Miracle-dz/UniFAR-FTUs huggingface dataset:
Do changes in health reveal the possibility of undiagnosed pancreatic cancer? Development of a risk-prediction model based on healthcare claims data

Background and objective Early detection methods for pancreatic cancer are lacking. We aimed to develop a prediction model for pancreatic cancer based on changes in health captured by healthcare claims data. Methods We conducted a case-control study on 29,646 Medicare-enrolled patients aged 68 years and above with pancreatic ductal adenocarcinoma (PDAC) reported to the Surveillance Epidemiology an End Results (SEER) tumor registries program in 2004–2011 and 88,938 age and sex-matched controls. We developed a prediction model using multivariable logistic regression on Medicare claims for 16 risk factors and pre-diagnostic symptoms of PDAC present within 15 months prior to PDAC diagnosis. Claims within 3 months of PDAC diagnosis were excluded in sensitivity analyses. We evaluated the discriminatory power of the model with the area under the receiver operating curve (AUC) and performed cross-validation by bootstrapping. Results The prediction model on all cases and controls reached AUC of 0.68. Excluding the final 3 months of claims lowered the AUC to 0.58. Among new-onset diabetes patients, the prediction model reached AUC of 0.73, which decreased to 0.63 when claims from the final 3 months were excluded. Performance measures of the prediction models was confirmed by internal validation using the bootstrap method. Conclusion Models based on healthcare claims for clinical risk factors, symptoms and signs of pancreatic cancer are limited in classifying those who go on to diagnosis of pancreatic cancer and those who do not, especially when excluding claims that immediately precede the diagnosis of PDAC.
Resident Education in Complex Obstetric Procedures: Are We Adequately Preparing Tomorrow's Obstetricians?

Abstract Objectives The Accreditation Council for Graduate Medical Education (ACGME) milestones for obstetrics and gynecology (OB/GYN) residents include obstetrical technical skills. We sought to describe resident experience with surgical obstetrics and comfort performing procedures independently postgraduation. Study Design An anonymous 27-question e-survey was sent to OB/GYN residents in United States in March 2018, using the Council of Resident Education in Obstetrics and Gynecology coordinator listserv. Complex obstetric procedures included: forceps-assisted vaginal delivery (FAVD) and vacuum-assisted vaginal delivery (VAVD), cerclage, breech second twin, breech delivery, perineal repairs, and cesarean hysterectomy. Technical skill questions included experience as primary surgeon, comfort performing procedures independently, and for 4th year residents—comfort performing procedures postresidency. Demographic information was queried. Descriptive statistics was used to analyze responses. Results A total of 417 residents completed the survey. Respondents were 88% female, 75% from academic programs, and 48% postgraduate year 3 and 4. Among all residents, many had been primary surgeon in operative vaginal deliveries (51% FAVD, 72% VAVD), fewer for breech vaginal delivery (21%), breech second twin (34%), cesarean hysterectomy (21%), and 4th degree repairs (37%). All 4th-year respondents stated that they would feel comfortable performing either VAVD or FAVD postresidency. Note that 17, 33, 28, and 74% would not feel comfortable performing a 4th degree repair, cesarean hysterectomy, breech second twin, and breech vaginal delivery, respectively, postresidency. Conclusion Despite ACGME recommendations, data suggest that many graduating residents may not be comfortable with these complex procedures.
CELF2 suppresses non-small cell lung carcinoma growth by inhibiting the PREX2-PTEN interaction.

The phosphoinositide 3-kinase (PI3-K)/Akt signaling pathway is important in the regulation of cell proliferation through its production of phosphatidylinositol 3,4,5-triphosphate (PIP3). Activation of this pathway is frequently observed in human cancers, including non-small cell lung carcinoma. The PI3-K/Akt pathway is negatively regulated by the dual-specificity phosphatase and tensin homolog (PTEN) protein. PTEN acts as a direct antagonist of PI3-K by dephosphorylating PIP3. Studies have shown that PTEN phosphatase activity is inhibited by PREX2, a guanine nucleotide exchanger factor (GEF). Multiple studies revealed that CELF2, an RNA binding protein, cooperates synergistically with PTEN as a tumor suppressor in multiple cancers. However, the underlying mechanism as to how CELF2 enhances PTEN activity remains unclear. Here, we report that CELF2 interacts with PREX2 and reduces the association of PREX2 with PTEN. Consistent with this observation, PTEN phosphatase activity is upregulated with CELF2 overexpression. In addition, overexpression of CELF2 represses both Akt phosphorylation and cell proliferation only in the presence of PTEN. In an ex vivo study, CELF2 gene delivery could significantly inhibit PDX tumor growth. To further investigate the clinical relevance of this finding, we analyzed 87 paired clinical lung adenocarcinoma samples and the results showed that CELF2 protein expression is downregulated in tumor tissues and associated with poor prognosis. The CELF2 gene is located on the chromosome 10p arm, a region frequently lost in human cancers, including breast invasive carcinoma, low-grade glioma, and glioblastoma. Analysis of TCGA datasets showed that CELF2 expression is also associated with shorter patient survival time in all these cancers. Overall, our work suggests that CELF2 plays a novel role in PI3-K signaling by antagonizing the oncogenic effect of PREX2.
Management of reproductive health after cardiac transplantation

Abstract Pregnancy after cardiac transplantation poses immense challenges. Maternal risks include hypertensive disorders of pregnancy, rejection, and failure of the cardiac allograft that may lead to death. Fetal risks include potential teratogenic effects of immunosuppression and prematurity. Because of the high-risk nature of pregnancy in a heart transplant patient, management of reproductive health after cardiac transplantation should include preconception counseling to all women in the reproductive age group before and after cardiac transplantation. Reliable contraception is vital as nearly half of the pregnancies in this population are unintended. Despite the associated risks, successful pregnancies after cardiac transplantation have been reported. A multidisciplinary approach proposed in this review is essential for successful outcomes. A checklist for providers to guide management is provided.
Hacking women’s health: A new methodology

Abstract The paper describes an innovative methodological approach to Public Engagement already tested by the Authors in the healthcare context. We propose to apply our methodology to social innovation projects, focusing on gender perspective when promoting enhancements in health-community. Methodology mixes Psychosocial Participatory Research, Service-Design and “Human-Centered” approach, promoting an interdisciplinary, technological, and sustainable process. The final aim is to find viable solutions to real problems through the engagement of a community of experts and citizens in a three-step process. Awareness-raising actions: to increase people’s knowledge—group understanding of the subject and to stimulate reflection. Activities: Gender-Cafés, Ethnographic-Observations and Narrative-Interviews. Activation actions: group interventions in which initial stimuli are collected and processed into proposals for services and tools aimed at targeted groups. Activities: Barcamps, Generative Labs. Participation actions: multidisciplinary teams realize prototypes and elaborate concrete solutions (tools, services) addressing crucial gender issues. Activities: Hackathon, Service-Design-Labs.
Circulating high mobility group box-1 and toll-like receptor 4 expressions increase the risk and severity of epilepsy

This study aimed to investigate the association of serum high-mobility group box-1 (HMGB1) and toll-like receptor 4 (TLR4) expressions with the risk of epilepsy as well as their correlations with disease severity and resistance to anti-epilepsy drugs. One hundred and five epilepsy patients and 100 healthy controls (HCs) were enrolled in this case-control study, and serum samples were collected from all participants to assess the HMGB1 and TLR4 expressions by enzyme-linked immunosorbent assay (ELISA). Both serum HMGB1 (P<0.001) and TLR4 (P<0.001) expressions were higher in epilepsy patients than in HCs, and they displayed good predictive values for risk of epilepsy. Moreover, HMGB1 was positively correlated with TLR4 level (r=0.735, P<0.001). HMGB1 and TLR4 levels were both elevated in patients with an average seizure duration >5 min compared to patients with a seizure duration ≤5 min (P=0.001 and P=0.014, respectively). Also, HMGB1 and TLR4 were increased in patients with seizure frequency >3 times per month compared to patients with seizure frequency ≤3 times per month (both P=0.001). In addition, HMGB1 and TLR4 expressions were higher in intractable cases compared to drug-responsive cases (P<0.001). In conclusion, both HMGB1 and TLR4 expressions were correlated with increased risk and severity of epilepsy and their level was higher in patients resistant to anti-epilepsy drugs.
Mechanical thrombectomy for basilar artery occlusion: efficacy, outcomes, and futile recanalization in comparison with the anterior circulation

Background Performing mechanical thrombectomy (MT) in patients with basilar artery occlusion (BAO) is currently not evidence-based. Objective To compare patients’ outcome, relative merits of achieving recanalization, and predictors of futile recanalization (FR) between BAO and anterior circulation large vessel occlusion (ACLVO) MT. Methods In the multicenter BEYOND-SWIFT registry (NCT03496064), univariate and multivariate (displayed as adjusted Odds Ratios, aOR and 95% confidence intervals, 95%-CI) outcome comparisons between BAO (N=165) and ACLVO (N=1574) were performed. The primary outcome was favorable outcome at 90 days (modified Rankin Scale, mRS 0-2). Secondary outcome included mortality, symptomatic intracranial hemorrhage (sICH) and FR. The relative merits of achieving successful recanalization between ACLVO and BAO were evaluated with interaction terms. Results MT in BAO was more often technically effective and equally safe in regards to mortality and sICH when compared to ACLVO. When adjusting for baseline differences, there was no significant difference between BAO vs ACLVO regarding rates of favorable outcome (aOR 0.986, 95%-CI 0.553 – 1.758). However, BAO were associated with increased rates of FR (aOR 2.146, 95%-CI 1.267 – 3.633). Predictors for FR were age, stroke severity, maneuver count and intracranial stenting. No significant heterogeneity on the relative merits of achieving successful recanalization on several outcome parameters were observed when comparing BAO and ACLVO. Conclusions In selected patients, similar outcomes can be achieved in BAO and ACLVO patients treated with MT. Randomized controlled trials comparing patient selection and interventional strategies seem warranted to avoid FR. Trial registration number NCT03496064
PKR activation by noncanonical ligands: a 5′-triphosphate requirement versus antisense contamination

Protein kinase RNA-activated (PKR) is an interferon-inducible kinase that is potently activated by long double-stranded RNA (dsRNA). In a previous study, we found that snoRNAs exhibit increased association with PKR in response to metabolic stress. While it was unclear if snoRNAs also activated PKR in cells, activation in vitro was observed. snoRNAs do not exhibit the double-stranded character typically required for activation of PKR, but some studies suggest such RNAs can activate PKR if triphosphorylated at the 5′ terminus, or if they are able to form intermolecular dimers. To interrogate the mechanism of PKR activation by snoRNAs in vitro we focused on SNORD113. Using multiple methods for defining the 5′-phosphorylation state, we find that activation of PKR by SNORD113 does not require a 5′-triphosphate. Gel purification from a native gel followed by analysis using analytical ultracentrifugation showed that dimerization was also not responsible for activation. We isolated distinct conformers of SNORD113 from a native polyacrylamide gel and tracked the activating species to dsRNA formed from antisense RNA synthesized during in vitro transcription with T7 RNA polymerase. Similar studies with additional snoRNAs and small RNAs showed the generality of our results. Our studies suggest that a 5′ triphosphate is not an activating ligand for PKR, and emphasize the insidious nature of antisense contamination.
Factors Related to Intention to Leave and Job Satisfaction among Registered Nurses at a Large Psychiatric Hospital

Abstract Introduction: Current shortages of registered nurses working in psychiatric hospitals in the United States are exacerbated by turnover. Aim: This research describes factors that are associated with intent to leave among nurses working in a large inpatient psychiatric hospital. Method: This was a descriptive, correlational study. Results: 75% of respondents (n = 94) reported that they were satisfied with their current positions. 36% (n = 34) reported actively seeking employment elsewhere. Intent to leave correlated with perceptions about workplace relationships and work environment factors. Discussion: Work relationships, opportunity for education, and recognition for education were factors that were primarily related to intent to leave.
Technical feasibility of umbilical cannulation in midgestation lambs supported by the EXTra-uterine Environment for Neonatal Development (EXTEND).

PURPOSE EXTEND (EXTra-uterine Environment for Neonatal Development) is a novel system for supporting extremely premature infants that replicates in utero conditions by maintaining a sterile fluid environment and providing gas exchange via a pumpless arteriovenous oxygenator circuit connected to the umbilical vessels. Target gestational age (GA) for EXTEND support in human infants is 23 to 27 weeks, when immature lungs are most susceptible to injury in the setting of air ventilation. We previously demonstrated physiologic support of premature lambs cannulated at 105-117 days GA (lungs developmentally analogous to the 23-27 week GA human infant) for up to 28 days on EXTEND. In the present study we sought to determine the technical feasibility of umbilical vessel cannulation in 85-96 day GA lambs delivered to EXTEND at weights equivalent to the 23-27 week GA human infant (500-850g). METHODS Five preterm lambs were cannulated at 85-96 days GA (term 145 days) and supported on EXTEND for 4-7 days. All lambs underwent umbilical artery and umbilical vein cannulation. Circuit flows and pressures were monitored continuously, and blood gases were obtained at regular intervals for assessment of oxygen parameters. Systemic pH and lactate were measured at least once daily. RESULTS Mean body weight at cannulation was 641±71g (range 480-850g). All lambs were cannulated successfully (cannula size varied from 8Fr to 12Fr), and mean survival on EXTEND was 140±7 hours. Mean circuit flow was 213±15 ml/kg*min, mean pH was 7.37±0.01, and mean lactate was 1.6±0.2 mmol/l. During the initial 120 hours after EXTEND cannulation, there were no significant differences between 85-96 day GA lambs and 105-117 day GA lambs in weight-adjusted circuit flows, oxygen delivery, pH, or lactate levels. CONCLUSIONS This study demonstrates successful umbilical cord cannulation and adequate circuit flows and oxygen delivery in midgestation lambs size-matched to the 23-27 week GA human fetus, which represents an important step in the translation of EXTEND to clinical practice. This article is protected by copyright. All rights reserved.
EN1 is a transcriptional dependency in triple-negative breast cancer associated with brain metastasis.

To define transcriptional dependencies of triple-negative breast cancer (TNBC), we identified transcription factors highly and specifically expressed in primary TNBCs and tested their requirement for cell growth in a panel of breast cancer cell lines. We found that EN1 (Engrailed 1) is overexpressed in TNBCs and its downregulation preferentially and significantly reduced viability and tumorigenicity in TNBC cell lines. By integrating gene expression changes after EN1 downregulation with EN1 chromatin binding patterns, we identified genes involved in WNT and Hedgehog signaling, neurogenesis, and axonal guidance as direct EN1 transcriptional targets. Quantitative proteomic analyses of EN1-bound chromatin complexes revealed association with transcriptional repressors and co-activators including TLE3, TRIM24, TRIM28, and TRIM33. High expression of EN1 correlated with short overall survival and increased risk of developing brain metastases in TNBC patients. Thus, EN1 is a prognostic marker and a potential therapeutic target in TNBC.
Knowledge, attitudes and practices related to hypertension among residents of a disadvantaged rural community in southern Zimbabwe

Background Hypertension contributes significantly to cardiovascular and renal diseases. It can be controlled by lifestyle modifications, however in poor communities there is lack of awareness, and treatment and control of hypertension is often poor. The aim of this study was to determine hypertension knowledge, attitudes and practices in a disadvantaged rural community in Matebeleland South province of Zimbabwe. Methods We conducted a descriptive cross-sectional survey on hypertensive patients in the community. A pre-tested and validated interviewer-administered questionnaire was used to collect demographic, awareness, treatment and control data among consenting hypertensive patients. Results 304 respondents were enrolled into the study (mean age, 59 years), and a majority were women (65.4%). The treatment default rate was 30.9%, and 25% of respondents on medication did not know their blood pressure control status. Knowledge on hypertension was poor, with 64.8% of respondents stating that stress was its main cause, 85.9% stated that palpitations were a symptom of hypertension and 59.8% of respondents added salt on the table. The more education respondents had received, the more likely they were knowledgeable about hypertension (odds ratio for secondary education, 3.68 [95% CI: 1.61–8.41], and for tertiary education, 7.52 [95% CI: 2.76–20.46], compared to those without formal education). Those who believed in herbal medicines (50.7%) and those who used traditional medicines (14.5%) were 53% (95% CI: 0.29–0.76) and 68% (95% CI: 0.29–0.76) less likely to be knowledgeable about hypertension compared to those who did not believe in or use traditional medicines, respectively. Conclusion Members of the community had poor knowledge on hypertension. This was associated with a lack of education and with strong beliefs in herbal and traditional medicines in the community, which influenced attitudes and practices on hypertension. Dietary risk factors were linked to poor knowledge. Hypertensive medicine shortages at the clinic resulted in worsened hypertension care and poor hypertension outcomes in the community.
Anthropometrics, diet, and resting energy expenditure in Norwegian adults with achondroplasia

Individuals with achondroplasia have a high prevalence of obesity and increased risk of cardiovascular disease. Fat distribution, diet, and caloric intake are known risk factors, but the literature concerning diet and energy balance in achondroplasia is limited. The main aim of this study was to describe the anthropometrics, diet, and resting energy expenditure (REE) in a Norwegian adult achondroplasia population. Here, we present a descriptive cross‐sectional study with the following variables: anthropometrics, the SmartDiet questionnaire, and dietary records. In addition, REE was measured and estimated using indirect calorimetry and prediction equations. A total of 33 adults with achondroplasia participated with a mean age of 40 years. Mean body mass index was 34.1 kg/m2, and mean waist circumference was 94.1 cm for men and 82.2 cm for women. Their diets were classified as unhealthy (38%) or in need of improvement (62%). The mean REE values for the total group were 21 kcal/kg for the male (n = 15) and 20 kcal/kg for the female (n = 18). This study revealed a high frequency of central obesity and unhealthy dietary habits in Norwegian adults with achondroplasia. Mean energy intake was low and only 10% higher than the mean REE, and does not explain the high prevalence of abdominal obesity in our population.
Perception and acoustics of voiceless initial stops produced by alaryngeal speakers in Taiwan

ABSTRACT This study investigates three aspirated voiceless stop consonants and their unaspirated counterparts produced in Taiwan’s Southern Min dialect by 10 laryngeal speakers (LA), 10 speakers with pneumatic artificial larynxes (PA), and 10 oesophageal speakers (ES). Listeners’ perceptions of the accuracy of the three groups in producing these six stop consonants were also examined. Each of the voiceless stop consonants /p, pʰ, t, tʰ, k, kʰ/, followed by the vowel /a/, was represented by a Southern Min character and appeared three times on a list in random order. Each character had a consonant-vowel syllable structure, and all were read with Tone 1 (high and level). Voice onset time (VOT) was measured for each stop consonant. A separate group of 20 listeners was then asked to identify the consonants produced by the LA, PA, and ES speakers. The VOT values of aspirated voiceless stop consonants from PA and ES were shorter than those from LA. Although PA and ES had aspiration contrast in their VOT values, perceived accuracy was low for PA (/pʰ/: 16.3%; /tʰ/: 13.5%; /kʰ/: 22.8%) and ES (/pʰ/: 33.7%; /tʰ/: 25.9%; /kʰ/: 31.9%). The mean percentages of correctly identified /pʰ, tʰ, kʰ/ produced by PA were at chance level. In terms of VOT values, it is recommended that, when producing aspirated voiceless stop consonants, PA and ES elongate the duration between the release of the oral constriction and the onset of their vibratory sound source. Moreover, it is also recommended that further investigation into other phonetic properties that support stop contrast is needed.
Impact of the odors of vanilla extract and breast milk on the frequency of apnea in preterm neonates.

AIM We developed this study using an experimental design to determine the impact of the odors of vanilla extract and breast milk on apnea frequency in preterm neonates. MATERIALS AND METHODS We obtained the study data from 42 preterm neonates (16 vanilla, 13 breast milk, 13 control group) who had been admitted to the Neonatal Intensive Care Unit of Istanbul University meeting the case selection criteria. All groups were monitored on the first day without any intervention. On the second and third days, breast milk was placed in the incubators of the babies in the breast milk group and the sterile gauze that was vanilla-impregnated was placed in the incubators of the babies in the vanilla group. On the fourth day, the babies were watched without any interference. RESULTS On the second, third and fourth days of the study, we determined that apnea frequency in the vanilla group neonates was significantly lower (P < .00) as compared to the breast milk and control groups. CONCLUSION Using vanilla extract in neonates suffering from apnea to reduce its frequency is an effective method.