Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparison of Clinical Features and Outcome of Pediatric Posttransplant Lymphoproliferative Disorder in Recipients of Small Bowel Allograft Versus Isolated Liver Transplantation

Background. Higher incidence of posttransplant lymphoproliferative disorder (PTLD) is reported in the pediatric small bowel transplant (SBTx) population, which may be associated with more aggressive disease and poorer outcome as compared to liver transplant (LTx) recipients. We aim to compare the characteristics and outcome of PTLD in pediatric SBTx against LTx patients at a single center. Methods. Retrospective review of pediatric SBTx and LTx patients diagnosed with PTLD from 1989 to 2016 was conducted. Diagnosis of PTLD was biopsy-proven based on World Health Organization histologic criteria. Treatment protocol consisted of reduction of immunosuppression (RIS), rituximab (from 2000), cytotoxic T-lymphocyte (CTL) therapy (available in 1999–2004 and from 2011), and chemotherapy. Results. Thirty-seven PTLD patients were included following LTx (n = 23, incidence = 2.8%) and SBTx (n = 14, incidence = 14.9%). Monomorphic PTLD made up 64% of SBTx and 43% of LTx cases. RIS alone resulted in remission in 50% of LTx patients but none of the SBTx patients (P = 0.002). Poorer overall remission (57% versus 96%, P = 0.004), 2-year (46% versus 91%, P = 0.003), and 5-year survival rates (39% versus 90%, P = 0.002) were observed in the SBTx group. Risk factors associated with mortality following PTLD were SBTx (odds ratio [OR], 12.00; 95% confidence interval [CI], 2.34-61.45; P = 0.003), monomorphic histology (OR, 10.63; 95% CI, 1.88-60.25; P = 0.008), multisite involvement (OR, 6.38; 95% CI, 1.35-30.14; P = 0.019), and tumor involvement of allograft (OR, 5.33; 95% CI, 1.14-24.90; P = 0.033). Introduction of CTL therapy was associated with improved survival. Conclusions. Majority of PTLD following pediatric SBTx are of monomorphic subtype and associated with poorer outcome as compared to LTx patients. RIS is inadequate as a single strategy in managing PTLD in SBTx and prompt escalation to rituximab and CTL is recommended.
Sex Differences in Kidney Replacement Therapy Initiation and Maintenance.

BACKGROUND AND OBJECTIVES More men than women undergo kidney replacement therapy (KRT) despite a larger number of women being affected by CKD. The aim of this multinational European study was to explore whether there might be historic and geographic trends in sex-specific incidence and prevalence of various KRT modalities. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We assessed sex-specific differences in KRT incidence and prevalence using data from nine countries reporting to the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry for at least 40 years, during the period 1965-2015. Sex distribution data were compared with the European general population (Eurostat). Statistical methodology included basic descriptive statistics, incidence and prevalence calculations per million population (pmp), as well as their male-to-female ratios. Analyses were stratified by age group and diabetic status. RESULTS We analyzed data from 230,378 patients receiving KRT (38% women). For all KRT modalities, the incidence and prevalence rates were consistently higher in men than women. For example, the KRT incidence increased from 8 pmp in 1965-1974 to 98 pmp in 2005-2015 in women, whereas it rose from 12 to 173 pmp in men during the same period. Male-to-female ratios, calculated for incident and prevalent KRT patients, increased with age (range 1.2-2.4), showing consistency over decades and for individual countries, despite marked changes in primary kidney disease (diabetes more prevalent than glomerulonephritis in recent decades). The proportion of kidney transplants decreased less with age in incident and prevalent men compared with women on KRT. Stratified analysis of patients who were diabetic versus nondiabetic revealed that the male-to-female ratio was markedly higher for kidney transplantation in patients with diabetes. CONCLUSIONS Since the beginning of KRT programs reporting to the ERA-EDTA Registry since the 1960s, fewer women than men have received KRT. The relative difference between men and women initiating and undergoing KRT has remained consistent over the last five decades and in all studied countries.
Organizational and Psychosocial Working Conditions and Their Relationship With Mental Health Outcomes In Patient-Care Workers.

OBJECTIVE The aim of this study was to investigate the relationship between both psychosocial and organizational working conditions with self-reported mental health and mental health expenditures. METHODS This study used worker survey and medical claims data from a sample of 1,594 patient-care workers from the Boston Hospital Workers Health Study (BHWHS) to assess the relationship of psychosocial (job demands, decision latitude, supervisor support, co-worker support) and organizational (job flexibility, people-oriented culture) working conditions with mental health outcomes using validated tools RESULTS:: People-oriented culture and co-worker support were negatively correlated with psychological distress and were predictive of lower expenditures in mental health services. Job demands was positively correlated with psychological distress. CONCLUSIONS Working conditions that promote trustful relationships and a cooperative work environment may render sustainable solutions to prevent ill mental health.
A systematic review and meta-analysis approach on diagnostic value of MLH1 promoter methylation for head and neck squamous cell carcinoma

Abstract Background: Head and neck squamous cell carcinoma (HNSCC) is the leading histological type among head and neck cancers. Several studies have explored an association between aberrant methylation of MutL homolog-1 (MLH1) promoter and HNSCC risk. We aimed to explore the associations between MLH1 promoter methylation and HNSCC by using a meta-analysis. Methods: Systematic literature search was conducted among PubMed, Google Scholar, Web of Science, and China National Knowledge Infrastructure, and Wanfang databases to retrieve relevant articles published up to June 30, 2018. A total of 12 studies were included in this meta-analysis (including 717 HNSCC and 609 controls). Results: The results demonstrated that MLH1 promoter methylation was notably higher in patients with HNSCC than in controls (odds ratios [ORs] = 2.52, 95% confidence intervals [CIs] = 1.33–4.79). Besides, MLH1 promoter methylation was not associated with tumor stage, lymph node status, smoking behavior, age, clinical stage, gender, and differentiation grade (all P > .05). The pooled sensitivity and specificity rates of MLH1 methylation for HNSCC were 0.23 (95% CI = 0.12–0.38) and 0.95 (95% CI, 0.82–0.99), respectively. The area under the receiver operating characteristic (ROC) curve was presented as 0.64 (95% CI = 0.60-0.68). Conclusion: The results of this meta-analysis suggested that hypermethylation of MLH1 promoter was associated with HNSCC. Methylated MLH1 could be a potential diagnostic biomarker for diagnose of HNSCC.
Developing a Hypothetical Implementation Framework of Expectations for Monitoring Early Signs of Psychosis Relapse Using a Mobile App: Qualitative Study

Background Relapse is a common experience for people diagnosed with psychosis, which is associated with increased service costs and profound personal and familial distress. EMPOWER (Early signs Monitoring to Prevent relapse in psychosis and prOmote Well-being, Engagement, and Recovery) is a peer worker–supported digital intervention that aims to enable service users to self-monitor their mental health with the aim of encouraging self-management and the shared use of personal data to promote relapse prevention. Digital interventions have not been widely used in relapse prevention and, therefore, little is currently known about their likely implementation—both within trials and beyond. Objective Seeking the perspectives of all relevant stakeholder groups is recommended in developing theories about implementation because this can reveal important group differences in understandings and assumptions about whether and for whom the intervention is expected to work. However, the majority of intervention implementation research has been retrospective. This study aimed to discover and theoretically frame implementation expectations in advance of testing and synthesize these data into a framework. Methods To develop a hypothetical implementation framework, 149 mental health professionals, carers, and people diagnosed with psychosis participated in 25 focus groups in both Australia and the United Kingdom. An interview schedule informed by the normalization process theory was used to explore stakeholders’ expectations about the implementation of the EMPOWER intervention. Data were analyzed using thematic analysis and then theoretically framed using the Medical Research Council guidelines for understanding the implementation of complex interventions. Results All groups expected that EMPOWER could be successfully implemented if the intervention generated data that were meaningful to mental health staff, carers, and service users within their unique roles. However, there were key differences between staff, carers, and service users about what facilitators and barriers that stakeholders believe exist for intervention implementation in both the cluster randomized controlled trial stage and beyond. For example, service user expectations mostly clustered around subjective user experiences, whereas staff and carers spoke more about the impact upon staff interactions with service users. Conclusions A hypothetical implementation framework synthesized from stakeholder implementation expectations provides an opportunity to compare actual implementation data gathered during an ongoing clinical trial, giving valuable insights into the accuracy of these stakeholders’ previous expectations. This is among the first studies to assess and record implementation expectations for a newly developed digital intervention for psychosis in advance of testing in a clinical trial. Trial Registration ISRCTN Registry ISRCTN99559262; http://www.isrctn. com/ISRCTN99559262
PD-1/PD-L1 pathway activation restores the imbalance of Th1/Th2 and treg/Th17 cells subtypes in immune thrombocytopenic purpura patients

Abstract This study aims to investigate the changes of cytokines and the effect of programmed death ligand 1 (PD-L1) signaling pathway on T cell function in patients with immune thrombocytopenic purpura (ITP). Totally, 40 untreated ITP patients were recruited and 30 healthy people were recruited as the healthy control. Then whole blood of ITP patients and healthy control was collected, respectively. The sPD-L1/anti-PD-1 was used to activate or block the programmed death (PD-1)/PD-L1 signaling pathway. The expression of PD-1 and PD-L1 on peripheral blood mononuclear cells (PBMCs) were detected by flow cytometry. PBMCs were treated with cluster of differentiation (CD3), cluster of differentiation 28 (CD28), and phytohaemagglutinin (PHA) for 48 hours. Serum levels of sPD-1, sPD-L1, and cytokines were measured by enzyme-linked immunosorbent assay (ELISA). Compared with the healthy control group, the percentages of PD-1+CD3+CD4+ T cells and PD-L1+HLA-DR+CD11c+ DC cells were increased in ITP patients. The levels of interferon-gamma (IFN-γ), interleukin-17 (IL-17), and sPD-1 in the serum of ITP patients were increased, while IL-4 and transforming growth factor-β (TGF-β) were decreased. Additionally, the level of sPD-1 was negatively correlated with the platelet count. Consistently, after treatment with CD3, CD28, and PHA, IFN-γ and IL-17 levels in culture supernatant of PBMCs from ITP patients were significantly higher than those from healthy controls whereas IL-4 and TGF-β levels were significantly lower. Furthermore, IFN-γ and IL-17 levels secreted by PBMCs from ITP patients decreased after sPD-L1 administration, however, IL-4 and TGF-β levels were increased. The level of IFN-γ in ITP group remained higher after anti-PD-1 blockage, but the levels of IL-4, TGF-β, and IL-17 were not significantly influenced. sPD-1 may cause the dysfunction of PD-1/PD-L1 signaling pathway, and its level is related to the severity of ITP patients. Activation of PD-1/PD-L1 with sPD-L1 may restore the imbalance of Th1/Th2 and Treg/Th17 cell subtypes in ITP patients but anti-PD-1 may exacerbate disease by enhancing IFN-γ production.
Atypical KRASG12R Mutant Is Impaired in PI3K Signaling and Macropinocytosis in Pancreatic Cancer.

Allele-specific signaling by different KRAS alleles remains poorly understood. The KRASG12R mutation displays uneven prevalence among cancers that harbor the highest occurrence of KRAS mutations: it is rare in lung and colorectal cancers (~1%), yet relatively common (~20%) in pancreatic ductal adenocarcinoma (PDAC), suggesting context-specific properties. We evaluated whether KRASG12R is functionally distinct from the more common KRASG12D or KRASG12V mutant proteins (KRASG12D/V). We found that KRASG12D/V but not KRASG12R drives macropinocytosis and that MYC is essential for macropinocytosis in KRASG12D/V but not KRASG12R-mutant PDAC. Surprisingly, we found that KRASG12R is defective for interaction with a key effector, p110a phosphoinositide 3-kinase (PI3Ka, due to structural perturbations in switch II. Instead, upregulated KRAS-independent PI3Kg activity was able to support macropinocytosis in KRASG12R-mutant PDAC. Finally, we determined that KRASG12R-mutant PDAC displayed a distinct drug sensitivity profile compared with KRASG12D-mutant PDAC but is still responsive to the combined inhibition of ERK and autophagy.
Unveiling introgression in bumblebee (Bombus terrestris) populations through mitogenome-based markers.

The bumblebee, Bombus terrestris, is an important pollinator commercially used on a global scale. The exported subspecies B. t. terrestris has colonised diverse environments, in some cases displacing wild pollinators to the verge of local extinction. In this sense, the native Iberian subspecies B. t. lusitanicus may be threatened by the subspecies B. t. terrestris, naturally distributed from the Pyrenees to Central Europe but also observed in southern Spain due to escapes from commercial nests. Mitochondrial genomes have a low recombination rate and a small effective population size owing to their maternal inheritance, thus providing an accurate approach to study hybridisation events between populations. Therefore, we present the sequences of the mitogenomes of both subspecies as a molecular framework to select suitable markers to detect possible introgression events between them. We used metagenomics to obtain approximately 17 kbp of the mitogenome from both subspecies. Their mitogenomes differed in 358 bp (excluding the AT-rich region). Four mitogenomic fragments were selected to be tested as subspecific diagnostic markers. A RFLP detected in the gene nad2 (NADH dehydrogenase subunit 2) has proven to be an efficient, quick and cost-effective tool to assess the dispersion of the non-endemic subspecies into Iberian native populations. Subspecific haplotypes were observed in both morphological subspecies, suggesting introgression events in the northern natural contact area and in the new human-mediated contact area in the south of the Iberian Peninsula.
Deep‐Subwavelength Holey Acoustic Second‐Order Topological Insulators

Higher‐order topological insulators (HOTIs) belong to a new class of materials with unusual topological phases. They have garnered considerable attention due to their capabilities in confining energy at the hinges and corners, which is entirely protected by the topology, and have thus become attractive structures for acoustic wave studies and control. However, for most practical applications at audible and low frequencies, compact and subwavelength implementations are desirable in addition to providing robust guiding of sound beyond a single‐frequency operation. Here, a holey HOTI capable of sustaining deeply confined corner states 50 times smaller than the wavelength is proposed. A remarkable resilience of these surface‐confined acoustic states against defects is experimentally observed, and topologically protected sound is demonstrated in three different frequency regimes. Concerning this matter, the findings will thus have the capability to push forward exciting applications for robust acoustic imaging way beyond the diffraction limit.
PHBV/PLGA nanoparticles for enhanced delivery of 5-fluorouracil as promising treatment of colon cancer

Abstract 5-Fluorouracil (5-FU) is one of the most widely used agents in the first-line chemotherapy for colon cancer. However, clinical use of 5-FU is limited because of the low efficacy of drug uptake and systemic toxic effects. Therefore, there is a critical need to find better drug delivery systems in order to improve the efficacy of the drug. In the present study, we have developed a novel combination drug delivery system based on PHBV/PLGA NPs for delivery of 5-FU to cancer cells. NPs were prepared by the double emulsion method and their optimization of preparation was evaluated using Box–Behnken design (BBD) of response surface methodology (RSM). 5-FU loaded NPs were characterized by scanning electron microscope (SEM), differential scanning calorimetry (DSC), thermogravimetry analysis (TGA), and Fourier transformed infra-red spectroscopy (FT-IR). SEM image implied that NPs were spherical in shape and the results of DSC, TGA, and FT-IR suggest that 5-FU was encapsulated into NPs. The obtained results revealed that 5-FU loaded PHBV/PLGA NPs induced significant higher cell death at concentration much lower than free 5-FU. Results of hemolysis assay indicated that the NPs were hemo-compatible. In vivo anti-tumor studies showed that 5-FU loaded NPs reduced tumor volume significantly in comparison with free 5-FU. As the first example of using PHBV/PLGA as nano-drug delivery system with enhanced anti-tumor activities, this study establishes PHBV/PLGA as a novel promising drug delivery platform for treatment of colon cancer.
Laboratory Monitoring of Biological Therapies in Rheumatology: The Role of Immunogenicity

Biological drugs, such as proteins and immunogens, are increasingly used to treat various diseases, including tumors and autoimmune diseases, and biological molecules have almost completely replaced synthetic drugs in rheumatology. Although biological treatments such as anti-tumor necrosis factor (TNF) drugs seem to be quite safe, they cause some undesirable effects, such as the onset of infections due to weakening of the immune system. Given the biological nature of these drugs, they might be recognized as extraneous; this would induce an immune reaction that neutralizes their effectiveness or lead to more serious consequences. Laboratories play a pivotal role in appropriate therapeutic management. The aim of this review was to underline the production of anti-drug antibodies during treatment with biological drugs and highlight the role of laboratories in ensuring appropriate use of these drugs.
Does Racial Disparity in Kidney Transplant Waitlisting Persist After Accounting for Social Determinants of Health?

Background. African Americans (AA) have lower rates of kidney transplantation (KT) compared with Whites (WH), even after adjusting for demographic and medical factors. In this study, we examined whether the racial disparity in KT waitlisting persists after adjusting for social determinants of health (eg, cultural, psychosocial, and knowledge). Methods. We prospectively followed a cohort of 1055 patients who were evaluated for KT between 3 of 10 to 10 of 12 and followed through 8 of 18. Participants completed a semistructured telephone interview shortly after their first KT evaluation appointment. We used the Wilcoxon rank-sum and Pearson chi-square tests to examine race differences in the baseline characteristics. We then assessed racial differences in the probability of waitlisting while accounting for all predictors using cumulative incidence curves and Fine and Gray proportional subdistribution hazards models. Results. There were significant differences in the baseline characteristics between non-Hispanic AA and non-Hispanic WH. AA were 25% less likely (95% confidence interval, 0.60-0.96) to be waitlisted than WH even after adjusting for medical factors and social determinants of health. In addition, being older, having lower income, public insurance, more comorbidities, and being on dialysis decreased the probability of waitlisting while having more social support and transplant knowledge increased the probability of waitlisting. Conclusions. Racial disparity in kidney transplant waitlisting persisted even after adjusting for medical factors and social determinants of health, suggesting the need to identify novel factors that impact racial disparity in transplant waitlisting. Developing interventions targeting cultural and psychosocial factors may enhance equity in access to transplantation.
Finger Joint Cartilage Evaluated by Semiquantitative Ultrasound Score in Patients With Rheumatoid Arthritis

Joint destruction in rheumatoid arthritis (RA) includes both bone and cartilage lesions. Since joint space narrowing (JSN) is not a direct evaluation of cartilage using radiography, we aimed to examine the validity of ultrasound (US) cartilage evaluation using a semiquantitative method in patients with RA.
The Effect of Sport-Related Concussion Injuries on Concussion Symptoms and Health-Related Quality of Life in Male and Female Adolescent Athletes: A Prospective Study

Background: Sport-related concussions (SRCs) are associated with short-term disablement, characterized as increased concussion symptoms and lower health-related quality of life (HRQoL). However, there are limited longitudinal data detailing how an SRC affects disablement beyond short-term injury recovery. Purpose: To longitudinally assess the effect of SRCs on symptoms and HRQoL in high school athletes through the 12 months after injury. Study Design: Cohort study; Level of evidence, 2. Methods: The 125 participants included high school athletes who sustained an SRC (female patients, 36%; mean ± SD age, 15.9 ± 1.1 years). The Post-concussion Symptom Scale (PCSS) from the Sport Concussion Assessment Tool–3 and the Pediatric Quality of Life Inventory 4.0 (PedsQL) were completed at enrollment and repeated at 24 to 72 hours (onset) and at 7 days (D7) after the SRC; on the date of return to play (RTP); and at 3, 6, and 12 months (M12) after the SRC. Scores at each time point were compared with the athletes’ own baseline via linear mixed models for repeated measures, controlling for age, sex, and history of previous SRC and with patient as a random effect. Results: Relative to baseline, female patients reported higher PCSS symptom and severity scores at onset (P < .001) and D7 (P < .001), while scores were not higher (P > .05) for RTP through M12. As compared with baseline, male patients reported higher PCSS scores at onset (P < .001) and D7 (P = .003) and severity scores at onset (P < .001) and D7 (P = .016), while the symptom and severity scores were not higher (P > .05) at RTP through M12. Female participants reported lower PedsQL physical scores at onset (P = .006), while scores were not lower (P > .05) from D7 through M12. Female psychosocial scores were not lower (P > .05) at any time after the SRC, while the total PedsQL score was lower at onset (P = .05) but not from D7 through M12. Male physical scores were lower at onset (P < .001) and D7 (P = .001) but not lower (P > .05) from RTP through M12. Male psychosocial and PedsQL scores were unchanged (P > .05) from baseline at onset through M12. Conclusion: After an SRC, high school athletes reported initial disablement (increased symptoms and lower HRQoL) through their RTP. However, after RTP, no similar disablement was detected through 12 months after injury.