Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparison of pregnancy outcome between immigrant women in couples with same ethnicity to mixed ethnicity couples

Abstract Aim: To compare the pregnancy outcome of immigrant women who became pregnant to the same ethnicity partner versus a partner from a different ethnicity. Methods: A retrospective cohort study on all singleton pregnancies of immigrant women who delivered between the years 2011–2015 in a single tertiary University Affiliated Hospital. Demographic and obstetrical data were collected. Same ethnicity couples and mixed couples were compared using the Pearson chi-square test for dichotomous variables, and Student’s T-test for normally distributed continuous variables. Results: Overall, 443 immigrant women delivered during the study period, of them, 294 (66.37%) had the same ethnicity spouse and 149 (33.63%) were part of a mixed couple. Women of same ethnicity couples were significantly younger (32.7 versus 35.05 years, p < .0001) and more likely to be nulliparous (48 versus 32%, p = .001), compared to women of mixed couples. The rate of episiotomy was significantly higher among women with the same ethnicity spouse in comparison to women of mixed couples (37.22 versus 23.85%, p = .01). There was no significant difference in all other obstetrical or perinatal outcomes tested. Conclusions: Maternal component is the main factor for perinatal outcomes among immigrant mothers.
Dynamically stiffened matrix promotes malignant transformation of mammary epithelial cells via collective mechanical signaling

Significance Gradual stiffening of the native extracellular matrix has been implicated in promoting breast cancer progression through stiffness-mediated signaling. Herein, we probe mammary epithelial cell responses to substrate stiffness with a dynamically stiffened hydrogel, enabling investigation of how the change in substrate stiffness impacts collective cell behaviors. We demonstrate that signaling pathways, both paracrine and mechanosensing, impact mammary epithelial cell response to stiffening and act in concert to drive epithelial-mesenchymal plasticity. Interestingly, previous static stiffness hydrogel studies did not observe this interplay of signaling, highlighting the need for dynamic materials to recapitulate disease development. These responses can also be inhibited, individually and together, demonstrating how dynamic stiffening drives cancer progression. Breast cancer development is associated with increasing tissue stiffness over years. To more accurately mimic the onset of gradual matrix stiffening, which is not feasible with conventional static hydrogels, mammary epithelial cells (MECs) were cultured on methacrylated hyaluronic acid hydrogels whose stiffness can be dynamically modulated from “normal” (<150 Pascals) to “malignant” (>3,000 Pascals) via two-stage polymerization. MECs form and remain as spheroids, but begin to lose epithelial characteristics and gain mesenchymal morphology upon matrix stiffening. However, both the degree of matrix stiffening and culture time before stiffening play important roles in regulating this conversion as, in both cases, a subset of mammary spheroids remained insensitive to local matrix stiffness. This conversion depended neither on colony size nor cell density, and MECs did not exhibit “memory” of prior niche when serially cultured through cycles of compliant and stiff matrices. Instead, the transcription factor Twist1, transforming growth factor β (TGFβ), and YAP activation appeared to modulate stiffness-mediated signaling; when stiffness-mediated signals were blocked, collective MEC phenotypes were reduced in favor of single MECs migrating away from spheroids. These data indicate a more complex interplay of time-dependent stiffness signaling, spheroid structure, and soluble cues that regulates MEC plasticity than suggested by previous models.
High-Resolution Retinal Imaging Reveals Preserved Cone Photoreceptor Density and Choroidal Thickness in Female Carriers of Choroideremia.

BACKGROUND AND OBJECTIVE To characterize the photoreceptors and choroidal morphology of heterozygous female carriers of choroideremia who typically do not have any visual defects but can have severe funduscopic changes. PATIENTS AND METHODS This was a clinical case series study. Detailed ophthalmic examinations were performed on six female carriers from four families with choroideremia. The subfoveal choroidal thickness (SFCT) was determined by spectral-domain optical coherence tomography (SD-OCT) and the cone photoreceptor density by adaptive optics (AO) retinal imaging. SFCT and cone densities of the carriers were compared to that of normal eyes of healthy subjects. RESULTS The mean age of the carriers was 42.5 years. Fundus photographs showed diffuse, patchy depigmentation; however, the SFCT was within the normal limits. AO retinal imaging revealed preserved cone densities at temporal eccentricities from 2 to 8 angular degrees. CONCLUSIONS The findings indicate that despite the presence of distinctive depigmentation of the retinal pigment epithelium in female carriers of choroideremia, their cone photoreceptor densities and SFCT are well-preserved. These observations may account for the good visual acuity and lack of an awareness of visual disturbances. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:76-85. ].
Plant Extracellular Vesicles Contain Diverse Small RNA Species and Are Enriched in 10- to 17-Nucleotide “Tiny” RNAs[OPEN]

The extracellular space of Arabidopsis leaves contains diverse small RNAs, both inside and outside of extracellular vesicles, with the former being enriched in 10- to 17-nucleotide–long “tiny” RNAs. Small RNAs (sRNAs) that are 21 to 24 nucleotides (nt) in length are found in most eukaryotic organisms and regulate numerous biological functions, including transposon silencing, development, reproduction, and stress responses, typically via control of the stability and/or translation of target mRNAs. Major classes of sRNAs in plants include microRNAs (miRNAs) and small interfering RNAs (siRNAs); sRNAs are known to travel as a silencing signal from cell to cell, root to shoot, and even between host and pathogen. In mammals, sRNAs are transported inside extracellular vesicles (EVs), which are mobile membrane-bound compartments that participate in intercellular communication. In addition to sRNAs, EVs carry proteins, lipids, metabolites, and potentially other types of nucleic acids. Here we report that Arabidopsis (Arabidopsis thaliana) EVs also contain diverse species of sRNA. We found that specific miRNAs and siRNAs are preferentially loaded into plant EVs. We also report a previously overlooked class of “tiny RNAs” (10 to 17 nt) that are highly enriched in EVs. This RNA category of unknown function has a broad and very diverse genome origin and might correspond to degradation products.
Disturbed thalamocortical connectivity in unaffected relatives of schizophrenia patients with a high genetic loading

Objectives: Alterations in thalamocortical anatomical connectivity, specifically the connection between the orbitofrontal cortex and thalamus, have been frequently reported in schizophrenia and are suggested to contribute to the pathophysiology of schizophrenia. The connectivity of the thalamocortical white matter in unaffected relatives of schizophrenia patients was compared to that of healthy controls. Methods: The unaffected relative group was defined as asymptomatic family members who had at least one first-degree relative with schizophrenia and one or more other affected first- to third-degree relatives. A total of 35 unaffected relatives and 34 healthy controls underwent diffusion-weighted and T1-weighted magnetic resonance imaging to examine the white matter connectivity between the thalamus and orbitofrontal cortex using probabilistic tractography. Results: After controlling for age and sex, the unaffected relatives exhibited significantly reduced fractional anisotropy values for the left thalamo-orbitofrontal tract compared to that of healthy controls, F(1, 65) = 6.93, p = 0.011, effect size partial η2 = 0.10. However, there was no association between the Genetic Liability Score and fractional anisotropy in the left thalamo-orbitofrontal tracts. Conclusion: Our findings in the unaffected relatives of schizophrenia patients, which are in line with the alterations reported in schizophrenia, first-episode psychosis and clinical high risk for psychosis, highlight a possible genetic contribution to the proposed biomarker of altered thalamocortical connectivity.
Integrating nutrition into health systems: What the evidence advocates

Abstract There is considerable evidence of positive health and nutrition outcomes resulting from integrating nutrition‐specific interventions into health systems; however, current knowledge on establishing and sustaining effective integration of nutrition into health systems is limited. The objective of this review is to map the existing types of integration platforms and review the evidence on integrated health and nutrition programmes' impacts on specific nutrition outcomes. A literature search was conducted, and integrated nutrition programmes were examined through the lens of the six World Health Organization (WHO) building blocks, including the demand side. Forty‐five studies were included in this review, outlining the integration of nutrition‐specific interventions with various programmes, including integrated community case management and Integrated Management of Childhood Illness, Child Health Days, immunization, early child development, and cash transfers. Limited quantitative data were suggestive of some positive impact on nutrition and non‐nutrition outcomes with no adverse effects on primary programme delivery. Through the lens of the six WHO building blocks, service delivery and health workforce were found to be well‐integrated, but governance, information systems, finance and supplies and technology were less well‐integrated. Integrating nutrition‐specific interventions into health systems may ensure efficient service delivery while having an impact on nutrition outcomes. There is no single successful model of integration; it varies according to the context and demands of the particular setting in which integration occurs. There is a need for more well‐planned programmes considering all the health systems building blocks to ensure compliance and sustainability.
Dose reduction in CT imaging for facial bone trauma in adults: A narrative literature review

Trauma to the facial area accounts for a significant number of admissions to the emergency department. Diagnostic imaging is almost always required, and is critical in determining patient management. Multi‐detector computed tomography (MDCT) appears consistently in the literature as the gold‐standard imaging modality for facial bones, but results in a high radiation dose to the patient. This makes the application and advancement of dose reduction and dose optimisation methods vital. This narrative review presents a critical analysis of the literature concerning diagnostic imaging of facial bone trauma, with an emphasis on dose reduction methods for MDCT. Databases including Pubmed, Medline, Web of Science and Scopus were used to investigate this topic, with the key words: facial bone trauma, computed tomography (CT) imaging and dose reduction. Exclusion criteria included studies on nasal bone fracturing, dental imaging, elective surgeries and paediatric imaging. The literature shows overwhelming support for MDCT, given its accuracy, efficiency and ease of operation. Noise reducing reconstruction algorithms show promise as a successful method of dose reduction in facial bone imaging. Investigations of more innovative techniques also appear within the literature, including diagnostic cone‐beam CT (CBCT), intraoperative CBCT and dual‐source CT (DSCT), but further research is required to confirm their clinical value.
Age-related decline in urine concentration may not be universal: Comparative study from the U.S. and two small-scale societies.

OBJECTIVES Evidence from industrialized populations suggests that urine concentrating ability declines with age. However, lifestyle factors including episodic protein intake and low hypertension may help explain differences between populations. Whether this age-related decline occurs among small-scale populations with active lifestyles and non-Western diets is unknown. We test the universality of age-related urine concentration decline. MATERIALS AND METHODS We used urine specific gravity (Usg) and urine osmolality (Uosm) data from 15,055 U.S. nonpregnant adults without kidney failure aged 18-80 in 2007-2012 participating in the National Health and Nutrition Examination Survey (NHANES). We tested the relationship of age on urine concentration biomarkers with multiple linear regressions using survey commands. We compared results to longitudinal data on Usg from 116 Tsimane' forager-horticulturalists (266 observations) adults aged 18-83 in 2013-2014 from Lowland Bolivia, and to 38 Hadza hunter-gatherers (156 observations) aged 18-75 in 2010-2015 from Tanzania using random-effects panel linear regressions. RESULTS Among U.S. adults, age was significantly negatively associated with Usg (Adjusted beta [B] = -0.0009 g/mL/10 years; SE = 0.0001; p < 0.001) and Uosm (B = -28.1 mOsm/kg/10 yr; SE = 2.4; p < 0.001). In contrast, among Tsimane' (B = 0.0003 g/mL/10 yr; SE = 0.0002; p = 0.16) and Hadza (B = -0.0004 g/mL/10 yr; SE = 0.0004; p = 0.29) age was not associated with Usg. Older Tsimane' and Hadza exhibited similar within-individual variability in Usg equivalent to younger adults. DISCUSSION While U.S. adults exhibited age-related declines in urine concentration, Tsimane' and Hadza adults did not exhibit the same statistical decline in Usg. Mismatches between evolved physiology and modern environments in lifestyle may affect kidney physiology and disease risk.
Sexual activity and weekly contraceptive use among young adult women in Michigan

Past studies on the influence of sexual activity on contraceptive behaviours are inconclusive, relying heavily on cross-sectional data. We used a population-based longitudinal sample of young women in Michigan to evaluate weekly associations between sexual activity and contraceptive use at three levels of measurement: comparing between women, among individual women’s partnerships, and from week to week within partnerships. We used multinomial logistic regression accounting for correlations within partnerships and women. Relative to use of least effective methods, weekly sexual activity was significantly associated with increased use of condoms, pills, and highly effective methods. For pills and highly effective methods, partnership-, woman-, and week-level effects were similar. For condoms, there was no significant woman-level effect. Evidence of immediate effects of sexual activity on contraceptive use highlights the importance of longitudinal data. These dynamics may be diluted or missed altogether when relying on cross-sectional data approaches that compare groups of individuals.
Impact of dose adaptations following voriconazole therapeutic drug monitoring in pediatric patients.

Voriconazole is the mainstay of treatment for invasive aspergillosis in immunocompromised pediatric patients. Although Therapeutic Drug Monitoring (TDM) of voriconazole is recommended, it remains unknown if TDM-based dose adaptations result in target attainment. Patients <19 years from two pediatric hematologic-oncology wards were retrospectively identified based on unexplained high voriconazole trough concentrations (Cmin > 6 mg/l). Patient demographics, clinical characteristics, treatment, voriconazole dosing information, voriconazole Cmin before and after adjustment based on TDM were obtained. Twenty-one patients, median (range) age 7.0 (1.2-18.5) years, were identified in two centers. First Cmin (3.1 mg/l [0.1-13.5]) was obtained after 3 days (1-27) of treatment. The median of all Cmin (n = 485, median 11 per patient) was 2.16 mg/l (0.0 (undetectable)-28.0), with 24.1% of Cmin < 1 mg/l, 48.9% 1-4 mg/l, 9.3% 4-6 mg/l, and 17.7% > 6 mg/l. Intrapatient variability was large (94.1% for IV, 88.5% for PO). Dose increases at Cmin < 1 mg/l resulted in an increased Cmin in 76.4%, with 60% between 1 and 4 mg/l. Dose decreases at Cmin > 6 mg/l resulted in a decreased Cmin in 80%, with 51% between 1 and 4 mg/l. Overall, in 45% of the cases (33 out of 55 and 12 out of 45) therapeutic targets were attained after dose adjustment. Fifty-five percent of initial Cmin was outside the therapeutic target of 1-4 mg/l, with multiple dose adaptations required to achieve therapeutic concentrations. Only 60% and 51% of dose adaptations following sub- and supra-therapeutic Cmin, respectively, did result in target attainment. Intensive and continuous TDM of voriconazole is a prerequisite for ensuring adequate exposure in pediatric patients.
The role of sodium glucose cotransporter-2 (SGLT-2) inhibitors in heart failure and chronic kidney disease in type 2 diabetes

Abstract Background: Heart failure (HF) and chronic kidney disease (CKD) are responsible for substantial morbidity and mortality in individuals with type 2 diabetes (T2D). Methods: This review discusses the significance of these comorbidities of T2D and current options for managing them, with a focus on sodium-glucose cotransporter-2 (SGLT-2) inhibitors. Based on a focused literature search of cardiovascular outcomes trials (CVOTs), this review assessed the effects of SGLT-2 inhibitors in individuals with T2D with or without established cardiovascular disease (CVD). Results: In addition to effective glycemic control and weight loss, SGLT-2 inhibitor treatment of T2D prevents adverse cardiovascular and renal outcomes in individuals with and without these comorbidities. Reduced rate of hospitalization due to HF (HHF) and improved renal outcomes appear to be class effects of SGLT-2 inhibitors. Reduction in CV events may be more significant in individuals with established cardiovascular disease. Conclusions: CVOTs and other studies confirm that the SGLT-2 inhibitors, mostly used in combination with other glucose-lowering drugs, offer several clinical benefits beyond improved glycemic control. These include reducing HHF risk and improving renal outcomes. HF and renal benefits are observed in individuals with and without established CVD, which may simplify therapeutic selection. Ongoing SGLT-2 inhibitor CVOTs will help clarify the potential of these drugs to treat T2D comorbid with different forms of HF (HF with preserved vs reduced ejection fraction) and different degrees of renal dysfunction, and in individuals with T2D vs pre-diabetes or normal glucose metabolism.
Neoplasm Risk Among Individuals With a Pathogenic Germline Variant in DICER1.

PURPOSE DICER1 syndrome is an autosomal-dominant, pleiotropic tumor-predisposition disorder caused by pathogenic germline variants in DICER1. We sought to quantify risk, hazard rates, and the probability of neoplasm incidence accounting for competing risks ("cumulative incidence") of neoplasms (benign and malignant) and standardized incidence ratios for malignant tumors in individuals with DICER1 pathogenic variation. PATIENTS AND METHODS We combined data from three large cohorts of patients who carry germline pathogenic variation in DICER1. To reduce ascertainment bias, we distinguished probands from nonprobands. Neoplasm diagnoses were confirmed by review of pathology reports and/or central review of surgical pathology materials. Standardized cancer incidence ratios were determined relative to the SEER program, which does not capture all DICER1-associated neoplasms. For all malignancies and benign tumors ("neoplasms," excluding type Ir pleuropulmonary blastoma and thyroid nodules), we used the Kaplan-Meier method and nonparametric cumulative incidence curves to estimate neoplasm-free survival. RESULTS We calculated the age at first neoplasm diagnosis (systematically ascertained cancers plus DICER1-associated neoplasms pleuropulmonary blastoma, cystic nephroma, and nasal chondromesenchymal hamartoma) in 102 female and male nonproband DICER1 carriers. By age 10 years, 5.3% (95% CI, 0.6% to 9.7%) of nonproband DICER1 carriers had developed a neoplasm (females, 4.0%; males, 6.6%). By age 50 years, 19.3% (95% CI, 8.4% to 29.0%) of nonprobands had developed a neoplasm (females, 26.5%; males, 10.2%). After age 10 years, female risk was elevated compared with male risk. Standardized cancer incidence ratio analysis of 102 nonproband DICER1 carriers, which represented 3,344 person-years of observation, showed significant cancer excesses overall, particularly of gynecologic and thyroid cancers. CONCLUSION This work provides the first quantitative analysis of site-specific neoplasm risk and excess malignancy risk in 102 systematically characterized nonproband DICER1 carriers. Our findings inform DICER1 syndrome phenotype, natural history, and genetic counseling.
Profiles of Human Enteroviruses Associated with Hand, Foot, and Mouth Disease in Nanjing, China

ABSTRACT Objective Hand, foot, and mouth disease (HFMD) is a common infectious disease caused by a group of viruses. The causative viruses have changed over time, and there is a need for a more effective protective vaccine. In this study, we investigated the profiles of human enteroviruses that caused HFMD outbreaks in Nanjing in 2015, with the goal of guiding the future prevention and treatment of HFMD. Methods Specimens were collected from 1097 patients admitted to our hospital and diagnosed with HFMD. Enteroviruses in the specimens were identified by real-time polymerase chain reaction and epidemiological patterns were analyzed with the clinical data. Results Among the 1097 clinically diagnosed HFMD cases, 916 cases were confirmed by laboratory tests. The results showed that the main infectious virus was coxsackievirus A6 (CVA6) (41.75%), followed by enterovirus 71 (EV71) (27.48%), coxsackievirus A16 (7.43%), coxsackievirus A10 (6.84%), and others (16.51%). Further investigation indicated that CVA6 caused mild cases of HFMD, while EV71 caused severe cases. More enterovirus positive cases were reported from rural areas than from urban areas. Conclusions CA6 and EV71 were the chief pathogenic viruses of HFMD cases in the present study. Schools, childcare centers, and families from rural areas should be the major targets for prevention and awareness of HFMD. This study will provide information useful in the prevention and management of HFMD and the development of relevant vaccines for HFMD in the future. (Disaster Med Public Health Preparedness. 2019;13:740–744).