Miracle-dz/UniFAR-FTUs huggingface dataset:
The influence of maternal and perinatal high-fat diet on ozone-induced pulmonary responses in offspring

ABSTRACT There is growing interest in understanding how maternal diet might affect the sensitivity of offspring to environmental exposures. Previous studies demonstrated that adult rat offspring (approximately 6-months-old) from dams given a high-fat diet (HFD) prior to, during, and after pregnancy displayed elevated pulmonary responses to an acute ozone (O3) exposure. The aim of this study was to examine the influence of maternal and perinatal HFD on pulmonary and metabolic responses to O3 in male and female young-adult offspring (approximately 3-month old). One-month-old F0 female Long–Evans rats commenced HFD (60% kcal from fat) or control diet (CD; 10.5% kcal from fat) and were bred on PND 72. Offspring were maintained on respective HFD or CD until PND 29 when all groups were switched to CD. The 3-months-old female and male offspring (n = 10/group) were exposed to air or 0.8 ppm O3 for 5hr/day for 2 consecutive days. Maternal and perinatal HFD significantly increased body weight and body fat % in offspring regardless of gender. Ozone exposure, but not maternal and perinatal diet, induced hyperglycemia and glucose intolerance in the offspring. Ozone-induced alterations in pulmonary function were exacerbated by maternal and perinatal HFD in both offspring genders. Pulmonary injury/inflammation markers in response to O3 exposure such as bronchoalveolar lavage fluid total protein, lactate dehydrogenase, total cells, and neutrophils were further augmented in offspring (males>females) from dams fed the HFD. Data suggest that maternal and perinatal HFD may enhance the susceptibility of offspring to O3-induced pulmonary injury and that these effects may be sex-specific.
Targeted thyroid testing in acute illness: Achieving success through audit

Thyroid tests are done in acutely ill patients who often have confusing transient thyroid abnormalities, despite a lack of clarity about intervention and cost benefit. A retrospective analysis of patients admitted to the Medical Assessment Unit (MAU) was undertaken in 2004 to assess the frequency and utility, pattern of abnormalities and cost of thyroid testing. Guidelines were issued and the audit was repeated in 2008. 53.8% of 1593 subjects were offered thyroid tests in 2004 with a significant reduction to 21.7% of 1176 in 2008 (p<0.001). Free T4 or TSH was outside the reference range in 11.2% (2004) and 7.5% (2008) (p=0.10) and low TSH (52.7% in 2004 and 64.3% in 2008) was commonly combined with normal free T4. Appropriate indications for testing were documented in 43.9 vs 73.7% of patients with abnormal thyroid results (p=0.004) and in 14.3 vs 16% (2004 vs 2008) of a random sample of subjects with normal thyroid results, respectively (p=0.77). Documentation of intervention (25.5. vs 92.9%; p=0.001) and follow-up (45.5 vs 85.7%; p=0.001) had also improved significantly in 2008. We have demonstrated a significant reduction in thyroid testing in acutely ill patients after audit and the issue of guidelines. We currently recommend thyroid tests only in those with previous thyroid disease, the presence of clinical features and risk factors for thyroid disease, the use of relevant drugs, and unexplained tachydysrhythmias. The difficulties in interpreting results, the lack of clarity about intervention and follow up and possible cost savings would argue against an unrestricted policy.
SNPs and Haplotypes in DPYD and Outcome of Capecitabine–Letter

In their recently published article in Clinical Cancer Research , Deenen and colleagues reported a number of single-nucleotide polymorphisms (SNP) and haplotypes in DPYD that were associated with toxicity of capecitabine ([1][1]). In particular, the silent c.1236G>A mutation was strongly associated
Pilot trial of a STOMA psychosocial intervention programme for colorectal cancer patients with stomas.

AIMS To evaluate preliminary effects of a newly developed STOMA psychosocial intervention programme that was delivered via a multi-modal and multi-dimensional approach on the improvement of outcomes of colorectal cancer patients with stoma. BACKGROUND With a distorted body image and the loss of an essential body function, stoma patients face difficulties in everyday life in terms of physical, psychological, and social aspects. Few studies have explored effects of psychosocial interventions on improving stoma-related health outcomes. DESIGN This was a two-group pre-test-post-test pilot randomized controlled trial. METHODS Fifty-three participants were recruited from July 2015-November 2016 in a tertiary public hospital in Singapore. They were randomized into either intervention group (N = 29) or control group (N = 24). Stoma care self-efficacy, acceptance of stoma, stoma proficiency, length of hospital stay, anxiety and depression and quality of life were measured. IBM SPSS 24.0 was used to analyse the data. RESULTS There was an improvement in acceptance of stoma in the intervention group (p < 0.05). Significant effects on stoma care self-efficacy, stoma proficiency, length of hospital stay, anxiety and depression level and quality of life were not shown. CONCLUSION This study developed a feasible and applicable psychosocial intervention programme and generated preliminary evidence in the positive outcomes of colorectal cancer patients with stoma. Future studies can explore technology-based interventions to provide a more sustainable support for patients with stoma.
Trends in BRCA Test Utilization in an Integrated Health System, 2005-2015.

Background Genetic testing to determine BRCA status has been available for over two decades, but there are few population-based studies of test diffusion. We report ten-year trends in BRCA testing in an integrated health care system with longstanding access to genetic services. Methods A cohort of women aged 18 years and older was created to ascertain BRCA testing (n = 295,087). Annual testing rates between 2005 and 2015 were calculated in all women with and without incident (i.e., newly diagnosed) breast and ovarian cancers and in clinically eligible subgroups by family cancer history, personal cancer history, and age at diagnosis. Secular trends were assessed using Poisson regression. Women tested early (2005-2008), midway (2009-2012), and late (2013-2015) in the study period were compared in cross-sectional analyses. Results Between 2005 and 2015, annual testing rates increased from 0.6/1,000 person years (pys) (95% confidence interval [CI]: 0.4 to 0.7/1,000 pys) to 0.8/1,000 pys (95% CI: 0.6 to 1.0/1,000 pys) in women without incident breast or ovarian cancers. Rates decreased from 71.5/1,000 pys (95% CI: 42.4 to 120.8/1,000 pys) to 44.4/1,000 pys (95% CI: 35.5 to 55.6/1,000 pys) in women with incident diagnoses, despite improvements in provision of timely BRCA testing during this timeframe. We found no evidence of secular trends in clinically eligible subgroups including women with family history indicating increased hereditary cancer risk, but no personal cancer history. At the end of the study period, 97.0% (95% CI = 96.6% to 97.3%) of these women remained untested. Conclusion Many eligible women did not receive BRCA testing despite having insurance coverage and access to specialty genetic services, underscoring challenges to primary and secondary hereditary cancer prevention.
Genetic polymorphism of methylenetetrahydrofolate reductase is associated with insulin resistance in Egyptian women with polycystic ovary syndrome

A common polymorphism (677C to T; Ala to Val) in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with decreased specific MTHFR activity and elevation of homocysteine. The present study aimed to investigate the association between a single nucleotide polymorphism (SNP) in the MTHFR 677C>T gene and insulin resistance in women with polycystic ovary syndrome (PCOS).
miR‐210 inhibits cell migration and invasion by targeting the brain‐derived neurotrophic factor in glioblastoma

Recently, there is increasing evidence that microRNAs are related to the development, diagnosis, treatment, and prognosis of glioblastoma. microRNA‐210 (miR‐210) had been identified in many human cancers, but the specific function of miR‐210 remains unclear in glioblastoma. The present study mainly focused on exploring its biological role and potential molecular mechanisms in glioblastoma. We found that miR‐210 expression was decreased in glioblastoma, and downregulation of miR‐210 was related to worse prognosis in glioblastoma patients. In addition, miR‐210 overexpression inhibited the migration and invasion of human glioblastoma cells. At the same time, we found that miR‐210 directly targets the brain‐derived neurotrophic factor (BDNF) and reduces BDNF expression level. Consistently, BDNF silencing had the same effects as miR‐210 overexpression in glioblastoma, and upregulation of BDNF counteracted the inhibitory effect of miR‐210 in glioblastoma. In conclusion, miR‐210 suppressed the migration and invasion of glioblastoma cells by targeting BDNF.
Cyclooxygenase‐2 in gastrointestinal malignancies

Cyclooxygenase (COX) is an enzyme complex that plays an important role in the conversion of arachidonic acid to prostaglandins. Prostaglandins are essential modulators of signal transduction pathways, which contribute to the metastatic properties of gastrointestinal (GI) malignancies. Although COX‐1 is constitutively active, COX‐2 is upregulated by cytokines, growth factors, and mitogen. COX‐2 is involved in malignant cell proliferation, angiogenesis, migration, invasion, and antiapoptotic activity. Thus, COX‐2 inhibitors may represent a promising therapeutic strategy for the treatment of GI cancers. In this review, the role of COX‐2 in GI cancers is explored, and its clinical applications as a therapeutic target are discussed.
The reproduction of child maltreatment: An examination of adolescent problem behavior, substance use, and precocious transitions in the link between victimization and perpetration

Abstract Growing evidence suggests that maltreatment is reproduced across generations as victims of maltreatment are at an increased risk for maltreatment perpetration. Unfortunately, little information about mediating pathways exists to provide an explanation for why maltreatment begets maltreatment. We use the number of types of maltreatment experienced to predict later maltreatment perpetration and then examine two developmental pathways that may serve as bridges between maltreatment victimization and perpetration: adolescent problem behaviors and precocious transitions to adulthood. With prospective, longitudinal data from the Rochester Youth Development Study, we assess the relevance of these pathways for the number of maltreatment experiences as well as the number of maltreatment victimization experiences by developmental period (i.e., childhood and adolescence). Our results demonstrate a significant relationship between maltreatment victimization and maltreatment perpetration. Adolescent delinquency and two precocious transitions, dropping out of school and independent living, as well as the accumulation of precocious transitions and problem behaviors, serve as mediators of this intergenerational relationship. Furthermore, the relationship between the number of types of maltreatment and subsequent perpetration is primarily driven by experiences of maltreatment during adolescence. We discuss the implications of these results and set an agenda for the development of programs and policies to interrupt the cycle of maltreatment.
Quantitative diagnosis of osteoporosis using lumbar spine signal intensity in magnetic resonance imaging.

OBJECTIVE Osteoporosis is the most common metabolic bone disease that is not recognized in many elderly people. To determine the cause of low back pain, lumbosacral MRI is done for a large population who may not have gone under dual energy X-ray absorptiometry (DXA). The aim of this study was to predict bone density using lumbar spine signals in lumbosacral MRI in high risk patients for osteoporosis including post-menopausal females and calculate a threshold for a new quantitative MRI-based score to be used in estimation of lumbar spine bone mass density. METHODS 82 menopaused females, who had undergone DXA before, were selected and MRI was done within 6 months after DXA. 69 healthy females aged 20-29 years who had undergone lumbar MRI were selected as reference group. Results were analyzed and threshold and diagnostic performance of MRI-based score (M-score) on the method of T-score was calculated. RESULTS Negative correlation between M-score and T-score was detected. Cut off point of 2.05 was found for M-score with near sensitivity of 90% and specificity of 87% for detecting osteoporotic patients from non-osteoporotic individuals. CONCLUSION M-score is a MRI-based method which can identify patients at risk of osteoporosis. Early diagnosis of osteoporosis can reduce morbidity and mortality caused by it. ADVANCES IN KNOWLEDGE The research introduced cut of points for M-score as a new MRI quantitative method to be used as an opportunistic technique for detecting osteoporotic patients.
Improvement of fertility in repeat breeder dairy cattle by embryo transfer following artificial insemination: possibility of interferon tau replenishment effect

Repeat breeder cattle do not become pregnant until after three or more breeding attempts; this represents a critical reproductive disorder. Embryo transfer (ET) following artificial insemination (AI) in repeat breeder cattle reportedly improves pregnancy rate, leading to speculation that interferon tau (IFNT) is associated with this phenomenon. However, the reason why the conception rate improves remains unknown. We investigated the effect of ET following AI on repeat breeder cattle in field tests, and determined whether adding an embryo affects the maternal immune cells detected by interferon-stimulated genes (ISGs), marker genes of IFN response. In total, 1122 repeat breeder cattle were implanted with in vitro fertilization (IVF) embryos after previous AI. ET following AI resulted in pregnancy rates of 46.9% in repeat breeder dairy cattle. In basic in vivo tests, to investigate the effect of adding embryos, ISGs mRNA expression levels were significantly higher in the AI + ET group than in the AI + sham group (transfer of only embryonic cryopreservation solution). Then, we examined the effect of cultured conditioned media (CM) of IVF embryos on splenic immune cells and Madin-Darby bovine kidney (MDBK) cells with stably introduced ISG15 promoter-reporter constructs. These cells exhibited a specific increase in ISG15 mRNA expression and promoter activity when treated with the CM of IVF embryos, suggesting that IVF embryos have the potential to produce and release IFNT. In conclusion, ET following AI is beneficial for improving conception in repeat breeder cattle. Added embryos may produce and secrete IFNT, resulting in the increased expression of ISGs.
Neutrophil Extracellular Traps Promote Angiogenesis: Evidence From Vascular Pathology in Pulmonary Hypertension

Objective— Inflammation and dysregulated angiogenesis are features of endothelial dysfunction in pulmonary hypertension. Neutrophil extracellular traps (NETs), produced by dying neutrophils, contribute to pathogenesis of numerous vascular disorders but their role in pulmonary hypertension has not been studied. We sought evidence of (NETs) formation in pulmonary hypertension and investigated the effect of NETs on endothelial function. Approach and Results— Plasma and lung tissues of patients with pulmonary hypertension were analyzed for NET markers. The effects of NETs on endothelial function were studied in vitro and in vivo. Patients with chronic thromboembolic pulmonary hypertension and idiopathic pulmonary hypertension showed elevated plasma levels of DNA, neutrophil elastase, and myeloperoxidase. NET-forming neutrophils and extensive areas of NETosis were found in the occlusive plexiform lesions and vascularized intrapulmonary thrombi. NETs induced nuclear factor &kgr;B–dependent endothelial angiogenesis in vitro and increased vascularization of matrigel plugs in vivo. Angiogenic responses were associated with increased release of matrix metalloproteinase-9, heparin-binding epidermal growth factor–like growth factor, latency-associated peptide of the transforming growth factor &bgr;1, and urokinase-type plasminogen activator, accompanied by increased endothelial permeability and cell motility. NETs-induced responses depended on myeloperoxidase/H2O2-dependent activation of Toll-like receptor 4/nuclear factor &kgr;B signaling. NETs stimulated the release of endothelin-1 in HPAECs (human pulmonary artery endothelial cells) and stimulated pulmonary smooth muscle cell proliferation in vitro. Conclusions— We are the first to implicate NETs in angiogenesis and provide a functional link between NETs and inflammatory angiogenesis in vitro and in vivo. We demonstrate the potential pathological relevance of this in 2 diseases of disordered vascular homeostasis, pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension.
Insights into the Unique Nature of the East Asian Clade of the Emerging Pathogenic Yeast Candida auris

The emerging yeast Candida auris can be highly drug resistant, causing invasive infections, and large outbreaks. C. auris went from an unknown pathogen a decade ago to being reported in over thirty countries on six continents. ABSTRACT The emerging yeast Candida auris can be highly drug resistant, causing invasive infections, and large outbreaks. C. auris went from an unknown pathogen a decade ago to being reported in over thirty countries on six continents. C. auris consists of four discrete clades, based on where the first isolates of the clade were reported, South Asian (clade I), East Asian (clade II), African (clade III), and South American (clade IV). These clades have unique genetic and biochemical characteristics that are important to understand and inform the global response to C. auris. Clade II has been underrepresented in the literature despite being the first one discovered. In this issue of the Journal of Clinical Microbiology, Y. J. Kwon et al. (J Clin Microbiol 57:e01624-18, 2019, https://doi.org/10.1128/JCM.01624-18) describe the largest collection of clinical isolates from Clade II, which is also the longest-running span of clinical cases, 20 years, from any single region to date. Clade II appears to have a propensity for the ear that is uncharacteristic of the other clades, which typically cause invasive infections and large-scale outbreaks. This study provides new information on an understudied lineage of C. auris and has important implications for future surveillance.
Demystification of enigma on antigen-presenting cell features of human basophils: data from secondary lymphoid organs

Antigen presenting cells (APCs) play a key role in the uptake of antigens, and processing and presentation of antigen-derived peptides in the context of MHC molecules to T cells. The co-stimulatory molecules CD80 and CD86 provide signals for T-cell activation and proliferation. Dendritic cells (DCs
Dynamic psychological and behavioral changes in the adoption and maintenance of exercise.

OBJECTIVE Although health cognitions are regarded as key determinants for health behavior change, they are rarely studied from a dynamic perspective, evaluating the impact of changes in cognitions on changes in behavior. In the present study, we examine how changes in phase-specific and generic health cognitions influence first, the adoption of exercise and later, the maintenance of the newly acquired behavior. METHODS Participants were middle-aged, Finnish adults participating in a lifestyle intervention to prevent Type 2 diabetes (N = 389). Health cognitions and exercise were measured at baseline (preintervention) and twice after a lifestyle intervention took place (at 3 months and after 1 year). RESULTS The results show that both phase-specific and generic health cognitions changed during the intervention. However, these changes were most pronounced within those participants who started at a lower level to begin with. Most important, evidence for the dynamic interplay between changes in health cognitions and health behavior was observed: Phase-specific health cognitions facilitated the adoption as well as the maintenance of behavior changes. CONCLUSIONS Thus, health cognitions are amenable to change, and these changes are adaptive in terms of initiating and maintaining health behavior change. This has implications both for practical intervention research, as well as for theory development.
Clinical Findings and Treatments of a Radially Deviated Type of Thumb Polydactyly.

BACKGROUND Patients with some thumb polydactyly subtypes are regarded as having a high risk of secondary deformities or poor treatment outcomes. Radially deviated type is one of these subtypes, but its characteristics and definitive treatment outcomes remain unclear. This study aimed to evaluate the pre- and intraoperative findings and surgical outcomes of this subtype. METHODS We identified eight patients with unilateral and proximal phalanx-type polydactyly. The mean age at surgery was 14.6 months, and the mean follow-up period was 7.2 years. We investigated the patients' initial radiograms, surgical procedures and findings, changes in alignment of the retained thumb, and postoperative outcomes using the Japanese Society for Surgery of the Hand scoring system. RESULTS Although the gross appearance of the thumb was a radial deviation, there was an ulnar deviation at the metacarpophalangeal joint on radiography. The ulnar proximal phalanges were delta phalanges in three patients and were connected with the radial proximal phalanges by cartilage in five patients. We retained the ulnar thumbs in all patients and corrected the alignment in seven cases; open wedge osteotomy was performed for three patients with a delta phalanx, and tendon transfers from the radial to ulnar thumb were performed for the other four. The mean outcome score was 17.6/20, with one patient with excellent, six with good, one with fair, and none with poor scores. One patient experienced recurrent radial deviation around the interphalangeal joint five years after surgery and underwent corrective osteotomy, but the other patients maintained good alignment. CONCLUSIONS Radially deviated thumb polydactyly is not simply radially deviated; the shape of the proximal phalanx of the ulnar thumb is important to determine the surgical procedure. However, our results indicated that the alignment is almost manageable, and the surgical outcome was comparable to that of patients with a proximal phalanx-type thumb polydactyly.
The administration route of tumor-antigen-specific T-helper cells differentially modulates the tumor microenvironment and senescence

Cancer treatment with adoptively transferred tumor-associated antigen-specific CD4+ T-helper cells is a promising immunotherapeutic approach. In the pancreatic cancer model RIP-Tag2, the intraperitoneal (i.p.) application of Tag-specific TH1 cells exhibited a profound antitumoral efficiency. We investigated, whether an intravenous (i.v.) application of Tag-TH1 cells induces an equivalent therapeutic effect. Adoptively transferred fluorescent Tag-TH1 cells revealed a pronounced homing to the tumors after either i.p. or i.v. transfer, and both routes induced an almost equivalent therapeutic effect as demonstrated by magnetic resonance imaging, blood glucose level course and histology. The i.v. administration of Tag-TH1 cells induced p16INK4-positive/Ki67-negative tumor senescence more efficiently than i.p. administration. Both routes replenish host CD4+ T cells by transferred T cells and recruitment of B and dendritic cells to the tumors while reducing CD8+ T cells and depleting macrophages. Both administration routes efficiently induced a similar antitumoral efficiency despite the pronounced senescence induction after i.v. administration. Thus, a combinatory i.v. /i.p. injection of therapeutic cells might overcome limitations of the individual routes and improve therapeutic efficacy in solid tumors.