Miracle-dz/UniFAR-FTUs huggingface dataset:
Usefulness of small bowel reexamination in obscure gastrointestinal bleeding patients with negative capsule endoscopy findings: Comparison of repeat capsule endoscopy and double-balloon enteroscopy

Background Although capsule endoscopy (CE) is a noninvasive diagnostic tool for patients with obscure gastrointestinal bleeding (OGIB), bleeding lesions are often not detected. No strategies have been established to determine whether CE or double-balloon enteroscopy (DBE) should be performed after negative CE. Methods Among 652 patients who underwent CE for OGIB, a total of 359 patients had negative findings. Of these, 41 and 48 patients underwent repeat CE and DBE for small bowel reexamination, respectively. We compared the rate of positive findings between the two groups. The findings were considered positive if mucosal break, vascular lesion, tumor, or active bleeding was observed. Results The rate of positive findings in the repeat CE group was significantly higher than that in the DBE group (73.2% vs. 39.6%; p = 0.001). Logistic regression analysis showed that the repeat CE group was significantly associated with positive findings (odds ratio (OR), 4.2; 95% confidence interval (CI), 1.7–10.2; p = 0.002). Inverse probability of treatment-weighted analysis revealed that repeat CE was significantly associated with positive findings (OR, 4.4; 95% CI, 1.6–12.2; p = 0.004). Conclusions Reexamination via CE appears to have more diagnostic value than DBE for OGIB patients with negative CE findings.
VAMP-associated protein-A and oxysterol-binding protein–related protein 3 promote the entry of late endosomes into the nucleoplasmic reticulum

The endocytic pathway plays an instrumental role in recycling internalized molecules back to the plasma membrane or in directing them to lysosomes for degradation. We recently reported a new role of endosomes–the delivery of components from extracellular vesicles (EVs) to the nucleoplasm of recipient cells. Using indirect immunofluorescence, FRET, immunoisolation techniques, and RNAi, we report here a tripartite protein complex (referred to as the VOR complex) that is essential for the nuclear transfer of EV-derived components by orchestrating the specific localization of late endosomes into nucleoplasmic reticulum. We found that the VOR complex contains the endoplasmic reticulum–localized vesicle-associated membrane protein (VAMP)-associated protein A (VAP-A), the cytoplasmic oxysterol-binding protein–related protein 3 (ORP3), and late endosome–associated small GTPase Rab7. The silencing of VAP-A or ORP3 abrogated the association of Rab7-positive late endosomes with nuclear envelope invaginations and, hence, the transport of endocytosed EV-derived components to the nucleoplasm of recipient cells. We conclude that the VOR complex can be targeted to inhibit EV-mediated intercellular communication, which can have therapeutic potential for managing cancer in which the release of EVs is dysregulated.
Quantitative Spatial Profiling of PD-1/PD-L1 Interaction and HLA-DR/IDO-1 Predicts Improved Outcomes of Anti–PD-1 Therapies in Metastatic Melanoma

Purpose: PD-1/L1 axis–directed therapies produce clinical responses in a subset of patients; therefore, biomarkers of response are needed. We hypothesized that quantifying key immunosuppression mechanisms within the tumor microenvironment by multiparameter algorithms would identify strong predictors of anti–PD-1 response. Experimental Design: Pretreatment tumor biopsies from 166 patients treated with anti–PD-1 across 10 academic cancer centers were fluorescently stained with multiple markers in discovery (n = 24) and validation (n = 142) cohorts. Biomarker-positive cells and their colocalization were spatially profiled in pathologist-selected tumor regions using novel Automated Quantitative Analysis algorithms. Selected biomarker signatures, PD-1/PD-L1 interaction score, and IDO-1/HLA-DR coexpression were evaluated for anti–PD-1 treatment outcomes. Results: In the discovery cohort, PD-1/PD-L1 interaction score and/or IDO-1/HLA-DR coexpression was strongly associated with anti–PD-1 response (P = 0.0005). In contrast, individual biomarkers (PD-1, PD-L1, IDO-1, HLA-DR) were not associated with response or survival. This finding was replicated in an independent validation cohort: patients with high PD-1/PD-L1 and/or IDO-1/HLA-DR were more likely to respond (P = 0.0096). These patients also experienced significantly improved progression-free survival (HR = 0.36; P = 0.0004) and overall survival (HR = 0.39; P = 0.0011). In the combined cohort, 80% of patients exhibiting higher levels of PD-1/PD-L1 interaction scores and IDO-1/HLA-DR responded to PD-1 blockers (P = 0.000004). In contrast, PD-L1 expression was not predictive of survival. Conclusions: Quantitative spatial profiling of key tumor-immune suppression pathways by novel digital pathology algorithms could help more reliably select melanoma patients for PD-1 monotherapy. Clin Cancer Res; 24(21); 5250–60. ©2018 AACR.
Sex differences in large conducting airway anatomy.

Airway luminal area is the major determinant of resistance to airflow in the tracheobronchial tree. Women may have smaller central conducting airways than men; however, previous evidence is confounded by an indirect assessment of airway geometry and by subjects with prior smoking history. The purpose of this study was to examine the effect of sex on airway size in healthy nonsmokers. Using low-dose high-resolution computed tomography, we retrospectively assessed airway luminal area in healthy men ( n = 51) and women ( n = 73) of varying ages (19-86 yr). Subjects with a positive smoking history, cardiopulmonary disease, or a body mass index > 40 kg/m2 were excluded. Luminal areas of the trachea, right and left main bronchus, bronchus intermediate, left and right upper lobes, and the left lower lobe were analyzed at three discrete points. The luminal areas of the conducting airways were ~26%-35% smaller in women. The trachea had the largest differences in luminal area between men and women (298 ± 47 vs. 195 ± 28 mm2 or 35% smaller for men and women, respectively), whereas the left lower lobe had the smallest differences (57 ± 15 vs. 42 ± 9 mm2 or 26% smaller for men and women, respectively). When a subset of subjects was matched for height, the sex differences in airway luminal area persisted, with women being ~20%-30% smaller. With all subjects, there were modest relationships between height and airway luminal area ( r = 0.73-0.53, P < 0.05). Although there was considerable overlap between sexes, the luminal areas of the large conducting airways were smaller in healthy women than in men. NEW & NOTEWORTHY Previous evidence for sex differences in airway size has been confounded by indirect measures and/or cohorts with significant smoking histories or pathologies. We found that central airways in healthy women were significantly smaller (~26%-35%) than men. The significant sex-difference in airway size was attenuated (20%-30% smaller) but preserved in a subset of subjects matched for height. Over a range of ages, healthy women have smaller central airways than men.
Assessment Practices in Secondary-school Mathematics Teaching in Brazil

Classroom-based assessment has been a matter of concern and discussion in academia, especially in recent years. Many studies have been conducted, particularly about the implementation of formative assessment. Although it has been heralded as an important practice, there is still little research about this subject related to mathematics education, particularly in Brazil. Aiming to seek information about the types of approach that secondary-school mathematics teachers in Brazil have been taking in their classrooms, survey research was conducted via an e-questionnaire. The teachers were asked, among other aspects, about the frequency with which they apply and the importance they give to specific assessment methods or procedures. The results from the quantitative analysis show that tests and homework assignments are the methods most commonly used by mathematics teachers, whereas selfand peer-assessment are still not common practice.
The impact of a history of cancer on pancreatic ductal adenocarcinoma survival

Background and objective Previous studies indicated cancer survivors had a higher risk of developing subsequent pancreatic ductal adenocarcinoma. However, the influence of prior cancer on survival outcomes of current pancreatic cancer remains unclear. Methods Eligible populations were selected from the Surveillance, Epidemiology, and End Results programs from 2000 to 2012. We adopted Kaplan–Meier curves and Cox analysis to compare survival differences between patients with and without prior cancer. Results Overall, 67,555 pancreatic cancer patients, including 5582 (8.26%) with and 61,973 (91.74%) without prior cancer, were included. The most common types of prior cancers were prostate, breast, and colorectal cancers. The median time from diagnosis of an initial malignancy to subsequent pancreatic cancer was 59.8 months. Patients with a prior cancer had higher overall one-year and three-year survival rates compared with those without a prior cancer. Multivariable Cox analysis demonstrated that a history of prior malignancy could independently predict the better overall survival outcome of pancreatic cancer (HR = 0.92, 95% CI, 0.89–0.94, p < 0.001), especially for colorectal, breast, corpus uteri and prostate cancer survivors. Conclusions A history of cancer did not contribute to a poor survival outcome for patients with pancreatic cancer. More prospective trials might be warranted to validate our findings.
Physical activity levels are low in patients with pulmonary hypertension.

Background Pulmonary hypertension (PH) leads to exercise capacity impairment, but limited data are available on the objective evaluation of physical activity (PA) levels in these patients. Methods We assessed PA levels using triaxial accelerometry in Spanish PH patients (n=75, 48±14 years, 65% female) and gender/age matched controls (n=107), and examined potential associations of meeting minimum international recommendations [moderate-vigorous PA (MVPA) ≥150 min/week] with survival predictors. Results With the exception of vigorous PA (with very low values in both groups), all accelerometry data showed significant differences between patients and controls, with lower PA levels and proportion of individuals meeting minimum PA guidelines, but higher inactivity time, in the former. Notably, the odds ratio (OR) of having a "low-risk" value of 6-minute walking distance (≥464 m) or ventilatory equivalent for carbon dioxide (≤39) was higher in patients following MVPA guidelines than in their less active peers [OR =4.3, 95% confidence interval (CI), 1.6-11.6, P=0.005, and OR =4.5, 95% CI, 0.9-21.1, P=0.054]. Conclusions Daily PA is reduced in patients with PH, often to a level that may decrease their odds of survival. Efforts should be made to promote the implementation of healthy PA habits in this patient population.
On the origin of lognormal network synchrony in CA1

The sharp wave ripple complex in rodent hippocampus is associated with a network burst in CA3 (NB) that triggers a synchronous event in the CA1 population (SE). The number of CA1 pyramidal cells participating in a SE has been observed to follow a lognormal distribution. However, the origin of this skewed and heavy‐tailed distribution of population synchrony in CA1 remains unknown. Because the size of SEs is likely to originate from the size of the NBs and the underlying neural circuitry, we model the CA3‐CA1 circuit to study the underlying mechanisms and their functional implications. We show analytically that if the size of a NB in CA3 is distributed according to a normal distribution, then the size of the resulting SE in CA1 follows a lognormal distribution. Our model predicts the distribution of the NB size in CA3, which remains to be tested experimentally. Moreover, we show that a putative lognormal NB size distribution leads to an extremely heavy‐tailed SE size distribution in CA1, contradicting experimental evidence. In conclusion, our model provides general insight on the origin of lognormally distributed network synchrony as a consequence of synchronous synaptic transmission of normally distributed input events.
Production of indole-3-acetic acid by Enterobacter sp. DMKU-RP206 using sweet whey as a low-cost feed stock.

In this study, we investigated IAA production by a rice phylloplane bacteria, Enterobacter sp. DMKU-RP206, using sweet whey as a feed stock instead of lactose. We succeeded in using sweet whey for Enterobacter sp. DMKU-RP206 to produce 3,963.0 mg IAA/l with the optimal medium containing1.48% sweet whey, 1.42% yeast extract and 0.88% L-tryptophan. The medium pH was adjusted to 6 and the culture conditions were shaking at 200 rpm on an orbital shaker at 30 °C for 3 days. We also evaluated the effect of IAA in culture filtrates of Enterobacter sp. DMKU-RP206 on the promotion of jasmine rice growth in a pot experiment. Compared with the negative control (without IAA), the result showed that biosynthetic IAA produced by Enterobacter sp. DMKU-RP206 significantly increased the growth of jasmine rice (Oryza sativa L. cv. KDML105) in terms of length and dry weight of shoot. This work thus reveals the impact of IAA produced by Enterobacter sp. on the promotion of jasmine rice growth.
Promoting Resilience in Individuals Aging With Multiple Sclerosis: Results From a Pilot Randomized Controlled Trial

Purpose/Objective: Starting in middle adulthood, individuals living with multiple sclerosis (MS) are confronted with the simultaneous challenge of coping with advancing MS alongside age-related changes. Psychological resilience is thought to play an important role in promoting healthy aging and thus may be important in the context of aging with MS. This study aimed to evaluate whether Everyday Matters, a novel positive psychology program, had a positive effect on resilience and other related outcomes in adults with MS relative to a wait-list control group. Research Method/Design: This was a single-center two-group pilot randomized (1:1) controlled trial comparing the Everyday Matters intervention to a waitlist control. Randomized participants were N = 31 adults with MS aged ≥45 years. The 6-week program, developed by the National MS Society, was delivered via group teleconference and supplemented with readings, videos, and online participation. Participants in both groups completed outcome assessments measuring resilience, satisfaction with social roles, mood, pain, fatigue, and sleep at baseline and posttreatment. Results: Analyses on N = 27 participants who completed study assessments revealed a significant group effect for resilience and satisfaction with social roles, and trend differences for positive affect and well-being and depressive symptom severity. At posttreatment, participants in the intervention group reported the group to be very helpful, found the telephone-based delivery convenient, and felt the benefits of participating outweighed the effort. Conclusions/Implications: These results suggest that the Everyday Matters program shows promise for increasing resilience in adults with MS and that a full-scale randomized controlled trial is warranted.
Relationship between PSA kinetics and Tc‐99m HYNIC PSMA SPECT/CT detection rates of biochemical recurrence in patients with prostate cancer after radical prostatectomy

Prostate‐specific antigen (PSA) levels should reflect or be proportional to the size and the metabolic activity of prostatic metastases. Moreover, a rapid change in PSA kinetics, either before or after treatment, is an indicator of poor prognosis after radical prostatectomy. Therefore, the purpose of this study was to investigate the effect of total PSA at the time of Tc‐99m HYNIC PSMA SPECT/CT (trigger PSA), PSA velocity (PSAvel), and PSA doubling time (PSAdt) on the Tc‐99m HYNIC PSMA SPECT/CT detection rate in prostate cancer patients who showed biochemical recurrence after radical prostatectomy during follow‐up.
Multidimensional factors of determining trajectories in self-rated health and depressive symptoms among Korean children and adolescents

ABSTRACT Understanding health disparities in the early stage of life is complicated by the complex interplay of psychosocial and environment factors. Despite these complexities, few studies have investigated multidimensional aspects of determining health trajectories of Korean children and adolescents. Thus, this study aims to investigate the impact of intrapersonal, interpersonal, and environmental factors on trajectories in self-rated health and depressive symptoms. Totally, 2378 Korean student samples were selected from the Korean Children and Young Panel Survey for data analysis. The findings indicated that higher levels of self-esteem, attachment to parents, and relationship with friends predicted better self-rated health and less depressive symptoms at baseline. Perception on community only predicted better self-rated health but not depressive symptoms at baseline. Among multidimensional factors, only self-esteem predicted the rate of changes in self-rated health and depressive symptoms. This study suggested that enhancing self-esteem and supportive environment should be provided throughout childhood and adolescence.
QTLseqr: An R package for bulk segregant analysis with next-generation sequencing

Summary QTL-seq is a relatively new and rapid way for performing bulk segregant analysis using next-generation sequencing data. However, no easy-to-use and multi-system compatible algorithms for performing this analysis are readily available. We developed the QTLseqr R package, that implements two methods, ∆SNP-index and G’, for quick identification of genomic regions associated with traits of interest in next-generation sequencing, bulk segregant analysis experiments. Availability and Implementation QTLseqr is available at https://github.com/bmansfeld/QTLseqr. Contact mansfeld@msu.edu Supplementary information Supplementary data are available at Bioinformatics online.
Language Disorders and Problem Behaviors: A Meta-analysis

We meta-analyzed 47 studies in which authors investigated the association between language disorders and problem behaviors and found a moderate effect size that changes over development. CONTEXT: A large number of studies have shown a relationship between language disorders and problem behaviors; however, methodological differences have made it difficult to draw conclusions from this literature. OBJECTIVE: To determine the overall impact of language disorders on problem behaviors in children and adolescents between the ages of birth and 18 years and to investigate the role of informant type, age, and type of problem behavior on this relationship. DATA SOURCES: We searched PubMed, EBSCO, and ProQuest. STUDY SELECTION: Studies were included when a group of children with language disorders was compared with a group of typically developing children by using at least 1 measure of problem behavior. DATA EXTRACTION: Effect sizes were derived from all included measures of problem behaviors from each study. RESULTS: We included 47 articles (63 153 participants). Meta-analysis of these studies revealed a difference in ratings of problem behaviors between children with language disorders and typically developing children of moderate size (g = 0.43; 95% confidence interval 0.34 to 0.53; P < .001). Age was entered as a moderator variable, and results showed that the difference in problem behavior ratings increases with child age (increase in g for each additional year in age = 0.06; 95% confidence interval 0.02 to 0.11; P = .004). LIMITATIONS: There was considerable heterogeneity in the measures of problem behaviors used across studies. CONCLUSIONS: Children with language disorders display greater rates of problem behaviors compared with their typically developing peers, and this difference is more pronounced in older children.
Integrative Review for Patients With Bilateral Total Knee Replacement: A Call for Nursing Practice Guidelines.

BACKGROUND The aim of this joint project between the National Association of Orthopaedic Nurses and the Association of Rehabilitation Nurses was to develop nursing practice guidelines for patients who experience bilateral knee arthroplasty (BTKA) across the continuum of care. No guidelines existed and an integrative review was completed to address this gap. METHODS An integrative review of refereed quantitative and qualitative research in published and gray literature was completed to answer the clinical questions: (1) What is the scope of evidence-based nursing interventions for patients undergoing BTKA? (2) What are patients' experiences with BTKA across the care continuum? The scope of the literature search was patients with bilateral and unilateral total knee arthroplasty. An evidence-based system was used to rate the strength of studies that met the criteria for inclusion in this review. RESULTS The search method identified 588 potential titles but the analysis of the abstracts supported only 128 studies for possible inclusion in this project. The authors independently reviewed these studies and concluded that 126 studies did not meet the inclusion criteria and 2 quantitative studies were eligible for inclusion. CONCLUSIONS Understanding which interventions are most effective for pain management, functional gains, quality of life, and other nurse-sensitive outcomes is best derived from empirical studies. Most likely, BTKA nursing care is being guided by clinical experts and not by empirical nursing evidence. In the absence of empirical evidence, it is feasible that nurses can extrapolate findings from other studies to guide and support the care of BTKA patients. Research recommendations include the exploration of early mobilization interventions, development of nursing care bundles, and evaluation of patient-centered outcomes at the points of transitional care.
Wnt5a Contributes to the Differentiation of Human Embryonic Stem Cells into Lentoid Bodies Through the Noncanonical Wnt/JNK Signaling Pathway.

Purpose Recent work has indicated that Wnt5a has a critical role in embryonic development. We investigate whether the Wnt5a-activated noncanonical Wnt pathway is capable of promoting embryonic lens differentiation. Methods A "three-stage" protocol was used to induce lens differentiation of human embryonic stem cells (hESCs) in vitro, and Wnt5a levels were modified by addition of exogenous protein and RNA interference. SP600125 was adopted to inhibit JNK cascades. The number and size of lentoid bodies obtained were measured, and quantitative RT-PCR, Western blotting, and immunofluorescence were used to detect gene and protein expression. Results The quantity and size of lentoid bodies generated were significantly increased by addition of exogenous Wnt5a. Moreover, expression of lens-specific genes, including CRYAA, CRYAB, BFSP1, and MIP, and the lens fiber differentiation regulator PROX1 were prominently increased. We also observed activation of noncanonical Wnt signaling via upregulation of Dvl2, Rac1, and JNK. When Wnt5a-knockdown hESCs were induced to differentiate, fewer and smaller lentoid bodies resulted. In addition, expression of genes specific to lens was decreased and noncanonical Wnt/JNK pathway activity was downregulated. Accordingly, inhibition of JNK cascade suppressed the formation of lentoid bodies as well, consistent with that of Wnt5a-knockdown group. Conclusions Wnt5a can promote the differentiation of hESCs into lentoid bodies through the noncanonical Wnt/JNK signaling pathway, thereby contributing to the study of human lens development and moreover the underlying etiology congenital cataracts.