Miracle-dz/UniFAR-FTUs huggingface dataset:
Triple-Negative Breast Cancer: Current Understanding and Future Therapeutic Breakthrough Targeting Cancer Stemness

Triple-negative breast cancer (TNBC) is cancer that tested as negative for estrogen receptors (ER), progesterone receptors (PR), and excess human epidermal growth factor receptor 2 (HER2) protein which accounts for 15%–20% of all breast cancer cases. TNBC is considered to be a poorer prognosis than other types of breast cancer, mainly because it involves more aggressive phenotypes that are similar to stem cell–like cancer cells (cancer stem cell, CSC). Thus, targeted treatment of TNBC remains a major challenge in clinical practice. This review article surveys the latest evidence concerning the role of genomic alteration in current TNBC treatment responses, current clinical trials and potential targeting sites, CSC and drug resistance, and potential strategies targeting CSCs in TNBC. Furthermore, the role of insulin-like growth factor 1 receptor (IGF-1R) and nicotinic acetylcholine receptors (nAChR) in stemness expression, chemoresistance, and metastasis in TNBC and their relevance to potential treatments are also discussed and highlighted.
Prospective international study of incidence and predictors of immune reconstitution inflammatory syndrome and death in people with HIV and severe lymphopenia.

BACKGROUND Patients with HIV and low CD4 counts starting antiretroviral therapy (ART) are at high risk for immune reconstitution inflammatory syndrome (IRIS) and death. METHODS To investigate the clinical impact of IRIS in adults with HIV and CD4 counts below 100 cells/µL starting ART, we designed an international, prospective, observational study in United States, Thailand, and Kenya. An independent review committee adjudicated IRIS events. We used Cox models to investigate associations between baseline biomarkers, IRIS, immune recovery at week 48, and death by week 48. RESULTS We enrolled 506 participants, 39.3% of whom were women. Median age was 37 years (IQR 31-45) and CD4 T cell count was 29 cells/µL (IQR 11-56). Within 6 months of ART initiation, 97 (19.2%) participants developed IRIS and 31 (6.5%) died. Participants with lower hemoglobin at study start were at higher risk of IRIS (HR 1.2, p=0.004). IRIS was independently associated with increased risk of death even after adjustment for known risk factors (HR 3.2, P=0.031). In addition, being female (P=0.004), having lower BMI (P=0.003), higher WBC (P=0.005) and higher D-dimer levels (P=0.044) were also significantly associated with increased risk of death. Decision tree analysis identified hemoglobin less than 8.5 g/dL as highly predictive of IRIS and CRP>106 µg/ml and BMI < 15.6 kg/m2 as predictive of death . CONCLUSIONS For patients with HIV and severe immunosuppression who are initiating ART, baseline low BMI and hemoglobin, and high CRP and D-dimer may be clinically useful predictors of IRIS and death risk.
Association of sociodemographic and clinical variables with time to start prostate cancer treatment.

INTRODUCTION Disparities in prostate cancer care have been evidenced and associated with sociodemographic and clinical factors, which establish the time for diagnosis and initiation of treatment. OBJECTIVE To evaluate the association of sociodemographic and clinical variables with the onset of prostate cancer treatment. METHODS This is a prospective longitudinal cohort study with secondary data with a population of men with prostate cancer attended in the periods 2010-2011 and 2013-2014 at the Santa Rita de Cássia Hospital in Vitória, Espírito Santo, Brazil. RESULTS The study population consisted of 1,388 men. Of the total, those younger than 70 years (OR = 1.85; CI = 1.49-2.31), nonwhite (OR = 1.30; CI = 1.00-1.70), less than 8 years of schooling (OR = 1.52; CI = 1.06-2.17) and referred by the Unified Health System services (OR = 2.52; CI = 1.84-3.46) were more likely to have a delayed treatment. Similarly, the lower the Gleason score (OR = 1.78; CI = 1.37-2.32) and Prostate-Specific Antigens levels (OR = 2.71; CI = 2.07-3.54), the greater the likelihood of delay for the onset of treatment. CONCLUSION Therefore, sociodemographic and clinical characteristics exerted a strong influence on the access to prostate cancer treatment.
Left ventricular mechanical dispersion in a general population: Data from the Akershus Cardiac Examination 1950 study.

AIMS Increased left ventricular mechanical dispersion by 2D speckle tracking echocardiography predicts ventricular arrhythmias in ischaemic heart disease and heart failure. However, little is known about mechanical dispersion in the general population. We aimed to study mechanical dispersion in the general population and in diseases associated with increased risk of cardiovascular disease. METHODS AND RESULTS The present cross-sectional study consists of 2529 subjects born in 1950 included in the Akershus Cardiac Examination (ACE) 1950 study. Global longitudinal strain (GLS) was assessed from 17 strain segments, and mechanical dispersion calculated as the standard deviation of contraction duration of all segments. The cohort was divided according to the median value of mechanical dispersion, and multivariable linear regression models were performed with mechanical dispersion as the dependent variable. The prevalence of coronary artery disease (CAD), hypertension, obesity, and diabetes (P < 0.01 for all) was significantly higher in subjects with supra-median mechanical dispersion. In a multivariable clinical model, CAD (B = 7.05), hypertension (B = 4.15; both P < 0.001), diabetes (B = 3.39), and obesity (B = 1.89; both P < 0.05) were independently associated with increasing mechanical dispersion. When echocardiographic indices were added to the multivariable model, CAD (B = 4.38; P < 0.01) and hypertension (B = 2.86; P < 0.001) remained significant in addition to peak early diastolic tissue velocity e' (B = -2.00), GLS (B = 1.68), and ejection fraction (B = 0.22; P < 0.001 for all). CONCLUSION In a general middle-aged population, prevalent CAD and hypertension were associated with increasing mechanical dispersion, possibly indicating elevated risk of fatal arrhythmias and sudden cardiac death. Albeit weaker, systolic and diastolic dysfunction, were also associated with increasing mechanical dispersion.
Place navigation in the Morris water task results in greater nuclear Arc mRNA expression in dorsal compared to ventral CA1

Previous work has shown that the dorsal hippocampus has greater activity than ventral regions during place navigation. Exposure to a novel context has also been found to increase hippocampal activation, possibly due to increased spatial demands. However, activation patterns in dorsal and ventral regions have not been investigated in the Morris water task (MWT), which remains the most popular assay of place memory in rodents. We measured activity in a large population of neurons across the CA1 dorsal–ventral axis by estimating nuclear Arc mRNA with stereologic systematic‐random sampling procedures following changes to goal location or spatial context in the MWT in rats. Following changes to goal location or spatial context in the MWT, we did not find an effect on Arc mRNA expression in CA1. However, Arc expression was greater in the dorsal compared to the ventral aspect of CA1 during task performance. Several views might account for these observed differences in dorsal–ventral Arc mRNA expression, including task parameters or the granularity of representation that differs along the dorsal–ventral hippocampal axis. Future work should determine the effects of task differences and required memory precision in relation to dorsal–ventral hippocampal neuronal activity.
Factors influencing the journey to work for young people with physical and/or neurological conditions

Abstract Purpose This study examined the challenges young people with a physical and/or neurological condition experience in their journey to work. This includes both their physical commute to work and transition to the workforce. Materials and methods Insight was established through the development and testing of a model which extended the model of goal directed behavior. A survey was distributed to 200 young people with a physical and/or neurological condition. PLS-SEM analysis was conducted to identify factors which influence a young person with a physical and/or neurological disability’s journey to work. Results The results suggest subjective norms, attitudes, anticipated negative emotions, and risk aversion underpin a young person’s desire to journey to work (both physical commute to work and transition to workforce). This desire then encourages an individual’s intentions to travel independently. Past behavior and perceived behavioral support are seen to encourage intentions, while employer support and social support lead to increased perceived behavioral control directly and intentions indirectly. Conclusions The study highlights the importance of mental preparedness, having support available from employers, friends, and families, and access to transport that supports independence in encouraging and facilitating the journey to work for young adults with a neurological and/or physical disability. IMPLICATIONS FOR REHABILITATIONf Positive attitude, risk aversion, and expected negative emotions are key factors in the decision to commute to work independently for a young person with a physical and/or neurological disability. The more support a young person with a physical and/or neurological disability feels from their employer and social circle, the more likely they feel in control of their actions and to plan to journey to work independently. Encouraging social norms are likely to impact the desire and intention to journey to work independently for young people with a physical and/or neurological disability. Feeling in control and having successful previous transport experiences is likely to help predict whether young people with a physical and/or neurological disability will plan on commuting to work independently in the future.
Comparing the Continuous Geboes Score With the Robarts Histopathology Index: Definitions of Histological Remission and Response and their Relation to Faecal Calprotectin Levels.

BACKGROUND AND AIMS The histological status of ulcerative colitis [UC] patients in clinical and endoscopic remission has gained space as an important prognostic marker and a key component of disease monitoring. Our main aims were to compare two histological indexes-the continuous Geboes score [GS] and the Robarts Histopathology index [RHI]-regarding their definitions of histological remission and response, and the ability of faecal calprotectin [FC] levels to discriminate between these statuses. METHODS This was an analysis of three prospective cohorts including 422 patients previously enrolled in other studies. RESULTS The two continuous scores [GS and RHI] were shown to be significantly correlated [correlation coefficient of 0.806, p < 0.001] and particularly close regarding their definition of histological response: 95% and 88% of all patients classified as having/not having [respectively] histological response according to RHI also did so according to GS. Moreover, median FC levels in patients with histological response were lower than those in patients without histological response [GS: 73.00 vs 525.00, p < 0.001; RHI: 73.50 vs 510.00, p < 0.001]; a similar trend was observed when FC levels of patients in histological remission were compared to those of patients with histological activity [GS: 76.00 vs 228.00, p < 0.001; RHI: 73.50 vs 467.00, p < 0.001]. FC levels allowed us to exclude the absence of histological remission [according to RHI] and absence of histological response [according to RHI and GS], with negative predictive values varying from 82% to 96%. However, optimization of the FC cut-off to exclude the absence of histological remission, as for the continuous GS, falls within values that resemble those of the healthy population. CONCLUSION The continuous GS and RHI histological scores are strongly correlated in their definitions of histological response. An absence of histological remission could only be excluded at physiological levels of FC.
Role of good oral hygiene on clinical evolution of rheumatoid arthritis: a randomized study nested in the ESPOIR cohort.

OBJECTIVE There is a relationship between RA and periodontal disease. We aimed to investigate if a good oral hygiene could improve activity of RA. METHODS The patients with RA according to ACR/EULAR 2010 criteria and included in the French early arthritis ESPOIR cohort were included in a randomized nested study into: (i) intervention group: general recommendations of good oral hygiene including teeth brushing, daily antiseptic mouthwash and twice a year scaling; and (ii) control group: no intervention. The primary end point was the delta DAS28-ESR. RESULTS Four hundred and seventy-two patients were randomized (238 in intervention and 234 in control). 92/238 from the intervention group accepted the procedure and 81 had a first visit to the dentist. 56% of patients had periodontal disease at baseline. Duration of RA was 9.0±0.7 years. Baseline DAS28-ESR was 2.7±1.3. After a median duration of 24 months, delta DAS28-ESR was -0.17±1.29 and -0.09±1.28 in intervention and control groups, respectively (mean difference (complier average causal effect): -0.37 (95% CI -1.12, 0.37), P = 0.33). In the intervention group, there was a significant decrease of the bacteria involved in the red complex: Porphyromonas gingivalis (P = 0.002), Tannerella forsythia (P = 0.002) and Treponema denticola (P = 0.019). The patients with baseline periodontal disease and those who became negative for one red complex bacterium had a slightly more important decrease of DAS28-ESR. CONCLUSION Oral hygiene instruction together with regular scaling and polishing of the teeth significantly decreased the load of periodontal pathogens but did not decrease RA activity. This intervention should be tested in patients with earlier RA and more active disease. TRIAL REGISTRATION ClinicalTrials.gov, http://clinicaltrials.gov, NCT01831648.
Do Barrier Test Results Predict Survival in Specialist Police Tactical Selection Courses?

Entry to specialist police tactical teams is governed by performance on a physically intense and psychologically demanding selection course. The aim of this study was to determine the attributes associated with completion of a specialist police selection course. Data pertaining to 18 candidates was obtained including 1 min push-ups, loaded pull-ups, loaded 30 m crawl, agility run, 1.2 km run and multi-stage fitness assessment. Comparisons from those who did and did not complete the selection week were performed and a hierarchical multiple regression performed. Eleven candidates finished, with significant difference found in those who completed the course in push-ups (+9.1 reps), loaded pull-ups (+2.9 reps), 1.2 km run (−16 s), loaded crawl (−6.3 s), agility (−0.67 s) and VO2max (+4.8 mL/kg/min). In combination, the fitness assessments pull-ups, 30 m loaded crawl and agility time were found to predict 70% of the variability in course completion (adjusted R2 = 0.70, F (3,14) = 14.373, p = 0.001). When assessed independently, push-ups, 1.2 km run and VO2max results only predicted a non-significant 0.02%, 0.29% and 0.12%, respectively, of course completion. Completion was influenced by aerobic fitness, upper limb strength and endurance and agility. These variables appear to be predictive of course success.
The Importance of Oral Health in Immigrant and Refugee Children

According to the Migration Policy Institute, 2017 data revealed that a historic high 44.5 million people living in the United States (US) were foreign-born (Zong, J., et.al., 2019), more than double the number from 1990 (U.S. Immigrant Population and Share over Time. 1850-Present, 2019). Since the creation of the Refugee Resettlement Program in 1980, refugee families have settled in the US more than in any other country in the world (Radford, J., 2019). In 2018, for the first time, Canada overtook the US in numbers of refugees accepted (Zong, J., et. al., 2019). Foreign-born people now account for 13.7% of the total US population (Zong, J., et. al., 2019). Further, a quarter of children in the United States currently live in households with at least one foreign-born parent (America’s Children in Brief: Key National Indicators of Well-Being, 2018). These population shifts are important to note because immigrant and refugee families bring cultural influences and health experiences from their home countries which can greatly affect the overall health and well-being of children. For these new arrivals, oral health is often a significant health issue. The severity of dental disease varies with country of origin as well as cultural beliefs that can hinder access to care even once it is available to them (Obeng, C.S. Culture and dental health among African immigrant school-aged children in the United States, 200; Tiwari, T.; Albino, J. Acculturation and Pediatric Minority Oral Health Interventions, 2017). As pediatricians and primary care providers, we should acknowledge that oral health is important and impacts overall health. Healthcare providers should be able to recognize oral health problems, make appropriate referrals, and effectively communicate with families to address knowledge gaps in high-risk communities.
Effect of exogenous phytase added to small-quantity lipid-based nutrient supplements (SQ-LNS) on the fractional and total absorption of zinc from a millet-based porridge consumed with SQ-LNS in young Gambian children: a randomized controlled trial.

BACKGROUND Dietary phytate inhibits zinc absorption from composite meals in adults. OBJECTIVE The objective of this study was to investigate the effect of adding exogenous phytase to a small-quantity lipid-based nutrient supplement (SQ-LNS) on zinc absorption among young children. METHODS In a double-blind randomized controlled trial, intraindividual differences in fractional and total absorption of zinc (FAZ and TAZ, respectively) from a millet-based porridge containing SQ-LNS with and without phytase were measured in 30 asymptomatic children 18-23 mo of age in the Kiang West district of The Gambia. Using a crossover design, children received for 1 d each porridge test meals with 20 g SQ-LNS containing 8 mg zinc and either 1) exogenous phytase or 2) no exogenous phytase. The test meals were provided on consecutive days in randomized order. FAZ was measured using a triple stable isotope tracer ratio technique with Zn-67 and Zn-70 as oral tracers and Zn-68 as the intravenous tracer. RESULTS Twenty-six participants completed the study. The prevalence of stunting and wasting were 20% and 13%, respectively; no children had low plasma zinc concentrations (<65 μg/dL). Total mean ± SD dietary zinc intake from the test meals was 7.3 ± 2.2 mg (phytate:zinc molar ratio = 3.1 ± 0.3, not accounting for phytase activity). Mean FAZ increased from 8.6% ± 1.3% to 16.0% ± 1.3% when exogenous phytase was added to the SQ-LNS product (P < 0.001). Mean TAZ from test meals containing SQ-LNS with phytase was more than double that from test meals containing SQ-LNS without phytase (1.1 ± 0.1 mg and 0.5 ± 0.1 mg, respectively; P < 0.001). CONCLUSIONS The addition of exogenous phytase to SQ-LNS increased both FAZ and TAZ. These results suggest that phytate reduction may be an important strategy to increase zinc absorption among young children. This trial was registered at clinicaltrials.gov as NCT02668133.
Fish skin grafts compared to human amnion/chorion membrane allografts: A double‐blind, prospective, randomized clinical trial of acute wound healing

Chronic, nonhealing wounds consume a great deal of healthcare resources and are a major public health problem, associated with high morbidity and significant economic costs. Skin grafts are commonly used to facilitate wound closure. The grafts can come from the patient's own skin (autograft), a human donor (allograft), or from a different species (xenograft). A fish skin xenograft from cold‐water fish (Atlantic cod, Gadus morhua) is a relatively recent option that shows promising preclinical and clinical results in wound healing. Chronic wounds vary greatly in etiology and nature, requiring large cohorts for effective comparison between therapeutic alternatives. In this study, we attempted to imitate the status of a freshly debrided chronic wound by creating acute full‐thickness wounds, 4 mm in diameter, on healthy volunteers to compare two materials frequently used to treat chronic wounds: fish skin and dHACM. The purpose is to give an indication of the efficacy of the two therapeutic alternatives in the treatment of chronic wounds in a simple, standardized, randomized, controlled, double‐blind study. All volunteers were given two identical punch biopsy wounds, one of which was treated with a fish skin graft and the other with dehydrated human amnion/chorion membrane allograft (dHACM). In the study, 170 wounds were treated (85 wounds per group). The primary endpoint was defined as time to heal (full epithelialization) by blinded assessment at days 14, 18, 21, 25, and 28. The superiority hypothesis was that the fish skin grafts would heal the wounds faster than the dHACM. To evaluate the superiority hypothesis, a mixed Cox proportional hazard model was used. Wounds treated with fish skin healed significantly faster (hazard ratio 2.37; 95% confidence interval: (1.75–3.22; p = 0.0014) compared with wounds treated with dHACM. The results show that acute biopsy wounds treated with fish skin grafts heal faster than wounds treated with dHACM.
Analysis of Serum Adiponectin Level and Related Factors in Nonalcoholic Fatty Liver Disease

Objective To study the level of adiponectin and the related factors in nonalcoholic fatty liver disease ( NAFLD)patients. Methods A total of 120 cases were enrolled and divided into two groups:NAFLD group(n =60),normal control group(n =60). Serum level of adiponectin was measured by ELISA. Body mass index (BMI),waist-to-hip ratio (WHR),triglyceride (TG),total cholesterol (Tchol),high-density lipoprotein cholesterol(HDL-C),aspartate aminotransferase(AST),alanine aminotransferase(ALT),gamma-glutamyl transpeptidase( GGT),fasting blood glucose(FBG),HOMA-IR(homeostasis model assessment insulin resistance)were evaluated. Results The serum adiponectin level in NAFLD group was significantly lower than that in control group[(12.69±2.83)mg/L vs(22.83±4.61)mg/L, P 0.01)]. Spearman analysis showed adiponectin was negatively correlated with ALT( r =-0.643,P 0.05 ),AST ( r =-0.472,P 0.05),GGT(r =-0.489,P 0.05),HOMA-IR(r =-0.752,P 0.05),TG(r =-0.671,P 0.05),FBG(r =-0.710,P 0.05),WHR(r =-0.732,P 0.05),BMI (r =-0.719,P 0.05),and positively correlated with HDL-C (r =0.567,P 0.05). Logistic analysis showed adiponectin was independently negatively associated with HOMA-IR(β=-0.495,P 0.05 )and BMI(β=-0.314,P 0.05 ). Conclusion The level of adiponectin decreases in NAFLD patients,adiponectin may be a protective adipokine in the pathogenesis of NAFLD.