Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibitory Immune Checkpoint Molecule Expression in Clinical Sepsis Studies: A Systematic Review

Supplemental Digital Content is available in the text. Objectives: Checkpoint inhibitors have been proposed for sepsis following reports of increased checkpoint molecule expression in septic patients. To determine whether clinical studies investigating checkpoint molecule expression provide strong evidence supporting trials of checkpoint inhibitors for sepsis. Data Sources: PubMed, EMBASE, Scopus, Web of Science, inception through October 2019. Study Selection: Studies comparing checkpoint molecule expression in septic patients versus healthy controls or critically ill nonseptic patients or in sepsis nonsurvivors versus survivors. Data Extraction: Two investigators extracted data and evaluated study quality. Data Synthesis: Thirty-six studies were retrieved. Across 26 studies, compared with healthy controls, septic patients had significantly (p ≤ 0.05) increased CD4+ lymphocyte programmed death-1 and monocyte programmed death-ligand-1 expression in most studies. Other checkpoint molecule expressions were variable and studied less frequently. Across 11 studies, compared with critically ill nonseptic, septic patients had significantly increased checkpoint molecule expression in three or fewer studies. Septic patients had higher severity of illness scores, comorbidities, and mortality in three studies providing analysis. Across 12 studies, compared with septic survivors, nonsurvivors had significantly increased expression of any checkpoint molecule on any cell type in five or fewer studies. Of all 36 studies, none adjusted for nonseptic covariates reported to increase checkpoint molecule expression. Conclusions: Although sepsis may increase some checkpoint molecule expression compared with healthy controls, the data are limited and inconsistent. Further, data from the more informative patient comparisons are potentially confounded by severity of illness. These clinical checkpoint molecule expression studies do not yet provide a strong rationale for trials of checkpoint inhibitor therapy for sepsis.
The effect of shoulder abduction and medial epicondylectomy on ulnar nerve strain: A preliminary study

Objectives: The primary aim was to determine whether a dynamic suture marker method of measuring ulnar nerve strain yields comparable results to strain gauges. The secondary aim was to assess the effect of elbow flexion, shoulder abduction and medial epicondylectomy on strain. Methods: In four embalmed elbows, ulnar nerve strain was measured using suture markers during elbow flexion and shoulder abduction before and after medial epicondylectomy. Linear regression analysis and Wilcoxon signed-rank test were used to analyse the results. Results: Ulnar nerve strain increased in direct proportion to elbow flexion angle before and after medial epicondylectomy, with one exception. At 90° shoulder abduction, strain was 0%–17%. Strain was greatest at 90° and least at 110° before and after medial epicondylectomy, P > 0.05. The effect of medial epicondylectomy varied. Strain was reduced at 90° by 5%, at 110° by 0% and at 120° by 1%; P > 0.05. Conclusions: The suture marker method yielded comparable results to strain gauges. Both shoulder abduction and medial epicondylectomy did not have statistically significant effects on ulnar nerve strain. However, only four embalmed elbows were studied in this preliminary study, so a large difference would be needed to produce a significant change. The finding that medial epicondylectomy fails to reduce strain raises questions about its role in treating cubital tunnel syndrome and highlights the need for further research. The authors believe that the technique described for dynamic strain assessment is applicable in an in vivo setting and therefore, should be used to compare strain properties of cadaveric and in vivo nerves.
Coupling Hydrogenation of Guaiacol with In Situ Hydrogen Production by Glycerol Aqueous Reforming over Ni/Al2O3 and Ni-X/Al2O3 (X = Cu, Mo, P) Catalysts

Biomass-derived liquids, such as bio-oil obtained by fast pyrolysis, can be a valuable source of fuels and chemicals. However, these liquids have high oxygen and water content, needing further upgrading typically involving hydrotreating using H2 at high pressure and temperature. The harsh reaction conditions and use of expensive H2 have hindered the progress of this technology and led to the search for alternative processes. In this work, hydrogenation in aqueous phase is investigated using in-situ produced hydrogen from reforming of glycerol, a low-value by-product from biodiesel production, over Ni-based catalysts. Guaiacol was selected as a bio-oil model compound and high conversion (95%) to phenol and aromatic ring hydrogenation products was obtained over Ni/γ-Al2O3 at 250 °C and 2-h reaction time. Seventy percent selectivity to cyclohexanol and cyclohexanone was achieved at this condition. Hydrogenation capacity of P and Mo modified Ni/γ-Al2O3 was inhibited because more hydrogen undergoes methanation, while Cu showed a good performance in suppressing methane formation. These results demonstrate the feasibility of coupling aqueous phase reforming of glycerol with bio-oil hydrogenation, enabling the reaction to be carried out at lower temperatures and pressures and without the need for molecular H2.
Hermaphroditism as a reproductive strategy for metazoans; some correlated benefits

Abstract The concept of hermaphroditism is examined, the terminology is reviewed, and several new terms are proposed: EUHERMAPHRODITISM for the occurrence together of eggs and sperm in the individual that produced them; TEMPORARY HERMAPHRODITISM for the few instances where euhermaphroditism is a brief transitional phase between sexes in protandry and protogyny, and opsiautogamy to designate the condition where sperm saved from an early male phase are used to fertilise eggs produced in a later female phase. An animal that functions successively in the different sex roles is considered to be quite distinct from one that functions as both male and female simultaneously. Further, the circumstances in which these different sexual modes are appropriate and the advantages that accrue from them are quite different. For this reason protandry, protogyny, and consecutive sexuality are not considered to be part of hermaphroditism, but rather aspects of labile gonochorism. A major idea advanced in this paper is that h.
Flavonoids as Potential Drugs for VPS13-Dependent Rare Neurodegenerative Diseases

Several rare neurodegenerative diseases, including chorea acanthocytosis, are caused by mutations in the VPS13A–D genes. Only symptomatic treatments for these diseases are available. Saccharomyces cerevisiae contains a unique VPS13 gene and the yeast vps13Δ mutant has been proven as a suitable model for drug tests. A library of drugs and an in-house library of natural compounds and their derivatives were screened for molecules preventing the growth defect of vps13Δ cells on medium with sodium dodecyl sulfate (SDS). Seven polyphenols, including the iron-binding flavone luteolin, were identified. The structure–activity relationship and molecular mechanisms underlying the action of luteolin were characterized. The FET4 gene, which encodes an iron transporter, was found to be a multicopy suppressor of vps13Δ, pointing out the importance of iron in response to SDS stress. The growth defect of vps13Δ in SDS-supplemented medium was also alleviated by the addition of iron salts. Suppression did not involve cell antioxidant responses, as chemical antioxidants were not active. Our findings support that luteolin and iron may target the same cellular process, possibly the synthesis of sphingolipids. Unveiling the mechanisms of action of chemical and genetic suppressors of vps13Δ may help to better understand VPS13A–D-dependent pathogenesis and to develop novel therapeutic strategies.
Polymeric Carbon Nitride Armored Centimeter-Wide Organic Droplets in Water for All-Liquid Heterophase Emission Technology

High potential of emission chemistry has been visualized in many fields, from sensors and imaging to displays. In general, conjugated polymers are the top rankers for such chemistry, despite the fact that they bring solubility problems, high expenses, toxicity and demanding synthesis. Metal-free polymeric semiconductor graphitic carbon nitride (g-CN) has been an attractive candidate for visible light-induced photocatalysis, and its emission properties have been optimized and explored recently. Herein, we present modified g-CN nanoparticles as organodispersible conjugated polymer materials to be utilized in a heterophase emission systems. The injection of a g-CN organic dispersion in aqueous polymer solution not only provides retention of the shape by Pickering stabilization of g-CN, but high intensity emission is also obtained. The heterophase all-liquid emission display can be further modified by the addition of simple conjugated organic molecules to the initial g-CN dispersion, which provides a platform for multicolor emission. We believe that such shape-tailored and stabilized liquid–liquid multicolor emission systems are intriguing for sensing, displays and photonics.
Composition and Formation of the Saccharomyces cerevisiae Centromeric Nucleosome

The kinetochore is a complex, multi-protein structure required for proper chromosome segregation in all eukaryotes. The Saccharomyces cerevisiae kinetochore consists of over 65 known proteins which work in concert to facilitate equal distribution of the replicated genome. The S. cerevisiae CenH3 histone variant Cse4 is an evolutionarily conserved histone H3-like inner kinetochore protein that is essential for kinetochore function. Through immunopurification of Cse4 interacting proteins we have identified the previously uncharacterized protein Scm3. Here we report the characterization of S. cerevisiae Scm3, an essential protein with putative orthologs in fungi which possess either point or regional centromeres. We find that Scm3 localizes to all budding yeast centromeres. Construction of a conditional allele of SCM3 has allowed us to characterize the phenotype of cells lacking Scm3. Scm3 depleted cells fail to properly localize the components of the inner kinetochore, including Cse4 and Ndc10, and arrest in metaphase with duplicated spindle poles, short spindles, and unequal DNA distribution in the daughter cells. Our data suggest that Scm3 is not an actual component of the centromeric nucleosome, but rather intimately associates with it. Additional in vivo and in vitro analysis of Cse4 reveals a single centromeric nucleosome that contains an octamer of Cse4, H2A, H2B, and H4. Based on these findings, we hypothesize that Scm3 is a novel yeast inner kinetochore protein that functions in the formation and maintenance of a segregation competent kinetochore through recruitment of the Cse4 octameric nucleosome.
In-Vitro Identification and In-Vivo Confirmation of DNA Methylation Biomarkers for Urothelial Cancer

We identified DNA methylation targets specific for urothelial cancer (UC) by genome-wide methylation difference analysis of human urothelial (RT4, J82, 5637), prostate (LNCAP, DU-145, PC3) and renal (RCC-KP, CAKI-2, CAL-54) cancer cell lines with their respective primary epithelial cells. A large overlap of differentially methylated targets between all organs was observed and 40 Cytosine-phosphate-Guanine motifs (CpGs) were only specific for UC cells. Of those sites, two also showed high methylation differences (≥47%) in vivo when we further compared our data to those previously obtained in our array-based analyses of urine samples in 12 UC patients and 12 controls. Using mass spectrometry, we finally assessed seven CpG sites in this “bladder-specific” region of interest in urine samples of patients with urothelial (n = 293), prostate (n = 75) and renal (n = 23) cancer, and 143 controls. DNA methylation was significantly increased in UC compared to non-UC individuals. The differences were more pronounced for males rather than females. Male UC cases could be distinguished from non-UC individuals with >30% sensitivity at 95% specificity (Area under the curve (AUC) 0.85). In summary, methylation sites highly specific in UC cell lines were also specific in urine samples of UC patients showing that in-vitro data can be successfully used to identify biomarker candidates of in-vivo relevance.
Understanding the Biosynthetic Changes that Give Origin to the Distinctive Flavor of Sotol: Microbial Identification and Analysis of the Volatile Metabolites Profiles During Sotol (Dasylirion sp.) Must Fermentation

In northern Mexico, the distilled spirit sotol with a denomination of origin is made from species of Dasylirion. The configuration of the volatile metabolites produced during the spontaneous fermentation of Dasylirion sp. must is insufficiently understood. In this study, the aim was to investigate the composition of the microbial consortia, describe the variation of volatile metabolites, and relate such profiles with their particular flavor attributes during the fermentation of sotol (Dasylirion sp.) must. Ascomycota was the phylum of most strains identified with 75% of total abundance. The genus of fermenting yeasts constituted of 101 Pichia strains and 13 Saccharomyces strains. A total of 57 volatile metabolites were identified and grouped into ten classes. The first stage of fermentation was composed of diesel, green, fruity, and cheesy attributes due to butyl 2-methylpropanoate, octan-1-ol, ethyl octanoate, and butanal, respectively, followed by a variation to pungent and sweet descriptors due to 3-methylbutan-1-ol and butyl 2-methylpropanoate. The final stage was described by floral, ethereal-winey, and vinegar attributes related to ethyl ethanimidate, 2-methylpropan-1-ol, and 2-hydroxyacetic acid. Our results improve the knowledge of the variations of volatile metabolites during the fermentation of sotol must and their contribution to its distinctive flavor.
A Smartphone Crowdsensing System Enabling Environmental Crowdsourcing for Municipality Resource Allocation with LSTM Stochastic Prediction

Resource allocation of the availability of certain departments for dealing with emergency recovery is of high importance in municipalities. Efficient planning for facing possible disasters in the coverage area of a municipality provides reassurance for citizens. Citizens can assist with such malfunctions by acting as human sensors at the edge of an infrastructure to provide instant feedback to the appropriate departments fixing the problems. However, municipalities have limited department resources to handle upcoming emergency events. In this study, we propose a smartphone crowdsensing system that is based on citizens’ reactions as human sensors at the edge of a municipality infrastructure to supplement malfunctions exploiting environmental crowdsourcing location-allocation capabilities. A long short-term memory (LSTM) neural network is incorporated to learn the occurrence of such emergencies. The LSTM is able to stochastically predict future emergency situations, acting as an early warning component of the system. Such a mechanism may be used to provide adequate department resource allocation to treat future emergencies.
Host-pathogen interaction in Aspergillus infection

A successful pathogen is one that is able to effectively survive and evade detection by the host innate immune defense. Fungal pathogens have adopted strategies which evade host defense and eventually cause disease in at-risk patients. Shielding of stimulatory surface recognition molecules, shedding of decoy components, induction of anti-inflammatory signals, complement evasion and resilient survival capacity are successful evasion mechanisms employed by fungal pathogens. Understanding these complex pathways of immune evasion can potentially contribute to development of novel therapeutic strategies against fungal infections.
Characteristics of Extracellular Vesicles Released by the Pathogenic Yeast-Like Fungi Candida glabrata, Candida parapsilosis and Candida tropicalis

Candida spp. yeast-like fungi are opportunistic pathogens in humans and have been recently found to release extracellular vesicles (EVs) that are involved in many vital biological processes in fungal cells. These include communication between microorganisms and host–pathogen interactions during infection. The production of EVs and their content have been significantly characterized in the most common candidal species Candida albicans, including the identification of numerous virulence factors and cytoplasmic proteins in the EV cargo. We have here conducted the isolation and proteomic characterization of EVs produced by the clinically important non-albicans Candida species C. glabrata, C. tropicalis and C. parapsilosis. With the use of ultracentrifugation of the cell-free culture supernatant, the candidal EVs were collected and found to be a heterogeneous population of particles for each species with sizes ranging from 60–280 nm. The proteinaceous contents of these vesicles were analyzed using LC-MS/MS, with particular attention paid to surface-expressed proteins that would come into immediate and direct contact with host cells. We thereby identified 42 extracellular and surface-connected proteins from C. glabrata, 33 from C. parapsilosis, and 34 from C. tropicalis, including membrane-associated transporters, glycoproteins and enzymes involved in the organization of the fungal cell wall, as well as several cytoplasmic proteins, including alcohol dehydrogenase, enolase, glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase and pyruvate kinase, for which the vesicular transport is a possible mechanism underlying their non-classical secretion.
ZSF1 rat as animal model for HFpEF: Development of reduced diastolic function and skeletal muscle dysfunction

The prevalence of heart failure with preserved ejection fraction (HFpEF) is still increasing, and so far, no pharmaceutical treatment has proven to be effective. A key obstacle for testing new pharmaceutical substances is the availability of suitable animal models for HFpEF, which realistically reflect the clinical picture. The aim of the present study was to characterize the development of HFpEF and skeletal muscle (SM) dysfunction in ZSF1 rats over time.
Redistribution of a Golgi glycoprotein in plant cells treated with Brefeldin A

The fungal fatty acid derivative Brefeldin A (BFA), has been used to study the reversible distribution of a Golgi glycoprotein, the JIM 84 epitope, into the cytosol of higher plant cells. Treatment of both maize and onion root tip cells resulted in a rearrangement of the Golgi stacks into either circular formations or a perinuclear distribution. The Golgi cisternae became curved and vesiculated and in cells where the Golgi apparatus was totally dispersed the JIM 84 epitope was associated with large areas in the cytosol which were also vesiculated. On removal of the BFA the Golgi apparatus reformed and the JIM 84 epitope was again located in the cisternal stacks. This mode of BFA action is compared with that so far described for animal cells.
Enhanced UV-Reflection Facilitated a Shift in the Pollination System of the Red Poppy, Papaver rhoeas (Papaveraceae)

Evolutionary change is considered a major factor influencing the invasion of new habitats by plants. Yet, evidence on how such modifications promote range expansion remains rather limited. Here we investigated flower color modifications in the red poppy, Papaver rhoeas (Papaveraceae), as a result of its introduction into Central Europe and the impact of those modifications on its interactions with pollinators. We found that while flowers of Eastern Mediterranean poppies reflect exclusively in the red part of the spectrum, those of Central European poppies reflect both red and ultraviolet (UV) light. This change coincides with a shift from pollination by glaphyrid beetles (Glaphyridae) to bees. Glaphyrids have red-sensitive photoreceptors that are absent in bees, which therefore will not be attracted by colors of exclusively red-reflecting flowers. However, UV-reflecting flowers are easily detectable by bees, as revealed by visual modeling. In the North Mediterranean, flowers with low and high UV reflectance occur sympatrically. We hypothesize that Central European populations of P. rhoeas were initially polymorphic with respect to their flower color and that UV reflection drove a shift in the pollination system of P. rhoeas that facilitated its spread across Europe.
LDH-Co-Fe-Acetate: A New Efficient Sorbent for Azoic Dye Removal and Elaboration by Hydrolysis in Polyol, Characterization, Adsorption, and Anionic Exchange of Direct Red 2 as a Model Anionic Dye

A new, double hydroxide based on Co and Fe was elaborated on by forced hydrolysis in a polyol medium. Complementary characterization techniques show that this new phase belongs to the layered double hydroxide family (LDH) with Co2+ and Fe3+ ions located in the octahedral sites of the bucite-like structure. The acetate anions occupy interlayer space with an interlamellar distance of 12.70 Å. This large distance likely facilitates the exchange reaction. Acetates were exchanged by carbonates. The as-obtained compound Co-Fe-Ac/Ex shows an interlamellar distance of 7.67 Å. The adsorption of direct red 2 by Co-Fe-Ac-LDH has been examined in order to measure the capability of this new LDH to eliminate highly toxic azoic anionic dyes from waste water and was compared with that of Co-Fe-Ac/Ex and Co-Fe-CO3/A (synthesized in an aqueous medium). The adsorption capacity was found to depend on contact time, pH, initial dye concentration, and heating temperature. Concerning CoFeAc-LDH, the dye uptake reaches a high level (588 mg/g) due to the occurrence of both adsorption processes: physisorption on the external surface and chemical sorption due to the intercalation of dye by exchange with an acetate anion. The study enables us to quantify the uptake amount of each effect in which the intercalation has the most important amount (418 mg/g).
Food Effects on Oral Drug Absorption: Application of Physiologically-Based Pharmacokinetic Modeling as a Predictive Tool

The bioavailability of an orally administered small molecule is often dictated by drug-specific physicochemical characteristics and is influenced by many biological processes. For example, in fed or fasted conditions, the transit time within the gastrointestinal tract can vary, confounding the ability to predict the oral absorption. As such, the effects of food on the pharmacokinetics of compounds in the various biopharmaceutics classification system (BCS) classes need to be assessed. The consumption of food leads to physiological changes, including fluctuations in the gastric and intestinal pH, a delay in gastric emptying, an increased bile secretion, and an increased splanchnic and hepatic blood flow. Despite the significant impact of a drug’s absorption and dissolution, food effects have not been fully studied and are often overlooked. Physiologically-based pharmacokinetic (PBPK) models can be used to mechanistically simulate a compound’s pharmacokinetics under fed or fasted conditions, while integrating drug properties such as solubility and permeability. This review discusses the PBPK models published in the literature predicting the food effects, the models’ strengths and shortcomings, as well as future steps to mitigate the current knowledge gap. We observed gaps in knowledge which limits the ability of PBPK models to predict the negative food effects and food effects in the pediatric population. Overall, the further development of PBPK models to predict food effects will provide a mechanistic basis to understand a drug’s behavior in fed and fasted conditions, and will help enable the drug development process.