Miracle-dz/UniFAR-FTUs huggingface dataset:
Consequences of Early Separation of Maternal-Newborn Dyad in Neonates Born to SARS-CoV-2 Positive Mothers: An Observational Study

As the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continues its spread all over the world, data on perinatal management of the maternal-infant dyad are urgent. We performed an observational study to describe the effects of the early separation of the maternal-infant dyad, in case of maternal SARS-CoV-2 infection. We reported the medical records for 37 neonates born to 37 SARS-CoV-2 positive mothers in a setting of separation of the dyad after birth. Data on neonatal infection, clinical condition, and breastfeeding rate were recorded until the first month of life. No maternal deaths were recorded; 37.8% of women had at least one pregnancy-related complication. We reported a high adherence to recommended safety measures after discharged with 84.8% of the mothers using at least one personal protective device and 51.5% using all the protective devices. We reported one case of vertical transmission and no cases of horizontal transmission. However, the separation of the dyad had a negative impact on breastfeeding because only 23.5% of the newborns received exclusively human milk during the first month of life. Despite early separation of the dyad protecting the newborns from possible horizontal transmission of SARS-CoV-2, it negatively affects breastfeeding during the first months of life.
Association of Water Intake with Hand Grip Strength in Community-Dwelling Older Adults

Although recent clinical studies have suggested that water intake enhances muscle mass, its impact on muscle strength remain unclear, especially in older adults. This cross-sectional, population-based study using a representative sample of Koreans investigated the relationship of water intake with hand grip strength (HGS) in 4443 older adults, including 2090 men aged ≥50 years and 2253 postmenopausal women. A digital grip strength dynamometer was used for HGS assessment. Low muscle strength was defined by the Korean-specific HGS cut-off value and adequate water intake was defined according to the Korean dietary reference intakes. In an unadjusted model, water intake was significantly higher in men and women without than with low muscle strength (both p < 0.001), but this difference disappeared after adjustment for confounding variables in both men (p = 0.050) and women (p = 0.245). Similarly, the correlation between water intake and HGS, the difference in HGS depending on adequate water intake status, and the risk of low muscle strength depending on water intake quartile were significant only in the unadjusted model. These data indicate that factors such as age, body size, and resistance exercise contribute to improvements in HGS in older adults, whereas water intake may not.
Magnetic Nanostructures as Emerging Therapeutic Tools to Boost Anti-Tumour Immunity

Simple Summary Immunotherapy represents an attractive therapeutic option for effective treatment of different forms of cancers. However, many patients exhibit primary or acquired resistance to conventional immunotherapies. In recent years, the encapsulation of immunotherapeutics into nanoparticles is emerging as a promising strategy to improve the responsiveness of immunologically “cold” tumors. Among the several types of nanoparticles explored for cancer immunotherapy, magnetic nanoparticles are particularly interesting since they act as carriers for immunotherapeutic agents and display self-adjuvanting properties. In addition, the ability of magnetic nanostructures to respond to an altering magnetic field (AMF) can be exploited to facilitate the movement of therapeutic-loaded nanoparticles at the desired site or promote localized heating for the thermal ablation of tumors. This review examines the peculiar properties of magnetic nanoparticles and how they can be harnessed for the design of innovative single or combinatorial cancer immunotherapies. Abstract Cancer immunotherapy has shown remarkable results in various cancer types through a range of immunotherapeutic approaches, including chimeric antigen receptor-T cell (CAR-T) therapy, immune checkpoint blockade (ICB), and therapeutic vaccines. Despite the enormous potential of cancer immunotherapy, its application in various clinical settings has been limited by immune evasion and immune suppressive mechanisms occurring locally or systemically, low durable response rates, and severe side effects. In the last decades, the rapid advancement of nanotechnology has been aiming at the development of novel synthetic nanocarriers enabling precise and enhanced delivery of immunotherapeutics, while improving drug stability and effectiveness. Magnetic nanostructured formulations are particularly intriguing because of their easy surface functionalization, low cost, and robust manufacturing procedures, together with their suitability for the implementation of magnetically-guided and heat-based therapeutic strategies. Here, we summarize and discuss the unique features of magnetic-based nanostructures, which can be opportunely designed to potentiate classic immunotherapies, such as therapeutic vaccines, ICB, adoptive cell therapy (ACT), and in situ vaccination. Finally, we focus on how multifunctional magnetic delivery systems can facilitate the anti-tumour therapies relying on multiple immunotherapies and/or other therapeutic modalities. Combinatorial magnetic-based therapies are indeed offering the possibility to overcome current challenges in cancer immunotherapy.
Large Clostridial Toxins: Mechanisms and Roles in Disease

Large clostridial toxins (LCTs) are a family of bacterial exotoxins that infiltrate and destroy target cells. Members of the LCT family include Clostridioides difficile toxins TcdA and TcdB, Paeniclostridium sordellii toxins TcsL and TcsH, Clostridium novyi toxin TcnA, and Clostridium perfringens toxin TpeL. SUMMARY Large clostridial toxins (LCTs) are a family of bacterial exotoxins that infiltrate and destroy target cells. Members of the LCT family include Clostridioides difficile toxins TcdA and TcdB, Paeniclostridium sordellii toxins TcsL and TcsH, Clostridium novyi toxin TcnA, and Clostridium perfringens toxin TpeL. Since the 19th century, LCT-secreting bacteria have been isolated from the blood, organs, and wounds of diseased individuals, and LCTs have been implicated as the primary virulence factors in a variety of infections, including C. difficile infection and some cases of wound-associated gas gangrene. Clostridia express and secrete LCTs in response to various physiological signals. LCTs invade host cells by binding specific cell surface receptors, ultimately leading to internalization into acidified vesicles. Acidic pH promotes conformational changes within LCTs, which culminates in translocation of the N-terminal glycosyltransferase and cysteine protease domain across the endosomal membrane and into the cytosol, leading first to cytopathic effects and later to cytotoxic effects. The focus of this review is on the role of LCTs in infection and disease, the mechanism of LCT intoxication, with emphasis on recent structural work and toxin subtyping analysis, and the genomic discovery and characterization of LCT homologues. We provide a comprehensive review of these topics and offer our perspective on emerging questions and future research directions for this enigmatic family of toxins.
Identification of Homologous Polyprenols from Thermophilic Bacteria

Sixteen strains of five genera of thermophilic bacteria, i.e., Alicyclobacillus, Brevibacillus, Geobacillus, Meiothermus, and Thermus, were cultivated at a temperature from 42 to 70 °C. Twelve strains were obtained from the Czech Collection of Microorganisms, while four were directly isolated and identified by 16S rRNA gene sequencing from the hot springs of the world-famous Carlsbad spa (Czech Republic). Polyprenol homologs from C40 to C65 as well as free undecaprenol (C55), undecaprenyl phosphate, and undecaprenyl diphosphate were identified by shotgun analysis and RP-HPLC/MS-ESI+ (reverse phase high-performance liquid chromatography–high-resolution positive electrospray ionization mass spectrometry). The limit of detection (50 pM) was determined for individual homologs and free polyprenols and their phosphates. Thus, it has been shown that at least some thermophilic bacteria produce not just the major C55 polyprenol as previously described, but a mixture of homologs.
Coordinate Descent Method for <inline-formula><tex-math notation="LaTeX">$k$</tex-math><alternatives><mml:math><mml:mi>k</mml:mi></mml:math><inline-graphic xlink:href="xue-ieq1-3085739.gif"/></alternatives></inline-formula>-means

<inline-formula><tex-math notation="LaTeX">$k$</tex-math><alternatives><mml:math><mml:mi>k</mml:mi></mml:math><inline-graphic xlink:href="xue-ieq2-3085739.gif"/></alternatives></inline-formula>-means method using Lloyd heuristic is a traditional clustering method which has played a key role in multiple downstream tasks of machine learning because of its simplicity. However, Lloyd heuristic always finds a bad local minimum, i.e., the bad local minimum makes objective function value not small enough, which limits the performance of <inline-formula><tex-math notation="LaTeX">$k$</tex-math><alternatives><mml:math><mml:mi>k</mml:mi></mml:math><inline-graphic xlink:href="xue-ieq3-3085739.gif"/></alternatives></inline-formula>-means. In this paper, we use coordinate descent (CD) method to solve the problem. First, we show that the <inline-formula><tex-math notation="LaTeX">$k$</tex-math><alternatives><mml:math><mml:mi>k</mml:mi></mml:math><inline-graphic xlink:href="xue-ieq4-3085739.gif"/></alternatives></inline-formula>-means minimization problem can be reformulated as a trace maximization problem, then a simple and efficient coordinate descent scheme is proposed to solve the maximization problem. Two interesting findings through theory are that Lloyd cannot decrease the objective function value of <inline-formula><tex-math notation="LaTeX">$k$</tex-math><alternatives><mml:math><mml:mi>k</mml:mi></mml:math><inline-graphic xlink:href="xue-ieq5-3085739.gif"/></alternatives></inline-formula>-means produced by our CD further, and our proposed method CD to solve <inline-formula><tex-math notation="LaTeX">$k$</tex-math><alternatives><mml:math><mml:mi>k</mml:mi></mml:math><inline-graphic xlink:href="xue-ieq6-3085739.gif"/></alternatives></inline-formula>-means problem can avoid produce empty clusters. In addition, according to the computational complexity analysis, it is verified CD has the same time complexity with original <inline-formula><tex-math notation="LaTeX">$k$</tex-math><alternatives><mml:math><mml:mi>k</mml:mi></mml:math><inline-graphic xlink:href="xue-ieq7-3085739.gif"/></alternatives></inline-formula>-means method. Extensive experiments including statistical hypothesis testing, on several real-world datasets with varying number of clusters, varying number of samples and varying number of dimensions show that CD performs better compared to Lloyd, i.e., lower objective value, better local minimum and fewer iterations. And CD is more robust to initialization than Lloyd whether the initialization strategy is random or initialization of <inline-formula><tex-math notation="LaTeX">$k$</tex-math><alternatives><mml:math><mml:mi>k</mml:mi></mml:math><inline-graphic xlink:href="xue-ieq8-3085739.gif"/></alternatives></inline-formula>-means++.
Se-Enrichment Pattern, Composition, and Aroma Profile of Ripe Tomatoes after Sodium Selenate Foliar Spraying Performed at Different Plant Developmental Stages

Foliar spray with selenium salts can be used to fortify tomatoes, but the results vary in relation to the Se concentration and the plant developmental stage. The effects of foliar spraying with sodium selenate at concentrations of 0, 1, and 1.5 mg Se L−1 at flowering and fruit immature green stage on Se accumulation and quality traits of tomatoes at ripening were investigated. Selenium accumulated up to 0.95 µg 100 g FW−1, with no significant difference between the two concentrations used in fruit of the first truss. The treatment performed at the flowering stage resulted in a higher selenium concentration compared to the immature green treatment in the fruit of the second truss. Cu, Zn, K, and Ca content was slightly modified by Se application, with no decrease in fruit quality. When applied at the immature green stage, Se reduced the incidence of blossom-end rot. A group of volatile organic compounds (2-phenylethyl alcohol, guaiacol, (E)-2-heptenal, 1-penten-3-one and (E)-2-pentenal), positively correlated with consumer liking and flavor intensity, increased following Se treatment. These findings indicate that foliar spraying, particularly if performed at flowering stage, is an efficient method to enrich tomatoes with Se, also resulting in positive changes in fruit aroma profile.
Serratia symbiotica Enhances Fatty Acid Metabolism of Pea Aphid to Promote Host Development

Bacterial symbionts associated with insects are often involved in host development and ecological adaptation. Serratia symbiotica, a common facultative endosymbiont harbored in pea aphids, improves host fitness and heat tolerance, but studies concerning the nutritional metabolism and impact on the aphid host associated with carrying Serratia are limited. In the current study, we showed that Serratia-infected aphids had a shorter nymphal developmental time and higher body weight than Serratia-free aphids when fed on detached leaves. Genes connecting to fatty acid biosynthesis and elongation were up-regulated in Serratia-infected aphids. Specifically, elevated expression of fatty acid synthase 1 (FASN1) and diacylglycerol-o-acyltransferase 2 (DGAT2) could result in accumulation of myristic acid, palmitic acid, linoleic acid, and arachidic acid in fat bodies. Impairing fatty acid synthesis in Serratia-infected pea aphids either by a pharmacological inhibitor or through silencing FASN1 and DGAT2 expression prolonged the nymphal growth period and decreased the aphid body weight. Conversely, supplementation of myristic acid (C14:0) to these aphids restored their normal development and weight gain. Our results indicated that Serratia promoted development and growth of its aphid host through enhancing fatty acid biosynthesis. Our discovery has shed more light on nutritional effects underlying the symbiosis between aphids and facultative endosymbionts.
Double network laminarin-boronic/alginate dynamic bioink for 3D bioprinting cell-laden constructs

The design of dynamically crosslinked hydrogel bioinks for three-dimensional (3D) bioprinting is emerging as a valuable strategy to advance the fabrication of mechanically tuneable cell-laden constructs for 3D in vitro disease modelling and tissue engineering applications. Herein, a dynamic bioink comprising boronic acid-functionalised laminarin and alginate is explored for bioprinting 3D constructs under physiologically relevant conditions. The formulated bioink takes advantage of a double crosslinked network that combines covalent but reversible boronate ester bonds and ionic gelation via divalent cations. Moreover, it exhibits suitable rheological properties and improved mechanical features owing to its modular crosslinking chemistry, yielding stable constructs with user-programmable architecture. We explored such dynamic bioink as a supporting matrix for different cell classes, namely osteoblast precursors, fibroblasts and breast cancer cells. The resulting cell-laden bioprinted hydrogels display a homogeneous cell distribution post-printing and exceptional cell viability (>90%) that can be maintained for prolonged time periods in culture (14 days) for all cell lines. This simple and chemically versatile approach is envisaged to accelerate the development of multifunctional bioinks and contribute towards the fabrication of biomimetic 3D scaffolds with applicability in a wide range of predictive or exploratory biomedical platforms.
The Evolution of Rag Gene Enhancers and Transcription Factor E and Id Proteins in the Adaptive Immune System

Adaptive immunity relies on the V(D)J DNA recombination of immunoglobulin (Ig) and T cell receptor (TCR) genes, which enables the recognition of highly diverse antigens and the elicitation of antigen-specific immune responses. This process is mediated by recombination-activating gene (Rag) 1 and Rag2 (Rag1/2), whose expression is strictly controlled in a cell type-specific manner; the expression of Rag1/2 genes represents a hallmark of lymphoid lineage commitment. Although Rag genes are known to be evolutionally conserved among jawed vertebrates, how Rag genes are regulated by lineage-specific transcription factors (TFs) and how their regulatory system evolved among vertebrates have not been fully elucidated. Here, we reviewed the current body of knowledge concerning the cis-regulatory elements (CREs) of Rag genes and the evolution of the basic helix-loop-helix TF E protein regulating Rag gene CREs, as well as the evolution of the antagonist of this protein, the Id protein. This may help to understand how the adaptive immune system develops along with the evolution of responsible TFs and enhancers.
Express Letter Detecting pyrolysis products from bacteria on Mars

A pyrolysis/sublimation technique was developed to isolate volatile amine compounds from a Mars soil analogue inoculated with V10 billion Escherichia coli cells. In this technique, the inoculated soil is heated to 500‡C for several seconds at Martian ambient pressure and the sublimate, collected by a cold finger, then analyzed using high performance liquid chromatography. Methylamine and ethylamine, produced from glycine and alanine decarboxylation, were the most abundant amine compounds detected after pyrolysis of the cells. A heating cycle similar to that utilized in our experiment was also used to release organic compounds from the Martian soil in the 1976 Viking gas chromatography/mass spectrometry (GC/MS) pyrolysis experiment. The Viking GC/MS did not detect any organic compounds of Martian origin above a level of a few parts per billion in the Martian surface soil. Although the Viking GC/MS instruments were not specifically designed to search for the presence of living cells on Mars, our experimental results indicate that at the part per billion level, the degradation products generated from several million bacterial cells per gram of Martian soil would not have been detected. fl 2001 Elsevier Science B.V. All rights reserved.
Rodent-Related Zoonotic Pathogens at the Human–Animal–Environment Interface in Qatar: A Systematic Review and Meta-Analysis

Rodents are one of the most diversified terrestrial mammals, and they perform several beneficial activities in nature. These animals are also important as carriers of many pathogens with public health importance. The current systematic review was conducted to formulate a true depiction of rodent-related zoonoses in Qatar. Following systematic searches on PubMed, Scopus, Science Direct, and Web of Science and a screening process, a total of 94 published articles were selected and studied. The studied articles reported 23 rodent-related zoonotic pathogens that include nine bacterial, eleven parasitic, and three viral pathogens, from which the frequently reported pathogens were Mycobacterium tuberculosis (32 reports), Escherichia coli (23), and Salmonella spp. (16). The possible pathway of entry of the rodent-borne pathogens can be the land port, seaports, and airport of Qatar through carrier humans and animals, contaminated food, and agricultural products. The pathogens can be conserved internally by rodents, pets, and livestock; by agricultural production systems; and by food marketing chains. The overall estimated pooled prevalence of the pathogens among the human population was 4.27% (95%CI: 4.03–4.51%; p < 0.001) with significant heterogeneity (I2 = 99.50%). The top three highest prevalent pathogens were M. tuberculosis (30.90%; 22.75–39.04%; p < 0.001; I2 = 99.70%) followed by Toxoplasma gondii (21.93%; 6.23–37.61%; p < 0.001; I2 = 99.30%) and hepatitis E virus (18.29%; 11.72–24.86%; p < 0.001; I2 = 96.70%). However, there is a knowledge gap about the listed pathogens regarding the occurrence, transmission pathways, and rodent role in transmission dynamics at the human–animal–environment interface in Qatar. Further studies are required to explore the role of rodents in spreading zoonotic pathogens through the One Health framework, consisting of zoologists, ecologists, microbiologists, entomologists, veterinarians, and public health experts in this country.
Process Development of Fly Ash-Based Geopolymer Mortars in View of the Mechanical Characteristics

This study aimed to determine the effects of design parameters, including the liquid/solid ratio (L/S), Na2SiO3/NaOH weight ratio, and curing temperature, on class F fly ash-based geopolymer composites. For this purpose, two disparate sources of fly ash were supplied from Çatalağzı (FA) and İsken Sugözü (FB) Thermal Power Plants in Turkey. Two different L/S ratios of 0.2 and 0.4 were used. The Na2SiO3/NaOH ratios in the alkaline solutions were 1, 1.5, 2, 2.5, and 3 by weight for each type of geopolymer mixture. Then, 40 different mixes were cured at two specific temperatures (70 °C and 100 °C) for 24 h and then preserved at room temperature until testing. Thereafter, the physical water absorption properties, apparent porosity, and bulk density were examined at 28 days on the hardened mortars. Additionally, compressive and flexural tests were applied to the geopolymers at 7, 28, and 90 days. It was found that the highest compressive strength was 60.1 MPa for the geopolymer manufactured with an L/S of 0.2 and Na2SiO3/NaOH ratio of 2. Moreover, the best thermal curing temperature for obtaining optimal strength characteristics was 100 °C for the FB.
Who’s Driving? Switch of Drivers in Immunotherapy-Treated Progressing Sinonasal Melanoma

Simple Summary Here, we monitored the course of the disease and treatment of sinonasal melanoma patients. Since treatment options are rare, immunotherapy is often the treatment of choice. However, intrinsic or acquired resistance to treatment may occur. We assessed the mutational status of the tumors and metastases during the course of therapy and recognized a switch of the oncogenic drivers to mutant NRAS in progressing disease. As a switch of drivers (other than the addition of a second driver) has not been reported yet, longitudinal molecular testing and the awareness of molecular heterogeneity of sinonasal melanoma is crucial. Abstract Mucosal melanoma can be driven by various driver mutations in genes such as NRAS, KIT, or KRAS. However, some cases present with only weak drivers, or lacking known oncogenic drivers, suggesting immunotherapy over targeted therapy. While resistance mechanisms to immunotherapy in cutaneous melanoma have been uncovered, including alterations in JAK1/2, B2M, or STK11, a switch of oncogenic drivers under immunotherapy has not yet been observed. We report three cases of metastatic sinonasal melanoma that switched oncogenic drivers from KRAS, KIT, or no driver to NRAS during or after immunotherapy, thereby showing progressive disease. One of the cases presented with three spatially separate driver mutations in the primary tumor, whereas the NRAS clone persisted under immunotherapy. In comparison, three different control cases receiving radiotherapy only did not show a change of the detectable molecular drivers in their respective recurrences or metastases. In summary, these data provide an important rationale for longitudinal molecular testing, based on evidence for an unforeseen recurrent event of molecular driver switch to NRAS in progressing sinonasal melanoma. These findings provide the basis for further studies on a potential causal relation of emerging NRAS mutant clones and immunotherapy.