Miracle-dz/UniFAR-FTUs huggingface dataset:
First year experience of a pulmonary embolism response team with comparisons of outcomes between catheter directed therapy versus standard anticoagulation

ABSTRACT Objectives: The Pulmonary Embolism Response Team (PERT) model is now widely adopted in many institutions to provide multidisciplinary care for patients with acute pulmonary embolism (PE). However, descriptive experiences of PERT operations and studies on clinical outcomes remain limited. Methods: We performed a retrospective review of PERT activations at an academic tertiary care center, with secondary aims to study outcomes associated with performing catheter directed therapies (CDT). Results: The intermediate high-risk PE category was most frequent (n = 40, 76.9%) among the 52 total cases evaluated during the study period. There was one in-hospital mortality, associated with hospice admission for a non-PE diagnosis. Six patients (11.5%) experienced a bleeding complication of any severity. Anticoagulation (AC) alone was recommended in 30 patients (57.7%) and CDT was performed in 16 patients (30.8%). There were no significant differences in patient characteristics or disease severity between patients in the AC group versus the CDT group, except for a higher prevalence of malignancy in the AC group (p = 0.037). Patients who underwent CDT demonstrated a lower, albeit non-significant, median intensive care unit (ICU) length of stay (LOS) (3 vs. 4 days, p = 0.34) and hospital LOS (4 vs. 5 days, p = 0.25), as compared to patients receiving AC alone. Bleeding rates were similar between the two groups (6.7% vs. 6.3%, p = 1.0). Conclusions: Adoption of the PERT model at an academic tertiary care center was associated with acceptably low rates of mortality and bleeding, similar to other published studies. Performing CDT in select patients under PERT consultation may be associated with shorter ICU and hospital LOS; however, larger studies are needed to validate this finding.
Decrease in the proportion of CD24hiCD38hi B cells and impairment of their regulatory capacity in type 1 diabetes patients

B10 cells restore immune balance by producing interleukin (IL)‐10. Impaired B10 cell responses are related to numerous autoimmune diseases. However, the function of B10 cells in type 1 diabetes (T1D) patients is controversial. We hypothesized that there are numerical and functional defects of B10 cells in T1D. Sixty‐two patients with T1D and 74 healthy volunteers were included in our study. We showed that B10 cells in human peripheral blood belong to a CD24hiCD38hi B cell subpopulation. CD24hiCD38hi B cells from healthy individuals possessed regulatory capacity, suppressed interferon (IFN)‐γ, tumor necrosis factor (TNF)‐α and IL‐17A production and promoted IL‐4 production and forkhead box protein 3 (FoxP3) expression in CD4+ T cells through an IL‐10‐dependent mechanism. Compared to healthy controls, B10 cell percentages in T1D were significantly lower (5·6 ± 3·5 versus 6·9 ± 3·3%; P < 0·05), produced less IL‐10 (15·4 ± 4·3 versus 29·0 ± 4·5%; P < 0·001) and lacked regulatory capacity. In addition, Pearson’s correlation analysis showed that the frequency of circulating B10 cells was negatively correlated with the frequency of CD4+IFN‐γ+ and CD4+TNF‐α+ T cells (r = −0·248 and r = −0·283, P = 0·008 and P = 0·017, respectively), positively correlating with the frequency of CD4+CD25+FoxP3+ T cells (r = 0·247, P = 0·001). These data offer direct proof that there is a deficiency of circulating CD24hiCD38hi B cells in peripheral blood of patients with T1D, which participate in the T1D immune imbalance involved in the development of T1D.
The Effect of Macronutrients on Reproductive Hormones in Overweight and Obese Men: A Pilot Study

Hypogonadal obese men find it difficult to lose weight. We investigated whether the modification of macronutrient intake can alter testosterone levels independently of the body mass index. Fasted overweight or obese fertile men were asked to consume meals of polyunsaturated fats (PUFA), monounsaturated fats (MUFA), refined carbohydrates (CHO, orange juice, OJ), whey and egg albumin and mixed meals of PUFA and CHO, PUFA and egg albumin, and CHO and egg albumin. Blood was collected at fasting, then hourly for 5 h and analysed to determine the levels of testosterone and other hormones. We found PUFA and MUFA or a mixed meal of PUFA and CHO significantly reduced serum testosterone production to a similar degree over a 5 h period. PUFA decreased serum testosterone levels by 3.2 nmol/L after 1 h compared to baseline (p = 0.023), with this suppression remaining significant up to 5 h postprandially (2.1 nmol/L; p = 0.012). The net overall testosterone levels were reduced by approximately 10 nmol/L × h by PUFA, MUFA and PUFA combined with CHO. CHO alone had little effect on testosterone levels, whereas egg albumin was able to increase them (7.4 cf 2.0 nmol/L × h). Therefore, for men wishing to optimize their testosterone levels, it may be wise to avoid a high fat intake, drink liquids such as water or OJ or even consider fasting. ANZCTR, Australia; ACTRN12617001034325.
Distinguishing Emotional Responses to Photographs and Artwork Using a Deep Learning-Based Approach

Visual stimuli from photographs and artworks raise corresponding emotional responses. It is a long process to prove whether the emotions that arise from photographs and artworks are different or not. We answer this question by employing electroencephalogram (EEG)-based biosignals and a deep convolutional neural network (CNN)-based emotion recognition model. We employ Russell’s emotion model, which matches emotion keywords such as happy, calm or sad to a coordinate system whose axes are valence and arousal, respectively. We collect photographs and artwork images that match the emotion keywords and build eighteen one-minute video clips for nine emotion keywords for photographs and artwork. We hired forty subjects and executed tests about the emotional responses from the video clips. From the t-test on the results, we concluded that the valence shows difference, while the arousal does not.
Long-term outcomes of the implants accidentally protruding into nasal cavity extended to posterior maxilla due to inferior meatus pneumatization.

BACKGROUND There is limited information about inferior meatus pneumatization in terms of implant treatment for the posterior maxilla. PURPOSE To demonstrate the clinical, radiologic, and nasal endoscopic outcomes of implants accidentally protruding into the nasal cavities with inferior meatus pneumatization in the posterior maxilla. MATERIALS AND METHODS A total of 560 implants (324 patients) with transcrestal sinus augmentation in the posterior maxilla were screened. On panoramic radiographs, 132 implants (78 patients) appear to penetrate the sinus floor, but cone-beam computed tomography demonstrated that 26 implants (13 patients) penetrated the nasal floor due to inferior meatus pneumatization. Width of nasal and sinus cavities and extent of penetration were radiographically measured. Nasal endoscopy was performed. RESULTS Two implants were lost during 13.81 ± 5.40 years due to peri-implantitis. However, no nasosinusal problem occurred in any patient. The nasal cavity was significantly larger in patients with implants penetrating the pneumatized inferior meatus than in those with implants penetrating the sinus floor (P< .05). Nasal endoscopy demonstrated that the apical portion of the implants was covered with thin mucosa without inflammation. CONCLUSION Implants accidentally penetrating the pneumatized inferior meatus demonstrated high survival with no specific nasosinusal complications. Inferior meatus pneumatization should be considered for implant treatment in the posterior maxilla.
Acute O2 sensing through HIF2α-dependent expression of atypical cytochrome oxidase subunits in arterial chemoreceptors

HIF2α-mediated gene expression enables the carotid body to respond to acute hypoxia. Breathing faster with HIF2α In response to hypoxia, glomus cells in the carotid body trigger an increase in ventilation. At the molecular level, hypoxia slows down the electron transport chain in mitochondria, resulting in the accumulation of ROS and NADH, which ultimately activate glomus cells. HIF2α is a hypoxia-induced transcription factor that is highly abundant in glomus cells. Moreno-Domínguez et al. found that HIF2α was necessary for acute responses to hypoxia (see the Focus by Bishop and Ratcliffe). HIF2α mediated the expression of three atypical electron transport chain subunits that were necessary for a rapid buildup of ROS and NADH under hypoxic conditions in glomus cells. Similar to mice deficient in HIF2α in glomus cells, mice that lacked at least one of these atypical electron transport chain subunits in glomus cells also failed to increase ventilation in response to hypoxia. The authors propose that HIF2α target gene expression may set a tissue’s acute O2-sensing ability. Acute cardiorespiratory responses to O2 deficiency are essential for physiological homeostasis. The prototypical acute O2-sensing organ is the carotid body, which contains glomus cells expressing K+ channels whose inhibition by hypoxia leads to transmitter release and activation of nerve fibers terminating in the brainstem respiratory center. The mechanism by which changes in O2 tension modulate ion channels has remained elusive. Glomus cells express genes encoding HIF2α (Epas1) and atypical mitochondrial subunits at high levels, and mitochondrial NADH and reactive oxygen species (ROS) accumulation during hypoxia provides the signal that regulates ion channels. We report that inactivation of Epas1 in adult mice resulted in selective abolition of glomus cell responsiveness to acute hypoxia and the hypoxic ventilatory response. Epas1 deficiency led to the decreased expression of atypical mitochondrial subunits in the carotid body, and genetic deletion of Cox4i2 mimicked the defective hypoxic responses of Epas1-null mice. These findings provide a mechanistic explanation for the acute O2 regulation of breathing, reveal an unanticipated role of HIF2α, and link acute and chronic adaptive responses to hypoxia.
Using Selection by Nonantibiotic Stressors to Sensitize Bacteria to Antibiotics

Abstract Evolutionary adaptation of bacteria to nonantibiotic selective forces, such as osmotic stress, has been previously associated with increased antibiotic resistance, but much less is known about potentially sensitizing effects of nonantibiotic stressors. In this study, we use laboratory evolution to investigate adaptation of Enterococcus faecalis, an opportunistic bacterial pathogen, to a broad collection of environmental agents, ranging from antibiotics and biocides to extreme pH and osmotic stress. We find that nonantibiotic selection frequently leads to increased sensitivity to other conditions, including multiple antibiotics. Using population sequencing and whole-genome sequencing of single isolates from the evolved populations, we identify multiple mutations in genes previously linked with resistance to the selecting conditions, including genes corresponding to known drug targets or multidrug efflux systems previously tied to collateral sensitivity. Finally, we hypothesized based on the measured sensitivity profiles that sequential rounds of antibiotic and nonantibiotic selection may lead to hypersensitive populations by harnessing the orthogonal collateral effects of particular pairs of selective forces. To test this hypothesis, we show experimentally that populations evolved to a sequence of linezolid (an oxazolidinone antibiotic) and sodium benzoate (a common preservative) exhibit increased sensitivity to more stressors than adaptation to either condition alone. The results demonstrate how sequential adaptation to drug and nondrug environments can be used to sensitize bacteria to antibiotics and highlight new potential strategies for exploiting shared constraints governing adaptation to diverse environmental challenges.
Incorporation of molecular characteristics into endometrial cancer management

Histopathological evaluation including subtyping and grading is the current cornerstone for endometrial cancer (EC) classification. This provides clinicians with prognostic information and input for further treatment recommendations. Nonetheless, patients with histologically similar ECs may have very different outcomes, notably in patients with high‐grade endometrial carcinomas. For endometrial cancer, four molecular subgroups have undergone extensive studies in recent years: POLE ultramutated (POLEmut), mismatch repair‐deficient (MMRd), p53 mutant (p53abn) and those EC lacking any of these alterations, referred to as NSMP (non‐specific molecular profile). Several large studies confirm the prognostic relevance of these molecular subgroups. However, this ‘histomolecular’ approach has so far not been implemented in clinical routine. The ongoing PORTEC4a trial is the first clinical setting in which the added value of integrating molecular parameters in adjuvant treatment decisions will be determined. For diagnostics, the incorporation of the molecular parameters in EC classification will add a level of objectivity which will yield biologically more homogeneous subclasses. Here we illustrate how the management of individual EC patients may be impacted when applying the molecular EC classification. We describe our current approach to the integrated diagnoses of EC with a focus on scenarios with conflicting morphological and molecular findings. We also address several pitfalls accompanying the diagnostic implementation of molecular EC classification and give practical suggestions for diagnostic scenarios.
Development and evaluation of a quantitative polymerase chain reaction for aquatic Streptococcus agalactiae based on the groEL gene

The aim of this study was to develop a TaqMan quantitative polymerase chain reaction (qPCR), based on the Streptococcus agalactiae groEL gene, to specifically quantify levels of bacteria within samples derived from aquatic sources, particularly aquaculture. Enumeration of bacteria by qPCR was compared with culture‐based methods.
Skim-Sequencing Reveals the Likely Origin of the Enigmatic Endangered Sunflower Helianthus schweinitzii

Resolving the origin of endangered taxa is an essential component of conservation. This information can be used to guide efforts of bolstering genetic diversity, and also enables species recovery and future evolutionary studies. Here, we used low-coverage whole genome sequencing to clarify the origin of Helianthus schweinitzii, an endangered tetraploid sunflower that is endemic to the Piedmont Plateau in the eastern United States. We surveyed four accessions representing four populations of H. schweinitzii and 38 accessions of six purported parental species. Using de novo approaches, we assembled 87,004 bp of the chloroplast genome and 6770 bp of the nuclear 35S rDNA. Phylogenetic reconstructions based on the chloroplast genome revealed no reciprocal monophyly of taxa. In contrast, nuclear rDNA data strongly supported the currently accepted sections of the genus Helianthus. Information from combined cpDNA and rDNA provided evidence that H. schweinitzii is likely an allo-tetraploid that formed as a result of hybridization between the diploids Helianthus giganteus and Helianthus microcephalus.
Prognostic Significance of Arterial Lactate Levels at Weaning from Postcardiotomy Venoarterial Extracorporeal Membrane Oxygenation

Background: The outcome after weaning from postcardiotomy venoarterial extracorporeal membrane oxygenation (VA-ECMO) is poor. In this study, we investigated the prognostic impact of arterial lactate levels at the time of weaning from postcardiotomy VA. Methods: This analysis included 338 patients from the multicenter PC-ECMO registry with available data on arterial lactate levels at weaning from VA-ECMO. Results: Arterial lactate levels at weaning from VA-ECMO (adjusted OR 1.426, 95%CI 1.157–1.758) was an independent predictor of hospital mortality, and its best cutoff values was 1.6 mmol/L (<1.6 mmol/L, 26.2% vs. ≥ 1.6 mmol/L, 45.0%; adjusted OR 2.489, 95%CI 1.374–4.505). When 261 patients with arterial lactate at VA-ECMO weaning ≤2.0 mmol/L were analyzed, a cutoff of arterial lactate of 1.4 mmol/L for prediction of hospital mortality was identified (<1.4 mmol/L, 24.2% vs. ≥1.4 mmol/L, 38.5%, p = 0.014). Among 87 propensity score-matched pairs, hospital mortality was significantly higher in patients with arterial lactate ≥1.4 mmol/L (39.1% vs. 23.0%, p = 0.029) compared to those with lower arterial lactate. Conclusions: Increased arterial lactate levels at the time of weaning from postcardiotomy VA-ECMO increases significantly the risk of hospital mortality. Arterial lactate may be useful in guiding optimal timing of VA-ECMO weaning.
Idiopathic pulmonary fibrosis and occupational risk factors

Idiopathic pulmonary fibrosis (IPF) is a rare lung disease of unknown origin that rapidly leads to death. However, the rate of disease progression varies from one individual to another and is still difficult to predict. The prognosis of IPF is poor, with a median survival of three to five years after diagnosis, without curative therapies other than lung transplantation. The factors leading to disease onset and progression are not yet completely known. The current disease paradigm is that sustained alveolar epithelial micro-injury caused by environmental triggers (e.g., cigarette smoke, microaspiration of gastric content, particulate dust, viral infections or lung microbial composition) leads to alveolar damage resulting in fibrosis in genetically susceptible individuals. Numerous epidemiological studies and case reports have shown that occupational factors contribute to the risk of developing IPF. In this perspective, we briefly review the current understanding of the pathophysiology of IPF and the importance of occupational factors in the pathogenesis and prognosis of the disease. Prompt identification and elimination of occult exposure may represent a novel treatment approach in patients with IPF.
Analysis of EYA3 Phosphorylation by Src Kinase Identifies Residues Involved in Cell Proliferation

Eyes absent (EYA) are non-thiol-based protein tyrosine phosphatases (PTPs) that also have transcriptional co-activator functions. Their PTP activity is involved in various pathologies. Recently, we demonstrated that Src tyrosine kinase phosphorylates human EYA3 by controlling its subcellular localization. We also found EYA3′s ability to autodephosphorylate, while raising the question if the two opposing processes could be involved in maintaining a physiologically adequate level of phosphorylation. Using native and bottom-up mass spectrometry, we performed detailed mapping and characterization of human EYA3 Src-phosphorylation sites. Thirteen tyrosine residues with different phosphorylation and autodephosphorylation kinetics were detected. Among these, Y77, 96, 237, and 508 displayed an increased resistance to autodephosphorylation. Y77 and Y96 were found to have the highest impact on the overall EYA3 phosphorylation. Using cell cycle analysis, we showed that Y77, Y96, and Y237 are involved in HEK293T proliferation. Mutation of the three tyrosine residues abolished the pro-proliferative effect of EYA3 overexpression. We have also identified a Src-induced phosphorylation pattern of EYA3 in these cells. These findings suggest that EYA3′s tyrosine phosphorylation sites are non-equivalent with their phosphorylation levels being under the control of Src-kinase activity and of EYA3′s autodephosphorylation.
HIV‐associated morbidity and mortality in a setting of high ART coverage: prospective surveillance results from a district hospital in Botswana

Antiretroviral therapy (ART) has significantly improved survival in Africa in recent years. In Botswana, where adult HIV prevalence is 21.9%, AIDS‐related mortality is estimated to have declined by 58% between 2005 and 2013 following the initial wide‐spread introduction of ART, and ART coverage has steadily increased reaching 84% in 2016. However, there remains little data about the burden of HIV and its impact on mortality in the hospital setting where most deaths occur. We aimed to describe the burden of HIV and related morbidity and mortality among hospitalized medical patients in a district hospital in southern Botswana in the era of widespread ART coverage.
Associations Between Hospital Volume and Outcomes of Robot-Assisted Radical Prostatectomy.

INTRODUCTION Robot-assisted radical prostatectomy (RARP) has become the predominant surgical modality to manage localized prostate cancer in the US. However, there are very few studies focusing on the associations between hospital volume and outcomes of RARP. METHODS We identified RARPs for clinically localized (cT1-2N0M0) prostate cancer diagnosed between 2010 and 2014 in the National Cancer Database. We categorized annual average hospital RARP volume into very low, low, medium, high, and very high by most closely sorting final included patients into five equal-sized groups (quintiles). Outcomes included 30-day mortality, 90-day mortality, conversion (to open), prolonged length of stay (PLOS, >2 d), 30-day (unplanned) readmission, positive surgical margin (PSM), and lymph node dissection (LND) rates. RESULTS A total of 114,957 patients were included and hospital volume was categorized into very low (3-45 cases/year), low (46-72 cases/year), medium (73-113 cases/year), high (114-218 cases/year), and very high (≥219 cases/year). Overall 30-day mortality (0.12%), 90-day mortality (0.16%), and conversion rate (0.65%) were low. Multivariable logistic regressions showed that compared with very low volume group, higher hospital volume was associated with lower odds of conversion to open surgery (OR=0.23, p<0.001 for very high), pLOS (OR=0.25, p<0.001 for very high), 30-day readmission (OR=0.53, p<0.001 for very high), and PSM (OR=0.61, p<0.001 for very high). Higher hospital volume was also associated with higher odds of LND in the intermediate/high-risk cohort (OR=3.23, p<0.001 for very high). CONCLUSION Patients undergoing RARP at higher volume hospitals are likely to have improved perioperative and superior oncologic outcomes than lower volume hospitals.
Muscle mass and plasma myostatin after exercise training: a substudy of Renal Exercise (RENEXC)—a randomized controlled trial

Abstract Background Sarcopenia increases as renal function declines and is associated with higher morbidity and mortality. Myostatin is a negative regulator of muscle growth. Its expression in response to exercise is unclear. In this prespecified substudy of the Renal Exercise (RENEXC) trial, we investigated the effects of 12 months of exercise training on sarcopenia, muscle mass and plasma myostatin and the relationships between physical performance, muscle mass and plasma myostatin. Methods A total of 151 non-dialysis-dependent patients (average measured glomerular filtration rate 23 ± 8 mL/min/1.73 m2), irrespective of age or comorbidity, were randomly assigned to either strength or balance in combination with endurance training. Body composition was measured with dual-energy X-ray absorptiometry. Plasma myostatin was analysed using enzyme-linked immunosorbent assay kits. Results After 12 months, the prevalence of sarcopenia was unchanged, leg and whole-body lean mass increased significantly in the balance group and was unchanged in the strength group. Whole fat mass decreased significantly in both groups. There were no significant between-group differences in sarcopenia or body composition. Plasma myostatin levels increased significantly in both groups, with a significant difference in favour of the strength group. Plasma myostatin was significantly positively related to muscle mass and physical performance at baseline, but these relationships were attenuated after 12 months. Conclusions Exercise training seems to be effective in preventing sarcopenia and maintaining muscle mass in non-dialysis-dependent patients with chronic kidney disease (CKD). However, the role of plasma myostatin on muscle mass and physical performance in patients with CKD warrants further study.