Miracle-dz/UniFAR-FTUs huggingface dataset:
Differences of Angiogenesis Factors in Tumor and Diabetes Mellitus

Abstract Angiogenesis, as a process occurring under the regulation of a variety of factors, is one of the important ways of vascular development. It coexists in a variety of pathological and physiological processes. Now a large number of studies have proved that tumor growth, metastasis, and various vascular complications of diabetes are closely related to angiogenesis, and an increasing number of studies have shown that there are many common factors between the two. But angiogenesis is the opposite of the two: it is enhanced in tumors and suppressed in diabetes. Therefore, this review discusses the causes of the phenomenon from the expression of various factors affecting angiogenesis in these two diseases and their effects on angiogenesis in the relevant microenvironment, as well as the application status of these factors or cells as therapeutic targets in the treatment of these two diseases.
Effects of lipid and starch supplementation as water intake mitigation techniques on performance and efficiency of nursing Holstein calves

Abstract Exploring alternative supplementation sources capable of maximizing feed and water efficiency in nursing Holstein calves is often ignored. The goals herein involve investigating the effects of two isoenergetic supplements on a nonmedicated milk replacer diet on total water intake, milk water intake, fresh water intake, feed intake parameters, and performance of Holstein nursing bull calves. Twenty-three animals (body weight [BW] = 94.67 ± 12.07 kg, age = 67 days old) were randomly assigned to one of three treatments for 68 days: control (CON; ad libitum milk replacer, n = 7), carbohydrate supplement (CHO; corn starch on top of ad libitum milk replacer-based diet, n = 8), or lipid supplement (FAT; menhaden fish oil on top of ad libitum milk replacer-based diet, n = 8). The isoenergetic supplementation consisted of 3% menhaden fish oil addition on DM basis for FAT. This was matched energetically with corn starch for the CHO group resulting in a 7% composition in DM basis. All animals were provided free access to mineral mix and 120 g daily dried microbrewer’s spent grains (BG). Data were analyzed with the GLMMIX procedure of SAS in a completely randomized design with the diets as a fixed effect. Dry matter intake (DMI) adjusted by average daily gain (ADG; DMI/ADG) resulted in significantly lower values for supplemented groups with CON = 2.48, CHO = 2.38, and FAT = 2.27 kg/kg (ADG) (P = 0.033). Energy intake values were lower for CON when analyzing metabolizable energy intake (P < 0.0001), net energy intake for maintenance (P < 0.0001), and net energy intake for gain (P < 0.0001), followed by CHO, and then FAT. Total water intake (P < 0.0001), milk water intake (P < 0.0001), and fresh water intake (P < 0.0001) all resulted in CHO consuming 0.5 L or less water than the other two treatments. Energy requirements as digestible energy (P < 0.0001), metabolizable energy (P < 0.0001), net energy for maintenance (P < 0.0001), and net energy for gain (P < 0.0001) were lower for CHO, followed by CON, and then FAT having the highest requirements. Similar results were observed for residual feed (RFI; P = 0.006) and residual water intakes (RTWI; P = 0.902). Ultimately, no performance differences were detected with regards to BW (CON = 146.71, CHO = 146.25, and FAT = 150.48 kg; P > 0.1). These results indicate that lipid-based and starch-based supplementation can potentially increase feed efficiency and decrease voluntary water intake without adversely affecting performance.
Early Functional Outcomes After Evolutionary Total Knee Arthroplasty

Background: Total knee replacement (TKR) designs continue to evolve with the aim of improving patient outcomes; however, there remains a significant patient dissatisfaction rate. We report the early functional outcomes of an evolutionary knee design in the context of a single-blinded, noninferiority, randomized controlled trial. Methods: Patients were randomized to receive either the P.F. C. SIGMA or ATTUNE knee implant systems (DePuy Synthes). All implants were fixed-bearing, cruciate-retaining, and cemented constructs. Patients were assessed at baseline and 6 weeks, 3 months, and 1 year postoperatively using clinical and functional outcome measures, including range of motion, Oxford Knee Score (OKS), Oxford Knee Score-Activity and Participation Questionnaire (OKS-APQ), Patient Knee Implant Performance (PKIP) score, 5-Level EuroQol 5 Dimensions (EQ-5D-5L), and Short Form-36 outcome measures. Results: There were 150 patients who underwent a surgical procedure (76 with the ATTUNE implant and 74 with the P.F.C. SIGMA implant), with 147 patients remaining at the final review. No differences were observed in any of the outcome measures between the groups at any time point. Tourniquet time was significantly shorter in the P.F. C. SIGMA arm (p = 0.001); however, this had no clinical impact on the OKS (analysis of covariance [ANCOVA] test) at the final review (p = 0.825). There was no difference in the numbers of patients achieving the minimal clinically important difference for the OKS between the groups (p = 0.817). Conclusions: This trial did not show inferiority of the ATTUNE implant when compared with the P.F. C. SIGMA implant. The authors believe that implant innovation should continue and that modern implants should be introduced into the market following randomized controlled trials. Further work should assess the effect of non-implant-related factors on patient outcomes. Level of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.
Clinical Predictors of Nondiabetic Kidney Disease in Patients with Diabetes: A Single-Center Study

Background Although diabetic kidney disease (DKD) could affect up to one-third of patients with diabetes mellitus (DM), these patients can develop kidney diseases different from DKD, or these conditions can superimpose on DKD. Several potential predictors of nondiabetic kidney disease (NDKD) have been proposed, but there are no definitive indications available for kidney biopsy in diabetic patients. Methods We designed a single-center, cross-sectional, and retrospective cohort study to identify clinical and laboratory factors associated with a diagnosis of NDKD after native kidney biopsy in diabetic patients and to investigate differences in time to end-stage kidney disease (ESKD) in patients with a diagnosis of DKD and NDKD. Results Of 142 patients included in our analysis, 89 (62.68%) had a histopathological diagnosis of NDKD or mixed NDKD + DKD. Patients in the NDKD group had significantly lower HbA1C, lower prevalence of diabetic retinopathy (DR), and less severe proteinuria, and there was a lower proportion of patients with nephrotic syndrome; the DKD group had significantly lower proportion of patients with hematological conditions. In the multivariate binary logistic regression, only absence of DR and presence of a hematological condition significantly predicted NDKD after adjustment for age and sex. Time to ESKD was significantly higher in patients with NDKD or mixed forms than in those with DKD. Conclusions After a careful selection, more than half of kidney biopsies performed in diabetic patients can identify NDKD (alone or with concomitant DKD). Absence of DR and coexistence of a hematological condition (especially MGUS) were strong predictors of NDKD in our cohort.
Circulating levels of cell adhesion molecules and risk of cardiovascular events in obstructive sleep apnea

Background Obstructive sleep apnea (OSA) patients are at increased risk of cardiovascular disease (CVD). Cell adhesion molecules (CAM) are increased in OSA and CAM are also implicated in the development of CVD. Research question Do CAM (ICAM-1, VCAM-1 and E-selectin) have prognostic value in identifying risk of cardiovascular events in OSA? Study design and methods Patients with suspected OSA referred for a polysomnogram provided a fasting blood sample. Plasma levels of ICAM-1, VCAM-1 and E-selectin were determined by multiplex Luminex Assay (Milliporesigma ON, Canada). Cardiovascular events were determined by deterministic linkage to provincial health databases. Results 418 patients were included in the analysis. Mostly male (68.2%), mean age of 50.7 yrs, median AHI 16.5 events/hour, and mean BMI of 31.7 kg/m2. 36 cardiovascular events occurred in 8-yrs of follow up. Higher levels of ICAM-1 were associated with developing CVD (HR = 3.65 95% CI 1.40–9.53, 2nd and 3rd tertiles vs. 1st tertile), including in patients with OSA (HR = 3.1 95% CI 1.16–8.25). E-selectin was significantly associated with cardiovascular events in patients with moderate to severe OSA (HR = 3.31 95% CI 0.94–11.72, 2nd and 3rd tertiles vs. 1st tertile) but not in patients without moderate to severe OSA (HR = 0.67 95% CI 0.19–2.38), p-value for interaction = 0.07. Interpretation In a suspected OSA cohort, patients with higher levels of ICAM-1 (>816 ng/ml) were significantly more likely to experience a cardiovascular event within 8 years after PSG. In moderate to severe OSA patients, a higher E-selectin (>36.4 ng/ml) was significantly associated with cardiovascular events.
Resveratrol Relieves Gouty Arthritis by Promoting Mitophagy to Inhibit Activation of NLRP3 Inflammasomes

Background Gouty arthritis (GA) is a common inflammatory disease with pain caused by the deposition of monosodium urate (MSU) crystals into joints and surrounding tissues. Resveratrol (Res), derived from grapes and peanuts and the traditional Chinese medicine (TCM) Reynoutria japonica for GA, acts against oxidation and inflammation. The present study aimed to investigate the therapeutic effect and mechanism of Res on GA. Methods Arthritis rat models, MSU-induced peritonitis mouse models, and inflammatory models of mouse bone marrow-derived macrophage (BMDM) were used in this study. Enzyme-linked immunosorbent assay (ELISA), JC-1, histopathological, immunofluorescence, flow cytometry, Western blot methods were applied to observe the effects of resveratrol on NLRP3 inflammasomes and mitophagy. Results Res significantly improves the gait score and synovitis of rats with GA and inhibits the peritoneal inflammation induced by MSU. Res inhibits the MSU-induced activation of NLRP3 inflammasomes by reducing the levels of IL-1β, IL-18, and Caspase-1 and the pyroptosis of macrophages. In addition, Res raises the level of mitochondrial membrane potential, inhibits the expression of P62 and Pink1, enhances the expressions of LC3B-II, Parkin, and TOMM20, and promotes mitophagy, while mitophagy inhibitors reverse the inhibitory effect of Res on the activation of NLRP3 inflammasomes. Conclusion Res significantly improves GA, and the underlying mechanism might be inhibiting the activation of NLRP3 inflammasomes by triggering the Pink1/Parkin pathway to promote mitophagy.
Rainfall, temperature, and Classic Maya conflict: A comparison of hypotheses using Bayesian time-series analysis

Studies published over the last decade have reached contrasting conclusions regarding the impact of climate change on conflict among the Classic Maya (ca. 250-900 CE). Some researchers have argued that rainfall declines exacerbated conflict in this civilisation. However, other researchers have found that the relevant climate variable was increasing summer temperatures and not decreasing rainfall. The goal of the study reported here was to test between these two hypotheses. To do so, we collated annually-resolved conflict and climate data, and then subjected them to a recently developed Bayesian method for analysing count-based times-series. The results indicated that increasing summer temperature exacerbated conflict while annual rainfall variation had no effect. This finding not only has important implications for our understanding of conflict in the Maya region during the Classic Period. It also contributes to the ongoing discussion about the likely impact of contemporary climate change on conflict levels. Specifically, when our finding is placed alongside the results of other studies that have examined temperature and conflict over the long term, it is clear that the impact of climate change on conflict is context dependent.
Role of liver-X-receptors in airway remodeling in mice with chronic allergic asthma

Liver X receptors (LXRs) exert anti-inflammatory effects in animal models of certain respiratory diseases. In the present study, a model of chronic airway remodeling was established in wild-type and LXR-deficient mice. Ovalbumin (OVA)-sensitized mice were chronically administered OVA via inhalation for 8 weeks. Prior to each stimulation, certain wild-type mice were treated with GW3965, which is a highly selective LXR agonist. The influence of LXRs on airway inflammation, airway hyperresponsiveness and airway remodeling was evaluated. LXRs were indicated to increase airway inflammation and airway hyperresponsiveness, as well as promote airway remodeling. These results suggest that inhibiting LXRs may be a potential method for the treatment of allergic asthma.
Association of Antibiotics and Other Drugs with Clinical Outcomes in Metastatic Melanoma Patients Treated with Immunotherapy

Immune checkpoint inhibitors (ICIs) targeting the programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1) have improved survival in many advanced cancers including advanced melanoma, renal cell, urothelial, and non-small-cell lung cancers. However, not all patients respond, and immune-related adverse events (irAEs) are common. Commensal gut bacteria may serve as an immunoregulatory link-mediating ICI response and toxicity. Recent studies have shown that a lack of bacterial diversity, known as gut dysbiosis, can have an adverse impact on patients' response to ICIs and predispose to the development of irAEs. Data were collected from 167 patients with metastatic melanoma who received antibiotics within 30 days prior to and/or after initiation of ICI and patients who received NSAIDs, statins, steroids, or proton-pump inhibitors (PPI) within 30 days prior to ICI initiation. The primary outcome was time-to-discontinuation (TTD) of ICI therapy, measured from the date of ICI initiation to the last treatment date. The secondary outcome of interest was toxicity, with incidence of irAEs graded as per the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Here, we demonstrate that individuals who received antibiotics had a significantly shorter time-to-discontinuation (TTD) of the ICI therapy as opposed those who were not administered antibiotics. Consistent with results from previous research, we propose that antibiotics have a negative effect on a patient's response to ICI therapy, most likely due to the result of gut dysbiosis, and should be critically assessed in terms of their use in patients undergoing ICI treatment.
Immunohistochemical Expression of FOXP3+ Regulatory T Cells in Proteinuric Primary Glomerulopathies

FOXP3+ regulatory T-cell (Tregs) detection in renal allograft biopsies has been associated with a less intense immune response. Data about FOXP3+ Tregs' presence and role in primary glomerulopathies of native kidneys are minimal. We comparatively studied the immunohistochemical expression of FOXP3+ Tregs, CD4+ and CD3+ T cells in IgA nephropathy (IgAN), focal segmental glomerulosclerosis (FSGS), and membranous glomerulopathy (MGN). We retrospectively reviewed 71 renal biopsies (28 from patients with IgAN, 22 from patients with FSGS and 21 from patients with MGN) performed with proteinuria as the main indication. FOXP3+ Tregs and CD4+ and CD3+ T cells in inflammatory cell infiltrates of the interstitial tissue and periglomerular space were automatically counted using image analysis software. Univariable and multivariable logistic regressions were applied for statistical analysis. Nuclear FOXP3+ immunohistochemical expression was observed in T cells in 64% of IgAN cases, 77% of FSGS cases, and 76% of MGN cases (p > 0.05). Absolute FOXP3+ Tregs count in the interstitial tissue was higher in patients without arteriolar hyalinosis than in those with arteriolar hyalinosis (1.814 ± 2.160 vs. 831 ± 696; p = 0.029). In patients with a high FOXP3+/CD4+ ratio in the interstitial tissue, the odds ratio for CKD-EPI eGFR ≥60 ml/min/1.73 m2 at biopsy was 4.80 (95% CI: 1.29–17.91; p = 0.019). FOXP3+ Tregs intrarenal infiltration in primary glomerulopathies is common. FOXP3+ Tregs' increased expression may be associated with milder histological lesions. High FOXP3+/CD4+ ratio in the interstitial tissue may have prognostic significance for renal function preservation.
Use of Supraclavicular Flap by End to Side Technique in Pharyngeal SCC: A Case Report and Review of Literature

Objectives In recent years, conservation laryngeal surgeries, including partial pharyngectomy, have been introduced as an alternative procedure for selected cases of hypopharyngeal squamous cell carcinoma (HSCC). Reconstruction of these defects presents a considerable challenge for the surgeon after partial pharyngectomy due to its circumferential nature. In this case report, we represent the innovative “End to side” technique to reconstruct hypopharyngeal defect using the rolled supraclavicular flap after laryngeal-preserving partial pharyngectomy. Methods and Results A 70-year-old female presented with a history of progressive dysphagia and odynophagia. The evaluations revealed a T3N0M0 SCC of pyriform sinus. The mass was successfully resected through partial pharyngectomy, and the hypopharyngeal defect reconstruction was achieved using the rolled supraclavicular flap via the “End to side” technique. The patient was discharged after decannulation on day 10. The 3-week barium swallow was performed with no evidence of anastomotic leakage, and the oral feeding was started after NG tube removal. At week 5, complete movement of the true vocal cord on the one side and good phonation and deglutition was observed. There was no evidence of recurrence after 1 year. Conclusions Laryngeal-preserving partial pharyngectomy and hypopharyngeal reconstruction with the rolled supraclavicular flap via the “End to side” technique could lead to good oncological and functional outcomes in selected cases of pyriform sinus.
Differential Prevalences of Pfmdr1 Polymorphisms in Symptomatic and Asymptomatic Plasmodium falciparum Infections in Lastoursville: A Rural Area in East-Central Gabon

Purpose Plasmodium falciparum malaria remains a major public health challenge in sub-Saharan Africa. Plasmodium falciparum drug resistance mediated by polymorphisms in the Pfmdr1 gene contributes to the persistence of the disease on the African continent. This study investigated P. falciparum infection features and differences in the Pfmdr1 genotypes between symptomatic and asymptomatic malaria cases in a rural area in east-central Gabon. Patients and Methods A total of 875 children aged from 5 to 185 months were screened for P falciparum infection using Optima-IT® rapid diagnostic tests and standard microscopy. Pfmdr1 polymorphisms at codons 86, 184 and 1246 were investigated using PCR-RFLP. Results Among the 448 P. falciparum-infected children, 57.08% (n=250) were symptomatic and 42.92% (n=198) were asymptomatic (p < 0.0001). In a sub-set of 79 isolates, the Pfmdr1 wild-type N86 was more prevalent in symptomatic (100%) than in asymptomatic infections (70.7%) (p=0.007). The mutant 86Y and mixed 86N/Y genotypes were observed only in asymptomatic infections. The Y184 and 184F genotype prevalences (39.1% vs 19.4% and 60.9% vs 80.6%, respectively) were not significantly different between the two groups (p=0.097). The prevalence of the wild-type D1246 differed significantly between symptomatic (10.3%) and asymptomatic (100%) (p < 0.0001). The NFD and YFD haplotypes were more prevalent in asymptomatic than in symptomatic infections [(61.9% vs 31%; p=0.005) and (16.7% vs 0.0%; p=0.01)], whereas the NYD and YYD haplotypes were not significantly different between the two groups [(21.4% vs 14.3%, p=0.39) and (0.0% vs 7.1%, p=0.24)]. Conclusion Our results confirm a high transmission of P. falciparum infection in rural Gabon, with a high prevalence of asymptomatic carriage. The higher prevalences of wild-type N86 in symptomatic infections and of D1246 in asymptomatic infections suggest a pathogenicity associated with polymorphisms in Pfmdr1. These results highlight the need to monitor the efficacy of artemisinin-based combination therapies in Gabon.
Psychophysical predictors of experimental muscle pain intensity following fatiguing calf exercise

Musculoskeletal pain affects approximately 20% of the population worldwide and represents one of the leading causes of global disability. As yet, precise mechanisms underlying the development of musculoskeletal pain and transition to chronicity remain unclear, though individual factors such as sleep quality, physical activity, affective state, pain catastrophizing and psychophysical pain sensitivity have all been suggested to be involved. This study aimed to investigate whether factors at baseline could predict musculoskeletal pain intensity to an experimental delayed onset of muscle soreness (DOMS) pain model. Demographics, physical activity, pain catastrophizing, affective state, sleep quality, isometric force production, temporal summation of pain, and psychophysical pain sensitivity using handheld and cuff algometry were assessed at baseline (Day-0) and two days after (Day-2) in 28 healthy participants. DOMS was induced on Day-0 by completing eccentric calf raises on the non-dominant leg to fatigue. On Day-2, participants rated pain on muscle contraction (visual analogue scale, VAS, 0-10cm) and function (Likert scale, 0–6). DOMS resulted in non-dominant calf pain at Day-2 (3.0±2.3cm), with significantly reduced isometric force production (P<0.043) and handheld pressure pain thresholds (P<0.010) at Day-2 compared to Day-0. Linear regression models using backward selection predicted from 39.3% (P<0.003) of VAS to 57.7% (P<0.001) of Likert score variation in DOMS pain intensity and consistently included cuff pressure pain tolerance threshold (P<0.01), temporal summation of pain (P<0.04), and age (P<0.02) as independent predictive factors. The findings indicate that age, psychological and central pain mechanistic factors are consistently associated with pain following acute muscle injury.