Miracle-dz/UniFAR-FTUs huggingface dataset:
Creating a maternal cardiac center of excellence: a call to action

Abstract In contrast to most industrialized countries, maternal mortality in the USA is rising. Cardiovascular disease, both acquired heart disease (e.g. coronary disease, arrhythmias, and heart failure), as well as congenital heart disease survivors, are all potentially important factors in explaining this worrisome trend. Increase in acquired cardiac disease is likely attributable to greater rates of obesity, diabetes, hypertension, and an increase in the incidence of advanced maternal age, while congenital heart disease in pregnancy is increasing due to advances in pediatric cardiovascular surgery. Despite the growing cardiovascular risk of pregnant women, most obstetricians and cardiologists have limited experience in caring for women with heart disease. Accordingly, management is largely guided by expert opinion likely to vary greatly across centers. To address these challenges, a multidisciplinary approach to care that includes both cardiologists and obstetricians could leverage the knowledge of both specialties and support streamlined communication between the patient and her providers. Our experience highlights the necessary components and essential infrastructure for building a center of excellence in treating pregnant women with heart disease. Condensation: A guide for creating a center of excellence for prenatal care for women with cardiovascular disease. The problem: Cardiac disease is the leading cause of maternal mortality, and pregnancies affected by cardiac disease continue to rise, both congenital and acquired. The solution: Maternal fetal medicine, obstetricians, and cardiologists can join together in tertiary facilities to create Maternal Cardiac Centers of Excellence to provide multidisciplinary, structured care for these high-risk patients.
What predicts quality of life after subthalamic deep brain stimulation in Parkinson’s disease? A systematic review

Subthalamic deep brain stimulation (STN DBS) is an effective therapy against medication‐refractory motor complications in patients with Parkinson’s disease. However, it remains difficult to predict which baseline patient characteristics are associated with quality of life (QoL) after surgery. The objective was to identify preoperative factors associated with QoL after STN DBS by systematically reviewing publications of sufficient methodological quality.
The effects of flutamide on the neonatal rat hypothalamic–pituitary–adrenal and gonadal axes in response to hypoxia

Hypoxia is common with preterm birth and may lead to long‐term effects on the adult hypothalamic–pituitary–adrenal (HPA) axis that are sexually dimorphic due to neonatal androgens. Although the adult rat adrenal does not express appreciable CYP17 activity, the neonatal rat adrenal may synthesize androgens that could be a critical local factor in the development of adrenal function. We evaluated these phenomena by pretreating the neonatal rats on postnatal days (PD) 1, 6, 13, 20 with flutamide (a nonsteroidal androgen receptor antagonist) at a standard or a high dose (10 mg/kg or 50 mg/kg) compared to vehicle control. One day later, neonatal rats were exposed to acute hypoxia and blood was sampled. We found that (a) in PD2 pups, flutamide augmented corticosterone responses in a sexually dimorphic pattern and without an increase in ACTH, (b) PD7 and PD14 pups had the smallest corticosterone response to hypoxia (c) PD21 pups had an adult‐like corticosterone response to hypoxia that was sexually dimorphic, (d) flutamide attenuated ACTH responses in PD7 hypoxic pups, and (e) high‐dose flutamide suppressed the HPA axis, FSH, and estradiol. Flutamide demonstrated mixed antagonist and agonist effects that changed during the first three weeks of neonatal life. We conclude that the use of flutamide in neonatal rats to evaluate androgen‐induced programming of subsequent adult behavior is not optimal. However, our studies suggest neonatal androgens play a role in regulation of adrenal function that is sexually dimorphic and changes during early development.
Use of Immunotherapy With Programmed Cell Death 1 vs Programmed Cell Death Ligand 1 Inhibitors in Patients With Cancer: A Systematic Review and Meta-analysis.

Importance Immune checkpoint inhibitors of programmed cell death 1 (PD-1) and its ligand (PD-L1) have led to a paradigm shift in cancer treatment. Understanding the clinical efficacy and safety profile of these drugs is necessary for treatment strategy in clinical practice. Objective To assess the differences between anti-PD-1 and anti-PD-L1 regarding efficacy and safety shown in randomized clinical trials across various tumor types. Data Sources Systematic searches of PubMed, Cochrane CENTRAL, and Embase were conducted from January 1, 2000, to March 1, 2019. In addition, abstracts and presentations from all major conference proceedings were reviewed. Study Selection All randomized clinical trials that compared anti-PD-1 and anti-PD-L1 with standard treatment in patients with cancer were selected as candidates. Retrospective studies, single-arm phase 1/2 studies, and trials comparing anti-PD-1 and anti-PD-L1 with other immunotherapies were excluded. Studies of anti-PD-1 and anti-PD-L1 therapy were screened and paired by the matching of clinical characteristics as mirror groups. Data Extraction and Synthesis Three investigators independently extracted data from each study following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guideline. Trial names, first author, year of publication, study design, National Clinical Trial identifier number, blinding status, study phase, pathologic characteristics, number of patients, patients' age and sex distribution, Eastern Cooperative Oncology Group Performance Status, lines of treatment, study drugs, biomarker status, follow-up time, incidence of adverse events, and hazard ratios (HRs) with 95% CIs for overall survival and progression-free survival were extracted. A random-effects model was applied for data analysis. Main Outcomes and Measures Differences in OS between anti-PD-1 and anti-PD-L1 across different cancer types were assessed. An effect size was derived from each mirror group and then pooled across all groups using a random-effects model. Results Nineteen randomized clinical trials involving 11 379 patients were included in the meta-analysis. Overall, anti-PD-1 exhibited superior overall survival (HR, 0.75; 95% CI, 0.65-0.86; P < .001) and progression-free survival (HR, 0.73; 95% CI, 0.56-0.96; P = .02) compared with anti-PD-L1. No significant difference was observed in their safety profiles. Sensitivity analysis presented consistency in the overall estimates across these analyses. Consistent results were observed through frequentist and bayesian approaches with the same studies. Conclusions and Relevance Comprehensive analysis suggests that anti-PD-1 exhibited favorable survival outcomes and a safety profile comparable to that of anti-PD-L1, which may provide a useful guide for clinicians.
Role of Interleukin 6 Inhibitors in the Management of Rheumatoid Arthritis

Abstract Rheumatoid arthritis (RA) is a multisystem disease that affects the joints and various organs, resulting in compromised quality of life and increased mortality. A wide spectrum of treatment options is available for RA. Conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) are the first-line of treatment for RA, whereas tumor necrosis factor α inhibitors are commonly used as a second-line biological disease-modifying antirheumatic drug following inadequate response to csDMARDs. However, remission remains difficult to achieve. No single agent is effective for all patients. It is important to consider patients' comorbidities, perspectives, and preferences when selecting treatment. Interleukin 6 (IL-6) plays a prominent role in the pathophysiology of RA and is an important therapeutic target for RA. Tocilizumab and sarilumab are approved IL-6 inhibitors, which have demonstrated good efficacy and tolerability as combination therapy or monotherapy in RA patients with inadequate response to csDMARDs or tumor necrosis factor α inhibitors. Apart from alleviating joint symptoms, inducing remission, and reducing structural damage, tocilizumab and sarilumab exhibit additional advantages in alleviating extra-articular symptoms, such as fatigue and morning stiffness, and have positive effect on anemia and glucose metabolism. Additionally, evidence showed that certain patient subgroups, such as those with comorbidities including anemia and diabetes mellitus, those with early RA, those with high baseline IL-6 levels, those at high risk of tuberculosis infection, or those intolerant to methotrexate monotherapy, may benefit from IL-6 inhibition. Given these advantages, tocilizumab and sarilumab can be considered earlier as a rational choice for treating RA in suitable patients. Future clinical investigations will help refine the use of these agents.
Pilot study for a novel and personalized voice restoration device for patients with laryngectomy

The main modalities for voice restoration after laryngectomy are the electrolarynx, and the tracheoesophageal puncture [Correction added on 30 January 2020 after first online publication: The preceding sentence has been revised. It originally read “The main modalities for voice restoration after laryngectomy are the electrolarynx and the tracheoesophageal puncture. ”]. All have limitations and new technologies may offer innovative alternatives via silent speech.
Blinatumomab vs historic standard‐of‐care treatment for minimal residual disease in adults with B‐cell precursor acute lymphoblastic leukaemia

Survival outcomes from a single‐arm phase 2 blinatumomab study in patients with minimal residual disease (MRD)‐positive B‐cell precursor (BCP)‐acute lymphoblastic leukaemia (ALL) were compared with those receiving standard of care (SOC) in a historic data set.
Are cerebral ischaemic complications more likely to occur in elderly patients undergoing transradial non‐coronary intervention: A single‐centre retrospective review

Transradial artery access (TRA) is an established technique employed by interventional cardiologists for diagnostic and therapeutic coronary interventions. The use of TRA has gained increasing traction amongst interventional radiologists in recent years. In transradial, non‐coronary interventions, the aorta has to be traversed. With increasing age, atherosclerotic changes in the aorta posed a theoretical risk of catheter‐related emboli. Currently, there is limited literature available on the cerebral ischaemic complication rates in transradial non‐coronary interventions.
Epidemiology and clinical outcomes of hospitalizations for acute respiratory or febrile illness and laboratory-confirmed influenza among pregnant women during six influenza seasons, 2010-2016.

BACKGROUND Pregnant women are at increased risk of seasonal influenza hospitalizations, but data about the epidemiology of severe influenza among pregnant women remain largely limited to pandemics. METHODS To describe the epidemiology of hospitalizations for acute respiratory infection or febrile illness (ARFI) and influenza-associated ARFI among pregnant women, administrative and electronic health record data were analyzed from retrospective cohorts of pregnant women hospitalized with ARFI who had testing for influenza viruses by RT-PCR in Australia, Canada, Israel and the United States during 2010-2016. RESULTS Of 18,048 ARFI-coded hospitalizations, 1,064 (6%) included RT-PCR testing for influenza viruses, of which 614 (58%) were influenza-positive. Of 614 influenza-positive ARFI hospitalizations, 35% were in women with low socioeconomic status, 20% with underlying conditions, and 67% in their third trimesters. The median length of influenza-positive hospitalizations was 2 days (IQR 1-4), 18% (95% confidence interval (CI) 15-21%) resulted in delivery, 10% (95% CI 8-12%) included a pneumonia diagnosis, 5% (95% CI 3-6%) required intensive care, 2% (95% CI 1-3%) included a sepsis diagnosis, and <1% (95% CI 0-1%) resulted in respiratory failure. CONCLUSIONS Our findings characterize seasonal influenza hospitalizations among pregnant women and can inform assessments of the public health and economic impact of seasonal influenza on pregnant women.
Daily Cigarette Consumption and Urine Cotinine Level between Dual Users of Electronic and Conventional Cigarettes, and Cigarette-Only Users

ABSTRACT The aim of this study was to identify whether or not the dual users of conventional cigarettes and e-cigs were naturally reducing the amount of their cigarette smoking while they were using e-cigs, and whether their urine cotinine level became similar or less compared to conventional cigarette-only smokers. We used data from the Korean National Health and Nutrition Examination Survey (KNHANES), a nationally representative sample collected in 2014–2016. We selected 2,442 participants who were over 19 years old and were current users of conventional cigarettes and e-cigs. Among the total sample, 12.8% were dual users of e-cigs and conventional cigarettes. Conventional cigarette-only users smoked 14.26 (±23.19) cigarettes a day, while dual users of electronic and conventional cigarettes smoked 14.46 (±7.88) cigarettes a day (p < .001). Means of urine cotinine level in conventional cigarette-only users and dual users were 1250.35 ng/mL (±832.75) and 1364.95 ng/mL (±827.96), respectively (p < .001). The result of a multiple linear regression analysis identified that dual users’ cotinine level was 136.80 ng/mL higher, compared to conventional cigarette smokers’ one (p = .011). Unlike the argument that e-cigs can be used as a smoking cessation aid, we found that using e-cigs might be less likely to support quitting smoking or reducing cigarette consumption.
Asymmetry in the aging brain: A narrative review of cortical activation patterns and implications for motor function

ABSTRACT Age-related changes have been identified in neural and motor level. A prominent change is reduced asymmetry in cortical activation as well as motor performance. Cortical activation models have been established based on cognitive research utilizing neuroimaging techniques to explain age-related effects on neural recruitment and reduced brain asymmetry. Recently, researchers in motor behaviour attempted to apply the models to explain motor pattern changes in aging and proposed compensation as the mechanism of the reduced motor asymmetry in older adults. Age-related alterations in movement patterns and brain activations seem to be correlated. However, based on the literature search result, no direct evidence substantiates the connection between reduced brain asymmetry and motor asymmetry in older adults. Therefore, a theoretical gap was identified. The theoretical gap exists because either neuroimaging studies have not considered motor asymmetry or motor asymmetry studies have not integrated neuroimaging techniques into study designs. Answering the research question can be valuable to both research and clinical practice. With the mechanisms of brain activation patterns during motor tasks in an aging population being better understood, protocols developed upon the new understandings can be applied to current motor interventions and better maintain the longevity of motor function of older adults.
The role of progestogen supplementation (dydrogesterone) in the prevention of preeclampsia

Abstract Our goal was determine the effects of dydrogesterone supplementation to reduce the incidence of preeclampsia (PE) in early pregnancy (from 6 to 20 weeks of gestation). A total of 406 pregnant women were involved into the study. The Study group enrolled 169 women, supplemented with dydrogesterone at a dose of 30 mg/d 6–20 weeks of gestation compared with the control group (237 subjects) – without dydrogesterone supplementation. The women were randomized by age, race, obstetrics complications, and their somatic history. The use of dydrogesterone in early pregnancy – before 20 weeks of gestation (at a dose of 30 mg/d) with high-risk factors of PE contributed to a statistically significant reduction in the frequency of this complication (13.1% and 71.4%, p < .001). It was seen, that women who took dydrogesterone developed significantly less such disorders like hypertension (3.2% and 71.2%, p < .001), proteinuria (0.0% and 66.18%, p < .001), fetal growth retardation syndrome (2.2% and 21.58%, p < .001), destroy of uteri-placenta velocity (3.2% and 21.58%, p < .001), preterm labor (8.6% and 53.95%, p < .001). Dydrogesterone supplementation in the first and second period of pregnancy (from 6 to 20 weeks of gestation) significantly reduced the incidence of PE in women with higher risk pregnancy.
Mapping geographical patterns and high rate areas for sexually transmitted infections in Portugal - a retrospective study based on the National Epidemiological Surveillance System.

OBJECTIVE Monitoring disease variation using finer scales to identify high rate communities is a critical aspect for precision public health and for efficient resource allocation. This study aimed to map the spatial patterns of chlamydia, gonorrhoea and syphilis, identify high rate areas across Portuguese municipalities and determine the association of these sexually transmitted infections (STIs) with socioeconomic deprivation, urbanicity level, and population density. METHODS STIs notifications at municipality-level for the period 2015-2017 were obtained from Portugal's Epidemiologic Surveillance System (SINAVE). Spatial Bayesian models were used to calculate smoothed standardised notification rates, identify high and low rate areas and estimate associations (Relative Risk, RR, 95% Credible Intervals, 95%CrI). RESULTS 4819 cases of chlamydia, gonorrhoea and syphilis were reported, accounting for 15.3%, 33.2%, and 51.5% of the notifications, respectively. STIs notification rates were substantially higher in Porto and Lisbon Metropolitan Areas and concentrically disperse around those. Notification rates of the three STIs were strongly correlated (r>0.8). Rates of gonorrhoea (Q1-lowest density vs. Q5-highest RR=2.10 95%CrI 1.08-4.25) and syphilis (RR=3.16 95%CrI 2.00-5.13) were associated with population density. Notifications of chlamydia (Q1-least urban vs. Q5-most RR=9.64, 95%CrI 1.73-93.59) and syphilis (RR=1.92, 95%CrI 1.30-2.88) increased with urbanicity level. We also found that notification rates of gonorrhoea were associated with socioeconomic deprivation (Q1-least vs. Q5-most deprived RR=1.75, 95%CrI 1.07-2.88). CONCLUSIONS Wide spatial inequalities in STIs notification rates were observed, which were predominantly concentrated in the two metropolitan areas of the country. Our findings can help guide more targeted interventions to reduce STIs incidence.
Immune checkpoint inhibitors in melanoma in the metastatic, neoadjuvant, and adjuvant setting.

PURPOSE OF REVIEW Immune checkpoint inhibitors (ICI) are now standards of care in metastatic melanoma. We highlight here the dramatic improvement that these drugs brought in the history of melanoma care. RECENT FINDINGS The monoclonal antibody directed against cytotoxic T-lymphocyte-associated protein 4, ipilimumab, was approved in 2011. Antiprogramed death cell protein 1 antibodies, nivolumab and pembrolizumab, were developed afterward and approved in 2014, demonstrating an improved efficacy/safety ratio as compared with ipilimumab. The association of ipilimumab and nivolumab now appears as the most efficient immunotherapy but the toxicity of this regimen is a limitation. These drugs have also been evaluated in the adjuvant setting for patients with stage III or IV resected melanoma where they have shown a significant benefit in terms of relapse-free survival. SUMMARY ICI-based immunotherapy radically modified melanoma management and now appear as the most efficient treatment for patients with metastatic melanoma with characterized by long-lasting cancer remissions, and a distinct spectrum of immune-related adverse events. Their efficacy is now also established in the adjuvant setting and they are now actively evaluated as neoadjuvant treatment with promising early results.Intensive translational work is ongoing to identify predictive biomarkers of efficacy and toxicity to improve ICI benefit/risk ratio.
Lactoperoxidase inhibition of some natural phenolic compounds: Kinetics and molecular docking studies.

The inhibition effects of some phenolic compounds from natural products such as taxifolin, resveratrol, olivetol, cynarine, and phloretin on bovine milk lactoperoxidase (LPO) enzyme were examined. For this aim, LPO was purified by the affinity chromatography technique with a yield of 77.68% in 421.32 times. The kinetic value, Ki , was calculated from the equations obtained from drawn graphs. In order to discover inhibition mechanism of phenolic compounds, induced fit docking process was performed on the LPO receptors. The binding affinity of the compounds was calculated and at the best-scored ligand-receptor complex, residues responsible for enzyme inhibition were detected. As a result, this molecule demonstrated the potential inhibitory effect on LPO. According to the results of kinetic study. It has shown a noncompetitive inhibition effect, Phloretin's Ki value was determined by 48.89 ± 14.22 nM. PRACTICAL APPLICATIONS: There are natural antimicrobial systems, such as the lactoperoxidase (E.C.1.11.1.7; LPO) system, which eliminates the harmful effects of microorganisms in milk. The chemical reactions in this system are catalyzed by the LPO. In the dairy industry, the LPO system is considered critical for the preservation of pasteurized milk, yogurt, raw milk, and cheese. The system is used for improvement the protection condition of milk at high temperatures.
A nomogram for preoperative prediction of lymphatic infiltration in colorectal cancer

Abstract Lymphatic infiltration (LI) is a key factor affecting the treatment of patients with colorectal cancer (CRC). Thus, the aim of this study was to develop and validate a nomogram for individual preoperative prediction of LI in patients with CRC. We conducted a retrospective analysis of 664 patients who received their initial diagnosis of CRC at our center. Those patients were allocated to a training dataset (n = 468) and a validation dataset (n = 196). The least absolute shrinkage and selection operator regression model was used for data dimension reduction and feature selection. The nomogram was constructed from the training dataset and internally verified using the concordance index (C-index), calibration, area under the receiver operating characteristic curve and decision curve analysis (DCA). The enhancement computed tomography reported N1/N2 classification, preoperative tumor differentiation, elevated carcinoembryonic antigen, and carbohydrate antigen19-9 level were selected as variables for the prediction nomogram. Encouragingly, the nomogram showed favorable calibration with C-index 0.757 in the training cohort and 0.725 in validation cohort. The DCA signified that the nomogram was clinically useful. The Kaplan–Meier survival curve showed that patients with LI had a worse prognosis and could benefit from postoperative adjuvant chemotherapy. Use common clinicopathologic factors, a non-invasive scale for individualized preoperative forecasting of LI was established conveniently. LI prediction has great significance for risk stratification of prognosis and treatment of resectable CRC.