Miracle-dz/UniFAR-FTUs huggingface dataset:
Crocin inhibits the migration, invasion, and epithelial‐mesenchymal transition of gastric cancer cells via miR‐320/KLF5/HIF‐1α signaling

The biological activities of crocin, one of the main bioactive compounds of saffron, include anti‐inflammatory, antioxidant, antidepressant, and anticancer effects. Crocin has been shown to trigger the apoptosis of gastric cancer cells, but its effect on the metastasis of gastric cancer cells remains unclear. Krüppel‐like factor 5 (KLF5) and hypoxia‐inducible factor‐1α (HIF‐1α) are important transcription factors in the development of gastric cancer. KLF5 and HIF‐1α expression were analyzed in gastric cancer tissues and cells. Following exposure to crocin, AGS and HGC‐27 gastric cancer cells were assessed with regard to migration, invasion, and epithelial‐mesenchymal transition (EMT) as well as the expression of KLF5, HIF‐1α, and microRNA‐320 (miR‐320). The miR‐320/KLF5/HIF‐1α signaling pathway became the focus for further investigation of the mechanism of crocin in gastric cancer cell migration, invasion, and EMT. KLF5 and HIF‐1α expression were elevated in gastric cancer tissues and cells, and KLF5 expression was positively correlated with the HIF‐1α level in gastric cancer tissues. Crocin was associated with reduced expression of KLF5 and HIF‐1α, whereas miR‐320 expression was increased. Crocin also inhibited the migration, invasion, and EMT of gastric cancer cells. Upregulation of KLF5 attenuated crocin's function and elevated HIF‐1α expression. Dual‐luciferase reporter assay demonstrated that KLF5 was a target gene of miR‐320. Crocin modulated KLF5 expression via elevation of miR‐320 expression. In conclusion, crocin inhibits the EMT, migration, and invasion of gastric cancer cells, and this activity is mediated through miR‐320/KLF5/HIF‐1α signaling.
Streptococcus Salivarius: A Potential Salivary Biomarker for Orofacial Granulomatosis and Crohn’s Disease?

Abstract Background Orofacial granulomatosis (OFG) is a rare disease characterised by chronic, noncaseating, granulomatous inflammation primarily affecting the oral cavity. Histologically, it is similar to Crohn’s disease (CD), and a proportion of patients have both OFG and CD. The cause of OFG remains elusive, but it has been suggested that microbial interactions may be involved. The aim of this study was to compare the salivary microbial composition of subjects with OFG and/or CD and healthy controls. Methods Two hundred sixty-one subjects were recruited, of whom 78 had OFG only, 40 had both OFG and CD, 97 had CD only with no oral symptoms, and 46 were healthy controls. Bacterial community profiles were obtained by sequencing the V1-V3 region of the 16S rRNA gene. Results There were no differences in richness or diversity of the salivary bacterial communities between patient groups and controls. The relative abundance of the Streptococcus salivarius group was raised in patients with OFG or CD only compared with controls, whereas that of the Streptococcus mitis group was lower in CD compared with both OFG and controls. One S. salivarius oligotype made the major contribution to the increased proportions seen in patients with OFG and CD. Conclusions The salivary microbiome of individuals with OFG and CD was similar to that found in health, although the proportions of S. salivarius, a common oral Streptococcus, were raised. One specific strain-level oligotype was found to be primarily responsible for the increased levels seen.
Core Dimensions of Anxiety and Depression Change Independently During Adolescence

The developmental trajectories of emotional disorder symptoms during adolescence remain elusive, owing in part to a shortage of intensive longitudinal data. In the present study, we charted the temporal course of the tripartite model of anxiety and depression—which posits an overarching negative affect dimension and specific anhedonia and anxious arousal dimensions—over adolescence and emerging adulthood to construct a developmental map of the core dimensions of emotional disorders. We recruited 604 high school juniors, overselecting those at high risk for emotional disorders, and assessed the tripartite symptom domains 5 times annually. Latent curve modeling revealed that negative affect and anxious arousal declined over follow up, whereas anhedonia did not. Moreover, the correlation in rate of change varied across pairs of symptom domains. Change in negative affect was moderately correlated with change in anxious arousal, but change in anhedonia was not significantly related to change in any other domain. Symptom trajectories, and the pattern of covariation among trajectories, were equivalent across gender and comorbidity status. We discuss implications of these findings for developmental models of anxiety and depression, as well as transdiagnostic frameworks for emotional disorders.
When a Woman Kills Her Man: Gender and Victim Precipitation in Homicide

This research revisited the claim that victim precipitation (VP) is especially prevalent in situations where women kill their male intimate partners. Using administrative data from the Finnish Homicide Monitor (N =1,494), we created a typology of homicide incidents to examine variation in VP across three factors: the gender of the offender, the gender of the victim, and the intimacy of the victim–offender relationship. The results from regression models demonstrated strong support for the assumption that killings by women of their male intimate partners are more likely to have been victim precipitated than other types of homicide. This homicide type stood out as having the strongest association with each measure of VP included in the analysis. We did not observe statistically significant differences in VP among other homicide types. For example, we did not observe gender differences in VP in homicides that did not involve intimate partners. This pattern of results contradicts prior evidence suggesting that VP is a general feature of female-perpetrated killings, independent of the gender of the victim and the intimacy of the victim–offender relationship. As such, the present study underscores the importance of replication in studies of interpersonal violence. Theoretically, the results support the gender–partner interaction hypothesis over gender differences hypothesis of VP.
Health facility service availability and readiness to provide basic emergency obstetric and newborn care in a low-resource setting: evidence from a Tanzania National Survey

Objective This study used a nationally representative sample from Tanzania as an example of low-resource setting with a high burden of maternal and newborn deaths, to assess the availability and readiness of health facilities to provide basic emergency obstetric and newborn care (BEmONC) and its associated factors. Design Health facility-based cross-sectional survey. Setting We analysed data for obstetric and newborn care services obtained from the 2014–2015 Tanzania Service Provision Assessment survey, using WHO-Service Availability and Readiness Assessment tool. Primary and secondary outcome measures Availability of seven signal functions was measured based on the provision of ‘parental administration of antibiotic’, ‘parental administration of oxytocic’, ‘parental administration of anticonvulsants’, ‘assisted vaginal delivery’, ‘manual removal of placenta’, ‘manual removal of retained products of conception’ and ‘neonatal resuscitation’. Readiness was a composite variable measured based on the availability of supportive items categorised into three domains: staff training, diagnostic equipment and basic medicines. Results Out of 1188 facilities, 905 (76.2%) were reported to provide obstetric and newborn care services and therefore were included in the analysis of the current study. Overall availability of seven signal functions and average readiness score were consistently higher among hospitals than health centres and dispensaries (p<0.001). Furthermore, the type of facility, performing quality assurance, regular reviewing of maternal and newborn deaths, reviewing clients’ opinion and number of delivery beds per facility were significantly associated with readiness to provide BEmONC. Conclusion The study findings show disparities in the availability and readiness to provide BEmONC among health facilities in Tanzania. The Tanzanian Ministry of Health should emphasise quality assurance efforts and systematic maternal and newborn death audits. Health leadership should fairly distribute clinical guidelines, essential medicines, equipment and refresher trainings to improve availability and quality BEmONC.
Colorectal Polyps Missed with Optical Colonoscopy Despite Previous Detection and Localization with CT Colonography.

PURPOSE To retrospectively evaluate and characterize nondiminutive colorectal polyps prospectively detected by using computed tomographic (CT) colonography but not confirmed with subsequent nonblinded optical colonoscopy (OC). MATERIALS AND METHODS This study was institutional review board approved; the need for signed informed consent was waived. Over 113 months, 9336 adults (mean age, 57.1 years) underwent CT colonography, which yielded 2606 nondiminutive (≥6 mm) polyps. Of 1731 polyps that underwent subsequent nonblinded OC (ie, endoscopists provided advanced knowledge of specific polyp size, location, and morphologic appearance at CT colonography), 181 (10%) were not confirmed with initial endoscopy (ie, discordant), of which 37 were excluded (awaiting or lost to follow-up). After discordant polyp review, 66 of the 144 lesions were categorized as likely CT colonography false-positive findings (no further action) and 78 were categorized as potential OC false-negative (FN) findings. RESULTS Thirty-one of 144 (21.5%) of all discordant lesions were confirmed as FN findings at OC, including 40% (31 of 78) of those with OC and/or CT colonography follow-up. OC FN lesions were an average of 8.5 mm ± 3.3 in diameter and were identified with higher confidence at prospective CT colonography (on a 3-point confidence scale: mean, 2.8 vs 2.3; P = .001). OC FN findings were more likely than concordant polyps to be located in the right colon (respectively, 71% [22 of 31] vs 47% [723 of 1535]; P = .010). Most (81% [21 of 26]) OC FN lesions that were ultimately resected were neoplastic (adenomas or serrated lesions), of which 43% (nine of 21) were characterized as advanced lesions, and 89% (eight of nine) of advanced lesions occurred in the right colon. CONCLUSION In clinical practice, polyps prospectively identified with CT colonography but not confirmed with subsequent nonblinded (ie, despite a priori knowledge of the CT colonography findings) OC require additional review because a substantial proportion may be FN findings. Most FN findings found with OC demonstrated clinically significant histopathologic results, and a majority of advanced lesions occurred in the right colon.
Comparable effect of tolvaptan in heart failure patients with preserved or reduced ejection fraction

ABSTRACT Background: It is unclear that the difference in efficacy of tolvaptan (TLV) on the length of hospital stay for both heart failure (HF) preserved ejection fraction (EF) (HFpEF) and reduced EF (HFrEF) patients. Methods: We investigated 369 patients who were hospitalized with HF from February 2011 to June 2016 and initiated TLV. Patients who died in hospital, transferred hospital or clinical scenario 4 or 5 were excluded. Finally, we analyzed 108 patients with HFpEF and 96 patients with HFrEF. We evaluated the relationship between the length of hospital stay and the date of TLV initiation. Moreover, we compared the early use (within the median) and delayed use (the median or later) of TLV. Results: The date of TLV initiation was statistically associated with the length of hospital stay in both HFpEF and HFrEF (HFpEF: r = 0.625, P < 0.001, HFrEF: r = 0.618, P < 0.001). In HFpEF, the length of hospital stay in delayed use group was significantly longer than the early use group (22.2 ± 10.7 days and 38.1 ± 22.6 days, P < 0.001). The result was similar in HFrEF (22.0 ± 15.0 days and 32.1 ± 22.0 days, P = 0.008). On the other hand, there were no statistically significant differences in the length of hospital stay after initiation of TLV in both HFpEF and HFrEF. Other findings (including the severity of HF) were similar between the early use group and the delayed group in HFpEF and HFrEF. Conclusions: The time until TLV initiation after hospitalization was related to the length of hospital stay in HFpEF and HFrEF patients.
Frontal Lobe Contributions to Theory of Mind

Theory of mind, the ability to make inferences about others' mental states, seems to be a modular cognitive capacity that underlies humans' ability to engage in complex social interaction. It develops in several distinct stages, which can be measured with social reasoning tests of increasing difficulty. Individuals with Asperger's syndrome, a mild form of autism, perform well on simpler theory of mind tests but show deficits on more developmentally advanced theory of mind tests. We tested patients with bilateral damage to orbito-frontal cortex (n = 5) and unilateral damage in left dorsolateral prefrontal cortex (n = 5) on a series of theory of mind tasks varying in difficulty. Bilateral orbito-frontal lesion patients performed similarly to individuals with Asperger's syndrome, performing well on simpler tests and showing deficits on tasks requiring more subtle social reasoning, such as the ability to recognize a faux pas. In contrast, no specific theory of mind deficits were evident in the unilateral dorsolateral frontal lesion patients. The dorsolateral lesion patients had difficulty only on versions of the tasks that placed demands on working memory.
Genetic Epidemiology of Breast Cancer in Latin America

The last 10 years witnessed an acceleration of our understanding of what genetic factors underpin the risk of breast cancer. Rare high- and moderate-penetrance variants such as those in the BRCA genes account for a small proportion of the familial risk of breast cancer. Low-penetrance alleles are expected to underlie the remaining heritability. By now, there are about 180 genetic polymorphisms that are associated with risk, most of them of modest effect. In combination, they can be used to identify women at the lowest or highest ends of the risk spectrum, which might lead to more efficient cancer prevention strategies. Most of these variants were discovered in populations of European descent. As a result, we might be failing to discover additional polymorphisms that could explain risk in other groups. This review highlights breast cancer genetic epidemiology studies conducted in Latin America, and summarizes the information that they provide, with special attention to similarities and differences with studies in other populations. It includes studies of common variants, as well as moderate- and high-penetrance variants. In addition, it addresses the gaps that need to be bridged in order to better understand breast cancer genetic risk in Latin America.
The Impact of Autoantibodies on IVF Treatment and Outcome: A Systematic Review

The role of autoantibodies in in vitro fertilization (IVF) has been discussed for almost three decades. Nonetheless, studies are still scarce and widely controversial. The aim of this study is to provide a comprehensive systematic review on the possible complications associated to autoantibodies (AA) impeding the chances of a successful IVF cycle. An Embase, PubMed/Medline and Cochrane Central Database search was performed on 1 December 2018, from 2006 until that date. From the 598 articles yielded in the search only 44 relevant articles ultimately fulfilled the inclusion criteria and were qualitatively analyzed. Five subsets of results were identified, namely, thyroid related AA, anti-phospholipid antibodies, anti-nuclear antibodies, AA affecting the reproductive system and AA related to celiac disease. It may be implied that the majority of auto-antibodies exert a statistically significant effect on miscarriage rates, whereas the effects on clinical pregnancy and live birth rates differ according to the type of auto-antibodies. While significant research is performed in the field, the quality of evidence provided is still low. The conduction of well-designed prospective cohort studies is an absolute necessity in order to define the impact of the different types of autoantibodies on IVF outcome.
Osteoporosis and skeletal dysplasia caused by pathogenic variants in SGMS2

Mechanisms leading to osteoporosis are incompletely understood. Genetic disorders with skeletal fragility provide insight into metabolic pathways contributing to bone strength. We evaluated 6 families with rare skeletal phenotypes and osteoporosis by next-generation sequencing. In all the families, we identified a heterozygous variant in SGMS2, a gene prominently expressed in cortical bone and encoding the plasma membrane–resident sphingomyelin synthase SMS2. Four unrelated families shared the same nonsense variant, c.148C>T (p.Arg50*), whereas the other families had a missense variant, c.185T>G (p.Ile62Ser) or c.191T>G (p.Met64Arg). Subjects with p.Arg50* presented with childhood-onset osteoporosis with or without cranial sclerosis. Patients with p.Ile62Ser or p.Met64Arg had a more severe presentation, with neonatal fractures, severe short stature, and spondylometaphyseal dysplasia. Several subjects had experienced peripheral facial nerve palsy or other neurological manifestations. Bone biopsies showed markedly altered bone material characteristics, including defective bone mineralization. Osteoclast formation and function in vitro was normal. While the p.Arg50* mutation yielded a catalytically inactive enzyme, p.Ile62Ser and p.Met64Arg each enhanced the rate of de novo sphingomyelin production by blocking export of a functional enzyme from the endoplasmic reticulum. SGMS2 pathogenic variants underlie a spectrum of skeletal conditions, ranging from isolated osteoporosis to complex skeletal dysplasia, suggesting a critical role for plasma membrane–bound sphingomyelin metabolism in skeletal homeostasis.
Cardiovascular effects of electronic cigarettes: A systematic review and meta-analysis

Aims The electronic cigarette is marketed as a safe alternative to tobacco smoking, but electronic cigarette cardiovascular effects remain largely unknown. We systematically reviewed and meta-analysed published literature to investigate the cardiovascular effects and associated risk from electronic cigarette use. Methods and results We searched PubMed from January 2000 to November 2017 for published studies assessing the cardiovascular effects of the electronic cigarette. Evidence suggests that the electronic cigarette negatively affects endothelial function, arterial stiffness and the long-term risk for coronary events, but these findings are from single study reports and have not been confirmed in additional studies. Conflicting evidence exists on the effects of the electronic cigarette on heart rate and blood pressure, which is mainly based on non-randomized clinical studies of moderate quality. The meta-analysis of 14 studies (N + 441 participants) suggested that despite the negative acute effects of the electronic cigarette on heart rate (pooled mean difference (MD) + 2.27, 95% confidence interval (CI): 1.64 to 2.89, p < 0.001), diastolic (pooled MD + 2.01 mmHg, 95% CI: 0.62 to 3.39, p + 0.004) and systolic blood pressure (pooled MD + 2.02 mmHg, 95% CI: 0.07 to 3.97, p + 0.042), benefits may be observed in terms of blood pressure regulation when switching from tobacco smoking to chronic electronic cigarette use (systolic blood pressure pooled MD + −7.00, 95% CI: −9.63 to −4.37, p < 0.001; diastolic blood pressure pooled MD + −3.65, 95% CI: −5.71 to −1.59, p + 0.001). Conclusions The existing evidence on the cardiovascular effects of the electronic cigarette is concerning, with several unexplored issues. Unless supported by stronger evidence, the electronic cigarette should not be labelled as a cardiovascular safe product. Future studies should delineate whether electronic cigarette use is less hazardous to cardiovascular health than conventional cigarette smoking.
Yersinia pestis Pla Protein Thwarts T Cell Defense against Plague

Plague is a rapidly lethal human disease caused by the bacterium Yersinia pestis. This study demonstrated that the Y. pestis plasminogen activator Pla, a protease that promotes fibrin degradation, thwarts T cell-mediated defense against fully virulent Y. pestis. ABSTRACT Plague is a rapidly lethal human disease caused by the bacterium Yersinia pestis. This study demonstrated that the Y. pestis plasminogen activator Pla, a protease that promotes fibrin degradation, thwarts T cell-mediated defense against fully virulent Y. pestis. Introducing a single point mutation into the active site of Pla suffices to render fully virulent Y. pestis susceptible to primed T cells. Mechanistic studies revealed essential roles for fibrin during T cell-mediated defense against Pla-mutant Y. pestis. Moreover, the efficacy of T cell-mediated protection against various Y. pestis strains displayed an inverse relationship with their levels of Pla activity. Together, these data indicate that Pla functions to thwart fibrin-dependent T cell-mediated defense against plague. Other important human bacterial pathogens, including staphylococci, streptococci, and borrelia, likewise produce virulence factors that promote fibrin degradation. The discovery that Y. pestis thwarts T cell defense by promoting fibrinolysis suggests novel therapeutic approaches to amplifying T cell responses against human pathogens.
Are ISPD Guidelines on Peritonitis Diagnosis Too Narrow? A 15-Year Retrospective Single-Center Cohort Study on PD-Associated Peritonitis Accounting for Untrained Patients

Background: Peritoneal dialysis (PD)-associated peritonitis remains by far the most important complication requiring patients to transfer to hemodialysis and has a major impact on patient morbidity and mortality. Current International Society for Peritoneal Dialysis (ISPD) guidelines on peritonitis recommend analysis of peritonitis episodes only in trained patients. In a large tertiary care center, we analyzed peritonitis episodes accounting for different groups of untrained patients and compared these with episodes in the trained patient population. Methods: We analyzed data collected prospectively over a 15-year time span regarding differences between peritonitis episodes in trained patients and episodes in untrained patients post-catheter insertion but prior to training completion as well as on in-center intermittent PD with respect to incidence rates, pathogenic organisms, outcome, and peritonitis predictors. Results: In 275 patients, a total of 160 peritonitis episodes in trained patients were counted. A total of 27 additional episodes in untrained patients were recorded. When accounting for these episodes, the peritonitis incidence significantly increased and the percentage of peritonitis-free patients decreased. Peritonitis episodes in untrained patients were most often culture-negative and the pathogen spectrum differed significantly compared with episodes counted as per ISPD recommendations, while outcome of peritonitis episodes did not differ. Predictors of peritonitis after multivariate logistic regression analysis included glomerulonephritis as primary kidney disease, being on home PD rather than being on in-center intermittent PD, and higher dialysis vintage. Conclusions: Depending on local practice patterns, we argue that centers should additionally monitor peritonitis episodes in untrained patients because computation of statistics as per ISPD recommendations could underestimate peritonitis incidence and may depict a distorted pathogen spectrum.