Miracle-dz/UniFAR-FTUs huggingface dataset:
Recently Discovered Interstitial Cell Population of Telocytes: Distinguishing Facts from Fiction Regarding Their Role in the Pathogenesis of Diverse Diseases Called “Telocytopathies”

In recent years, the interstitial cells telocytes, formerly known as interstitial Cajal-like cells, have been described in almost all organs of the human body. Although telocytes were previously thought to be localized predominantly in the organs of the digestive system, as of 2018 they have also been described in the lymphoid tissue, skin, respiratory system, urinary system, meninges and the organs of the male and female genital tracts. Since the time of eminent German pathologist Rudolf Virchow, we have known that many pathological processes originate directly from cellular changes. Even though telocytes are not widely accepted by all scientists as an individual and morphologically and functionally distinct cell population, several articles regarding telocytes have already been published in such prestigious journals as Nature and Annals of the New York Academy of Sciences. The telocyte diversity extends beyond their morphology and functions, as they have a potential role in the etiopathogenesis of different diseases. The most commonly described telocyte-associated diseases (which may be best termed “telocytopathies” in the future) are summarized in this critical review. It is difficult to imagine that a single cell population could be involved in the pathogenesis of such a wide spectrum of pathological conditions as extragastrointestinal stromal tumors (“telocytomas”), liver fibrosis, preeclampsia during pregnancy, tubal infertility, heart failure and psoriasis. In any case, future functional studies of telocytes in vivo will help to understand the mechanism by which telocytes contribute to tissue homeostasis in health and disease.
First-line Nivolumab Plus Ipilimumab vs Sunitinib for Metastatic Renal Cell Carcinoma: A Cost-effectiveness Analysis

Importance Recently, new drugs have been approved for the first-line treatment of metastatic renal cell carcinoma (mRCC). Nivolumab plus ipilimumab significantly increases overall survival for intermediate- and poor-risk patients with mRCC. However, considering the high cost of nivolumab plus ipilimumab, there is a need to assess its value by considering both efficacy and cost. Objective To evaluate the cost-effectiveness of nivolumab plus ipilimumab vs sunitinib in the first-line setting for intermediate- and poor-risk patients with mRCC from the US payer perspective. Design, Setting, and Participants A Markov model was developed to compare the lifetime cost and effectiveness of nivolumab plus ipilimumab vs sunitinib in the first-line treatment of mRCC using outcomes data from the CheckMate 214 phase 3 randomized clinical trial, which included 1096 patients with mRCC (median age, 62 years) and compared nivolumab plus ipilimumab vs sunitinib as first-line treatment of mRCC. In the analysis, patients were modeled to receive sunitinib or nivolumab plus ipilimumab for 4 doses followed by nivolumab monotherapy. Main Outcomes and Measures Life-years, quality-adjusted life-years (QALYs), and lifetime costs were estimated, at a willingness-to-pay threshold of $100 000 to $150 000 per QALY. Univariable, 2-way, and probabilistic sensitivity analyses were performed to evaluate the model uncertainty. Additional subgroup analyses were performed. Results Nivolumab plus ipilimumab provided an additional 0.96 QALYs, at a cost of $108 363 per QALY. Sensitivity analyses found the results to be most sensitive to overall survival hazard ratio (0.63; 95% CI, 0.44-0.89) and mean patient weight (70 kg, range, 40-200 kg). Other variables, such as the cost of nivolumab plus ipilimumab (mean, $32 213.44; range, $25 770.75-$38 656.13), utility values for nivolumab plus ipilimumab (mean, 0.82; range, 0.65-0.98), and proportion receiving nivolumab in sunitinib arm (mean, 0.27; range, 0.22-0.32), had a moderate or minor influence on model results. Subgroup analyses demonstrated that nivolumab plus ipilimumab was most cost-effective for patients with programmed cell death 1 ligand 1 expression of at least 1% ($86 390 per QALY). Conclusions and Relevance In this model, nivolumab plus ipilimumab was estimated to be cost-effective compared with sunitinib for intermediate- and poor-risk patients with mRCC at a willingness-to-pay threshold from $100 000 to $150 000 per QALY.
Effects of turmeric and curcumin on oral mucositis: A systematic review

The aim of this study was to evaluate the effects of turmeric and curcumin in the management of oral mucositis in cancer patients undergoing chemo and/or radiotherapy. The systematic review was reported according to the Preferred Reporting Items for Systematic reviews and Meta‐Analyses. The search was performed in the following database: Cochrane Library, LILACS, LIVIVO, PubMed, Scopus, and Web of Science. A gray literature search was undertaken using Google Scholar, Open Grey, and ProQuest. The methodology of included studies was evaluated by the Meta‐Analysis of Statistics Assessment and Review Instrument. After a two‐step selection process, four randomized and one nonrandomized clinical trials were included in the analysis. Two studies were categorized as low and three as moderate risk of bias. Turmeric/curcumin was applied topically as a gel or as a mouthwash. Patients treated with turmeric/curcumin experienced reduced grade of mucositis, pain, erythema intensity, and ulcerative area. Current evidence suggests that topical application of turmeric or curcumin is effective in controlling signs and symptoms of oral mucositis. Thus, further investigation is required to confirm the promising effect of turmeric and curcumin in oral inflammatory lesions.
Apolipoprotein E4 Polymorphism and Outcomes from Traumatic Brain Injury: A Living Systematic Review and Meta-Analysis

The mortality of traumatic brain injury (TBI) has been largely static despite advances in monitoring and imaging techniques. Substantial variance exists in outcome, not fully accounted for by baseline characteristics or injury severity, and genetic factors likely play a role in this variance. The aims of this systematic review were to examine the evidence for a link between the apolipoprotein E4 (APOE4) polymorphism and TBI outcomes and where possible, to quantify the effect size via meta-analysis. We searched EMBASE, MEDLINE, CINAHL, and gray literature in December 2017. We included studies of APOE genotype in relation to functional adult TBI outcomes. Methodological quality was assessed using the Quality in Prognostic Studies Risk of Bias Assessment Instrument and the prognostic studies adaptation of the Grading of Recommendations Assessment, Development and Evaluation tool. In addition, we contacted investigators and included an additional 160 patients whose data had not been made available for previous analyses, giving a total sample size of 2593 patients. Meta-analysis demonstrated higher odds of a favorable outcome following TBI in those not possessing an ApoE ɛ4 allele compared with ɛ4 carriers and homozygotes (odds ratio 1.39, 95% confidence interval 1.05 to 1.84; p = 0.02). The influence of APOE4 on neuropsychological functioning following TBI remained uncertain, with multiple conflicting studies. We conclude that the ApoE ɛ4 allele confers a small risk of poor outcome following TBI, with analysis by TBI severity not possible based on the currently available published data. Further research into the long-term neuropsychological impact and risk of dementia is warranted.
The Association between Plasma Omega-6/Omega-3 Ratio and Anthropometric Traits Differs by Racial/Ethnic Groups and NFKB1 Genotypes in Healthy Young Adults

Evidence for a relationship between omega-6/omega-3 (n-6/n-3) polyunsaturated fatty acid (PUFA) ratio and obesity in humans is inconsistent, perhaps due to differences in dietary intake or metabolism of PUFAs between different subsets of the population. Since chronic inflammation is central to obesity and inflammatory pathways are regulated by PUFAs, the objective of this study was to examine whether variants in the NFKB1 gene, an upstream regulator of the inflammatory response, modify the association between the n-6/n-3 ratio (from diet and plasma) and anthropometric traits in a multiethnic/multiracial population of young adults. Participants’ (n = 898) dietary PUFA intake was assessed using a food frequency questionnaire and plasma PUFA concentrations by gas chromatography. Nine tag single nucleotide polymorphisms (SNP) in NFKB1 were genotyped. Significant interactions were found between racial/ethnic groups and plasma n-6/n-3 ratio for body mass index (BMI) (p = 0.02) and waist circumference (WC) (p = 0.007). Significant interactions were also observed between racial/ethnic groups and three NFKB1 genotypes (rs11722146, rs1609798, and rs230511) for BMI and WC (all p ≤ 0.04). Significant interactions were found between two NFKB1 genotypes and plasma n-6/n-3 ratio for BMI and WC (rs4648090 p = 0.02 and 0.03; rs4648022 p = 0.06 and 0.04, respectively). Our findings suggest that anthropometric traits may be influenced by a unique combination of n-6/n-3 ratio, racial/ethnic background, and NFKB1 genotypes.
Occasional and persistent frequent attenders and sickness absences in occupational health primary care: a longitudinal study in Finland

Objectives Frequent attenders (FAs) create a substantial portion of primary care workload but little is known about FAs’ sickness absences. The aim of the study is to investigate how occasional and persistent frequent attendance is associated with sickness absences among the working population in occupational health (OH) primary care. Setting and participants This is a longitudinal study using medical record data (2014–2016) from an OH care provider in Finland. In total, 59 676 patients were included and categorised into occasional and persistent FAs or non-FAs. Sick-leave episodes and their lengths were collected along with associated diagnostic codes. Logistic regression was used to analyse associations between FA status and sick leaves of different lengths (1–3, 4–14 and ≥15 days). Results Both occasional and persistent FA had more and longer duration of sick leave than non-FA through the study years. Persistent FAs had consistently high absence rates. Occasional FAs had elevated absence rates even 2 years after their frequent attendance period. Persistent FAs (OR=11 95% CI 7.54 to 16.06 in 2016) and occasional FAs (OR=2.95 95% CI 2.50 to 3.49 in 2016) were associated with long (≥15 days) sickness absence when compared with non-FAs. Both groups of FAs had an increased risk of long-term sick leaves indicating a risk of disability pension. Conclusion Both occasional and persistent FAs should be identified in primary care units caring for working-age patients. As frequent attendance is associated with long sickness absences and possibly disability pensions, rehabilitation should be directed at this group to prevent work disability.
Decreased Early Mortality in Young Adult Patients With Acute Lymphoblastic Leukemia Treated at Specialized Cancer Centers in California.

PURPOSE Studies suggest that patients with acute lymphoblastic leukemia (ALL) have superior survival when treated at specialized cancer centers (SCCs). However, the association of early mortality (< 60 days) with location of initial care, sociodemographic factors, and complications has not been evaluated in pediatric and young adult (YA) patients with ALL. METHODS Using the California Cancer Registry linked to hospitalization data, we identified pediatric and YA patients with ALL who received inpatient leukemia treatment between 1991 and 2014. Patients were classified as receiving all or part/none of their care at an SCC (Children's Oncology Group- or National Cancer Institute-designated cancer center). Propensity scores were created for treatment at an SCC in each age group. Multivariable, inverse probability-weighted Cox proportional hazards regression models identified factors associated with early mortality. Results are presented as hazard ratios (HRs) and 95% CIs. RESULTS Among 6,531 newly diagnosed pediatric (≤ 18 years) and YA (19 to 39 years of age) patients with ALL, 1.6% of children and 5.4% of YAs died within 60 days of diagnosis. Most children received all of their care at an SCC (n = 4,752; 85.7%) compared with 35.5% of YAs (n = 1,779). Early mortality rates were lower in pediatric patients and those receiving all care at an SCC (pediatric: all, 1.5%, v part/none, 2.4%; P = .049; YAs: all, 3.2%, v part/none, 6.6%; P = .001). However, in adjusted models, receiving all care at an SCC was associated with significantly lower early mortality in YAs (HR, 0.51; 95% CI, 0.32 to 0.81), but not in pediatric patients (HR, 0.77; 95% CI, 0.47 to 1.25). CONCLUSION YAs with ALL experience significant reductions in early mortality after treatment at SCCs.
Systems biology identifies preserved integrity but impaired metabolism of mitochondria due to a glycolytic defect in Alzheimer's disease neurons

Mitochondrial dysfunction is implicated in most neurodegenerative diseases, including Alzheimer's disease (AD). We here combined experimental and computational approaches to investigate mitochondrial health and bioenergetic function in neurons from a double transgenic animal model of AD (PS2APP/B6.152H). Experiments in primary cortical neurons demonstrated that AD neurons had reduced mitochondrial respiratory capacity. Interestingly, the computational model predicted that this mitochondrial bioenergetic phenotype could not be explained by any defect in the mitochondrial respiratory chain (RC), but could be closely resembled by a simulated impairment in the mitochondrial NADH flux. Further computational analysis predicted that such an impairment would reduce levels of mitochondrial NADH, both in the resting state and following pharmacological manipulation of the RC. To validate these predictions, we utilized fluorescence lifetime imaging microscopy (FLIM) and autofluorescence imaging and confirmed that transgenic AD neurons had reduced mitochondrial NAD(P)H levels at rest, and impaired power of mitochondrial NAD(P)H production. Of note, FLIM measurements also highlighted reduced cytosolic NAD(P)H in these cells, and extracellular acidification experiments showed an impaired glycolytic flux. The impaired glycolytic flux was identified to be responsible for the observed mitochondrial hypometabolism, since bypassing glycolysis with pyruvate restored mitochondrial health. This study highlights the benefits of a systems biology approach when investigating complex, nonintuitive molecular processes such as mitochondrial bioenergetics, and indicates that primary cortical neurons from a transgenic AD model have reduced glycolytic flux, leading to reduced cytosolic and mitochondrial NAD(P)H and reduced mitochondrial respiratory capacity.
Asymmetrical Training Scheme of Binary-Memristor-Crossbar-Based Neural Networks for Energy-Efficient Edge-Computing Nanoscale Systems

For realizing neural networks with binary memristor crossbars, memristors should be programmed by high-resistance state (HRS) and low-resistance state (LRS), according to the training algorithms like backpropagation. Unfortunately, it takes a very long time and consumes a large amount of power in training the memristor crossbar, because the program-verify scheme of memristor-programming is based on the incremental programming pulses, where many programming and verifying pulses are repeated until the target conductance. Thus, this reduces the programming time and power is very essential for energy-efficient and fast training of memristor networks. In this paper, we compared four different programming schemes, which are F-F, C-F, F-C, and C-C, respectively. C-C means both HRS and LRS are coarse-programmed. C-F has the coarse-programmed HRS and fine LRS, respectively. F-C is vice versa of C-F. In F-F, both HRS and LRS are fine-programmed. Comparing the error-energy products among the four schemes, C-F shows the minimum error with the minimum energy consumption. The asymmetrical coarse HRS and fine LRS can reduce the time and energy during the crossbar training significantly, because only LRS is fine-programmed. Moreover, the asymmetrical C-F can maintain the network’s error as small as F-F, which is due to the coarse-programmed HRS that slightly degrades the error.
Pregnancy outcomes in women with bariatric surgery as compared with morbidly obese women

Abstract Objective: Pregnancies among morbidly obese women are associated with serious adverse maternal and neonatal outcomes. Our study objective is to evaluate the effect of bariatric surgery on obstetrical outcomes. Methods: We carried out a retrospective cohort study using the healthcare cost and utilization project – Nationwide Inpatient Sample from 2003 to 2011 comparing outcome of births among women who had undergone bariatric surgery with births among women with morbid obesity. Logistic regression was used to estimate the adjusted effect of bariatric surgery on maternal and newborn outcomes. Results: There were 8 475 831 births during the study period (221 580 (2.6%) in morbidly obese women and 9587 (0.1%) in women with bariatric surgery). Women with bariatric surgery were more likely to be Caucasian and ≥35 years old as compared with morbidly obese women. As compared with women with morbid obesity, women with bariatric surgery had lower rates of hypertensive disorders, premature rupture of membrane, chorioamnionitis, cesarean delivery, instrumental delivery, postpartum hemorrhage, and postpartum infection. Induction of labor, postpartum blood transfusions, venous thromboembolisms, and intrauterine fetal growth restriction were more common in the bariatric surgery group. There were no differences observed in preterm births, fetal deaths, or reported congenital anomalies. Conclusion: In general, women who undergo bariatric surgery have improved pregnancy outcomes as compared with morbidly obese women. However, the bariatric surgery group was more likely to have venous thromboembolisms, to require a blood transfusion, to have their labor induced and to experience fetal growth restriction.
Increased Plasma Adenosine Concentration in the Subacute Phase May Contribute to Attenuation of Left Ventricular Dilation in the Chronic Phase in Patients With Acute Myocardial Infarction.

BACKGROUND Changes in the plasma adenosine concentration and the effects on left ventricular (LV) function and remodeling in patients with acute myocardial infarction (AMI) remain unclear. Methods and Results: In 58 patients with AMI and 14 subjects without cardiac disease (controls), we measured the plasma adenosine concentration by LC-MS/MS. Blood samples were taken from the antecubital vein on days 0, 1, 7, and 14 after AMI, and from the controls on admission. Cardiac echocardiography was performed in the acute (within 7 days) and chronic (6 months) phases of AMI. There were no significant differences in the plasma adenosine concentrations among days 0 (211.5±150.2 nmol/L), 1 (192.7±141.3 nmol/L), 7 (218.8±154.1 nmol/L), and the controls (136.0±50.9 nmol/L). The plasma adenosine concentration increased significantly on day 14 (321.1±195.4 nmol/L) after AMI as compared with days 0, 1 and 7. AMI patients with a greater increase in the plasma adenosine concentration in the subacute phase showed an attenuation of LV dilation in the chronic phase. The plasma adenosine concentration in the acute phase did not affect the LV ejection fraction in the chronic phase. CONCLUSIONS The plasma adenosine concentration significantly increased 14 days after AMI, which may contribute to attenuation of LV dilation in the chronic phase.
Post hoc analyses of surrogate markers of non-alcoholic fatty liver disease (NAFLD) and liver fibrosis in patients with type 2 diabetes in a digitally supported continuous care intervention: an open-label, non-randomised controlled study

Objective One year of comprehensive continuous care intervention (CCI) through nutritional ketosis improves glycosylated haemoglobin(HbA1c), body weight and liver enzymes among patients with type 2 diabetes (T2D). Here, we report the effect of the CCI on surrogate scores of non-alcoholic fatty liver disease (NAFLD) and liver fibrosis. Methods This was a non-randomised longitudinal study, including adults with T2D who were self-enrolled to the CCI (n=262) or to receive usual care (UC, n=87) during 1 year. An NAFLD liver fat score (N-LFS) >−0.640 defined the presence of fatty liver. An NAFLD fibrosis score (NFS) of >0.675 identified subjects with advanced fibrosis. Changes in N-LFS and NFS at 1 year were the main endpoints. Results At baseline, NAFLD was present in 95% of patients in the CCI and 90% of patients in the UC. At 1 year, weight loss of ≥5% was achieved in 79% of patients in the CCI versus 19% of patients in UC (p<0.001). N-LFS mean score was reduced in the CCI group (−1.95±0.22, p<0.001), whereas it was not changed in the UC (0.47±0.41, p=0.26) (CCI vs UC, p<0.001). NFS was reduced in the CCI group (−0.65±0.06, p<0.001) compared with UC (0.26±0.11, p=0.02) (p<0.001 between two groups). In the CCI group, the percentage of individuals with a low probability of advanced fibrosis increased from 18% at baseline to 33% at 1 year (p<0.001). Conclusions One year of a digitally supported CCI significantly improved surrogates of NAFLD and advanced fibrosis in patients with T2D. Trial registration number NCT02519309; Results.
The Association Between State-Level Health Information Exchange Laws and Hospital Participation in Community Health Information Organizations

Evidence suggests that health information exchange (HIE) is an effective strategy to improve efficiency and quality of care, as well as reduce costs. A complex patchwork of federal and state legislation has developed over time to encourage HIE activity. Hospitals and health systems have adopted various HIE models to meet the requirements of these statutes and regulations. Given the complexity of HIE laws, it is important to understand how these legal levers influence HIE engagement. We combined data from two unique data sources to examine the association between state-level HIE laws and hospital engagement in community HIEs. Our results identified three legal provisions of state laws (HIE authorization, financial & non-financial incentives, opt-out consent) that increased the likelihood of community HIE engagement. Other provisions decreased the likelihood of engagement. This analysis provides foundational evidence about the utility of HIE laws. More research is needed to determine causal relationships.
Evaluation of Modified Sequential Multiplex PCR for Streptococcus pneumoniae Serotyping.

The aims of this study were to develop modified SM-PCR primer sets and to evaluate their ability and efficiency for serotype determination. We selected target serotypes for SM-PCR testing according to the prevalence of serotypes as reported in papers published in Asian countries. The modified SM-PCR consisted of six groups of PCRs, with each reaction being carried out using five pairs of primers. We evaluated the efficiency and performance of this modified multiplex PCR using 378 pneumococcal strains by comparing the findings with the results of the Quellung reaction. A total of 30 primer pairs were used for a consecutive set of six reactions. All results were concordant with those of the Quellung reaction, and there was no cross reactivity on multiplex PCR. We could identify the final serotypes of 370 isolates (97.9%). The coverage rates of modified SM-PCR were 42.6%, 65.8%, and 79.4% in Reactions 1, 2, and 3, respectively. The modified SM-PCR showed good performance in detecting pneumococcal serotypes and could be used as a helpful alternative to the Quellung reaction.