Miracle-dz/UniFAR-FTUs huggingface dataset:
Medical Treatment of Gastrointestinal Neuroendocrine Neoplasms

Abstract Neuroendocrine neoplasms (NENs) are rare tumours that arise mainly in the gastrointestinal or pulmonary system. Most NENs are well-differentiated and may obtain prolonged survival besides the presence of metastatic disease; however, a subset (poorly differentiated NENs) may display a truly aggressive behaviour exhibiting a poor prognosis. The recently developed classification systems along with advances in functional imaging have helped stratify patients to the administration of appropriate therapeutic options. Surgery is the mainstay of treatment of NENs, but in recent decades there has been a considerable evolution of medical treatments that are used for locally advanced or metastatic disease not amenable to surgical resection. Long acting somatostatin analogues are the main therapeutic modality for patients with functioning and well-differentiated low grade NENs exhibiting symptomatic control and mainly stabilisation of tumour growth. Other systemic treatments include chemotherapy, molecular targeted agents, interferon-α, peptide receptor radionuclide therapy (PRRT), and immunotherapy. In addition, new agents such as telotristat may be used for the control of symptoms of carcinoid syndrome. The choice and/or sequence of therapeutic agents should be individualized according to tumour origin and differentiation, disease burden, presence of clinical symptoms and patients’ performance status in the context of a multidisciplinary approach. Recent advances in the molecular pathogenesis of NENs set the field for a more personalised treatment approach.
The Association Between Interlimb Asymmetry and Athletic Performance Tasks: A Season-Long Study in Elite Academy Soccer Players

Abstract Bishop, C, Read, P, Bromley, T, Brazier, J, Jarvis, P, Chavda, S, and Turner, A. The association between interlimb asymmetry and athletic performance tasks: A season-long study in elite academy soccer players. J Strength Cond Res 36(3): 787–795, 2022—The aims of this study were to determine the association between asymmetry and measures of speed and change of direction speed (CODS) performance throughout a competitive soccer season and, determine whether any observed changes in asymmetry were associated with changes in speed and CODS performance. Eighteen elite male under-23 academy soccer players performed unilateral countermovement jumps, unilateral drop jumps (DJ), 10- and 30-m sprints, and 505 CODS tests at pre, mid, and end of season. No significant relationships were evident during preseason or midseason between asymmetry and speed or CODS performance. Significant correlations were shown at the end of season between DJ height asymmetry and 10-m sprint time (ρ = 0.62; p = 0.006) and 505 time on the right limb (ρ = 0.65; p = 0.003). No significant correlations between changes in asymmetry and changes in speed or CODS were evident at any time point. Although numerous studies have reported associations between asymmetry and reduced athletic performance, it seems that these associations with speed and CODS do not track consistently over time. Thus, suggestions for the reduction of asymmetry that may indirectly enhance athletic performance cannot be made.
Monocytes from men living with HIV exhibit heightened atherogenic potential despite long term viral suppression with ART.

OBJECTIVE People living with HIV have an increased risk of cardiovascular disease (CVD) despite effective antiretroviral therapy (ART). Monocytes play a key role in the early stages of atherosclerosis-driven CVD by forming lipid-laden foam cells within artery walls. HIV infection potentiates foam cell formation ex vivo, but the mechanisms contributing to this are not known. METHODS We investigated the atherosclerosis-promoting potential of monocytes from 39 virologically suppressed men living with HIV (MLHIV) on ART and no evidence of CVD, and 25 HIV-uninfected controls of comparable age, sex, smoking status and CVD risk. RESULTS Despite absence of clinical atherosclerosis in both MLHIV and uninfected cohorts (evidenced by a carotid intima-media thickness of 0.6 mm for both groups; p = 0.254), monocytes from MLHIV showed increased potential to form atherosclerosis-promoting foam cells compared to controls in an ex vivo assay (36.6% vs 27.6% respectively, p = 0.003). Consistent with observations of persistent inflammation and immune/endothelial activation in ART-treated HIV infection, levels of soluble TNF receptor II, CXCL10 and soluble VCAM-1 were elevated in MLHIV (p≤0.005 for all), but were not significantly associated with foam cell formation. Foam cell formation was associated with an impaired ability of monocytes to undergo reverse transmigration, and a reduced ability to efflux cholesterol ex vivo (p < 0.05 for both). Importantly, foam cell formation declined significantly with duration of viral suppression (p = 0.004). CONCLUSIONS These findings highlight the persistence of HIV-related changes to the atherogenic potential of monocytes despite long-term viral suppression, and provide insights into mechanisms potentially driving increased CVD in ART-treated HIV infection.
Identification of Novel Prognosis and Prediction Markers in Advanced Prostate Cancer Tissues Based on Quantitative Proteomics

Background/Aim: Prostate cancer (PCa) is the most frequent cancer found in males worldwide, and its mortality rate is increasing every year. However, there are no known molecular markers for advanced or aggressive PCa, and there is an urgent clinical need for biomarkers that can be used for prognosis and prediction of PCa. Materials and Methods: Mass spectrometry-based proteomics was used to identify new biomarkers in tissues obtained from patients with PCa who were diagnosed with T2, T3, or metastatic PCa in regional lymph nodes. Results: Among 1,904 proteins identified in the prostate tissues, 344 differentially expressed proteins were defined, of which 124 were up-regulated and 216 were down-regulated. Subsequently, based on the results of partial least squares discriminant analysis and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, we proposed that spermidine synthase (SRM), nucleolar and coiled-body phosphoprotein 1 (NOLC1), and prostacyclin synthase (PTGIS) represent new protein biomarkers for diagnosis of advanced PCa. These proteomics results were verified by immunoblot assays in metastatic PCa cell lines and by indirect enzyme-linked immunosorbent assay in prostate specimens. Conclusion: SRM was significantly increased depending on the cancer stage, confirming the possibility of using SRM as a biomarker for prognosis and prediction of advanced PCa.
Spinal cord neural network interactions: implications for sympathetic control of the porcine heart.

BACKGROUND Coordinated interactions within central and peripheral neural networks determine the integrated autonomic response to cardiovascular stressors. Excessive sympathoexcitation in response to ischemia is a major contributor to sudden cardiac death. OBJECTIVE To define fundamental aspects of cardiac-related autonomic neural network interactions within the thoracic cord, and those specifically related to modulating sympathetic preganglionic (SPN) neural activity during cardiovascular stress. METHODS Adult, anesthetized Yorkshire pigs (n=10) were implanted with penetrating high-density microarrays (64 electrodes) at the T2level of the thoracic spinal cord to record extracellular potentials concurrently from left-sided dorsal horn (DH) and SPN neurons. Electrical stimulation of the T2paravertebral chain allowed for antidromic identification of SPNs located in the intermediolateral cell column (57 of total 1,703 recorded neurons). Cardiac stressors included epicardial touch, occlusion of great vessels to transiently alter preload/afterload and transient occlusion of the left anterior descending (LAD) coronary artery. Spatial/temporal assessment of network interactions was characterized by cross-correlation analysis. RESULTS While some DH neurons responded solely to changes in preload/afterload (8.5±1.9%) or ischemic stress (10.5±3.9%), the majority of cardiovascular-related DH neurons were multimodal (30.2±4.7%) with ischemia sensitivity being one of the modalities (26.1±4.7%). The sympathoexcitation associated with transient LAD occlusion was associated with increased correlations from baseline within DH neurons (2.43±0.61 to 7.30 ±1.84%, p=0.04) and between SPN to DH neurons (1.32±0.78 to 7.24±1.84%, p=0.02). DH to SPN network correlations were reduced during great vessel occlusion. CONCLUSION Increased intra-segmental network coherence within the thoracic spinal cord contributes to myocardial ischemia-induced sympathoexcitation.
Clinical pharmacology of imeglimin for the treatment of type 2 diabetes

ABSTRACT Introduction With the rising prevalence of type 2 diabetes (T2D), there is a substantial interest in novel, glucose-lowering drugs that may complement existing treatment options. Imeglimin is an oral antidiabetic agent currently in clinical development. Areas covered This review is based on a literature search using PubMed and Embase including all published manuscripts and presentations concerning imeglimin. Supplementary information was retrieved from the manufacturer’s official webpage. Preclinical and clinical data are summarized with a focus on mechanisms of action as well as clinical efficacy and safety in T2D. Expert opinion Imeglimin’s mode of action seems to be improved mitochondrial function in pancreatic beta cells leading to improved insulin secretion and lowering of plasma glucose levels. In clinical trials of up to 24 weeks, imeglimin in doses of 1,000–1,500 mg twice daily conferred modest reductions in glycates hemoglobin A1c of 6–11 mmol/mol (0.5–1.0%) (placebo-adjusted) as a monotherapy and 7 mmol/mol (0.6%) as an add-on therapy to metformin or sitagliptin in patients with T2D. Reported adverse effects were mainly gastrointestinal discomfort. The position of imeglimin among other pharmacotherapies in the treatment of T2D will be determined based on future studies more clearly outlining the safety and long-term cardiovascular effects. Abbreviations AUC: area under the curve; BID: twice daily; DPP-4: dipeptidyl peptidase 4; GLP-1R: glucagon-like peptide-1 receptor; HbA1c: glycated hemoglobin A1c; HFHSD: high-fat high-sucrose diet; OAD: oral antidiabetic; OD: once daily; OGTT: oral glucose tolerance test; PPAR-γ: peroxisome proliferator-activated receptor gamma; PTP: permeability transition pore; SGLT-2: sodium-glucose transport protein 2; STZ: streptozotocin; T2D: type 2 diabetes
Variation in Practice Related to the Use of High Flow Nasal Cannula in Critically Ill Children

Supplemental Digital Content is available in the text. Objectives: To determine current management of critically ill children and gather views regarding high flow nasal cannula therapy and to evaluate research priorities for a large prospective randomized controlled trial of noninvasive respiratory support in children. Design: Multinational cross-sectional questionnaire survey conducted in 2018. Setting: The sample included pediatric intensive care physicians in North and South America, Asia, Europe, and Australia/New Zealand. Measurement: Questions consisted of: 1) characteristics of intensivists and hospital, 2) practice of high flow nasal cannula, 3) supportive treatment, and 4) research of high flow nasal cannula. Interventions: None. Main Results: We collected data from 1,031 respondents; 919 (North America, 215; Australia/New Zealand, 34; Asia, 203; South America, 186; Europe, 281) were analyzed. Sixty-nine percent of the respondents used high flow nasal cannula in non-PICU settings in their institutions. For a case of bronchiolitis/pneumonia infant, 2 L/kg/min of initial flow rate was the most commonly used. For a scenario of pneumonia with 30 kg weight, more than 60% of the respondents initiated flow based on patient body weight; while, 18% applied a fixed flow rate. Noninvasive ventilation was considered as a next step in more than 85% of respondents when the patient is failing with high flow nasal cannula. Significant practice variations were observed in clinical practice markers used, flow weaning strategy, and supportive practices. Views comparing high flow nasal cannula to continuous positive airway pressure also noticeably varied across the respondents. Conclusions: Significant practice variations including views of high flow nasal cannula compared to continuous positive airway pressure was found among pediatric intensive care physicians. To expedite establishment and standardization of high flow nasal cannula practice, research aimed at understanding the heterogeneity found in this study should be undertaken.
Distribution and malignancy risk of six categories of the pathology reporting system for thyroid core-needle biopsy in 1,216 consecutive thyroid nodules

Purpose The purpose of this study was to present the distribution of lesions among the six categories of the pathology reporting system for thyroid core-needle biopsy (CNB), along with the range of malignancy risk of each category based on different diagnostic criteria for benignity in a clinical cohort. Methods For 1,216 consecutive nodules (≥1 cm) of 1,125 patients who underwent CNB at two hospitals, the diagnostic results based on the six categories of thyroid CNB were analyzed. Patients were divided into three groups according to prior fine-needle aspiration (FNA) status: second-line CNB for nodules where prior FNA yielded nondiagnostic or unsatisfactory results (n=57), second-line CNB for nodules with prior FNA results of atypia/follicular lesion of undetermined significance (AUS/FLUS) (n=303), and first-line CNB (n=856). Results The proportion of nodules in each CNB category and the range of the malignancy rate for each category was as follows, in order from category I to VI: 1.8%, 23.1%-75.0%; 57.9%, 0.7%-16.7%; 16.0%, 13.2%-46.7%; 8.8%, 53.8%-56.8%; 2.0%, 100%; and 13.5%, 100%. First-line CNB was associated with a higher rate of conclusive diagnoses (category II, IV, or VI) (725 of 856, 84.7%) than second-line CNB with prior nondiagnostic or AUS/FLUS FNA results (241 of 360, 66.9%; P<0.001). Conclusion The overall distribution of nodules across the six categories of thyroid CNB and the ranges of malignancy risk for those categories were presented in a clinical cohort. First-line CNB tended to produce a higher rate of conclusive results than second-line CNB with prior inconclusive FNA results.
Disposable DNA Amplification Chips with Integrated Low-Cost Heaters

Fast point-of-use detection of, for example, early-stage zoonoses, e.g., Q-fever, bovine tuberculosis, or the Covid-19 coronavirus, is beneficial for both humans and animal husbandry as it can save lives and livestock. The latter prevents farmers from going bankrupt after a zoonoses outbreak. This paper describes the development of a fabrication process and the proof-of-principle of a disposable DNA amplification chip with an integrated heater. Based on the analysis of the milling process, metal adhesion studies, and COMSOL MultiPhysics heat transfer simulations, the first batch of chips has been fabricated and successful multiple displacement amplification reactions are performed inside these chips. This research is the first step towards the development of an early-stage zoonoses detection device. Tests with real zoonoses and DNA specific amplification reactions still need to be done.
Gut microbiota and metabolic syndrome

Abstract Metabolic syndrome (MetS) describes a set of risk factors that can eventually lead to the occurrence of cardiovascular and cerebrovascular disease. A detailed understanding of the MetS mechanism will be helpful in developing effective prevention strategies and appropriate intervention tools. In this article, we discuss the relationship between the clinical symptoms of MetS and differences in the gut microbial community compared with healthy individuals, characterized by the proliferation of potentially harmful bacteria and the inhibition of beneficial ones. Interactions between gut microbiota and host metabolism have been shown to be mediated by a number of factors, including inflammation caused by gut barrier defects, short-chain fatty acids metabolism, and bile acid metabolism. However, although we can clearly establish a causal relationship between gut microbial profiles and MetS in animal experiments, the relationship between them is still controversial in humans. Therefore, we need more clinical studies to augment our understanding of how we can manipulate the gut microbiota and address the role of the gut microbiota in the prevention and treatment of MetS.
Immunoexpression of estrogen receptor-β and progesterone receptor in prostate adenocarcinoma, does it inhibit neoplastic proliferation and invasion?

Context: The roles of estrogen and progesterone in human prostate carcinogenesis have been only recently recognized. Aims: This study was conducted to evaluate the expressions of esterone receptor-beta (ER-β), progesterone receptor (PR), and Ki-67 in benign and malignant lesions of the prostate. Settings and Design: The study was conducted at a tertiary care hospital. It was an analytical cross-sectional study. Materials and Methods: We selected a total of 39 cases including 26 cases of benign prostatic hyperplasia and 13 cases of adenocarcinoma prostate. The proportion of cases showing expression for ER-β, PR, and Ki-67 was noted for both groups. A difference in immunoexpression between benign and malignant cases was evaluated. Association between receptor expression and Gleason grade was evaluated for malignant cases. Statistical Analysis Used: To compare the difference in expressions of ER-β, PR, and Ki-67 Mann–Whitney U test was used. Association between ER-β, PR, and Ki-67 expression and Gleason grade was analyzed using the Chi-square test. Results: ER-β expression was seen in all benign and malignant cases, whereas the majority of the malignant cases (61.54%) were negative for progesterone expression. Epithelial expressions of ER-β and PR were significantly higher in benign as compared with malignant lesions. Malignant cases showed a significantly higher expression of Ki-67. However, we did not find any association between the expressions of these markers with Gleason grade. Conclusions: The expressions of ER-β and PR were significantly higher in the epithelium in benign cases as compared with malignant cases. Ki-67 expression was significantly higher in the malignant group as compared with the benign group.
DSM-5 Latent Classes of Alcohol Users among Treatment Seeking Older Adults

Abstract Objective: Understanding the variation of alcohol use disorder (AUD) among a clinical sample of patients aged 60 and older, by identifying latent classes of AUD and exploring risk factors and outcomes of treatment associated with the class. Method: We used the Danish subsample (n = 341) from the Elderly Study. Latent class analysis was used to identify classes based on the 11 symptoms of DSM-5 AUD. We analyzed the associations between class membership and sociodemographic variables, alcohol consumption, and drinking-related outcome of treatment. Results: Three latent classes were identified. Individuals in the low-symptomatic class (34.85%) displayed low endorsement of DSM-5 criteria “Withdrawal”, “Time Spent”, “Less activities” compared to the other classes, and had fewest drinks per drinking day. Individuals in the moderate-symptomatic class (32.69%) were most likely to be intoxicated in hazardous situations, and those in the high-symptomatic class (32.47%) displayed, with a few exceptions, the highest probabilities of all DSM-5 criteria. Female gender, living alone and prior AUD treatment was associated with increased risk of being in the high-symptomatic class. No difference between classes was found with respect to years with AUD and frequency of drinking days, and latent class membership had no effect on drinking outcome after treatment, when controlling for baseline. Conclusions: Three classes of DSM-5 AUD among older adults in treatment emerged, displaying a low-moderate-high distribution, advocating for a unidimensional construct of DSM-5 AUD. Although different with respect to baseline risk factors, no strong connection between DSM-5 latent class and alcohol consumption after AUD treatment was found. Highlights Among 341 older alcohol use disorder (AUD) outpatients, three latent classes of DSM-5 AUD emerged. The classes of DSM-5 AUD displayed a low-moderate-high endorsement of DSM-5 AUD characteristics. The three classes had similar alcohol-related treatment outcomes.
Cost-Effectiveness Analysis of First-Line FOLFIRI Combined With Cetuximab or Bevacizumab in Patients With RAS Wild-Type Left-Sided Metastatic Colorectal Cancer

Background: The FIRE-3 phase III clinical trial demonstrated the marked advantage of prolonging the median overall survival of patients with final RAS wild-type (WT) left-sided metastatic colorectal cancer (mCRC) by 38.3 months after treatment with irinotecan, fluorouracil, and leucovorin (FOLFIRI) plus cetuximab and by 28.0 months after treatment with FOLFIRI plus bevacizumab. However, the substantial cost increase and economic impact of using cetuximab imposes a considerable burden on patients and society. Methods: A Markov model based on the data collected in the FIRE-3 trial was developed to investigate the cost-effectiveness of treating patients with FOLFIRI plus either cetuximab or bevacizumab from the perspective of the Chinese health-care system. Costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated over a lifetime horizon. One-way and probabilistic sensitivity analyses were performed by varying potentially modifiable parameters. Results: In our analysis, the total treatment costs in the bevacizumab and cetuximab groups were $92 549.31 and $94 987.31, respectively, and the QALYs gained were 1.58 and 2.05. In the base-case analysis, compared with bevacizumab, left-sided RAS WT patients receiving cetuximab gained 0.47 more QALYs at an ICER of $5187.23/QALY ($3166.23/LY). The 1-way sensitivity analysis showed that the most influential parameter was the cost of cetuximab. Probabilistic sensitivity analysis indicated that the cost-effective probability of cetuximab group was 92.8% under the willingness-to-pay threshold of $24 081. Conclusions: Treatment with FOLFIRI plus cetuximab in Chinese patients with left-sided RAS WT mCRC may improve health outcomes and use financial resources more efficiently than FOLFIRI plus bevacizumab.