Miracle-dz/UniFAR-FTUs huggingface dataset:
Antiangiogenesis therapy in ovarian cancer patients

Background: Antiangiogenesis therapy has been demonstrated to prolong the free survival with tolerable toxicity. However the efficacy of these drugs in overall survival (OS) remains controversial. This study was designed to assess the overall performance of antiangiogenesis therapy in improving the survival of ovary cancer (OC) patients. Methods: Electronic database of PubMed, Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials were searched to identify relevant clinical randomized control trial (RCTs) assessing the therapeutic value of antiangiogenesis therapy in OC patients during 2011 to 2017. Additionally, abstracts of annual meetings were also conducted. Only English articles were considered. Progression free survival (PFS), OS, and objective response rate (ORR) were obtained from eligible RCTs. The HRs for time-to-event variables and ORs for dichotomous outcomes with their 95% CIs were used for this meta-analysis. All the statistical analyses were carried out by Stata 11.0 software using a fixed or random-models according to heterogeneity. Results: A total of 15 RCTs including 9359 patients were recruited into this meta-analysis. Addition of antiangiogenic agents improved PFS (HR = 0.71, 95% CI 0.62–0.81, P < .001), OS (HR = 0.92, 95% CI 0.86–0.98, P = .008) and ORR (OR = 1.74, 95% CI 1.27–2.39, P = .001) compared to placebo or chemotherapy alone in overall analysis. Antiangiogenic agents prolonged both PFS (HR = 0.58, 95% CI 0.52–0.65, P = .000) and OS (HR=0.84, 95% CI 0.76–0.92, P = .000) in recurrent settings but only PFS in primary settings (HR = 0.88, 95% CI 0.79–0.98, P = .020), longer PFS and OS in both platinum-sensitive recurrent patients (HR = 0.56, 95% CI 0.48–0.64, P = .000, PFS; HR = 0.86, 95% CI 0.76–0.98, P = .027, OS) as well as platinum-resistant recurrent cases (HR = 0.54, 95% CI 0.41–0.71, P = .000, PFS; HR = 0.84, 95% CI 0.71–0.98, P = .029, OS). Throughout therapy improved PFS (HR = 0.66, 95% CI 0.57–0.76, P < .001) and OS (HR = 0.89, 95% CI 0.83–0.96, P = .001). However the maintenance therapy of antiangiogenic agents was irrelevant to a longer PFS or OS. Conclusion: Based on the available studies, antiangiogenic agents play an important role in the survival of OC patients. More randomized controlled trials are needed to reach more convinced conclusion.
Assessment of Glomerular and Tubular Function in the Evaluation of Diabetic Nephropathy: A Cross-sectional Study

Background: Diabetic nephropathy (DN) occurs in 20%–40% of patients with diabetes, and it is characterized by proteinuria and progressive loss of renal functions ultimately leading to end-stage renal disease. Classically, albuminuria is regarded as a consequence of diabetes-induced glomerular damage. It is now being appreciated that the renal tubulointerstitium also plays a role in the development of DN. [1] Urinary cystatin C (UCC) is an emerging marker of DN. It is totally catabolized by proximal tubular cells and is not normally present in the urine. However, in the presence of tubulopathy, it is excreted in urine, and serum levels also are elevated due to lack of catabolism. Materials and Methods: The present study was conducted to evaluate the presence of glomerulopathy and tubulopathy in patients with type 2 diabetes mellitus (T2DM) and to correlate them with established risk factors for nephropathy. We aimed at evaluating the level of UCC as a marker of tubulointerstitial damage in patients with T2DM in relation to the level of albuminuria and other parameters. Seventy-two patients with T2DM (mean age, 47.44 ± 10.40 years) and 45 healthy age- and sex-matched subjects were evaluated for UCC, serum creatinine, and urinary albumin-creatinine ratio (UACR) along with other parameters. Results: Of the 72 patients included in the study, microalbuminuria was found in 26% and macroalbuminuria in 10% of cases. UCC was significantly higher in micro- and macro-albuminuric groups in comparison with normoalbuminuric patients and correlated positively with UACR. Among the 46 patients with normoalbuminuria, 11 had elevated UCC levels indicating early tubular dysfunction. Conclusions: This finding may support the hypothesis of a “tubular phase” of diabetic kidney disease preceding overt DN, and hence, the use of UCC measurement for early evaluation of renal involvement.
Atrial fibrillation and type 2 diabetes: Prevalence, etiology, pathophysiology and effect of anti‐diabetic therapies

New‐onset atrial fibrillation (NAF) is increased in the type 2 diabetic patient because of the presence of the metaboli syndrome and increased sympathetic activity. This results in inflammation, endothelial dysfunction and myocardial steatosis which, in turn, lead to atrial fibrosis and dilatation. The end result is the development of structural and electrical atrial remodeling. Drugs that lower insulin resistance, particularly pioglitazone, decrease the incidence of NAF while drugs that, through hypoglycaemia, stimulate the sympathetic nervous system, insulin and secretagogues, increase the incidence of NAF. Currently there is no evidence that GLP‐1 agonists, SGLT2 inhibitors and DPP‐4 inhibitors either accelerate or decelerate the development of NAF.
Differential Claudin 3 and EGFR Expression Predicts BRCA1 Mutation in Triple-Negative Breast Cancer

Abstract BRCA-1 mutation-associated triple-negative breast cancer (TNBC) has been hypothesized to exhibit a phenotype that is distinct from non-mutation carriers. We have analyzed immunohistochemically detected cytokeratins 5 and 14, epidermal growth factor receptor (EGFR), claudin (CLDN) 3, 4, and 7, and E-cadherin in 57 TNBC (32 BRCA1 and 8 BRCA2 tumors, 17 WT tumors). Positive staining of CLDN3 and negative EGFR expression in TNBC are associated with a BRCA1 mutation. EGFR and CLDN3 expression was able to predict the presence of BRCA1 mutation (area under curve 0.802, p < 0.001). This could help in guiding the decision for BRCA testing.
Clinical value of circulating ESR1 mutations for patients with metastatic breast cancer: a meta-analysis

Background The clinical implication of plasma ESR1 mutations in the estrogen receptor (ER)-positive metastatic breast cancer (MBC) patients who had progressed after prior aromatase inhibitor (AI)-based therapy remains controversial. We conducted the first meta-analysis to investigate the prognostic significance and predictive role of plasma ESR1 mutations in MBC patients with prior exposure to AI therapy. Materials and methods We searched PubMed, Embase, and Cochrane Library databases for eligible studies. Meta-analysis was conducted to calculate combined hazard ratios (HRs) with 95% CIs for progression-free survival (PFS) and overall survival (OS). Subgroup and sensitivity analyses were also performed. Results This study enrolled a total of 1,530 patients with ER-positive MBC cases from six articles, including 429 ESR1 mutation carriers (28.04%). Meta-analysis demonstrated that plasma ESR1 mutation carriers had significantly worse PFS (HR: 1.40, 95% CI: 1.17–1.66; P<0.0001) and OS (HR: 1.65, 95% CI: 1.36–2.01; P<0.0001) compared to wild-type ESR1. Subgroup analysis showed that plasma ESR1 mutations were associated with shorter PFS after AI-based treatment, but were not significantly predictive of outcome on fulvestrant-containing therapy (HR: 1.26, 95% CI: 0.98–1.62; P=0.077). As for different ESR1 mutations, D538G mutation implied significantly worse PFS (HR: 1.50, 95% CI: 1.18–1.91; P=0.01), while Y537S mutation was not correlated with PFS (HR: 1.65, 95% CI: 0.87–1.73; P=0.134). Conclusion The meta-analysis indicated that plasma ESR1 mutation assessment may have prognostic significance and clinical value in guiding further endocrine therapy choice in ER+ MBC patients who received prior AI therapy.
Clinical Evaluation of Different Delivery Methods of At-Home Bleaching Gels Composed of 10% Hydrogen Peroxide.

OBJECTIVES: This study aimed to compare the tooth sensitivity, gingival irritation, and bleaching efficacy of at-home whitening performed with 10% hydrogen peroxide (HP) using a conventional tray-delivered system or two different bleaching systems (strips or prefilled disposable trays). METHODS AND MATERIALS: Sixty patients, with maxillary incisors darker than A2 were selected for this single-blind, parallel randomized clinical trial. Teeth were bleached during 14 days with a 30-minute gel contact with teeth per day. The 10% HP was delivered in a bleaching tray (White Class, FGM) in strips (White Strips, Oral-B) or prefilled disposable trays (Opalescence Go, Ultradent). The color changes were evaluated by subjective (Vita Classical and Vita Bleachedguide) and objective (Easyshade Spectrophotometer) methods at baseline and 30 days after the second bleaching session. Tooth sensitivity was recorded during 14 days with a five-point numeric rating scale (NRS) and 0-10 visual analog scale (VAS). The risk of gingival irritation was also recorded during 14 days on a dichotomous scale. All data were submitted to appropriate statistical analysis (α=0.05). RESULTS: No significant difference was observed in the risks of tooth sensitivity among groups ( p>0.09). However, the conventional bleaching tray produced a higher intensity of tooth sensitivity when compared with the strips and prefilled disposable tray systems ( p<0.04). Regarding gingival irritation, the prefilled disposable tray system showed a lower risk of gingival irritation when compared with the conventional bleaching tray ( p=0.003). Significant whitening was observed in all groups after 30 days of clinical evaluation with no significant difference between them ( p>0.06). CONCLUSIONS: All 10% HP bleaching systems showed similar whitening after a 14-day use. However, the strips and prefilled disposable trays produced lower intensity of tooth sensitivity than the conventional bleaching tray system. The prefilled disposable tray produced lower risk of gingival irritation when compared to the conventional bleaching tray.
Current trends in opportunistic infections in children living with HIV/AIDS in a tertiary care hospital in Northern India

Introduction: A prospective cohort study was undertaken from November 2010 to March 2012 at Kalawati Saran Children's Hospital (KSCH), Lady Hardinge Medical College (LHMC), New Delhi. The study included all HIV positive children aged between 0-15 years that were registered in the anti-retroviral therapy (ART) centre during the study period. HIV +ve children enrolled at the ART centre were started on ART on the basis of CD4counts (National/NACO guidelines). Materials and Methods: Various samples were collected from the patients depending on their presenting complaints as per the standard protocols. These included stool, sputum, gastric aspirate, urine, blood, pus and CSF. All the samples were processed in the microbiology laboratory as per the standard techniques. Majority of children presented to the hospital with respiratory system involvement. Fever with cough was the presenting symptom in around half of all the children suggesting involvement of upper and/or lower respiratory tract. Diarrhea and protein energy malnutrition (PEM) were the next most common findings. Clinical presentations more suggestive of HIV (e.g. generalized lymphadenopathy, mucocutaneous lesions, oral thrush etc.) were less commonly the presenting complaints. Results: OIs are still a major health hazard in children living with HIV/AIDS. The pattern of OIs encountered in a developing country like ours is different from the pattern observed in western countries. Tuberculosis is still a major problem as well as other bacterial infections. Fungal and parasitic infections are also a common health hazard. ART is a major pillar for combat against this dreadful disease. As suggested by our study, timely initiation of ART leads to an increase in CD4+ counts which is imperative in protection against OIs in HIV infected patients. Hence, routine monitoring of CD4+ counts and timely initiation and continuation of ART should be a major event in the life of a child infected with HIV.
Oleuropein and rutin protect against 6-OHDA-induced neurotoxicity in PC12 cells through modulation of mitochondrial function and unfolded protein response

Abstract Parkinson’s disease (PD) is a highly prevalent neurodegenerative disorder, often associated with oxidative stress-induced transcriptional changes in dopaminergic neurons. Phenolic antioxidants, oleuropein (OLE) and rutin (RUT) have attracted a great interest due to their potential to counteract oxidative protein aggregation and toxicity. This study aimed at examining the effects of OLE and RUT against 6-OHDA-induced stress response in rat pheochromocytoma cells. When differentiated PC12 cells were exposed to oxidative stress composer 6-OHDA (100 μM, 8 h), a decreased mitochondrial membrane potential (ΔΨm) was observed along with a significant loss of cell viability and apoptotic nuclear changes. Exposure to 6-OHDA resulted in unfolded protein response (UPR) in differentiated PC12 cells as evidenced by an increased level of endoplasmic reticulum (ER)-localized transmembrane signal transducer IRE1α, adaptive response proteins ATF-4 and proapoptotic transcription factor CHOP. OLE or RUT pretreatment (24 h) at low doses (1-50 μM) protected the differentiated PC12 cells from 6-OHDA-induced cytotoxicity as assessed by increased viability, improved ΔΨm and inhibited apoptosis, whereas relatively high doses of OLE or RUT (>50 μM) inhibited cell growth and proliferation, indicating a typical hormetic effect. In hormetic doses, OLE and RUT up-regulated 6-OHDA-induced increase in IRE1α, ATF-4 and inhibited CHOP, PERK, BIP and PDI. 6-OHDA-activated XBP1 splicing was also inhibited by OLE or RUT. The presented results suggest that neuroprotection against 6-OHDA-induced oxidative toxicity may be attributable to neurohormetic effects of OLE or RUT at low doses through regulating mitochondrial functions, controlling persistent protein misfolding, activating and/or amplificating the adaptive response-related signaling pathways, leading to UPR prosurvival output.
Structural brain maturation differs between preterm and term piglets, whereas brain activity does not

The aim of the study was to investigate whether amplitude‐integrated electroencephalography (aEEG) and cerebral magnetic resonance imaging (MRI) in preterm piglets would provide measures of cerebral functional, microstructural and anatomical maturation, which might reflect the signs of functional brain immaturity, documented in preterm piglets.
The role of executive function in autobiographical memory retrieval: does the type of cue word matter?

ABSTRACT Autobiographical memories are memories for personally experienced life events. Previous research has revealed individual differences in the ability to recall specific memories that happened at a particular time and place. Some studies suggest such differences can be attributed to the varying capacity of executive function. However, little is known regarding which specific executive function skills predict autobiographical memory specificity. Participants were asked to complete multiple measures of executive function as well as an autobiographical memory task in which they were asked to recall a specific personal memory connected to concrete and abstract cue words. We hypothesised that executive function will be positively related to autobiographical memory specificity and that this relation will be moderated by the cue word type. The results revealed that individuals with higher executive function skills, specifically, higher inhibitory control and cognitive flexibility, recalled significantly more specific memories than those with lower executive function skills; however, no significant interaction between executive function ability and cue word type was found.
Life-threatening influenza pneumonitis in a child with inherited IRF9 deficiency

Life-threatening pulmonary influenza can be caused by inborn errors of type I and III IFN immunity. We report a 5-yr-old child with severe pulmonary influenza at 2 yr. She is homozygous for a loss-of-function IRF9 allele. Her cells activate gamma-activated factor (GAF) STAT1 homodimers but not IFN-stimulated gene factor 3 (ISGF3) trimers (STAT1/STAT2/IRF9) in response to IFN-&agr;2b. The transcriptome induced by IFN-&agr;2b in the patient’s cells is much narrower than that of control cells; however, induction of a subset of IFN-stimulated gene transcripts remains detectable. In vitro, the patient’s cells do not control three respiratory viruses, influenza A virus (IAV), parainfluenza virus (PIV), and respiratory syncytial virus (RSV). These phenotypes are rescued by wild-type IRF9, whereas silencing IRF9 expression in control cells increases viral replication. However, the child has controlled various common viruses in vivo, including respiratory viruses other than IAV. Our findings show that human IRF9- and ISGF3-dependent type I and III IFN responsive pathways are essential for controlling IAV.
Hazards of Repeat Pregnancy during Adolescence: A Case-control Study

Abstract Objective To evaluate the social, obstetric and psychological risk factors related to repeat pregnancy in teenagers. Methods A case control study conducted at Centro de Atenção à Saúde Integral da Mulher (Caism, in the Portuguese acronym), in Campinas, Brazil, from 2015 to 2017. Three groups were selected: a case-group of adolescents who had repeat pregnancy and two control-groups, one consisting of adolescents who had delivered at first time and another one of adult women with more than one deliveries. Participants were asked about habits, socio-demographics characteristics, reproductive and obstetric history and assessed psychological issues. Results Ninety women were enrolled, 30 in each study group. Adolescents with repeat pregnancy have lower self-esteem scores and more ineffective contraceptive use. When compared with teens at first delivery, they had less schooling level (odds ratio [OR] 4.03 [1.37–11.8]), more school abandon (OR 8.16 [2.36–28.2]) and drugs use (OR 4.97[1.39–17.8]). Non-white skin color (OR 6.2 [1.15–41.0]), drugs use (OR 17.5 [2.62–116.6]) and first sexual intercourse under 15y (OR 18.0[2.82–115.0]) were found as higher risk factors for repeat pregnancy when comparing adolescents and adults. Moreover, adolescents with more than one gestation had lower self-esteem and greater susceptibility to unplanned pregnancy. Conclusion There was an association between repeat pregnancy among adolescents and lower education, early onset of sexual activity, non-white skin color, low use of contraception and increased use of drugs.
Serum Lipid and Leptin Concentrations in Patients with Sheehan Syndrome

Background: Sheehan syndrome (SS) refers to the occurrence of hypopituitarism after parturition. Hypopituitary adults with growth hormone (GH) deficiency have abnormal body composition with increased fat mass. As leptin is secreted almost exclusively by fat cells and the circulating leptin level is proportional to total fat mass, it is expected that abnormal elevations of leptin concentrations are found in GH deficient hypopituitary patients. The present study was undertaken to evaluate the anthropometric, lipid and leptin levels in patients with SS. Materials and Methods: Thirty patients with SS and 30 age and body mass index (BMI) matched controls were part in this study. All patients were stable on conventional replacement therapy for at least 6 months before the study. The subjects underwent detail clinical, biochemical, and hormone analysis. Results: Patients with SS on conventional replacement therapy showed significantly higher mean triglyceride, total cholesterol, low density lipoprotein cholesterol and lower high density cholesterol concentrations. The leptin levels were significantly raised in the patients with SS on standard replacement therapy compared with controls. The difference was more marked in obese cases versus obese controls than in lean cases and controls (P = 0.001). Conclusion: SS, a cause of GH deficiency. Our study demonstrated that patients with SS have an abnormal lipid profile, and raised leptin levels as compared to age and BMI matched controls.
Genomic analysis reveals recurrent deletion of JAK‐STAT signaling inhibitors HNRNPK and SOCS1 in mycosis fungoides

Mycosis fungoides (MF) is the most common cutaneous T‐cell lymphoma (CTCL). Causative genetic alterations in MF are unknown. The low recurrence of pathogenic small‐scale mutations (ie, nucleotide substitutions, indels) in the disease, calls for the study of additional aspects of MF genetics. Here, we investigated structural genomic alterations in tumor‐stage MF by integrating whole‐genome sequencing and RNA‐sequencing. Multiple genes with roles in cell physiology (n = 113) and metabolism (n = 92) were found to be impacted by genomic rearrangements, including 47 genes currently implicated in cancer. Fusion transcripts involving genes of interest such as DOT1L, KDM6A, LIFR, TP53, and TP63 were also observed. Additionally, we identified recurrent deletions of genes involved in cell cycle control, chromatin regulation, the JAK‐STAT pathway, and the PI‐3‐K pathway. Remarkably, many of these deletions result from genomic rearrangements. Deletion of tumor suppressors HNRNPK and SOCS1 were the most frequent genetic alterations in MF after deletion of CDKN2A. Notably, SOCS1 deletion could be detected in early‐stage MF. In agreement with the observed genomic alterations, transcriptome analysis revealed up‐regulation of the cell cycle, JAK‐STAT, PI‐3‐K and developmental pathways. Our results position inactivation of HNRNPK and SOCS1 as potential driver events in MF development.
Extending the developmental origins of disease model: Impact of preconception stress exposure on offspring neurodevelopment

The concept of the developmental origins of health and disease via prenatal programming has informed many etiologic models of health and development. Extensive experimental research in non-human animal models has revealed the impact of in utero exposure to stress on fetal development and neurodevelopment later in life. Stress exposure, however, is unlikely to occur de novo following conception, and pregnancy health is not independent of the health of the system prior to conception. For these reasons, the preconception period is emerging as an important new focus for research on adverse birth outcomes and offspring neurodevelopment. In this review, we summarize the existing evidence for the role of preconception stress exposure on pregnancy health and offspring neurodevelopment across species and discuss the implications of this model for addressing health disparities in obstetrics and offspring outcomes.
Relative periodic orbits form the backbone of turbulent pipe flow

The chaotic dynamics of low-dimensional systems, such as Lorenz or Rössler flows, is guided by the infinity of periodic orbits embedded in their strange attractors. Whether this is also the case for the infinite-dimensional dynamics of Navier–Stokes equations has long been speculated, and is a topic of ongoing study. Periodic and relative periodic solutions have been shown to be involved in transitions to turbulence. Their relevance to turbulent dynamics – specifically, whether periodic orbits play the same role in high-dimensional nonlinear systems like the Navier–Stokes equations as they do in lower-dimensional systems – is the focus of the present investigation. We perform here a detailed study of pipe flow relative periodic orbits with energies and mean dissipations close to turbulent values. We outline several approaches to reduction of the translational symmetry of the system. We study pipe flow in a minimal computational cell at $Re=2500$ , and report a library of invariant solutions found with the aid of the method of slices. Detailed study of the unstable manifolds of a sample of these solutions is consistent with the picture that relative periodic orbits are embedded in the chaotic saddle and that they guide the turbulent dynamics.