bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quasi-linear Cox proportional hazards model with cross- L1 penalty
Authors: Omae Katsuhiro , Eguchi Shinto 
Published: July 2020

AbstractBackgroundTo accurately predict the response to treatment, we need a stable and effective risk score that can be calculated from patient characteristics. When we evaluate such risks from time-to-event data with right-censoring, Cox’s proportional hazards model is the most popular for estimating the linear risk score. However, the intrinsic heterogeneity of patients may prevent us from obtaining a valid score. It is therefore insufficient to consider the regression problem with a single linear predictor.Methodswe propose the model with a quasi-linear predictor that combines several linear predictors. This provides a natural extension of Cox model that leads to a mixture hazards model. We investigate the property of the maximum likelihood estimator for the proposed model. Moreover, we propose two strategies for getting the interpretable estimates. The first is to restrict the model structure in advance, based on unsupervised learning or prior information, and the second is to obtain as parsimonious an expression as possible in the parameter estimation strategy with cross- L1penalty. The performance of the proposed method are evaluated by simulation and application studies.ResultsWe showed that the maximum likelihood estimator has consistency and asymptotic normality, and the cross- L1-regularized estimator has root-nconsistency. Simulation studies show these properties empirically, and application studies show that the proposed model improves predictive ability relative to Cox model.ConclusionsIt is essential to capture the intrinsic heterogeneity of patients for getting more stable and effective risk score. The proposed hazard model can capture such heterogeneity and achieve better performance than the ordinary linear Cox proportional hazards model.
Using CT texture analysis to differentiate between peripheral lung cancer and pulmonary inflammatory pseudotumor
Authors: Liu Chenlu , Ma Changsheng , Duan Jinghao , Qiu Qingtao , Guo Yanluan , Zhang Zhenhua , Yin Yong 
Published: July 2020

AbstractBackgroundThis study is to distinguish peripheral lung cancer and pulmonary inflammatory pseudotumor using CT-radiomics features extracted from PET/CT images.MethodsIn this study, the standard 18F-fluorodeoxyglucose positron emission tomography/ computed tomography (18 F-FDG PET/CT) images of 21 patients with pulmonary inflammatory pseudotumor (PIPT) and 21 patients with peripheral lung cancer were retrospectively collected. The dataset was used to extract CT-radiomics features from regions of interest (ROI), The intra-class correlation coefficient (ICC) was used to screen the robust feature from all the radiomic features. Using, then, statistical methods to screen CT-radiomics features, which could distinguish peripheral lung cancer and PIPT. And the ability of radiomics features distinguished peripheral lung cancer and PIPT was estimated by receiver operating characteristic (ROC) curve and compared by the Delong test.ResultsA total of 435 radiomics features were extracted, of which 361 features showed relatively good repeatability (ICC ≥ 0.6). 20 features showed the ability to distinguish peripheral lung cancer from PIPT. these features were seen in 14 of 330 Gray-Level Co-occurrence Matrix features, 1 of 49 Intensity Histogram features, 5 of 18 Shape features. The area under the curves (AUC) of these features were 0.731 ± 0.075, 0.717, 0.748 ± 0.038, respectively. ThePvalues of statistical differences among ROC were 0.0499 (F9, F20), 0.0472 (F10, F11) and 0.0145 (F11, Mean4). The discrimination ability of forming new features (Parent Features) after averaging the features extracted at different angles and distances was moderate compared to the previous features (Child features).ConclusionRadiomics features extracted from non-contrast CT based on PET/CT images can help distinguish peripheral lung cancer and PIPT.
Whole-exome sequencing identifies a de novo PDE3A variant causing autosomal dominant hypertension with brachydactyly type E syndrome: a case report
Authors: Li Xianqing , Li Zongzhe , Chen Peng , Wang Yan , Wang Dao Wen , Wang Dao Wu 
Published: July 2020

Abstract
Background
Autosomal dominant hypertension with brachydactyly type E syndrome caused by pathogenic variants in the PDE3A gene was first reported in 2015. To date, there are only a few reports of this kind of syndrome. Other patients still lack a genetic diagnosis.

Case presentation
Whole-exome sequencing was performed in an 18-year-old female proband with a clinical diagnosis of hypertension with brachydactyly syndrome. Quantitative real-time PCR was used to identify pathogenic copy number variations (CNVs). After bioinformatics analysis and healthy control database filtering, we revealed a heterozygous missense PDE3A variant (c.1346G > A, p.Gly449Asp). The variant was absent in the ExAC database and located in a highly evolutionarily conserved cluster of reported PDE3A pathogenic variants. Importantly, this variant was predicted to affect protein function by both SIFT (score = 0) and PolyPhen-2 (score = 1). After Sanger sequencing, the variant was determined to be absent in the healthy parents of the proband as well as 800 ethnically and geographically matched healthy controls.

Conclusion
We present a report linking a de novo PDE3A variant to autosomal dominant hypertension with brachydactyly type E syndrome.
Markers of potassium homeostasis in salt losing tubulopathies- associations with hyperaldosteronism and hypomagnesemia
Authors: Eder Michael , Darmann Elisabeth , Haller Maria C. , Bojic Marija , Peck-Radosavljevic Markus , Huditz Rainer , Bond Gregor , Vychytil Andreas , Reindl-Schwaighofer Roman , Kikić Željko 
Published: July 2020

Abstract
Background
Renal loss of potassium (K+) and magnesium (Mg2+) in salt losing tubulopathies (SLT) leads to significantly reduced Quality of Life (QoL) and higher risks of cardiac arrhythmia. The normalization of K+ is currently the most widely accepted treatment target, however in even excellently designed RCTs the increase of K+ was only mild and rarely normalized. These findings question the role of K+ as the ideal marker of potassium homeostasis in SLT. Aim of this hypothesis-generating study was to define surrogate endpoints for future treatment trials in SLT in terms of their usefulness to determine QoL and important clinical outcomes.

Methods
Within this prospective cross-sectional study including 11 patients with SLTs we assessed the biochemical, clinical and cardiological parameters and their relationship with QoL (RAND SF-36). The primary hypothesis was that QoL would be more dependent of higher aldosterone concentration, assessed by the transtubular-potassium-gradient (TTKG). Correlations were evaluated using Pearson’s correlation coefficient.

Results
Included patients were mainly female (82%, mean age 34 ± 12 years). Serum K+ and Mg2+ was 3.3 ± 0.6 mmol/l and 0.7 ± 0.1 mmol/l (mean ± SD). TTKG was 9.5/3.4–20.2 (median/range). While dimensions of mental health mostly correlated with serum Mg2+ (r = 0.68, p = 0.04) and K+ (r = 0.55, p = 0.08), better physical health was associated with lower aldosterone levels (r = -0.61, p = 0.06). TTKG was neither associated with aldosterone levels nor with QoL parameters. No relevant abnormalities were observed in neither 24 h-ECG nor echocardiography.

Conclusions
Hyperaldosteronism, K+ and Mg2+ were the most important parameters of QoL. TTKG was no suitable marker for hyperaldosteronism or QoL. Future confirmatory studies in SLT should assess QoL as well as aldosterone, K+ and Mg2+.
Association of urinary non-albumin protein with the different urinary marker for glomerular and tubular damage in patients with type 2 diabetes
Authors: Siddiqui Khalid , Joy Salini Scaria , Nawaz Shaik Sarfaraz , Alnaqeb Dhekra , Mujammami Muhammad , Al-Rubeaan Khalid 
Published: July 2020

Abstract
Background/aim
In recent years, the diagnostic utility of urinary protein levels has been demonstrated for the early detection and progression of kidney disease. This study aimed to evaluate the associations of the non-albumin protein (NAP) with different urinary marker for tubular and glomerular damage in patients with type 2 diabetes (T2D).

Methods
In this observational cross-sectional study, 424 patients with T2D duration > 10 years were classified into two groups according to estimated glomerular filtration rate (eGFR). The ratios of different urinary markers (albumin, NAP, total protein, transferrin, retinol-binding protein (RBP), and neutrophil gelatinase-associated lipocalin (NGAL) to creatinine were analyzed.

Results
The levels of urinary biomarkers increased significantly with decrease in eGFR levels. In the group with moderately decreased eGFR, the albumin to-creatinine ratio (ACR), non-albumin protein-to-creatinine ratio (NAPCR), and total protein-to-creatinine ratio (PCR) were independently associated with all urinary markers after being adjusted for risk factors. The area under the receiver operating characteristics (ROC) curve for ACR and PCR had a better diagnostic value than other urinary biomarkers. Comparing ROC curve of NAPCR with other urinary biomarkers, it was significantly better than NGAL/Cr (p = 0.033).

Conclusions
The findings of the present study confirm that ACR and PCR are diagnostic biomarkers in T2D patients with decreased eGFR. NAPCR in these patients diagnostically only outperformed NGAL/Cr.
Effects of pre-pregnancy body mass index and gestational weight gain on maternal and infant complications
Authors: Sun Yin , Shen Zhongzhou , Zhan Yongle , Wang Yawen , Ma Shuai , Zhang Suhan , Liu Juntao , Wu Sansan , Feng Yahui , Chen Yunli , Cai Shuya , Shi Yingjie , Ma Liangkun , Jiang Yu 
Published: July 2020

AbstractBackgroundThe potential effects of pre-pregnancy body mass (BMI) and gestational weight gain (GWG) on pregnancy outcomes remain unclear. Thus, we investigated socio-demographic characteristics that affect pre-pregnancy BMIs and GWG and the effects of pre-pregnancy BMI and GWG on Chinese maternal and infant complications.Methods3172 women were enrolled in the Chinese Pregnant Women Cohort Study-Peking Union Medical College from July 25, 2017 to July 24, 2018, whose babies were delivered before December 31, 2018. Regression analysis was employed to evaluate the socio-demographic characteristics affecting pre-pregnancy BMI and GWG values and their effects on adverse maternal and infant complications.ResultsMultivariate logistic regression analysis revealed that age groups < 20 years (OR: 1.97), 25–30 years (OR: 1.66), 30–35 years (OR: 2.24), 35–40 years (OR: 3.90) and ≥ 40 years (OR: 3.33) as well as elementary school or education below (OR: 3.53), middle school (OR: 1.53), high school (OR: 1.40), and living in the north (OR: 1.37) were risk factors in maintaining a normal pre-pregnancy BMI. An age range of 30–35 years (OR: 0.76), living in the north (OR: 1.32) and race of ethnic minorities (OR: 1.51) were factors affecting GWG. Overweight (OR: 2.01) and inadequate GWG (OR: 1.60) were risk factors for gestational diabetes mellitus (GDM). Overweight (OR: 2.80) and obesity (OR: 5.42) were risk factors for gestational hypertension (GHp). Overweight (OR: 1.92), obesity (OR: 2.48) and excessive GWG (OR: 1.95) were risk factors for macrosomia. Overweight and excessive GWG were risk factors for a large gestational age (LGA) and inadequate GWG was a risk factor for low birth weights.ConclusionsOverweight and obesity before pregnancy and an excessive GWG are associated with a greater risk of developing GDM, GHp, macrosomia and LGA. The control of body weight before and during the course of pregnancy is recommended to decrease adverse pregnancy outcomes, especially in pregnant women aged < 20 or > 25 years old educated below university and college levels, for ethnic minorities and those women who live in the north of China.Trial registrationRegistered at Clinical Trials (NCT03403543), September 29, 2017.
Starvation stress attenuates the miRNA-target interaction in suppressing breast cancer cell proliferation
Authors: Lü Jinhui , Zhang Chuyi , Han Junyi , Xu Zhen , Li Yuan , Zhen Lixiao , Zhao Qian , Guo Yuefan , Wang Zhaohui , Bischof Evelyne , Yu Zuoren 
Published: July 2020

AbstractBackgroundEmerging evidence has demonstrated the limited access to metabolic substrates as an effective approach to block cancer cell growth. The mechanisms remain unclear. Our previous work has revealed that miR-221/222 plays important role in regulating breast cancer development and progression through interaction with target gene p27.ResultsHerein, we determined the miRNA-mRNA interaction in breast cancer cells under induced stress status of starvation. Starvation stimulation attenuated the miR-221/222-p27 interaction in MDA-MB-231 cells, thereby increased p27 expression and suppressed cell proliferation. Through overexpression or knockdown of miR-221/222, we found that starvation-induced stress attenuated the negative regulation of p27 expression by miR-221/222. Similar patterns for miRNA-target mRNA interaction were observed between miR-17-5p and CyclinD1, and between mR-155 and Socs1. Expression of Ago2, one of the key components of RNA-induced silencing complex (RISC), was decreased under starvation-induced stress status, which took responsibility for the impaired miRNA-target interaction since addition of exogenous Ago2 into MDA-MB-231 cells restored the miR-221/222-p27 interaction in starvation condition.ConclusionsWe demonstrated the attenuated interaction between miR-221/222 and p27 by starvation-induced stress in MDA-MB-231 breast cancer cells. The findings add a new page to the general knowledge of negative regulation of gene expression by miRNAs, also demonstrate a novel mechanism through which limited access to nutrients suppresses cancer cell proliferation. These insights provide a basis for development of novel therapeutic options for breast cancer.
Oncolytic vaccinia virus GLV-1h68 exhibits profound antitumoral activities in cell lines originating from neuroendocrine neoplasms
Authors: Kloker Linus D. , Berchtold Susanne , Smirnow Irina , Beil Julia , Krieg Andreas , Sipos Bence , Lauer Ulrich M. 
Published: July 2020

Abstract
Background
Oncolytic virotherapy is an upcoming treatment option for many tumor entities. But so far, a first oncolytic virus only was approved for advanced stages of malignant melanomas. Neuroendocrine tumors (NETs) constitute a heterogenous group of tumors arising from the neuroendocrine system at diverse anatomic sites. Due to often slow growth rates and (in most cases) endocrine non-functionality, NETs are often detected only in a progressed metastatic situation, where therapy options are still severely limited. So far, immunotherapies and especially immunovirotherapies are not established as novel treatment modalities for NETs.

Methods
In this immunovirotherapy study, pancreatic NET (BON-1, QGP-1), lung NET (H727, UMC-11), as well as neuroendocrine carcinoma (NEC) cell lines (HROC-57, NEC-DUE1) were employed. The well characterized genetically engineered vaccinia virus GLV-1 h68, which has already been investigated in various clinical trials, was chosen as virotherapeutical treatment modality.

Results
Profound oncolytic efficiencies were found for NET/NEC tumor cells. Besides, NET/NEC tumor cell bound expression of GLV-1 h68-encoded marker genes was observed also. Furthermore, a highly efficient production of viral progenies was detected by sequential virus quantifications. Moreover, the mTOR inhibitor everolimus, licensed for treatment of metastatic NETs, was not found to interfere with GLV-1 h68 replication, making a combinatorial treatment of both feasible.

Conclusions
In summary, the oncolytic vaccinia virus GLV-1 h68 was found to exhibit promising antitumoral activities, replication capacities and a potential for future combinatorial approaches in cell lines originating from neuroendocrine neoplasms. Based on these preliminary findings, virotherapeutic effects now have to be further evaluated in animal models for treatment of Neuroendocrine neoplasms (NENs).
Multiple recurrent myxofibrosarcoma of the orbit: case report and review of the literature
Authors: Du Baixue , He Xin , Wang Yujiao , He Weimin 
Published: July 2020

Abstract
Background
Although myxofibrosarcoma (MFS) is the most common mesenchymal tumor, occurrence in the orbit is extremely rare. A characteristic clinical feature of MFS is its propensity for local recurrence (LR). Still, none of published literature has described the entire clinical course of multiple recurrences of MFS in the orbit. Here we present an unusual case in which a patient with multiple recurrences of MFS in the orbit followed-up for 5 years. We describe its clinical-pathological correlation, treatment, and prognosis.

Case presentation
A 70-year-old woman sought treatment for a year history of right upper eyelid swelling in May 2014. Since then, she underwent three surgical procedures in the right orbit in the same region (in 2014, 2016, and 2017). The pathology analysis of the three surgical tissue samples was consistent with myxofibrosarcoma, characterized by spindle-shaped cells and variably myxoid stroma. In the 2 years follow-up after the third surgery, there was no evidence of tumor recurrence.

Conclusion
Myxofibrosarcoma of the orbit is extremely rare. Since few reports are available in the literature, the diagnosis and management of the orbit myxofibrosarcoma is still a challenge to ophthalmologists. Histopathology is highly valuable in the diagnosis. As a clinical characteristic, the lesions have a high risk of local recurrence; therefore, aggressive resection and careful postoperative follow-up are paramount.
Metacognitive Training for Obsessive-Compulsive Disorder: a study protocol for a randomized controlled trial
Authors: Miegel Franziska , Demiralay Cüneyt , Moritz Steffen , Wirtz Janina , Hottenrott Birgit , Jelinek Lena 
Published: July 2020

AbstractBackgroundA high number of patients with obsessive-compulsive disorder (OCD) do not receive cognitive-behavioral therapy with exposure and response prevention, which is the most effective treatment for OCD. Therefore, Metacognitive Training for OCD (MCT-OCD) was developed, which is a structured group therapy aiming at the modification of dysfunctional (meta-)cognitive biases, beliefs and coping styles. It can be administered by less trained personnel, thus may reach a higher number of patients.An uncontrolled pilot study (MCT-OCD pilot version) provided first evidence that the training is highly accepted by patients; OC symptoms decreased with a high effect size (η2partial = 0.50). The aim of the present study is to address the shortcomings of the pilot study (e.g., no control group) and to assess the efficacy of the revised version of the MCT-OCD in the framework of a randomized controlled trial.MethodsEighty patients with OCD will be recruited. After a blinded assessment at baseline (−t1), patients will be randomly assigned either to the intervention group (MCT-OCD;n = 40) or to a care as usual control group (n = 40). The MCT-OCD aims to enhance patients’ metacognitive competence in eight modules by addressing dysfunctional (meta-)cognitive biases and beliefs associated with OCD (e.g., intolerance of uncertainty). After 8 weeks, patients will be invited to a post assessment (t1), and then they will receive a follow-up online questionnaire 3 months following t1 (t2). The primary outcome is the Y-BOCS total score, and the secondary outcomes include the HDRS, OCI-R, OBQ-44, MCQ-30, WHOQOL-BREF, BDI-II, and subjective appraisal ratings of the MCT-OCD. We expect that OC symptoms will decrease more in the intervention group compared with the care as usual control group from –t1 to t1 and that treatment gains will be maintained until t2.DiscussionThe planned study is the first to investigate the MCT-OCD, a promising new treatment, in a randomized controlled trial. The MCT-OCD may help to overcome existing treatment barriers for patients with OCD.Trial registrationGerman Registry for Clinical Studies (DRKS00013539), 22.02.2018.
The Characteristics and Social Functioning of Pathological Social Withdrawal, “Hikikomori,” in a Secondary Care Setting: a One-Year Cohort Study
Authors: Imai Hissei , Takamatsu Toko , Mitsuya Hideaki , Yoshizawa Hajime , Mitsuya Hidehiko , Furukawa Toshi A. 
Published: July 2020

Abstract
Background
Pathological social withdrawal, named “Hikikomori,” is a Japanese culture-bound syndrome and a serious social problem in Japan. The number of Hikikomori cases in Japan was estimated at about 563,000 in 2016 according to governmental surveys. However, no studies have reported how many people with Hikikomori have access to community-based psychiatry clinics, and how different they are from non-Hikikomori patients regarding their baseline characteristics and outcomes. The aim of the present study is to evaluate the baseline characteristics, clinical attendance, and social functioning of community psychiatric clinic patients treated for social withdrawal at one-year follow-up.

Method
Participants (n = 304) were all patients (aged under 65) of a psychiatric clinic in a one-year period. Baseline patient characteristics were compared among “current” Hikikomori patients, “past” Hikikomori,” and “other” patients. Logistic regression analysis of clinic attendance status and social functioning at one-year follow-up was used to assess patient outcomes. Independent variables were age, gender, Hikikomori status, and support from clinical staff.

Results
Numbers of “current”, “past” Hikikomori, and “other” patients were 60 (19.7%), 81 (26.6%), and 163 (53.6%), respectively. The percentage of “current” Hikikomori who attended in person (56.7%) was significantly smaller than for “past” (92.6%) and “other” (92.6) (p < .001). The age distribution of “current” Hikikomori patients was bimodal, peaking at 20 and 40–45 years. The “current” state predicted significantly fewer regular visits (OR = 0.43; 95% CI = 0.22–0.83; p = .012); support from psychiatric social workers increased visits (OR = 2.35; 95% CI = 1.14–4.86; p = .021). Among the “current” Hikikomori patients, first visit attendance in person predicted regular attendance; no factor consistently predicted working/schooling status.

Conclusion
A sizable percentage of community clinic patients experienced Hikikomori. The “current” Hikikomori state corresponded with low clinic attendance and social function; “support from clinical staff” may increase visit regularity; no factors consistently improved social functioning. Further multi-site study is warranted to examine the generalizability of the findings from the current single-center study.