bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deconvolution of bulk blood eQTL effects into immune cell subpopulations
Authors: Aguirre-Gamboa Raúl , de Klein Niek , di Tommaso Jennifer , Claringbould Annique , van der Wijst Monique GP , de Vries Dylan , Brugge Harm , Oelen Roy , Võsa Urmo , Zorro Maria M. , Chu Xiaojin , Bakker Olivier B. , Borek Zuzanna , Ricaño-Ponce Isis , Deelen Patrick , Xu Cheng-Jiang , Swertz Morris , Jonkers Iris , Withoff Sebo , Joosten Irma , Sanna Serena , Kumar Vinod , Koenen Hans J. P. M. , Joosten Leo A. B. , Netea Mihai G. , Wijmenga Cisca ,   BIOS Consortium, Franke Lude , Li Yang 
Published: June 2020

Abstract
Background
Expression quantitative trait loci (eQTL) studies are used to interpret the function of disease-associated genetic risk factors. To date, most eQTL analyses have been conducted in bulk tissues, such as whole blood and tissue biopsies, which are likely to mask the cell type-context of the eQTL regulatory effects. Although this context can be investigated by generating transcriptional profiles from purified cell subpopulations, current methods to do this are labor-intensive and expensive. We introduce a new method, Decon2, as a framework for estimating cell proportions using expression profiles from bulk blood samples (Decon-cell) followed by deconvolution of cell type eQTLs (Decon-eQTL).

Results
The estimated cell proportions from Decon-cell agree with experimental measurements across cohorts (R ≥ 0.77). Using Decon-cell, we could predict the proportions of 34 circulating cell types for 3194 samples from a population-based cohort. Next, we identified 16,362 whole-blood eQTLs and deconvoluted cell type interaction (CTi) eQTLs using the predicted cell proportions from Decon-cell. CTi eQTLs show excellent allelic directional concordance with eQTL (≥ 96–100%) and chromatin mark QTL (≥87–92%) studies that used either purified cell subpopulations or single-cell RNA-seq, outperforming the conventional interaction effect.

Conclusions
Decon2 provides a method to detect cell type interaction effects from bulk blood eQTLs that is useful for pinpointing the most relevant cell type for a given complex disease. Decon2 is available as an R package and Java application (https://github.com/molgenis/systemsgenetics/tree/master/Decon2) and as a web tool (www.molgenis.org/deconvolution).
AllesTM: predicting multiple structural features of transmembrane proteins
Authors: Hönigschmid Peter , Breimann Stephan , Weigl Martina , Frishman Dmitrij 
Published: June 2020

Abstract
Background
This study is motivated by the following three considerations: a) the physico-chemical properties of transmembrane (TM) proteins are distinctly different from those of globular proteins, necessitating the development of specialized structure prediction techniques, b) for many structural features no specialized predictors for TM proteins are available at all, and c) deep learning algorithms allow to automate the feature engineering process and thus facilitate the development of multi-target methods for predicting several protein properties at once.

Results
We present AllesTM, an integrated tool to predict almost all structural features of transmembrane proteins that can be extracted from atomic coordinate data. It blends several machine learning algorithms: random forests and gradient boosting machines, convolutional neural networks in their original form as well as those enhanced by dilated convolutions and residual connections, and, finally, long short-term memory architectures. AllesTM outperforms other available methods in predicting residue depth in the membrane, flexibility, topology, relative solvent accessibility in its bound state, while in torsion angles, secondary structure and monomer relative solvent accessibility prediction it lags only slightly behind the currently leading technique SPOT-1D. High accuracy on a multitude of prediction targets and easy installation make AllesTM a one-stop shop for many typical problems in the structural bioinformatics of transmembrane proteins.

Conclusions
In addition to presenting a highly accurate prediction method and eliminating the need to install and maintain many different software tools, we also provide a comprehensive overview of the impact of different machine learning algorithms and parameter choices on the prediction performance.
AllesTM is freely available at https://github.com/phngs/allestm.
Intraoperative hypotension is associated with increased postoperative complications in patients undergoing surgery for pheochromocytoma-paraganglioma: a retrospective cohort study
Authors: Li Nan , Kong Hao , Li Shuang-Ling , Zhu Sai-Nan , Zhang Zheng , Wang Dong-Xin 
Published: June 2020

AbstractBackgroundDramatic hemodynamic fluctuation occurs frequently during surgery for pheochromocytoma or paraganglioma. However, the criteria of intraoperative hemodynamic instability vary widely, and most of them were defined arbitrarily but not according to patients’ prognosis. The objective was to analyze the relationship between different thresholds and durations of intraoperative hyper−/hypotension and the risk of postoperative complications in patients undergoing surgery for pheochromocytoma or paraganglioma.MethodsThis was a retrospective single-center cohort study performed in a tertiary care hospital from January 1, 2005 to December 31, 2017. Three hundred twenty-seven patients who underwent surgery for pheochromocytoma or paraganglioma, of which the diagnoses were confirmed by postoperative pathologic examination, were enrolled. Those who were less than 18 years, underwent surgery involving non-tumor organs, or had incomplete data were excluded. The primary endpoint was a composite of the occurrence of AKI or other complications during hospital stay after surgery. Multivariate Logistic regression models were used to analyze the association between different thresholds and durations of intraoperative hyper−/hypotension and the development of postoperative complications.ResultsForty three (13.1%) patients developed complications during hospital stay after surgery. After adjusting for confounding factors, intraoperative hypotension, defined as systolic blood pressure (SBP) of ≤95 mmHg for ≥20 min (OR 3.211; 99% CI 1.081–9.536;P = 0.006), SBP of ≤90 mmHg for ≥20 min (OR 3.680; 98.8% CI 1.107–12.240;P = 0.006), SBP of ≤85 mmHg for ≥10 min (OR 3.975; 98.3% CI 1.321–11.961;P = 0.003), and SBP of ≤80 mmHg for ≥1 min (OR 3.465; 95% CI 1.484–8.093;P = 0.004), were associated with an increased risk of postoperative complications. On the other hand, intraoperative hypertension was not significantly associated with the development of postoperative complications.ConclusionsFor patients undergoing surgery for pheochromocytoma or paraganglioma, intraoperative hypotension is associated with increased postoperative complications; and the harmful effects are level- and duration-dependent. The effects of intraoperative hypertension need to be studied further.
Short-course Rifaximin therapy efficacy and lactulose hydrogen breath test in Chinese patients with diarrhea-predominant irritable bowel syndrome
Authors: Zhuang Xiaojun , Tian Zhenyi , Luo Mei , Xiong Lishou 
Published: June 2020

Abstract
Background
Gut microbiota alterations including small intestinal bacterial overgrowth (SIBO) might play a role in pathogenesis of irritable bowel syndrome (IBS). Rifaximin could effectively and safely improve IBS symptoms. The aim of this study was to investigate the effect of rifaximin on Gastrointestinal (GI) symptoms, quality of life (QOL) and SIBO eradication in Chinese IBS-D patients.

Methods
This study included 78 IBS-D patients defined by the Rome IV criteria. Patients received 400 mg rifaximin twice daily for 2 weeks and 10-week follow-up. GI symptoms were assessed at week 0, 2, 4, 8 and 12. QOL and lactulose hydrogen breath test (LHBT) results were estimated at week 0 and 4.

Results
All participants showed significant improvements in GI symptom subdomains after rifaximin treatment (all P < 0.05), which could maintain at least 10 weeks of follow-up. Additionally, QOL scores were increased with concomitant improvement of clinical symptoms (all P < 0.05). The 45 rifaximin-responsive patients (57.7%) achieved significantly greater GI-symptom improvement than non-responders (all P < 0.05). No GI symptoms were associated with SIBO (all P > 0.05). SIBO normalization after rifaximin treatment measured by LHBT was found in 44.4% (20/45) of patients with SIBO before treatment.

Conclusion
A short course (2 weeks) of rifaximin improved GI symptoms and QOL in Chinese IBS-D patients whether they had SIBO or not. However, the efficacy of rifaximin could not be explained by the successful eradication of SIBO. Further studies on the therapeutic mechanisms of rifaximin in IBS are urgently needed.
Multimorbidity patterns, polypharmacy and their association with liver and kidney abnormalities in people over 65 years of age: a longitudinal study
Authors: Villén Noemí , Guisado-Clavero Marina , Fernández-Bertolín Sergio , Troncoso-Mariño Amelia , Foguet-Boreu Quintí , Amado Ester , Pons-Vigués Mariona , Roso-Llorach Albert , Violán Concepción 
Published: June 2020

Abstract
Background
The implementation of individual clinical practice guidelines in patients with multimorbidity often results in polypharmacy. Our aim was to analyse medication use according to longitudinal multimorbidity patterns (MP) and determine during a 5-year period (2012–16) which MP are associated with abnormal liver and kidney function in primary care patients over 65 years of age living in Catalonia.

Methods
Design: Longitudinal study (years 2012 to 2016) based on the electronic health records contained in Information System for Research in Primary Care database of the Catalan Institute of Health (SIDIAP). Variables: age, sex, MP, medication and polypharmacy (drug exposure obtained from the Pharmacy Invoice Registry). Medicines were classified in accordance with the Anatomical Therapeutic Chemical Classification System (ATC). Glomerular filtration rate was used to determine abnormal kidney function, and serum levels of alkaline phosphatase, alanine transaminase and gamma-glutamyl transpeptidase were used to diagnose abnormal liver function. Statistics: For medication use in MP, we calculated annual mean packages of each drug in each MP, and observed/expected ratios were obtained by dividing mean packages in the cluster by mean packages of the same drug in the overall population. Logistic regression models were fitted to estimate the association between MP at baseline and abnormal kidney and liver function tests during follow up.

Results
Nine hundred sixteen thousand six hundred nineteen patients were included, and 743,827 completed the follow up. We identified one polypharmacy profile per MP, and concluded that the most prescribed drugs in each pattern corresponded to the diseases overrepresented in that specific MP. The median of drugs ranged from 3 (Cluster 1 - Non-Specific) to 8 (Cluster 10 - Multisystem Pattern). Abnormal kidney function was most commonly observed in the Cluster 4 - Cardio-Circulatory and Renal (Odds Ratio [OR] 2.19; Confidence interval [CI] 95% 2.15–2.23) and Cluster 3 - Minority Metabolic Autoimmune-Inflammatory (OR 2.16; CI 95% 2.12–2.20) MP. A higher risk of abnormal liver function was observed in the Cluster 8 - Digestive (OR 3.39; CI 95% 3.30–3.49), and Cluster 4 - Cardio-Circulatory and Renal (OR 1.96; CI 95% 1.91–2.02) MP.

Conclusions
A higher risk of abnormal kidney and liver function was observed in specific MP. The long-term characterisation of MP and polypharmacy illustrates the burden of chronic multimorbidity and polypharmacy in the elderly population.
Simulating transmission of ESKAPE pathogens plus C. difficile in relevant clinical scenarios
Authors: Weber Katharina L. , LeSassier Danielle S. , Kappell Anthony D. , Schulte Kathleen Q. , Westfall Nicole , Albright Nicolette C. , Godbold Gene D. , Palsikar Veena , Acevedo Carlos A. , Ternus Krista L. , Hewitt F. Curtis 
Published: June 2020

Abstract
Background
The prevalence of healthcare-acquired infections (HAI) and rising levels of antimicrobial resistance places significant economic and public health burdens on modern healthcare systems. A group of highly drug resistant pathogens known as the ESKAPE pathogens, along with C. difficile, are the leading causes of HAIs. Interactions between patients, healthcare workers, and environmental conditions impact disease transmission. Studying pathogen transfer under varying contact scenarios in a controlled manner is critical for understanding transmission and disinfectant strategies. In lieu of human subject research, this method has the potential to contribute to modeling the routes of pathogen transmission in healthcare settings.

Methods
To overcome these challenges, we have developed a method that utilizes a synthetic skin surrogate to model both direct (skin-to-skin) and indirect (skin-to fomite-to skin) pathogen transfer between infected patients and healthy healthcare workers. This surrogate material includes a background microbiome community simulating typical human skin flora to more accurately mimic the effects of natural flora during transmission events.

Results
We demonstrate the ability to modulate individual bacterial concentrations within this microbial community to mimic bacterial concentrations previously reported on the hands of human subjects. We also explore the effect of various decontamination approaches on pathogen transfer between human subjects, such as the use of handwashing or surface disinfectants. Using this method, we identify a potential outlier, S. aureus, that may persist and retain viability in specific transfer conditions better than the overall microbial community during decontamination events.

Conclusions
Our work describes the development of an in vitro method that uses a synthetic skin surrogate with a defined background microbiota to simulate skin-to-skin and skin-to fomite-to skin contact scenarios. These results illustrate the value of simulating a holistic microbial community for transfer studies by elucidating differences in different pathogen transmission rates and resistance to common decontamination practices. We believe this method will contribute to improvements in pathogen transmission modeling in healthcare settings and increase our ability to assess the risk associated with HAIs, although additional research is required to establish the degree of correlation of pathogen transmission by skin or synthetic alternatives.
Myasthenia gravis with anti-muscle-specific tyrosine kinase antibodies during therapy for multiple myeloma: a case report
Authors: Sakano Shoko , Matsuyama Hirofumi , Ishikawa Hidehiro , Shindo Akihiro , Ii Yuichiro , Matsuura Keita , Mizutani Minoru , Kawada Norikazu , Tomimoto Hidekazu 
Published: June 2020

Abstract
Background
The onset of myasthenia (MG) gravis with anti-muscle-specific tyrosine kinase (MuSK) antibodies most commonly peaks in the fourth decade of life, and MG with MuSK antibodies (MuSK-MG) rarely coexists with a malignant tumor. To date, MuSK-MG has not been reported in multiple myeloma (MM).

Case presentation
A 60-year-old male with MM who was receiving treatment with bortezomib and thalidomide presented diplopia, ptosis, and limb weakness. A diagnosis of MM with Bence-Jones proteinuria was established when he was 56 years old, and he received chemotherapy with four courses of bortezomib and dexamethasone. Although he received thalidomide as maintenance therapy, it was discontinued a year before hospital admission because of sensory neuropathy as a side effect. Six months before hospital admission, he developed mild diplopia. One month before admission, his chemotherapy was interrupted because of viral infection and fatigability. Then he developed neck weakness and bilateral ptosis. A diagnosis of MuSK-MG was made based on neurological and serological examinations. According to the previous relevant literature, this is the first report of MuSK-MG in a patient with MM.

Conclusions
In patients with MM, the possibility of co-existing of autoimmune disease, including MuSK-MG, should be considered. This case emphasizes the need to still consider testing for anti-MuSK antibodies in older MM patients where there is clinical suspicion for possible MG despite negative anti-acetylcholine receptor antibodies and lacking classic MuSK MG phenotype at onset.
Pharmacological treatment of increased vascular risk and cognitive performance in middle-aged and old persons: six-year observational longitudinal study
Authors: van Eersel Marlise E. A. , Visser Sipke T. , Joosten Hanneke , Gansevoort Ron T. , Slaets Joris P. J. , Izaks Gerbrand J. 
Published: June 2020

Abstract
Background
Lowering vascular risk is associated with a decrease in the prevalence of cardiovascular disease and dementia. However, it is still unknown whether lowering of vascular risk with pharmacological treatment preserves cognitive performance in general. Therefore, we compared the change in cognitive performance in persons with and without treatment of vascular risk factors.

Methods
In this longitudinal observational study, 256 persons (mean age, 58 years) were treated for increased vascular risk during a mean follow-up period of 5.5 years (treatment group), whereas 1678 persons (mean age, 50 years) did not receive treatment (control group). Cognitive performance was three times measured during follow-up using the Ruff Figural Fluency Test (RFFT) and Visual Association Test (VAT), and calculated as the average of standardized RFFT and VAT score per participant. Because treatment allocation was nonrandomized, additional analyses were performed in demographic and vascular risk-matched samples and adjusted for propensity scores.

Results
In the treatment group, mean (SD) cognitive performance changed from − 0.30 (0.80) to − 0.23 (0.80) to 0.02 (0.87), and in control group, from 0.08 (0.77) to 0.24 (0.79) to 0.49 (0.74) at the first, second and third measurement, respectively (ptrend < 0.001). After adjustment for demographics and vascular risk, the change in cognitive performance during follow-up was not statistically significantly different between the treatment and control group: mean estimated difference, − 0.10 (95%CI − 0.21 to 0.01; p = 0.08). Similar results were found in matched samples and after adjustment for propensity score.

Conclusion
Change in cognitive performance during follow-up was similar in treated and untreated persons. This suggests that lowering vascular risk preserves cognitive performance.
Changes in choroidal thickness in advanced diabetic retinopathy treated with pan-retinal photocoagulation using a pattern scanning laser versus a conventional laser
Authors: Park Nari , Lee In Gul , Kim Jee Taek 
Published: June 2020

Abstract
Background
To compare the effect of pan-retinal photocoagulation (PRP) using pattern scanning or conventional laser on subfoveal choroidal thickness (SFChT).

Methods
Thirty-eight patients (64 eyes) with advanced diabetic retinopathy (DR) who underwent PRP using pattern scanning or conventional laser were included. Changes in SFChT were compared with baseline values at 1, 3, 6, and 12 months after PRP using swept-source optical coherence tomography.

Results
The conventional laser group showed a statistically significant decrease in SFChT at 1, 3, 6, and 12 months after PRP (P < 0.001). SFChT was significantly decreased at 3 (P = 0.025), 6 (P = 0.004), and 12 (P < 0.001) months after treatment in the pattern laser group.

Conclusion
Eyes with advanced DR showed a significant reduction in SFChT over 12 months regardless of the type of laser used; however, the reduction was sooner after conventional laser than after pattern laser.
Gender difference in the association between education and schizophrenia in Chinese adults
Authors: Luo Yanan , Pang Lihua , Zhao Yihao , Guo Chao , Zhang Lei , Zheng Xiaoying 
Published: June 2020

AbstractBackgroundImproving education level was evidenced to decrease the risk of schizophrenia, but whether this strength of education role depends on gender is not. This study aimed to investigate whether there was gender difference in the association between education and schizophrenia in Chinese adults.MethodsData were obtained from the Second China National Sample Survey on Disability in 2006, including 1,909,205 participants aged 18 years or older. Schizophrenia was ascertained according to the International Statistical Classification of Diseases, Tenth Revision. Logistics regression models were fitted to examine the combined effect of gender and education on schizophrenia.ResultsThe lifetime prevalence of schizophrenia in female groups was higher than in male groups, with 0.44% (95%CI: 0.42–0.45%) and 0.36% (95%CI: 0.35–0.37%), respectively. Compared with schizophrenia male patients, more females with schizophrenia experienced severe or extreme difficulty in understanding and communicating. However, more males with schizophrenia suffered from severe or extreme difficulty in the function of daily activities. The combined effect of education and schizophrenia was statistically significant, indicating that, as the level of education increased, schizophrenia risk of females decreased faster than the risk of males.ConclusionsThis study showed that additional years of education associated with lower risk of schizophrenia, and this association was stronger in females than in males. As education elevated, the risk of schizophrenia decreased more for women than for men. The findings indicate that improving education level may have an effect on reducing the gender disparities in mental health of China. Actions to prevent schizophrenia and address its gender disparities will require attention to the improving educational opportunities.
Declining trend in HIV new infections in Guangxi, China: insights from linking reported HIV/AIDS cases with CD4-at-diagnosis data
Authors: Sun Xiaodan , Yang Wenmin , Tang Sanyi , Shen Mingwang , Wang Tianyang , Zhu Qiuying , Shen Zhiyong , Tang Shuai , Chen Huanhuan , Ruan Yuhua , Xiao Yanni 
Published: June 2020

AbstractBackgroundThe Guangxi Zhuang Autonomous Region bears a relatively high burden of HIV/AIDS infection. The number of accumulatively reported HIV/AIDS cases in Guangxi is the third highest among 31 provinces or Autonomous Region from 2004 to 2007, changed to the second highest between 2011 and 2013, then returned to the third highest again after 2014. We aim to estimate the new infections and evaluate the real-time HIV epidemic in Guangxi, China, in order to reveal the rule of HIV transmission.MethodsFirstly, the number of annually reported HIV and AIDS cases, as well as the number of cases linked with CD4 data are extracted from the HIV/AIDS information system in China. Secondly, two CD4-staged models are formulated by linking the with-host information on CD4 level to between-host transmission and surveillance data. Thirdly, new HIV infections, diagnosis rates and undiagnosed infections over time are estimated by using Bayesian method and Maximum Likelihood Estimation method.ResultsThe data reveal that the newly reported cases have been decreasing since 2011, while lots of cases are identified at late CD4 stage. The data fitted results indicate that both models can describe the trend of the epidemic well. The estimation results show that the new and undiagnosed infections began to decrease from the period2006 - 2008. However, the diagnosis probabilities/rates keep at a very low level, and there are still a large number of infections undiagnosed, most of which have a large probability to be identified at late CD4 stage.ConclusionsOur findings suggest that HIV/AIDS epidemic in Guangxi has been controlled to a certain extent, while the diagnosis rate still needs to be improved. More attentions should be paid to identify infections at their early CD4 stages. Meanwhile, comprehensive intervention measures should be continually strengthened in avoid of the rebound of new infections.