Miracle-dz/UniFAR-FTUs huggingface dataset:
Multiplex Quantitative Analysis of Tumor-Infiltrating Lymphocytes and Immunotherapy Outcome in Metastatic Melanoma

Purpose: Because durable response to programmed cell death 1 (PD-1) inhibition is limited to a subset of melanoma patients, new predictive biomarkers could have clinical utility. We hypothesize that pretreatment tumor-infiltrating lymphocyte (TIL) profiles could be associated with response. Experimental Design: Pretreatment whole tissue sections from 94 melanoma patients treated with anti–PD-1 therapy were profiled by multiplex immunofluorescence to perform TIL quantification (CD4, CD8, CD20) and assess TIL activation (CD3, GZMB, Ki67). Two independent image analysis technologies were used: inForm (PerkinElmer) to determine cell counts, and AQUA to measure protein by quantitative immunofluorescence (QIF). TIL parameters by both methodologies were correlated with objective response or disease control rate (ORR/DCR) by RECIST 1.1 and survival outcome. Results: Pretreatment lymphocytic infiltration, by cell counts or QIF, was significantly higher in complete or partial response than in stable or progressive disease, particularly for CD8 (P < 0.0001). Neither TIL activation nor dormancy was associated with outcome. CD8 associations with progression-free survival (HR > 3) were independently significant in multivariable analyses and accounted for similar CD3 associations in anti–PD-1-treated patients. CD8 was not associated with melanoma prognosis in the absence of immunotherapy. Predictive performance of CD8 cell count (and QIF) had an area under the ROC curve above 0.75 (ORR/DCR), which reached 0.83 for ipilimumab plus nivolumab. Conclusions: Pretreatment lymphocytic infiltration is associated with anti–PD-1 response in metastatic melanoma. Quantitative TIL analysis has potential for application in digital precision immuno-oncology as an “indicative” companion diagnostic.
Interventions to enhance access to and utilization of formal community care services for home dwelling persons with dementia and their informal carers. A scoping review

Abstract Objectives: Home dwelling people with dementia and their informal carers often do not receive the formal care services they need. This study examined and mapped the research regarding interventions to improve access and use of formal community care services. Method: This is a scoping review with searches in PubMed, CINAHL, PsychINFO, Medline, Cochrane Database of Systematic Reviews, Social Science Citation index and searches of grey literature in international and national databases. Studies were categorized according to the measure used to enhance access or use. Results: From international databases, 2833 studies were retrieved, 11 were included. Five studies were included from other sources. In total, 16 studies published between 1989 and 2018 were examined; seven randomized controlled trials, six pretest-posttest studies and three non-randomized controlled studies. Sample sizes varied from 29 to 2682 participants, follow-up from four weeks to four years. Five types of interventions were identified: Case management, monetary support, referral enhancing, awareness & information focused and inpatient focused. Only two studies had access or use of community services as the primary outcome. Fourteen studies, representing all five types of interventions, had positive effects on one or more relevant outcomes. Two interventions had no effect on relevant outcomes. Conclusion: The included studies varied widely regarding design, type of intervention and outcomes. Based on this, the evidence base for interventions to enhance access to and use of formal community services is judged to be limited. The most studied type of intervention was case management. More research is recommended in this field.
Associations between Breastfeeding and Type 2 Diabetes Mellitus and Glycemic Control in Parous Women: A Nationwide, Population-Based Study

We investigated associations between breastfeeding duration and number of children breastfed and type 2 diabetes mellitus (T2DM) and glycemic control among parous women. We performed a cross-sectional analysis of data for 9,960 parous women from the Korea National Health and Nutritional Examination Survey (2010 to 2013). Having ever breastfed was inversely associated with prevalent T2DM (adjusted odds ratio [OR], 0.60; 95% confidence interval [CI], 0.42 to 0.87). All ranges of total and average breastfeeding duration showed inverse associations with T2DM. Even short periods of breastfeeding were inversely associated with T2DM (adjusted OR, 0.61; 95% CI, 0.38 to 0.99 for a total breastfeeding duration ≤12 months; adjusted OR, 0.65; 95% CI, 0.42 to 0.99 for an average breastfeeding duration per child ≤6 months). A longer duration of breastfeeding was associated with better glycemic control in parous women with T2DM (P trend=0.004 for total breastfeeding duration; P trend <0.001 for average breastfeeding duration per child). Breastfeeding may be associated with a lower risk of T2DM and good glycemic control in parous women with T2DM. Breastfeeding may be a feasible method to prevent T2DM and improve glycemic control.
EFEK EKSTRAK DAUN PEGAGAN (Centella asiatica) DALAM MEMPERCEPAT PENYEMBUHAN LUKA TERKONTAMINASI PADA TIKUS PUTIH (Rattus novergicus) GALUR WISTAR

Insiden luka terkontaminasi sangat tinggi dalam kehidupan sehari-hari dan memerlukan perawatan yang tepat untuk mencegah terjadinya infeksi lebih lanjut. Pada umunya luka terkontaminasi dirawat menggunakan povidone iodine 10% yang memiliki efek samping yaitu iritasi, alergi, residu, toksik pada sel dan rasa panas pada kulit. Daun pegagan dapat digunakan sebagai alternatif perawatan luka terkontaminasi karena mengandung triterpene yang berfungsi sebagai antiinflamasi, antibakteri dan mendorong pembentukan kolagen tipe I serta mengandung minyak esensial yang berfungsi sebagai antibakteri. Penelitian ini dilakukan untuk mengetahui Efek Ekstrak Daun Pegagan (Centella asiatica) dalam Mempercepat Penyembuhan Luka Terkontaminasi pada Tikus Putih (Rattus norvegicus) Galur Wistar. Penelitian ini termasuk true experiment dengan desain post test group only. Sampel yang digunakan adalah dua puluh ekor tikus putih jantan yang dipilih dengan simple random sampling dan dibagi menjadi lima kelompok yaitu kelompok ekstrak daun pegagan 25%, 50% dan 75%, serta kelompok povidone iodine 10% dan aquades sebagai kontrol. Pengambilan data setiap 24 jam selama 12 hari. Data yang diperoleh dianalisis dengan one way anova kemudian dilanjutkan dengan uji Post Hoc dan didapatkan hasil bahwa ekstrak daun pegagan dapat mempercepat penyembuhan luka (dengan p value = 0,008; < 0,05) dan konsentrasi 25% memiliki efek penyembuhan luka yang paling baik dibanding konsentrasi 50% dan 75%. Kesimpulan dari penelitian ini adalah ekstrak daun pegagan dapat mempercepat penyembuhan luka terkontaminasi. Disarankan untuk dilakukan penelitian secara mikroskopis terhadap proses penyembuhan luka terkontaminasi. Kata kunci : Ekstrak Daun Pegagan, Luka Terkontaminasi, Penyembuhan Luka
[National variation in molecular diagnostics in metastatic lung cancer].

OBJECTIVE The objective of this study is to determine at a national level whether patients with metastatic non-small cell lung cancer (NSCLC) are adequately tested for EGFR mutations and ALK rearrangement, because targeted therapy is tailored to the results of molecular diagnostics. DESIGN Retrospective cohort study. METHOD Data from all patients with metastatic non-squamous NSCLC diagnosed in 2013 or 2015 were identified from the Netherlands Cancer Registry, and coupled with data from the Netherlands national pathology registry (PALGA). Using information extracted from PALGA we determined what percentage of the tumours were tested for EGFR or KRAS mutations and ALK rearrangement, identified the variables that were associated with the performance of molecular diagnostics and investigated the differences between 48 laboratories. RESULTS A total of 6,619 patients were included (2013: n = 3,195; 2015: n = 3,424). In 2013, EGFR or KRAS testing was performed on 73.1% of the tumours (variation between laboratories 30.6-91.7%); in 2015 this was 78.9% (variation 40.0-91.0%). In 2013 49.5% of the tumours without EGFR or KRAS mutations underwent ALK testing (variation between laboratories 6.3-100%) and in 2015 ALK testing was performed on 77.4% (32.5-100%). In 2015, 6 and 7 laboratories tested significantly fewer EGFR and ALK tests, respectively, than the national average. CONCLUSION In 2013, molecular testing for EGFR and KRAS mutations and, in particular, for ALK rearrangement was suboptimal. EGFR and ALK testing was performed significantly more often in 2015. Despite this increase, there is room for improvement in a number of laboratories and hospitals, considering that some patients were possibly wrongly not eligible for targeted therapy.
Sexual system, reproductive cycle and embryonic development of the red-striped shrimp Lysmata vittata, an invader in the western Atlantic Ocean

Several decapod crustaceans are invaders, but little is known about the biological characteristics that potentiate the success of these decapods in invaded ecosystems. Here, we evaluate and describe some aspects of the reproductive biology and development of Lysmata vittata, an invasive shrimp species in the Atlantic Ocean. In addition, we intend to provide important insights into the biology of invasion by comparing the reproductive traits of this shrimp with some of the predictions about aquatic invasive species. We used experimental and laboratory observations to evaluate the functionality of protandric simultaneous hermaphroditism (PSH), the macro and microscopic development of the ovarian portion of the ovotestes, the reproductive cycle, and the embryonic development of L. vittata. We confirm the functionality of PSH in L. vittata. This shrimp has a rapid reproductive cycle; the ovarian portion of the ovotestes develops (mean ± SD) 6.28 ± 1.61 days after spawning. Embryonic development also occurs over a short time, with a mean (± SD) of 8.37 ± 0.85 days. The larvae hatch without macroscopically visible yolk reserves. Our study provides evidence that the invasive shrimp L. vittata has reproductive and embryonic developmental characteristics (i.e., short generation time and high reproductive capacity) that may be favorable to the establishment of populations during invasive processes.
Analysis of the Behavior of SMA Mixtures with Different Fillers Through the Semicircular Bend (SCB) Fracture Test

In most cases, stone mastic asphalt (SMA) mixtures placed in thin layers and subjected to stress develop early cracks (potentially resulting from being improperly affixed to the underlying layer, placed over previously cracked asphalt pavement, or placed over Portland cement concrete slabs). However, the filler used in SMA production is very influential on the performance of the mix. Fillers used in this type of mixture have a low plastic index or are inert (calcium carbonate or lime), so it is important to understand the effect of each material on the possible fissuring and cracking process of the SMA mixture. The objective of this study is to present an evaluation of the behavior of SMA asphalt mixtures with different types of filler and at different temperatures using the semicircular bend (SCB) fracture energy test. This research compares results between fracture energy and different types of filler in SMA asphalt mixtures at temperatures ranging from −10 to 25 °C.
Are school‐based physical activity interventions effective and equitable? A meta‐analysis of cluster randomized controlled trials with accelerometer‐assessed activity

The prevalence of childhood obesity is increasing at epidemic rates globally, with widening inequalities between advantaged and disadvantaged groups. Despite the promise of schools as a universal context to access and influence all children, the potential of school‐based interventions to positively impact children's physical activity behaviour, and obesity risk, remains uncertain. We searched six electronic databases to February 2017 for cluster randomized trials of school‐based physical activity interventions. Following data extraction, authors were sent re‐analysis requests. For each trial, a mean change score from baseline to follow‐up was calculated for daily minutes of accelerometer‐assessed moderate‐to‐vigorous physical activity (MVPA), for the main effect, by gender, and by socio‐economic position (SEP). Twenty‐five trials met the inclusion criteria; 17 trials provided relevant data for inclusion in the meta‐analyses. The pooled main effect for daily minutes of MVPA was nonexistent and nonsignificant. There was no evidence of differential effectiveness by gender or SEP. This review provides the strongest evidence to date that current school‐based efforts do not positively impact young people's physical activity across the full day, with no difference in effect across gender and SEP. Further assessment and maximization of implementation fidelity is required before it can be concluded that these interventions have no contribution to make.
White matter during concussion recovery: Comparing diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI)

Concussion pathophysiology in humans remains incompletely understood. Diffusion tensor imaging (DTI) has identified microstructural abnormalities in otherwise normal appearing brain tissue, using measures of fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD). The results of prior DTI studies suggest that acute alterations in microstructure persist beyond medical clearance to return to play (RTP), but these measures lack specificity. To better understand the observed effects, this study combined DTI with neurite orientation dispersion and density imaging (NODDI), which employs a more sophisticated description of water diffusion in the brain. A total of 66 athletes were recruited, including 33 concussed athletes, scanned within 7 days after concussion and at RTP, along with 33 matched controls. Both univariate and multivariate methods identified DTI and NODDI parameters showing effects of concussion on white matter. Spatially extensive decreases in FA and increases in AD and RD were associated with reduced intra‐neurite water volume, at both the symptomatic phase of injury and RTP, indicating that effects persist beyond medical clearance. Subsequent analyses also demonstrated that concussed athletes with higher symptom burden and a longer recovery time had greater reductions in FA and increased AD, RD, along with increased neurite dispersion. This study provides the first longitudinal evaluation of concussion from acute injury to RTP using combined DTI and NODDI, significantly enhancing our understanding of the effects of concussion on white matter microstructure.
Information, Systems and Information Systems: Making Sense of the Field

From the Publisher: This book makes sense of the large, sprawling, confusing field of information systems (IS) and helps readers distinguish between information systems and information technology (IT). Based on author Peter Checkland's years of experience working with top international companies, this book explores the concept of IS as well as its practice in the real world.
Diarrheal bacterial pathogens and multi-resistant enterobacteria in the Choqueyapu River in La Paz, Bolivia

Water borne diarrheal pathogens might accumulate in river water and cause contamination of drinking and irrigation water. The La Paz River basin, including the Choqueyapu River, flows through La Paz city in Bolivia where it is receiving sewage, and residues from inhabitants, hospitals, and industry. Using quantitative real-time PCR (qPCR), we determined the quantity and occurrence of diarrheagenic Escherichia coli (DEC), Salmonella enterica, Klebsiella pneumoniae, Shigella spp. and total enterobacteria in river water, downstream agricultural soil, and irrigated crops, during one year of sampling. The most abundant and frequently detected genes were gapA and eltB, indicating presence of enterobacteria and enterotoxigenic E. coli (ETEC) carrying the heat labile toxin, respectively. Pathogen levels in the samples were significantly positively associated with high water conductivity and low water temperature. In addition, a set of bacterial isolates from water, soil and crops were analyzed by PCR for presence of the genes blaCTX-M, blaKPC, blaNDM, blaVIM and blaOXA-48. Four isolates were found to be positive for blaCTX-M genes and whole genome sequencing identified them as E. coli and one Enterobacter cloacae. The E. coli isolates belonged to the emerging, globally disseminated, multi-resistant E. coli lineages ST648, ST410 and ST162. The results indicate not only a high potential risk of transmission of diarrheal diseases by the consumption of contaminated water and vegetables but also the possibility of antibiotic resistance transfer from the environment to the community.
An integrated framework for the identification of potential miRNA-disease association based on novel negative samples extraction strategy

ABSTRACT MicroRNAs (miRNAs) play an important role in prevention, diagnosis and treatment of human complex diseases. Predicting potential miRNA-disease associations could provide important prior information for medical researchers. Therefore, reliable computational models are expected to be an effective supplement for inferring associations between miRNAs and diseases. In this study, we developed a novel calculative model named Negative Samples Extraction based MiRNA-Disease Association prediction (NSEMDA). NSEMDA filtered reliable negative samples by two positive-unlabeled learning models, namely, the Spy and Rocchio techniques and calculated similarity weights for ambiguous samples. The positive samples, reliable negative samples and ambiguous samples with similarity weights were used to construct a Support Vector Machine-Similarity Weight model to predict miRNA-disease associations. NSEMDA improved the credibility of negative samples and reduced the impact of noise samples by introducing ambiguous samples with similarity weights to train prediction model. As a result, NSEMDA achieved the AUC of 0.8899 in global leave-one-out cross validation (LOOCV) and AUC of 0.8353 under local LOOCV. In 100 times 5-fold cross validation, NSEMDA obtained an average AUC of 0.8878 and standard deviation of 0.0014. These AUCs are higher than many classical models. Besides, we also carried out three kinds of case studies to evaluate the performance of NSEMDA. Among the top 50 potential related miRNAs of esophageal neoplasms, lung neoplasms and carcinoma hepatocellular predicted by NSEMDA, 46, 50 and 45 miRNAs were verified to be associated with the investigated disease by experimental evidences, respectively. Therefore, NSEMDA would be a reliable calculative model for inferring miRNA-disease associations.
The Role of Prostaglandins in Disrupted Gastric Motor Activity Associated With Type 2 Diabetes

Patients with diabetes often develop gastrointestinal motor problems, including gastroparesis. Previous studies have suggested this gastric motor disorder was a consequence of an enteric neuropathy. Disruptions in interstitial cells of Cajal (ICC) have also been reported. A thorough examination of functional changes in gastric motor activity during diabetes has not yet been performed. We comprehensively examined the gastric antrums of Lepob mice using functional, morphological, and molecular techniques to determine the pathophysiological consequences in this type 2 diabetic animal model. Video analysis and isometric force measurements revealed higher frequency and less robust antral contractions in Lepob mice compared with controls. Electrical pacemaker activity was reduced in amplitude and increased in frequency. Populations of enteric neurons, ICC, and platelet-derived growth factor receptor α+ cells were unchanged. Analysis of components of the prostaglandin pathway revealed upregulation of multiple enzymes and receptors. Prostaglandin-endoperoxide synthase-2 inhibition increased slow wave amplitudes and reduced frequency of diabetic antrums. In conclusion, gastric pacemaker and contractile activity is disordered in type 2 diabetic mice, and this appears to be a consequence of excessive prostaglandin signaling. Inhibition of prostaglandin synthesis may provide a novel treatment for diabetic gastric motility disorders.
Multilab EcoFAB study shows highly reproducible physiology and depletion of soil metabolites by a model grass

There is a dynamic reciprocity between plants and their environment: On one hand, the physiochemical properties of soil influence plant morphology and metabolism, while on the other, root morphology and exudates shape the environment surrounding roots. Here, we investigate both of these aspects as well as the reproducibility of these responses across laboratories. The model grass Brachypodium distachyon was grown in phosphate-sufficient and phosphate-deficient mineral media, as well as in sterile soil extract, within fabricated ecosystem (EcoFAB) devices across four laboratories. Tissue weight and phosphate content, total root length, root tissue and exudate metabolic profiles were found to be consistent across laboratories and distinct between experimental treatments. Plants grown in soil extract were morphologically and metabolically distinct in all laboratories, with root hairs four times longer compared to other growth conditions. Further, plants depleted half of the investigated metabolites from the soil extract. To interact with their environment, plants not only adapt morphology and release complex metabolite mixtures; they also selectively deplete a range of soil-derived metabolites. The EcoFABs utilized here generated high inter-laboratory reproducibility, demonstrating that their value in standardized investigations of plant traits.
Priapisme drépanocytaire : Prise en charge par injections intracaverneuses d'étiléfrine

Les injections intracaverneuses (IIC) d'alphastimulants sont apparues recemment dans l'arsenal therapeutique du priapisme drepanocytaire et seraient efficaces lorsque le priapisme evolue depuis moins de 28 heures. Ce travail a ete realise pour preciser cette efficacite sur une serie importante. De janvier 1996 a septembre 1998, 72 IIC consecutives ont ete faites seules (avant la 6 e heure de priapisme) ou precedees de drainage (dans les priapismes de plus de 6 heures) chez 19 patients drepanocytaires qui presentaient un ou plusieurs episodes de priapisme de bas debit de duree comprise entre 2 heures et 15 jours. L'efficacite des IIC d'etilefrine a ete essentiellement fonction du delai pretherapeutique. Avant la 29 e heure, la detumescence a ete obtenue dans tous les cas, alors que les IIC n'ont ete efficaces que dans 2 cas sur 9 traites apres ce delai. Ceci est conforme aux donnees histologiques experimentales qui observent une necrose des cellules endotheliales et des fibres musculaires lisses caverneuses a partir de la 24 e heure. Neanmoins, la possibilite d'un bon resultat chez des patients traites meme au dela de la 40 e heure (42 heures et 5 jours respectivement pour deux malades), avec une conservation de la capacite erectile, incite a preconiser egalement les IIC dans les priapismes drepanocytaires de longue duree d'evolution, et a reserver la chirurgie aux seuls echecs therapeutiques. Des effets indesirables ont ete releves en post-injection chez 4 patients (douleur generalisee de la verge, douleur retrosternale). Les IIC d'alphastimulants representent actuellement l'une des meilleures armes therapeutiques du priapisme drepanocytaire et devraient permettre de reduire les indications de la chirurgie aux seuls echecs therapeutiques.