Miracle-dz/UniFAR-FTUs huggingface dataset:
Predictors of Response and Survival in Immune Checkpoint Inhibitor-Treated Unresectable Hepatocellular Carcinoma

Immune checkpoint inhibitors (ICIs) with nivolumab and pembrolizumab are promising agents for advanced hepatocellular carcinoma (HCC) but lack of effective biomarkers. We aimed to investigate the potential predictors of response and factors associated with overall survival (OS) for ICI treatment in unresectable HCC patients. Ninety-five patients who received nivolumab or pembrolizumab for unresectable HCC were enrolled for analyses. Radiologic evaluation was based on RECIST v1.1. Factors associated with outcomes were analyzed. Of 90 patients with evaluable images, the objective response rate (ORR) was 24.4%. Patients at Child–Pugh A or received combination treatment had higher ORR. Early alpha-fetoprotein (AFP) >10% reduction (within 4 weeks) was the only independent predictor of best objective response (odds ratio: 7.259, p = 0.001). For patients with baseline AFP ≥10 ng/mL, significantly higher ORR (63.6% vs. 10.2%, p < 0.001) and disease control rate (81.8% vs. 14.3%, p < 0.001) were observed in those with early AFP reduction than those without. In addition, early AFP reduction and albumin-bilirubin (ALBI) grade or Child–Pugh class were independent factors associated with OS in different models. In conclusion, a 10-10 rule of early AFP response can predict objective response and survival to ICI treatment in unresectable HCC. ALBI grade and Child–Pugh class determines survival by ICI treatment.
The effect of fluid shear stress on fibroblasts and stem cells on plane and groove topographies

ABSTRACT In this study, we aimed to study the effect of fluid shear stress on fibroblasts and BMSCs on plane and groove topographies. The results showed that 0.6-Hz stress had the greatest influence on the alignment, polarity, migration and adhesion of fibroblasts on plane by increasing the expression of reoriented actin and vinculin; whereas 1.0-Hz stress promoted differentiation of fibroblasts into myofibroblasts by increasing Col-I and α-SMA expression. Interestingly, under the given frequency stress, the groove structure strengthened the above characteristics of fibroblasts beyond adhesion, and promoted differentiation of BMSCs into myofibroblasts. The above results indicate that 0.6 Hz may improve the implant-tissue sealing, while 1.0-Hz stress probably causes the disordered fiber deposition around implants.
Urbanization and Waterborne Pathogen Emergence in Low-Income Countries: Where and How to Conduct Surveys?

A major forthcoming sanitary issue concerns the apparition and spreading of drug-resistant microorganisms, potentially threatening millions of humans. In low-income countries, polluted urban runoff and open sewage channels are major sources of microbes. These microbes join natural microbial communities in aquatic ecosystems already impacted by various chemicals, including antibiotics. These composite microbial communities must adapt to survive in such hostile conditions, sometimes promoting the selection of antibiotic-resistant microbial strains by gene transfer. The low probability of exchanges between planktonic microorganisms within the water column may be significantly improved if their contact was facilitated by particular meeting places. This could be specifically the case within biofilms that develop on the surface of the myriads of floating macroplastics increasingly polluting urban tropical surface waters. Moreover, as uncultivable bacterial strains could be involved, analyses of the microbial communities in their whole have to be performed. This means that new-omic technologies must be routinely implemented in low- and middle-income countries to detect the appearance of resistance genes in microbial ecosystems, especially when considering the new ‘plastic context. ’ We summarize the related current knowledge in this short review paper to anticipate new strategies for monitoring and surveying microbial communities.
Continuous decline in bone mineral density and deterioration of bone microarchitecture 7 years after Roux-en-Y gastric bypass surgery

Objective Roux-en-Y-gastric bypass (RYGB) surgery is an effective treatment for morbid obesity. A possible overlooked side effect is negative bone metabolic consequences. Design A seven-year prospective study following ten women and seven men after RYGB (baseline mean age 43 ± 8 years, BMI 42 ± 6 kg/m2). Methods Lumbar spine and total hip bone mineral density (BMD) using dual energy x-ray absorptiometry, distal radius and tibia bone geometry, volumetric BMD, microarchitecture and finite element estimated bone strength using high-resolution peripheral quantitative CT and biochemical markers of bone remodelling were assessed at baseline, 2 and 7 years. Results Compared to baseline, body weight was 24 ± 10% lower after 2 years and 21 ± 11% after 7 years. During the 7 years of follow-up, radius and tibia vBMD had declined 13 ± 8% and 8 ± 7% from baseline to 2 years and further 10 ± 7% and 7 ± 8% from 2 to 7 years (all P < 0.001). At both radius and tibia, cortical thickness declined and cortical porosity increased. From baseline to 7 years, there were clear indications of deteriorations of the trabecular network with fewer, more widely spaced and more in-homogeneously distributed trabeculae in both radius and tibia. Overall, declines in estimated bone strength of 16 ± 9% in radius and 16 ± 7% in tibia were observed (both P < 0.001). Conclusion Seven years after RYGB, evidence of continuous declines in BMD and ongoing deterioration of bone microarchitecture and reduced estimated bone strength compared to baseline and 2 years post-surgery results were found. These findings emphasize the need for regular assessment of bone health in patients with prior RYGB.
The brain acid‐soluble protein 1 (BASP1) interferes with the oncogenic capacity of MYC and its binding to calmodulin

The MYC protein is a transcription factor with oncogenic potential controlling fundamental cellular processes such as cell proliferation, metabolism, differentiation, and apoptosis. The MYC gene is a major cancer driver, and elevated MYC protein levels are a hallmark of most human cancers. We have previously shown that the brain acid‐soluble protein 1 gene (BASP1) is specifically downregulated by the v‐myc oncogene and that ectopic BASP1 expression inhibits v‐myc‐induced cell transformation. The 11‐amino acid effector domain of the BASP1 protein interacts with the calcium sensor calmodulin (CaM) and is mainly responsible for this inhibitory function. We also reported recently that CaM interacts with all MYC variant proteins and that ectopic CaM increases the transactivation and transformation potential of the v‐Myc protein. Here, we show that the presence of excess BASP1 or of a synthetic BASP1 effector domain peptide leads to displacement of v‐Myc from CaM. The protein stability of v‐Myc is decreased in cells co‐expressing v‐Myc and BASP1, which may account for the inhibition of v‐Myc. Furthermore, suppression of v‐Myc‐triggered transcriptional activation and cell transformation is compensated by ectopic CaM, suggesting that BASP1‐mediated withdrawal of CaM from v‐Myc is a crucial event in the inhibition. In view of the tumor‐suppressive role of BASP1 which was recently also reported for human cancer, small compounds or peptides based on the BASP1 effector domain could be used in drug development strategies aimed at tumors with high MYC expression.
Between Mainstream and Marginality: The Case of Men and Women of Mixed-Orientation Relationships

ABSTRACT The literature regarding mixed-orientation relationships (MORs) focuses on individual and relationship aspects. Our study, informed by the social construction of reality theory, illuminates social aspects by examining social attitudes toward MORs as they are experienced and perceived by individuals of MOR. Within the scope of this study, we focused on self-identified non-straight men (gays, bisexuals, or men who have sex with men) who are in a relationship with self-identified straight women. Based on the phenomenological paradigm, we conducted 38 interviews with men and eight with women currently in MOR. The findings show that individuals of MOR primarily encounter negative attitudes from people in society regarding themselves and the nature of their relationship. Participants perceived that others viewed their relationships in terms of conflict, impossibility, or transitional stage. Social attitudes individuals of MOR encounter affect the degree of closeness of these couples to others in their social environment, resulting in constant tension between the participants’ desire to be open to and close to others and the need to conceal and keep a distance. We argue that the dialectical tensions between disclosure-concealment and autonomy-closeness are related to the marginalization of these couples as a social category.
Visual snow syndrome

Objective To validate the current criteria of visual snow and to describe its common phenotype using a substantial clinical database. Methods We performed a web-based survey of patients with self-assessed visual snow (n = 1,104), with either the complete visual snow syndrome (n = 1,061) or visual snow without the syndrome (n = 43). We also describe a population of patients (n = 70) with possible hallucinogen persisting perception disorder who presented clinically with visual snow syndrome. Results The visual snow population had an average age of 29 years and had no sex prevalence. The disorder usually started in early life, and ≈40% of patients had symptoms for as long as they could remember. The most commonly experienced static was black and white. Floaters, afterimages, and photophobia were the most reported additional visual symptoms. A latent class analysis showed that visual snow does not present with specific clinical endophenotypes. Severity can be classified by the amount of visual symptoms experienced. Migraine and tinnitus had a very high prevalence and were independently associated with a more severe presentation of the syndrome. Conclusions Clinical characteristics of visual snow did not differ from the previous cohort in the literature, supporting validity of the current criteria. Visual snow likely represents a clinical continuum, with different degrees of severity. On the severe end of the spectrum, it is more likely to present with its common comorbid conditions, migraine and tinnitus. Visual snow does not depend on the effect of psychotropic substances on the brain.
Rules and Exceptions: The Role of Chromosomal ParB in DNA Segregation and Other Cellular Processes

The segregation of newly replicated chromosomes in bacterial cells is a highly coordinated spatiotemporal process. In the majority of bacterial species, a tripartite ParAB-parS system, composed of an ATPase (ParA), a DNA-binding protein (ParB), and its target(s) parS sequence(s), facilitates the initial steps of chromosome partitioning. ParB nucleates around parS(s) located in the vicinity of newly replicated oriCs to form large nucleoprotein complexes, which are subsequently relocated by ParA to distal cellular compartments. In this review, we describe the role of ParB in various processes within bacterial cells, pointing out interspecies differences. We outline recent progress in understanding the ParB nucleoprotein complex formation and its role in DNA segregation, including ori positioning and anchoring, DNA condensation, and loading of the structural maintenance of chromosome (SMC) proteins. The auxiliary roles of ParBs in the control of chromosome replication initiation and cell division, as well as the regulation of gene expression, are discussed. Moreover, we catalog ParB interacting proteins. Overall, this work highlights how different bacterial species adapt the DNA partitioning ParAB-parS system to meet their specific requirements.
GENDER GAP IN PHYSICAL EDUCATION: TEACHERS' ATTITUDES TOWARDS EQUALITY

The aim of this paper is to analyse the Physical Education teachers' attitudes towards gender equality, and compare attitudinal differences between male and female teachers. This study follows a survey-type quantitative descriptive methodology in which 526 Spanish PE teachers have taken part. Data were collected using the Likert-type Scale SDG/t (School Doing Gender /teachers), made up of 30 items separated in three subscales. PE teachers mainly showed an adaptive attitude towards gender changes. Nevertheless, differences were observed with regard to the participants' attitude towards gender issues depending on their sex. More specifically, female teachers achieved higher scores than males. This result suggests a better training in gender issues should be carried out in order to raise awareness and update the PE teachers' knowledge, especially in the case of male teachers.
Quality Improvement Project to Promote Identification and Treatment of Children With Obesity Admitted to Hospital

Among children hospitalized for acute problems, comorbid obesity is commonly unaddressed. The objective was to improve identification and initial management of obesity among hospitalized children. In collaboration with nurses and dietitians, pediatric hospitalists of 2 children’s hospitals conducted a quality improvement project to improve body mass index (BMI) documentation, obesity diagnosis, diet, and nutrition consultation through clinician education, development of computerized clinical decision-support system tools, and workflow modifications. Participants received monthly performance feedback. Among those with elevated BMI, diagnosis rose to 70.2%; a documented obesity diagnosis was associated with being 35 times more likely (P < .001) to receive at least 1 intervention while hospitalized. Participants reported an increase in skill in (27%), comfort with (27%), and knowledge of (33%) obesity management. Improvement in health care provider recognition and management of obesity in the inpatient setting is achievable. Additional work is needed to identify how best to sustain desired practice patterns.
Serological relationship between a novel ovine pestivirus and classical swine fever virus.

The genus Pestivirus comprises globally distributed members of the family Flaviviridae, which cause severe losses in livestock. The most common species of the genus are bovine viral diarrhea virus type 1 (BVDV-1) and type 2 (BVDV-2), classical swine fever virus (CSFV), and border disease virus (BDV). Recently, a novel ovine pestivirus was repeatedly detected in aborted lamb fetuses on a farm located in the Brescia Province (Italy). Complete genome characterization of this isolate showed that it was highly divergent from known pestivirus species and that it was genetically closely related to CSFV. The aim of this study was to determine the serological relatedness between the identified novel pestivirus and BVDV, BDV, and CSFV selected strains for which homologous serum was available, by antigenic characterization performed using cross-neutralization assays. The serological relatedness was expressed as the coefficient of antigenic similarity (R). Both field and specific antisera raised against the ovine pestivirus neutralized the CSFV reference strain Diepholz with titers significantly higher than those specific for the BDV and BVDV strains. Furthermore, the calculated R values clearly indicated that the novel ovine pestivirus is antigenically more related to CSFV than to ruminant pestiviruses, in agreement with the results of the genomic analysis. This would have severe consequences on CSFV serology in the event of a switch to porcine hosts with implications for CSFV surveillance and porcine health management.
The role of extracellular vesicles in skeletal muscle and systematic adaptation to exercise

Regular exercise has a central role in human health by reducing the risk of type 2 diabetes, obesity, stroke and cancer. How exercise is able to promote such systemic benefits has remained somewhat of a mystery but has been thought to be in part mediated by the release of myokines, skeletal muscle‐specific cytokines, in response to exercise. Recent studies have revealed skeletal muscle can also release extracellular vesicles (EVs) into circulation following a bout of exercise. EVs are small membrane‐bound vesicles capable of delivering biomolecules to recipient cells and subsequently altering their metabolism. The notion that EVs may have a role in both skeletal muscle and systemic adaptation to exercise has generated a great deal of excitement within a number of different fields including exercise physiology, neuroscience and metabolism. The purpose of this review is to provide an introduction to EV biology and what is currently known about skeletal muscle EVs and their potential role in the response of muscle and other tissues to exercise.
Avian and serpentine endogenous foamy viruses, and new insights into the macroevolutionary history of foamy viruses

Abstract This study reports and characterises two novel distinct lineages of foamy viruses (FVs) in the forms of endogenous retroviruses (ERVs). Several closely related elements were found in the genome of oriental stork (Ciconia boyciana) and other was found in the genome of spine-bellied sea snake (Hydrophis hardwickii), designated ERV-Spuma.N-Cbo (where 'N' runs from one to thirteen) and ERV-Spuma.1-Hha, respectively. This discovery of avian and serpentine endogenous FVs adds snakes, and perhaps more crucially, birds to the list of currently known hosts of FVs, in addition to mammals, reptiles, amphibians, and fish. This indicates that FVs are, or at least were, capable of infecting all major lineages of vertebrates. Moreover, together with other FVs, phylogenetic analyses showed that both of them are most closely related to mammalian FVs. Further examination revealed that reptilian FVs form a deep paraphyletic group that is basal to mammalian and avian FVs, suggesting that there were multiple ancient FV cross-class transmissions among their hosts. Evolutionary timescales of various FV lineages were estimated in this study, in particular, the timescales of reptilian FVs and that of the clade of mammalian, avian, and serpentine FVs. This was accomplished by using the recently established time-dependent rate phenomenon models, inferred using mainly the knowledge of the co-speciation history between FVs and mammals. It was found that the estimated timescales matched very well with those of reptiles. Combined with the observed phylogenetic patterns, these results suggested that FVs likely co-speciated with ancient reptilian animals, but later jumped to a protomammal and/or a bird, which ultimately gave rise to mammalian and avian FVs. These results contribute to our understanding of FV emergence, specifically the emergence of mammalian and avian FVs, and provide new insights into how FVs co-evolved with their non-mammalian vertebrate hosts in the distant past.
Current Genetic Landscape in Common Variable Immune Deficiency.

Using whole exome sequencing to examine the genetic causes of immune deficiency in 235 CVID patients seen in New York, 128 patients from Sweden, and 208 from Iran, revealed 73 known disease-causing genes associated with this heterogeneous immune defect. The patients at the time of study ranged from age 4 to age 90. Overall, for 31%, 36% and 54% of the patients in United States, Swedish or Iranian cohorts, mutations were identified. The multiplicity of genes identified reflects the complex requirements of B cell antigen signaling, activation, survival, migration, maturation and maintenance of antibody-secreting memory B cell populations to the plasma cell stage. For the United States and Swedish cohorts, CVID subjects with non-infectious complications, lymphoid infiltrations, inflammatory, or autoimmunity, were more likely to have an identifiable gene, but in both cohorts, numerous subjects with these medical conditions had no potential gene that could be assigned. Specific clinical patterns of illnesses were also not linked to any given gene defect as there was considerable overlap in clinical presentations. These observations provide a broad perspective on the complexity of the genetic and immunologic phenotypes found in 571 CVID subjects of different ages and backgrounds.
A Biostimulant Obtained from the Seaweed Ascophyllum nodosum Protects Arabidopsis thaliana from Severe Oxidative Stress

Abiotic stresses cause oxidative damage in plants. Here, we demonstrate that foliar application of an extract from the seaweed Ascophyllum nodosum, SuperFifty (SF), largely prevents paraquat (PQ)-induced oxidative stress in Arabidopsis thaliana. While PQ-stressed plants develop necrotic lesions, plants pre-treated with SF (i.e., primed plants) were unaffected by PQ. Transcriptome analysis revealed induction of reactive oxygen species (ROS) marker genes, genes involved in ROS-induced programmed cell death, and autophagy-related genes after PQ treatment. These changes did not occur in PQ-stressed plants primed with SF. In contrast, upregulation of several carbohydrate metabolism genes, growth, and hormone signaling as well as antioxidant-related genes were specific to SF-primed plants. Metabolomic analyses revealed accumulation of the stress-protective metabolite maltose and the tricarboxylic acid cycle intermediates fumarate and malate in SF-primed plants. Lipidome analysis indicated that those lipids associated with oxidative stress-induced cell death and chloroplast degradation, such as triacylglycerols (TAGs), declined upon SF priming. Our study demonstrated that SF confers tolerance to PQ-induced oxidative stress in A. thaliana, an effect achieved by modulating a range of processes at the transcriptomic, metabolic, and lipid levels.
Optimization of Ultrasonic Flavonoid Extraction from Saussurea involucrate, and the Ability of Flavonoids to Block Melanin Deposition in Human Melanocytes

(1) Background: Flavonoids are the primary medicinal ingredient of Saussurea involucrate, which have significant antioxidant capacity. Optimizing the extraction of Saussurea involucrate flavonoids (SIFs) and exploring the ability to block melanin deposition caused by reactive oxygen can greatly promote the development of S. involucrate whitening products. (2) Methods: Ultrasonic extraction process was optimized using the Box–Behnken design (BBD) and response surface methodology (RSM). Then, the effect of SIFs on antioxidant activity and anti-deposition of melanin, and genes related to the melanin synthesis are studied. (3) Results: The optimal extraction procedures are as follows: the extraction time, ethanol content, and solvent ratio (v/w) are 64 min, 54%, and 54:1, respectively. The reducing activity and scavenging rates of 2,2-diphenyl-1-picrylhydrazyl (DPPH), superoxide anion, hydroxyl radical, and ABTS+ were promoted as more S. involucrate flavonoid extract was added. The SIFs extract induced a decrease in the melanin synthesis by inhibiting the human melanoma A375 cell tyrosinase activity. SIFs also depress expression of melanin synthesis related genes. (4) Conclusions: the highest SIFs content was obtained by using 54% ethanol and 54:1 solvent ratio (v/w) for 64 min. The extract of SIFs exhibited good ability of antioxidant and anti-deposition of melanin in human melanocytes.