Miracle-dz/UniFAR-FTUs huggingface dataset:
In search of definitions: Cancer‐associated fibroblasts and their markers

The tumor microenvironment has been identified as one of the driving factors of tumor progression and invasion. Inside this microenvironment, cancer‐associated fibroblasts (CAFs), a type of perpetually activated fibroblasts, have been implicated to have a strong tumor‐modulating effect and play a key role in areas such as drug resistance. Identification of CAFs has typically been carried based on the expression of various “CAF markers”, such as fibroblast activation protein alpha (FAP) and alpha smooth muscle actin (αSMA), which separates them from the larger pool of fibroblasts present in the body. However, as outlined in this Review, the expression of various commonly used fibroblast markers is extremely heterogeneous and varies strongly between different CAF subpopulations. As such, novel selection methods based on cellular function, as well as further characterizing research, are vital for the standardization of CAF identification in order to improve the cross‐applicability of different research studies in the field. The aim of this review is to give a thorough overview of the commonly used fibroblast markers in the field and their various strengths and, more importantly, their weaknesses, as well as to highlight potential future avenues for CAF identification and targeting.
Five‐year trends in acetaminophen use exceeding the recommended daily maximum dose

Temporal patterns of acetaminophen use exceeding the recommended daily maximum dosage of 4 g over a 5-year period (4/1/2011-3/31/2016) were evaluated in an online 1-week diary study of 14 434 adult acetaminophen users who also reported acetaminophen use in the previous month. Specific medications taken were identified by list-based prompting; respondents were not required to know their medications contained acetaminophen. Details of use were recorded daily; total daily dosage was determined programmatically. Prevalence of >4 g use over time was modelled and tested for linear changes. The overall prevalence of >4 g use (6.3% of users and 3.7% of usage days) did not change over the 5 years: odds ratio (OR) persons, 1.02 (95% CI, 0.98-1.09); OR days, 0.98 (0.92-1.05). Deviations from label directions were largely unchanged, though concomitant use increased slightly. Thus, over a recent 5-year period, there was no evidence of change in how often acetaminophen use exceeded the labelled maximum daily dose.
Validation of the radiosurgery-based arteriovenous malformation score in a large linear accelerator radiosurgery experience.

OBJECT The radiosurgery-based arteriovenous malformation (AVM) score (RBAS) is a grading system designed to predict patient outcomes after Gamma Knife surgery for AVMs. This study seeks to validate independently the predictive nature of the RBAS, not only after single treatment but for retreatment, and to assess the overall outcome regardless of number of radiosurgeries. METHODS The authors analyzed 403 patients treated with linear accelerator (LINAC) radiosurgery for AVMs between May 1988 and June 2008. The AVM scores were determined by the following equation: AVM score = (0.1 x volume in cm(3)) + (0.02 x age in years) + (0.3 x location). The location values are as follows: frontal/temporal = 0, parietal/occipital/corpus callosum/cerebellar = 1, and basal ganglia/thalamus/brainstem = 2. RESULTS Testing demonstrated that the RBAS correlated with excellent outcomes after single or repeat radiosurgery (p < 0.001 for both variables). One hundred sixty-two (49%) of 330 patients had excellent outcomes (obliteration without deficit) after a single treatment. Excellent outcomes were achieved in 74, 64, 50, and 11% of patients with AVM scores of < 1.0 (Group 1), between 1.0 and < 1.8 (Group 2), between 1.8 and < 2.5 (Group 3), and >or= 2.5 (Group 4), respectively. Fifty-one patients (70%) obtained radiosurgical cure and 46 (63%) achieved excellent outcomes after repeat radiosurgery. Of these, 100% achieved excellent outcomes in Group 1, 70% did so in Group 2, 47% in Group 3, and 14% in Group 4. The RBAS correlated with excellent outcomes after overall treatment (p < 0.001). Two hundred seventy-seven patients (69%) obtained AVM obliteration, and 62% achieved excellent outcomes. In Group 1, 87% achieved excellent outcomes, 75% did so in Group 2, 61% in Group 3, and 24% in Group 4. CONCLUSIONS The RBAS is a good predictor of patient outcomes after LINAC radiosurgery.
Effects of Abdominal Aortic Aneurysm Size on Mid- and Long-term Mortality After Endovascular Aneurysm Repair

Purpose: To investigate the effect of abdominal aortic aneurysm (AAA) size on mid- and long-term survival after endovascular aneurysm repair (EVAR). Materials and Methods: Retrospective data were collected from 325 consecutive patients (mean age 69.7 ± 8.5 years; 323 men) who underwent EVAR for intact AAA at a single institution between January 2003 and December 2013. The primary endpoint was death at 3, 5, and 10 years after EVAR. Optimal cutoff points for AAA size and age were determined using receiver operating characteristics (ROC) curves. Time to event analyses (Kaplan-Meier curves and Cox proportional hazard models) were employed to determine any differences in all-cause mortality outcomes between AAA size groups. Cox models were adjusted for age and other comorbidities (hypertension, hyperlipidemia, coronary artery disease, smoking status, symptomatic status, and creatinine); the outcomes are reported as the hazard ratio (HR) with 95% confidence interval (CI). Results: The cohort was dichotomized according to the ROC analysis, which defined an optimal cutoff point of 5.6 cm for AAA size and >70 years for age. The mean follow-up period post EVAR was 45.5±29.2 months. In total, 134 (41.2%) patients died during the 10-year follow-up. Thirty-day mortality was 1.1% (2/184) in the patients with AAA <5.6 cm and 2.1% (3/141) in patients with AAA ≥5.6 cm (p=0.45). All-cause mortality was not significantly affected by comorbidities. However, AAA size ≥5.6 cm was associated with increased 3-year mortality risk (HR 1.59, 95% CI 1.001 to 2.52, p<0.049) but not 5-year (HR 1.44, 95% CI 0.98 to 2.10, p=0.062) or 10-year mortality (HR 1.28, 95% CI 0.91 to 1.80, p=0.149). After adjusting for comorbidities, AAA size ≥5.6 cm was no longer significantly associated with morality at any time point. Using a larger size cutoff (AAA size ≥6.0 cm) resulted in improved statistical significance in the unadjusted model. In the adjusted Cox model, AAA size ≥6.0 cm was significantly associated with increased risk of mortality at 3 years (HR 1.67, 95% CI 1.01 to 2.77, p<0.047), but not at longer time points. Conclusion: Our study demonstrates that midterm survival after EVAR is significantly and independently associated with AAA size even after correcting for comorbidities. However, in the long term, preoperative AAA size is not an independent predictor of mortality.
Safety and feasibility of minocycline in treatment of acute traumatic brain injury

ABSTRACT Background: Minocycline is a pleomorphic neuroprotective agent well studied in animal models of traumatic brain injury (TBI) and brain ischemia. Methods: To test the hypothesis that administration of minocycline in moderate to severe TBI (Glasgow Coma Score 3–12). Fifteen patients were enrolled in a two-dose escalation study of minocycline to evaluate the safety of twice the recommended antibiotic dosage; tier 1 n = 7 at a loading dose of 800 mg followed by 200 mg twice a day (BID) for 7 days; tier 2 n = 8 at a loading dose of 800 mg followed by 400 mg BID for 7 days. Results: The mean initial GCS was 5.6 for Tier 1 patients and 5.4 for Tier 2. The Disability Rating Scale (DRS) had a trend towards improvement with the higher dose 12.5 SD ± 7.7 (N = 5) for Tier 1 at 4 weeks and 8.5 SD ± 9.9 at week 12 (N = 5), whereas for Tier 2 it was 9.7 ± 6.9 (N = 6) for week 4 and 6.0 SD ± 6.1 (N = 7) for week 12 (p = .251 repeated measures ANOVA). Liver function tests increased but resolved after the first week and there were no infections. Conclusions: Minocycline was safe for moderate to severe TBI at a dose twice that as recommended for treatment of infection. The higher dose did trend towards an improved outcome.
Daily activity, mood, and quality of life in colorectal cancer patients with chemotherapy‐induced peripheral neuropathy: A mediation effect analysis

Chemotherapy‐induced peripheral neuropathy (CIPN) with restriction of daily activity (RDA) was common consequence of oxaliplatin‐based chemotherapy in colorectal cancer patients. CIPN with RDA and negative mood may impact the quality of life (QoL). However, the relationships among RDA, mood, and QoL remain unclear. This was a cross‐sectional relative study in which four instruments were used: the Neuropathic Pain Symptom Inventory was used to measure the severity of CIPN; the Screening of Activity Limitation and Safety Awareness scale was used to evaluate RDA; the Profile of Mood States Short Form was used to assess negative mood; and the Functional Assessment Cancer Center Therapy‐Colorectal scale version 4 was used to evaluate QoL. Relationships among the variables were analyzed by bivariate correlation, hierarchical multiple linear regression, and Baron and Kenny's mediation testing. One hundred three colorectal adenocarcinoma patients with CIPN after receiving oxaliplatin‐based chemotherapy were enrolled. Patients had mild‐to‐moderate CIPN and mild RDA. Significant correlations were found between CIPN and mood (r = 0.425, P < 0.001), between RDA and mood (r = 0.343, P < 0.001), and between RDA and QoL (r = 0.285, P < 0.01). RDA and mood may impact QoL. Under mediation effect analysis, mood mediated 38.48% of the effect of RDA on QoL (P < 0.001). Negative mood is the major factor impacting QoL in colorectal cancer patients with CIPN. Although the management of CIPN and RDA can prevent irreversible functional problems, enhancing the adaption of mood disturbance can strongly promote their QoL.
Caregiving, Recovery, and Death After Incident ADL/IADL Disability Among Older Adults in the United States

This study assesses patterns of caregiving, death, and recovery after incident disability in older adults. We used the Health and Retirement Study to follow of a cohort of adults age ≥65 years in the United States with incident disability in activities of daily living (ADLs) or instrumental activities of daily living (IADLs; n = 8,713). Rates of care and function state were assessed biennially: deceased, nursing home dwelling, at home with paid help, at home with both paid and unpaid help, at home with unpaid help, at home with no assistance and recovered. In the 2 years after incident disability, 22.1% recovered and 46.8% died. Transitions between care and function states occurred frequently, with more than 20% of the cohort living at home with no assistance despite disability at least once. This study demonstrates the high levels of care and function state fluctuation and unmet needs after functional disability.
Arcanobacterium haemolyticum Utilizes Both Phospholipase D and Arcanolysin To Mediate Its Uptake into Nonphagocytic Cells

Arcanobacterium haemolyticum is an emerging human pathogen that causes pharyngitis and wound infections. A few studies have suggested that A. haemolyticum is able to induce its uptake into nonphagocytic epithelial cells, but the bacterial factors associated with host cell invasion and the host cell processes involved have yet to be studied. ABSTRACT Arcanobacterium haemolyticum is an emerging human pathogen that causes pharyngitis and wound infections. A few studies have suggested that A. haemolyticum is able to induce its uptake into nonphagocytic epithelial cells, but the bacterial factors associated with host cell invasion and the host cell processes involved have yet to be studied. We investigated how two A. haemolyticum virulence factors, arcanolysin (ALN) and phospholipase D (PLD), affect the ability of the bacteria to adhere to and subsequently invade Detroit 562 pharyngeal epithelial cells. The sphingomyelinase activity of phospholipase D was necessary to increase bacterial adherence, while the absence of a functional arcanolysin had no effect on A. haemolyticum adherence but did lead to a decrease in A. haemolyticum invasion into Detroit 562 cells. Because of the known roles of cholesterol-dependent cytolysins in disrupting calcium gradients and inducing F-actin-mediated bacterial internalization, we sought to determine whether ALN and PLD played a similar role in the ability of A. haemolyticum to invade nonphagocytic cells. Elimination of extracellular calcium and inhibition of the Arp2/3 complex or F-actin polymerization also caused a decrease in the ability of A. haemolyticum to invade Detroit 562 cells. Overall, our findings suggest that A. haemolyticum utilizes phospholipase D primarily for adherence and utilizes arcanolysin primarily for invasion into Detroit 562 cells in a process dependent on extracellular calcium and F-actin polymerization. Our work marks the first insight into how the individual activities of arcanolysin and phospholipase D affect A. haemolyticum host-pathogen interactions using the biologically relevant Detroit 562 cell line.
Evaluation of the need for routine feeding jejunostomy for enteral nutrition after esophagectomy.

Background Previous studies have shown that enteral nutrition (EN) helps reduce severe postoperative complications after esophagectomy. However, the incidence of jejunostomy-related complications is approximately 30%. We evaluated the operative outcomes in patients who did not receive EN via feeding jejunostomy after esophagectomy. Methods We retrospectively reviewed 76 consecutive patients with esophageal cancer who received radical esophagectomy. Operative outcomes were compared between 33 patients who received postoperative EN via feeding jejunostomy (group A; from May 2014 to September 2015) and 43 patients who did not receive EN via feeding jejunostomy (group B; from September 2015 to December 2017). Results The American Society of Anesthesiologists performance status score of the patients in group B was significantly higher than that of patients in group A (P=0.002). The postoperative morbidity rate was comparable between the two groups (group A, 30.3% vs. group B, 44.2%, P=0.217). No significant between-group differences were observed in the incidence of infectious complications, postoperative hospital stay, readmission within 30 days after discharge, or pneumonia after discharge within 6 months. The incidence of bowel obstruction was significantly higher in group A than in group B (group A, 9.1% vs. group B, 0%, P=0.044). Two patients in group B required nutritional support via total parenteral nutrition due to bilateral vocal cord palsy or pneumonia. Conclusions Jejunostomy-related bowel obstruction in the patients with feeding jejunostomy was significantly higher than that in the patients without jejunostomy. There was no increase in postoperative complications (including pneumonia) in the patients who did not receive EN via feeding jejunostomy. Our results suggest that routine feeding jejunostomy may not be necessary for all patients undergoing esophagectomy.
Comparison of genome-wide association and genomic prediction methods for milk production traits in Korean Holstein cattle

Objective The objectives of this study were to compare identified informative regions through two genome-wide association study (GWAS) approaches and determine the accuracy and bias of the direct genomic value (DGV) for milk production traits in Korean Holstein cattle, using two genomic prediction approaches: single-step genomic best linear unbiased prediction (ss-GBLUP) and Bayesian Bayes-B. Methods Records on production traits such as adjusted 305-day milk (MY305), fat (FY305), and protein (PY305) yields were collected from 265,271 first parity cows. After quality control, 50,765 single-nucleotide polymorphic genotypes were available for analysis. In GWAS for ss-GBLUP (ssGWAS) and Bayes-B (BayesGWAS), the proportion of genetic variance for each 1-Mb genomic window was calculated and used to identify informative genomic regions. Accuracy of the DGV was estimated by a five-fold cross-validation with random clustering. As a measure of accuracy for DGV, we also assessed the correlation between DGV and deregressed-estimated breeding value (DEBV). The bias of DGV for each method was obtained by determining regression coefficients. Results A total of nine and five significant windows (1 Mb) were identified for MY305 using ssGWAS and BayesGWAS, respectively. Using ssGWAS and BayesGWAS, we also detected multiple significant regions for FY305 (12 and 7) and PY305 (14 and 2), respectively. Both single-step DGV and Bayes DGV also showed somewhat moderate accuracy ranges for MY305 (0.32 to 0.34), FY305 (0.37 to 0.39), and PY305 (0.35 to 0.36) traits, respectively. The mean biases of DGVs determined using the single-step and Bayesian methods were 1.50±0.21 and 1.18±0.26 for MY305, 1.75±0.33 and 1.14±0.20 for FY305, and 1.59±0.20 and 1.14±0.15 for PY305, respectively. Conclusion From the bias perspective, we believe that genomic selection based on the application of Bayesian approaches would be more suitable than application of ss-GBLUP in Korean Holstein populations.
Consistency, Inconsistency, and Ambiguity of Metabolite Names in Biochemical Databases Used for Genome-Scale Metabolic Modelling

Genome scale metabolic models (GEMs) are manually curated repositories describing the metabolic capabilities of an organism. GEMs have been successfully used in different research areas, ranging from systems medicine to biotechnology. However, the different naming conventions (namespaces) of databases used to build GEMs limit model reusability and prevent the integration of existing models. This problem is known in the GEM community but its extent has not been analyzed in depth. In this study, we investigate the name ambiguity and the multiplicity of non-systematic identifiers and we highlight the (in)consistency in their use in eleven biochemical databases of biochemical reactions and the problems that arise when mapping between different namespaces and databases. We found that such inconsistencies can be as high as 83.1%, thus emphasizing the need for strategies to deal with these issues. Currently, manual verification of the mappings appears to be the only solution to remove inconsistencies when combining models. Finally, we discuss several possible approaches to facilitate (future) unambiguous mapping.
Changes over time in the reported risk for childhood leukaemia and magnetic fields

There have been many studies from 1979 to the present reporting raised risks for childhood leukaemia with exposure to power-frequency magnetic fields. There are also suggestions that the reported risk has been decreasing. We examine trends in the risk over time from all available studies. For 41 studies, we combine reported risks using inverse-variance weighting, drawing risk estimates from previous pooled analyses where possible for greater consistency. We examine the cumulative risk for studies published up to each successive calendar year for all studies and for various subsets, and test for a trend over the period. The cumulative relative risk has indeed declined, for our most rigorous analysis from a maximum 2.44 in 1997 to 1.58 in 2017, but not statistically significantly when tested as a linear trend. We find suggestions of higher risks in studies looking at higher exposures and in studies with better quality exposure assessment. We conclude that there is a decline in reported risk from the mid 1990s to now, which is unlikely to be solely explained by improving study quality but may be due to chance, and an elevated risk remains.
Amplatzer patent foramen ovale occluder: safety and efficacy

ABSTRACT Introduction: The patent foramen ovale (PFO) is a common anatomical variant in humans (prevalence 25%). Most often asymptomatic, it may engender paradoxically embolic strokes, myocardial infarctions, or visceral or peripheral ischemia. It is causatively related to migraine, positional or exertional hypoxemia with dyspnea, diving incidents, high altitude edema, and sleep apnea. Percutaneous closure of atrial septal defects was first performed in the seventies. A dedicated PFO occluder (Amplatzer PFO Occluder) was first used on 10 September 1997 by Kurt Amplatz and Bernhard Meier. Since, percutaneous PFO closure has evolved into one of the most common and the simplest and safest catheter-based intervention in adult cardiology. Randomized studies have proved its benefit for prevention of recurrent ischemic events (particularly strokes) in patients without competing stroke etiology. There are also supportive clinical data for PFO closure in other situations. Areas covered: The Amplatzer PFO Occluder, the first, most implanted, and best-studied PFO occluder, is reviewed, presenting implantation technique, possible complications, and pertinent scientific data of efficacy and safety. Expert commentary: Percutaneous PFO closure has grown to one of the most common procedures in interventional cardiology. Implantation of the Amplatzer PFO Occluder is simple, safe, and effective.
Long noncoding RNA Crnde attenuates cardiac fibrosis via Smad3‐Crnde negative feedback in diabetic cardiomyopathy

Diabetic cardiomyopathy (DCM)—ventricular dysfunction in the absence of underlying heart disease—is a common complication of diabetes and a leading cause of mortality associated with the disease. In DCM, cardiac fibrosis is the main cause of heart failure. Although it is well‐established that the transforming growth factor‐beta signaling pathway plays a part in inducing cardiac fibrosis in DCM, details of the molecular mechanism involved remain elusive. Therefore, it is crucial to study the gene reg;ulation of key signaling effectors in DCM‐associated cardiac fibrosis. A recently emerged hotspot in the field of gene regulation is the role of long noncoding RNAs (lncRNAs). Recent evidence indicates that lncRNAs play a critical role in cardiac fibrosis; however, in DCM, the function of these regulatory RNAs have not been studied in depth. In this study, we identified a conserved cardiac‐specific lncRNA named colorectal neoplasia differentially expressed (Crnde). By analyzing 376 human heart tissues, it was found that Crnde expression is negatively correlated with that of cardiac fibrosis marker genes. Moreover, Crnde expression was shown to be enriched in cardiac fibroblasts (CFs). Overexpression of Crnde attenuated cardiac fibrosis and enhanced cardiac function in mice with DCM. Further, in vitro experiments showed that Crnde negatively regulates the myofibroblast differentiation of CFs. The expression of Crnde was activated by SMAD family member 3 (Smad3), shedding light on the underlying molecular mechanism. Interestingly, Crnde also inhibited the transcriptional activation of Smad3 on target genes, thereby inhibiting the expression of myofibroblastic marker genes in CFs. Overall, our data provide valuable insights into the development of potential anti‐cardiac fibrosis strategies centered on lncRNAs, for the treatment of DCM.