bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variable selection in social-environmental data: sparse regression and tree ensemble machine learning approaches
Authors: Handorf Elizabeth , Yin Yinuo , Slifker Michael , Lynch Shannon 
Published: December 2020

AbstractBackgroundSocial-environmental data obtained from the US Census is an important resource for understanding health disparities, but rarely is the full dataset utilized for analysis. A barrier to incorporating the full data is a lack of solid recommendations for variable selection, with researchers often hand-selecting a few variables. Thus, we evaluated the ability of empirical machine learning approaches to identify social-environmental factors having a true association with a health outcome.MethodsWe compared several popular machine learning methods, including penalized regressions (e.g. lasso, elastic net), and tree ensemble methods. Via simulation, we assessed the methods’ ability to identify census variables truly associated with binary and continuous outcomes while minimizing false positive results (10 true associations, 1000 total variables). We applied the most promising method to the full census data (p = 14,663 variables) linked to prostate cancer registry data (n = 76,186 cases) to identify social-environmental factors associated with advanced prostate cancer.ResultsIn simulations, we found that elastic net identified many true-positive variables, while lasso provided good control of false positives. Using a combined measure of accuracy, hierarchical clustering based on Spearman’s correlation with sparse group lasso regression performed the best overall. Bayesian Adaptive Regression Trees outperformed other tree ensemble methods, but not the sparse group lasso. In the full dataset, the sparse group lasso successfully identified a subset of variables, three of which replicated earlier findings.ConclusionsThis analysis demonstrated the potential of empirical machine learning approaches to identify a small subset of census variables having a true association with the outcome, and that replicate across empiric methods. Sparse clustered regression models performed best, as they identified many true positive variables while controlling false positive discoveries.
Management of chlamydia and gonorrhoea infections diagnosed in primary care using a centralised nurse-led telephone-based service: mixed methods evaluation
Authors: Horwood Jeremy , Brangan Emer , Manley Petra , Horner Paddy , Muir Peter , North Paul , Macleod John 
Published: December 2020

Abstract
Background
Up to 18% of genital Chlamydia infections and 9% of Gonorrhoea infections in England are diagnosed in Primary Care. Evidence suggests that a substantial proportion of these cases are not managed appropriately in line with national guidelines. With the increase in sexually transmitted infections and the emergence of antimicrobial resistance, their timely and appropriate treatment is a priority. We investigated feasibility and acceptability of extending the National Chlamydia Screening Programme’s centralised, nurse-led, telephone management (NLTM) as an option for management of all cases of chlamydia and gonorrhoea diagnosed in Primary Care.

Methods
Randomised feasibility trial in 11 practices in Bristol with nested qualitative study. In intervention practices patients and health care providers (HCPs) had the option of choosing NLTM or usual care for all patients tested for Chlamydia and Gonorrhoea. In control practices patients received usual care.

Results
One thousand one hundred fifty-four Chlamydia/gonorrhoea tests took place during the 6-month study, with a chlamydia positivity rate of 2.6% and gonorrhoea positivity rate of 0.8%. The NLTM managed 335 patients. Interviews were conducted with sixteen HCPs (11 GPs, 5 nurses) and 12 patients (8 female). HCPs were positive about the NLTM, welcomed the partner notification service, though requested more timely feedback on the management of their patients. Explaining the NLTM to patients didn’t negatively impact on consultations. Patients found the NLTM acceptable, more convenient and provided greater anonymity than usual care. Patients appreciated getting a text message regarding a negative result and valued talking to a sexual health specialist about positive results.

Conclusion
Extension of this established NLTM intervention to a greater proportion of patients was both feasible and acceptable to both patients and HCP, could provide a better service for patients, whilst decreasing primacy care workload. The study provides evidence to support the wider implementation of this NLTM approach to managing chlamydia and gonorrhoea diagnosed in primary care.
Decision-making capacity evaluations: the role of neuropsychological assessment from a multidisciplinary perspective
Authors: Wood Sarah , Bally Klaus , Cabane Christine , Fassbind Patrick , Jox Ralf J. , Leyhe Thomas , Monsch Andreas , Trachsel Manuel 
Published: December 2020

AbstractDecision-making capacity (DMC) in aging adults has become increasingly salient as the number of older adults, life expectancy, and the amount of wealth to be transferred from older generations have all increased. The accurate and reliable determination of older adults’ DMC is a particularly important topic given its implication in legal, financial, and health decisions. Based upon the four-ability DMC model promulgated by Appelbaum and Grisso in the 1980’s, a number of MacArthur Competence Assessment Tools have been developed and widely utilized. However, these tools do not include cognitive testing or other sources of objective data and have limited validity in a medico-legal setting, necessitating additional options for the evaluation of DMC. This is significant from the perspective of the patient because they have a vested interest in accurate and objective assessment of their DMC across domains.Given the disparities in the assessment of DMC, the authors propose, through this debate article, that the evaluation of DMC in the aging adult population utilize a combination of traditional interview and domain specific instruments and neuropsychological testing. To achieve a consensus on the issue, medical experts in a number of fields related to capacity evaluation, including psychiatry, neurology, neuropsychology, and general medicine were consulted and recruited as authors. Experts in Swiss law and ethics were also consulted and provided input.A tendency to focus on a single capacity, and in particular, the ability to consent to medical treatment, arose in the literature. Similarly, there are many instruments purporting to evaluate a single capacity (e.g., consenting to medical treatment, managing finances), while other areas important to the evaluation of DMC received little attention (e.g., activities of daily living, the ability to live independently, to marry, to resist undue influence, and to make a will or advanced care directive). Medical and legal experts in the multidisciplinary group agreed that there is a clear need for more consistency across evaluation of DMC domains and that a combined approach of traditional methods and neuropsychological testing provides a more thorough evaluation and better serves the patient.
Serum neopterin levels in relation to mild and severe COVID-19
Authors: Robertson Josefina , Gostner Johanna M. , Nilsson Staffan , Andersson Lars-Magnus , Fuchs Dietmar , Gisslen Magnus 
Published: December 2020

Abstract
Background
The COVID-19 pandemic, caused by the coronavirus SARS-CoV-2, is rapidly spreading worldwide. There is limited information about prognostic markers that could help clinicians to identify COVID-19 patients with a poor prognosis. Serum levels of the immune activation marker neopterin has shown to be of prognostic value in patients with SARS. The aim of this study was to investigate whether serum neopterin is associated with the severity of COVID-19.

Methods
We included 34 patients with confirmed COVID-19 between March 3 and March 30, 2020. Fifteen patients had mild disease and did not require hospitalization, whereas 19 patients developed severe COVID-19 requiring intensive care. Concentrations of serum neopterin, tryptophan, and kynurenine were measured at and repeatedly after inclusion.

Results
We found a more than two-fold higher mean concentration of neopterin in severely ill patients (mean value 42.0 nmol/L (SD 18.2)) compared to patients with mild symptoms (16.9 nmol/L (SD 11.0)). All of the severe cases had elevated neopterin concentrations (> 9.1 nmol/L) at the initial sampling with values ranging from 17.2 to 86.7 nmol/L. In comparison, 10 of 15 patients with mild disease had neopterin levels above 9.1 nmol/L, with concentrations in the range from 4.9 to 31.6 nmol/L. Neopterin levels gradually decreased during the course of COVID-19, but severe cases maintained elevated levels for a longer period. Moreover, lower levels of tryptophan and higher levels of kynurenine, indicating an increased tryptophan catabolism, were seen in the group with severe cases.

Conclusions
In conclusion, we found that serum neopterin levels are associated with the severity of COVID-19. Our findings suggest that neopterin could be used as a prognostic marker, but further studies are needed to elucidate how it can be used in the clinic.
Risk factors and clinical features of deterioration in COVID-19 patients in Zhejiang, China: a single-centre, retrospective study
Authors: Yi Ping , Yang Xiang , Ding Cheng , Chen Yanfei , Xu Kaijin , Ni Qing , Zhao Hong , Li Yongtao , Zhang Xuan , Liu Jun , Sheng Jifang , Li Lanjuan 
Published: December 2020

Abstract
Background
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection swept through Wuhan and spread across China and overseas beginning in December 2019. To identify predictors associated with disease progression, we evaluated clinical risk factors for exacerbation of SARS-CoV-2 infection.

Methods
A retrospective analysis was used for PCR-confirmed COVID-19 (coronavirus disease 2019)-diagnosed hospitalized cases between January 19, 2020, and February 19, 2020, in Zhejiang, China. We systematically analysed the clinical characteristics of the patients and predictors of clinical deterioration.

Results
One hundred patients with COVID-19, with a median age of 54 years, were included. Among them, 49 patients (49%) had severe and critical disease. Age ([36–58] vs [51–70], P = 0.0001); sex (49% vs 77.6%, P = 0.0031); Body Mass Index (BMI) ([21.53–25.51] vs [23.28–27.01], P = 0.0339); hypertension (17.6% vs 57.1%, P < 0.0001); IL-6 ([6.42–30.46] vs [16.2–81.71], P = 0.0001); IL-10 ([2.16–5.82] vs [4.35–9.63], P < 0.0001); T lymphocyte count ([305–1178] vs [167.5–440], P = 0.0001); B lymphocyte count ([91–213] vs [54.5–163.5], P = 0.0001); white blood cell count ([3.9–7.6] vs [5.5–13.6], P = 0.0002); D2 dimer ([172–836] vs [408–953], P = 0.005), PCT ([0.03–0.07] vs [0.04–0.15], P = 0.0039); CRP ([3.8–27.9] vs [17.3–58.9], P < 0.0001); AST ([16, 29] vs [18, 42], P = 0.0484); artificial liver therapy (2% vs 16.3%, P = 0.0148); and glucocorticoid therapy (64.7% vs 98%, P < 0.0001) were associated with the severity of the disease. Age and weight were independent risk factors for disease severity.

Conclusion
Deterioration among COVID-19-infected patients occurred rapidly after hospital admission. In our cohort, we found that multiple factors were associated with the severity of COVID19. Early detection and monitoring of these indicators may reduce the progression of the disease. Removing these factors may halt the progression of the disease. In addition, Oxygen support, early treatment with low doses of glucocorticoids and artificial liver therapy, when necessary, may help reduce mortality in critically ill patients.
A real-time PCR assay for rapid identification of inducible and acquired clarithromycin resistance in Mycobacterium abscessus
Authors: Sharma Meenu Kaushal , La Yanni , Janella Debra , Soualhine Hafid 
Published: December 2020

Abstract
Background
Mycobacterium abscessus is a rapidly growing mycobacteria involved in severe infections of the lung, skin, or soft tissue. Macrolides such as clarithromycin are the recommended first line drugs for treatment of M. abscessus infections. However, M. abscessus has dual mechanisms of resistance to macrolides, making treatment by macrolides difficult. A functional erm(41) gene confers for inducible resistance while acquired mutations on the 23S rRNA rrl gene confer for constitutive resistance.

Methods
We have developed a real-time PCR assay to detect both inducible and acquired resistance to clarithromycin, and compared the results to traditional erm(41) and rrl sequencing and phenotypic susceptibility testing using Sensititre™ plates.

Results
Of the total 126 M. abscessus isolates tested, truncated erm(41) was found in 23/126 (18.3%) of the samples, 27/126 (21.4%) had a T28C mutation in erm(41), and 2/126 (1.6%) had an acquired A2058C mutation in rrl. The phenotypic results correlated with the expected sequencing results in 121/126 samples (96%). Phenotypic testing compared to real-time PCR resolved 2 of these discrepancies by showing the existence of both erm(41) alleles in the isolates that sequencing missed. One culture was found to be mixed with two M. abscessus subsp. as per hsp65 sequencing and 2 isolates had discordance between molecular and phenotypic results. It was presumed that 3 isolates showed discrepancy between sequencing and real-time PCR, but one culture was mixed and other 2 detected both alleles by real-time PCR leading to 100% concordance when compared to sequencing.

Conclusion
In conclusion, real-time PCR is more accurate for detection of both acquired and induced clarithromycin resistance, specifically when mixed genic profiles are present in a sample.
Combination of biomarker with clinical risk factors for prediction of severe acute kidney injury in critically ill patients
Authors: Jia Lan , Sheng Xiaohua , Zamperetti Anna , Xie Yun , Corradi Valentina , Chandel Shikha , De Cal Massimo , Montin Diego Pomarè , Caprara Carlotta , Ronco Claudio 
Published: December 2020

AbstractBackgroundAcute kidney injury (AKI) occurs commonly in the intensive care unit (ICU). Insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinase-2 (TIMP-2), known as [TIMP-2] x [IGFBP7] (NephroCheck), have been identified as novel biomarkers for the prediction of AKI risk. However, the effective use of disease biomarkers is indispensable from an appropriate clinical context. We conducted a retrospective cohort study to find risk factors and assess the performance of the combination of NephroCheck with risk factors, so as to provide feasible information for AKI prediction.MethodsAll patients who were admitted in the ICU (from June 2016 to July 2017) participated in the study. The primary outcome was the detection of severe AKI within the first 7 days after patients being admitted to the ICU. The predictors were separated into three categories: chronic risk factors, acute risk factors and biochemical indicators.ResultsThe study included 577 patients. 96 patients developed to severe AKI (16.6%) within 7 days. In addition to NephroCheck (+) (OR = 2.139, 95% CI (1.260–3.630),P = 0.005), age > 65 years (OR = 1.961, 95% CI (1.153–3.336),P = 0.013), CKD (OR = 2.573, 95% CI (1.319–5.018),P = 0.006) and PCT (+)(OR = 3.223, 95% CI (1.643–6.321),P = 0.001) were also the independent predictors of severe AKI within 7 days. Compared to NephroCheck (+) only (AUC = 0.66, 95% CI:0.60–0.72), the combination of NephroCheck (+) and risk factors (age > 65 years, CKD and PCT positive) (AUC = 0.75, 95% CI:0.70–0.81) led to a significant increase in the area under ROC curve for severe AKI prediction within 7 days.ConclusionsAlthough NephroCheck is an effective screening tool for recognizing high-risk patients, we found that combination with biomarker and risk factors (age > 65 years, CKD, procalcitonin positive) for risk assessment of AKI has the greatest significance to patients with uncertain disease trajectories.
Predisposing factors and radiological features in patients with internal carotid artery dissection or vertebral artery dissection
Authors: Wu Yongjun , Chen Hongbin , Xing Shihui , Tan Shuangquan , Chen Xinran , Tan Yan , Zeng Jinsheng , Zhang Jian 
Published: December 2020

Abstract
Background
Cervicocerebral artery dissection is an important cause of ischemic stroke in young and middle-aged individuals. However, very few studies have compared the differential features between internal carotid artery dissection (ICAD) and vertebral artery dissection (VAD), including both cervical and intracranial artery dissections. We conducted a study to investigate the predisposing factors and radiological features in patients with ICAD or VAD.

Methods
All cases diagnosed with cervicocerebral artery dissection, ICAD, or VAD were identified through a medical records database, between January 2010 and January 2020. Baseline characteristics, predisposing factors, and radiological features of ICAD versus VAD were compared.

Results
A total of 140 patients with cervicocerebral artery dissection were included in the study, including 84 patients in the ICAD group and 56 in the VAD group. The mean age of patients in the ICAD and VAD groups was 43.37 ± 14.01 and 41.00 ± 12.98 years old, respectively. Patients with ICAD were more likely to be men compared with VAD (85.71% vs. 67.86%, p = 0.012). The frequency of hypertension, diabetes, smoking, drinking, and cervical trauma did not differ between ICAD and VAD. Dissections of ICAD were more frequently at the extracranial portions of the artery compared with those of VAD (70.24% vs. 44.64%, p = 0.003). In contrast, dissections of VAD were more common in the intracranial artery (55.36% vs. 29.76%, p = 0.003). Radiologically, double lumen (36.90% vs. 19.64%, p = 0.029) and intimal flap (11.90% vs. 1.79%, p = 0.029) were more frequently observed in ICAD than in VAD, and dissecting aneurysms were less frequent (13.10% vs. 26.79%, p = 0.041).

Conclusions
The distributions of cervical and intracranial artery dissections were different between ICAD and VAD. The frequencies of radiological features detected in patients with ICAD and VAD also differed.
Study of thyroid function in pregnancy, its feto-maternal outcome; a prospective observational study
Authors: Mahadik Kalpana , Choudhary Payal , Roy P. K. 
Published: December 2020

Abstract
Background
Pregnancy is a stress test of maternal thyroid function. The prevalence of thyroid dysfunction in pregnant women is high. Subclinical hypothyroidism occurs in 10% of all pregnancies. Effects of hypothyroidism in pregnancy are anemia, low birth weight and mental retardation in neonate. This study is aimed to evaluate maternal and fetal outcomes in pregnant women with deranged thyroid profile. The relevance of this study is to document the association of hypothyroidism and its adverse effects on mother and fetus.

Methods
This prospective observational study was carried out at R.D. Gardi Medical College, Ujjain, India. Subjects of this study were 198 antenatal women in third trimester with singleton pregnancy admitted in the obstetric ward, and informed consent was obtained. Women were chosen irrespective of age, parity, residence and socioeconomic status. Women with multiple pregnancy, a known case of thyroid disorder, or any pre-existing medical disorder were excluded. Routine hematological parameters and estimation of T3, T4 and TSH was conducted. Patients with deranged thyroid profile were subsequently assessed for maternal and fetal complications. History of infertility, family history of thyroid disease, menstrual pattern, recurrent abortion, hemoglobin level and fetal outcome were the main study variables. Data was analysed in SPSS software for statistical co-relation.

Results
Prevalence of thyroid disorder is 11%; with subclinical hypothyroidism, overt hypothyroidism and subclinical hyperthyroidism occurring in 5.6, 3.5 and 1.5% of subjects respectively. In women with subclinical and overt hypothyroidism, anemia was present in 26.3% being significantly associated with hypothyroidism (p = 0.008). With respect to fetal outcome, LBW 31.6% (p = 0.001), NICU admission 42.1%, (p = 0.000) and low APGAR Score (21.1%, p = 0.042) were statistically associated with hypothyroidism. Risk of anemia, Low Birth weight, NICU admissions, and low APGAR score was 4.8, 6.3, 0.14 and 3.64 times higher respectively in women with hypothyroidism than in women who are euthyroid.

Conclusion
Prevalence of subclinical hypothyroidism is 5.6% in 3rd trimester of pregnancy. Anemia, pre-eclampsia, high caesarean rates and neonatal morbidities is significantly associated with hypothyroidism.
Semaphorin 3A mediated brain tumor stem cell proliferation and invasion in EGFRviii mutant gliomas
Authors: Higgins Dominique M. O. , Caliva Maisel , Schroeder Mark , Carlson Brett , Upadhyayula Pavan S. , Milligan Brian D. , Cheshier Samuel H. , Weissman Irving L. , Sarkaria Jann N. , Meyer Fredric B. , Henley John R. 
Published: December 2020

Abstract
Background
Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults, with a median survival of approximately 15 months. Semaphorin 3A (Sema3A), known for its axon guidance and antiangiogenic properties, has been implicated in GBM growth. We hypothesized that Sema3A directly inhibits brain tumor stem cell (BTSC) proliferation and drives invasion via Neuropilin 1 (Nrp1) and Plexin A1 (PlxnA1) receptors.

Methods
GBM BTSC cell lines were assayed by immunostaining and PCR for levels of Semaphorin 3A (Sema3A) and its receptors Nrp1 and PlxnA1. Quantitative BrdU, cell cycle and propidium iodide labeling assays were performed following exogenous Sema3A treatment. Quantitative functional 2-D and 3-D invasion assays along with shRNA lentiviral knockdown of Nrp1 and PlxnA1 are also shown. In vivo flank studies comparing tumor growth of knockdown versus control BTSCs were performed. Statistics were performed using GraphPad Prism v7.

Results
Immunostaining and PCR analysis revealed that BTSCs highly express Sema3A and its receptors Nrp1 and PlxnA1, with expression of Nrp1 in the CD133 positive BTSCs, and absence in differentiated tumor cells. Treatment with exogenous Sema3A in quantitative BrdU, cell cycle, and propidium iodide labeling assays demonstrated that Sema3A significantly inhibited BTSC proliferation without inducing cell death. Quantitative functional 2-D and 3-D invasion assays showed that treatment with Sema3A resulted in increased invasion. Using shRNA lentiviruses, knockdown of either NRP1 or PlxnA1 receptors abrogated Sema3A antiproliferative and pro-invasive effects. Interestingly, loss of the receptors mimicked Sema3A effects, inhibiting BTSC proliferation and driving invasion. Furthermore, in vivo studies comparing tumor growth of knockdown and control infected BTSCs implanted into the flanks of nude mice confirmed the decrease in proliferation with receptor KD.

Conclusions
These findings demonstrate the importance of Sema3A signaling in GBM BTSC proliferation and invasion, and its potential as a therapeutic target.