Miracle-dz/UniFAR-FTUs huggingface dataset:
Viral FLIP blocks Caspase-8 driven apoptosis in the gut in vivo

A strict cell death control in the intestinal epithelium is indispensable to maintain barrier integrity and homeostasis. In order to achieve a balance between cell proliferation and cell death, a tight regulation of Caspase-8, which is a key player in controlling apoptosis, is required. Caspase-8 activity is regulated by cellular FLIP proteins. These proteins are expressed in different isoforms (cFLIPlong and cFLIPshort) which determine cell death and survival. Interestingly, several viruses encode FLIP proteins, homologous to cFLIPshort, which are described to regulate Caspase-8 and the host cell death machinery. In the current study a mouse model was generated to show the impact of viral FLIP (vFLIP) from Kaposi’s Sarcoma-associated Herpesvirus (KSHV)/ Human Herpesvirus-8 (HHV-8) on cell death regulation in the gut. Our results demonstrate that expression of vFlip in intestinal epithelial cells suppressed cFlip expression, but protected mice from lethality, tissue damage and excessive apoptotic cell death induced by genetic cFlip deletion. Finally, our model shows that vFlip expression decreases cFlip mediated Caspase-8 activation in intestinal epithelial cells. In conclusion, our data suggests that viral FLIP neutralizes and compensates for cellular FLIP, efficiently counteracting host cell death induction and facilitating further propagation in the host organism.
Role of a DEF/Y motif in histone H2A-H2B recognition and nucleosome editing

Significance Eukaryotic cells mobilize histones at specific locations along the chromosome to regulate genomic processes, such as transcription. DEF/Y motifs are short amino acid sequences that are known to bind to histones. We found that a tandem DEF/Y motif in the Swc5 subunit of the SWR complex is required for SWR’s nucleosome editing function, a process that involves the replacement of H2A within nucleosomes with the variant histone H2A.Z. Swc5 DEF/Y preferentially binds to histone H2A over H2A.Z. In yeast, the DEF/Y–histone interaction is partially dependent on SWR’s ATPase activity. We solved an X-ray crystal structure of Swc5 DEF/Y in complex with H2A, providing the structural basis for how Swc5 contributes to the directionality of the H2A-to-H2A.Z nucleosome editing process. The SWR complex edits the histone composition of nucleosomes at promoters to facilitate transcription by replacing the two nucleosomal H2A-H2B (A-B) dimers with H2A.Z-H2B (Z-B) dimers. Swc5, a subunit of SWR, binds to A-B dimers, but its role in the histone replacement reaction was unclear. In this study, we showed that Swc5 uses a tandem DEF/Y motif within an intrinsically disordered region to engage the A-B dimer. A 2.37-Å X-ray crystal structure of the histone binding domain of Swc5 in complex with an A-B dimer showed that consecutive acidic residues and flanking hydrophobic residues of Swc5 form a cap over the histones, excluding histone–DNA interaction. Mutations in Swc5 DEF/Y inhibited the nucleosome editing function of SWR in vitro. Swc5 DEF/Y interacts with histones in vivo, and the extent of this interaction is dependent on the remodeling ATPase of SWR, supporting a model in which Swc5 acts as a wedge to promote A-B dimer eviction. Given that DEF/Y motifs are found in other evolutionary unrelated chromatin regulators, this work provides the molecular basis for a general strategy used repeatedly during eukaryotic evolution to mobilize histones in various genomic functions.
The Practice of Child Neuropsychology in Spanish-speaking Countries: What We’ve Learned and Where to Go from Here

ABSTRACT The characteristics and current situation of pediatric neuropsychologists across Spanish-speaking countries was examined. A total of 409 self-identified professionals working in child neuropsychology from 12 Latin American countries and Spain completed an online survey between June and October 2018. Results revealed that pediatric neuropsychology as a related but distinct discipline within neuropsychology presents with a series of unique challenges to practitioners in Spanish-speaking countries. Efforts and initiatives are required to increase awareness of the field, define the core competencies, foster more opportunities for training, and conduct research to understand sociocultural characteristics and develop culturally specific tools.
Direct Comparison of Cervical and High Thoracic Spinal Cord Injury Reveals Distinct Autonomic and Cardiovascular Consequences.

A wide range of spinal cord levels (Cervical 8-Thoracic 6) project to the stellate ganglia (which provides over 90% of sympathetic supply to the heart), with a peak at the Thoracic 2 (T2) level. We hypothesize that despite the proximity of the lesions, high-thoracic spinal cord injuries (i.e. T2-3 SCI) do not closely mimic the hemodynamic responses recorded with cervical SCI (i.e. C6-7 SCI). To test this hypothesis, rats were instrumented with an intra-arterial telemetry device (Data Sciences International, PA-C40) for recording arterial pressure, heart rate, and locomotor activity as well as a catheter within the intraperitoneal space. After recovery, rats were subjected to complete C6-7 spinal cord transection (n=8), sham transection (n=4) or T2-3 spinal cord transection (n=7). Following the spinal cord transection or sham transection, arterial pressure, heart rate, and activity counts were recorded in conscious animals, in a thermoneutral environment, for 20 seconds every minute, 24 hours/day for 12 consecutive weeks. After 12 weeks, chronic reflex and stress-induced cardiovascular, and hormonal responses were compared in all groups. C6-7 rats had hypotension, bradycardia and reduced physical activity. In contrast T2-3 rats were tachycardic. C6-7 rats compared with T2-3 and spinal intact rats also had reduced cardiac sympathetic tonus, reduced reflex and stress induced cardiovascular responses and reduced sympathetic support of blood pressure as well as enhanced reliance on angiotensin to maintain arterial blood pressure. Thus, injuries above and below the peak level (T2) of spinal cord projections to the stellate ganglia have remarkably different outcomes.
Contribution of green turtles Chelonia mydas to total herbivore biomass in shallow tropical reefs of oceanic islands

Green turtles are megaherbivores with a key role in the dynamics of tropical seagrass meadows, but little is known about their relevance as herbivores in tropical reef habitats. We conducted underwater censuses of green turtles, herbivorous fishes and sea urchins in two distinct tropical regions: Fernando de Noronha (Western Atlantic Ocean) and the Hawaiian Archipelago (Central Pacific Ocean), to assess the contribution of green turtles to the total herbivore biomass in shallow reef habitats of tropical oceanic islands. Juvenile green turtles ranging 40–60 cm were observed at most of the surveyed sites, and hence, could be considered typical components of the shallow reef fauna of tropical oceanic islands. Furthermore, they were usually one of the most abundant species of roving herbivores in many of the sites surveyed. However, the biomass of green turtles was usually much lower than the aggregated biomass of fishes or sea urchins, which usually constituted most of the total herbivore biomass. Green turtles made a major contribution to the total herbivore biomass only in sheltered sites with low rugosity, low coral cover and high algal cover. Further investigation on the trophic redundancy between herbivores is required to assess the actual relevance of green turtles in reef ecosystems of oceanic islands, compared to herbivorous fishes and sea urchins, because different herbivores may target different algal resources and complementarity may be needed to maintain ecosystem functioning across large, naturally varied reefscapes.
Nutrition and gut health: the impact of specific dietary components – it's not just five-a-day

The health benefits of fruit, vegetables and dietary fibre have been promoted for many years. Much of the supporting evidence is circumstantial or even contradictory and mechanisms underlying health benefits of specific foods are poorly understood. Colorectal cancer shows marked geographical differences in incidence, probably linked with diet, and explanations for this require knowledge of the complex interactions between diet, microbiota and the gut epithelium. Dietary fibres can act as prebiotics, encouraging growth of saccharolytic bacteria, but other mechanisms are also important. Some but not all soluble fibres have a ‘contrabiotic’ effect inhibiting bacterial adherence to the epithelium. This is particularly a property of pectins (galacturonans) whereas dietary fructans, previously regarded as beneficial prebiotics, can have a proinflammatory effect mediated via toxic effects of high butyrate concentrations. This also suggests that ulcerative colitis could in part result from potentially toxic faecal butyrate concentrations in the presence of a damaged mucus layer. Epithelial adherence of lectins, either dietary lectins as found in legumes, or bacterial lectins such as the galactose-binding lectin expressed by colon cancer-associated Fusobacterium nucleatum, may also be important and could be inhibitable by specific dietary glycans. Conversely, emulsifiers in processed foods may increase bacterial translocation and alter the microbiota thus promoting inflammation or cancer. Focusing on one condition is of limited value although in developing public health messages and growing evidence for impacts of dietary components on all-cause mortality is gaining more attention. We are only just starting to understand the complex interactions between food, the microbiota and health.
Die Rolle der Anaerobier im Wochenbett: klinische Bedeutung und Therapie

: Anaerobic bacteria in the lochia are frequently isolated healthy post-partum patients and from those with post-partum infections. The true pathogenic significance of these anaerobic bacteria is uncertain. Investigations appeared to show that the incidence of anaerobic bacteria is by and large the same as in the vaginal and intestinal flora. In this investigation we showed: 1) anaerobic bacteria are rare in the vaginal flora of pregnant patients in the third trimester, 2) a definite difference exists in the number of anaerobic bacteria in normal lochia versus infected lochia, 3) in post-partum infections qualitative differences exist between the anaerobic isolates. The strains of the bacteroides oralis group become the predominant anaerobic bacteria. It is concluded that members of the bacteroides oralis group which are normally not present in the human intestinal flora play a specific role in post-partum infections. The anti-microbial treatment of post-partum infections has to take this into account. The eminent therapeutic importance of the 5-Nitro-Imidazoles is discussed.
A Culturally Adapted Cognitive Behavioral Internet-Delivered Intervention for Depressive Symptoms: Randomized Controlled Trial

Background Internet-delivered treatments for depressive symptoms have proved to be successful in high-income Western countries. There may be potential for implementing such treatments in low- and middle-income countries such as Colombia, where access to mental health services is limited. Objective The objective of this study was to assess the efficacy of a culturally adapted cognitive behavioral internet-delivered treatment for college students with depressive symptoms in Colombia. Methods This was a randomized controlled trial with a 3-month follow-up. The program comprised seven modules. A total of 214 Colombian college students were recruited. They were assessed and randomly assigned to either the treatment group (n=107) or a waiting list (WL) control group (n=107). Participants received weekly support from a trained supporter. The primary outcome was symptoms of depression, as measured by the Patient Health Questionnaire - 9, and the secondary outcomes were anxiety symptoms assessed by the Generalized Anxiety Disorder questionnaire - 7. Other measures, including satisfaction with treatment, were evaluated after 7 weeks. Results Research attrition and treatment dropouts were high in this study. On average, 7.6 sessions were completed per user. The mean time spent on the program was 3 hours and 18 min. The linear mixed model (LMM) showed significant effects after treatment (t 197.54=−5.189; P<.001) for the treatment group, and these effects were maintained at the 3-month follow-up (t 39.62=4.668; P<.001). Within-group results for the treatment group yielded a large effect size post treatment (d=1.44; P<.001), and this was maintained at the 3-month follow-up (d=1.81; P<.001). In addition, the LMM showed significant differences between the groups (t 197.54=−5.189; P<.001). The results showed a large effect size between the groups (d=0.91; P<.001). In the treatment group, 76.0% (16/107) achieved a reliable change, compared with 32.0% (17/107) in the WL control group. The difference between groups was statistically significant (X22=10.5; P=.001). Conclusions This study was the first contribution to investigating the potential impact of a culturally adapted internet-delivered treatment on depressive symptoms for college students as compared with a WL control group in South America. Future research should focus on identifying variables associated both with premature dropout and treatment withdrawal at follow-up. Trial Registration ClinicalTrials.gov NCT03062215; https://clinicaltrials.gov/ct2/show/NCT03062215
Association between VEGF gene polymorphisms (11 sites) and polycystic ovary syndrome risk

Abstract Vascular endothelial growth factor (VEGF) plays a critical role in ovarian folliculogenesis and normal reproductive function. So far, several studies focusing on association between VEGF gene polymorphisms and polycystic ovary syndrome (PCOS). However, above association between the VEGF gene polymorphisms and PCOS susceptibility is uncertain. Hence, we performed a timely meta-analysis containing all current publications to make clear this relationship. We searched articles from the PubMed, Embase and Chinese language (WanFang and CNKI) databases that were published up until May 10, 2019. Finally, we obtained 9 studies, containing 29 case–control studies and 11 different polymorphisms. The odds ratios (OR) and 95% confidence intervals (CI) were revealed association strengths. There were significantly decreased associations between rs2010963 (-634), +9812, +405 polymorphisms and PCOS risk. Nevertheless, there existed increased associations between rs699947 (-2578), rs833061, rs1570360 (-1154), rs3025020, rs3025039 polymorphisms and PCOS susceptibility. Our current analysis suggested VEGF gene polymorphisms may be associated with PCOS risk, which is possible to be expected to become biomarkers of early detection for women.
Hydropic anthelmintics against parasitic nematodes

Hydrodynamic forces that typically act in healthy cells maintain fluid osmoregulation by balancing hydrostatic and oncotic pressures [1]. The sodium–potassium pump has a fundamental role in the maintenance of cellular osmoregulation [2]. Functionally, the sodium– potassium pump is regulated by Na/K adenosine triphosphate (ATP)ase, a ubiquitous enzyme that continually uses ATP by pumping 3 Na ions out of and importing 2 K ions into cells. When a constant sodium gradient is upheld, water molecules cross the plasma membrane by passive diffusion, maintaining dynamic homeostasis. Failure of the Na/K ATPase pump to regulate homeostasis results in membrane depolarization and eventually cellular swelling and death [2]. Any form of stress or injury to the membrane or the molecular pump adversely affects cell-resting potential and causes rapid Na, Ca, and water influx. The water influx causes vacuoles, mitochondria, rough endoplasmic reticulum, and Golgi bodies to dilate and deteriorate, and under these circumstances, small vacuoles fuse to form giant vacuoles (Fig 1), which might be a hindrance to cell convalescence. Overall, abnormal water ingress disrupts normal cell hydrodynamics and eventually stimulates cell-death pathways.
Non-specific chronic low back pain and physical activity: A comparison of postural control and hip muscle isometric strength

Abstract Most research on sedentary lifestyle has focused on pain and disability, while neuromuscular outcomes (postural control and strength) have received less attention. The objective of the study was to determine whether low level of physical activity is negatively associated with measures of lower body muscular strength and postural control in individuals with and without non-specific chronic low back pain (NSCLBP). Twenty-four subjects with NSCLBP (28.8 ± 5.9 years) and 24 age, gender, and body mass index matched healthy controls participated in the study. Subjects were sub-classified into 4 subgroups based on their physical activity level: Non-active NSCLBP; Active NSCLBP; Non-active healthy control; and Active healthy control. Each subgroup consisted of 12 subjects. Peak force of hip muscles strength was assessed using a handheld dynamometer. Postural control was assessed using computerized posturography and the Y Balance Test. There was no significant group by physical activity interaction for strength and static and dynamic postural control, except for static control during left single leg stance with eyes closed (P = .029). However, there was a significant difference in strength and postural control by physical activity (P < .05). Postural control and peak force of hip muscles strength were significantly associated with physical activity (r ranged from 0.50 to 0.66, P < .001 and r ranged from 0.40 to 0.59, P < .05, respectively). Postural control and hip strength were independently related to physical activity behavior. A sedentary behavior may be an important risk factor for impaired postural control and hip muscles strength, and that physical fitness is vital to neuromuscular outcomes.
The parallel programming of landing position in saccadic eye movement sequences

Saccadic eye movements occur in sequences, gathering new information about the visual environment to support successful task completion. Here, we examine the control of these saccadic sequences and specifically the extent to which the spatial aspects of the saccadic responses are programmed in parallel. We asked participants to saccade to a series of visual targets and, while they shifted their gaze around the display, we displaced select targets. We found that saccade landing position was deviated toward the previous location of the target suggesting that partial parallel programming of target location information was occurring. The saccade landing position was also affected by the new target location, which demonstrates that the saccade landing position was also partially updated following the shift. This pattern was present even for targets that were the subject of the next fixation. Having a greater preview about the sequence path influenced saccade accuracy with saccades being less affected by relocations when there is less preview information. The results demonstrate that landing positions from a saccade sequence are programmed in parallel and combined with more immediate visual signals.
Temozolomide plus whole brain radiotherapy for the treatment of non-small-cell lung cancer patients with brain metastases

Abstract Introduction: Whole brain radiotherapy (WBRT) has been the mainstay treatment of brain metastases (BM) in non-small cell lung cancer (NSCLC) patients for years. Temozolomide (TMZ) could penetrate the blood–brain barrier and some studies showed that TMZ plus MBRT may improve clinical effectiveness. This meta-analysis is aim to evaluate the clinical effectiveness and safety of TMZ plus MBRT in the NSCLC patients with BM. Methods and analysis: We systematically searched databases including PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and four Chinese databases (Chinese Biomedical Database, China National Knowledge Infrastructure, Wanfang Database and Chinese Scientific Journal Database) without language restrictions from inception until July 26, 2019. Randomized controlled trials (RCTs) which compared TMZ plus WBRT with single WBRT in the advanced NSCLC patients with BM were included. The outcomes analysis reported objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), quality of life (QOL), and adverse effects. Two reviewers will independently extract data from the selected studies and assess the quality of studies. Statistical analyses will be performed using Review manager 5.3 software. Random-effects or fixed models were used to estimate pooled hazard ratio and relative risk. Results: This systemic review and meta-analysis will evaluate the effects of TMZ plus MBRT in the NSCLC patients with BM in RCTs. Conclusion: Our study will provide evidence to judge if TMZ plus MBRT are effective treatment for NSCLC patients with BM.
The Burden of Cough and Phlegm in People With COPD: A COPD Patient-Powered Research Network Study.

Rationale Cough and phlegm are common symptoms of chronic obstructive pulmonary disease (COPD) and may significantly affect quality of life. This study assessed the burden of cough and phlegm on clinical outcomes and quality of life among people with a self-reported physician diagnosis of COPD. Methods Patient-reported data from the COPD Foundation's Patient-Powered Research Network (COPD PPRN) were utilized. Cough and phlegm severity and frequency were assessed by responses to questions on the COPD Assessment Test (CAT) and categorized into none/low, moderate and severe. Quality of life domains were evaluated using the Patient-Reported Outcome Measurement Information System (PROMIS-29). Associations between cough and phlegm levels and PROMIS-29 domains were examined using multivariate analysis of variance (MANOVA). Results The 5286 participants were average age 64.4 years (SD=11.4), 87.9% white, 60.4% female, 51.2% married, and 42.2% with caregivers. Approximately three-fourths of the participants had moderate or severe cough or phlegm levels. Respondents with moderate and high cough or phlegm had significantly worse dyspnea (p<0.0001), more exacerbations in the previous one year (p<0.0001), worse physical and social functioning, and more symptoms of anxiety and depression on PROMIS-29 compared to those with no/low cough and phlegm. Conclusions In this group of people with COPD, higher levels of cough and phlegm are associated with worse clinical and quality of life outcomes.
Role of Interatrial Block Recognition: A closer look to the Bayés Syndrome.

Corresponding Author Prof. Dr. Osmar Antonio Centurión, MD, PhD, FACC, FAHA Professor of Medicine. Faculty of Medical Sciences. Asunción National University (UNA). Chief, Department of Cardiology. Hospital de Clínicas. Address: Av. Mariscal López e/ Coronel Cazal. San Lorenzo, Paraguay
Complex reconstruction technique applied in advanced head and neck cancer

Abstract Complex reconstruction skills in advanced head and neck cancer (HNC) could resolve the key problem of large defects after tumor resection. We combined the anterolateral thigh free flap, fascia lata flap, and greater saphenous vein graft in the reconstruction process of salvage surgery. Seven patients suffering from advanced HNC who experienced the failure of multiple therapeutic methods were enrolled in our study between June 2017 and January 2018. They all agreed to voluntarily undergo the tumor excision and complex reconstruction procedure we developed. The total flap size ranged from 20 × 13 cm to 30 × 15 cm. The length of the greater saphenous vein graft ranged from 4 to 11 cm. The hospitalization period ranged from 7 to 33 days. All of the flaps were viable, but in 1 patient, oral flap edge infection and necrosis necessitated partial debridement on day 7 postoperatively. All donor sites were closed primarily. We report our experience with this surgical method for complex reconstruction in advanced HNC patients.