Miracle-dz/UniFAR-FTUs huggingface dataset:
Perineural invasion by prostate adenocarcinoma in needle biopsies predicts bone metastasis: Ten year data from the TROG 03.04 RADAR Trial

Perineural invasion (PNI) by prostatic adenocarcinoma is debated as a prognostic parameter. This study investigates the prognostic predictive value of PNI in a series of patients with locally advanced prostate cancer treated with radiotherapy and androgen deprivation using 10 years outcome data from the TROG 03.04 RADAR trial.
Ovarian cyst formation in women of reproductive age receiving mitotane as part of the treatment of adrenocortical carcinoma: Clinical and experimental observations

Mitotane is an adrenolytic drug that is used as an adjuvant to treat adrenocortical carcinoma. This study aimed to evaluate the clinical course and pathogenetic mechanisms underlying ovarian cyst formation in women of reproductive age diagnosed with adrenocortical carcinoma and being treated with mitotane as an adjuvant to surgery.
ML264 inhibits osteosarcoma growth and metastasis via inhibition of JAK2/STAT3 and WNT/β‐catenin signalling pathways

Osteosarcoma, the most common bone malignancy, has a high morbidity rate and poor prognosis. Krüppel‐like factor 5 (KLF5) is a key transcriptional regulator of cellular proliferation whose overexpression is observed in osteosarcoma cell lines (U2OS, 143B, MG63 and SAOS2). ML264, a small‐molecule inhibitor of KLF5, exerts antiproliferative effects in colorectal cancer; however, its function in osteosarcoma remains unknown. Here, we explored the possible antitumour effects of ML264 on 143B and U2OS cell lines and murine tumour xenograft model. ML264 suppressed proliferation and clonogenic ability of osteosarcoma cells in a dose‐dependent manner. Moreover, ML264 induced G0/G1 cell cycle arrest, with no influence on apoptosis, and inhibited the migratory and invasive abilities of osteosarcoma cells, as demonstrated by wound‐healing and Transwell assays. Exposure to ML264 reduced the mRNA and protein levels of molecules associated with epithelial‐mesenchymal transition phenotype, including N‐cadherin, vimentin, Snail, matrix metalloproteinase (MMP) 9 and MMP13. Inhibition of signal transducer and activator of transcription (STAT) 3 phosphorylation and Wnt signalling was also observed. In the murine model of osteosarcoma, tumour growth was efficiently suppressed following a 10‐day treatment with ML264. Collectively, our findings demonstrate the potential value of ML264 as a novel anticancer drug for osteosarcoma.
The Effects of Low-Nickel Diet Combined with Oral Administration of Selected Probiotics on Patients with Systemic Nickel Allergy Syndrome (SNAS) and Gut Dysbiosis

Background: Nickel (Ni) oral consumption may elicit systemic reactions in patients affected by systemic nickel allergy syndrome (SNAS), including gastrointestinal symptoms, which in turn are associated with gut dysbiosis. We evaluated the effects of a low-Ni diet alone or in combination with the oral consumption of appropriate probiotics on Ni-sensitivity and urinary dysbiosis markers in SNAS patients. Methods: n = 51 patients with SNAS and concomitant intestinal dysbiosis were enrolled in the study. According to the urinary indican/skatole levels, quantified through a colorimetric and a high-performance liquid chromatographic method, respectively, patients were assigned to a dysbiosis type/grade and followed a low-Ni diet for three months. Along with the diet, 22 patients also consumed probiotics based on the dysbiosis type. In particular, a Lactobacilli- or Bifidobacteria-containing formulation was administered to patients with fermentative or putrefactive dysbiosis, respectively, while a broad-spectrum probiotic formulation containing both Lactobacilli and Bifidobacteria was administered to patients with mixed dysbiosis. After three months, patients were invited to repeat the Ni-stimulation and the dysbiosis tests. Results: The fermentative dysbiosis group represented the largest group followed by the mixed dysbiosis group, while only two patients had putrefactive dysbiosis. Overall, at three months of treatment in general (diet alone with or without probiotics), the Ni-sensitivity and dysbiosis levels were strongly ameliorated. The association of a low-Ni diet with a specific probiotic oral supplementation was significantly more effective in decreasing dysbiosis levels or reaching eubiosis than with diet alone. Conclusion: Our results, while confirming the benefits of a low-Ni diet in SNAS patients, strongly support that appropriate adjuvant treatment with probiotics significantly helps to improve intestinal dysbiosis or restore a healthy microbiota.
Comparative Efficacy of Targeted Therapies in Patients with Non-Small Cell Lung Cancer: A Network Meta-Analysis of Clinical Trials

This study aims to investigate the efficacy of targeted therapies in the treatment of non-small cell lung cancer (NSCLC) by using a network meta-analysis of clinical trials. PubMed, EMBASE, Cochrane Library, and Clinicaltrials.gov were searched by using keywords related to the topic on 19 September 2018. Two investigators independently selected relevant trials by pre-determined criteria. A pooled response ratio (RR) for overall response rate (ORR) and a hazard ratio (HR) for progression-free survival (PFS) were calculated based on both the Bayesian and frequentist approaches. A total of 128 clinical trials with 39,501 participants were included in the final analysis of 14 therapeutic groups. Compared with chemotherapy, both ORR and PFS were significantly improved for afatinib, alectinib, and crizotinib, while only PFS was significantly improved for cabozantinib, ceritinib, gefitinib, and osimertinib. Consistency was observed between the direct and indirect comparisons based on the Bayesian approach statistically and the frequentist approach visually. Cabozantinib and alectinib showed the highest probability for the first-line treatment ranking in ORR (62.5%) and PFS (87.5%), respectively. The current network meta-analysis showed the comprehensive evidence-based comparative efficacy of different types of targeted therapies, which would help clinicians use targeted therapies in clinical practice.
Weight-lowering Effects of Glucagon-like Peptide-1 Receptor Agonists and Detection of Breast Cancer Among Obese Women with Diabetes

Supplemental Digital Content is available in the text. Background: It has been proposed that the weight loss associated with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may improve detection of breast cancer in patients undergoing this treatment. We aimed to determine whether the weight-lowering effects of GLP-1 RAs are associated with an increased detection of breast cancer among obese women with type 2 diabetes. Methods: Using the UK Clinical Practice Research Datalink, we conducted a propensity score-matched cohort study among female obese patients with type 2 diabetes newly treated with antidiabetic drugs between 1 January 2007 and 31 January 2018. New users of GLP-1 RAs (n = 5,510) were matched to new users of second- to third-line noninsulin antidiabetic drugs (n = 5,510). We used time-dependent Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of breast cancer associated with different GLP-1 RA maximal weight loss categories (<5%, 5%–10%, >10%). Results: Breast cancer incidence gradually increased with GLP-1 RA maximal weight loss categories, with the highest HR observed for patients achieving at least 10% weight loss (HR = 1.8, 95% CI = 1.1, 2.8). In secondary analyses, the HR for >10% weight loss was highest in the 2–3 years since treatment initiation (HR = 2.9, 95% CI = 1.2, 6.9). Conclusions: In this population-based study, the detection of breast cancer gradually increased with GLP-1 RA weight loss categories, particularly among those achieving >10% weight loss. These results are consistent with the hypothesis that substantial weight loss with GLP-1 RAs may improve detection of breast cancer among obese patients with type 2 diabetes.
Effect of X-rays on transcript expression of rat brain microvascular endothelial cells: role of calcium signaling in X-ray-induced endothelium damage

Abstract Radiation-induced brain edema is a serious adverse effect of radiotherapy. Although there are many causes of radiation-induced brain edema, the pathogenesis is not clear and clinical treatment is not ideal. Therefore, knowing the differential expression of the brain microvascular endothelial cell (BMEC) transcriptome after brain radiotherapy may shed light on the pathogenesis of radiation-induced brain edema. The present study used RNA-Seq technique to identify 383 BMEC transcripts differentially expressed (many 2-fold or higher; P < 0.05) between control and X-ray–treated primary cultured rat BMECs. Compared with controls, X-ray–treated BMECs had 183 significantly up-regulated transcripts and 200 significantly down-regulated transcripts. The differentially expressed genes were associated with the biological processes of the cell cycle, apoptosis, vascular permeability, and extracellular junctions. The functional changes identified in the X-ray–treated BMECs included Ca2+ signaling, phosphoinositide 3-kinase–Akt signaling, and methionine degradation. These results indicated that transcript expression was substantially affected by radiation exposure and the proteins encoded by these differentially expressed genes may play a significant role in radiotherapy-induced brain edema. Our findings provide additional insight into the molecular mechanisms of radiation-induced brain edema and may be helpful in the development of clinical treatment of this adverse reaction to radiotherapy.
Trauma and Suicide

Abstract This pilot study explored suicide risk in patients suffering from trauma and psychosis. Forty-seven participants diagnosed with schizophrenia spectrum disorders participated in the study. An archival design was used to identify the severity of suicide risk in participants with trauma and psychosis. Data included a chart review of documented trauma and responses to the Childhood Experience of Care and Abuse Questionnaire, Columbia–Suicide Severity Rating Scale, Beck Depression Inventory-II, and the Positive and Negative Syndrome Scale. Results of a linear regression indicated that chart-documented trauma and heightened depression scores were predictive of increased suicidality. Results suggest that, for patients with schizophrenia, depression severity and chart-documented trauma may be strong predictors of suicidality. Interestingly, data also revealed that, although depression and trauma were predictors of suicidality, psychosis was not. The implications of these results are discussed, in addition to suggestions for future research.
Perceptions and utilization of traditional healing among Marshallese adults residing in Arkansas

1 College of Pharmacy, University of Arkansas forMedical Sciences Northwest, 1125 N. College Ave, Fayetteville, AR, USA, Email: tadickey@uams.edu, Lmlpiel@uams.edu, twarmack@uams.edu, jshudson@uams.edu, vsseaton@uams.edu 2 Office of Community Health and Research, University of Arkansas forMedical Sciences Northwest, 1125 N. College Ave, Fayetteville, AR, USA, E-mail: MBRowland@uams.edu, rspurvis@uams.edu 3 College ofMedicine, University of Arkansas forMedical Sciences Northwest, 1125 N. College Ave, Fayetteville, AR 72703-5011, USA, E-mail: SRiklon@uams.edu, PAMcelfish@uams.edu
Loss of RBBP4 results in defective inner cell mass, severe apoptosis, hyperacetylated histones and preimplantation lethality in mice†

Abstract Retinoblastoma-binding protein 4 (RBBP4) (also known as chromatin-remodeling factor RBAP48) is an evolutionarily conserved protein that has been involved in various biological processes. Although a variety of functions have been attributed to RBBP4 in vitro, mammalian RBBP4 has not been studied in vivo. Here we report that RBBP4 is essential during early mouse embryo development. Although Rbbp4 mutant embryos exhibit normal morphology at E3.5 blastocyst stage, they cannot be recovered at E7.5 early post-gastrulation stage, suggesting an implantation failure. Outgrowth (OG) assays reveal that mutant blastocysts cannot hatch from the zona or can hatch but then arrest without further development. We find that while there is no change in proliferation or levels of reactive oxygen species, both apoptosis and histone acetylation are significantly increased in mutant blastocysts. Analysis of lineage specification reveals that while the trophoblast is properly specified, both epiblast and primitive endoderm lineages are compromised with severe reductions in cell number and/or specification. In summary, these findings demonstrate the essential role of RBBP4 during early mammalian embryogenesis. Summary sentence RBBP4 is essential during early embryo development in vivo, loss of RBBP4 results in defective inner cell mass (ICM), severe DNA damage and apoptosis, hyperacetylated histones and preimplantation lethality in mice.
Influence of Phosphorus Fertilizer on Potato Seed Production in Acid Soils in Kenya

One of the major challenges facing potato (Solanum Tuberosum L) production in Kenya is the inadequate supply of high-quality seed. The required amount of potato seed in Kenya is about 70,000 tones annually but, only 1 % is available. Otherwise, farmers use low quality farm saved seed (KEPHIS, 2016). A major contributor to this situation is low and declining soil fertility, particularly phosphorus, among other challenges. Unfortunately, there is no available phosphorus fertilizer rate recommendation for seed potato production in Kenya. This hinders economic utilization of phosphorus fertilizers to achieve optimal production of quality potato seed in Kenya where its deficiencies are dominant. Therefore, this study investigated influence of different rates of phosphorus fertilizer on seed potato tuber yield and quality in three acidic (pH ≤ 5.8) test sites: Lari, Ainabkoi and Saboti sub Counties. Unica and Shangi varieties were tested. The field experiment was a split plot arrangement in Randomised Complete Block Design (RCBD) with six treatments (0 N & 0 P), 0, 30, 60, 90 and 120 kg ha-1 phosphorus, replicated three times. Data collected included tuber weight, number of tubers, tuber grade, number of eyes per tuber, tuber specific density and final germination percentage. To monitor soil nutrient dynamics, soil pH, soil available phosphorus, total nitrogen, total carbon, potassium, calcium, magnesium, copper, iron, zinc, sodium and exchangeable acidity (Lari only) were determined at planting while available phosphorus and potato tuber phosphorus were determined at harvesting. Data was statistically analysed using ANOVA at 5 % confidence levels with General Statistics (GENSTAT) and excel softwares. Results indicated that phosphorus rate significantly influenced seed tuber yield in the test sites. At Saboti, (0N & 0P) and no phosphorus application treatments for Shangi and Unica resulted in the highest seed tuber yield of 33.7 t ha-1 and 33.2 t ha-1, respectively. At Ainabkoi, application of 60 kg ha-1 and 30 kg ha-1 phosphorus produced the highest seed tuber yields of 20.0 t ha-1 and 18.9 t ha-1 of Shangi and Unica, respectively. In Lari, application of 60 kg ha-1 and 90 kg ha-1 phosphorus produced the highest seed tuber yields of 19.0 t ha-1 and 10.4 t ha-1 of Shangi and Unica, respectively. Unica had better final germination percentage than Shangi. During the season, there was a build-up of soil available phosphorus. Thus, there is need for farmers to test their soils at the onset of every potato season.
Maternal Outcome of Cases of Placenta Previa with and without Morbidly Adherent Placenta at King Abdul-Aziz University Hospital, Saudi Arabia

Introduction: Worldwide increasing cesarean section rates are expected to have a parallel increase in the number of cases of Placenta Previa with all the expected complications, including pathologically adherent placenta. This morbidly adherent placenta constitutes a serious and possibly a life threatening complication. An efficient team capable for managing possible complicated situations will be able to reduce mortality and morbidity. Objectives: The aim of our study was to evaluate maternal outcome in cases of Placenta Previa with and without morbidly adherent placenta. Methods: Analysis of all pregnancies complicated by antepartum hemorrhage during the period from January 2013 to September 2017 at King Abdul-Aziz University Hospital (KAUH), Jeddah, Kingdom of Saudi Arabia (KSA) was done. Cases of Placenta Previa with gestational age > 28 weeks were included. They were classified into 2 groups; Group (A) included Placenta Previa cases without morbidly adherent placenta and Group (B) included cases with morbidly adherent placenta. Maternal outcomes were recorded. Results: Placenta Previa was the leading cause of antepartum hemorrhage constituting 76.8%, out of them 52% were unbooked. Morbidly adherent placenta constituted 13.5% of total Placenta Previa cases and was diagnosed prenatally in only 1 case. Morbidity rate in placenta previa patients with adherent placenta (Group B) was higher than in placenta previa without adherent placenta (Group A). We considered the occurrence of intrapartum hypovolemic shock, Intensive care unit admission, surgical complications and peripartum hysterectomy as parameters for morbidity. P value for hypovolemic shock was insignificant (P = 0.580), significant for Intensive care unit admission (P = 0.008), significant for surgical complications (P = 0.009) and significant for peripartum hysterectomy
Lactate, Heart Rate and Rating of Perceived Exertion Responses to Shorter and Longer Duration CrossFit® Training Sessions

The aim of this study was to analyze blood lactate concentration (LAC), heart rate (HR), and rating perceived exertion (RPE) during and after shorter and longer duration CrossFit® sessions. Nine men (27.7 ± 3.2 years; 11.3 ± 4.6% body fat percentage and training experience: 41.1 ± 19.6 months) randomly performed two CrossFit® sessions (shorter: ~4 min and longer: 17 min) with a 7-day interval between them. The response of LAC and HR were measured pre, during, immediately after, and 10, 20, and 30 min after the sessions. RPE was measured pre and immediately after sessions. Lactate levels were higher during the recovery of the shorter session as compared with the longer session (shorter: 15.9 ± 2.2 mmol/L/min, longer: 12.6 ± 2.6 mmol/L/min; p = 0.019). There were no significant differences between protocols on HR during (shorter: 176 ± 6 bpm or 91 ± 4% HRmax, longer: 174 ± 3 bpm or 90 ± 3% HRmax, p = 0.387). The LAC was significantly higher throughout the recovery period for both training sessions as compared to pre-exercise. The RPE was increased immediately after both sessions as compared to pre-exercise, while there was no significant difference between them (shorter: 8.7 ± 0.9, longer: 9.6 ± 0.5; p = 0.360). These results demonstrated that both shorter and longer sessions induced elevated cardiovascular responses which met the recommendations for gains in cardiovascular fitness. In addition, both training sessions had a high metabolic and perceptual response, which may not be suitable if performed on consecutive days.
OBSERVATIONS ON THE ECOLOGY AND REPRODUCTION OF THE NEW ZEALAND LEIOPELMID FROGS

Field surveys of leiopelmid frogs in New Zealand show ecological separation of the sympatric Leiopelma archeyi and L. hochstetteri, but habitats of the allopatric L. archeyi and L. hamiltoni are similar. Differences in coloration, size, and body proportions are described. Snout-vent lengths of frogs are 7-37 mm in L. archeyi, 10-44 mm in L. hochstetteri, and 10-49 mm in L. hamiltoni, while an undescribed subfossil species probably attained 100 mm. Leiopelma archeyi and L. hamiltoni are similar in body proportions, but L. hochstetteri is more robust, with broader limbs and body but shorter snout and digits. Sexual dimorphism of the forelimbs occurs in L. hochstetteri, but not in the other two species. Amplexus and breeding of Leiopelnm in captivity are detailed, including the development of L. hamiltoni which was previously unknown. The frogs appear to be mostly nocturnal, although some captive L. archeyi emerged from cover by day. Leiopelma hamiltoni on Maud Island emerged in greater numbers and tended to climb higher up in vegetation on wet nights. This study further emphasizes the dichotomy between L. hochstetteri and the other two closely related species. A revised identification key to the three species and their larvae is presented.
Human anti-Gal heavy chain genes

Anti-Gal is the most abundant natural Ab known in humans. It interacts specifically with the carbohydrate structure Gal{alpha}1-3Gal{beta}1-4GlcNAc-R (termed the {alpha}-galactosyl epitope), constitutes approximately 1% of circulating Ig, and is found in all three isotypes in the serum. Anti-Gal is produced in Old World monkeys, apes, and humans, and in no other mammalian species. The objective of this study was to determine the V{sub H} genes involved in the synthesis of anti-Gal. B lymphocytes from various individuals were transformed by EBV, the clones producing anti-Gal were isolated, the specificity and affinity of the Abs were determined, and the V{sub H} genes were sequenced. The affinity of anti-Gal clones for the free radiolabeled {alpha}-galactosyl epitope ranged between 1.1 x 10{sup 6} M{sup -1} and 5 x 10{sup 8} M{sup -1}. Eight of the nine clones studied used V{sub H}3 family genes and one clone used a V{sub H}1 family gene. Four of the five V{sub H}3 genes used were found to form a cluster of related sequences, suggesting that functional constraints may lead to the use of V{sub H}3 genes with structural motifs that are suited for specific interactions with the {alpha}-galactosyl epitope. Comparison with known germ-line sequences for all themore » clones studied and analysis of autologous germ-line genes in two of the clones indicate that anti-Gal V{sub H} genes undergo somatic mutations. These somatic mutations may provide a pool of variants that are available for affinity maturation. « less
Rickettsial Infection in Patients with Acute Febrile Illness at a Tertiary Care Hospital in Bengaluru, India - Serological, Demographic and Clinical Profile

Background and Objectives: Rickettsial infections are under recognised cause of acute febrile illness (AFI) in India. The reason being low index of suspicion, the absence of specific signs/ symptoms and lack of access to confirmatory laboratory tests. These diseases have a high mortality, which can be averted if diagnosed and treated early. WeilFelix test is the cheapest and widely used test for diagnosis in India. The present study was undertaken with the objective of evaluating the patients with AFI, for rickettsial infection using WeilFelix test and study their demographic and clinical profile. Materials and Methods: One hundred Patients with AFI, from June 2015 to December 2016 were evaluated for Rickettsial infection. Detailed history, signs, symptoms were recorded. The serum samples were analysed by Weil-Felix test. Original Research Article Chunchanur et al.; IJTDH, 32(4): 1-6, 2018; Article no.IJTDH. 44504 2 Results: Of the 100 patients, 69 showed a titre of 1:80/>. The disease was more common in children and in the cooler months. Rash, headache, vomiting, pain abdomen and altered sensorium were common symptoms. Most common signs were hepatomegaly/ splenomegaly (51%), rash (40%), CNS involvement (26%). All 69 patients diagnosed with Rickettsial infection, were started on Doxycycline, however 07% of patients succumbed. Interpretation and Conclusions: Rickettsial infection should be considered in the differential diagnosis of AFI, especially when associated with rash, gastrointestinal symptoms, seasonality etc. Weil Felix test is useful for initial diagnosis and timely treatment of Rickettsial infection. Delay in diagnosis and treatment can lead to increased mortality.