Miracle-dz/UniFAR-FTUs huggingface dataset:
Enhancing gastric cancer conventional chemotherapy effects by triple angiokinase inhibitor nintedanib in preclinical models

Background Gastric adenocarcinoma (GAC) is the fourth leading cause of cancer death worldwide. Systemic chemotherapy is a preferred treatment option for advanced and recurrent GAC, but response rates and survival prolongation remain limited. Tumor angiogenesis plays a critical role in GAC growth, invasion and metastasis. We investigated the antitumor efficacy of nintedanib, a potent triple angiokinase inhibitor for VEGFR-1/2/3, PDGFR-α/β and FGFR-1/2/3, alone or in combination with chemotherapy, in preclinical models of GAC. Methods Animal survival studies were performed in peritoneal dissemination xenografts in NOD/SCID mice using human GAC cell lines MKN-45 and KATO-III. Tumor growth inhibition studies were performed in subcutaneous xenografts in NOD/SCID mice using human GAC cell lines MKN-45 and SNU-5. The mechanistic evaluation involved Immunohistochemistry analyses in tumor tissues obtained from subcutaneous xenografts. In vitro cell viability assays were performed using a colorimetric WST-1 reagent. Results In MKN-45 GAC cell-derived peritoneal dissemination xenografts, animal survival was improved by nintedanib (33%), docetaxel (100%) and irinotecan (181%), while oxaliplatin, 5-FU and epirubicin had no effect. The addition of nintedanib to docetaxel (157%) or irinotecan (214%) led to a further extension in animal survival. In KATO-III GAC cell-derived xenografts carrying FGFR2 gene amplification, nintedanib extended survival by 209%. Again, the addition of nintedanib further enhanced the animal survival benefits of docetaxel (273%) and irinotecan (332%). In MKN-45 subcutaneous xenografts, nintedanib, epirubicin, docetaxel and irinotecan reduced tumor growth (range: 68-87%), while 5-FU and oxaliplatin had a smaller effect (40%). Nintedanib addition to all chemotherapeutics demonstrated a further reduction in tumor growth. Subcutaneous tumor analysis revealed that nintedanib attenuated tumor cell proliferation, reduced tumor vasculature and increased tumor cell death. Conclusion Nintedanib showed notable antitumor efficacy and significantly improved taxane or irinotecan chemotherapy responses. These findings indicate that nintedanib, alone and in combination with a taxane or irinotecan, has the potential for improving clinical GAC therapy.
Winter and summer sedimentary dynamic process observations in the sea area off Qinhuangdao in the Bohai Sea, China

Sedimentary processes in marginal seas play an important role in the biology, physics, and geochemistry as well as ecology of coastal environments and contain abundant information about the material transfer from land to ocean and the regional circulation. Due to the huge sediment discharge of the Yellow River, the Bohai Sea, China is one of the areas with the highest suspended sediment concentration (SSC) in the world. Interestingly, the SSC at the west of the Bohai Sea is low all year round. Thus, it is of great significance to examine the sedimentary dynamic process in this area for better understanding the circulation structure, material exchange and regional environment of the Bohai Sea. Using seabed base observation platform measurements obtained in February 2017 and August 2019, this study examines the winter and summer hydrography and suspended sediment concentration in the sea area off Qinhuangdao located to the west of the Bohai Sea. In summer, the relatively weak residual currents flowed northeastward and showed little correlation with the wind field, especially in the middle layer of the water column. In winter, the residual currents were strengthened, flowing to the northeast during strong wind periods, and predominantly to the southwest during intermittent periods. Moreover, driven by the pressure gradient force associated with the wind-induced sea surface height variations, the winter current was closely related to the wind speed, with correlation coefficients ranging from 0.4 to 0.6 and a time lag of 10 h. The summer SSC was lower and mainly controlled by the tidal current, whereas in winter, owing to the enhanced Reynolds stress and turbulent kinetic energy, strong wind bursts triggered significant sediment resuspension and led to a higher SSC. For the suspended sediment flux (SSF), the advection terms contributed more than 80% in the winter and summer, while the vertical circulation terms contributed 13% in winter, and approximately half that much in summer. Generally, the suspended sediment is transported back and forth, with a little net northward and northeastward motions in winter and summer, respectively. This may explain the low SSC sustaining in coastal Qinhuangdao all year round. These results provide a reference for sedimentary studies conducted in other coastal waters, especially in monsoon-dominating shelf seas.
Characteristics of resistance training-based protocols in older adults with sarcopenic obesity: a scoping review of training procedure recommendations

Background Sarcopenic obesity (SO) is a clinical and functional disease characterized by the coexistence of obesity and sarcopenia. Resistance training (RT) characteristics for older adults with sarcopenia or obesity are already well established in the scientific literature. Nonetheless, we still do not know how detailed the RT protocols are described for older adults with SO. Therefore, we aimed to analyze the characteristics of RT programs, including each of their variables, recommended for older adults with SO. Methods This is a scoping review study that was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis for Scoping Reviews. The search was carried out until November 2022 in PubMed/MEDLINE, EMBASE, Cochrane Library, Web of Science, Scopus, LILACS, Google Scholar, and medRxiv databases. The studies included SO diagnosis and RT as an intervention strategy. The RT variables analyzed were as follows: exercise selection, the volume of sets, the intensity of load, repetition cadence, rest interval between sets, and weekly frequency. Results A total of 1,693 studies were identified. After applying the exclusion criteria, 15 studies were included in the final analysis. The duration of the RT intervention ranged from 8 to 24 weeks. All studies included full-body routines, with single/multi-joint exercises. Regarding the volume of sets, some studies fixed it in three sets, whereas others varied between one and three sets. The load was reported by repetition range and the weight lifted, elastic-band color/resistance, percentage of one repetition maximum, or perceived exertion scale. Repetition cadence was fixed in some studies, while it was self-selected between concentric and eccentric phases in others. The interval between sets of rest varied from 30 to 180 s. All studies reported progression overload during the interventions. Not all studies reported how the exercise selection, repetition cadence, and rest interval were made. Conclusion The characteristics of RT protocols and their variables prescribed in the literature for older adults with SO were mapped. The lack of detail on some training variables (i.e., exercise selection, repetition cadence, and rest interval) was identified. RT protocols are heterogeneous and described only partially among studies. The recommendations for RT prescription details in older adults with SO are provided for future studies. Systematic review registration https://osf.io/wzk3d/.
Characterization of pharmacogenomic variants in a Brazilian admixed cohort of elderly individuals based on whole-genome sequencing data

Introduction: Research in the field of pharmacogenomics (PGx) aims to identify genetic variants that modulate response to drugs, through alterations in their pharmacokinetics (PK) or pharmacodynamics (PD). The distribution of PGx variants differs considerably among populations, and whole-genome sequencing (WGS) plays a major role as a comprehensive approach to detect both common and rare variants. This study evaluated the frequency of PGx markers in the context of the Brazilian population, using data from a population-based admixed cohort from Sao Paulo, Brazil, which includes variants from WGS of 1,171 unrelated, elderly individuals. Methods: The Stargazer tool was used to call star alleles and structural variants (SVs) from 38 pharmacogenes. Clinically relevant variants were investigated, and the predicted drug response phenotype was analyzed in combination with the medication record to assess individuals potentially at high-risk of gene-drug interaction. Results: In total, 352 unique star alleles or haplotypes were observed, of which 255 and 199 had a frequency < 0.05 and < 0.01, respectively. For star alleles with frequency > 5% (n = 97), decreased, loss-of-function and unknown function accounted for 13.4%, 8.2% and 27.8% of alleles or haplotypes, respectively. Structural variants (SVs) were identified in 35 genes for at least one individual, and occurred with frequencies >5% for CYP2D6, CYP2A6, GSTM1, and UGT2B17. Overall 98.0% of the individuals carried at least one high risk genotype-predicted phenotype in pharmacogenes with PharmGKB level of evidence 1A for drug interaction. The Electronic Health Record (EHR) Priority Result Notation and the cohort medication registry were combined to assess high-risk gene-drug interactions. In general, 42.0% of the cohort used at least one PharmGKB evidence level 1A drug, and 18.9% of individuals who used PharmGKB evidence level 1A drugs had a genotype-predicted phenotype of high-risk gene-drug interaction. Conclusion: This study described the applicability of next-generation sequencing (NGS) techniques for translating PGx variants into clinically relevant phenotypes on a large scale in the Brazilian population and explores the feasibility of systematic adoption of PGx testing in Brazil.
Biocrust carbon exchange varies with crust type and time on Chihuahuan Desert gypsum soils

Introduction In dryland systems, biological soil crusts (biocrusts) can occupy large areas of plant interspaces, where they fix carbon following rain. Although distinct biocrust types contain different dominant photoautotrophs, few studies to date have documented carbon exchange over time from various biocrust types. This is especially true for gypsum soils. Our objective was to assess the carbon exchange of biocrust types established at the world’s largest gypsum dune field at White Sands National Park. Methods We sampled five different biocrust types from a sand sheet location in three different years and seasons (summer 2020, fall 2021, and winter 2022) for carbon exchange measurements in controlled lab conditions. Biocrusts were rehydrated to full saturation and light incubated for 30 min, 2, 6, 12, 24, and 36 h. Samples were then subject to a 12-point light regime with a LI-6400XT photosynthesis system to determine carbon exchange. Results Biocrust carbon exchange values differed by biocrust type, by incubation time since wetting, and by date of field sampling. Lichens and mosses had higher gross and net carbon fixation rates than dark and light cyanobacterial crusts. High respiration rates were found after 0.5 h and 2 h incubation times as communities recovered from desiccation, leveling off after 6 h incubation. Net carbon fixation of all types increased with longer incubation time, primarily as a result of decreasing respiration, which suggests rapid recovery of biocrust photosynthesis across types. However, net carbon fixation rates varied from year to year, likely as a product of time since the last rain event and environmental conditions preceding collection, with moss crusts being most sensitive to environmental stress at our study sites. Discussion Given the complexity of patterns discovered in our study, it is especially important to consider a multitude of factors when comparing biocrust carbon exchange rates across studies. Understanding the dynamics of biocrust carbon fixation in distinct crust types will enable greater precision of carbon cycling models and improved forecasting of impacts of global climate change on dryland carbon cycling and ecosystem functioning.
Do young children, like young adults, remember animates better than inanimates?

It has repeatedly been shown in adults that animates are remembered better than inanimates. According to the adaptive view of human memory this is due to the fact that animates are generally more important for survival than inanimates. Animacy enhances not only the quantity but also the quality of remembering. The effect is primarily driven by recollection. Virtually all studies have been conducted in adults, and we believe that the investigation of animacy effects in children is also highly relevant. The present study therefore tested the animacy effect on recollection in young (6–7 years, M = 6.6 years) and older children (10–12 years, M = 10.83 years) using the Remember/Know paradigm. As found in adults, an animacy effect on memory was found, but only in older children, and specifically in the “remember” responses, suggesting, once again, its episodic nature.
Comparative genomics of the Leukocyte Receptor Complex in carnivores

Background The mammalian Leukocyte Receptor Complex (LRC) chromosomal region may contain gene families for the killer cell immunoglobulin-like receptor (KIR) and/or leukocyte immunoglobulin-like receptor (LILR) collections as well as various framing genes. This complex region is well described in humans, mice, and some domestic animals. Although single KIR genes are known in some Carnivora, their complements of LILR genes remain largely unknown due to obstacles in the assembly of regions of high homology in short-read based genomes. Methods As part of the analysis of felid immunogenomes, this study focuses on the search for LRC genes in reference genomes and the annotation of LILR genes in Felidae. Chromosome-level genomes based on single-molecule long-read sequencing were preferentially sought and compared to representatives of the Carnivora. Results Seven putatively functional LILR genes were found across the Felidae and in the Californian sea lion, four to five genes in Canidae, and four to nine genes in Mustelidae. They form two lineages, as seen in the Bovidae. The ratio of functional genes for activating LILRs to inhibitory LILRs is slightly in favor of inhibitory genes in the Felidae and the Canidae; the reverse is seen in the Californian sea lion. This ratio is even in all of the Mustelidae except the Eurasian otter, which has a predominance of activating LILRs. Various numbers of LILR pseudogenes were identified. Conclusions The structure of the LRC is rather conservative in felids and the other Carnivora studied. The LILR sub-region is conserved within the Felidae and has slight differences in the Canidae, but it has taken various evolutionary paths in the Mustelidae. Overall, the process of pseudogenization of LILR genes seems to be more frequent for activating receptors. Phylogenetic analysis found no direct orthologues across the Carnivora which corroborate the rapid evolution of LILRs seen in mammals.
Creating mindful heroes: a case study with ninth grade students

The Heroic Imagination Project (HIP) aims to redefine heroism as a set of habits that anyone can achieve. Research findings on the psychological foundations of negative forms of social influence that can lead to bystander behavior are translated into tools that individuals can use in their daily lives. Habits of wise and effective helping behavior are learned, modeled, and encouraged through the training of the “heroic imagination. ” According to the literature, practicing mindfulness can increase empathy, compassion, and prosocial behaviors. There is empirical evidence that compassion can act as a mediator between mindfulness and prosocial helping behaviors toward strangers, suggesting that mindfulness promotes this behavior and thus helps to overcome the bystander effect. With this hypothesis in mind, we created a program that combined mindfulness and HIP sessions. Five participants volunteered to participate in the “Creating Mindful Heroes” 9-week program. Throughout the sessions, they filled in a diary, and at the end of the program, they answered two feedback questionnaires. They were then invited to participate in individual interviews. The participants reported a positive overall perspective regarding the program, mentioning several improvements in their relationships with their family, peers, and others in society. Moreover, participants reported that the program promoted prosocial behaviors and aided them in developing empathy.
Metabolic phenotypes and risk of end-stage kidney disease in patients with type 2 diabetes

Background Obesity often initiates or coexists with metabolic abnormalities. This study aimed to investigate the pathological characteristics and the independent or mutual relations of obesity and metabolic abnormalities with end-stage kidney disease (ESKD) in patients with type 2 diabetes (T2D) and associated diabetic kidney disease (DKD). Methods A total of 495 Chinese patients with T2D and biopsy-confirmed DKD between 2003 and 2020 were enrolled in this retrospective study. The metabolic phenotypes were based on the body weight index (BMI)-based categories (obesity, BMI ≥ 25.0 kg/m2) and metabolic status (metabolically unhealthy status, ≥ 1 criterion National Cholesterol Education Program Adult Treatment Panel III (NCEP/ATP III) excluding waist circumference and hyperglycemia) and were categorized into four types: metabolically healthy non-obesity (MHNO), metabolically healthy obesity (MHO), metabolically unhealthy non-obesity (MUNO), and metabolically unhealthy obesity (MUO). The pathological findings were defined by the Renal Pathology Society classification. Cox proportional hazards models were used to estimate hazard ratios (HRs) for ESKD. Results There are 56 (11.3%) MHNO patients, 28 (5.7%) MHO patients, 176 (35.6%) MUNO patients, and 235 (47.5%) MUO patients. The high prevalence of the Kimmelstiel–Wilson nodule and severe mesangial expansion were associated with obesity, whereas severe IFTA was related to metabolically unhealthy status. In the multivariate analysis, the adjusted HR (aHR) was 2.09 [95% confidence interval (CI) 0.99–4.88] in the MHO group, 2.16 (95% CI 1.20–3.88) in the MUNO group, and 2.31 (95% CI 1.27–4.20) in the MUO group compared with the MHNO group. Furthermore, the presence of obesity was insignificantly associated with ESKD compared with non-obese patients (aHR 1.22, 95% CI 0.88–1.68), while the metabolically unhealthy status was significantly associated with ESKD compared to the metabolically healthy status in the multivariate analysis (aHR 1.69, 95% CI 1.10–2.60). Conclusion Obesity itself was insignificantly associated with ESKD; however, adding a metabolically unhealthy status to obesity increased the risk for progression to ESKD in T2D and biopsy-proven DKD.
Detection of herpes simplex virus in oral tongue squamous cell carcinoma

Introduction: Oral tongue squamous cell carcinoma (OTSCC) is the most common cancer of the oral cavity. Contradictory results have been observed on the involvement of herpes simplex virus 1 (HSV-1) in oral squamous cell carcinomas. Here, we aimed to study the predominance of HSV-1 or HSV-2 in oral HSV infections and to investigate the presence of HSV-1 in OTSCC and its effect on carcinoma cell viability and invasion. Methods: The distribution of HSV types one and two in diagnostic samples taken from suspected oral HSV infections was determined from the Helsinki University Hospital Laboratory database. We then analysed 67 OTSCC samples for HSV-1 infection using immunohistochemical staining. We further tested the effects of HSV-1 using six concentrations (0.00001–1.0 multiplicity of infection [MOI]) on viability and two concentrations (0.001 and 0.1 MOI) on invasion of highly invasive metastatic HSC-3 and less invasive primary SCC-25 OTSCC cell lines using MTT and Myogel-coated Transwell invasion assays. Results: Altogether 321 oropharyngeal samples were diagnosed positive for HSV during the study period. HSV-1 was the predominant (97.8%) HSV type compared with HSV-2 (detected in 2.2% of samples). HSV-1 was also detected in 24% of the OTSCC samples and had no association with patient survival or recurrence. OTSCC cells were viable even after 6 days with low viral load (0.00001, 0.0001, 0.001 MOI) of HSV-1. In both cell lines, 0.001 MOI did not affect cell invasion. However, 0.1 MOI significantly reduced cell invasion in HSC-3 cells. Discussion: HSV-1 infection is predominant compared with HSV-2 in the oral cavity. HSV-1 is detected in OTSCC samples without clinical significance, and OTSCC cell survival or invasion was not affected at low doses of HSV-1.
Lacking ARHGAP25 mitigates the symptoms of autoantibody-induced arthritis in mice

Objective Despite intensive research on rheumatoid arthritis, the pathomechanism of the disease is still not fully understood and the treatment has not been completely resolved. Previously we demonstrated that the GTPase-activating protein, ARHGAP25 has a crucial role in the regulation of basic phagocyte functions. Here we investigate the role of ARHGAP25 in the complex inflammatory process of autoantibody-induced arthritis. Methods Wild-type and ARHGAP25 deficient (KO) mice on a C57BL/6 background, as well as bone marrow chimeric mice, were treated i.p. with the K/BxN arthritogenic or control serum, and the severity of inflammation and pain-related behavior was measured. Histology was prepared, leukocyte infiltration, cytokine production, myeloperoxidase activity, and superoxide production were determined, and comprehensive western blot analysis was conducted. Results In the absence of ARHGAP25, the severity of inflammation, joint destruction, and mechanical hyperalgesia significantly decreased, similarly to phagocyte infiltration, IL-1β, and MIP-2 levels in the tibiotarsal joint, whereas superoxide production or myeloperoxidase activity was unchanged. We observed a significantly mitigated phenotype in KO bone marrow chimeras as well. In addition, fibroblast-like synoviocytes showed comparable expression of ARHGAP25 to neutrophils. Significantly reduced ERK1/2, MAPK, and I-κB protein signals were detected in the arthritic KO mouse ankles. Conclusion Our findings suggest that ARHGAP25 has a key role in the pathomechanism of autoantibody-induced arthritis in which it regulates inflammation via the I-κB/NF-κB/IL-1β axis with the involvement of both immune cells and fibroblast-like synoviocytes.