bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic characterization of HIV-1 epidemic in Anhui Province, China
Authors: Zhang Dong , Wu Jianjun , Zhang Yu , Shen Yuelan , Dai Sheying , Wang Xiaolin , Xing Hui , Lin Jin , Han Jingwan , Li Jingyun , Qin Yizu , Liu Yongjian , Miao Lifeng , Su Bin , Li Hanping , Li Lin 
Published: February 2020

Abstract
Background
Anhui Province in China is facing a severe HIV epidemic with an increasing number of newly diagnosed cases.

Methods
In this study, HIV genetic characteristics in the province were investigated. Newly reported HIV-positive individuals from 15 districts of Anhui Province were enrolled and interviewed. Total viral RNA was extracted from plasma isolated from blood samples. We amplified and sequenced an HIV pol fragment of the 1062 bp. The sequences were used for determination of HIV subtypes and the presence of drug resistance mutations. Transmission networks were constructed to explore possible relationships. And all of assembled partial pol genes were submitted to the Stanford HIV Drug Resistance Database website to find the transmitted drug resistance.

Results
Partial pol gene sequences were obtained from 486 cases. The results showed that MSM was the most dominant transmission route (253, 52.06%), followed by heterosexual transmission (210, 43.21%) and blood-borne transmission (1, 0.21%). Many subtypes were identified, including CRF01_AE (226, 46.50%), CRF07_BC (151, 31.07%), subtype B (28, 5.76%), CRF08_BC (20, 4.12%), CRF55_01B (15, 3.09%), CRF68_01B (7, 1.44%), CRF67_01B (3, 0.62%), CRF57_BC (2, 0.41%), CRF59_01B (2, 0.41%), CRF79_0107 (2, 0.41%), subtype C (2, 0.41%), CRF64_BC (1, 0.21%), and circulating recombinant forms (URFs) (27, 5.55%). Four transmission subnetworks containing high transmission risk individuals (with degree ≥4) were identified based on CRF01_AE and CRF07_BC sequences, including two CRF01_AE transmission subnetworks constituted by elderly people with average ages of 67.9 and 61.5 years. Infection occurred most likely through heterosexual transmission, while the other two CRF07_BC transmission subnetworks consist mainly of MSMs with average ages of 31.73 and 34.15. The level of HIV-transmitted drug resistance is 3.09%.

Conclusions
The simultaneous spread of multiple HIV subtypes in Anhui province underscores that close surveillance of the local HIV epidemic is necessary. Furthermore, the elderly people were frequently involved, arguing for behaviour intervention in this specific population besides the MSM risk group.
A native chromatin immunoprecipitation (ChIP) protocol for studying histone modifications in strawberry fruits
Authors: Huang Xiaorong , Pan Qinwei , Lin Ying , Gu Tingting , Li Yi 
Published: February 2020

AbstractBackgroundCovalent modifications of histones and histone variants have great influence on chromatin structure, which is involved in the transcriptional regulation of gene expression. Chromatin immunoprecipitation (ChIP) is a powerful tool for studying in vivo DNA-histone interactions. Strawberry is a model for Rosaceae and non-climacteric fruits, in which histone modifications have been implicated to affect fruit development and ripening. However, a validated ChIP method has not been reported in strawberry, probably due to its high levels of polysaccharides which affect the quality of prepared chromatin and the efficiency of immunoprecipitation.ResultsWe describe a native chromatin immunoprecipitation (N-ChIP) protocol suitable for strawberry by optimizing the parameters for nuclei isolation, chromatin extraction, DNA fragmentation and validation analysis using quantitative real-time PCR (qRT-PCR). The qRT-PCR results show that both the active mark H3K36me3 and the silent mark H3K9me2 are efficiently immunoprecipitated for the enriched regions. Compared to X-ChIP (cross-linked chromatin followed by immunoprecipitation), our optimized N-ChIP procedure has a higher signal-to-noise ratio and a lower background for both the active and the silent histone modifications. Furthermore, high-throughput sequencing following N-ChIP demonstrates that nearly 90% of the enriched H3K9/K14ac peaks are overlapped between biological replicates, indicating its remarkable consistency and reproducibility.ConclusionsAn N-ChIP method suitable for the fleshy fruit tissues of woodland strawberryFragaria vescais described in this study. The efficiency and reproducibility of our optimized N-ChIP protocol are validated by both qRT-PCR and high-throughput sequencing. We conclude that N-ChIP is a more suitable method for strawberry fruit tissues relative to X-ChIP, which could be combined with high-throughput sequencing to investigate the impact of histone modifications in strawberry and potentially in other fruits with high content of polysaccharides.
Computerized clinical decision support system for diabetes in primary care does not improve quality of care: a cluster-randomized controlled trial
Authors: Heselmans Annemie , Delvaux Nicolas , Laenen Annouschka , Van de Velde Stijn , Ramaekers Dirk , Kunnamo Ilkka , Aertgeerts Bert 
Published: February 2020

Abstract
Background
The EBMeDS system is the computerized clinical decision support (CCDS) system of EBPNet, a national computerized point-of-care information service in Belgium. There is no clear evidence of more complex CCDS systems to manage chronic diseases in primary care practices (PCPs). The objective of this study was to assess the effectiveness of EBMeDS use in improving diabetes care.

Methods
A cluster-randomized trial with before-and-after measurements was performed in Belgian PCPs over 1 year, from May 2017 to May 2018. We randomly assigned 51 practices to either the intervention group (IG), to receive the EBMeDS system, or to the control group (CG), to receive usual care. Primary and secondary outcomes were the 1-year pre- to post-implementation change in HbA1c, LDL cholesterol, and systolic and diastolic blood pressure. Composite patient and process scores were calculated. A process evaluation was added to the analysis. Results were analyzed at 6 and 12 months. Linear mixed models and logistic regression models based on generalized estimating equations were used where appropriate.

Results
Of the 51 PCPs that were enrolled and randomly assigned (26 PCPs in the CG and 25 in the IG), 29 practices (3815 patients) were analyzed in the study: 2464 patients in the CG and 1351 patients in the IG. No change differences existed between groups in primary or secondary outcomes. Change difference between CG and IG after 1-year follow-up was − 0.09 (95% CI − 0.18; 0.01, p-value = 0.06) for HbA1c; 1.76 (95% CI − 0.46; 3.98, p-value = 0.12) for LDL cholesterol; and 0.13 (95% CI − 0.91; 1.16, p-value = 0.81) and 0.12 (95% CI − 1.25;1.49, p-value = 0.86) for systolic and diastolic blood pressure respectively. The odds ratio of the IG versus the CG for the probability of no worsening and improvement was 1.09 (95% CI 0.73; 1.63, p-value = 0.67) for the process composite score and 0.74 (95% CI 0.49; 1.12, p-value = 0.16) for the composite patient score. All but one physician was satisfied with the EBMeDS system.

Conclusions
The CCDS system EBMeDS did not improve diabetes care in Belgian primary care. The lack of improvement was mainly caused by imperfections in the organizational context of Belgian primary care for chronic disease management and shortcomings in the system requirements for the correct use of the EBMeDS system (e.g., complete structured records). These shortcomings probably caused low-use rates of the system.

Trial registration
ClinicalTrials.gov, NCT01830569, Registered 12 April 2013.
Neurofibromatosis 1 French national guidelines based on an extensive literature review since 1966
Authors:   NF France Network, Bergqvist Christina , Servy Amandine , Valeyrie-Allanore Laurence , Ferkal Salah , Combemale Patrick , Wolkenstein Pierre 
Published: February 2020

AbstractNeurofibromatosis type 1 is a relatively common genetic disease, with a prevalence ranging between 1/3000 and 1/6000 people worldwide. The disease affects multiple systems with cutaneous, neurologic, and orthopedic as major manifestations which lead to significant morbidity or mortality. Indeed, NF1 patients are at an increased risk of malignancy and have a life expectancy about 10–15 years shorter than the general population. The mainstay of management of NF1 is a patient-centered longitudinal care with age-specific monitoring of clinical manifestations, aiming at the early recognition and symptomatic treatment of complications as they occur. Protocole national de diagnostic et de soins (PNDS) are mandatory French clinical practice guidelines for rare diseases required by the French national plan for rare diseases. Their purpose is to provide health care professionals with guidance regarding the optimal diagnostic and therapeutic management of patients affected with a rare disease; and thus, harmonizing their management nationwide. PNDS are usually developed through a critical literature review and a multidisciplinary expert consensus. The purpose of this article is to present the French guidelines on NF1, making them even more available to the international medical community. We further dwelled on the emerging new evidence that might have therapeutic potential or a strong impact on NF1 management in the coming feature. Given the complexity of the disease, the management of children and adults with NF1 entails the full complement healthcare providers and communication among the various specialties.
Reduced chronic restraint stress in mice overexpressing hyperactive proteasomes in the forebrain
Authors: Kim Ji Hyeon , Kim Ahbin , Yun Yejin , Park Seoyoung , Lee Jung Hoon , Lee Yong-Seok , Lee Min Jae 
Published: February 2020

AbstractWhile chronic restraint stress (CRS) results in depression-like behaviors possibly through oxidative stress in the brain, its molecular etiology and the development of therapeutic strategies remain elusive. Since oxidized proteins can be targeted by the ubiquitin-proteasome system, we investigated whether increased proteasome activity might affect the stress response in mice. Transgenic mice, expressing the N-terminally deleted version of α3 subunit (α3ΔN) of the proteasome, which has been shown to generate open-gated mutant proteasomes, in the forebrain were viable and fertile, but showed higher proteasome activity. After being challenged with CRS for 14 d, the mutant mice with hyperactive proteasomes showed significantly less immobility time in the forced swimming test compared with their wild-type littermates, suggesting that the α3ΔN transgenic mice are resistant to CRS. The accumulation of ER stress markers, such as polyubiquitin conjugates and phospho-IRE1α, was also significantly delayed in the hippocampus of the mutants. Notably, α3ΔN mice exhibited little deficits in other behavioral tasks, suggesting that stress resilience is likely due to the degradation of misfolded proteins by the open-gated proteasomes. These data strongly indicate that not only is the proteasome a critical modulator of stress response in vivo but also a possible therapeutic target for reducing chronic stress.
KDM4B facilitates colorectal cancer growth and glucose metabolism by stimulating TRAF6-mediated AKT activation
Authors: Li Haijie , Lan Jingqin , Wang Guihua , Guo Kaixuan , Han Caishun , Li Xiaolan , Hu Junbo , Cao Zhixin , Luo Xuelai 
Published: February 2020

Abstract
Background
Histone lysine demethylase 4B (KDM4B) has been implicated in various pathological processes and human diseases. Glucose metabolism is the main pattern of energy supply in cells and its dysfunction is closely related to tumorigenesis. Recent study shows that KDM4B protects against obesity and metabolic dysfunction. We realized the significant role of KDM4B in metabolism. However, the role of KDM4B in glucose metabolism remains unclear. Here, we sought to delineate the role and mechanism of KDM4B in glucose metabolism in colorectal cancer (CRC).

Methods
We first analyzed the role of KDM4B in glucose uptake and CRC growth. We then investigated the consequences of KDM4B inhibition on the expression of GLUT1 and AKT signaling, also explored the underlying mechanism. Finally, we detected the mechanism in vivo and assessed the potential correlation between the expression of KDM4B and CRC prognosis.

Results
We found that KDM4B promoted glucose uptake and ATP production by regulating the expression of GLUT1 via the AKT signaling pathway. KDM4B could interact with TRAF6 and promote TRAF6-mediated ubiquitination of AKT for AKT activation. Furthermore, we demonstrated that KDM4B was overexpressed in CRC specimens and high level of KDM4B was associated with a poor survival rate in CRC patients.

Conclusions
These findings reveal that KDM4B plays an important role in promoting CRC progression by enhancing glucose metabolism.
Real-time shear wave ultrasound elastography: a new tool for the evaluation of diaphragm and limb muscle stiffness in critically ill patients
Authors: Flatres Aurelien , Aarab Yassir , Nougaret Stephanie , Garnier Fanny , Larcher Romaric , Amalric Mathieu , Klouche Kada , Etienne Pascal , Subra Gilles , Jaber Samir , Molinari Nicolas , Matecki Stefan , Jung Boris 
Published: February 2020

Abstract
Background
Muscle weakness following critical illness is the consequence of loss of muscle mass and alteration of muscle quality. It is associated with long-term disability. Ultrasonography is a reliable tool to quantify muscle mass, but studies that evaluate muscle quality at the critically ill bedside are lacking. Shear wave ultrasound elastography (SWE) provides spatial representation of soft tissue stiffness and measures of muscle quality. The reliability and reproducibility of SWE in critically ill patients has never been evaluated.

Methods
Two operators tested in healthy controls and in critically ill patients the intra- and inter-operator reliability of the SWE using transversal and longitudinal views of the diaphragm and limb muscles. Reliability was calculated using the intra-class correlation coefficient and a bootstrap sampling method assessed their consistency.

Results
We collected 560 images. Longitudinal views of the diaphragm (ICC 0.83 [0.50–0.94]), the biceps brachii (ICC 0.88 [0.67–0.96]) and the rectus femoris (ICC 0.76 [0.34–0.91]) were the most reliable views in a training set of healthy controls. Intra-class correlation coefficient for inter-operator reproducibility and intra-operator reliability was above 0.9 for all muscles in a validation set of healthy controls. In critically ill patients, inter-operator reproducibility and intra-operator 1 and 2 reliability ICCs were respectively 0.92 [0.71–0.98], 0.93 [0.82–0.98] and 0.92 [0.81–0.98] for the diaphragm; 0.96 [0.86–0.99], 0.98 [0.94–0.99] and 0.99 [0.96–1] for the biceps brachii and 0.91 [0.51–0.98], 0.97 [0.93–0.99] and 0.99 [0.97–1] for the rectus femoris. The probability to reach intra-class correlation coefficient greater than 0.8 in a 10,000 bootstrap sampling for inter-operator reproducibility was respectively 81%, 84% and 78% for the diaphragm, the biceps brachii and the rectus femoris respectively.

Conclusions
SWE is a reliable technique to evaluate limb muscles and the diaphragm in both healthy controls and in critically ill patients.

Trial registration
The study was registered (ClinicalTrial NCT03550222).
Impact of a posttraumatic cerebral infarction on outcome in patients with TBI: the Italian multicenter cohort INCEPT study
Authors: Latronico Nicola , Piva Simone , Fagoni Nazzareno , Pinelli Lorenzo , Frigerio Michele , Tintori Davide , Berardino Maurizio , Bottazzi Andrea , Carnevale Livio , Casalicchio Tiziana , Castioni Carlo Alberto , Cavallo Simona , Cerasti Davide , Citerio Giuseppe , Fontanella Marco , Galiberti Serena , Girardini Alan , Gritti Paolo , Manara Ornella , Maremmani Paolo , Mazzani Roberta , Natalini Giuseppe , Patassini Mirko , Perna Maria Elena , Pesaresi Ilaria , Radolovich Danila Katia , Saini Maurizio , Stefini Roberto , Minelli Cosetta , Gasparotti Roberto , Rasulo Francesco A. 
Published: February 2020

AbstractBackgroundPost-traumatic cerebral infarction (PTCI) is common after traumatic brain injury (TBI). It is unclear what the occurrence of a PTCI is, how it impacts the long-term outcome, and whether it adds incremental prognostic value to established outcome predictors.MethodsThis was a prospective multicenter cohort study of moderate and severe TBI patients. The primary objective was to evaluate if PTCI was an independent risk factor for the 6-month outcome assessed with the Glasgow Outcome Scale (GOS). We also assessed the PTCI occurrence and if it adds incremental value to the International Mission for Prognosis and Clinical Trial design in TBI (IMPACT) core and extended models.ResultsWe enrolled 143 patients, of whom 47 (32.9%) developed a PTCI. In the multiple ordered logistic regression, PTCI was retained in both the core and extended IMPACT models as an independent predictor of the GOS. The predictive performances increased significantly when PTCI was added to the IMPACT core model (AUC = 0.73, 95% C.I. 0.66–0.82; increased to AUC = 0.79, 95% CI 0.71–0.83,p = 0.0007) and extended model (AUC = 0.74, 95% C.I. 0.65–0.81 increased to AUC = 0.80, 95% C.I. 0.69–0.85;p = 0.00008). Patients with PTCI showed higher ICU mortality and 6-month mortality, whereas hospital mortality did not differ between the two groups.ConclusionsPTCI is a common complication in patients suffering from a moderate or severe TBI and is an independent risk factor for long-term disability. The addition of PTCI to the IMPACT core and extended predictive models significantly increased their performance in predicting the GOS.Trial registrationThe present study was registered in ClinicalTrial.gov with the ID numberNCT02430324.
HER2 heterogeneity and resistance to anti-HER2 antibody-drug conjugates
Authors: Ocaña Alberto , Amir Eitan , Pandiella Atanasio 
Published: February 2020

Abstract
Background
There has been substantial interest in HER2 intratumoral heterogeneity as an explanation for the development of resistance to anti-HER2 therapies in breast cancer, particularly to trastuzumab emtansine (T-DM1).

Methods
Through a literature-based approach, we discuss mechanisms of resistance to HER2-targeting antibody-drug conjugates (ADCs) in breast cancer.

Results
We describe results from clinical studies reporting the effect of anti-HER2 strategies particularly ADCs and their mechanistic effect. We review biological findings underlying HER2 heterogeneity and its implication in the development of novel anti-HER2 drugs including new ADCs in clinical development like trastuzumab deruxtecan (DS-8201).

Conclusions
We suggest potential mechanisms to optimize these compounds and their future clinical implementation.
Host-associated microbiomes are predicted by immune system complexity and climate
Authors: Woodhams Douglas C. , Bletz Molly C. , Becker C. Guilherme , Bender Hayden A. , Buitrago-Rosas Daniel , Diebboll Hannah , Huynh Roger , Kearns Patrick J. , Kueneman Jordan , Kurosawa Emmi , LaBumbard Brandon C. , Lyons Casandra , McNally Kerry , Schliep Klaus , Shankar Nachiket , Tokash-Peters Amanda G. , Vences Miguel , Whetstone Ross 
Published: February 2020

AbstractBackgroundHost-associated microbiomes, the microorganisms occurring inside and on host surfaces, influence evolutionary, immunological, and ecological processes. Interactions between host and microbiome affect metabolism and contribute to host adaptation to changing environments. Meta-analyses of host-associated bacterial communities have the potential to elucidate global-scale patterns of microbial community structure and function. It is possible that host surface-associated (external) microbiomes respond more strongly to variations in environmental factors, whereas internal microbiomes are more tightly linked to host factors.ResultsHere, we use the dataset from the Earth Microbiome Project and accumulate data from 50 additional studies totaling 654 host species and over 15,000 samples to examine global-scale patterns of bacterial diversity and function. We analyze microbiomes from non-captive hosts sampled from natural habitats and find patterns with bioclimate and geophysical factors, as well as land use, host phylogeny, and trophic level/diet. Specifically, external microbiomes are best explained by variations in mean daily temperature range and precipitation seasonality. In contrast, internal microbiomes are best explained by host factors such as phylogeny/immune complexity and trophic level/diet, plus climate.ConclusionsInternal microbiomes are predominantly associated with top-down effects, while climatic factors are stronger determinants of microbiomes on host external surfaces. Host immunity may act on microbiome diversity through top-down regulation analogous to predators in non-microbial ecosystems. Noting gaps in geographic and host sampling, this combined dataset represents a global baseline available for interrogation by future microbial ecology studies.
Paragraph: a graph-based structural variant genotyper for short-read sequence data
Authors: Chen Sai , Krusche Peter , Dolzhenko Egor , Sherman Rachel M. , Petrovski Roman , Schlesinger Felix , Kirsche Melanie , Bentley David R. , Schatz Michael C. , Sedlazeck Fritz J. , Eberle Michael A. 
Published: February 2020

AbstractAccurate detection and genotyping of structural variations (SVs) from short-read data is a long-standing area of development in genomics research and clinical sequencing pipelines. We introduce Paragraph, an accurate genotyper that models SVs using sequence graphs and SV annotations. We demonstrate the accuracy of Paragraph on whole-genome sequence data from three samples using long-read SV calls as the truth set, and then apply Paragraph at scale to a cohort of 100 short-read sequenced samples of diverse ancestry. Our analysis shows that Paragraph has better accuracy than other existing genotypers and can be applied to population-scale studies.