictions services on discharge to break the cycle of reinfection.
Clinicopathologic and Genomic Landscape of Breast Carcinoma Brain Metastases.

BACKGROUND Among breast carcinoma patients with metastatic disease, 15-30% will eventually develop brain metastases. We examined the genomic landscape of a large cohort of breast carcinoma brain metastases (BCBMs) and compared them to a cohort of primary breast carcinomas (BCs). MATERIAL AND METHODS We retrospectively analyzed 733 BCBMs tested with comprehensive genomic profiling (CGP) and compared them to 10,772 primary breast carcinomas (not-paired) specimens. For a subset of 16 triple-negative breast carcinoma (TNBC)-brain metastasis (BM) samples, PD-L1 immunohistochemistry was performed concurrently. RESULTS A total of 733 consecutive BCBMs were analyzed. Compared to primary BCs, BCBMs were enriched for genomic alterations in TP53 (72.0%, 528/733), ERBB2 (25.6%. 188/733), RAD21 (14.1%, 103/733), NF1 (9.0%, 66/733), BRCA1 (7.8%, 57/733), and ESR1 (6.3%,46/733) (p < 0.05 for all comparisons). Immune checkpoint inhibitor (ICPI) biomarkers such as tumor mutational burden (TMB)-High (16.2%, 119/733), microsatellite instability (MSI)-High (1.9%, 14/733), CD274 amplification (3.6%, 27/733), and APOBEC mutational signature (5.9%, 43/733) were significantly higher in the BCBM cohort compared to the primary BC cohort (p < 0.05 for all comparisons). When using both CGP and PD-L1 IHC, 37.5% (6/16) of the TNBC brain metastasis patients were eligible for atezolizumab based on PD-L1 IHC, and 18.8% (3/16) were eligible for pembrolizumab based on TMB-High status. CONCLUSION We found a high prevalence of clinically relevant genomic alterations in BCBM patients, suggesting that tissue acquisition (surgery) and or cerebrospinal fluid (CSF) for CGP in addition to CGP of the primary tumor may be clinically warranted. IMPLICATIONS FOR PRACTICE We found a high prevalence of clinically relevant genomic alterations in BCBM patients, suggesting that tissue acquisition (surgery) and or cerebrospinal fluid (CSF) for CGP in addition to CGP of the primary tumor may be clinically warranted. In addition, we identified higher positive rates for FDA-approved immunotherapy biomarkers detected by CGP in BCBM patients, opening the possibility for new on-label treatments. Last, we noted limited correlation between TMB and PD-L1 IHC which exemplifies the importance to test with both PD-L1 IHC and CGP for ICPI eligibility of TNBC patients with brain metastases.
Choice of measurement approach for area-level social determinants of health and risk prediction model performance

ABSTRACT Objective The objective of this paper is to provide empirical guidance by comparing the performance of six different area-level SDoH measurement approaches in predicting patient referral to a social worker and hospital admission after a primary care visit. Methods We compared the performance of six area-level SDoH measurement approaches in predicting patient referral to a social worker and hospital admission after a primary care visit using random forest classification algorithm. Data came from 209,605 patient encounters at a federally qualified health center. Models with each area-based measurement approach were compared against the patient-level data only model using area under the curve, sensitivity, specificity, and precision. Results Addition of area-level features to patient-level data improved the overall performance of models predicting need for a social worker referral. Entering area-level measures as individual features resulted in highest model performance. Conclusion Researchers seeking to include area-level SDoH measures in risk prediction may be able to forego more complex measurement approaches.
Spatiotemporal variability of fire effects on soil carbon and nitrogen: A global meta‐analysis

A consensus about the fire‐related soil carbon (C) and nitrogen (N) impacts that determine soil health and ecosystem services at the global scale remains elusive. Here, we conducted a global meta‐analysis of 3173 observations with 1444, 1334, 228, and 167 observations for soil C, N, pyrogenic C (PyC), and the percent of PyC to total organic C (PyC/TOC) from 296 field studies. Results showed that fire significantly decreased soil C (−15.2%) and N (−14.6%) but increased soil PyC (40.6%) and PyC/TOC (30.3%). Stronger negative fire impacts on soil C and N were found in tropical and temperate climates than in Mediterranean and subtropical climates; stronger effects were found in forest ecosystems than in non‐forest ecosystems. Wildfire and high‐severity fire led to greater soil C and N losses than prescribed and low‐severity fires, respectively, while they promoted greater increases in soil PyC and PyC/TOC than prescribed and low‐severity fires, respectively. However, soil C and N recovered to control levels approximately 10 years after fire, which is a shorter period than previously determined. These results suggest that fire‐induced PyC production should be accounted for in the C budget under global change. These results will improve our knowledge of the spatiotemporal variability of fire effects on soil C and N storage and have implications for fire management and ecosystem recovery.
Argo-Two Decades: Global Oceanography, Revolutionized.

Argo, an international, global observational array of nearly 4,000 autonomous robotic profiling floats, each measuring ocean temperature and salinity from 0 to 2,000 m on nominal 10-day cycles, has revolutionized physical oceanography. Argo started at the turn of the millennium, growing out of advances in float technology over the previous several decades. After two decades, with well over 2 million profiles made publicly available in real time, Argo data have underpinned more than 4,000 scientific publications and improved countless nowcasts, forecasts, and projections. We review a small subset of those accomplishments, such as elucidating remarkable zonal jets spanning the deep tropical Pacific; increasing understanding of ocean eddies and the roles of mixing in shaping water masses and circulation; illuminating interannual to decadal ocean variability; quantifying, in concert with satellite data, contributions of ocean warming and ice melting to sea level rise; improving coupled numerical weather predictions; and underpinning decadal climate forecasts. Expected final online publication date for the Annual Review of Marine Science, Volume 14 is January 2022. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
Synergistic roles for human U1 snRNA stem-loops in pre-mRNA splicing

ABSTRACT During spliceosome assembly, interactions that bring the 5′ and 3′ ends of an intron in proximity are critical for the production of mature mRNA. Here, we report synergistic roles for the stem-loops 3 (SL3) and 4 (SL4) of the human U1 small nuclear RNA (snRNA) in maintaining the optimal U1 snRNP function, and formation of cross-intron contact with the U2 snRNP. We find that SL3 and SL4 bind distinct spliceosomal proteins and combining a U1 snRNA activity assay with siRNA-mediated knockdown, we demonstrate that SL3 and SL4 act through the RNA helicase UAP56 and the U2 protein SF3A1, respectively. In vitro analysis using UV crosslinking and splicing assays indicated that SL3 likely promotes the SL4-SF3A1 interaction leading to enhancement of A complex formation and pre-mRNA splicing. Overall, these results highlight the vital role of the distinct contacts of SL3 and SL4 in bridging the pre-mRNA bound U1 and U2 snRNPs during the early steps of human spliceosome assembly.
The protein modifier SUMO is critical for integrity of the Arabidopsis shoot apex at warm ambient temperatures.

SUMO is a protein modification whose conjugate levels peak during acute heat stress. We find that SUMO is also critical for plant longevity when Arabidopsis experiences a prolonged non-damaging period of only 28 degrees Celsius. Remarkably, this thermo-lethality at 28 degrees was not seen with any other mutant of the SUMO pathway tested. Autoimmunity due to low SUMO1/2 expression levels was not causal for this thermo-lethality. The role of SUMO for thermo-resilience was also distinct from its requirement for thermomorphogenesis - a growth response triggered by the same warm temperature, as only the latter response was dependent on the SUMO ligase SIZ1 as well. Thermo-resilience at 28 degrees Celsius and (acquired) thermotolerance (a response that allows plants to recover and acclimate to brief extreme temperatures) both depend on the HEAT SHOCK TRANSCRIPTION FACTOR A1 (HSFA1). Acquired thermotolerance was, however, normal in the sumo1/2 knockdown mutant. Thus, SUMO-dependent thermo-resilience is potentially controlled in a different way than the protein damage pathway that underpins thermotolerance. Close inspection of shoot apices revealed that the cell patterning and tissue integrity of the shoot apex of the SUMO1/2 knockdown mutant was lost at 28, but not 22 degrees Celsius. We thus describe a novel SUMO-dependent phenotype.
Human leptospirosis in the municipality of São Paulo, SP, Brazil: distribution and trend according to sociodemographic factors, 2007-2016.

OBJECTIVES This study aimed to describe the incidence and proportional lethality of human leptospirosis in the municipality of São Paulo, between 2007 and 2016, according to sociodemographic factors and characteristics of the disease, and to assess the temporal trends of incidence, according to age group and region of residence. METHODS Proportional distributions of leptospirosis cases of residents in the municipality were built and regression models with a Binomial Negative response were adjusted. RESULTS 2,201 cases of leptospirosis were registered, most of them being males (82%), aged between 20 to 59 years (64.6%), white (39%) or brown (32.8%), residing in the South (27.8%), East (23.8%) and North (18.5%) regions. The overall lethality was 15.1%. The risk was higher in the 20 to 59 age group. There was a downward trend in incidence in all age groups and regions, estimated at 5.6% per year. CONCLUSIONS Despite the downward trend in incidence, leptospirosis is a serious disease with high lethality, affecting mainly male individuals in the age groups considered economically active and living in the peripheral regions of the municipality.
Enhanced Thermal Conductivity in Oriented Polyvinyl Alcohol/Graphene Oxide Composites

Polymer composites have attracted increasing interest as thermal management materials for use in devices owing to their ease of processing and potential lower costs. However, most polymer composites have only modest thermal conductivities, even at high concentrations of additives, resulting in high costs and reduced mechanical properties, which limit their applications. To achieve high thermally conductive polymer materials with a low concentration of additives, anisotropic, solid-state drawn composite films were prepared using water-soluble polyvinyl alcohol (PVA) and dispersible graphene oxide (GO). A co-additive (sodium dodecyl benzenesulfonate) was used to improve both the dispersion of GO and consequently the thermal conductivity. The hydrogen bonding between GO and PVA and the simultaneous alignment of GO and PVA in drawn composite films contribute to an improved thermal conductivity (∼25 W m–1 K–1), which is higher than most reported polymer composites and an approximately 50-fold enhancement over isotropic PVA (0.3–0.5 W m–1 K–1). This work provides a new method for preparing water-processable, drawn polymer composite films with high thermal conductivity, which may be useful for thermal management applications.
Ge0.95Sn0.05 Gate-All-Around p-Channel Metal-Oxide-Semiconductor Field-Effect Transistors with Sub-3 nm Nanowire Width.

We demonstrate Ge0.95Sn0. 05 p-channel gate-all-around field-effect transistors (p-GAAFETs) with sub-3 nm nanowire width (WNW) on a GeSn-on-insulator (GeSnOI) substrate using a top-down fabrication process. Thanks to the excellent gate control by employing an aggressively scaled nanowire structure, Ge0.95Sn0. 05 p-GAAFETs exhibit a small subthreshold swing (SS) of 66 mV/decade, a decent on-current/off-current (ION/IOFF) ratio of ∼1.2 × 106, and a high-field effective hole mobility (μeff) of ∼115 cm2/(V s). In addition, we also investigate quantum confinement effects in extremely scaled GeSn nanowires, including threshold voltage (VTH) shift and IOFF reduction with continuous scaling of WNW under 10 nm. The phenomena observed from experimental results are substantiated by the calculation of GeSn bandgap and TCAD simulation of electrical characteristics of devices with sub-10 nm WNW. This study suggests Ge-based nanowire p-FETs with extremely scaled dimension hold promise to deliver good performance to enable further scaling for future technology nodes.
Heat shock protein 27 (hsp27) in patients with ovarian cancer.

OBJECTIVES Ovarian cancer remains a very common cause of death among women worldwide. The cause is to be found in too late of a diagnostic process and therapeutic difficulties The presence of heat shock proteins in the serum of ovarian cancer patients is still a new area of study. It is necessary to continue studies on the possibilities for using these markers to predict a patient's response to a specific therapy and to monitor treatment progress. MATERIAL AND METHODS The study included 52 women with ovarian cancer, hospitalised at the Department of Obstetrics, Gynaecology and Oncological Gynaecology, Medical University of Silesia. The control group consisted of 25 healthy women. The levels of HSP27 in the studied sera were determined by an immunoenzymatic method (ELISA). RESULTS The mean concentration of HSP27 in the group of patients with ovarian cancer was significantly higher than in the control group of healthy women. We have shown that mean HSP27 levels in ovarian cancer patients increase with tumour progression and further depend on the clinical stage of the disease (FIGO). Positivity values analysis revealed in all clinical stages of ovarian cancer, excluding stage 1, it was significantly higher than in the control group, and at the 4th stage, it is significantly higher than at the 1st, 2nd, and 3rd stages. However, both for the untreated patients and those patients after chemotherapy, the mean HSP27 levels were significantly higher than in the control group. CONCLUSIONS Our studies indicate a significant contribution of HSP27 to the pathogenesis of ovarian cancer. It seems that serum HSP27 can be a marker for this cancer's development, and a marker for the clinical stage.
Positron Emission Tomography Imaging of Regional Versus Global Myocardial Sympathetic Activity to Improve Risk Stratification in Patients With Ischemic Cardiomyopathy

Supplemental Digital Content is available in the text. Background: Current risk assessment approaches fail to identify the majority of patients at risk of sudden cardiac arrest (SCA). Noninvasive imaging of the cardiac sympathetic nervous system using single-photon emission computed tomography and positron emission tomography offers the potential for refining SCA risk assessment. While various [11C]meta-hydroxyephedrine quantification parameters have been proposed, it is currently unknown whether regional denervation or global innervation yields greater SCA risk discrimination. The aim of the study was to determine whether the global innervation parameters yield any independent and additive prognostic value over the regional denervation alone. Methods: In a post hoc competing-risks analysis of the PAREPET trial (Prediction of Arrhythmic Events With Positron Emission Tomography), we compared global innervation and regional denervation parameters using the norepinephrine analog [11C]meta-hydroxyephedrine for SCA risk discrimination. Patients with ischemic cardiomyopathy (n=174) eligible for an implantable cardioverter-defibrillator for the primary prevention of SCA were recruited into the trial. [11C]meta-hydroxyephedrine uptake and clearance rates were measured to assess global (left ventricle mean) retention index and volume of distribution. Regional defects were quantified as the percentage of the left ventricle having values <75% of the maximum. Results: During a median follow-up of 4.2 years, there were 56 cardiac-related deaths, of which 26 were SCAs. For any given regional denervation volume, there was substantial heterogeneity in global innervation scores. Global retention index and distribution volume did not decrease until regional defects exceeded 40% left ventricle. Global scale parameters, retention index, and distribution volume (area under the curve=0.61, P=0.034, P=0.046, respectively), yielded inferior SCA risk discrimination compared to regional heterogeneity (area under the curve=0.74). Conclusions: Regional denervation volume has superior cause-specific mortality prediction for SCA versus global parameters of sympathetic innervation. These results have widespread implications for future cardiac sympathetic imaging, which will greatly simplify innervation analysis. Registration: URL: https://www.clinicaltrials. gov; Unique identifier: NCT01400334.
Impact of type 1 diabetes on the composition and functional potential of gut microbiome in children and adolescents: possible mechanisms, current knowledge, and challenges

ABSTRACT Diabetes prevalence and incidence among youth have been increasing globally. Type 1 Diabetes (T1D) in children or adolescents accounts for 5–10% of all diagnosed cases of diabetes. Emerging evidence indicates that genetic factors, especially genes in the human leukocyte antigen region, are not the only factors involved in the predisposition of an individual to T1D. The pathogenesis and development of T1D is driven by both genetic predisposition and environmental factors. Studies indicate that gut microbiota is one of the potential environmental influencers involved in the pathophysiology of TID. Gut microbiota mediates the development of diabetes by altering intestinal permeability, modifying intestinal immunity, and molecular mimicry. The gut microbial diversity, taxonomic profile, and functional potential of gut microbes are significantly altered in individuals with T1D as compared to healthy individuals. However, studies are still needed to identify the specific microbes and microbial metabolites that are involved in the development and pathogenesis of T1D. This will help the development of microbiome-based therapeutic strategies for the prevention and treatment of T1D. The present review article highlights the following: (i) the current knowledge and knowledge gaps in understanding the association between T1D and gut microbiome specifically focusing on the composition and functional potential of gut microbiome in children and adolescents, (ii) the possible mechanisms involved in gut microbiome-mediated T1D pathogenesis, and (iii) challenges and future direction in this field. Abbreviations: B/F ratio: Bacteroidetes to Firmicutes ratio; F/B ratio: Firmicutes to Bacteroidetes ratio; FDR: First-degree relatives; GPR: G protein-coupled receptors; HLA: human leucocyte antigen; IL: interleukin; IFN- γ: interferon-γ; KEGG: Kyoto Encyclopedia of Genes and Genomes; LPS: lipopolysaccharide; mTOR: mammalian target of rapamycin; PICRUSt: Phylogenetic Investigation of Communities by Reconstruction of Unobserved States; SCFA: short chain fatty acids; T1D: Type 1 diabetes; T2D: Type 2 diabetes; TJ: tight junction; Tregs: regulatory T cells.
Social status and previous experience in the group as predictors of welfare of sows housed in large semi-static groups

Mixing gestating sows implies hierarchy formation and has detrimental consequences on welfare. The effects of social stress on the most vulnerable individuals may be underestimated and it is therefore important to evaluate welfare between individuals within groups. This study aimed at investigating the impact of social status and previous experience in the group on well-being of sows housed in large semi-static groups. We assessed aggression (d0 (mixing), d2, d27, d29), body lesions (d1, d26, d84) and feeding order on 20 groups of 46–91 animals. Social status was based on the proportion of fights won during a 6-hr observation period between d0 and d2. Dominants (29%) were those who won more fights than they lost, Subdominants (25%) won fewer fights than they lost, Losers (23%) never won any fight in which they were involved while Avoiders (23%) were never involved in fights. Resident sows (70%) were already present in the group in the previous gestation while New sows (30%) were newly introduced at mixing. Subdominants and Dominants were highly involved in fights around mixing but this was more detrimental for Subdominants than Dominants, Losers and Avoiders since they had the highest body lesion scores at mixing. Avoiders received less non-reciprocal agonistic acts than Losers on d2 (P = 0.0001) and had the lowest body lesion scores after mixing. However, Avoiders and Losers were more at risk in the long-term since they had the highest body lesions scores at d26 and d84. They were followed by Subdominants and then Dominants. New sows fought more (P<0.0001), tended to be involved in longer fights (P = 0.075) around mixing and had more body lesions throughout gestation than Resident sows. Feeding order from one-month post-mixing was influenced both by the previous experience in the group and social status (P<0.0001). New sows, especially with a low social status, are more vulnerable throughout gestation and could serve as indicators of non-optimal conditions.