Miracle-dz/UniFAR-FTUs huggingface dataset:
Retinoblastoma: A retrospective analysis of 141 patients from 1983 to 2013 at a tertiary care hospital in Nagpur, India

Abstract Purpose: There is scarcity of data regarding clinical presentation and outcome of retinoblastoma patients in India. Objectives: The objective of this study was to assess the clinical profile of retinoblastoma patients in a tertiary care hospital in India from 1983 to 2013. Subjects and Methods: A retrospective analysis of clinical records of 141 patients with retinoblastoma registered from 1983 to 2013 at Government Medical College, Nagpur, India, was conducted. Demographics, clinical features, modes of treatment, and outcome of the patients were assessed. Results: Majority of patients (81 [57.45%]) presented in the age group of 1–3 years and were males. One hundred and fourteen patients (80.85%) had unilateral disease, while rare presentations of trilateral/quadrilateral retinoblastoma were also noted. Proptosis was seen in 81 (57.45%) patients as presenting symptom. Eighty-nine patients (63.12%) had locally invasive disease-involving sites. Forty-four patients (31.19%) developed distant metastasis. Surgical management and external beam radiotherapy were followed in majority of patients. Trend of increased usage of chemotherapy was seen from the mid-1990s. One hundred and twelve patients (79.43%) died with the disease. Conclusions: Data from this study show late diagnosis, leading to poor outcome for patients with advanced retinoblastoma, which is in accordance with data from other developing countries. Even though management of patients changed in accordance with changing standard of care over the decade, mortality remained high.
Haemostatic responsiveness and release of biological response modifiers following cryopreservation of platelets treated with amotosalen and ultraviolet A light.

BACKGROUND Due to the risk of replication of contaminating pathogens, platelets have a limited storage time of 5 days, which can be prolonged to 7 days by the use of pathogen inactivation technologies. Cryopreservation (CP) may be an alternative to permit longer storage periods and increased availability. However, the preparation of platelets can result in secretion of biological response modifiers (BRM), which can cause adverse transfusion reactions in the recipient. We investigated the impact of CP on platelet function and release of BRM in untreated (conventional) and pathogen-inactivated (PI) platelet concentrates. MATERIALS AND METHODS Twelve buffy coat-derived platelet units were treated with amotosalen and ultraviolet A light to inactivate pathogens. Twelve untreated units were used as controls. The 24 units were cryopreserved and in vitro variables were analysed before and after CP. The in vitro variables investigated included platelet surface receptors and activation markers by flow cytometry, and coagulation time by viscoelastography. A panel of BRM, including cytokines, was investigated. RESULTS CP of both conventional and PI platelets resulted in a significant increase of BRM with similar increases of most of the BRM after CP of conventional and PI platelet concentrates. The increase in some of the BRM correlated significantly with shortened coagulation time, increased P-selectin expression, reduced mitochondrial transmembrane potential, and reduced capacity to respond to stimulation with ADP and collagen. DISCUSSION Cryopreservation of both conventional and PI platelets results in secretion of BRM. The increase in some of the BRM correlated with changes in platelet function variables and suggests that BRM release is affected, in part, in a similar way by CP as are changes in platelet function variables. PI with amotosalen and ultraviolet A light in combination with CP did not affect the release of immunomodulatory factors more than CP alone did.
Evaluation of the dietary intake data coding process in a clinical setting: Implications for research practice

Background High quality dietary intake data is required to support evidence of diet-disease relationships exposed in clinical research. Source data verification may be a useful quality assurance method in this setting. The present pilot study aimed to apply source data verification to evaluate the quality of the data coding process for dietary intake in a clinical trial and to explore potential barriers to data quality in this setting. Methods Using a sample of 20 cases from a clinical trial, source data verification was conducted between three sets of data derived documents: transcripts of audio-recorded diet history interviews, matched paper-based diet history forms and outputs from nutrition analysis software. The number of cases and rates of discrepancies between documents were calculated. A total of five in-depth interviews with dietitians collecting and coding dietary data were thematically analysed. Results Some 2024 discrepancies were identified. The highest discrepancy rate was 57.49%, and occurred between diet history interviews and nutrition analysis software outputs. Sources of the discrepancies included both quantities and frequencies of food intake. The highest discrepancy rate was for the food group “vegetable products and dishes”. In-depth interviews implicated recall bias of trial participants as a cause of discrepancies, but dietitians also acknowledged a possible subconscious influence of having to code reported foods into nutrition analysis software programs. Conclusion The accuracy of dietary intake data appeared to depend on the level of detailed food data required. More support for participants on reporting consumption, and incorporating supportive tools to guide estimates of food quantities may facilitate a more consistent coding process and improve data quality. This pilot study offers a novel method and an overview of dietary intake data coding measurement errors. These findings may warrant further investigation in a larger sample.
Postsurgical Opioid Prescriptions and Risk of Long-term Use: An Observational Cohort Study Across the United States.

OBJECTIVE The aim of this study was to evaluate differences in risk of long-term opioid therapy after surgery among an opioid-naive population using varying cutoffs based on days supplied (DS), total morphine milligram equivalents (MME) dispensed, and quantity of pills (QTY) dispensed. BACKGROUND In response to the US opioid crisis, opioid prescription (Rx) limits have been implemented on a state-by-state basis beginning in 2016. However, there is limited evidence informing appropriate prescribing limits, and the effect of these policies on long-term opioid therapy. METHODS Using the MarketScan claims databases, we identified all opioid-naive patients undergoing outpatient surgery between July 1, 2006 and June 30, 2015. We identified the initial postsurgical opioid prescribed, examining the DS, total MME, and QTY dispensed. We used Poisson to estimate adjusted risk differences and risk ratios of long-term opioid use comparing those receiving larger versus smaller volume of opioids. RESULTS We identified 5,148,485 opioid-naive surgical patients. Overall, 55.5% received an opioid for postoperative pain, with median days supply = 5 and median total MME = 240. The proportion of patients receiving prescriptions above 7 DS increased from 11% in 2006 to 19% in 2015. Among those receiving postoperative opioids, 8% had long-term opioid use, and risk of long-term use was 1.16 times [95% confidence interval (CI), 1.10-1.25] higher among those receiving >7 days compared with those receiving ≤7 days. Those receiving >400 total MME (15% of patients) were at 1.17 times (95% CI, 1.10-1.25) the risk of long-term use compared with those receiving ≤400 MME. CONCLUSIONS Between 2005 and 2015, the amounts of opioids prescribed for postoperative pain increased dramatically, and receipt of larger volume of opioids was associated with increased risk of long-term opioid therapy.
Exercise Training in Amnestic Mild Cognitive Impairment: A One-Year Randomized Controlled Trial.

BACKGROUND The current evidence is inconclusive to support the benefits of aerobic exercise training (AET) for preventing neurocognitive decline in patients with amnestic mild cognitive impairment (aMCI). OBJECTIVE To examine the effect of a progressive, moderate-to-high intensity AET program on memory and executive function, brain volume, and cortical amyloid-β (Aβ) plaque deposition in aMCI patients. METHODS This is a proof-of-concept trial that randomized 70 aMCI patients to 12 months of AET or stretching and toning (SAT, active control) interventions. Primary neuropsychological outcomes were assessed by using the California Verbal Learning Test-second edition (CVLT-II) and the Delis-Kaplan Executive Function System (D-KEFS). Secondary outcomes were the global and hippocampal brain volumes and the mean cortical and precuneus Aβ deposition. RESULTS Baseline cognitive scores were similar between the groups. Memory and executive function performance improved over time but did not differ between the AET and SAT groups. Brain volume decreased and precuneus Aβ plaque deposition increased over time but did not differ between the groups. Cardiorespiratory fitness was significantly improved in the AET compared with SAT group. In amyloid positive patients, AET was associated with reduced hippocampal atrophy when compared with the SAT group. CONCLUSION The AET and SAT groups both showed evidence of slightly improved neuropsychological scores in previously sedentary aMCI patients. However, these interventions did not prevent brain atrophy or increases in cortical Aβ deposition over 12 months. In amyloid positive patients, AET reduced hippocampal atrophy when compared with the SAT group.
Ancient pigs reveal a near-complete genomic turnover following their introduction to Europe

Significance Archaeological evidence indicates that domestic pigs arrived in Europe, alongside farmers from the Near East ∼8,500 y ago, yet mitochondrial genomes of modern European pigs are derived from European wild boars. To address this conundrum, we obtained mitochondrial and nuclear data from modern and ancient Near Eastern and European pigs. Our analyses indicate that, aside from a coat color gene, most Near Eastern ancestry in the genomes of European domestic pigs disappeared over 3,000 y as a result of interbreeding with local wild boars. This implies that pigs were not domesticated independently in Europe, yet the first 2,500 y of human-mediated selection applied by Near Eastern Neolithic farmers played little role in the development of modern European pigs. Archaeological evidence indicates that pig domestication had begun by ∼10,500 y before the present (BP) in the Near East, and mitochondrial DNA (mtDNA) suggests that pigs arrived in Europe alongside farmers ∼8,500 y BP. A few thousand years after the introduction of Near Eastern pigs into Europe, however, their characteristic mtDNA signature disappeared and was replaced by haplotypes associated with European wild boars. This turnover could be accounted for by substantial gene flow from local European wild boars, although it is also possible that European wild boars were domesticated independently without any genetic contribution from the Near East. To test these hypotheses, we obtained mtDNA sequences from 2,099 modern and ancient pig samples and 63 nuclear ancient genomes from Near Eastern and European pigs. Our analyses revealed that European domestic pigs dating from 7,100 to 6,000 y BP possessed both Near Eastern and European nuclear ancestry, while later pigs possessed no more than 4% Near Eastern ancestry, indicating that gene flow from European wild boars resulted in a near-complete disappearance of Near East ancestry. In addition, we demonstrate that a variant at a locus encoding black coat color likely originated in the Near East and persisted in European pigs. Altogether, our results indicate that while pigs were not independently domesticated in Europe, the vast majority of human-mediated selection over the past 5,000 y focused on the genomic fraction derived from the European wild boars, and not on the fraction that was selected by early Neolithic farmers over the first 2,500 y of the domestication process.
[Applying remote ischemic pre- and postconditioning for the correction of experimental depression].

AIM To assess antidepressant properties of remote ischemic limb pre- and post-conditioning. MATERIAL AND METHODS The study was performed with rats that were subjected to unavoidable aversive stress in the 'learned helplessness' paradigm for developing experimental depression, or were additional exposed to three brief episodes of ischemia/reperfusion of the limb before or after stressing. RESULTS Remote ischemic preconditioning completely prevented depressive-like behavior and caused hyperactivation of the pituitary-adrenal hormonal axis. Ischemic post-conditioning did not completely correct post-stress hormone dysregulation and animal stress-reactivity. CONCLUSION Remote ischemic pre- and post-conditioning has a pronounced antidepressant effect and prevents the formation of the main behavioral and endocrine signs of experimental depression.
Effects of Moderate Chronic Food Restriction on the Development of Postprandial Dyslipidemia with Ageing

Ageing is a major risk factor for the development of metabolic disorders linked to dyslipidemia, usually accompanied by increased adiposity. The goal of this work was to investigate whether avoiding an excessive increase in adiposity with ageing, via moderate chronic food restriction (FR), ameliorates postprandial dyslipidemia in a rat model of metabolic syndrome associated with ageing. Accordingly, we performed an oral lipid loading test (OLLT) in mature middle-aged (7 months) and middle-old-aged (24 months) Wistar rats fed ad libitum (AL) or under moderate FR for 3 months. Briefly, overnight fasted rats were orally administered a bolus of extra-virgin olive oil (1 mL/Kg of body weight) and blood samples were taken from the tail vein before fat load (t = 0) and 30, 60, 90, 120, 180, and 240 min after fat administration. Changes in serum lipids, glucose, insulin, and glucagon levels were measured at different time-points. Expression of liver and adipose tissue metabolic genes were also determined before (t = 0) and after the fat load (t = 240 min). Postprandial dyslipidemia progressively increased with ageing and this could be associated with hepatic ChREBP activity. Interestingly, moderate chronic FR reduced adiposity and avoided excessive postprandial hypertriglyceridemia in 7- and 24-month-old Wistar rats, strengthening the association between postprandial triglyceride levels and adiposity. The 24-month-old rats needed more insulin to maintain postprandial normoglycemia; nevertheless, hyperglycemia occurred at 240 min after fat administration. FR did not alter the fasted serum glucose levels but it markedly decreased glucagon excursion during the OLLT and the postprandial rise of glycemia in the 24-month-old rats, and FGF21 in the 7-month-old Wistar rats. Hence, our results pointed to an important role of FR in postprandial energy metabolism and insulin resistance in ageing. Lastly, our data support the idea that the vWAT might function as an ectopic site for fat deposition in 7-month-old and in 24-month-old Wistar rats that could increase their browning capacity in response to an acute fat load.
Physical contact, volatiles, and acoustic signals contribute to monogamy in an invasive aggregating bark beetle

The behavioral strategies and mechanisms by which some insects maintain monogamous mating systems are not well understood. We investigated the mating system of the bark beetle Dendroctonus valens, and identified several contributing mechanisms. Field and laboratory observations suggest the adults commonly form permanent bonds during host colonization. Moreover, it showed mated females that remained paired with males produced more offspring than mated females that were alone in galleries. In bioassays, a second female commonly entered a gallery constructed by a prior female. Videos show she commonly reached the location of the first female, but they did not engage in actual fighting. Rather, the second female typically departs to form her own gallery. Acoustic signaling likewise does not appear to influence female‐female encounters, based on controlled muting experiments. Instead, the intruder appears to perceive the resident's presence by physical contact. Both acoustic signals and volatiles released by females during gallery constructing were shown to attract males. After a male joined a female in a gallery, the male‐produced aggressive sounds, which were shown by playback to deter other males from entering the gallery. Unlike female‐female interactions, resident males use their head and rear to push intruders out of galleries. Additionally, volatiles released by males during feeding repelled intruding males, discouraging them from entering the gallery. Males also construct plugs that block the entrance, which may prevent subsequent males and predators from entering the gallery. Thus, D. valens has evolved multifaceted mechanisms contributing to single pairings that confer benefits to both sexes.
Proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors

PCSK9 is a protease that degrades hepatic LDL-C receptors. Evolocumab and alirocumab are fully human monoclonal antibodies administered as subcutaneous injections that inhibit PCSK9, preserving receptor availability to clear circulating LDL-C. [1][1],[2][2] In randomized, placebo-controlled trials
STEM Outreach: Assessing Computational Thinking and Problem Solving

: The ever-growing popularity of computer science has fostered the need for computational thinking (CT), especially in K-12 education. Pedagogy that infuses CT, as well as reliable methods for assessing CT, remain open problems. In this paper, we describe a 5th-9th grade STEM outreach program. Classes on micro controllers and computer programming are presented. Data collected through a newly designed self-efficacy instrument is used to determine effectiveness of these curricula at improving confidence in CT and problem solving skills.
Histone H4 induces platelet ballooning and microparticle release during trauma hemorrhage

Significance Membrane ballooning is a fundamental mechanism by which platelets contribute to thrombin generation. However, this process has not previously been described in human disease. In this study, we demonstrated the presence of ballooning procoagulant platelets free in the circulation of critically injured humans, a phenomenon which results in systemic generation of thrombin and contributes to an acute coagulopathy. The surfaces of ballooning platelets were decorated with the damage-associated molecular pattern histone H4, and exposure of healthy platelets to histone caused membrane disruption and recapitulated the phenotypic changes in injured patients. These findings provide a description of platelet ballooning contributing to human disease and identify histone release from injured tissues as a driver of the procoagulant ballooning process. Trauma hemorrhage is a leading cause of death and disability worldwide. Platelets are fundamental to primary hemostasis, but become profoundly dysfunctional in critically injured patients by an unknown mechanism, contributing to an acute coagulopathy which exacerbates bleeding and increases mortality. The objective of this study was to elucidate the mechanism of platelet dysfunction in critically injured patients. We found that circulating platelets are transformed into procoagulant balloons within minutes of injury, accompanied by the release of large numbers of activated microparticles which coat leukocytes. Ballooning platelets were decorated with histone H4, a damage-associated molecular pattern released in massive quantities after severe injury, and exposure of healthy platelets to histone H4 recapitulated the changes in platelet structure and function observed in trauma patients. This is a report of platelet ballooning in human disease and of a previously unrecognized mechanism by which platelets contribute to the innate response to tissue damage.
Digital Mammography versus Breast Tomosynthesis: Impact of Breast Density on Diagnostic Performance in Population-based Screening.

BackgroundPrevious studies comparing digital breast tomosynthesis (DBT) to digital mammography (DM) have shown conflicting results regarding breast density and diagnostic performance.PurposeTo compare true-positive and false-positive interpretations in DM versus DBT according to volumetric density, age, and mammographic findings.Materials and MethodsFrom November 2010 to December 2012, 24 301 women aged 50-69 years (mean age, 59.1 years ± 5.7) were prospectively included in the Oslo Tomosynthesis Screening Trial. Participants received same-compression DM and DBT with independent double reading for both DM and DM plus DBT reading modes. Eight experienced radiologists rated the images by using a five-point scale for probability of malignancy. Participants were followed up for 2 years to assess for interval cancers. Breast density was assessed by using automatic volumetric software (scale, 1-4). Differences in true-positive rates, false-positive rates, and mammographic findings were assessed by using confidence intervals (Newcombe paired method) and P values (McNemar and χ2 tests). ResultsThe true-positive rate of DBT was higher than that of DM for density groups (range, 12%-24%; P < .001 for density scores of 2 and 3, and P > .05 for density scores of 1 and 4) and age groups (range, 15%-35%; P < .05 for all age groups), mainly due to the higher number of spiculated masses and architectural distortions found at DBT (P < .001 for density scores of 2 and 3; P < .05 for women aged 55-69 years). The false-positive rate was lower for DBT than for DM in all age groups (range, -0.6% to -1.2%; P < .01) and density groups (range, -0.7 to -1.0%; P < .005) owing to fewer asymmetric densities (P ≤ .001), except for extremely dense breasts (0.1%, P = .82). ConclusionDigital breast tomosynthesis enabled the detection of more cancers in all density and age groups compared with digital mammography, especially cancers classified as spiculated masses and architectural distortions. The improvement in cancer detection rate showed a positive correlation with age. With use of digital breast tomosynthesis, false-positive findings were lower due to fewer asymmetric densities, except in extremely dense breasts. © RSNA, 2019Online supplemental material is available for this article.See also the editorial by Fuchsjäger and Adelsmayr in this issue.