julilili42/papers huggingface dataset:
Study design of a randomised, placebo-controlled trial of nintedanib in children and adolescents with fibrosing interstitial lung disease
2021-03-11

Childhood interstitial lung disease (chILD) comprises &gt;200 rare respiratory disorders, with no currently approved therapies and variable prognosis. Nintedanib reduces the rate of forced vital capacity (FVC) decline in adults with progressive fibrosing interstitial lung diseases (ILDs). We present the design of a multicentre, prospective, double-blind, randomised, placebo-controlled clinical trial of nintedanib in patients with fibrosing chILD (1199-0337 or InPedILD; ClinicalTrials.gov : NCT04093024 ). Male or female children and adolescents aged 6–17 years (≥30; including ≥20 adolescents aged 12–17 years) with clinically significant fibrosing ILD will be randomised 2:1 to receive oral nintedanib or placebo on top of standard of care for 24 weeks (double-blind), followed by variable-duration nintedanib (open-label). Nintedanib dosing will be based on body weight-dependent allometric scaling, with single-step dose reductions permitted to manage adverse events. Eligible patients will have evidence of fibrosis on high-resolution computed tomography (within 12 months of their first screening visit), FVC ≥25% predicted, and clinically significant disease (Fan score of ≥3 or evidence of clinical progression over time). Patients with underlying chronic liver disease, significant pulmonary arterial hypertension, cardiovascular disease, or increased bleeding risk are ineligible. The primary endpoints are pharmacokinetics and the proportion of patients with treatment-emergent adverse events at week 24. Secondary endpoints include change in FVC% predicted from baseline, Pediatric Quality of Life Questionnaire, oxygen saturation, and 6-min walk distance at weeks 24 and 52. Additional efficacy and safety endpoints will be collected to explore long-term effects.
Genitourinary syndrome of menopause in Chinese perimenopausal and postmenopausal women
2021-03-11

Within 2 years, more than 4000 women with GSM traveled from all over China to our specialized clinic, indicating the great importance of GSM. Hysterectomy can increase the risk of GSM, and GSM symptoms increase from perimenopause to postmenopause and with an increase of time since menopause, pointing to the dependency on the loss of ovarian function.
Photophysics of Charge Transfer Complexes Formed by Tetracene and Strong Acceptors
2021-03-11

Organic charge transfer complexes (CTCs) with near-infrared absorption received growing interest in the past years, but the details of their photophysics, especially in thin films, remain largely unknown. We combined experimental and computational methods to thoroughly investigate and compare CTCs formed by tetracene with 2,2′-(perfluoronaphthalene-2,6-diylidene)dimalononitrile and 2,3,5,6-tetrafluoro-7,7,8,8,-tetracyanoquinodimethane, respectively. Using ultrafast transient absorption spectroscopy, the photophysics of these small bandgap CTCs was revealed, which is dominated by a sub-picosecond relaxation of the excitons back to the ground state. In equimolar blends, tetracene singlet fission is suppressed while in blends with excess of tetracene reduced lifetimes of tetracene, singlet and triplet excitons were found.
Dual immune check point blockade or immune check point-tyrosine kinase inhibitor combination: as a first-line treatment in metastatic renal cell carcinoma?
2021-03-11

Purpose of review To discuss treatment decisions in the first-line setting of metastatic renal cell carcinoma (mRCC). Recent findings Immune check point inhibitor (ICI) combinations have replaced sunitinib as the standard of care in the first-line treatment of mRCC. Dual ICI treatment with nivolumab and ipilimumab was shown to significantly improve overall survival and objective response rates. Similarly, the ICI–tyrosine kinase inhibitor combinations pembrolizumab and axitinib and nivolumab and cabozantinib have demonstrated superiority in terms of overall survival, objective response rates and progression-free survival versus sunitinib. The lack of both comparative trials and predictive markers impedes individualized treatment decisions. Clinicians are left to make treatment choices based on clinical and biological factors. These factors may include differences in toxicity profiles, the rate of complete remission, a clinical situation that requires urgent tumor shrinkage, the presence of inflammation, histological or immune-histochemical features and others. Summary In the absence of comparative trials, clinical and biological factors may facilitate the choice between various treatment options in the first-line setting of mRCC. In addition, both the experience of the physician with a specific treatment together with patient's preferences and expectations of systemic therapy may be part of the decision-making process.
Evaluation of Resection Margin after Image-Guided Dural Tail Resection in Convexity Meningiomas
2021-03-11

Infiltration of adjacent dura with meningioma cells is a common phenomenon. Wide resection of the dural tail (DT) to achieve a gross total resection is a general recommendation. We aimed to investigate a tumor cell infiltration of the DT after image-guided resection of convexity meningiomas. The study’s inclusion criteria were the diagnosis of convexity meningioma, planned Simpson I° resection, and an identifiable DT. Intraoperative image-guidance was applied to identify the outer edge of the DT and to guide resection. After resection, en-bloc specimen or four samples of outermost pieces of DT in case of piecemeal resection were sent for histological analysis. In addition to resection margin infiltration, the radiological extent of DT, radiomic characteristics (109 in total), histology, and demographic data were assessed. Hierarchical clustering was used to generate patient clusters for radiomic analysis. Twenty-two patients were included in the study, while 20 (91%) were female. The mean age was 54.2 (Standard deviation (SD) 13.9, range 30–85) years. En-bloc resection could be achieved in 4 patients. The remaining patients received piecemeal resection. 2 DT samples were omitted due to tumor infiltration of the superior sagittal sinus. None of the en-bloc resection samples demonstrated dural infiltration on the resection margin. Tumor cells were detected in 4 of 70 (5.7%) dural tail samples and could not be excluded in another 5 of 70 (7.1%). No tumor recurrences were detected at follow-up MRI examinations after a mean follow-up of 27.5 (SD 13.2, range 0 to 50.0) months. There was no significant association between DT infiltration and histological subtype or patient characteristics and between DT extent and tumor infiltration. Clustering according to radiomic characteristics was not associated with tumor infiltration (p = 0.89). The radiological dural tail does not reliably outline the extent of tumor cell infiltration in convexity meningiomas. Hence, the extent of dural tail resection should not exclusively be guided by preoperative radiological appearance.
Sleep, pain, and neurodegeneration: A Mendelian randomization study
2021-03-11

Abstract Objective To examine whether sleep and pain-related traits have a causal effect on the risk of neurodegeneration. Design Two-sample Mendelian randomization using an inverse-variance weighted (IVW) estimate of the summary effect estimates. Setting Genetic data on sleep and pain-related traits and neurodegenerative disorders (NDD) from various cohorts comprising individuals predominantly of European ancestry. Participants Participants from the International Sleep Genetic Epidemiology Consortium (ISGEC), UK Biobank sleep and chronotype research group, International Genomics of Alzheimer’s patients (IGAP), project MinE, International Age-related Macular Degeneration Consortium (IAMDGC), International Multiple Sclerosis Genetics Consortium (IMSGC), International Parkinson’s Disease Genomics Consortium (IPDGC) Exposures Self-reported chronotype (CHR), morning preference (MP), insomnia symptoms (INS), sleep duration (SP), short sleep (SS), long sleep (LS), and multisite chronic pain (MCP) Main outcome measures Age-related macular degeneration (AMD), Alzheimer’s disease (AD), Amyotrophic lateral sclerosis (ALS), Multiple sclerosis (MS), and Parkinson’s disease (PD) Results We considered a threshold of P=0.00142 as significant accounting for multiple testing, and P&lt;0.05 was considered to be suggestive evidence for a potential association. Using direct MR, MP was observed as the strongest risk factor for AMD (OR IVW = 1.19, 95% CI 1.08, 1.32, P = 0.00073). We observed suggestive evidence of influence of different sleep traits on neurodegeneration: CHR on AMD (OR IVW = 1.27, 95% CI 1.08, 1.49, P = 0.0034), SS on AD (OR IVW 1.26, 95% CI 1.08, 1.46, P = 0.0044), and INS on ALS (OR IVW 1.55, 95% CI 1.12, 2.14, P = 0.0123). The association of SS with AD was, however, lost after the exclusion of overlapping UKB samples. Using pain as exposure, our study failed to observe any role of pain in neurodegeneration. Results were largely robust to reverse causal analyses and sensitivity analyses accounting for horizontal pleiotropy. Conclusions Our study highlighted the role of morning preference as a risk factor for AMD and provided suggestive evidence of different sleep traits on a wide spectrum of neurodegenerative diseases.
An updated genome-scale metabolic network reconstruction ofPseudomonas aeruginosaPA14 to characterize mucin-driven shifts in bacterial metabolism
2021-03-11

Abstract Mucins are present in mucosal membranes throughout the body and play a key role in the microbe clearance and infection prevention. Understanding the metabolic responses of pathogens to mucins will further enable the development of protective approaches against infections. We update the genome-scale metabolic network reconstruction (GENRE) of one such pathogen, Pseudomonas aeruginosa PA14, through metabolic coverage expansion, format update, extensive annotation addition, and literature-based curation to produce iPau21. We then validate iPau21 through MEMOTE, growth rate, carbon source utilization, and gene essentiality testing to demonstrate its improved quality and predictive capabilities. We then integrate the GENRE with transcriptomic data in order to generate context-specific models of P. aeruginosa metabolism. The contextualized models recapitulated known phenotypes of unaltered growth and a differential utilization of fumarate metabolism, while also revealing an increased utilization of propionate metabolism upon MUC5B exposure. This work serves to validate iPau21 and demonstrate its utility for providing biological insights.
Formamidinium‐Based Dion‐Jacobson Layered Hybrid Perovskites: Structural Complexity and Optoelectronic Properties
2021-03-11

Raw data corresponding to the publication entitled "Formamidinium‐Based Dion‐Jacobson Layered Hybrid Perovskites: Structural Complexity and Optoelectronic Properties" including:<br> <br> - X-ray diffraction spectra and projected densities of states <br> - Isosurfaces of HOMO and LUMO levels
Global Tuberculosis Report 2020 – Reflections on the Global TB burden, treatment and prevention efforts
2021-03-12

The October 2020 Global TB report reviews TB control strategies and United Nations (UN) targets set in the political declaration at the September 2018 UN General Assembly high-level meeting on TB held in New York. Progress in TB care and prevention has been very slow. In 2019, TB remained the most common cause of death from a single infectious pathogen. Globally, an estimated 10.0 million people developed TB disease in 2019, and there were an estimated 1.2 million TB deaths among HIV-negative people and an additional 208, 000 deaths among people living with HIV. Adults accounted for 88% and children for 12% of people with TB. The WHO regions of South-East Asia (44%), Africa (25%), and the Western Pacific (18%) had the most people with TB. Eight countries accounted for two thirds of the global total: India (26%), Indonesia (8.5%), China (8.4%), the Philippines (6.0%), Pakistan (5.7%), Nigeria (4.4%), Bangladesh (3.6%) and South Africa (3.6%). Only 30% of the 3.5 million five-year target for children treated for TB was met. Major advances have been development of new all oral regimens for MDRTB and new regimens for preventive therapy. In 2020, the COVID-19 pandemic dislodged TB from the top infectious disease cause of mortality globally. Notably, global TB control efforts were not on track even before the advent of the COVID-19 pandemic. Many challenges remain to improve sub-optimal TB treatment and prevention services. Tuberculosis screening and diagnostic test services need to be ramped up. The major drivers of TB remain undernutrition, poverty, diabetes, tobacco smoking, and household air pollution and these need be addressed to achieve the WHO 2035 TB care and prevention targets. National programs need to include interventions for post-tuberculosis holistic wellbeing. From first detection of COVID-19 global coordination and political will with huge financial investments have led to the development of effective vaccines against SARS-CoV2 infection. The world now needs to similarly focus on development of new vaccines for TB utilizing new technological methods.
Segregation of functional networks is associated with cognitive resilience in Alzheimer’s disease
2021-03-12

Abstract Cognitive resilience is an important modulating factor of cognitive decline in Alzheimer’s disease, but the functional brain mechanisms that support cognitive resilience remain elusive. Given previous findings in normal ageing, we tested the hypothesis that higher segregation of the brain’s connectome into distinct functional networks represents a functional mechanism underlying cognitive resilience in Alzheimer’s disease. Using resting-state functional MRI, we assessed both resting-state functional MRI global system segregation, i.e. the balance of between-network to within-network connectivity, and the alternate index of modularity Q as predictors of cognitive resilience. We performed all analyses in two independent samples for validation: (i) 108 individuals with autosomal dominantly inherited Alzheimer’s disease and 71 non-carrier controls; and (ii) 156 amyloid-PET-positive subjects across the spectrum of sporadic Alzheimer’s disease and 184 amyloid-negative controls. In the autosomal dominant Alzheimer’s disease sample, disease severity was assessed by estimated years from symptom onset. In the sporadic Alzheimer’s sample, disease stage was assessed by temporal lobe tau-PET (i.e. composite across Braak stage I and III regions). In both samples, we tested whether the effect of disease severity on cognition was attenuated at higher levels of functional network segregation. For autosomal dominant Alzheimer’s disease, we found higher functional MRI-assessed system segregation to be associated with an attenuated effect of estimated years from symptom onset on global cognition (P = 0.007). Similarly, for patients with sporadic Alzheimer’s disease, higher functional MRI-assessed system segregation was associated with less decrement in global cognition (P = 0.001) and episodic memory (P = 0.004) per unit increase of temporal lobe tau-PET. Confirmatory analyses using the alternate index of modularity Q revealed consistent results. In conclusion, higher segregation of functional connections into distinct large-scale networks supports cognitive resilience in Alzheimer’s disease.
Synchronous activity patterns in the dentate gyrus during immobility
2021-03-12

The hippocampal dentate gyrus is an important relay conveying sensory information from the entorhinal cortex to the hippocampus proper. During exploration, the dentate gyrus has been proposed to act as a pattern separator. However, the dentate gyrus also shows structured activity during immobility and sleep. The properties of these activity patterns at cellular resolution, and their role in hippocampal-dependent memory processes have remained unclear. Using dual-color in-vivo two-photon Ca 2+ imaging, we show that in immobile mice dentate granule cells generate sparse, synchronized activity patterns associated with entorhinal cortex activation. These population events are structured and modified by changes in the environment; and they incorporate place- and speed cells. Importantly, they are more similar than expected by chance to population patterns evoked during self-motion. Using optogenetic inhibition, we show that granule cell activity is not only required during exploration, but also during immobility in order to form dentate gyrus-dependent spatial memories.
The emerging and diverse roles of the SLy/SASH1‐protein family in health and disease—Overview of three multifunctional proteins
2021-03-12

Abstract Intracellular adaptor proteins are indispensable for the transduction of receptor‐derived signals, as they recruit and connect essential downstream effectors. The SLy/SASH1‐adaptor family comprises three highly homologous proteins, all of them sharing conserved structural motifs. The initial characterization of the first member SLy1/SASH3 (SH3 protein expressed in lymphocytes 1) in 2001 was rapidly followed by identification of SLy2/HACS1 (hematopoietic adaptor containing SH3 and SAM domains 1) and SASH1/SLy3 (SAM and SH3 domain containing 1). Based on their pronounced sequence similarity, they were subsequently classified as one family of intracellular scaffold proteins. Despite their obvious homology, the three SLy/SASH1‐members fundamentally differ with regard to their expression and function in intracellular signaling. On the contrary, growing evidence clearly demonstrates an important role of all three proteins in human health and disease. In this review, we systematically summarize what is known about the SLy/SASH1‐adaptors in the field of molecular cell biology and immunology. To this end, we recapitulate current research about SLy1/SASH3, SLy2/HACS1, and SASH1/SLy3, with an emphasis on their similarities and differences.
Emergent Bloch Oscillations in a Kinetically Constrained Rydberg Spin Lattice
2021-03-12

We explore the relaxation dynamics of elementary spin clusters in a kinetically constrained spin system. Inspired by experiments with Rydberg lattice gases, we focus on the situation in which an excited spin leads to a "facilitated" excitation of a neighboring spin. We show that even weak interactions that extend beyond nearest neighbors can have a dramatic impact on the relaxation behavior: they generate a linear potential, which under certain conditions leads to the onset of Bloch oscillations of spin clusters. These hinder the expansion of a cluster and, more generally, the relaxation of many-body states toward equilibrium. This shows that nonergodic behavior in kinetically constrained systems may occur as a consequence of the interplay between reduced connectivity of many-body states and weak interparticle interactions. We furthermore show that the emergent Bloch oscillations identified here can be detected in experiment through measurements of the Rydberg atom density and discuss how spin-orbit coupling between internal and external degrees of freedom of spin clusters can be used to control their relaxation behavior.
Advancements in capacitance‐to‐digital converter‐based C4D technology for detection in capillary electrophoresis using amplified excitation voltages and comparison to classical and open‐source C4Ds
2021-03-12

Abstract This work introduces new hardware configurations for a capacitively coupled contactless conductivity detector (C 4 D) based on capacitance‐to‐digital conversion (CDC) technology for CE. The aim was to improve sensitivity, handling, price, and portability of CDC‐based C 4 D detectors (CDCD) to reach LODs similar to classic C 4 Ds with more sophisticated electric circuits. To achieve this, a systematic study on the CDCDs was carried out including a direct comparison to already established C 4 D setups. Instrumental setups differing in electrode lengths, measurement modes, and amplification of excitation voltages were investigated to achieve LODs for alkali metal ions of 4 to 12 μM, similar to LODs obtained by classic C 4 D setups. Lowest LODs were achieved for a setup with two 10 mm electrodes at a distance of 0.2 mm and an excitation voltage of 24 V. The detection head was exceptionally lightweight with only 2.6 g and covered only 20 mm of the capillary on total. This allowed the use of multiple detectors along the separation path to enable spatial tracking of analytes during separation. The entirely battery‐powered detector assembly weighs less than 200 g, and the data are transmitted wirelessly for possible portable applications. The freely accessible hardware and software were optimized for fully automated measurements with real time data plotting and allowed handling multidetector setups. The new developments were applied to quantify the potassium salt of glyphosate in its herbicide formulation.
From Micro to Macro
2021-03-12

Transition into higher education (HE) remains at the forefront of policy and practice in education worldwide (Gale &amp; Parker, 2014). Transition as a process (Nicholson, 1990) in which individuals move from one stage to another may cause stress and discomfort that possibly lead to negative outcomes. Transition into HE is a particularly challenging process for the student due to a large variety of difficulties and requirements which could impede study success (Trautwein &amp; Bosse, 2017). Moreover, increasing student numbers and diversity in European HE have reinforced concerns about study success in general and the successful transition to university in particular (Abbott-Chapmann, 2006, 2011; Vossensteyn et al., 2015; Wolter, 2013). Consequently, it is important to further develop our understanding of factors that can contribute to a successful and less stressful transitions into higher education for a diverse student body. In this special issue, we go beyond considering individual factors, such as student characteristics (micro level). In addition to student diversity, we investigate the impact of the learning environment/ institution (meso level) and national educational policies (macro level). Each study contributes to this endeavour by connecting two of the three levels of higher education.
Activities of the Right Temporo-Parieto-Occipital Junction Reflect Spatial Hearing Ability in Cochlear Implant Users
2021-03-12

Spatial hearing is critical for us not only to orient ourselves in space, but also to follow a conversation with multiple speakers involved in a complex sound environment. The hearing ability of people who suffered from severe sensorineural hearing loss can be restored by cochlear implants (CIs), however, with a large outcome variability. Yet, the causes of the CI performance variability remain incompletely understood. Despite the CI-based restoration of the peripheral auditory input, central auditory processing might still not function fully. Here we developed a multi-modal repetition suppression (MMRS) paradigm that is capable of capturing stimulus property-specific processing, in order to identify the neural correlates of spatial hearing and potential central neural indexes useful for the rehabilitation of sound localization in CI users. To this end, 17 normal hearing and 13 CI participants underwent the MMRS task while their brain activity was recorded with a 256-channel electroencephalography (EEG). The participants were required to discriminate between the probe sound location coming from a horizontal array of loudspeakers. The EEG MMRS response following the probe sound was elicited at various brain regions and at different stages of processing. Interestingly, the more similar this differential MMRS response in the right temporo-parieto-occipital (TPO) junction in CI users was to the normal hearing group, the better was the spatial hearing performance in individual CI users. Based on this finding, we suggest that the differential MMRS response at the right TPO junction could serve as a central neural index for intact or impaired sound localization abilities.