Miracle-dz/UniFAR-FTUs huggingface dataset:
Effectiveness of Percutaneous Electrolysis in Supraspinatus Tendinopathy: A Single-Blinded Randomized Controlled Trial

Supraspinatus tendinopathy is one of the most common causes of shoulder pain. Many studies support conservative treatments such as exercise, trigger point dry needling or corticosteroid injections. Otherwise, a minimally invasive approach with percutaneous electrolysis (PE) has also been used successfully in shoulder pain, although evidence about its long-term effects is scarce. The aim of this trial was to determine the effects of PE on supraspinatus tendinopathy compared with trigger point dry needling (TDN). Thirty-six patients with supraspinatus tendinopathy were randomly assigned to either a PE group (n = 18) or a TDN group (n = 18). Both groups also performed eccentric exercises. The main outcome to be measured was the Numerical Pain Rating Scale (NPRS), but the shoulder range of motion (ROM) and trigger point pressure pain threshold (PPT) were also considered. A one-year follow-up was conducted. Significant differences favoring the PE group were found regarding pain at one-year follow-up (p = 0.002). The improvement achieved in the PE group was greater in the NPRS (p < 0.001), proximal PPT, middle PPT, distal PPT (all p < 0.001) and ranges of movement. PE seems to be more effective than TDN in relieving pain and improving ROM and PPT supraspinatus values in patients with supraspinatus tendinopathy, both right after treatment and at one-year follow-up.
Molecular Interactions Stabilizing the Promatrix Metalloprotease-9·Serglycin Heteromer

Previous studies have shown that THP-1 cells produced an SDS-stable and reduction-sensitive complex between proMMP-9 and a chondroitin sulfate proteoglycan (CSPG) core protein. The complex could be reconstituted in vitro using purified serglycin (SG) and proMMP-9 and contained no inter-disulfide bridges. It was suggested that the complex involved both the FnII module and HPX domain of proMMP-9. The aims of the present study were to resolve the interacting regions of the molecules that form the complex and the types of interactions involved. In order to study this, we expressed and purified full-length and deletion variants of proMMP-9, purified CSPG and SG, and performed in vitro reconstitution assays, peptide arrays, protein modelling, docking, and molecular dynamics (MD) simulations. ProMMP-9 variants lacking both the FnII module and the HPX domain did not form the proMMP-9∙CSPG/SG complex. Deletion variants containing at least the FnII module or the HPX domain formed the proMMP-9∙CSPG/SG complex, as did the SG core protein without CS chains. The interacting parts covered large surface areas of both molecules and implicated dynamic and complementary ionic, hydrophobic, and hydrogen bond interactions. Hence, no short single interacting linear motifs in the two macromolecules could explain the strong SDS-stable and reduction-sensitive binding.
Proposal of the optimal numbers of examined and positive lymph nodes to the 8th edition of American Joint Committee on Cancer (AJCC) staging for 758 patients with distal cholangiocarcinoma

Introduction The American Joint Committee on Cancer (AJCC) recommended retrieval of at least 12 lymph nodes and firstly classified N category by the number of positive lymph nodes (PLNs) for Distal Cholangiocarcinoma (DCC). Objective The end of this cohort study was to explore the optimal cut-off values of the number of examined lymph nodes (ELNs) and PLNs to better stratify patients by utilizing a population-based database. Methods A number of 758 patients with DCC from the Surveillance, Epidemiology, and End Results (SEER) database were enrolled in the study and comparing by the survival analysis. Results Survival analysis found that patients with ELNs < 5 had a lower 3-year disease-specific survival rate than ELNs ≥ 5 in N0M0 cohort (35.3% vs. 53.0%, P = 0.001) and in M0 cohort (42.7% vs. 32.8%, P = 0.006); survival curves between patients with ELNs < 12 and ELNs ≥ 12 were overlapped in N0M0 cohort (P = 0.256) and in M0 cohort (P = 0.233). Among patients with ELNs ≥ 5, using the optimal cut-off value of the number of PLNs (0, 2) could accurately stratify patients, but the recommendation of the number of PLNs (0, 3) by the AJCC could not. Conclusions This study recommended examining at least 5 lymph nodes and defining PLNs = 1–2 as the N1 category and PLNs ≥ 3 as the N2 category, which may better stratify distal cholangiocarcinoma patients and improve the accuracy of the eighth edition AJCC staging.
On the Dependence of Rheology of Hyaluronic Acid Solutions and Frictional Behavior of Articular Cartilage

Hyaluronic acid (HA) injections represent one of the most common methods for the treatment of osteoarthritis. However, the clinical results of this method are unambiguous mainly because the mechanism of action has not been clearly clarified yet. Viscosupplementation consists, inter alia, of the improvement of synovial fluid rheological properties by injected solution. The present paper deals with the effect of HA molecular weight on the rheological properties of its solutions and also on friction in the articular cartilage model. Viscosity and viscoelastic properties of HA solutions were analyzed with a rotational rheometer in a cone–plate and plate–plate configuration. In total, four HA solutions with molecular weights between 77 kDa and 2010 kDa were tested. The frictional measurements were realized on a commercial tribometer Bruker UMT TriboLab, while the coefficient of friction (CoF) dependency on time was measured. The contact couple consisted of the articular cartilage pin and the plate made from optical glass. The contact was fully flooded with tested HA solutions. Results showed a strong dependency between HA molecular weight and its rheological properties. However, no clear dependence between HA molecular weight and CoF was revealed from the frictional measurements. This study presents new insight into the dependence between rheological and frictional behavior of the articular cartilage, while such an extensive investigation has not been presented before.
Assessing the Costs and Benefits of Capital-Based Macroprudential Policy

We develop an integrated Early Warning Global Vector Autoregressive (EW-GVAR) model to quantify the costs and benefits of capital-based macroprudential policy measures. Our findings illustrate that capital-based measures are transmitted both via their impact on the banking system's resilience and via indirect macro-financial feedback effects. The feedback effects relate to dampened credit and asset price growth and, depending on how banks move to higher capital ratios, can account for up to a half of the overall effectiveness of capital- based measures. Moreover, we document significant cross-country spillover effects, especially for measures implemented in larger countries. Overall, our model helps to understand how and through which channels changes in capitalization affect bank lending and the wider economy and can inform policy makers on the optimal calibration and timing of capital-based macroprudential instruments. JEL Classification: G01, G21, G28
The Risk of Drug Abuse among Preschool Students in Phuket, Thailand

Background: There have been scientific studies on risk and protective factors associated with child outcomes. However, how risk factors interact to produce outcomes is not clearly understood. We assessed the association between school location, grade, and drug abuse risks among preschoolers. Methods: This cross-sectional study included 3353 participants aged 2–6 yr (mean: 4.6, SD: 1.03) enrolled in childcare centers and kindergarten classes in 2016 in Phuket, Thailand. The risk of drug abuse was measured using questionnaires, completed by teachers and caregivers. Data were analyzed using descriptive statistics, odds ratio with 95% confidence intervals and Chi-square. Results: The prevalence of drug abuse risk factors was as follows: sleep problems=1.28%, aggression=1.10%, attention-deficit hyperactivity disorder (ADHD)=3.61%, learning disabilities (LDs)=4%, family members’ substance abuse=12.53%, parents’ changing marital status=6.53%, conflict between parents/guardians=1.88%, family poverty=3.37%, and easy access to drugs in the community=5.16%. Sleep problems in children were significantly related to family members’ substance abuse, family poverty, and easy access to drugs in the community (PS<.05). LDs were significantly related to parents’ changing marital status, conflict between parents/guardians, family poverty, and easy access to drugs in the community (PS<.05). ADHD was significantly related to family members’ substance abuse, parents’ changing marital status, conflict between parents/guardians, and family poverty (PS<.05). Conclusion: The prevalence of drug abuse risks among preschoolers was 25.86%. Multidisciplinary teams should provide appropriate interventions.
Potential of Flavonoid-Inspired Phytomedicines against COVID-19

Flavonoids are widely used as phytomedicines. Here, we report on flavonoid phytomedicines with potential for development into prophylactics or therapeutics against coronavirus disease 2019 (COVID-19). These flavonoid-based phytomedicines include: caflanone, Equivir, hesperetin, myricetin, and Linebacker. Our in silico studies show that these flavonoid-based molecules can bind with high affinity to the spike protein, helicase, and protease sites on the ACE2 receptor used by the severe acute respiratory syndrome coronavirus 2 to infect cells and cause COVID-19. Meanwhile, in vitro studies show potential of caflanone to inhibit virus entry factors including, ABL-2, cathepsin L, cytokines (IL-1β, IL-6, IL-8, Mip-1α, TNF-α), and PI4Kiiiβ as well as AXL-2, which facilitates mother-to-fetus transmission of coronavirus. The potential for the use of smart drug delivery technologies like nanoparticle drones loaded with these phytomedicines to overcome bioavailability limitations and improve therapeutic efficacy are discussed.
Daxx Inhibits HIV-1 Reverse Transcription and Uncoating in a SUMO-Dependent Manner

Death domain-associated protein 6 (Daxx) is a multifunctional, ubiquitously expressed and highly conserved chaperone protein involved in numerous cellular processes, including apoptosis, transcriptional repression, and carcinogenesis. In 2015, we identified Daxx as an antiretroviral factor that interfered with HIV-1 replication by inhibiting the reverse transcription step. In the present study, we sought to unravel the molecular mechanism of Daxx-mediated restriction and, in particular, to identify the protein(s) that Daxx targets in order to achieve its antiviral activity. First, we show that the SUMO-interacting motif (SIM) located at the C-terminus of the protein is strictly required for Daxx to inhibit HIV-1 reverse transcription. By performing a quantitative proteomic screen combined with classical biochemical analyses, we found that Daxx associated with incoming HIV-1 cores through a SIM-dependent interaction with cyclophilin A (CypA) and capsid (CA). Daxx was found to reside within a multiprotein complex associated with viral capsids, also containing TNPO3, TRIM5α, and TRIM34. Given the well-known influence of these cellular factors on the stability of HIV-1 cores, we investigated the effect of Daxx on the cytoplasmic fate of incoming cores and found that Daxx prevented HIV-1 uncoating in a SIM-dependent manner. Altogether, our findings suggest that, by recruiting TNPO3, TRIM5α, and TRIM34 and possibly other proteins onto incoming HIV-1 cores through a SIM-dependent interaction with CA-bound CypA, Daxx increases their stability, thus preventing uncoating and reverse transcription. Our study uncovers a previously unknown function of Daxx in the early steps of HIV-1 infection and further illustrates how reverse transcription and uncoating are two tightly interdependent processes.
Impact of TREM2R47H variant on tau pathology-induced gliosis and neurodegeneration.

Alzheimer's disease (AD) is characterized by amyloid-β-containing plaques and neurofibrillary tangles composed of aggregated, hyperphosphorylated tau. Beyond tau and Aβ, evidence suggests that microglia play an important role in AD pathogenesis. Rare variants in the microglial-expressed triggering receptor expressed on myeloid cells 2 (TREM2) gene increase AD risk 2-4-fold. It is likely that these TREM2 variants increase AD risk by decreasing the response of microglia to Aβ and its local toxicity. However, neocortical Aβ pathology occurs many years before neocortical tau pathology in AD. Thus, it will be important to understand the role of TREM2 in the context of tauopathy. We investigated the impact of the AD-associated TREM2 variant (R47H) on tau-mediated neuropathology in the PS19 mouse model of tauopathy. We assessed PS19 mice expressing human TREM2CV (common variant) or human TREM2R47H. PS19-T2R47H mice had significantly attenuated brain atrophy and synapse loss versus PS19-T2CV mice. Gene expression analyses and CD68 immunostaining revealed attenuated microglial reactivity in PS19-T2R47H versus PS19-T2CV mice. There was also a decrease in phagocytosis of postsynaptic elements by microglia expressing TREM2R47H in the PS19 mice and in human AD brains. These findings suggest that impaired TREM2 signaling reduces microglia-mediated neurodegeneration in the setting of tauopathy.
THE SCHEDULING OF ANGIOGENIC INHIBITORS MINIMIZING TUMOR

The efficiency of piecewise constant protocols with a small number of switchings is investigated for a mathematical model of tumor anti-angiogenesis formulated originally by Hahnfeldt et al. in [8]. By comparing with the theoretically optimal solution derived earlier [12] it will be seen that for the problem of minimizing the primary cancer volume with a given amount of angiogenic inhibitors to be administered constant protocols already provide very good suboptimal strategies.
Increased Acid-Producing Diet and Past Smoking Intensity Are Associated with Worse Prognoses among Breast Cancer Survivors: A Prospective Cohort Study

Current dietary guidelines do not consider cancer survivors’ and past smokers’ low capacity to regulate their acid–base balance. People with a low capacity to regulate their acid–base balance are more susceptible to acid-producing diets. We studied a cohort of 2950 early stage breast cancer survivors who provided dietary information at baseline and during follow-up. We assessed the intakes of acid-producing diets via two commonly used dietary acid load scores: potential renal acid load (PRAL) and net endogenous acid production (NEAP). We assessed past smoking intensity by pack-years of smoking. After an average of 7.3 years of follow-up, there were 295 total deaths, 249 breast cancer-specific deaths, and 490 cases of recurrent breast cancer. Increased intakes of dietary acid load and pack-years of smoking were each independently and jointly associated with increased total mortality and breast cancer-specific mortality; tests for trends and overall associations were statistically significant for NEAP and marginally significant for PRAL. Compared to women in the lowest tertile of NEAP and pack-year of smoking = 0, women in the highest tertile of NEAP and pack-years of smoking >15 had the greatest increased risk of total mortality (HR = 3.23, 95%CI 1.99–5.26). Further, dietary acid scores were associated with increased breast cancer recurrence among women with pack-years of smoking >0 but not in those with pack-years of smoking = 0 (p values for interactions <0.05). Our study provides valuable evidence for adding dietary acid load scores to dietary guidelines for breast cancer survivors and developing specific guidelines for past smokers among these survivors.
Macrophage activation syndrome as a complication of dermatomyositis: A case report.

BACKGROUND Macrophage activation syndrome (MAS) can be a fatal complication of rheumatic disorders, which occurs most commonly in patients with systemic juvenile idiopathic arthritis or systemic lupus erythematosus. It has rarely been reported in patients with dermatomyositis. Here, we describe a fatal case of MAS that developed in an adult patient with dermatomyositis. CASE SUMMARY A 44-year-old woman was admitted to our hospital with fever, generalized rash and muscle weakness. Fifteen days later, the fever persisted after the use of antibiotics, and repeat blood culture was negative. The patient then exhibited a typical Gottron sign and diffuse erythema on the face and neck, which were consistent with a diagnosis of dermatomyositis. The patient exhibited limb muscle strength of 2, and electromyography was suggestive of muscle-derived damage, which also supported a diagnosis of dermatomyositis. In addition, the patient exhibited high serum ferritin level, cytopenia, liver dysfunction, coagulopathy, enlarged spleen and hypertriglyceridemia, all of which are typical manifestations of MAS. The patient was diagnosed with dermatomyositis complicated by MAS. Although a high dose of methylprednisolone was administered for 15 d, the patient's condition continued to deteriorate and central nervous system symptoms developed. Eventually, treatment was discontinued, and the patient died. CONCLUSION MAS is an important, potentially fatal, complication of dermatomyositis. Although MAS is rare in dermatomyositis, it should be considered in the differential diagnosis of an unexplained change of hemoglobin, platelet, fibrinogen, ferritin and triglyceride, which may complicate dermatomyositis.
Follicular wave dynamics and Growth factors gene expression in Braford heifers

The objectives of the present study were (experiment 1) to characterized development and dynamics of the dominant follicles (DF) and the corpus luteum (CL) to determine patterns of two (W2) and three (W3) follicular waves in beef heifers, and (experiment 2) to determine gene expression of growth factors gene expression in follicular cells of W2 and W3 heifer. Twenty‐eight Braford heifers were used. Dominant follicular and CL were monitored daily by ultrasonography to identify the development W2 and W3 in heifers. Pre‐ovulatory DF were aspirated on day 19 in W2 and on day 22 in W3 heifers. In W2 and W3, follicular cells (FC) of gene expression of growth differentiation factor 9, bone morphogenetic protein 15 (BMP15), fibroblast growth factor basic, transforming growth factor beta receptor 1, bone morphogenetic protein receptor type IB and fibroblast growth factor receptor 2 were evaluated. The regression of the DF of the first follicular wave and the emergency of the DF of the second follicular wave began later in the heifers W2 than in W3 (p = .02 and p < .01). The regression of the CL began earlier in the W2 than in W3 group (p < .01). Gene expression of growth factors and receptors was similar between groups. However, higher relative levels of BMP15 was observed in W2 group (p = .07). Results propose that wave patterns were regulated by the development time of the DF in the first wave and the life of the CL. Furthermore, higher levels of BMP15 could produce shorter life of CL. The present work suggest that ultrasonography associated with molecular assays could be used as an easy and effective tool to characterize follicular wave patterns.
Noncooperative Collusion in Durable Goods Oligopoly

Coase conjectured that a durable goods monopolist who can make offers to sell arbitrarily frequently will lose the ability to extract positive profits. This result, which has now been proved, can be attributed to the inability of the monopolist to commit to maintaining sufficiently high prices in the near future. For the case of durable-goods oligopoly, we show that letting the firms make offers arbitrarily frequently enhances their ability to commit to high prices and in the limit enables the firms to enjoy total market profits equal to the full commitment (one-shot) monopoly profit.
Genome-Wide Gene–Diabetes and Gene–Obesity Interaction Scan in 8,255 Cases and 11,900 Controls from PanScan and PanC4 Consortia

Background: Obesity and diabetes are major modifiable risk factors for pancreatic cancer. Interactions between genetic variants and diabetes/obesity have not previously been comprehensively investigated in pancreatic cancer at the genome-wide level. Methods: We conducted a gene–environment interaction (GxE) analysis including 8,255 cases and 11,900 controls from four pancreatic cancer genome-wide association study (GWAS) datasets (Pancreatic Cancer Cohort Consortium I–III and Pancreatic Cancer Case Control Consortium). Obesity (body mass index ≥30 kg/m2) and diabetes (duration ≥3 years) were the environmental variables of interest. Approximately 870,000 SNPs (minor allele frequency ≥0.005, genotyped in at least one dataset) were analyzed. Case–control (CC), case-only (CO), and joint-effect test methods were used for SNP-level GxE analysis. As a complementary approach, gene-based GxE analysis was also performed. Age, sex, study site, and principal components accounting for population substructure were included as covariates. Meta-analysis was applied to combine individual GWAS summary statistics. Results: No genome-wide significant interactions (departures from a log-additive odds model) with diabetes or obesity were detected at the SNP level by the CC or CO approaches. The joint-effect test detected numerous genome-wide significant GxE signals in the GWAS main effects top hit regions, but the significance diminished after adjusting for the GWAS top hits. In the gene-based analysis, a significant interaction of diabetes with variants in the FAM63A (family with sequence similarity 63 member A) gene (significance threshold P < 1.25 × 10−6) was observed in the meta-analysis (PGxE = 1.2 ×10−6, PJoint = 4.2 ×10−7). Conclusions: This analysis did not find significant GxE interactions at the SNP level but found one significant interaction with diabetes at the gene level. A larger sample size might unveil additional genetic factors via GxE scans. Impact: This study may contribute to discovering the mechanism of diabetes-associated pancreatic cancer.
Ig-like ACE2 protein therapeutics: A revival in development during the COVID-19 pandemic

ABSTRACT While the potential therapeutic utility of angiotensin-converting enzyme 2 (ACE2) is well established, the clinical development of ACE2 drugs has been limited, likely due in part to the short half-life of the protein. In contrast, Ig-like ACE2 fusion proteins have exhibited greatly extended plasma half-life in vivo, and they have been shown to have a potent neutralization effect against SARS-CoV-2. Clinical investigation of Ig-like ACE2 fusion proteins as COVID-19 interventions is thus warranted.