Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinicopathological and Prognostic Characteristics of Malaysian Triple Negative Breast Cancer Patients Undergoing TAC Chemotherapy Regimen

Triple negative breast cancer (TNBC) is associated with aggressive tumour phenotype and early tumour relapse following diagnosis. Generally, clinicopathological features such as tumour size, patient's age at diagnosis, tumour histology subtypes, grade and stage, involvement of lymph nodes, and menopausal status are commonly used for predicting disease progression, prospects of recurrence, and treatment response. Prognostic value of clinicopathological features on Malaysian TNBC patients is limited. Thus, this study is aimed at investigating the association of clinicopathological features on disease-free survival (DFS) and overall survival (OS) of Malaysian TNBC patients undergoing TAC chemotherapy. Seventy-six (76) immunohistochemistry-confirmed TNBC patients were recruited. The clinicopathological features of TNBC patients were collected and recorded. Kaplan-Meier and log-rank followed by a Cox proportional hazard regression model were performed to evaluate the TNBC patients' survival. Out of 76 TNBC patients, 25 were chemoresistant and 51 were chemoresponders to the TAC chemotherapy regimen. The overall 5-year cumulative DFS and OS of TNBC patients were 63.5% and 76.3%, respectively. Multivariate Cox analysis demonstrated that medullary and metaplastic histology subtypes and positive axillary lymph node metastasis were significant prognostic factors associated with relapse with adjusted HR: 5.76, 95% CI: 2.35, 14.08 and adjusted HR: 3.55, 95% CI: 1.44, 8.74, respectively. Moreover, TNBC patients with medullary and metaplastic histology subtypes and positive axillary lymph node metastases had a higher risk to death than patients who had infiltrating ductal carcinoma and negative axillary lymph node metastasis (adjusted HR: 8.30, 95% CI: 2.38, 28.96 and adjusted HR: 6.12, 95% CI: 1.32, 28.42, respectively). Our results demonstrate the potential use of medullary and metaplastic histology subtype and positive axillary lymph node metastasis as a potential biomarker in predicting relapse and survival of the TNBC patients. This warrants further studies on intensification of chemotherapy and also identification and development of targeted therapy to reduce relapses and improve survival of TNBC patients.
Insulin Autoimmune Syndrome (Hirata Disease): A Comprehensive Review Fifty Years After Its First Description

Abstract Insulin autoimmune syndrome (IAS), also named Hirata’s disease, is a rare condition characterized by hypoglycemic episodes due to the presence of high titers of insulin autoantibodies (IAA). IAS is a form of immune-mediated hypoglycemia, which develops when a triggering factor (ie, a medication or a viral infection) acts on an underlying predisposing genetic background. IAS pathogenesis involves the formation of insulin-IAA complexes that induce glycemic alterations with a double-phase mechanism: IAA prevent insulin to bind its receptor in the postprandial phase, possibly resulting in mild hyperglycemia; thereafter, insulin is released from the complexes irrespective of blood glucose concentrations, thus inducing hypoglycemia. The diagnosis of IAS is challenging, requiring a careful workup aimed at excluding other causes of hyperinsulinemic hypoglycemia. The gold standard for the definitive diagnosis is the finding of IAA in a blood sample. Because IAS is frequently a self-remitting disease, its management mostly consists of supportive measures, such as dietary modifications, aimed at preventing the development of hypoglycemia. Pharmacological therapies may occasionally be necessary for patients presenting with severe manifestations of IAS. Available therapies may include drugs that reduce pancreatic insulin secretion (somatostatin analogues and diazoxide, for instance) and immunosuppressive agents (glucocorticoids, azathioprine and rituximab). The purpose of this review is to provide a comprehensive analysis of the disease, by describing the burden of knowledge that has been obtained in the 50 years following its first description, took in 1970, and by highlighting the points that are still unclear in its pathogenesis and management.
Urine Recirculation Improves Hemodynamics and Enhances Function in Normothermic Kidney Perfusion

Supplemental Digital Content is available in the text. Background. The study compares urine recirculation (URC) to urine replacement (UR) with Ringer’s lactate in a porcine normothermic kidney machine perfusion (NMP) model using a preclinical prototype device. Methods. Kidney pairs were recovered uninjured (as live-donor nephrectomy) and perfused consecutively. Pig kidneys (n = 10) were allocated to either NMP with URC (n = 5) or NMP with volume replacement (n = 5). Cold ischemia time was either 2 or 27 hours for the first or second perfusion (URC or UR) of a kidney pair. An autologous blood-based perfusate, leukocyte-filtered, was used and NMP performed up to 24 hours. Perfusion parameters, biochemistry/metabolic parameters were monitored and samples collected. Results. Physiological mean arterial pressures and flows were achieved in both groups but were sustainable only with URC. Significantly higher arterial flow was observed with URC (326.7 ± 1.8 versus 242.5 ± 14.3 mL/min, P = 0.001). Perfusate sodium levels were lower with URC, 129.6 ± 0.7 versus 170.3±2.7 mmol/L, P < 0.001). Stable physiological pH levels were only observed with URC. Perfusate lactate levels were lower with URC (2.2 ± 0.1 versus 7.2 ± 0.5 mmol/L, P < 0.001). Furthermore, the hourly rate of urine output was lower with URC and closer to physiological levels (150 versus 548 mL/h, P = 0.008). Normothermic kidney perfusion with URC was associated with longer achievable durations of perfusion: the objective in all experiments was a 24-hour perfusion, but this was not achieved in every case. The mean perfusions were 17.3 ± 9.2 hours with URC versus 5.3 ± 1.3 hours NMP with UR; P = 0.02. There appeared to be no differences in baseline tubular condition with and without URC. Conclusions. URC facilitates long-term kidney NMP in a porcine model. Perfusate homeostasis and stability of renal arterial flow throughout the perfusion period was only achievable with URC, independent of cold ischemia time duration.
The contribution of proprioceptive acuity to upper limb motor performance in older and younger adults

As we get older there is an increase in the variability of upper limb movements which typically require greater reliance on online corrective mechanisms. However, the relative contribution of proprioceptive loss to the development of these impairments in the upper limb is not well understood. The work in this thesis aimed to address this by presenting a novel method of measuring upper limb proprioception using a 2D-robotic manipulandum with older and younger adults. We show that this task provides distinct measures from traditional methods, and that despite physically inactive older adults having larger systematic errors in judging limb position, this was not related to motor performance during rapid target reaching. Furthermore, there was also a null relationship with the extent of motor adaptation to novel field dynamics even when only proprioceptive information regarding the perturbation was available. We were unable to measure robust effects of ageing on proprioceptive acuity throughout the thesis, and suggest that the level of impairment may have been previously over-inflated due to task and population specific limitations as a result. Collectively, we found a limited role of proprioceptive loss in the presentation of age-related impairments in motor control.
Inhaled Corticosteroid Treatment Regimens and Health Outcomes in a UK COPD Population Study

Background Inhaled corticosteroids (ICS) are a prevailing treatment option for COPD patients but recent guidelines have relegated their use predominantly to patients with frequent exacerbations. Yet large numbers of patients worldwide are currently treated with ICS-containing regimens. We wished to determine in routine clinical practice how common ICS withdrawal is and the differences in health outcomes between patients managed on ICS-containing and non-ICS containing regimens. Patients and Methods COPD patients were identified from the UK primary care electronic healthcare records, between 2014 and 2018. Patients were grouped into three treatment regimens: long-acting beta-agonist (LABA) and inhaled corticosteroids (ICS), LABA and long-acting muscarinic antagonist (LAMA), and triple therapy (LABA, LAMA and ICS). Annual incidence of ICS withdrawal was measured. Multivariable logistic regression was used to identify patient factors associated with withdrawal. Multivariable Poisson regression was used to assess the association of exacerbations and hospitalised pneumonia between the ICS-containing regimens (LABA-ICS and triple therapy) and patients prescribed LABA-LAMA. Results Of 117,046 patients, around three-quarters were prescribed ICS-containing inhalers but ICS withdrawal occurred annually in only approximately 2–3% of patients. Exacerbations in the past year, but not a past history of pneumonia, were associated with ICS withdrawal. A total of 31,034 patients using three treatment regimens (LABA-ICS, LABA-LAMA or triple therapy) were assessed for their relative risk of exacerbations and pneumonia; the exacerbation risk was slightly lower in LABA-ICS users but the same in triple therapy users, as compared to LABA-LAMA users (LABA-ICS adjusted IRR=0.82 (95% CI 0.73–0.93), triple adjusted IRR=0.99 (95% CI 0.88–1.11)). There was no difference in the pneumonia risk (LABA-ICS adjusted IRR=0.96 (95% CI 0.71–1.31), triple adjusted IRR=1.16 (95% CI 0.87–1.57)). Conclusion Use of ICS-containing inhaled medication is prevalent across the UK while ICS withdrawal from established treatment was relatively uncommon. Exacerbations and pneumonia risk was similar between the ICS-containing and non-ICS containing treatment regimens.
Low dose bitter leaf improves sperm quality disrupted in immunosuppressed Wistar rats: An experimental study

Abstract Background Synthetic prednisolone (PRED) is a widely used over-the-counter glucocorticoid. Glucocorticoids have inhibitory effects on the immune system and are often used as immunosuppressive agents. Suppressed immunity may impact fertility via the hypothalamic-pituitary-adrenal axis. Bitter leaf (BL) has been shown to improve sperm parameters, but its effects on immunosuppression-associated infertility have not yet been documented. Objective To determine the fertility effects of bitter leaf on immunosuppressed Wistar rats. Materials and Methods A total of 30 male adult Wistar rats were randomly assigned to 6 groups (n = 5/each). Group A served as a control and were given distilled water in addition to normal feeds, group B received 2 mg/kg PRED for 14 days and served as the standard immunosuppressed group, and groups C-F were immunosuppressed as in B but in addition received 50 mg/kg levamisole, low-dose (250 mg/kg) BL, high-dose (375 mg/kg) BL, and low-dose BL + levamisole, respectively. The CD4 counts, hematological parameters, and sperm parameters were analyzed and compared. Results There were significant decreases in sperm motility, progressive motility, morphology, and life/death ratio in the animals given PRED only compared to the controls (p = 0.002, 0.001, 0.001, and 0.01, respectively). These were significantly increased in the treated groups, and animals given levamisole and 250 mg/kg BL showed significantly increased sperm counts compared to the controls (p = 0.04 and p = 0.04, respectively). Conclusion Low-dose BL (250 mg/kg) restored the sperm parameters altered by prednisolone administration.
Molecular Characterization of Carbapenem-Resistant Serratia marcescens Clinical Isolates in a Tertiary Hospital in Hangzhou, China

Introduction Although carbapenem-resistant Enterobacteriaceae (CRE) have been thoroughly investigated as the pathogens most commonly associated with clinical infections, data on Serratia marcescens are inadequate and superficial. Methods In this study, we characterized 36 carbapenem-resistant Serratia marcescens (CRSM) isolates in our hospital from April 2018 to March 2019 by analysing whole-genome sequencing (WGS) data. The molecular typing of the isolates was performed using both pulsed-field gel electrophoresis (PFGE) and core genome multilocus sequence typing (cgMLST). Results Thirty-three of the 36 isolates showed carbapenem resistance conferred by a blaKPC-2-harbouring plasmid, while the remaining three isolates were characterized by overexpression of beta-lactamase combined with porin loss. The blaKPC-2 genes in all the isolates were located on a plasmid of ~103 kb, except one, which was on a plasmid of ~94 kb. The gene structure surrounding blaKPC-2 in the plasmids was confirmed by integration of a partial Tn4401 structure and an intact IS26 as previously reported. Most of the plasmids also contained a mobile genetic element (MGE) comprising qnr and ISKpn19, which provided evidence of horizontal transfer of antibiotic resistance genes. Conclusion The thirty-six CRSM isolates were mainly clonally disseminated with a blaKPC-2-harbouring plasmid in our hospital. The gene structure surrounding blaKPC-2 as an MGE, as well as the qnr segment, might be acquired by horizontal gene transfer, and it could aggravate the infection and increase the difficulty of clinical treatment.
Low-dose interleukin-2 alleviates dextran sodium sulfate-induced colitis in mice by recovering intestinal integrity and inhibiting AKT-dependent pathways

Several phase 1/2 clinical trials showed that low-dose interleukin-2 (IL-2) treatment is a safe and effective strategy for the treatment of chronic graft-versus-host disease, hepatitis C virus-induced vasculitis, and type 1 diabetes. Ulcerative colitis (UC) is a chronic inflammatory condition of the colon that lacks satisfactory treatment. In this study, we aimed to determine the effects of low-dose IL-2 as a therapeutic for UC on dextran sulfate sodium (DSS)-induced colitis. Methods: Mice with DSS-induced colitis were intraperitoneally injected with low-dose IL-2. Survival, body weight, disease activity index, colon length, histopathological score, myeloperoxidase activity and inflammatory cytokine levels as well as intestinal barrier integrity were examined. Differential gene expression after low-dose IL-2 treatment was analyzed by RNA-sequencing. Results: Low-dose IL-2 significantly improved the symptoms of DSS-induced colitis in mice and attenuated pro-inflammatory cytokine production and immune cell infiltration. The most effective dose range of IL-2 was 16K-32K IU/day. Importantly, low-dose IL-2 was effective in ameliorating the disruption of epithelial barrier integrity in DSS-induced colitis tissues by restoring tight junction proteins and mucin production and suppressing apoptosis. The colon tissue of DSS-induced mice exposed to low-dose IL-2 mimic gene expression patterns in the colons of control mice. Furthermore, we identified the crucial role of the PI3K-AKT pathway in exerting the therapeutic effect of low-dose IL-2. Conclusions: The results of our study suggest that low-dose IL-2 has therapeutic effects on DSS-induced colitis and potential clinical value in treating UC.
Molecular docking and dynamics simulation of FDA approved drugs with the main protease from 2019 novel coronavirus

Design and development of an effective drug to combat the 2019 novel coronavirus remains a challenge. Therefore, it is of interest to study the binding features of 1615 FDA approved drugs with the recently known 2019-nCoV main protease structure having high sequence homology with that from SARS-CoV. We document the binding features of top 10 drugs with the target protein. We further report that Conivaptan and Azelastine are mainly involved in hydrophobic interactions with active site residues. Both drugs can maintain close proximity to the binding pocket of main protease during simulation. However, these data need further in vitro and in vivo evaluation to repurpose these two drugs against 2019-nCoV.
Cancer Detection Rates of Systematic and Targeted Prostate Biopsies after Biparametric MRI

Objective To compare prostate cancer detection rates (CDRs) and pathology results with targeted prostate biopsy (TB) and systematic prostate biopsy (SB) in biopsy-naive men. Methods An in-patient control study of 82 men undergoing SB and subsequent TB in case of positive prostate MRI between 2015 and 2017 in the Jeroen Bosch Hospital, the Netherlands. Results Prostate cancer (PCa) was detected in 54.9% with 70.7% agreement between TB and SB. Significant PCa (Gleason score ≥7) was detected in 24.4%. The CDR with TB and SB was 35.4% and 48.8%, respectively (p=0.052). The CDR of significant prostate cancer with TB and SB was both 20.7%. Clinically significant pathology upgrading occurred in 7.3% by adding TB to SB and 22.0% by adding SB to TB. Conclusions There is no statistically significant difference between CDRs of SB and TB. Both SB and TB miss significant PCas. Moreover, pathology upgrading occurred more often by adding SB to TB than vice versa. This indicates that the omission of SB in this study population might not be justified.
The Effect of Visceral Abdominal Fat Volume on Oxidative Stress and Proinflammatory Cytokines in Subjects with Normal Weight, Overweight and Obesity

Purpose The increase of visceral abdominal fat (VAF) and oxidative stress (OS) are independent predictors for cardiovascular risk. This study aimed to determine the association of VAF with proinflammatory cytokines, oxidants, antioxidants, and oxidative damage to DNA in subjects with normal weight, overweight, and obesity. Patients and Methods A cross-sectional study that included 21 men and 71 women who attended for a medical check-up was conducted. Dual-energy X-ray absorptiometry (DXA) was used to measure the VAF volume. ELISA and colorimetric techniques were used for chemical analysis. Results Low activity of superoxide dismutase (SOD) was found in overweight and obese subjects compared to the normal weight group (p=0.005). In contrast, the activity of glutathione peroxidase (GPx) was higher in the overweight and obesity groups compared to the normal weight subjects (p=0.017). The total antioxidant capacity (TAC) was also increased in the overweight group compared to the normal weight group (p=0.04). According to the volume of VAF, the levels of tumor necrosis factor alfa and interleukin 6 showed no differences between subjects with normal and high VAF. Subjects with high VAF show higher levels of 8-isoprostans compared to normal VAF group (p=0.039). Less concentration of 8-oxoguanine-DNA-N-glycosylase-1 (hOGG1) was found in the high VAF group (p=0.032) compared to the normal VAF subjects. VAF was positively correlated with lipoperoxides (LPO) (r=0.27, p<0.05) and 8-isoprostanes (r=0.25, p<0.05). We also found correlations between oxidative stress markers and anthropometric ratios for intra-abdominal fat. The waist-hip ratio was positively correlated with LPO (r=0.30, p<0.05) and TAC (r=0.24, p<0.05). Conclusion These findings suggest that the predominantly oxidative damage associated with VAF in overweight or obesity is lipoperoxidation and oxidative DNA damage. Alterations in endogenous antioxidant defenses may not be linked to the amount of VAF.
Scientific Opinion on porcine epidemic diarrhoea and emerging porcine deltacoronavirus

Abstract In the last decade, many porcine epidemic diarrhoea (PED) outbreaks have been reported by several countries in Asia whereas only a few Member States of the European Union (EU) have reported PED clinical cases and/or PED virus (PEDV)‐seropositive animals. This alphacoronavirus was first reported in the USA in May 2013, followed by rapid spread throughout the country and outbreaks reported by several countries in the Americas. The recent PEDV‐EU isolates have high level of sequence identity to PEDV‐Am isolates. Based on nucleotide sequencing, multiple variants of PEDV are circulating in Europe, the Americas and Asia but any difference in virulence and antigenicity is currently unknown. Serological cross‐reactivity has been reported between PEDV isolated in Europe and in the Americas; however no data regarding cross‐protection are available. The impact of different PEDV strains is difficult to compare between one country and another, since impact is dependent not only on pathogenicity but also on factors such as biosecurity, farm management, sanitary status or herd immune status. However, the clinical signs of PEDV infections in naive pigs are similar in different countries with mortalities up to 100% in naive newborn piglets. The impact of recently reported PED outbreaks in Asia and the USA seems to be more severe than what has been described in Europe. Infected animals, faeces, feed and objects contaminated with faeces are matrices that have been reported to transmit PEDV between farms. Infectious PEDV has been detected in spray‐dried porcine plasma (SDPP) in one study but the origin of the infectious PEDV in SDPP is not clear. Detection of porcine deltacoronavirus (PDCoV) has been reported in a few countries but only limited testing has been done. Based on the currently available information, it seems that PDCoV would have a lower impact than PEDV.
Prevalencia de los ácaros Demodex folliculorum y Demodex brevis en una población mexicana

Background: Demodex folliculorum and Demodex brevis are the most pervasive ectoparasites of man. Its prevalence is described ranging from 0 to 100% in different human populations. Objective: To determine prevalence of infestation by Demodex in our community. Material and methods: We conducted in Monterrey a survey in 315 individuals, with a range of age from 11-50, using two different techniques for recollection of parasites. Results: We found a global prevalence of 27.3%, with the highest prevalence among the 41-50 age group, and an infestation malefemale ratio of 1:1. Conclusions: D. folliculorum was more frequently found than D. brevis.
Empirical Characterization of the NLOS Component for Vehicular Visible Light Communication

We investigate the influence of Non Line Of Sight (NLOS) components on the performance of Vehicular VLC (V-VLC). Given the steep rise of Intelligent Transportation Systems (ITS) for road safety applications, the need for reliable technologies for Vehicle-to-Vehicle (V2V) communication rises. Among others, V-VLC turned out to be a promising candidate to enhance vehicular connectivity, which nicely complements Radio Frequency (RF)-based technologies. V-VLC is supposed to be a Line Of Sight (LOS) communication technology, nevertheless, there is also a NLOS component caused by reflection on the road surface. In this paper, we investigate this influence in a real-world measurement campaign for different ground surfaces. Our results are very interesting as they (a) confirm a huge impact, and (b) indicate such reflections being actually helpful as they improve the received signal strength.