julilili42/papers huggingface dataset:
AUF-1 knock down in mice overarches butyrate driven hypo-cholesteraemia by conjuring AUF-1-Dicer-1-miR122 hierarchy
2022-06-16

Abstract This discourse probes the mechanistic molecular details of butyrate action in maintaining host-cholesterol balance. Hepatic miR122 being the most indispensable regulator of cholesterol metabolic enzymes, we studied upstream players of miR122 biogenesis in the presence and absence of butyrate in Huh7 cells and mice model. We showed that butyrate treatment caused upregulation of RNA-binding protein, AUF-1 resulting in RNase-III nuclease, Dicer-1 instability, and significant diminution of miR122. We proved its importance of AUF-1 and sequential downstream players in AUF-1-knock-down mice. We synthesized unique self-transfecting GMO (guanidinium-morpholino-oligonucleotides) linked PMO (Phosphorodiamidate-Morpholino Oligonucleotides)-based antisense reagent and injection of which in mouse caused near absence of AUF-1 coupled with increased Dicer-1 and miR122, and reduced serum cholesterol regardless of butyrate treatment indicating that butyrate acts though AUF-1. The roster of intracellular players was as follows: AUF-1-Dicer-1-miR122 for triggering butyrate driven hypocholesterlaemia. To our knowledge this is the first report linking AUF-1 with cholesterol biogenesis.
Seroepidemiological Reconstruction of Long-term Chikungunya Virus Circulation in Burkina Faso and Gabon
2022-06-17

Abstract Chikungunya virus (CHIKV) is a major public health concern worldwide. However, infection levels are rarely known, especially in Africa. We recruited individuals from Ouagadougou, Burkina Faso and Lambaréné, Gabon (age range, 1–55 years), tested their blood for CHIKV antibodies, and used serocatalytic models to reconstruct epidemiological histories. In Ouagadougou, 291 of 999 (29.1%) individuals were seropositive, ranging from 2% among those aged &amp;lt;10 years to 66% in those aged 40–55 years. We estimated there were 7 outbreaks since the 1970s but none since 2001, resulting in 600 000 infections in the city, none of which were reported. However, we could not definitively conclude whether infections were due to CHIKV or o’nyong-nyong, another alphavirus. In Lambaréné, 117 of 427 (27%) participants were seropositive. Our model identified a single outbreak sometime since 2007, consistent with the only reported CHIKV outbreak in the country. These findings suggest sporadic outbreaks in these settings and that the burden remains undetected or incorrectly attributed.
Computational methods and theory for ion channel research
2022-06-17

Ion channels are fundamental biological devices that act as gates in order to ensure selective ion transport across cellular membranes; their operation constitutes the molecular mechanism through which basic biological functions, such as nerve signal transmission and muscle contraction, are carried out. Here, we review recent results in the field of computational research on ion channels, covering theoretical advances, state-of-the-art simulation approaches, and frontline modeling techniques. We also report on few selected applications of continuum and atomistic methods to characterize the mechanisms of permeation, selectivity, and gating in biological and model channels.
Combination of Whole-Body Baseline CT Radiomics and Clinical Parameters to Predict Response and Survival in a Stage-IV Melanoma Cohort Undergoing Immunotherapy
2022-06-17

Background: This study investigated whether a machine-learning-based combination of radiomics and clinical parameters was superior to the use of clinical parameters alone in predicting therapy response after three months, and overall survival after six and twelve months, in stage-IV malignant melanoma patients undergoing immunotherapy with PD-1 checkpoint inhibitors and CTLA-4 checkpoint inhibitors. Methods: A random forest model using clinical parameters (demographic variables and tumor markers = baseline model) was compared to a random forest model using clinical parameters and radiomics (extended model) via repeated 5-fold cross-validation. For this purpose, the baseline computed tomographies of 262 stage-IV malignant melanoma patients treated at a tertiary referral center were identified in the Central Malignant Melanoma Registry, and all visible metastases were three-dimensionally segmented (n = 6404). Results: The extended model was not significantly superior compared to the baseline model for survival prediction after six and twelve months (AUC (95% CI): 0.664 (0.598, 0.729) vs. 0.620 (0.545, 0.692) and AUC (95% CI): 0.600 (0.526, 0.667) vs. 0.588 (0.481, 0.629), respectively). The extended model was not significantly superior compared to the baseline model for response prediction after three months (AUC (95% CI): 0.641 (0.581, 0.700) vs. 0.656 (0.587, 0.719)). Conclusions: The study indicated a potential, but non-significant, added value of radiomics for six-month and twelve-month survival prediction of stage-IV melanoma patients undergoing immunotherapy.
The State of the UBI Debate: Mapping the Arguments for and against UBI
2022-06-17

Abstract This article provides a map of the UBI debate, structured into the main themes that guide and group the arguments on both sides. It finds that UBI’s supporters and opponents both draw on core principles of justice and freedom, focusing on need and poverty, discrimination and inequality, growth, social opportunity, individuality, and self-development. From an economic perspective, they both appeal to business concerns about efficiency, risk, flexibility, and consumption, as well as labour interests on work fulfilment, working conditions, remuneration, and bargaining. Likewise, they focus on political questions around welfare state reforms, redistribution, taxation and funding sources, democratic citizenship, and the prospects for cross-party policy coalitions. By providing an overview of the thematic pillars of the UBI debate, this article helps researchers and activists locate and orient themselves within the wider spectrum of opinion on UBI.
Molecular basis of intraspecific differentiation for heavy metal tolerance in the copper moss Scopelophila cataractae
2022-06-17

The remarkable capacity of bryophytes to tolerate extremely challenging abiotic conditions allows us to enhance our understanding of the diversity of molecular mechanisms involved in plant stress response. Here, we used next generation sequencing to study DNA methylation and gene expression changes in plants from four populations of the metallophyte moss Scopelophila cataractae experimentally exposed to either Cd or Cu. These populations previously showed differences in tolerance to both metals, so here, we aimed to investigate the molecular basis of this phenotypic differentiation. We found no evidence of genetic differentiation among the populations studied. The epigenetic data, however, showed limited but significant population-specific changes in DNA methylation in response to both metals. Exposure to acute Cu stress in the laboratory led to the downregulation of genes involved in heavy metal tolerance in both the more and the less tolerant populations, but this response was quantitatively higher in the most tolerant. We propose that chronic exposure to varying levels of heavy metals in the field led to potentially non-genetically-based intraspecific differentiation for heavy metal tolerance in S. cataractae. The most tolerant plants invested more in constitutive protection and were more efficient at entering a conservative state when faced with acute Cu stress
Reciprocal Interactions between Oligodendrocyte Precursor Cells and the Neurovascular Unit in Health and Disease
2022-06-17

Oligodendrocyte precursor cells (OPCs) are mostly known for their capability to differentiate into oligodendrocytes and myelinate axons. However, they have been observed to frequently interact with cells of the neurovascular unit during development, homeostasis, and under pathological conditions. The functional consequences of these interactions are largely unclear, but are increasingly studied. Although OPCs appear to be a rather homogenous cell population in the central nervous system (CNS), they present with an enormous potential to adapt to their microenvironment. In this review, it is summarized what is known about the various roles of OPC-vascular interactions, and the circumstances under which they have been observed.
Steady state entanglement of distant nitrogen-vacancy centers in a coherent thermal magnon bath
2022-06-17

We investigate steady state entanglement (SSE) between two nitrogen-vacancy (NV) center defects in a diamond host on an ultrathin yttrium iron garnet (YIG) strip. We determine the dephasing and dissipative interactions of the qubits with the quanta of spin waves (magnon bath) in the YIG depending on the qubit positions on the strip. We show that the magnon's dephasing effect can be eliminated, and we can transform the bath into a multimode displaced thermal state using external magnetic fields. Entanglement dynamics of the qubits in such a displaced thermal bath have been analyzed by deriving and solving the master equation. An additional electric field is considered to engineer the magnon dispersion relation at the band edge to control the Markovian character of the open system dynamics. We determine the optimum geometrical parameters of the system of distant qubits and the YIG strip to get SSE. Furthermore, parameter regimes for which the shared displaced magnon bath can sustain significant SSE against the local dephasing and decoherence of NV centers to their nuclear spin environments have been determined. Along with SSE, we investigate the steady state coherence (SSC) and explain the physical mechanism of how delayed SSE appears following a rapid generation and sudden death of entanglement using the interplay of decoherence-free subspace states, system geometry, displacement of the thermal bath, and enhancement of the qubit dissipation near the magnon band edge. A nonmonotonic relation between bath coherence and SSE is found, and critical coherence for maximum SSE is determined. Our results illuminate the efficient use of system geometry, band edge in bath spectrum, and reservoir coherence to engineer system-reservoir interactions for robust SSE and SSC.
Time-resolved observation of a dynamical phase transition with atoms in a cavity
2022-06-17

The transparence of a laser-driven optical resonator containing an ensemble\\nof cold atoms can have two distinct, robust states. Atoms in their initially\\nprepared pure state blockade the transmission by detuning the cavity mode from\\nthe laser drive. The interacting system can, however, transition into an\\nuncoupled state via a non-linear channel opening up in a critical run-away\\nprocess toward a transparent bright phase. The experiment enables a\\ntime-resolved observation of the dynamical transmission blockade breakdown\\nphase transition as well as quantification of enhanced fluctuations in the\\ncritical region.\\n
Generating iPSCs with a High-Efficient, Non-Invasive Method—An Improved Way to Cultivate Keratinocytes from Plucked Hair for Reprogramming
2022-06-17

Various somatic cell types are suitable for induced pluripotency reprogramming, such as dermal fibroblasts, mesenchymal stem cells or hair keratinocytes. Harvesting primary epithelial keratinocytes from plucked human hair follicles (HFs) represents an easy and non-invasive alternative to a fibroblast culture from invasive skin biopsies. Nevertheless, to facilitate and simplify the process, which can be divided into three main steps (collecting, culturing and reprogramming), the whole procedure of generating hair keratinocytes has to be revised and upgraded continuously. In this study, we address advancements and approaches which improve the generation and handling of primary HF-derived keratinocytes tremendously, e.g., for iPSCs reprogramming. We not only evaluated different serum- and animal-origin-free media, but also supplements and coating solutions for an enhanced protocol. Here, we demonstrate the importance of speed and accuracy in the collecting step, as well as the choice of the right transportation medium. Our results lead to a more defined approach that further increases the reliability of downstream experiments and inter-laboratory reproducibility. These improvements will make it possible to obtain keratinocytes from plucked human hair for the generation of donor-specific iPSCs easier and more efficient than ever before, whilst preserving a non-invasive capability.
Remote eye care method for compensation of defocus aberration in an unbalanced peripheral refraction aberrometer
2022-06-17

The link between retinal peripheral defocus, and its influence on myopia development has opened the need for accurate scientific investigations to understand the peripheral mechanisms of action. In such a manner, high-quality peripheral refractometry has become the cornerstone of myopia research. A clinical aberrometer is an efficient and robust instrument for measuring wavefront error for central vision. However, several difficulties prevent standardization in clinical use to measure aberrations in the peripheral field. In this work, we developed a new scanning Shack Hartmann aberrometer using a different economical customized relay telescope and a dual-axis fast steering mirror. The study aims to investigate the characteristics of defocus aberration in the instrument with support of digitalization techniques. Two physical eye models were built and analyzed to show and validate the working principle. The results of this research provide knowledge for remote maintenance and calibration of ophthalmological instruments, remote visual care and telemedicine.
Precision medicine for genetic epilepsy on the horizon: Recent advances, present challenges, and suggestions for continued progress
2022-06-18

Abstract The genetic basis of many epilepsies is increasingly understood, giving rise to the possibility of precision treatments tailored to specific genetic etiologies. Despite this, current medical therapy for most epilepsies remains imprecise, aimed primarily at empirical seizure reduction rather than targeting specific disease processes. Intellectual and technological leaps in diagnosis over the past 10 years have not yet translated to routine changes in clinical practice. However, the epilepsy community is poised to make impressive gains in precision therapy, with continued innovation in gene discovery, diagnostic ability, and bioinformatics; increased access to genetic testing and counseling; fuller understanding of natural histories; agility and rigor in preclinical research, including strategic use of emerging model systems; and engagement of an evolving group of stakeholders (including patient advocates, governmental resources, and clinicians and scientists in academia and industry). In each of these areas, we highlight notable examples of recent progress, new or persistent challenges, and future directions. The future of precision medicine for genetic epilepsy looks bright if key opportunities on the horizon can be pursued with strategic and coordinated effort.
Surgery and perioperative management of patients with Cushing's disease
2022-06-18

Abstract Transsphenoidal surgery (TSS) is the initial treatment modality of first choice in Cushing's disease (CD). With microscopic TSS and endoscopic TSS, two operative techniques with equally favourable remission rates and operative morbidity are available. On average, remission is achieved with primary TSS in 80% of patients with microadenomas and 60% of patients with macroadenomas. The current literature indicates that remission rates in repeat TSS for microadenomas can also exceed 70%. Experience with TSS in CD plays an important role in the success rate and centralization in Pituitary Centres of Excellence has been proposed. Microadenoma stage, imaging‐visible adenoma, confirmation of ACTH‐positive adenoma on histopathology and noninvasiveness are positive predictors for postoperative remission. In postoperative management, a steroid‐sparing protocol with early postoperative assessment of remission status is recommended. Convincing evidence suggests that prolonged postoperative prophylactic antithrombotic measures can significantly reduce the risk of postoperative thromboembolic events in CD. Prevention or successful treatment of cortisol withdrawal syndrome remains an unsolved issue that should be a focus of future research. The further development and broad availability of functional imaging hold promise for improved preoperative detection of microadenomas. Intraoperative identification of microadenomas by specific fluorescent targeting could be a promising future avenue for the treatment of patients with negative imaging.
Identification and RNAi‐based functional analysis of chitinase family genes in Agrotis ipsilon
2022-06-18

Abstract BACKGROUND Chitin is a major component in the extracellular matrix of insects, and its metabolism largely affects insect development and molting. As essential degradative enzymes, chitinases are encoded by multiple genes that differ in size, expression pattern and function in insects. However, our limited knowledge on the functions of different chitinases in Agrotis ipsilon has prevented our application of new technologies to target these genes as new pest management strategies. RESULTS We revealed 11 full‐length complementary DNA sequences of chitinase genes ( AiChts ) from A. ipsilon transcriptome. Although the domain architecture of these chitinases varied greatly, they all contained at least one chitinase catalytic domain. Developmental stage‐ and tissue‐dependent expression profiles showed that most AiCht s had the highest expression in the pupal stage. Furthermore, AiCht2 , AiCht6 , AiCht7 and AiCht10 were mainly expressed in the integument, whereas AiCht8 and AiCht‐h had the highest expression in the midgut. The RNA interference (RNAi) experiment revealed that knockdown of AiCht10 or the imaginal disc growth factor gene ( AiIDGF ) induced high larval mortality. Larvae failed to shed the old cuticle during molting after the injection of double‐stranded RNA targeting AiCht10 (ds AiCht10 ), whereas the larval bodies shrunk and blackened after the injection of dsRNA targeting AiIDGF (ds AiIDGF ). CONCLUSION Our results revealed for the first time the important functions of AiCht10 and AiIDGF in A. ipsilon . These genes are essential for larval development, and can potentially serve as new targets for RNAi‐based pest management. © 2022 Society of Chemical Industry.
Methods of Esthetic Assessment after Adjuvant Whole-Breast Radiotherapy in Breast Cancer Patients: Evaluation of the BCCT.core Software and Patients’ and Physicians’ Assessment from the Randomized IMRT-MC2 Trial
2022-06-18

The present analysis compares the esthetics assessment by the BCCT.core software in relation to patients’ and physicians’ ratings, based on the IMRT-MC2 trial. Within this trial, breast cancer patients received breast-conserving surgery (BCS) and adjuvant radiotherapy. At the baseline, 6 weeks, and 2 years after radiotherapy, photos of the breasts were assessed by the software and patients’ and physicians’ assessments were performed. Agreement rates of the assessments and their correlation with breast asymmetry indices were evaluated. The assessments of the software and the physicians were significantly correlated with asymmetry indices. Before and 6 weeks after radiotherapy, the patients’ self-assessment was only correlated with the lower breast contour (LBC) and upward nipple retraction (UNR), while after 2 years, there was also a correlation with other indices. Only a slight agreement between the BCCT.core software and the physicians’ or patients’ assessment was seen, while a moderate and substantial agreement was detected between the physicians’ and the patients’ assessment after 6 weeks and 2 years, respectively. The BCCT.core software is a reliable tool to measure asymmetries, but may not sufficiently evaluate the esthetic outcome as perceived by patients. It may be more appropriate for a long-term follow-up, when symmetry appears to increase in importance.
Preference for Porphyry: Petrographic Insights into Lithic Raw Material Procurement from Palaeolithic Kazakhstan
2022-06-18

Only a handful of stratified sites are known in loess, spring, and river contexts in the northern piedmonts of the Tian Shan, and the majority are dated to the Upper Palaeolithic. These sites have been studied from a geoarchaeological perspective, however, lithic procurement activities remain unknown. To address this deficiency, we present the results of the extensive field surveys aimed at locating prehistoric raw material sources in the Inner Asian Mountain Corridor of Kazakhstan. We also provide a detailed petrographic description of the lithologies exploited during the Palaeolithic of Kazakhstan. Based on the field survey results, combined with petrographic data, we conclude that the direct procurement strategy was the most common at the stratified sites. However, evidence of both direct and embedded procurement is found in the northern piedmonts of the Ili Alatau range at the site of Maibulaq. Additionally, we highlight the variation of chert lithologies within the larger Qaratau region, laying a foundation for future provenance studies.
Antibody Binding and Angiotensin-Converting Enzyme 2 Binding Inhibition Is Significantly Reduced for Both the BA.1 and BA.2 Omicron Variants
2022-06-19

Abstract Background The rapid emergence of the Omicron variant and its large number of mutations led to its classification as a variant of concern (VOC) by the World Health Organization. Subsequently, Omicron evolved into distinct sublineages (eg, BA.1 and BA.2), which currently represent the majority of global infections. Initial studies of the neutralizing response toward BA.1 in convalescent and vaccinated individuals showed a substantial reduction. Methods We assessed antibody (immunoglobulin G [IgG]) binding, ACE2 (angiotensin-converting enzyme 2) binding inhibition, and IgG binding dynamics for the Omicron BA.1 and BA.2 variants compared to a panel of VOCs/variants of interest, in a large cohort (N = 352) of convalescent, vaccinated, and infected and subsequently vaccinated individuals. Results While Omicron was capable of efficiently binding to ACE2, antibodies elicited by infection or immunization showed reduced binding capacities and ACE2 binding inhibition compared to wild type. Whereas BA.1 exhibited less IgG binding compared to BA.2, BA.2 showed reduced inhibition of ACE2 binding. Among vaccinated samples, antibody binding to Omicron only improved after administration of a third dose. Conclusions Omicron BA.1 and BA.2 can still efficiently bind to ACE2, while vaccine/infection-derived antibodies can bind to Omicron. The extent of the mutations within both variants prevents a strong inhibitory binding response. As a result, both Omicron variants are able to evade control by preexisting antibodies.
Additional file 3 of Cellular and antibody response in GMZ2-vaccinated Gabonese volunteers in a controlled human malaria infection trial
2022-06-19

Additional file 3: Table S3. The antibody response against the vaccine antigen (GMZ2) or any of the main components (MSP3, GLURP), estimated before vaccination, was tested for correlation with any of the antibody responses, as estimated by the protein microarray before CHMI. The log-transformed ELISA data and the protein microarray data were tested usind Student's t-test for correlation. Antigens with correlations resulting in p-values &lt; 0.05 are shown.