Miracle-dz/UniFAR-FTUs huggingface dataset:
Cell Cycle Progression Regulates Biogenesis and Cellular Localization of Lipid Droplets

Intracellular lipid accumulation has been associated with a poor prognosis in cancer. We have previously reported the involvement of lipid droplets in cell proliferation in colon cancer cells, suggesting a role for these organelles in cancer development. ABSTRACT Intracellular lipid accumulation has been associated with a poor prognosis in cancer. We have previously reported the involvement of lipid droplets in cell proliferation in colon cancer cells, suggesting a role for these organelles in cancer development. In this study, we evaluate the role of lipid droplets in cell cycle regulation and cellular transformation. Cell cycle synchronization of NIH 3T3 cells revealed increased numbers and dispersed distribution of lipid droplets specifically during S phase. Also, the transformed cell lineage NIH 3T3-H-rasV12 showed an accumulation of both lipid droplets and PLIN2 protein above the levels in NIH 3T3 cells. PLIN2 gene overexpression, however, was not able to induce NIH 3T3 cell transformation, disproving the hypothesis that PLIN2 is an oncogene. Furthermore, positive PLIN2 staining was strongly associated with highly proliferative Ki-67-positive areas in human colon adenocarcinoma tissue samples. Taken together, these results indicate that cell cycle progression is associated with tight regulation of lipid droplets, a process that is altered in transformed cells, suggesting the existence of a mechanism that connects cell cycle progression and cell proliferation with lipid accumulation.
Is Variation in Biological and Residential Ties to Children Linked to Mothers’ Parental Stress and Perceptions of Coparenting?

Mothers with children from prior relationships or with stepchildren may perceive greater challenges in parenting than their counterparts in less complex families. We use the Families and Relationships Study to analyze parental stress and perceptions of coparenting among cohabiting and married mothers with resident minor children (N = 679). Compared with mothers with only shared children, parental stress and perceptions of coparenting generally do not differ when mothers have children from prior unions. However, mothers with resident stepchildren evaluate the distribution of child care as less fair, consider their partners as less reliable coparents, and rate their partner more poorly as a coparent relative to those with no stepchildren. These findings suggest that creating a stepfamily through one’s own children may not present additional parenting challenges or stressors, whereas having stepchildren introduced through a partner may be linked to a different, and less positive, parenting experience.
The Oral Health of Refugees and Asylum Seekers in Canada: A Mixed Methods Study Protocol

Canada received over 140,000 refugees and asylum seekers between 2015 and 2017. This paper presents a protocol with the purpose of generating robust baseline data on the oral health of this population and build a long-term program of research to improve their access to dental care in Canada. The three-phase project uses a sequential mixed methods design, with the Behavioral Model for Vulnerable Populations as the conceptual framework. In Phase 1a, we will conduct five focus groups (six to eight participants per group) in community organizations in Ontario, Canada, to collect additional sociocultural data for the research program. In Phase 1b, we will use respondent-driven sampling to recruit 420 humanitarian migrants in Ontario and Quebec. Participants will complete a questionnaire capturing socio-demographic information, perceived general health, diet, smoking, oral care habits, oral symptoms, and satisfaction with oral health. They will then undergo dental examination for caries experience, periodontal health, oral pain, and traumatic dental injuries. In Phase 2, we will bring together all qualitative and quantitative results by means of a mixed methods matrix. Finally, in Phase 3, we will hold a one-day meeting with policy makers, dentists, and community leaders to refine interpretations and begin designing future oral health interventions for this population.
Burden and Correlates of Hospital Readmissions among U.S. Peritoneal Dialysis Patients

Background: Hospital readmissions are common among in-center hemodialysis patients, but little is known about readmissions among peritoneal dialysis (PD) patients. Using national administrative data, we aimed to examine the burden and correlates of hospital readmissions among U.S. PD patients. Methods: Among 10,505 adult U.S. PD patients with an index admission (first admission after 120 days on dialysis) between 31 January 2011 and 30 November 2014, readmissions were defined as new hospital admissions within 30 days of index discharge. Multivariable logistic regression was used to obtain adjusted odds ratios (ORs) for readmission. Results: Overall, 26.8% of index admissions were followed by a readmission. Readmitted patients were more likely to have congestive heart failure (31.0% vs 25.4%; p < 0.001) and peripheral arterial disease (11.6% vs 8.6%; p < 0.001) and had longer index admission length of stay (median = 4 vs 3 days; p < 0.001) than those who were not; age, sex, and race did not differ by readmission status. After adjustment for patient and index admission characteristics, longer length of stay (≥ 4 vs < 4 days, OR = 1.48, 95% confidence interval [CI] 1.35 – 1.62), peripheral arterial disease (OR = 1.31, 95% CI 1.16 – 1.57), congestive heart failure (OR = 1.25, 95% CI 1.13 – 1.39), and ischemic heart disease (OR = 1.12, 95% CI 1.01 – 1.24) were associated with higher likelihood of readmission; index admission due to peritonitis vs other causes was associated with lower likelihood of readmission (OR = 0.80, 95% CI 0.70 – 0.92). Conclusions: Our results suggest that, particularly in the absence of a PD-related cause of hospitalization such as peritonitis, PD patients may be at high risk for readmission and may benefit from closer post-discharge monitoring.
Dietary Components That May Influence the Disturbed Gut Microbiota in Chronic Kidney Disease

Gut microbiota imbalance is common in patients with chronic kidney disease (CKD) and associates with factors such as increased circulating levels of gut-derived uremic toxins, inflammation, and oxidative stress, which are linked to cardiovascular disease and increased morbimortality. Different nutritional strategies have been proposed to modulate gut microbiota, and could potentially be used to reduce dysbiosis in CKD. Nutrients like proteins, fibers, probiotics, and synbiotics are important determinants of the composition of gut microbiota and specific bioactive compounds such as polyphenols present in nuts, berries. and fruits, and curcumin, may also play a key role in this regard. However, so far, there are few studies on dietary components influencing the gut microbiota in CKD, and it is therefore not possible to conclude which nutrients should be prioritized in the diet of patients with CKD. In this review, we discuss some nutrients, diet patterns and bioactive compounds that may be involved in the modulation of gut microbiota in CKD and provide the background and rationale for studies exploring whether nutritional interventions with these dietary components could be used to alleviate the gut dysbiosis in patients with CKD.
Psychological morbidity is the main predictor of quality of life among caregivers of individuals in first-episode psychosis: data from a year-long longitudinal study in Brazil

Objective: To investigate quality of life (QoL) and QoL predictors among caregivers of individuals in first-episode psychosis (FEP). Methods: This longitudinal study investigated predictors of QoL in caregivers of 80 individuals in FEP over a 1-year follow-up period, measured using a single component extracted from the 36-item Short-Form Health Survey (SF-36). Results: Mediation analysis demonstrated that, at 1 year, high scores in the Self-Report Questionnaire (SRQ-20) were associated with high scores on the negative sub-scale of the Experience of Caregiving Inventory (ECI), which was also associated with low scores in the Essential Quality of Life (Essential QoL) component extracted from the SEF-36. Clinically, the resulting association indicates that depression and anxiety symptoms in caregivers at baseline are predictors of their 1-year quality of life, based on self-assessment of the caregiving experience. Conclusion: Supporting an individual in FEP can have a negative impact on QoL. Maintaining caregivers’ mental health and subjective evaluation of the caregiving experience must be primary goals of FEP services. Complementary studies of FEP caregivers’ QoL can support the design of personalized interventions in the near future.
High Burden of Extended-Spectrum β-Lactamase–Producing Escherichia coli and Klebsiella pneumoniae Bacteremia in Older Adults: A Seven-Year Study in Two Rural Thai Provinces

Abstract. Bloodstream infection surveillance conducted from 2008 to 2014 in all 20 hospitals in Sa Kaeo and Nakhon Phanom provinces, Thailand, allowed us to look at disease burden, antibiotic susceptibilities, and recurrent infections caused by extended-spectrum β-lactamase (ESBL)–producing Escherichia coli and Klebsiella pneumoniae. Of 97,832 blood specimens, 3,338 were positive for E. coli and 1,086 for K. pneumoniae. The proportion of E. coli isolates producing ESBL significantly increased from 19% to 22% in 2008–2010 to approximately 30% from 2011 to 2014 (P-value for trend = 0.02), whereas ESBL production among K. pneumoniae cases was 27.4% with no significant trend over time. Incidence of community-onset ESBL-producing E. coli increased from 5.4 per 100,000 population in 2008 to 12.8 in 2014, with the highest rates among persons aged ≥ 70 years at 79 cases per 100,000 persons in 2014. From 2008 to 2014, community-onset ESBL-producing K. pneumoniae incidence was 2.7 per 100,000, with a rate of 12.9 among those aged ≥ 70 years. Although most (93.6% of E. coli and 87.6% of K. pneumoniae) infections were community-onset, hospital-onset infections were twice as likely to be ESBL. Population-based surveillance, as described, is vital to accurately monitor emergence and trends in antimicrobial resistance, and in guiding the development of rational antimicrobial therapy recommendations.
First Report of Leaf Spot Caused by Cylindrocladium pauciramosum on Acacia retinodes, Arbutus unedo, Feijoa sellowiana, and Dodonaea viscosa in Southern Italy.

In October 1997, severe leaf spotting was observed on several ornamental plants growing in different nurseries in southern Italy. These symptoms were detected for the first time on strawberry tree (Arbutus unedo L.) and water wattle (Acacia retinodes Schltdl.). In the latter species, diseased plants showed also stem canker and shoot blight symptoms. Cylindrocladium pauciramosum C.L. Schoch & Crous (teleomorph Calonectria pauciramosa) were found associated with these symptoms (2). More recently, leaf spots were found also on feijoa (Feijoa sellowiana Berg.) and on Florida hopbush (Dodonaea viscosa (L.) Jacq. ) in two other nurseries located in Sicily. Infected tissues were surface-sterilized and plated on potato dextrose agar. Plates were incubated at room temperature under fluorescent cool white lights on a 12-h light/dark regime. A Cylindrocladium species was consistently associated with diseased tissues. The isolates of Cylindrocladium collected from feijoa and Florida hopbush were identified on carnation leaf agar as C. pauciramosum on the basis of their obpyriform to broadly ellipsoidal terminal vesicles, conidiophore branching pattern, and conidium morphology, as well as mating type studies with tester strains of C. pauciramosum (1,3). Koch's postulates were fulfilled by inoculating 6-month-old seedlings of the four ornamental plants with a spore suspension of the fungus (104 conidia per ml). Following inoculation, all plants were maintained in a glasshouse where the temperature was 15 to 25° C and relative humidity was 80 to 90%. After 6 to 8 days, symptoms resembling those seen in the nurseries were apparent. The Cylindrocladium species was reisolated from lesions on inoculated plants, thus confirming it to be the causal organism of these diseases. This is apparently the first report of C. pauciramosum leaf spot on these hosts. References: (1) P. W. Crous and M. J. Wingfield. Mycotaxon 51: 341, 1994. (2) G. Polizzi and P.W. Crous. Eur. J. Plant Pathol. 105:407, 1999. (3) C. L. Schoch et al. Mycologia 91:286, 1999.
Detection of Circulating Tumor DNA in Patients With Leiomyosarcoma With Progressive Disease.

Purpose Leiomyosarcoma (LMS) is a soft tissue sarcoma characterized by multiple copy number alterations (CNAs) and without common recurrent single nucleotide variants. We evaluated the feasibility of detecting circulating tumor DNA (ctDNA) with next-generation sequencing in a cohort of patients with LMS whose tumor burden ranged from no evidence of disease to metastatic progressive disease. Patients and Methods Cell-free DNA in plasma samples and paired genomic DNA from resected tumors were evaluated from patients with LMS by ultra-low passage whole genome sequencing (ULP-WGS). Sequencing reads were aligned to the human genome and CNAs identified in cell-free DNA and tumor DNA by ichorCNA software to determine the presence of ctDNA. Clinical data were reviewed to assess disease burden and clinicopathologic features. Results We identified LMS ctDNA in eleven of sixteen patients (69%) with disease progression and total tumor burden over 5 cm. Sixteen patients with stable disease or low disease burden at the time of blood draw were found to have no detectable ctDNA. Higher ctDNA fraction of total cell-free DNA was associated with increasing tumor size and disease progression. Conserved CNAs were found between primary tumors and ctDNA in each case, and recurrent CNAs were found across LMS samples. ctDNA levels declined following resection of progressive disease in one case and became detectable upon disease relapse in another individual patient. Conclusion These results suggest that ctDNA, assayed by a widely available sequencing approach, may be useful as a biomarker for a subset of uterine and extrauterine LMS. Higher levels of ctDNA correlate with tumor size and disease progression. Liquid biopsies may assist in guiding treatment decisions, monitoring response to systemic therapy, surveying for disease recurrence and differentiating benign and malignant smooth muscle tumors.
Genome‐wide analysis reveals miR‐3184‐5p and miR‐181c‐3p as a critical regulator for adipocytes‐associated breast cancer

Obesity is considered as an independent risk factor for breast cancer (BCa) and plays a major role in the breast tumor microenvironment. The etiology and mechanisms by which obesity contributes to BCa development is not yet understood. Herein, we show that in vitro coculture of BCa cells with mature adipocytes (MA‐BCa) increased proliferation, migration, and invasive phenotype of BCa cells. MA‐BCa coculture led to increased production of proinflammatory cytokines and chemokines. To identify microRNAs (miRNAs) in BCa cells that are modulated by the presence of adipocytes, we used small RNA sequencing analysis. Sequencing data revealed that 98 miRNAs were differentially expressed in MA‐BCa. Among them, miR‐3184‐5p and miR‐181c‐3p were found to be the most upregulated and downregulated miRNAs, and direct targets are FOXP4 and PPARα, respectively. In vitro functional assays using a combination of miR‐3184‐5p inhibitor and miR‐181c‐3p mimic synergistically decreased adipocytes‐induced cell proliferation and invasive capacity of BCa cells. Gene Set Enrichment analysis indicated that transcription factors were highly enriched followed by protein kinases, oncogene, and protein regulators in MA‐BCa. GeneGo Metacore pathway analysis uncovered “NOTCH‐induced EMT pathway” was found to be the most abundant in MA‐BCa. Consistently, epithelial–mesenchymal transition‐associated markers were also increased in MA‐BCa. The disease enrichment analysis of the predict target genes revealed that diabetes mellitus was significantly affected disease in MA‐BCa. Taken together, our data suggest that miRNA‐based regulatory mechanism associated with deregulation of pathways and biological functions orchestrated by adipocytes‐secreted factors might drive the BCa progression and metastasis in obese patients.
National Survey on the Management of Adult Bronchiectasis in Belgium

Abstract The increasing prevalence and incidence of bronchiectasis leads to a substantial health care burden. Quality standards for the management of bronchiectasis were formulated by the British Thoracic Society following publication of guidelines in 2010. They can be used as a benchmark for quality of care. It is, however, unclear how and whether they apply outside of the UK. Between May and November 2017, we conducted an online survey among respiratory physicians caring for adult bronchiectasis patients in Belgium. About 186 cases were submitted by 117 treating physicians. Patients were mostly female (58%), of Caucasian descent (84%) with a remarkably low median age of 59.8 (IQR 47–73) years. 41% had Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus and/or Enterobacteriaceae isolated from respiratory samples in the past. 21% had three or more exacerbations, however, more than 58% were receiving long-term oral antibiotics (of which 90% azithromycin). In 40% of patients the diagnostic testing was insufficient. Surveillance of sputum bacteriology in stable patients and composing a self-management plan was missing in 53% and 68% of patients, respectively. Airway clearance techniques were implemented in 84%. Respiratory physicians complied with 60% or more to five out of the eight applicable quality standards, which is encouraging. Increasing educational act could further raise awareness and increase quality of care.
Maladaptive Rumination as a Transdiagnostic Mediator of Vulnerability and Outcome in Psychopathology

Background: Maladaptive rumination is a form of negative repetitive thinking which has attracted the interest of researchers, as it is considered a cognitive vulnerability to depression. Some of the original beliefs regarding rumination, in particular its exclusive link with depression, have been questioned in the light of research findings. At present, the very concept of rumination is still unclear, so research has been investigating this topic from different, and somewhat inconsistent, perspectives. Methods: A literature review was performed in order to outline some core characteristics of rumination, explain its determinants, and discuss its possible role as a transdiagnostic mediator of vulnerability and outcome in psychopathology. Results: Maladaptive rumination could be interpreted as a dysfunctional coping strategy strictly linked to emotion regulation and metacognition that may occur in several psychopathological conditions, such as psychosis, eating disorders, and alcohol dependence. Conclusion: Evidence allows the interpretation of maladaptive rumination as a transdiagnostic mediator of vulnerability and outcome in psychopathology. Therefore, investigating it from a dimensional perspective may represent a valid research strategy.
FAIL Is Not a Four-Letter Word: A Theoretical Framework for Exploring Undergraduate Students’ Approaches to Academic Challenge and Responses to Failure in STEM Learning Environments

Navigating scientific challenges, persevering through difficulties, and coping with failure are considered hallmarks of a successful scientist. However, relatively few studies investigate how undergraduate science, technology, engineering, and mathematics (STEM) students develop these skills and dispositions or how instructors can facilitate this development in undergraduate STEM learning contexts. This is a critical gap, because the unique cultures and practices found in STEM classrooms are likely to influence how students approach challenges and deal with failures, both during their STEM education and in the years that follow. To guide research aimed at understanding how STEM students develop a challenge-engaging disposition and the ability to adaptively cope with failure, we generate a model representing hypotheses of how students might approach challenges and respond to failures in undergraduate STEM learning contexts. We draw from theory and studies investigating mindset, goal orientations, attributions, fear of failure, and coping to inform our model. We offer this model as a tool for the community to test, revise, elaborate, or refute. Finally, we urge researchers and educators to consider the development, implementation, and rigorous testing of interventions aimed at helping students develop a persevering and challenge-engaging disposition within STEM contexts.
Association of Genetic Variants in NUDT15 With Thiopurine-Induced Myelosuppression in Patients With Inflammatory Bowel Disease

Importance Use of thiopurines may be limited by myelosuppression. TPMT pharmacogenetic testing identifies only 25% of at-risk patients of European ancestry. Among patients of East Asian ancestry, NUDT15 variants are associated with thiopurine-induced myelosuppression (TIM). Objective To identify genetic variants associated with TIM among patients of European ancestry with inflammatory bowel disease (IBD). Design, Setting, and Participants Case-control study of 491 patients affected by TIM and 679 thiopurine-tolerant unaffected patients who were recruited from 89 international sites between March 2012 and November 2015. Genome-wide association studies (GWAS) and exome-wide association studies (EWAS) were conducted in patients of European ancestry. The replication cohort comprised 73 patients affected by TIM and 840 thiopurine-tolerant unaffected patients. Exposures Genetic variants associated with TIM. Main Outcomes and Measures Thiopurine-induced myelosuppression, defined as a decline in absolute white blood cell count to 2.5 × 109/L or less or a decline in absolute neutrophil cell count to 1.0 × 109/L or less leading to a dose reduction or drug withdrawal. Results Among 1077 patients (398 affected and 679 unaffected; median age at IBD diagnosis, 31.0 years [interquartile range, 21.2 to 44.1 years]; 540 [50%] women; 602 [56%] diagnosed as having Crohn disease), 919 (311 affected and 608 unaffected) were included in the GWAS analysis and 961 (328 affected and 633 unaffected) in the EWAS analysis. The GWAS analysis confirmed association of TPMT (chromosome 6, rs11969064) with TIM (30.5% [95/311] affected vs 16.4% [100/608] unaffected patients; odds ratio [OR], 2.3 [95% CI, 1.7 to 3.1], P = 5.2 × 10−9). The EWAS analysis demonstrated an association with an in-frame deletion in NUDT15 (chromosome 13, rs746071566) and TIM (5.8% [19/328] affected vs 0.2% [1/633] unaffected patients; OR, 38.2 [95% CI, 5.1 to 286.1], P = 1.3 × 10−8), which was replicated in a different cohort (2.7% [2/73] affected vs 0.2% [2/840] unaffected patients; OR, 11.8 [95% CI, 1.6 to 85.0], P = .03). Carriage of any of 3 coding NUDT15 variants was associated with an increased risk (OR, 27.3 [95% CI, 9.3 to 116.7], P = 1.1 × 10−7) of TIM, independent of TPMT genotype and thiopurine dose. Conclusions and Relevance Among patients of European ancestry with IBD, variants in NUDT15 were associated with increased risk of TIM. These findings suggest that NUDT15 genotyping may be considered prior to initiation of thiopurine therapy; however, further study including additional validation in independent cohorts is required.