Miracle-dz/UniFAR-FTUs huggingface dataset:
A case-control study

It has been proposed that cytotoxic T-lymphocyte antigen 4 (CTLA-4) may attenuate the T-cell activation threshold, thereby decreasing the antitumor response and conferring susceptibility to hepatocellular carcinoma (HCC). In the present study, we selected CTLA-4 tagging single nucleotide polymorphisms (SNPs) and explored the relationship between these polymorphisms and susceptibility to HCC. A hospital-based case-control study, comprising 584 cases with HCC and 923 controls, was performed in an eastern Chinese Han population. CTLA-4 SNPs were genotyped using a custom-by-design 48-Plex SNPscan Kit. We found that the CTLA-4 rs3087243 G>A polymorphism might be associated with increased risk of HCC (GA vs GG: adjusted odds ratio [OR], 1.38; 95% confidence interval [CI], 1.04–1.85; P= .028 and AA/GA vs GG: adjusted OR, 1.43; 95% CI, 1.08–1.89; P= .012). After using Bonferroni correction, this association remained (P= .012 for the AA/GA vs GG genetic model). In addition, the power value was 0.904 in the AA/GA versus GG genetic model. Haplotype analysis showed that CTLA4 Crs16840252Ars231775Ars3087243Trs733618, Crs16840252Grs231775Ars3087243Trs733618, and other haplotypesmight increase the risk of HCC risk (P= .018, <.001, and .017, respectively). However, we found that CTLA4 Trs16840252A rs231775Grs3087243Trs733618 decreased the risk of HCC (P= .020). Our results suggest that the CTLA-4 rs3087243 G>A polymorphism increases susceptibility to HCC in an eastern Chinese Han population. CTLA-4 haplotypes may influence the development of HCC. In the future, a population-based fine-mapping study with functional assessment should be performed to further determine these potential correlations. Abbreviations: CI = confidence interval, CTLA-4 = cytotoxic T-lymphocyte antigen 4, HBV = hepatitis B virus, HCC = hepatocellular carcinoma, HWE =Hardy–Weinberg equilibrium, IgSF = immunoglobulin superfamily, IL-2 = interleukin-2, OR = odds ratio, SNP = single nucleotide polymorphisms.
Effect of coexisting vascular disease on long-term risk of recurrent events after TIA or stroke

Objective To determine whether patients with TIA or ischemic stroke with coexisting cardiovascular disease (i.e., history of coronary or peripheral artery disease) are still at high risk of recurrent ischemic events despite current secondary prevention guidelines. Methods In a population-based study in Oxfordshire, UK (Oxford Vascular Study), we studied consecutive patients with TIA or ischemic stroke for 2002–2014. Patients were treated according to current secondary prevention guidelines and we determined risks of coronary events, recurrent ischemic stroke, and major bleeding stratified by the presence of coexisting cardiovascular disease. Results Among 2,555 patients (9,148 patient-years of follow-up), those (n = 640; 25.0%) with coexisting cardiovascular disease (449 coronary only; 103 peripheral only; 88 both) were at higher 10-year risk of coronary events than those without (22.8%, 95% confidence interval 17.4–27.9; vs 7.1%, 5.3–8.8; p < 0.001; age- and sex-adjusted hazard ratio [HR] 3.07, 2.24–4.21) and of recurrent ischemic stroke (31.5%, 25.1–37.4; vs 23.4%, 20.5–26.2; p = 0.0049; age- and sex-adjusted HR 1.23, 0.99–1.53), despite similar rates of use of antithrombotic and lipid-lowering medication. However, in patients with noncardioembolic TIA/stroke, risk of extracranial bleeds was also higher in those with coexisting cardiovascular disease, particularly in patients aged <75 years (8.1%, 2.8–13.0; vs 3.4%, 1.6–5.3; p = 0.0050; age- and sex-adjusted HR 2.71, 1.16–6.30), although risk of intracerebral hemorrhage was not increased (age- and sex-adjusted HR 0.36, 0.04–2.99). Conclusions As in older studies, patients with TIA/stroke with coexisting cardiovascular disease remain at high risk of recurrent ischemic events despite current management. More intensive lipid-lowering might therefore be justified, but benefit from increased antithrombotic treatment might be offset by the higher risk of extracranial bleeding.
Anterior tibial artery occlusion post total knee arthroplasty

Abstract Rationale: Total knee arthroplasty (TKA) is a globally well-accepted surgery because of its good outcome and safety. Although TKA-associated arterial injuries occur, postoperative anterior tibial artery (ATA) occlusion has not been reported yet. Herein, we present a case of ATA occlusion after TKA. Patient concerns: A 42-year-old man with a 6-year history of right knee pain after right patella fracture treated with open reduction was referred to our clinic. Valgus and contracture deformities were detected in the right knee. Severe osteoarthritis (OA) in the right knee and multiple osteochondromas were observed on radiography. Diagnosis: On the basis of clinical and imaging findings, the patient was diagnosed with OA and multiple osteochondromas. Interventions: TKA was performed in the right knee and the osteochondromas were resected. ATA occlusion was found postoperatively and was treated conservatively. Outcomes: Although the right ATA occlusion did not resolve, the patient recovered well postoperatively, with pain relief and recovery of right knee range of motion. Lessons: The clinical outcome in a case of ATA occlusion after TKA demonstrates that conservative treatment could be appropriate in this context.
Effectiveness of the American College of Surgeons Bleeding Control Basic Training Among Laypeople Applying Different Tourniquet Types: A Randomized Clinical Trial.

Importance More than 500 000 laypeople in the United States have been trained in hemorrhage control, including tourniquet application, under the Stop the Bleed campaign. However, it is unclear whether after hemorrhage control training participants become proficient in a specific type of tourniquet or can also use other tourniquets effectively. Objective To assess whether participants completing the American College of Surgeons Bleeding Control Basic (B-Con) training with Combat Application Tourniquets (CATs) can effectively apply bleeding control principles using other tourniquet types (commercial and improvised). Design, Setting, and Participants This nonblinded, crossover, sequential randomized clinical trial with internal control assessed a volunteer sample of laypeople who attended a B-Con course at Gillette Stadium and the Longwood Medical Area in Boston, Massachusetts, for correct application of each of 5 different tourniquet types immediately after B-Con training from April 4, 2018, to October 9, 2018. The order of application varied for each participant using randomly generated permutated blocks. Interventions Full B-Con course, including cognitive and skill sessions, that taught bleeding care, wound pressure and packing, and CAT application. Main Outcomes and Measures Correct tourniquet application (applied pressure of ≥250 mm Hg with a 2-minute time cap) in a simulated scenario for 3 commercial tourniquets (Special Operation Forces Tactical Tourniquet, Stretch-Wrap-and-Tuck Tourniquet, and Rapid Application Tourniquet System) and improvised tourniquet compared with correct CAT application as an internal control using 4 pairwise Bonferroni-corrected comparisons with the McNemar test. Results A total of 102 participants (50 [49.0%] male; median [interquartile range] age, 37.5 [27.0-53.0] years) were included in the study. Participants correctly applied the CAT at a significantly higher rate (92.2%) than all other commercial tourniquet types (Special Operation Forces Tactical Tourniquet, 68.6%; Stretch-Wrap-and-Tuck Tourniquet, 11.8%; Rapid Application Tourniquet System, 11.8%) and the improvised tourniquet (32.4%) (P < .001 for each pairwise comparison). When comparing tourniquets applied correctly, all tourniquet types had higher estimated blood loss, had longer application time, and applied less pressure than the CAT. Conclusions and Relevance The B-Con principles for correct CAT application are not fully translatable to other commercial or improvised tourniquet types. This study demonstrates a disconnect between the B-Con course and tourniquet designs available for bystander first aid, potentially stemming from the lack of consensus guidelines. These results suggest that current B-Con trainees may not be prepared to care for bleeding patients as tourniquet design evolves. Trial Registration ClinicalTrials.gov identifier:NCT03538379.
Clinical practice guidelines for hepatocellular carcinoma: The Japan Society of Hepatology 2017 (4th JSH‐HCC guidelines) 2019 update

The fourth version of Clinical Practice Guidelines for Hepatocellular Carcinoma was revised by the Japan Society of Hepatology, according to the methodology of evidence‐based medicine and partly to the Grading of Recommendations Assessment, Development, and Evaluation system, which was published in October 2017 in Japanese. New or revised recommendations were described, herein, with a special reference to the surveillance, diagnostic, and treatment algorithms.
Attitude of clinicians towards hospital-based antimicrobial stewardship programs: a multicenter cross-sectional study from Punjab, Pakistan

ABSTRACT Background: Antimicrobial resistance (AMR) is a major threat to global health and antimicrobial stewardship programs (ASPs) are useful to limit the momentum of AMR. This study was intended to determine the attitudes of clinicians about AMR, ASP strategies, and their readiness to participate in ASPs. Methods: A cross-sectional survey was carried out among clinicians working in teaching hospitals of Punjab between August and November 2018. A multistage sampling method was used. Descriptive statistics and Kruskal-Wallis tests were employed for data analysis. Results: A response rate of 77.9% (670 ⁄ 859) was achieved. Most of the physicians (n = 302, 71.7%) compared to surgeons (n = 134, 70.9%) and anesthetists (n = 25, 41.7%) considered AMR as a serious health problem in Pakistani hospitals (p < 0.001). Clinicians were agreed that hospital audit and feedback (n = 434, 64.8%), restriction of certain antibiotics (n = 424, 63.3%), readily accessible microbiological data (n = 453, 67.6%), and regular educational sessions (n = 496, 74.0%) are imperative approaches to implement ASPs. Median ASP and AMR scores were significantly associated with age, experience, and types of clinicians (p < 0.05). Conclusions: Despite poor previous knowledge of ASPs, all clinicians showed a positive attitude towards hospital ASPs. Several approaches suggested by clinicians will be helpful to implement hospital ASPs in Pakistan.
Introduction To Geochemistry

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Design and Thermal Comparison of Random Structures Realized by Indirect Additive Manufacturing

Additive manufacturing (AM) processes are used to fabricate three-dimensional complex geometries. There are several technologies that use laser or electron beam over metal powder beds. However, the direct AM processes have inconveniences such as specific set of materials, high thermal stress traced, high local energy absorbed, poor surface finish, anisotropic properties, high cost of material powder, and manufacturing with high-power beams. In this paper, an alternative process was developed. An indirect additive manufacturing (I-AM) combining a 3D print of castable resin and metal casting in order to obtain a cellular structure similar in shape to commercial metal foams but completely definable as design features was developed. Design of the cellular structure was made by the graphical algorithm editor Grasshopper®. Designed structures were realized by a lost-wax casting process and compared with commercial foam specimens by a system designed for this work. The designed metal foams showed a performance superior to that of commercial metal foam; in particular, the heat thermal coefficient of designed metal foams in the better case was 870 W/m2·K, almost doubled in comparison with the commercial foam tested in this work.
Visit-to-Visit Hemoglobin A1c Variability Is Associated With Later Cancer Development in Patients With Diabetes Mellitus

Purpose Recent studies have shown that patients with diabetes mellitus have a higher risk of tumorigenesis. However, the effect of glycemic variability on tumorigenesis among diabetic patients has not been well investigated. Hence, we performed a retrospective cohort study to analyze the effect of visit-to-visit hemoglobin A1c (HbA1c) variability and later onset of malignancies. Methods This study included 2640 patients with diabetes mellitus 50 years or older. To analyze visit-to-visit glycemic activity, we calculated intrapersonal SD of all recorded HbA1c and used SD-HbA1c as a measure of glycemic variability. Because the number of individual visits varied, we divided SD-HbA1c by visit times in order to adjust for the potential influence of visit time difference between individuals. Patients were divided into quartiles according to their HbA1c variability, and Cox regression models were used to evaluate the association between glycemic variability and later onset of tumorigenesis. Results Three hundred thirty patients (12.5%) developed malignancy during follow-up. The median follow-up period was 1511 days (4.1 years; interquartile range, 2487.5 days). Relative to the group with the lowest glycemic variability (first quartile), the groups with higher glycemic variability showed a dose-dependent association with tumorigenesis. The odds ratios for the second, third, and fourth quartiles were 1.20 (95% confidence interval, 0.88–1.65), 1.43 (1.02–2.00), and 2.19 (1.52–3.17), respectively. The mean HbA1c and diabetes mellitus duration periods were not significantly associated with tumorigenesis. This result was consistent when limiting the number of covariates. Conclusions These results demonstrated that visit-to-visit HbA1c variability is a potential risk factor for later tumorigenesis. The association may be mediated by oxidative stress or hormone variability. Routine cancer screening may be suggested for diabetic patients with unstable glycemic control.
Expression of TMBIM6 in Cancers: The Involvement of Sp1 and PKC

Transmembrane Bax Inhibitor Motif-containing 6 (TMBIM6) is upregulated in several cancer types and involved in the metastasis. Specific downregulation of TMBIM6 results in cancer cell death. However, the TMBIM6 gene transcriptional regulation in normal and cancer cells is least studied. Here, we identified the core promoter region (−133/+30 bp) sufficient for promoter activity of TMBIM6 gene. Reporter gene expression with mutations at transcription factor binding sites, EMSA, supershift, and ChIP assays demonstrated that Sp1 is an essential transcription factor for basal promoter activity of TMBIM6. The TMBIM6 mRNA expression was increased with Sp1 levels in a concentration dependent manner. Ablation of Sp1 through siRNA or inhibition with mithramycin-A reduced the TMBIM6 mRNA expression. We also found that the protein kinase-C activation stimulates promoter activity and endogenous TMBIM6 mRNA by 2- to 2.5-fold. Additionally, overexpression of active mutants of PKCι, PKCε, and PKCδ increased TMBIM6 expression by enhancing nuclear translocation of Sp1. Immunohistochemistry analyses confirmed that the expression levels of PKCι, Sp1, and TMBIM6 were correlated with one another in samples from human breast, prostate, and liver cancer patients. Altogether, this study suggests the involvement of Sp1 in basal transcription and PKC in the enhanced expression of TMBIM6 in cancer.
KEtaminE/ProPofol Admixture vs Etomidate for Intubation in the Critically-Ill: KEEP PACE Randomized Clinical Trial.

BACKGROUND Peri-intubation hypotension is associated with poor outcomes in the critically-ill. We aimed to determine if an admixture of ketamine and propofol for emergent endotracheal intubation in critically-ill patients was superior to etomidate. Primary endpoint was the change in mean arterial pressure from baseline to 5 minutes post-drug administration. METHODS Emergent-use, stratified (shock status and unit type), multi-unit, randomized, parallel-group superiority clinical trial was conducted at a tertiary academic medical center. Adult medical/surgical and transplant/oncologic intensive care unit patients undergoing emergent intubation were assigned randomly to receive either ketamine/propofol admixture [0.5 mg/kg of ketamine and propofol each] or reduced dose etomidate [0.15 mg/kg] for emergent intubation. RESULTS One hundred and sixty participants were randomized and 152 (79 ketamine/propofol admixture, 73 etomidate) were included in the intention-to-treat analysis. There was no statistically significant difference in mean arterial pressure change from baseline to 5 minutes post-drug administration [treatment difference (ketamine/propofol admixture - etomidate): -2.1 mmHg 95% C.I. (-6.9 mmHg, +2.7 mmHg); P=0.385]. In addition, no statistically significant difference was demonstrated in the change of mean arterial pressure from baseline at 10 and 15 minutes post-drug administration, no statistical difference in the use of new-onset vasoactive agents or difficulty of intubation between groups. More patients in the etomidate group required non-red blood cell transfusions [16 (22%) vs. 8 (10%), P=0.046]. For patients who had adrenal testing performed, more patients in the etomidate group developed immediate adrenal insufficiency [13/16 (81%) vs. 5/13 (38%), P=0.027]. Serious adverse events were rare, 2 (3%) [cardiac arrest, hypotension] in ketamine/propofol admixture and 4 (5%) [hypertension, hypotension] in etomidate (P=0.430). CONCLUSIONS In a heterogeneous critically-ill population, ketamine/propofol admixture was not superior to a reduced dose of etomidate at preserving per-intubation hemodynamics and appears to be a safe alternative induction agent in the critically-ill. LEVEL OF EVIDENCE Level 1, TherapeuticClinicalTrials.gov, # NCT02105415, Ketamine / Propofol Admixture 'Ketofol' at Induction in the Critically Ill Against Etomidate: KEEP PACE Trial, IRB# 13-000506, Trial Registration: 03/31/2014.
Metagenomic Analysis of the Fecal Microbiomes of Wild Asian Elephants Reveals Microflora and Enzymes that Mainly Digest Hemicellulose.

To investigate the diversity of gastrointestinal microflora and lignocellulose-degrading enzymes in wild Asian elephants, three wild Asian elephants living in the same group were selected for study from the Wild Elephant Valley in Xishuangbanna nature reserve of Yunnan Province, China. The fresh fecal samples from the three wild Asian elephants were analyzed by metagenomic sequencing to study the diversity of their gastrointestinal microbes and cellulolytic enzymes. There were a high abundance of Firmicutes and a higher abundance of hemicellulose-degrading hydrolases than cellulose-degrading hydrolases in the wild Asian elephants. Furthermore, there were high abundance and rich diversity of carbohydrate active enzymes (CAZymes) obtained from the gene set annotation of the three samples, the majority of them showed low identity with the CAZy database entry. About half of the CAZymes had no species source at the phylum and genus level. These indicated that the wild Asian elephants might possess greater ability to digest hemicellulose than cellulose to provide energy, and the gastrointestinal tract of wild Asian elephants might be a potential source of novel efficient lignocellulose-degrading enzymes. Therefore, the exploitation and utilization of these enzyme resources would help us to alleviate the current energy crisis and ensure food security.
Scaled-Up Production and Tableting of Grindable Electrospun Fibers Containing a Protein-Type Drug

The aims of this work were to develop a processable, electrospun formulation of a model biopharmaceutical drug, β-galactosidase, and to demonstrate that higher production rates of biopharmaceutical-containing fibers can be achieved by using high-speed electrospinning compared to traditional electrospinning techniques. An aqueous solution of 7.6 w/w% polyvinyl alcohol, 0.6 w/w% polyethylene oxide, 9.9 w/w% mannitol, and 5.4 w/w% β-galactosidase was successfully electrospun with a 30 mL/h feeding rate, which is about 30 times higher than the feeding rate usually attained with single-needle electrospinning. According to X-ray diffraction measurements, polyvinyl alcohol, polyethylene oxide, and β-galactosidase were in an amorphous state in the fibers, whereas mannitol was crystalline (δ-polymorph). The presence of crystalline mannitol and the low water content enabled appropriate grinding of the fibrous sample without secondary drying. The ground powder was mixed with excipients commonly used during the preparation of pharmaceutical tablets and was successfully compressed into tablets. β-galactosidase remained stable during each of the processing steps (electrospinning, grinding, and tableting) and after one year of storage at room temperature in the tablets. The obtained results demonstrate that high-speed electrospinning is a viable alternative to traditional biopharmaceutical drying methods, especially for heat sensitive molecules, and tablet formulation is achievable from the electrospun material prepared this way.
Bergamot (Citrus bergamia, Risso): The Effects of Cultivar and Harvest Date on Functional Properties of Juice and Cloudy Juice

Reggio Calabria province (South Italy) is known for being almost the only area of cultivation of the bergamot fruit, grown principally for its essential oil, but today much studied for the health benefits of its juice. The biometrics and physico-chemical properties of the three (Citrus bergamia Risso) existing genotypes namely Castagnaro, Fantastico and Femminello were studied during fruit ripening from October to March. Castagnaro cultivar had the biggest and heaviest fruit during this harvest period. °Brix (7.9–10.0), pH (2.2–2.8) and formol number (1.47–2.37 mL NaOH 0.1 N/100 mL) were shown to be influenced by both the genotype and harvest date. Titratable acidity (34.98–59.50 g/L) and vitamin C (ascorbic acid) (341–867 g/L) decreased during fruit ripening. The evolution of flavonoids such as neoeriocitrin, naringin, neohesperidin, brutieridin and melitidin was studied both in bergamot juice and in the bergamot cloudy juice which is the aqueous extract of bergamot during fruit processing. Bergamot cloudy juice contained a higher quantity of flavonoids compared to the juice. This study gives important information regarding the cultivar and the harvest date for producers who want to obtain the highest juice quantity or the highest juice quality from the bergamot fruit.