Miracle-dz/UniFAR-FTUs huggingface dataset:
Preventive Effect of Spontaneous Physical Activity on the Gut-Adipose Tissue in a Mouse Model That Mimics Crohn’s Disease Susceptibility

Crohn’s disease is characterized by abnormal ileal colonization by adherent-invasive E. coli (AIEC) and expansion of mesenteric adipose tissue. This study assessed the preventive effect of spontaneous physical activity (PA) on the gut-adipose tissue in a mouse model that mimics Crohn’s disease susceptibility. Thirty-five CEABAC10 male mice performed spontaneous PA (wheel group; n = 24) or not (controls; n = 11) for 12 weeks. At week 12, mice were orally challenged with the AIEC LF82 strain for 6 days. Body composition, glycaemic control, intestinal permeability, gut microbiota composition, and fecal short-chain fatty acids were assessed in both groups. Animals were fed a high fat/high sugar diet throughout the study. After exposure to AIEC, mesenteric adipose tissue weight was lower in the wheel group. Tight junction proteins expression increased with spontaneous PA, whereas systemic lipopolysaccharides were negatively correlated with the covered distance. Bifidobacterium and Lactobacillus decreased in controls, whereas Oscillospira and Ruminococcus increased in the wheel group. Fecal propionate and butyrate were also higher in the wheel group. In conclusion, spontaneous physical activity promotes healthy gut microbiota composition changes and increases short-chain fatty acids in CEABAC10 mice fed a Western diet and exposed to AIEC to mimic Crohn’s disease.
Influence of Body Fat on Oxidative Stress and Telomere Length of Master Athletes

Abstract Aguiar, SS, Rosa, TS, Sousa, CV, Santos, PA, Barbosa, LP, Deus, LA, Rosa, EC, Andrade, RV, and Simões, HG. Influence of body fat on oxidative stress and telomere length of master athletes. J Strength Cond Res 35(6): 1693–1699, 2021—The present investigation analyzed the role of body fat and training history on biological aging of master athletes by comparing and verifying the relationships between markers of adiposity, oxidative balance, and telomere length (TL) in middle-aged runners and untrained individuals. Master athletes (sprinters and endurance runners, n = 21; 51.62 ± 8.19 years) and untrained age-matched controls (n = 11; 45.41 ± 10.34 years) had blood samples collected for biochemical and biomolecular analyzes. Pro-oxidant and antioxidant measures as well as DNA extraction were performed using commercial kits. Relative TL (T/S) was determined in leukocytes through quantitative polymerase chain reaction analyses. Master athletes had lower body fat and longer TL than untrained controls (body fat: 12.21 ± 4.14% vs. 26.03 ± 4.29%; TL: 1.10 ± 0.84 vs. 0.56 ± 0.56 T/S; p < 0.05). Furthermore, master athletes also showed a better oxidative balance than untrained controls (p < 0.05). A negative correlation was observed between TL and body fat (r = −0.471; p = 0.007), and conicity index (r = −0.407; p = 0.021), catalase activity (r = −0.569; p = 0.001), and CAT/TBARS ratio (r = −0.463; p = 0.008) for the whole sample. In conclusion, master athletes have longer TL, better oxidative profile, and lower body fat than untrained individuals. Moreover, for this middle-aged sample, body fat was inversely correlated with both TL and markers of oxidative balance, demonstrating the key role of adiposity in biological aging.
Trends in epidemiology and outcomes of respiratory distress syndrome in the United States

The management practices of Respiratory Distress Syndrome (RDS) in the newborn have changed over time. We examine the trends in the epidemiology, resource utilization, and outcomes (mortality and bronchopulmonary dysplasia [BPD]) of RDS in preterm neonates ≤34 weeks gestational age (GA) in the United States.
Epidural Spinal Cord Stimulation Facilitates Immediate Restoration of Dormant Motor and Autonomic Supraspinal Pathways after Chronic Neurologically Complete Spinal Cord Injury

Epidural Spinal Cord Stimulation (eSCS) in combination with extensive rehabilitation has been reported to restore volitional movement in a select group of subjects after motor-complete spinal cord injury (SCI). Numerous questions about the generalizability of these findings to patients with longer term SCI have arisen, especially regarding the possibility of restoring autonomic function. To better understand the effect of eSCS on volitional movement and autonomic function, two female participants five and 10 years after injury at ages 48 and 52, respectively, with minimal spinal cord preservation on magnetic resonance imaging were implanted with an eSCS system at the vertebral T12 level. We demonstrated that eSCS can restore volitional movement immediately in two female participants in their fifth and sixth decade of life with motor and sensory-complete SCI, five and 10 years after sustaining severe radiographic injuries, and without prescribed or significant pre-habilitation. Both patients experienced significant improvements in surface electromyography power during a volitional control task with eSCS on. Cardiovascular function was also restored with eSCS in one participant with cardiovascular dysautonomia using specific eSCS settings during tilt challenge while not affecting function in a participant with normal cardiovascular function. Orgasm was achieved for the first time since injury in one participant with and immediately after eSCS. Bowel-bladder synergy improved in both participants while restoring volitional urination in one with eSCS. While numerous questions remain, the ability to restore some supraspinal control over motor function below the level of injury, cardiovascular function, sexual function, and bowel and bladder function should promote intense efforts to investigate and develop optimization strategies to maximize recovery in all participants with chronic SCI.
The Context Sensitivity Index (CSI): Measuring the Ability to Identify the Presence and Absence of Stressor Context Cues

The ability to accurately perceive cues to contextual demands across different situations has been identified as a crucial component of successful self-regulation. However, previous attempts to measure context sensitivity have suffered from serious methodological limitations, most notably the possibility that respondents may not possess sufficient knowledge of their own abilities, the confounding of perception of context with response to context, the use of only one or two contextual variations, and the failure to consider the abilities to both accurately detect contextual cues and accurately determine cue absence. This article reports a new, easy-to-administer scenario-based questionnaire measure, the Context Sensitivity Index (CSI), that addressed each of these limitations. The 20-item CSI was iteratively developed and normed using data from five studies to create separate indices to capture sensitivity to the presence of contextual cues (Cue Presence index) and to the relative absence of cues (Cue Absence index). We validated these indices against measures of flexibility, psychopathology, and other scales. Results are discussed in terms of the CSI’s implications, limitations, and future applications.
A secreted schistosome cathepsin B1 cysteine protease and acute schistosome infection induce a transient T helper 17 response

The natural history of schistosome infection in the mammalian host is determined by CD4+ T helper responses mounted against different parasite life cycle stages. A T helper 2 (TH2) response to schistosome eggs is required for host survival and establishment of chronic infection. However, a TH2 cell-derived cytokine also contributes to an immune milieu that is conducive to schistosome growth and development. Thus, the same responses that allow for host survival have been co-opted by schistosomes to facilitate parasite development and transmission, underscoring the significance of CD4+ T cell responses to both worms and eggs in the natural history of schistosome infection. Here we show that a cathepsin B1 cysteine protease secreted by schistosome worms not only induces TH2 responses, but also TH1 and TH17 responses, by a mechanism that is dependent on the proteolytic activity of the enzyme. Further investigation revealed that, in addition to the expected TH1 and TH2 responses, acute schistosome infection also induces a transient TH17 response that is rapidly down-regulated at the onset of oviposition. TH17 responses are implicated in the development of severe egg-induced pathology. The regulation of worm-induced TH17 responses during acute infection could therefore influence the expression of high and low pathology states as infection progresses.
Systematic screening and identification of novel psoriasis-specific genes from the transcriptome of psoriasis-like keratinocytes

Psoriasis is a chronic inflammatory skin disease. Keratinocytes (KCs), as skin-specific cells, serve an important role in the immunopathogenesis of psoriasis. In the present study, transcriptome data derived from psoriasis-like KCs were used together with the reported transcriptome data from the skin/epidermis of patient with psoriasis, excluding known psoriasis-associated genes that have been well described in the previous studies according to GeneCards database, to screen for novel psoriasis-associated genes. According to the human expressed sequence tag of UniGene dataset, six genes that are located near psoriasis-associated loci were highly expressed in skin. Among these six genes, four genes (epiregulin, NIPA like domain containing 4, serpin family B member 7 and WAP four-disulfide core domain 12) were highly expressed in normal mouse epidermis (mainly KCs) and mouse psoriatic epidermis cells, but not in psoriatic dermis cells, which further emphasized the specificity of these genes. Furthermore, in systemic inflammatory response syndrome (SIRS), SERPINB7 showed no difference in expression in immune-activated tissues from SIRS and control mice. It was also found that the mRNA expression levels of SERPINB in lesional skin of patients with psoriasis were significantly higher than in non-lesional psoriatic skin from the same patients. SERPINB7 may be a valuable candidate for further studies. In the present study, a method for identifying novel key pathogenic skin-specific molecules is presented, which may be used for investigating and treating psoriasis.
Utilization of Interactive Clinical Video Telemedicine by Rural and Urban Veterans in the Veterans Health Administration Health Care System.

PURPOSE Interactive clinical video telemedicine (CVT) has the potential to benefit health care systems and patients by improving access, lowering costs, and more efficiently distributing providers. However, there is a gap in current knowledge around the demand for and potential uses of CVT in large integrated health care systems. METHODS We conducted an observational study using Veterans Health Administration (VHA) administrative databases to analyze trends in CVT utilization, and types of care received, among 7.65 million veterans during fiscal years (FY) 2009-2015 (October 1, 2008-September 30, 2015). Trends were stratified by veteran rurality and analyzed using linear regression. Among 4.95 million veterans in FY2015, we used logistic regression to identify characteristics associated with CVT utilization for any care, mental health care, and major specialties. FINDINGS Over 6 years, the annual CVT utilization grew from 30 to 124 encounters per 1,000 veterans (>300% increase), with faster growth among rural veterans than urban veterans. Over the study period, ≥50% of all CVT-delivered care was mental health care. In FY2015, 3.2% of urban and 7.2% of rural veterans utilized CVT for nearly 725,000 clinical encounters. Rural residence, younger age, longer driving distance to VHA facilities, one or more comorbidities, and higher rates of traditional, non-video utilization were independently associated with higher odds of CVT use. CONCLUSIONS CVT utilization in VHA has increased quickly and exceeds published rates in the private health care market. The availability of CVT has likely increased access to VHA care for rural veterans, especially for mental health care.
Mutational landscape of primary, metastatic, and recurrent ovarian cancer reveals c-MYC gains as potential target for BET inhibitors

Significance Ovarian cancer has the propensity for early dissemination of microscopic metastases, making early detection challenging. Development of treatments for patients with advanced/recurrent chemotherapy-resistant disease remains an unmet need. We sequenced primary, synchronous bilateral ovarian cancer (SBOC), metastatic, and recurrent ovarian tumors. We found primary and metastatic tumors to be remarkably similar and SBOC to be clonally related in all cases, suggesting early dissemination to represent an intrinsic feature of ovarian cancer. c-MYC and PIK3CA amplifications were prevalent and maintained in progression to metastasis and enriched in tumor recurrence. c-MYC amplified chemotherapy-resistant cell lines and xenografts were sensitive to JQ1 and GS-626510, suggesting Bromodomain and Extra-Terminal motif (BET) inhibitors as effective targeted agents in patients with c-MYC–amplified recurrent/chemotherapy-resistant ovarian tumors. Ovarian cancer remains the most lethal gynecologic malignancy. We analyzed the mutational landscape of 64 primary, 41 metastatic, and 17 recurrent fresh-frozen tumors from 77 patients along with matched normal DNA, by whole-exome sequencing (WES). We also sequenced 13 pairs of synchronous bilateral ovarian cancer (SBOC) to evaluate the evolutionary history. Lastly, to search for therapeutic targets, we evaluated the activity of the Bromodomain and Extra-Terminal motif (BET) inhibitor GS-626510 on primary tumors and xenografts harboring c-MYC amplifications. In line with previous studies, the large majority of germline and somatic mutations were found in BRCA1/2 (21%) and TP53 (86%) genes, respectively. Among mutations in known cancer driver genes, 77% were transmitted from primary tumors to metastatic tumors, and 80% from primary to recurrent tumors, indicating that driver mutations are commonly retained during ovarian cancer evolution. Importantly, the number, mutation spectra, and signatures in matched primary–metastatic tumors were extremely similar, suggesting transcoelomic metastases as an early dissemination process using preexisting metastatic ability rather than an evolution model. Similarly, comparison of SBOC showed extensive sharing of somatic mutations, unequivocally indicating a common ancestry in all cases. Among the 17 patients with matched tumors, four patients gained PIK3CA amplifications and two patients gained c-MYC amplifications in the recurrent tumors, with no loss of amplification or gain of deletions. Primary cell lines and xenografts derived from chemotherapy-resistant tumors demonstrated sensitivity to JQ1 and GS-626510 (P = 0.01), suggesting that oral BET inhibitors represent a class of personalized therapeutics in patients harboring recurrent/chemotherapy-resistant disease.
Specificity rates for non-clinical, bilingual, Mexican Americans with California Verbal Learning Test3, verbal fluency, and Rey 15-IR performance validity measures

Abstract Objective: To measure failure rates among non-clinical, Mexican American, bilinguals on embedded performance validity measures from the California Verbal Learning Test3 and verbal fluency and the stand-alone Rey 15-item test plus recognition (Rey 15-IR) using valid/invalid performance cut scores developed for monolingual, English-speakers. Method: Participants were 60 consecutive recruits, aged between 18 and 75 years, with ≤16 years of education who self-identified as bilingual (confirmed via formal assessment) and chose the language of assessment, Spanish or English, for the performance validity tests. Results: The only performance validity measure studied with a higher failure rate (19%) than that for monolingual, English-speakers (9%) was semantic fluency administered in Spanish. Conclusions: Valid/invalid performance cut scores derived for monolingual English-speakers generated comparable or lower failure rates among Mexican American bilinguals on CVLT3 forced-choice recognition, CVLT3 yes–no recognition hits, letter fluency, semantic fluency in English, and the Rey 15-IR.
Musculoskeletal models with generic and subject-specific geometry estimate different joint biomechanics in dysplastic hips

Abstract Optimizing the geometric complexity of musculoskeletal models is important for reliable yet feasible estimation of joint biomechanics. This study investigated the effects of subject-specific model geometry on hip joint reaction forces (JRFs) and muscle forces in patients with developmental dysplasia of the hip (DDH) and healthy controls. For nine DDH and nine control subjects, three models were created with increasingly subject-specific pelvis geometry, hip joint center locations and muscle attachments. Hip JRFs and muscle forces during a gait cycle were compared among the models. For DDH subjects, resultant JRFs from highly specific models including subject-specific pelvis geometry, joint locations and muscle attachments were not significantly different compared to models using generic geometry in early stance, but were significantly higher in late stance (p = 0.03). Estimates from moderately specific models using CT-informed scaling of generic pelvis geometry were not significantly different from low specificity models using generic geometry scaled with skin markers. For controls, resultant JRFs in early stance from highly specific models were significantly lower than moderate and low specificity models (p ≤ 0.02) with no significant differences in late stance. Inter-model JRF differences were larger for DDH subjects than controls. Inter-model differences for JRF components and muscle forces were similar to resultant JRFs. Incorporating subject-specific pelvis geometry significantly affects JRF and muscle force estimates in both DDH and control groups, which may be especially important for reliable estimation of pathomechanics in dysplastic hips.
Highly sensitive fiber Bragg grating-based pressure sensor using side-hole packaging.

In this work, an analysis of pressure response of a fiber Bragg grating (FBG) sensor in a side-hole package is presented using the finite element method. Various parameters of the side-hole packaging such as hole radius, the distance of separation between them, the radius and length of the package, and the choice of the package material are considered and optimized in order to promote maximum pressure sensitivity of the FBG sensor. This investigation on optimization of the side-hole package parameters gives rise to pressure sensitivity of nearly 105 times as compared with the bare FBG sensor, with the numerical values of 3 pm/MPa for a bare FBG sensor to ∼280,000 pm/MPa for an optimized side-hole package FBG sensor. Such high-pressure sensitivity of an FBG sensor is being reported for the very first time in this work, to the best of our knowledge, and can be considered as the initial step toward the realization of a highly sensitive hydrophone based on FBG for sensing underwater acoustic signals.
Profiles of Psychological Flexibility: A Latent Class Analysis of the Acceptance and Commitment Therapy Model

There exists uncertainty for clinicians over how the separate subcomponent processes of psychological flexibility, a core construct of the Acceptance and Commitment Therapy model, interact and influence distress experienced. The present study (N = 567) employed latent class analysis to (a) identify potential classes (i.e., subgroups) of psychological flexibility based on responses on measures of key subcomponent process and (b) examine whether such classes could reliably differentiate levels of self-reported psychological distress and positive and negative emotionality. We found three distinct classes: (a) High Psychological Flexibility, (b) Moderate Psychological Flexibility, and (c) Low Psychological Flexibility. Those in the Low Psychology Flexibility class reported highest levels of psychological distress, whereas those in the High Psychological Flexibility class reported lowest levels of psychological distress. This study provides a clearer view to clinicians of the profile of the broader spectrum of the psychological flexibility model to facilitate change in clients.
PARP inhibition enhances tumor cell–intrinsic immunity in ERCC1-deficient non–small cell lung cancer

The cyclic GMP-AMP synthase/stimulator of IFN genes (cGAS/STING) pathway detects cytosolic DNA to activate innate immune responses. Poly(ADP-ribose) polymerase inhibitors (PARPi) selectively target cancer cells with DNA repair deficiencies such as those caused by BRCA1 mutations or ERCC1 defects. Using isogenic cell lines and patient-derived samples, we showed that ERCC1-defective non–small cell lung cancer (NSCLC) cells exhibit an enhanced type I IFN transcriptomic signature and that low ERCC1 expression correlates with increased lymphocytic infiltration. We demonstrated that clinical PARPi, including olaparib and rucaparib, have cell-autonomous immunomodulatory properties in ERCC1-defective NSCLC and BRCA1-defective triple-negative breast cancer (TNBC) cells. Mechanistically, PARPi generated cytoplasmic chromatin fragments with characteristics of micronuclei; these were found to activate cGAS/STING, downstream type I IFN signaling, and CCL5 secretion. Importantly, these effects were suppressed in PARP1-null TNBC cells, suggesting that this phenotype resulted from an on-target effect of PARPi on PARP1. PARPi also potentiated IFN-&ggr;–induced PD-L1 expression in NSCLC cell lines and in fresh patient tumor cells; this effect was enhanced in ERCC1-deficient contexts. Our data provide a preclinical rationale for using PARPi as immunomodulatory agents in appropriately molecularly selected populations.
Structural Determinants of the Prion Protein N-Terminus and Its Adducts with Copper Ions

The N-terminus of the prion protein is a large intrinsically disordered region encompassing approximately 125 amino acids. In this paper, we review its structural and functional properties, with a particular emphasis on its binding to copper ions. The latter is exploited by the region’s conformational flexibility to yield a variety of biological functions. Disease-linked mutations and proteolytic processing of the protein can impact its copper-binding properties, with important structural and functional implications, both in health and disease progression.
The Myth of the Seven

Mathematics has been called the one area of inquiry that would retain its point even were the physical world to entirely disappear. This might be heard as an argument for platonism: the view that mathematics describes a special abstract department of reality lying far above the physical fray. The necessary truth of mathematics would be due to the fact that the mathematical department of reality has its properties unchangingly and essentially.