Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of tracheal intubation and tracheal tube position on regional lung ventilation: an observational study

Anaesthesia and positive pressure ventilation cause ventral redistribution of regional ventilation, potentially caused by the tracheal tube. We used electrical impedance tomography to map regional ventilation during anaesthesia in 10 patients with and without a tracheal tube. We recorded impedance data in subjects who were awake, during bag‐mask ventilation, with the tracheal tube positioned normally, rotated 90° to each side and advanced until in an endobronchial position. We recorded the following measurements: ventilation of the right lung (proportion, %); centre of ventilation (100% = entirely ventral); global inhomogeneity (0% = homogenous); and regional ventilation delay, an index of temporal heterogeneity. We compared the results using Student's t‐tests. Relative to subjects who were awake, anaesthesia with bag‐mask ventilation reduced right‐sided ventilation by 5.6% (p = 0.002), reduced regional ventilation delay by 1.6% (p = 0.025), and moved the centre of ventilation ventrally from 51.4% to 58.2% (p = 0.0001). Tracheal tube ventilation caused a further centre of ventilation increase of 1.3% (p = 0.009). With the tube near the carina, right‐sided ventilation increased by 3.2% (p = 0.031) and regional ventilation delay by 2.8% (p = 0.049). Tube rotation caused a 1.6% increase in right‐sided ventilation compared with normal position (p = 0.043 left and p = 0.031 right). Global inhomogeneity remained mostly unchanged. Ventral ventilation with positive pressure ventilation occurred with bag‐mask ventilation, but was exacerbated by a tracheal tube. Tube position influenced ventilation of the right and left lungs, while ventilation overall remained homogenous. Tube rotation in either direction resulted in ventilation patterns being closer to when awake than either bag‐mask ventilation or a normally positioned tube. These results suggest that even ideal tube positioning cannot avoid the ventral shift in ventilation.
IL (Interleukin)-15 Bridges Astrocyte-Microglia Crosstalk and Exacerbates Brain Injury Following Intracerebral Hemorrhage

Supplemental Digital Content is available in the text. Background and Purpose— Microglia are among the first cells to respond to intracerebral hemorrhage (ICH), but the mechanisms that underlie their activity following ICH remain unclear. IL (interleukin)-15 is a proinflammatory cytokine that orchestrates homeostasis and the intensity of the immune response following central nervous system inflammatory events. The goal of this study was to investigate the role of IL-15 in ICH injury. Methods— Using brain slices of patients with ICH, we determined the presence and cellular source of IL-15. A transgenic mouse line with targeted expression of IL-15 in astrocytes was generated to determine the role of astrocytic IL-15 in ICH. The expression of IL-15 was controlled by a glial fibrillary acidic protein promoter (GFAP-IL-15tg). ICH was induced by intraparenchymal injection of collagenase or autologous blood. Results— In patients with ICH and wild-type mice subjected to experimental ICH, we found a significant upregulation of IL-15 in astrocytes. In GFAP-IL-15tg mice, we found that astrocyte-targeted expression of IL-15 exacerbated brain edema and neurological deficits following ICH. This aggravated ICH injury in GFAP-IL-15tg mice is accompanied by increased microglial accumulation in close proximity to astrocytes in perihematomal tissues. Additionally, microglial expression of CD86, IL-1β, and TNF-α is markedly increased in GFAP-IL-15tg mice following ICH. Furthermore, depletion of microglia using a colony stimulating factor 1 receptor inhibitor diminishes the exacerbation of ICH injury in GFAP-IL-15tg mice. Conclusions— Our findings identify IL-15 as a mediator of the crosstalk between astrocytes and microglia that exacerbates brain injury following ICH.
Vitiligo: Mechanisms of Pathogenesis and Treatment.

Vitiligo is an autoimmune disease of the skin that targets pigment-producing melanocytes and results in patches of depigmentation that are visible as white spots. Recent research studies have yielded a strong mechanistic understanding of this disease. Autoreactive cytotoxic CD8+ T cells engage melanocytes and promote disease progression through the local production of IFN-γ, and IFN-γ-induced chemokines are then secreted from surrounding keratinocytes to further recruit T cells to the skin through a positive-feedback loop. Both topical and systemic treatments that block IFN-γ signaling can effectively reverse vitiligo in humans; however, disease relapse is common after stopping treatments. Autoreactive resident memory T cells are responsible for relapse, and new treatment strategies focus on eliminating these cells to promote long-lasting benefit. Here, we discuss basic, translational, and clinical research studies that provide insight into the pathogenesis of vitiligo, and how this insight has been utilized to create new targeted treatment strategies. Expected final online publication date for the Annual Review of Immunology, Volume 38 is April 26, 2020. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
Cataract Formation and Low-Dose Radiation Exposure from Head Computed Tomography (CT) Scans in Ontario, Canada, 1994–2015

Ionizing radiation exposure to the lens of the eye is a known cause of cataractogenesis. Administrative data from the Ontario Health Insurance Program was used to examine the association between low-dose radiation exposure from head CT scans and cataract extraction surgery for 16 million Ontarians over a 22-year period (1994–2015). Subjects were grouped based on the number of head CT scans they received, and a Cox proportional hazards analysis was used to determine if there was a correlation with cataract surgery. Covariates included in the analysis were age, sex, diabetes, hypertension and prior history of intraocular surgery. To account for the potentially long latency period between radiation exposure and cataract formation, the data were analyzed incorporating a 5- and 10-year lag between head CT scan exposure and cataract surgery. Both the 5- and 10-year lagged models followed a similar trend, where only the first three head CT scans significantly increased the risk of cataract surgery by 3–8%. Individuals receiving four or more head CT scans did not have an increased cataract risk and in several cases the risk was reduced. Overall, no positive dose-response relationship was seen between the number of head CT scans received and the risk of cataract surgery. Due to the nature of the data extracted from medical records, several uncertainties exist in the analysis related to dosimetry, ultraviolet light exposure and smoking status. Nonetheless, these results do not support an association between ionizing radiation from repeated head CT scans and cataract formation.
The pre-HFpEF stage: a new entity that requires proper phenotyping for better management.

The diagnosis of heart failure (HF) with preserved ejection fraction remains challenging. In heart failure with preserved ejection fraction (HFpEF), left ventricular ejection fraction (LVEF) is normal and signs and symptoms of HF are often non-specific and do not allow for clear discrimination of HF from other clinical conditions. According to the 2016 European Society of Cardiology guidelines for HF diagnosis and treatment, improving the specificity of HFpEF diagnosis requires that the following criteria be met: the presence of symptoms and/or signs of HF, a ‘preserved’ ejection fraction (LVEF 50%), elevated levels of natriuretic peptides (B-type natriuretic peptide >35pg/mL and/or N-terminal prohormone B-type natriuretic peptide (NT-proBNP) >125pg/mL) and objective evidence of other cardiac functional and structural alterations underlying HF. These features may include relevant structural heart disease criteria (such as left ventricular mass index 115g/m for men and 95g/m for women and/or left atrial enlargement >34mL/m) and/or diastolic dysfunction (E/E0 13). This definition has recently been updated to account for many additional comorbidities needed to support a proper diagnosis of HFpEF syndrome. Even as defining HFpEF represents a daunting task, a new entity is being characterised: the ‘pre-HFpEF stage’. The pre-HFpEF stage may affect even a larger number of patients than other HF entities and requires the urgent attention of practising clinicians. A few questions relate to what is and is not the pre-HFpEF stage. First, is pre-HFpEF the same as the American College of Cardiology Foundation (ACCF)/American Heart Association (AHA) stage A, defined by a high risk of HF but without structural heart disease or symptoms of HF? No, it is not. Second, is pre-HFpEF the same as ACCF/AHA stage B, defined by structural heart disease without signs or symptoms of HF? No, it is not that either. The definition of pre-HFpEF is taking shape as presenting in an asymptomatic patient (absence of signs or symptoms of HF) with preserved LVEF, structural heart abnormalities (similar to those reported for HFpEF), and elevated biomarker surrogates of cardiac dysfunction (mainly natriuretic peptides, with cut-point values similar to those reported for HFpEF; Table 1). In contrast to ‘true HFpEF’, the key clinical component of pre-HFpEF is the absence of HF signs and symptoms. Granularity in phenotyping the preHFpEF stage may require evaluation of structural and molecular abnormalities assessed on an increasing gradient of risk. Pre-HFpEF may thus be recognised as a combination of AHA stages A and B plus cardiac biomarkers of risk. In the current issue of the European Journal of Preventive Cardiology, Gori et al. report on this incompletely characterised clinical phenotype. These authors explored the value of predicting new-onset HF and death by combining diastolic dysfunction (DD; E/E0>15) and NT-proBNP values in an asymptomatic population at risk of AHA HF stages A and B (n1⁄4 623). This group was selected in northern Italy (Bergamo) from among 4047 patients aged 55–80
The Dutch Childhood Oncology Group guideline for follow-up of asymptomatic cardiac dysfunction in childhood cancer survivors.

BACKGROUND The Late Effects of Childhood Cancer task force of the Dutch Childhood Oncology Group (DCOG LATER) developed a guideline for follow-up of asymptomatic cardiac dysfunction in childhood cancer survivors (CCS). In this paper, we present the methods, available evidence and final recommendations of our guideline. MATERIALS AND METHODS A multidisciplinary working group specified clinical questions that should be answered to get to recommendations for the guideline. We carried out short or extensive evidence summaries and determined methodological quality of studies and levels of evidence in order to answer all clinical questions. When evidence was lacking for CCS, we carefully extrapolated evidence from other populations. Final recommendations were based on evidence and consensus. RESULTS There was high-level evidence for the increased risk of cardiac dysfunction in CCS and its main risk factors. Evidence was lacking regarding the prognosis, diagnosis and treatment of cardiac dysfunction in CCS. We recommended echocardiographic screening for asymptomatic cardiac dysfunction in CCS treated with cardiotoxic treatments and counseling about potential advantages and disadvantages of our screening recommendations. CONCLUSION The DCOG LATER guideline recommends risk-based screening for asymptomatic cardiac dysfunction in CCS, but it should be noted that recommendations are not completely supported by evidence in CCS.
The Non-Coding RNA Landscape of Plasma Cell Dyscrasias

Despite substantial advancements have been done in the understanding of the pathogenesis of plasma cell (PC) disorders, these malignancies remain hard-to-treat. The discovery and subsequent characterization of non-coding transcripts, which include several members with diverse length and mode of action, has unraveled novel mechanisms of gene expression regulation often malfunctioning in cancer. Increasing evidence indicates that such non-coding molecules also feature in the pathobiology of PC dyscrasias, where they are endowed with strong therapeutic and/or prognostic potential. In this review, we aim to summarize the most relevant findings on the biological and clinical features of the non-coding RNA landscape of malignant PCs, with major focus on multiple myeloma. The most relevant classes of non-coding RNAs will be examined, along with the mechanisms accounting for their dysregulation and the recent strategies used for their targeting in PC dyscrasias. It is hoped these insights may lead to clinical applications of non-coding RNA molecules as biomarkers or therapeutic targets/agents in the near future.
Intraoperative hyperthermic versus postoperative normothermic intraperitoneal chemotherapy for colonic peritoneal carcinomatosis: a case-control study.

BACKGROUND Cytoreductive surgery and intraperitoneal chemotherapy has improved prognosis in patients with peritoneal carcinomatosis. The main modes of intraperitoneal chemotherapy treatment are peroperative hyperthermic intraperitoneal chemotherapy (HIPEC) and normothermic sequential postoperative intraperitoneal chemotherapy (SPIC). The aim of this study was to compare HIPEC and SPIC with respect to overall survival, disease-free survival, morbidity, and mortality in patients with peritoneal carcinomatosis from colon cancer. PATIENTS AND METHODS A matched case-control study was conducted in patients with surgical macroscopic complete removal of carcinomatosis; matching was according to the peritoneal cancer index score. Thirty-two patients were included, 16 in each group (HIPEC and SPIC). Overall survival, disease-free survival, morbidity, mortality, and clinicopathological parameters were compared. RESULTS Median overall survival was 36.5 months in the HIPEC group and 23.9 months in the SPIC group (P = 0.01). Median disease-free survival for these groups was 22.8 (HIPEC) and 13.0 months (SPIC; P = 0.02). Morbidity was not statistically different, 19% in SPIC and 37% in HIPEC. Postoperative mortality was observed in one patient in each group. CONCLUSION HIPEC was associated with improved overall survival and disease-free survival compared with SPIC at similar morbidity and mortality, suggesting that HIPEC is the treatment of choice in colonic peritoneal carcinomatosis.
Lung cancer incidence in young women vs. young men: A systematic analysis in 40 countries

Previous studies have reported converging lung cancer rates between sexes. We examine lung cancer incidence rates in young women vs. young men in 40 countries across five continents. Lung and bronchial cancer cases by 5‐year age group (ages 30–64) and 5‐year calendar period (1993–2012) were extracted from Cancer Incidence in Five Continents. Female‐to‐male incidence rate ratios (IRRs) and 95% confidence intervals (95%CIs) were calculated by age group and birth cohort. Among men, age‐specific lung cancer incidence rates generally decreased in all countries, while in women the rates varied across countries with the trends in most countries stable or declining, albeit at a slower pace compared to those in men. As a result, the female‐to‐male IRRs increased among recent birth cohorts, with IRRs significantly greater than unity in Canada, Denmark, Germany, New Zealand, the Netherlands and the United States. For example, the IRRs in ages 45–49 year in the Netherlands increased from 0.7 (95% CI: 0.6–0.8) to 1.5 (95% CI: 1.4–1.7) in those born circa 1948 and 1963, respectively. Similar patterns, though nonsignificant, were found in 23 additional countries. These crossovers were largely driven by increasing adenocarcinoma incidence rates in women. For those countries with historical smoking data, smoking prevalence in women approached, but rarely exceeded, those of men. In conclusion, the emerging higher lung cancer incidence rates in young women compared to young men is widespread and not fully explained by sex differences in smoking patterns. Future studies are needed to identify reasons for the elevated incidence of lung cancer among young women.
Higher anhedonia and dysphoric arousal relate to lower relationship satisfaction among trauma-exposed female service members/veterans.

OBJECTIVE Posttraumatic stress disorder (PTSD) symptoms of detachment, anhedonia, and hyperarousal are associated with poorer relationship satisfaction. Such findings are limited to earlier models of PTSD and samples that were almost exclusively male. The association of current PTSD symptom clusters with relationship satisfaction in partnered female service members/veterans (SM/Vs) are understudied. METHODS This study examined the association of PTSD (PTSD Checklist-5 [PCL-5]) symptom clusters identified in the anhedonia model and relationship satisfaction (Couples' Satisfaction Index-4) in 477 partnered female SM/Vs. RESULTS Higher anhedonia and dysphoric arousal were associated with lower relationship satisfaction. Among those who scored 31+ on the PCL-5 (n = 255, 53.46%), which is a suggested cutoff for a probable PTSD diagnosis, only higher anhedonia was associated with poorer relationship satisfaction. CONCLUSIONS The association of PTSD symptom clusters with relationship satisfaction are similar for male and female SM/Vs. Interventions to improve relationship satisfaction may focus on reducing anhedonia and dysphoric arousal.
Low SOX12 Expression Is Correlated With Poor Prognosis in Patients With Gastric Cancer

Background: SRY-related HMG box-12, which is associated with the prognosis of cancer, has been frequently described. However, both SRY-related HMG box-12 expression and its relationship with clinicopathological variables and patient survival have not been defined in gastric cancer. The aim of our study was to examine the prognostic value of SRY-related HMG box-12 expression in patients with gastric cancer. Methods: In this study, we determined SRY-related HMG box-12 expression in 79 primary gastric cancer tissues and 79 matched adjacent nontumor tissues by immunohistochemistry and then calculated the survival rate using the Kaplan-Meier method. Cox proportional hazard regression model was used to analyze predictors of gastric cancer. Western blot and quantitative real-time polymerase chain reaction were used to investigate the difference in SRY-related HMG box-12 expression between normal gastric epithelial cells and gastric cancer cells at the protein level and RNA level, respectively. Results: SRY-related HMG box-12 was downregulated in gastric cancer tissues. Low SRY-related HMG box-12 expression was significantly associated not only with lymph node metastasis (P = .027) and TNM stage (P = .021) but also with disease-specific survival in patients with gastric cancer. Multivariate analysis demonstrated TNM stage was an independent factor predicting poor survival (P = .034). Conclusions: Low SRY-related HMG box-12 expression is associated with poor clinical outcomes in gastric cancer.
In vivo modulation of cervicovaginal drug transporters and tissue distribution by film-released tenofovir and darunavir for topical prevention of HIV-1.

Clinical trials have demonstrated partial protection against HIV-1 infection by vaginal microbicide formulations based on antiretroviral (ARV) drugs. Improved formulations that will maintain sustained drug concentrations at viral target sites in the cervicovaginal mucosa are needed. We have previously demonstrated that treatment of cervicovaginal cell lines with ARV drugs can alter gene expression of drug transporters, suggesting that the mucosal disposition of ARV drugs delivered vaginally can be modulated by drug transporters. This study aimed to investigate in vivo modulation of drug transporter expression in a non-human primate model by tenofovir and darunavir released from film formulations. Cervicovaginal tissues were collected from drug-naïve macaques and from macaques vaginally treated with film formulations of tenofovir or darunavir. Drug release in vaginal fluid as well as drug absorption in cervicovaginal tissues and lymph nodes were verified by mass spectrometry. The effects of exposure to drugs on the expression of transporters relevant to ARV drugs were evaluated by quantitative PCR. We showed expression in cervicovaginal tissue of drug-naïve macaques of transporters important for distribution of ARV drugs, albeit at lower levels compared to human tissue for key transporters including P-glycoprotein. Concentrations of tenofovir and darunavir well above the EC50 values determined in vitro were detected in vaginal fluid and vaginal tissues of macaques treated with drug-dissolving films over 24 hours and were also comparable to those shown previously to modulate drug transporter expression. Accordingly, Multidrug Resistance associated Protein 2 (MRP2) in cervicovaginal tissue was upregulated by both tenofovir and darunavir. The two drugs also differentially induced and/or inhibited expression of key uptake transporters for reverse transcriptase inhibitors and protease inhibitors. The lower expression of key transporters in macaques may result in increased retention of ARV drugs at the simian cervicovaginal mucosa compared to the human mucosa and has implications for translation of pre-clinical data. Modulation of drug transporter expression by tenofovir and darunavir points to the potential benefit of MRP2 inhibition to increase ARV drug penetration through the cervicovaginal epithelium.
Cochlear Implantation in Patients with Chronic Suppurative Otitis Media: Surgical Outcomes and a Management Algorithm

Background: Chronic suppurative otitis media (CSOM) was considered as a contraindication of cochlear implantation (CI) in the past. Recently, various surgical options have been adopted for CI in CSOM patients with showing a low complication rate. Objectives: To evaluate surgical outcomes of CI in patients with CSOM and to propose a management algorithm for those patients. Methods: Thirty-six consecutive patients with CSOM who underwent single stage or staged CI were enrolled. Speech performance, including Categories of Auditory Performance (CAP) test and sentence score, and complications were retrospectively analyzed. Results: The average follow-up was 3.1 years (range 0.5–9.2 years). Postoperative median CAP and sentence scores were 6 and 78%, respectively. Three (8.3%) of the 36 patients had postoperative complications. One experienced breakdown of the ear canal closure. Recurrence of the pars tensa retraction was observed in another patient with adhesive otitis media who underwent CI and cartilage tympanoplasty as a single stage operation. Electrode extrusion occurred in another patient who underwent staged CI with maintenance of a previous open cavity. Subtotal petrosectomy and cavity obliteration were used to manage the latter 2 complications. All implant patients with good mastoid pneumatization exhibited no complications. There were no significant differences in postoperative speech performance and complication rates between single stage CI and staged CI. Based on these current findings, a management algorithm was proposed according to type of CSOM, presence of open cavity, and mastoid pneumatization. Conclusions: Patients with CSOM show good postoperative speech performance after CI. Proper surgical options according to type of CSOM, presence of open cavity, and mastoid pneumatization may help in reducing complications.