Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of key genes, pathways and potential therapeutic agents for liver fibrosis using an integrated bioinformatics analysis

Background Liver fibrosis is often a consequence of chronic liver injury, and has the potential to progress to cirrhosis and liver cancer. Despite being an important human disease, there are currently no approved anti-fibrotic drugs. In this study, we aim to identify the key genes and pathways governing the pathophysiological processes of liver fibrosis, and to screen therapeutic anti-fibrotic agents. Methods Expression profiles were downloaded from the Gene Expression Omnibus (GEO), and differentially expressed genes (DEGs) were identified by R packages (Affy and limma). Gene functional enrichments of each dataset were performed on the DAVID database. Protein–protein interaction (PPI) network was constructed by STRING database and visualized in Cytoscape software. The hub genes were explored by the CytoHubba plugin app and validated in another GEO dataset and in a liver fibrosis cell model by quantitative real-time PCR assay. The Connectivity Map L1000 platform was used to identify potential anti-fibrotic agents. Results We integrated three fibrosis datasets of different disease etiologies, incorporating a total of 70 severe (F3–F4) and 116 mild (F0–F1) fibrotic tissue samples. Gene functional enrichment analyses revealed that cell cycle was a pathway uniquely enriched in a dataset from those patients infected by hepatitis B virus (HBV), while the immune-inflammatory response was enriched in both the HBV and hepatitis C virus (HCV) datasets, but not in the nonalcoholic fatty liver disease (NAFLD) dataset. There was overlap between these three datasets; 185 total shared DEGs that were enriched for pathways associated with extracellular matrix constitution, platelet-derived growth-factor binding, protein digestion and absorption, focal adhesion, and PI3K-Akt signaling. In the PPI network, 25 hub genes were extracted and deemed to be essential genes for fibrogenesis, and the expression trends were consistent with GSE14323 (an additional dataset) and liver fibrosis cell model, confirming the relevance of our findings. Among the 10 best matching anti-fibrotic agents, Zosuquidar and its corresponding gene target ABCB1 might be a novel anti-fibrotic agent or therapeutic target, but further work will be needed to verify its utility. Conclusions Through this bioinformatics analysis, we identified that cell cycle is a pathway uniquely enriched in HBV related dataset and immune-inflammatory response is clearly enriched in the virus-related datasets. Zosuquidar and ABCB1 might be a novel anti-fibrotic agent or target.
Trends in the Management of Isolated SLAP Tears in the United States

Background: The management of superior labrum anterior and posterior (SLAP) tears remains controversial, with surgical treatment options including SLAP repair, debridement, and open or arthroscopic biceps tenodesis (BT), based on patient factors and the type of tear. Hypothesis: We hypothesized that SLAP repair has become less frequently performed over time, while BT is more frequently performed, particularly in patients ≥ 40 years. Study Design: Descriptive epidemiology study. Methods: A retrospective query was performed using the Humana insurance database from years 2007 to 2016. For the management of a SLAP tear diagnosis (International Classification of Diseases–Ninth Edition [ICD-9] code: 840.7), independent and exclusive cohorts were formed using Current Procedural Terminology (CPT) codes for debridement (29822, 29823), SLAP repair (29807), open or arthroscopic BT (29828, 23430), and SLAP repair combined with BT (29828 OR 23430 AND 29807). Results: Of 46,650 diagnoses of a SLAP tear, there were 3347 patients who underwent operative management for an isolated SLAP tear from 2007 to 2016. There was a linear increase of SLAP tear diagnoses per year (r 2 = 0.800, P < .001) during this period. Overall, SLAP repair was performed in 1629 patients (48.7%), debridement was performed in 1076 patients (32.1%), BT was performed in 552 patients (16.5%), and combined SLAP repair and BT was performed in 90 patients (2.7%). There was a 69.3% decrease in isolated SLAP repair from 2007 to 2016 (r 2 = 0.882, P < .001). BT for the diagnosis of an isolated SLAP tear increased by 370.0% over the same period (r 2 = 0.800, P < .001). SLAP repair had an equivalent percentage of being performed in patients both older and younger than 40 years (P = .218). There was a 1500.0% increase in BT performed in patients older than 40 years during the study period. There were no statistical differences in the postoperative incidence of stiffness, surgical site infections, and reoperations between all surgical treatment groups (P > .05). Conclusion: An analysis of a large private-payer database revealed that surgical treatment of isolated SLAP tears in the United States has shifted from 2007 to 2016, with an increase in the frequency of BT and a decline in the frequency of SLAP repair, particularly in patients older than 40 years.
Effect of Oral Contraceptives on Soft Tissue Injury Risk, Soft Tissue Laxity, and Muscle Strength: A Systematic Review of the Literature

Background: Female patients are more likely than male patients to experience various musculoskeletal (MSK) injuries. Because MSK tissues are sensitive to the female hormones relaxin, estrogen, and progesterone, studies have examined whether hormonal contraceptives, which change female hormone levels, can alter the female MSK injury risk. These studies have reached contradictory conclusions, leaving unclear the influence of hormonal contraception on female MSK injury risk. Hypothesis: Hormonal contraceptives act to decrease female soft tissue injury risk and soft tissue laxity. Study Design: Systematic review; Level of evidence, 3. Methods: Reviewers searched for clinically relevant studies evaluating the relationship between hormonal contraceptive use and soft tissue injuries, soft tissue laxity, muscle injuries, and muscle strength in the PubMed, Cochrane, Scopus, CINAHL, and Embase databases. Studies meeting inclusion criteria were scored by 2 independent researchers for risk of bias, imprecision, inconsistency, and indirectness with a template designed using the British Medical Journal Clinical Evidence GRADE (Grades of Recommendation Assessment, Development and Evaluation) scoring system and GRADEPro guidelines. Scores were uploaded into the GRADEPro scoring system software, which calculated each study’s final GRADE score (very low, low, moderate, or high quality). Results: A total of 29 studies met inclusion criteria. Of the 7 studies evaluating oral contraceptive (OC) use and soft tissue injury risk, only 2 received a high quality-of-evidence score; all other studies received a very low score. The high-quality studies concluded that OC use decreases anterior cruciate ligament (ACL) injury risk. Only 1 of the 10 studies evaluating OC use and soft tissue laxity was found to have a high quality of evidence; this study determined that OC use decreases ACL laxity. Conclusion: Higher quality studies suggest that OCs decrease a female patient’s risk of ACL injuries and ACL laxity. The strength of these findings, however, is weak. Female patients are up to 8 times more likely to tear their ACLs than male patients. OCs may serve a therapeutic role in decreasing the sex disparity in ACL injury rates.
Direct Oral Anticoagulants in Patients Undergoing Urgent Reperfusion for Nonvalvular Atrial Fibrillation-Related Ischemic Stroke: A Brief Report on Literature Evidence

Introduction The optimal timing for starting anticoagulation in the early phase of nonvalvular atrial fibrillation (NVAF)-related acute ischemic stroke (AIS) remains a challenge, especially in patients undergoing urgent reperfusion by systemic thrombolysis or mechanical thrombectomy. The aim of our study was to review the literature evidence reporting on safety of direct oral anticoagulants (DOACs) starting in the early phase of NVAF-related AIS undergoing systemic thrombolysis and/or mechanical thrombectomy. Materials and Methods We reviewed the PubMed databases searching articles reporting on efficacy and safety of DOACs starting time within two weeks from AIS onset in patients undergoing systemic thrombolysis and/or mechanical thrombectomy. Results Three studies were selected, overall including one hundred and six patients (62 females, 58.4%). Median National Institute of Health Stroke Scale (NIHSS) score at hospital admission ranged from 9 to 13 points. Median DOACs starting time ranged from 2 to 6 days. Median CHA2DS2-VASC score ranged from 4 to 6 points. Follow-up was limited to 14 days in one study, 30 days in another, and 90 days in a third one. Overall, stroke recurrence and/or intracranial bleeding occurred in two patients (1.9%) and no patient died at follow-up. Conclusion Small sample size real life studies seem to demonstrate that the introduction of DOACs in the early phase of NVAF-related AIS undergoing urgent reperfusion is efficacious and safe. Prospective RCTs are necessary to confirm these findings.
Students' Perceptions of Collaborative Summary Writing

Writing is one of the four main language skills that are given emphasis in Second Language Learning. Summary writing is often viewed as a difficult and a challenging skill in learning a second language, which may result in negative attitudes forming, both toward summary writing and to writing in general. The main purpose of this study is to investigate students’ perceptions and problems related to collaborative summary writing in a university in Saudi Arabia. The study involved five undergraduate EFL Saudi female students as a case study and who were exposed to writing course participated in this study. The students were given different collaborative writing tasks during the semester and completed one summary writing task collaboratively for the purpose of this study. Then their views about the task were recorded via semi-structured interview. The findings suggest that most of the participants express positive attitudes toward collaborative writing and consider it beneficial for improving different aspects of writing skills, second language proficiency, and confidence. Several problems occurred during the process of collaboration, and these are also identified and discussed.
To Re-use is to Re-write: Experiences with Re-using IIR Experiment Software

Interactive Information Retrieval experiments have two main requirements. They need to follow a workflow that takes the participant through the individual steps of the experiment and they need to show the user an interface to interact with. Both of these aspects look like they should lend themselves to re-use. This paper analyses the experience of developing and re-using software for both of these aspects across a time period of approximately five years. The main conclusion is that re-use of workflow management software should be possible, but for software for interface creation the question of whether re-use is possible is still open.
Susceptibility Weighted Imaging (SWI) Recommended as a Regular Magnetic Resonance Diagnosis for Vascular Dementia to Identify Independent Idiopathic Normal Pressure Hydrocephalus Before Ventriculo-Peritoneal (V-P) Shunt Treatment: A Case Study

Idiopathic normal pressure hydrocephalus (INPH) with comorbid vascular dementia (VD) often have poor response to ventriculo-peritoneal (V-P) shunt. Here, three patients over the age of 60 came to the hospital with the similar clinical symptoms, Evan index over 0.3, mini-mental state examination (MMSE) score <27, and cerebrospinal fluid (CSF) pressure under 200 mmH2O. They accepted conventional brain imaging scanning, followed by magnetic resonance-susceptibility weighted imaging (MR-SWI) scanning. We found that MR-SWI could distinguish INPH from leukoaraiosis (LA) and cerebral amyloid angiopathy (CAA), through cerebral microbleed (CMB) images, sharply. We highly recommended incorporation of MR-SWI into INPH international guidance as a routine pre-operative diagnostic method preceding V-P shunt treatment.
Neural Networks for Modeling Neural Spiking in S1 Cortex

Somatosensation is composed of two distinct modalities: touch, arising from sensors in the skin, and proprioception, resulting primarily from sensors in the muscles, combined with these same cutaneous sensors. In contrast to the wealth of information about touch, we know quite less about the nature of the signals giving rise to proprioception at the cortical level. Likewise, while there is considerable interest in developing encoding models of touch-related neurons for application to brain machine interfaces, much less emphasis has been placed on an analogous proprioceptive interface. Here we investigate the use of Artificial Neural Networks (ANNs) to model the relationship between the firing rates of single neurons in area 2, a largely proprioceptive region of somatosensory cortex (S1) and several types of kinematic variables related to arm movement. To gain a better understanding of how these kinematic variables interact to create the proprioceptive responses recorded in our datasets, we train ANNs under different conditions, each involving a different set of input and output variables. We explore the kinematic variables that provide the best network performance, and find that the addition of information about joint angles and/or muscle lengths significantly improves the prediction of neural firing rates. Our results thus provide new insight regarding the complex representations of the limb motion in S1: that the firing rates of neurons in area 2 may be more closely related to the activity of peripheral sensors than it is to extrinsic hand position. In addition, we conduct numerical experiments to determine the sensitivity of ANN models to various choices of training design and hyper-parameters. Our results provide a baseline and new tools for future research that utilizes machine learning to better describe and understand the activity of neurons in S1.
Antigenic Site-Specific Competitive Antibody Responses to the Fusion Protein of Respiratory Syncytial Virus Were Associated With Viral Clearance in Hematopoietic Cell Transplantation Adults

Background: Recent studies of human sera showed that the majority of the respiratory syncytial virus (RSV) neutralizing antibodies are directed against pre-fusion conformation of the fusion (F) protein of RSV and revealed the importance of pre-fusion antigenic site Ø specific antibodies. However, detailed analysis of multiple antigenic site-specific competitive antibody responses to RSV F protein and their contribution to virus clearance in humans are lacking. Methods: We prospectively enrolled a cohort of RSV infected hematopoietic cell transplantation (HCT) adults (n = 40). Serum samples were collected at enrollment (acute, n = 40) and 14 to 60 days post-enrollment (convalescent, n = 40). Antigenic site-specific F protein antibodies were measured against pre-fusion site Ø, post-fusion site I, and sites II and IV present in both the pre-fusion and post-fusion F protein conformations utilizing four different competitive antibody assays developed with biotinylated monoclonal antibodies (mAb) D25, 131-2A, palivizumab, and 101F, respectively. The lower limit of detection were 7.8 and 1.0 μg/mL for the competitive antibody assays that measured site Ø specific response, as well as sites I, II, and IV specific responses, respectively. Neutralizing antibody titers to RSV A and B subgroups was determined by microneutralization assays. Results: The overall findings in RSV infected HCT adults revealed: (1) a significant increase in antigenic site-specific competitive antibodies in convalescent sera except for site Ø competitive antibody (p < 0.01); (2) comparable concentrations in the acute and convalescent serum samples of antigenic site-specific competitive antibodies between RSV/A and RSV/B infected HCT adults (p > 0.05); (3) significantly increased concentrations of the antigenic site-specific competitive antibodies in HCT adults who had genomic RSV detected in the upper respiratory tract for <14 days compared to those for ≥14 days (p < 0.01); and (4) statistically significant correlation between the antigenic site-specific competitive antibody concentrations and neutralizing antibody titers against RSV/A and RSV/B (r ranged from 0.33 to 0.83 for acute sera, and 0.50–0.88 for convalescent sera; p < 0.05). Conclusions: In RSV infected HCT adults, antigenic site-specific antibody responses were induced against multiple antigenic sites found in both the pre-fusion and post-fusion F conformations, and were associated with a more rapid viral clearance and neutralizing antibody activity. However, the association is not necessarily the cause and the consequence.
The Differential Effect of Excess Aldosterone on Skeletal Muscle Mass by Sex

The effects of excess aldosterone on skeletal muscle in individuals with primary aldosteronism (PA) are unknown. To examine the effects of aldosterone on skeletal muscle mass in patients with PA, by sex, 309 consecutive patients were enrolled. Skeletal muscle and fat mass of 62 patients with PA were compared with those of 247 controls with non-functioning adrenal incidentaloma (NFAI). Body composition parameters were measured using bioelectrical impedance analysis, and plasma aldosterone concentration (PAC) was measured using radioimmunoassay. The PAC in all women, but not in men, showed an inverse association with both appendicular skeletal muscle mass (ASM) (β = −0.197, P = 0.016) and height-adjusted ASM (HA-ASM) (β = −0.207, P = 0.009). HA-ASM in women (but not in men) with PA was 5.0% lower than that in women with NFAI (P = 0.036). Furthermore, women with PA had a lower HA-ASM than 1:1 age- and sex-matched controls with NFAI by 5.7% (P = 0.049) and tended to have a lower HA-ASM than 1:3 age-, sex-, and menopausal status-matched controls without adrenal incidentaloma (AI) by 7.3% (P = 0.053). The odds ratio (OR), per quartile increase in PAC, of low HA-ASM in women was 1.18 [95% confidence interval (CI), 1.01–1.39; P = 0.035]. The odds of HA-ASM in subjects with PA were 10.63-fold (95% CI: 0.83–135.50) higher, with marginal significance (P = 0.069) than in those with NFAI. Skeletal muscle mass in women with PA was lower than that in women with NFAI; suggesting that excess aldosterone has adverse effects on skeletal muscle metabolism.
Ab initio Study of Anchoring Groups for CuGaO2 Delafossite-Based p-Type Dye Sensitized Solar Cells

Here we report the first theoretical characterization of the interface between the CuGaO2 delafossite oxide and the carboxylic (–COOH) and phosphonic acid (–PO3H2) anchoring groups. The promising use of delafossites as effective alternative to nickel oxide in p-type DSSC is still limited by practical difficulties in sensitizing the delafossite surface. Thus, this work provides atomistic insights on the structure and energetics of all the possible interactions between the anchoring functional groups and the CuGaO2 surface species, including the effects of the Mg doping and of the solvent medium. Our results highlight the presence of a strong selectivity toward the monodentate binding mode on surface Ga atoms for both the carboxylic and phosphonic acid groups. Since the binding modes have a strong influence on the hole injection thermodynamics, these findings have direct implications for further development of delafossite based p-type DSSCs.
Stereocomplexation of Poly(Lactic Acid)s on Graphite Nanoplatelets: From Functionalized Nanoparticles to Self-assembled Nanostructures

The control of nanostructuration of graphene and graphene related materials (GRM) into self-assembled structures is strictly related to the nanoflakes chemical functionalization, which may be obtained via covalent grafting of non-covalent interactions, mostly exploiting π-stacking. As the non-covalent functionalization does not affect the sp2 carbon structure, this is often exploited to preserve the thermal and electrical properties of the GRM and it is a well-known route to tailor the interaction between GRM and organic media. In this work, non-covalent functionalization of graphite nanoplatelets (GnP) was carried out with ad-hoc synthesized pyrene-terminated oligomers of polylactic acid (PLA), aiming at the modification of GnP nanopapers thermal properties. PLA was selected based on the possibility to self-assemble in crystalline domains via stereocomplexation of complementary poly(L-lactide) (PLLA) and poly(D-lactide) (PDLA) enantiomers. Pyrene-initiated PLLA and PDLA were indeed demonstrated to anchor to the GnP surface. Calorimetric and X-ray diffraction investigations highlighted the enantiomeric PLAs adsorbed on the surface of the nanoplatelets self-organize to produce highly crystalline stereocomplex domains. Most importantly, PLLA/PDLA stereocomplexation delivered a significantly higher efficiency in nanopapers heat transfer, in particular through the thickness of the nanopaper. This is explained by a thermal bridging effect of crystalline domains between overlapped GnP, promoting heat transfer across the nanoparticles contacts. This work demonstrates the possibility to enhance the physical properties of contacts within a percolating network of GRM via the self-assembly of macromolecules and opens a new way for the engineering of GRM-based nanostructures.
Climate‐change refugia in boreal North America: what, where, and for how long?

H latitude regions around the world are experiencing particularly rapid climate change. These regions include the 625 million ha North American boreal region, which contains 16% of the world’s forests and plays a major role in the global carbon cycle (Brandt et al. 2013). Boreal ecosystems are particularly susceptible to rapid climatedriven vegetation change initiated by standreplacing natural disturbances (notably fires), which have increased in number, extent, and frequency (Kasischke and Turetsky 2006; Hanes et al. 2018) and are expected to continue under future climate change (Boulanger et al. 2014). Such disturbances will increasingly complicate species persistence, and it will therefore be critical to identify locations of possible climatechange refugia (areas “relatively buffered from contemporary climate change”) (Morelli et al. 2016). These “slow lanes” for biodiversity will be especially important for conservation and management of boreal species and ecosystems (Morelli et al. 2020). Practically speaking, the refugia concept can translate into specific sites or regions that are expected to be more resistant to the influence of climate change than other areas (“in situ refugia”; Ashcroft 2010). Refugia may also encompass sites or regions to which species may more readily retreat as climate conditions change (“ex situ refugia”; Ashcroft 2010; Keppel et al. 2012), as well as temporary “stepping stones” (Hannah et al. 2014) linking current and future habitats. In addition to areas that are climatically buffered, fire refugia – “places that are disturbed less frequently or less severely by wildfire” (Krawchuk et al. 2016) – may also play key roles in promoting ecosystem persistence under changing conditions (Meddens et al. 2018). Previous examinations of climatechange refugia have primarily emphasized external, terrainmediated mechanisms. Factors such as topographic shading and temperature inverClimatechange refugia in boreal North America: what, where, and for how long?