Miracle-dz/UniFAR-FTUs huggingface dataset:
On the research for big data uses for public good purposes. Opportunities and challenges

Ces dernieres annees, beaucoup de nos habitudes ont change, suite a l’arrivee des big data, et de l’offre de services donnant des informations mises a jour en temps reel, basees sur les donnees produites par les utilisateurs. Cette revolution a egalement apporte de nouvelles opportunites pour les compagnies privees, mais aussi pour les gouvernements et chercheurs, les applications potentielles des analyses de ces donnees etant nombreuses. Dans cet article, nous presentons quelques avancees faites dans ce domaine, et montrons quelques opportunites d’applications pour le bien public, telles que l’aide aux actions humanitaires et la reponse aux situations extremes, rendues possibles par ces grandes masses de donnees, montrant egalement que dans certains cas, l’analyse de donnees peut etre utilisee pour sauver des vies. Enfin, a cote des nouvelles opportunites, se sont aussi presentes de nouveaux challenges, dont l’evaluation de la robustesse et representativite d’une base de donnees, ou bien les dangers pour la vie privee, qui seront l’objet d’une derniere section de cet article.
Harvesting at the Right Time: Maturity and its Effects on the Aromatic Characteristics of Cabernet Sauvignon Wine

The aim of this paper was to investigate how maturity affects the aroma characteristics of Cabernet Sauvignon wine. A series of four Vitis vinifera cv. Cabernet Sauvignon wines were produced from grapes of different harvest dates. The berries of sequential harvest treatments showed an increase in total soluble solids and anthocyanin and a decrease in titratable acidity. Berry shriveling was observed as berry weight decreased. In the wines, anthocyanin, dry extract, alcoholic strength, and pH were enhanced with the sequential harvest, whereas polyphenol and tannin were decreased. The concentrations of volatile compounds in sequential harvests were found to be at higher levels. Isopentanol, phenylethyl alcohol, ethyl acetate, ethyl lactate, benzaldehyde, citronellol, and linalool significantly increased when harvest was delayed by one or two weeks. Through a principal component analysis, the volatile compounds and phenols characterizing each harvest date were clearly differentiated. These results suggest that sequential harvest may be an optional strategy for winemakers to produce high-quality wine.
Pancreatic HB9 protein level is affected by early life stress in young adult rats: possible involvement of TNF-α and corticosterone

Abstract This study examined foot shock stress effects, during weaning, on pancreatic HB9 protein expression in young adult male rats in the presence or absence of adulthood stress. The pups were divided into Control, Early life stress, Young adult stress, and Early + young adult stress groups. Plasma corticosterone, insulin, glucose, and TNF-α concentrations, and pancreatic HB9 protein expression were assessed. At 2 weeks of age, stress increased plasma corticosterone level. During young adulthood, plasma TNF-α and glucose concentrations increased, whereas plasma insulin and pancreatic HB9 protein levels decreased in Early life stress group. Whereas, Early + young adulthood stress group showed no change in the study parameters, except for plasma corticosterone and insulin concentrations. Overall, early life stress reduced pancreatic HB9 protein expression possibly by elevating plasma corticosterone and TNF-α levels in early life and adulthood, respectively. However, combined with adulthood stress, HB9 protein expression increased to the level of Control.
First Experience of Robotic-assisted Percutaneous Coronary Intervention in Japan

In 2018, the CorPath GRX system (Corindus) was approved for use in Japan, marking the introduction of the first robotic-assisted system for percutaneous coronary intervention (PCI) in the country. The present report describes the first experience of robotic-assisted PCI for four coronary lesions in two cases in a single center. All procedures succeeded without any complications, although one procedure was converted to manual PCI by the operator’s decision. Post-marketing surveillance to assess the impact of this novel system on both Japanese patients and physicians is currently ongoing in Japan.
Exercise training and cardiac rehabilitation in cardiovascular disease

ABSTRACT Introduction: The aim of this review is to introduce the audience to exercise training (ET) as a therapeutic tool in coronary heart disease (CHD) and to discuss the role of and advances in cardiac rehabilitation (CR) as a means of effectively delivering ET. Areas covered: The physiological mechanisms behind ET effects on the cardiovascular (CV) system as well as the implementation of ET in CR and the effects of CR on CV morbidity, risk factor modification, and mortality will be reviewed. Additionally, the clinical and financial impact of CR in today’s healthcare systems will be discussed. Expert opinion: It is well-established that CR continues to be under-utilized despite significant benefits to patients and healthcare systems alike. Innovation in the structure of CR (such as the implementation of high-intensity protocols) and in accessibility (home and tele-health CR programs) is already helping improve efficacy and increase utilization of CR. However, the efficacy of home/remote delivery protocols is not well established and they comprise a minority of available CR services. More data and efforts are needed to improve such protocols and maximize the reach of remote delivery systems in order to effectively deliver CR services to more eligible individuals at lower costs.
New Insights into Bioactive Compounds of Traditional Chinese Medicines for Insulin Resistance Based on Signaling Pathways

Type 2 diabetes is a serious metabolic disease as a long‐term threat to human health. Insulin resistance is not only the basis and major feature of type 2 diabetes, but also the main etiology of diseases such as hypertension, hyperlipidemia and coronary heart disease. It has been shown that Traditional Chinese Medicines (TCMs) play an important role in the treatment of type 2 diabetes, through attenuating insulin resistance, whereas the mechanism involved is not yet well understood. Therefore, it is important to elucidate the pharmacological mechanism of these bioactive compounds so that one can pave the way for the modernization of TCMs. In this review, we focus on the recent progresses of some bioactive ingredients from TCMs with different functional groups, which exhibit therapeutic potential for the treatment of diabetic insulin resistance. It is expected that this review can provide new references for developing TCM‐derived drugs against diabetes and insulin resistance in the future.
Metabolic phenotypes of obese, overweight, and normal weight individuals and risk of chronic kidney disease: a systematic review and meta-analysis

ABSTRACT Objective Chronic kidney disease (CKD) risk is inconsistent in the normal-weight, overweight, and obese individuals due to the heterogeneity of metabolic status. This meta-analysis aimed to examine the combined effects of body mass index (BMI) and metabolic status on CKD risk. Materials and methods The MEDLINE, EMBASE, and Web of Knowledge databases were systematically searched up to March 2019 to identify all eligible studies investigating the CKD risk (defined as GFR < 60 mL/min per 1.73 m2 and/or microalbuminuria or proteinuria) associated with the body size phenotypes which are known as metabolically unhealthy normal-weight (MUNW), metabolically healthy overweight (MHOW), metabolically unhealthy overweight, metabolically healthy obese (MHO) and metabolically unhealthy obese (MUHO). The classification of subjects in included studies as metabolically unhealthy was based on the presence of three components of metabolic syndrome. BMI categorization was based on the criteria of included studies. The risk estimates and 95% confidence intervals (CIs) were extracted and pooled using random effects analysis. Results A total of 9 prospective cohort studies with 128773 participants and 4797 incident cases were included in the meta-analysis. Compared with healthy normal-weight individuals as reference, MUNW and MHO subjects showed an increased risk for CKD events with a pooled RR of 1.58 (95% CI = 1.28-1.96) in MUNW and 1.55 (95% CI = 1.34-1.79) in MHO persons. Also, MHOW was at increased risk for CKD (RR = 1.34, 95% CI = 1.20-1.51). MUHO individuals were at the highest risk for the development of CKD (RR = 2.13, 95% CI = 1.66-2.72). Conclusions Individuals with metabolic abnormality, although at normal-weight, have an increased risk for CKD. Healthy overweight and obese individuals had higher risk; refuting the notion that metabolically healthy overweight and obese phenotypes are benign conditions.
Cellular and Molecular Mechanisms Underlying Prostate Cancer Development: Therapeutic Implications

Prostate cancer is the most frequent nonskin cancer and second most common cause of cancer-related deaths in man. Prostate cancer is a clinically heterogeneous disease with many patients exhibiting an aggressive disease with progression, metastasis, and other patients showing an indolent disease with low tendency to progression. Three stages of development of human prostate tumors have been identified: intraepithelial neoplasia, adenocarcinoma androgen-dependent, and adenocarcinoma androgen-independent or castration-resistant. Advances in molecular technologies have provided a very rapid progress in our understanding of the genomic events responsible for the initial development and progression of prostate cancer. These studies have shown that prostate cancer genome displays a relatively low mutation rate compared with other cancers and few chromosomal loss or gains. The ensemble of these molecular studies has led to suggest the existence of two main molecular groups of prostate cancers: one characterized by the presence of ERG rearrangements (~50% of prostate cancers harbor recurrent gene fusions involving ETS transcription factors, fusing the 5′ untranslated region of the androgen-regulated gene TMPRSS2 to nearly the coding sequence of the ETS family transcription factor ERG) and features of chemoplexy (complex gene rearrangements developing from a coordinated and simultaneous molecular event), and a second one characterized by the absence of ERG rearrangements and by the frequent mutations in the E3 ubiquitin ligase adapter SPOP and/or deletion of CDH1, a chromatin remodeling factor, and interchromosomal rearrangements and SPOP mutations are early events during prostate cancer development. During disease progression, genomic and epigenomic abnormalities accrued and converged on prostate cancer pathways, leading to a highly heterogeneous transcriptomic landscape, characterized by a hyperactive androgen receptor signaling axis.
Cryo-EM structure of calcium-bound TMEM16F in nanodisc with supplement of PIP2 in Cl1

As a Ca2+-activated lipid scramblase and ion channel that mediates Ca2+ influx, TMEM16F relies on both functions to facilitate extracellular vesicle generation, blood coagulation, and bone formation. How a bona fide ion channel scrambles lipids remains elusive. Our structural analyses revealed the coexistence of an intact channel pore and PIP2-dependent protein conformation changes leading to membrane distortion. Correlated to the extent of membrane distortion, many tightly bound lipids are slanted. Structure-based mutagenesis studies further reveal that neutralization of some lipid-binding residues or those near membrane distortion specifically alters the onset of lipid scrambling, but not Ca2+ influx, thus identifying features outside of channel pore that are important for lipid scrambling. Together, our studies demonstrate that membrane distortion does not require open hydrophilic grooves facing the membrane interior and provide further evidence to suggest separate pathways for lipid scrambling and ion permeation.
Blocking the transient receptor potential vanilloid-1 does not reduce the exercise pressor reflex in healthy rats.

Controversy exists regarding the role played by transient receptor potential vanilloid-1 (TRPV1) in evoking the exercise pressor reflex. Here, we determine the role played by TRPV1 in evoking this reflex while assessing possible confounding factors arising from TRPV1 antagonists or from the vehicle in which they were dissolved. The exercise pressor reflex was evoked in decerebrated anesthetized Sprague-Dawley rats by electrical stimulation of the tibial nerve to statically contract the triceps surae muscles. This procedure was repeated before and after injecting the TRPV1 blockers - capsazepine (100μg100μL-1), ruthenium red (100μg100μL-1) or IRTX (1μg100μL-1). We found that capsazepine decreased the exercise pressor reflex when the drug was dissolved in DMSO (-10±9 mmHg; P=0.015; n=7). However, similar reduction was found when DMSO alone was injected (-8±5 mmHg; P=0.023; n=5). Capsazepine dissolved in ethanol (2±6 mmHg;P=0.49; n=7), ruthenium-red (-4±12 mmHg; P=0.41; n=7) or IRTX (4±18 mmHg; P=0.56; n=7) did not significantly decrease the exercise pressor reflex. In addition, we found that capsazepine and ruthenium-red had "off-target" effects. Capsazepine decreased the pressor response evoked by intra-arterial injection of bradykinin (500ngkg-1; -12±13 mmHg; P=0.028; n=9)and α-β-Methylene ATP (10μgkg-1; -7±8 mmHg; P=0.019; n=10) while ruthenium red decreased the ability of the muscle to produce and sustain force (-99±83 g; P=0.020; n=7). Our data therefore suggest that TRPV1 do not play a role in evoking the exercise pressor reflex. Additionally, given their strong "off-target" effects, capsazepine, and ruthenium-red should not be used for studying the role played by TRPV1 in evoking the exercise pressor reflex.
An Effective Protocol for Proteome Analysis of Medaka (Oryzias latipes) after Acute Exposure to Ionizing Radiation

All terrestrial organisms are subject to evolutionary pressures associated with natural sources of ionizing radiation (IR). The legacy of human-induced IR associated with energy, weapons production, medicine, and research has changed the distribution and magnitude of these evolutionary pressures. To date, no study has systematically examined the effects of environmentally relevant doses of radiation exposure across an organismal proteome. This void in knowledge has been due, in part, to technological deficiencies that have hampered quantifiable environmentally relevant IR doses and sensitive detection of proteomic responses. Here, we describe a protocol that addresses both needs, combining quantifiable IR delivery with a reliable method to yield proteomic comparisons of control and irradiated Medaka fish. Exposures were conducted at the Savannah River Ecology Laboratory (SREL, in Aiken, SC), where fish were subsequently dissected into three tissue sets (carcasses, organs and intestines) and frozen until analysis. Tissue proteins were extracted, resolved by Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis (SDS-PAGE), and each sample lane was divided into ten equal portions. Following in-gel tryptic digestion, peptides released from each gel portion were identified and quantified by Liquid Chromatography-Mass Spectrometry (LC-MS/MS) to obtain the most complete, comparative study to date of proteomic responses to environmentally relevant doses of IR. This method provides a simple approach for use in ongoing epidemiologic studies of chronic exposure to environmentally relevant levels of IR and should also serve well in physiological, developmental, and toxicological studies.
The Transcription Factor PLZF Is Necessary for the Development and Function of Mouse Basophils

Key Points PLZF-deficient mice have reduced numbers of basophil progenitors and mature basophils. PLZF-deficient basophils respond poorly to the protein allergen papain. PLZF-deficient basophils are refractory to activation and produce less IL-4. Basophils are innate immune cells associated with type 2 immunity, allergic reactions, and host defense against parasite infections. In this study, we show that the transcription factor PLZF, which is known for its essential role in the function and development of several innate lymphocyte subsets, is also important for the myeloid-derived basophil lineage. PLZF-deficient mice had decreased numbers of basophil progenitors in the bone marrow and mature basophils in multiple peripheral tissues. Functionally, PLZF-deficient basophils were less responsive to IgE activation and produced reduced amounts of IL-4. The altered function of basophils resulted in a blunted Th2 T cell response to a protein allergen. Additionally, PLZF-deficient basophils had reduced expression of the IL-18 receptor, which impacted migration to lungs. PLZF, therefore, is a major player in controlling type 2 immune responses mediated not only by innate lymphocytes but also by myeloid-derived cells.
Twin-Twin Transfusion Syndrome with Anemia-Polycythemia: Prevalence, Characteristics, and Outcome

The aim of this study was to estimate the prevalence of co-existing anemia-polycythemia (AP) in twin pregnancies with twin-twin transfusion syndrome (TTTS) prior to laser surgery, and to evaluate the characteristics and outcomes in TTTS twins with and without AP. All TTTS cases treated with laser between 2001 and 2019 were retrospectively reviewed for the presence of AP before surgery. AP was defined as delta middle cerebral artery–peak systolic velocity > 0.5 multiples of the median. The primary outcome was a composite of perinatal survival and severe neurodevelopmental impairment (NDI). Secondary outcomes included procedure-related characteristics, severe neonatal morbidity, and disease-free survival. In total, 66% (461/696) of TTTS twin pregnancies were eligible for analysis. AP was detected in 15% (70/461) of the TTTS twins prior to laser surgery. Gestational age at laser was higher in the TTTS+AP group compared to the TTTS-only group—21.0 weeks (interquartile rage (IQR): 18.8–24.0) versus 19.3 weeks (IQR: 17.3–21.9), respectively (p < 0.0001). Fewer placental anastomoses were detected in the TTTS+AP group than in the TTTS-only group—five (IQR: 4–6) versus six (IQR: 5–8), respectively (p < 0.0001). Perinatal survival was 77% (599/782) in the TTTS-only group and 83% (118/142) in the TTTS+AP group (p = 0.130). Severe NDI was 8% (28/370) in TTTS-only and 3% (2/74) in TTTS+AP. TTTS-only twins showed more severe neonatal morbidity than twins with TTTS+AP—23% (132/575) versus 11% (13/115), respectively (p = 0.005). Disease-free survival was lower in the TTTS-only group compared to the TTTS+AP group—62% (341/548) versus 73% (72/98), respectively (p = 0.046). Thus, AP complicates 15% of TTTS twins prior to laser. TTTS+AP twins show a different placental angioarchitecture, a later time of onset of the disease, and a more favorable outcome.
Current understanding of the fundamental mechanisms of doped and loaded semiconducting metal oxide-based gas sensing materials.

Introducing additives in semiconducting metal oxides is, besides the use of filters, dynamic operation procedures and chemometric approaches, the most common way of tuning the sensitivity, selectivity and stability of chemoresitsive gas sensors. For the vast majority of commercially used gas sensing materials the introduction of additives is essential and is one of the longest lasting topics in gas sensor research. This article reviews the different chemical and electrical sensitization mechanisms of additives as well as the role of different structures. Based on state-of-the-art experimental findings, this article revises and updates the concepts that are used to explain the mechanisms through which the additives influence the performance of typical gas sensing materials, i.e. oxide nanoparticles arranged in a porous layer. The first sections classify the different additive structures, namely doped or loaded oxides as well as mixtures of oxides, and describe the basic working principle of pristine semiconducting metal oxide gas sensors. The subsequent sections discuss different chemical and/or electrical contributions to the sensitization by additive structures, their mutual influ-ence on each other and the way they impact the sensing properties. The presented concepts and models are essential for understanding the complex role of additives and provide the basis for a knowledge-based design of gas sensors based on semiconducting metal oxide nanoparticles, which is outlined in a separate section.
PyMethylProcess - convenient high-throughput preprocessing workflow for DNA methylation data

SUMMARY Performing highly parallelized preprocessing of methylation array data using Python can accelerate data preparation for downstream methylation analyses, including large scale production-ready machine learning pipelines. We present a highly reproducible, scalable pipeline (PyMethylProcess) that can be quickly set-up and deployed through Docker and PIP. AVAILABILITY AND IMPLEMENTATION Project Home Page: https://github.com/Christensen-Lab-Dartmouth/PyMethylProcess. Available on PyPI (pymethylprocess), Docker (joshualevy44/pymethylprocess).
Chaperone OsmY facilitates the biogenesis of a major family of autotransporters

OsmY is a widely conserved but poorly understood 20 kDa periplasmic protein. Using a folding biosensor, we previously obtained evidence that OsmY has molecular chaperone activity. To discover natural OsmY substrates, we screened for proteins that are destabilized and thus present at lower steady‐state levels in an osmY‐null strain. The abundance of an outer membrane protein called antigen 43 was substantially decreased and its β‐barrel domain was undetectable in the outer membrane of an osmY‐null strain. Antigen 43 is a member of the diffuse adherence family of autotransporters. Like strains that are defective in antigen 43 production, osmY‐null mutants failed to undergo cellular autoaggregation. In vitro, OsmY assisted in the refolding of the antigen 43 β‐barrel domain and protected it from added protease. Finally, an osmY‐null strain that expressed two members of the diffuse adherence family of autotransporters that are distantly related to antigen 43, EhaA and TibA, contained reduced levels of the proteins and failed to undergo cellular autoaggregation. Taken together, our results indicate that OsmY is involved in the biogenesis of a major subset of autotransporters, a group of proteins that play key roles in bacterial pathogenesis.
Intracellular Trapping of the Selective Phosphoglycerate Dehydrogenase (PHGDH) Inhibitor BI-4924 Disrupts Serine Biosynthesis.

Phosphoglycerate dehydrogenase (PHGDH) is known to be the rate limiting enzyme in the serine synthesis pathway (SSP) in humans. It converts glycolysis derived 3-phosphoglycerate to 3-phosphopyruvate in a NADH/NAD+-dependent oxidation reaction. Herein we report the discovery of BI-4916, a prodrug of the NADH/NAD+-competitive PHGDH inhibitor BI-4924 which has shown high selectivity against the majority of other dehydrogenase targets. Starting with a fragment-based screening (FBS) a subsequent hit optimization using structure based drug design (SBDD) was conducted to deliver a single digit nanomolar lead series and to improve potency by six orders of magnitude. To this end, an intracellular ester cleavage mechanism of the ester prodrug was utilized to achieve intracellular enrichment of the actual carboxylic acid based drug and thus overcome high cytosolic levels of the competitive cofactors NADH/NAD+.
Cannabis hyperalgesia: A phenomenon underestimated in the peri-operative period?

Patient’s pre-operative characteristics including severe pre-operative pain (at the surgery site or elsewhere) and its treatment may strongly influence postoperative recovery. In relation to the ‘opioid crisis’, pre-operative opioid intake in particular has been studied, and is implicated in poor early and late postoperative outcomes after various surgical procedures, particularly orthopaedic surgery.