bluuebunny/crossref_metadata_2025_split huggingface dataset:
Altered alcohol consumption during COVID-19 pandemic lockdown
Authors: Steffen Julius , Schlichtiger Jenny , Huber Bruno C. , Brunner Stefan 
Published: May 2021

Abstract
Background
Since the onset of the COVID-19 pandemic in December 2019, many countries around the world have imposed lockdown measures in order to reduce virus spread. Social isolation is known to have a significant psychological impact, potentially triggering alcohol misuse in adults. In our study, we aimed to investigate the effect of COVID-19 lockdown measures on alcohol consumption in adults in Bavaria.

Methods
In this cross-sectional study, we enrolled 2067 participants, with 1961 young adults (mean age 23.3 ± 4.1) and 106 mature adults (mean age 66.7 ± 9.7). Participants were asked to complete a standardized questionnaire, semi-quantitatively evaluating the alcohol drinking behaviour before and during the pandemic lockdown.

Results
After implementation of lockdown, the alteration of alcohol consumption was significantly different between young and mature adults (p <  0.001). Among young adults, 42% reported unchanged drinking behaviour compared to 76% in the mature adult group; 44% of young adults reported to drink less compared to only 7% of mature adults. An increase in alcohol consumption was only reported by 14% of young adults and 17% of mature adults. Interestingly, in the entire cohort, the change of alcohol intake was most pronounced among moderate drinkers (> 0 to < 5 drinks/week) in both age groups (p <  0.001). Ordinal logistic regression revealed female sex, low BMI and younger age to be associated with a decrease in number of self-reported drinks/week.

Conclusion
The COVID-19 pandemic lockdown significantly affected alcohol drinking behaviour. Further studies exploring long-term effects on potential alcohol misuse and the relevance on public health are warranted.

Trial registration
The study was retrospectively registered at ClinicalTrials.gov (NCT04361877) on April 24, 2020.
Understanding the influence of left ventricular assist device inflow cannula alignment and the risk of intraventricular thrombosis
Authors: Neidlin Michael , Liao Sam , Li Zhiyong , Simpson Benjamin , Kaye David M. , Steinseifer Ulrich , Gregory Shaun 
Published: May 2021

Abstract
Background
Adverse neurological events associated with left ventricular assist devices (LVADs) have been suspected to be related to thrombosis. This study aimed to understand the risks of thrombosis with variations in the implanted device orientation. A severely dilated pulsatile patient-specific left ventricle, modelled with computational fluid dynamics, was utilised to identify the risk of thrombosis for five cannulation angles. With respect to the inflow cannula axis directed towards the mitral valve, the other angles were 25° and 20° towards the septum and 20° and 30° towards the free wall.

Results
Inflow cannula angulation towards the free wall resulted in longer blood residence time within the ventricle, slower ventricular washout and reduced pulsatility indices along the septal wall. Based on the model, the ideal inflow cannula alignment to reduce the risk of thrombosis was angulation towards the mitral valve and up to parallel to the septum, avoiding the premature clearance of incoming blood.

Conclusions
This study indicates the potential effects of inflow cannulation angles and may guide optimised implantation configurations; however, the ideal approach will be influenced by other patient factors and is suspected to change over the course of support.
Concurrent smoking and alcohol consumers had higher triglyceride glucose indices than either only smokers or alcohol consumers: a cross-sectional study in Korea
Authors: Baek Wonhee , Lee Ji-Won , Lee Hye Sun , Han Donghee , Choi Su-Yeon , Chun Eun Ju , Han Hae-Won , Park Sung Hak , Sung Jidong , Jung Hae Ok , Lee Hyangkyu , Chang Hyuk-Jae 
Published: May 2021

Abstract
Background
The triglyceride glucose (TyG) index is a noninsulin-based marker for insulin resistance (IR) in general practice. Although smoking and heavy drinking have been regarded as major risk factors for various chronic diseases, there is limited evidence regarding the combined effects of smoking and alcohol consumption on IR. This study aimed to investigate the relationship between the TyG index and smoking and alcohol consumption using two Korean population-based datasets.

Methods
This study included 10,568 adults in the Korean National Health and Nutrition Examination Survey (KNHANES) and 9586 adults in the Korean Initiatives on Coronary Artery Calcification (KOICA) registry datasets. Multivariate logistic analysis was conducted to explore the relationship between smoking and alcohol consumption and the TyG index. To assess the predictive value of smoking and alcohol consumption on high TyG index, the area under the curve (AUC) were compared and net reclassification improvement (NRI) and integrated discrimination improvement (IDI) analyses were derived.

Results
The combined effect of smoking and alcohol consumption was an independent risk factor of a higher TyG index in the KNHANES (adjusted odds ratio: 4.33, P < .001) and KOICA (adjusted odds ratio: 1.94, P < .001) datasets. Adding smoking and alcohol consumption to the multivariate logistic models improved the model performance for the TyG index in the KNHANES (AUC: from 0.817 to 0.829, P < .001; NRI: 0.040, P < .001; IDI: 0.017, P < .001) and KOICA (AUC: from 0.822 to 0.826, P < .001; NRI: 0.025, P = .006; IDI: 0.005, P < .001) datasets.

Conclusions
Smoking and alcohol consumption were independently associated with the TyG index. Concurrent smokers and alcohol consumers were more likely to have a TyG index that was ≥8.8 and higher than the TyG indices of non-users and those who exclusively consumed alcohol or smoking tobacco.
ROS-responsive liposomes with NIR light-triggered doxorubicin release for combinatorial therapy of breast cancer
Authors: Yi Hanxi , Lu Wangxing , Liu Fan , Zhang Guoqing , Xie Feifan , Liu Wenjie , Wang Lei , Zhou Wenhu , Cheng Zeneng 
Published: May 2021

Abstract
Background
Reactive oxygen species (ROS)-responsive drug delivery systems (DDSs) are potential tools to minimize the side effects and substantially enhance the therapeutic efficacy of chemotherapy. However, it is challenging to achieve spatially and temporally controllable and accurate drug release in tumor sites based on ROS-responsive DDSs. To solve this problem, we designed a nanosystem combined photodynamic therapy (PDT) and ROS-responsive chemotherapy.

Methods
Indocyanine green (ICG), an ROS trigger and photosensitizer, and pB-DOX, a ROS-responsive prodrug of doxorubicin (DOX), were coencapsulated in polyethylene glycol modified liposomes (Lipo/pB-DOX/ICG) to construct a combination therapy nanosystem. The safety of nanosystem was assessed on normal HEK-293 cells, and the cellular uptake, intracellular ROS production capacity, target cell toxicity, and combined treatment effect were estimated on human breast cancer cells MDA-MB-231. In vivo biodistribution, biosafety assessment, and combination therapy effects were investigated based on MDA-MB-231 subcutaneous tumor model.

Results
Compared with DOX·HCl, Lipo/pB-DOX/ICG showed higher safety on normal cells. The toxicity of target cells of Lipo/pB-DOX/ICG was much higher than that of DOX·HCl, Lipo/pB-DOX, and Lipo/ICG. After endocytosis by MDA-MB-231 cells, Lipo/pB-DOX/ICG produced a large amount of ROS for PDT by laser irradiation, and pB-DOX was converted to DOX by ROS for chemotherapy. The cell inhibition rate of combination therapy reached up to 93.5 %. After the tail vein injection (DOX equivalent of 3.0 mg/kg, ICG of 3.5 mg/kg) in mice bearing MDA-MB-231 tumors, Lipo/pB-DOX/ICG continuously accumulated at the tumor site and reached the peak at 24 h post injection. Under irradiation at this time point, the tumors in Lipo/pB-DOX/ICG group almost disappeared with 94.9 % tumor growth inhibition, while those in the control groups were only partially inhibited. Negligible cardiotoxicity and no treatment-induced side effects were observed.

Conclusions
Lipo/pB-DOX/ICG is a novel tool for on-demand drug release at tumor site and also a promising candidate for controllable and accurate combinatorial tumor therapy.
Intracranial VCAM1 at time of mechanical thrombectomy predicts ischemic stroke severity
Authors: Maglinger Benton , Sands Madison , Frank Jacqueline A. , McLouth Christopher J. , Trout Amanda L. , Roberts Jill M. , Grupke Stephen , Turchan-Cholewo Jadwiga , Stowe Ann M. , Fraser Justin F. , Pennypacker Keith R. 
Published: May 2021

Abstract
Background
Emergent large vessel occlusion (ELVO) strokes are devastating ischemic vascular events for which novel treatment options are needed. Using vascular cell adhesion molecule 1 (VCAM1) as a prototype, the objective of this study was to identify proteomic biomarkers and network signaling functions that are potential therapeutic targets for adjuvant treatment for mechanical thrombectomy.

Methods
The blood and clot thrombectomy and collaboration (BACTRAC) study is a continually enrolling tissue bank and registry from stroke patients undergoing mechanical thrombectomy. Plasma proteins from intracranial (distal to clot) and systemic arterial blood (carotid) were analyzed by Olink Proteomics for N=42 subjects. Statistical analysis of plasma proteomics used independent sample t tests, correlations, linear regression, and robust regression models to determine network signaling and predictors of clinical outcomes. Data and network analyses were performed using IBM SPSS Statistics, SAS v 9.4, and STRING V11.

Results
Increased systemic (p<0.001) and intracranial (p=0.013) levels of VCAM1 were associated with the presence of hypertension. Intracranial VCAM1 was positively correlated to both infarct volume (p=0.032; r=0.34) and edema volume (p=0.026; r=0.35). The %∆ in NIHSS from admittance to discharge was found to be significantly correlated to both systemic (p=0.013; r = −0.409) and intracranial (p=0.011; r = −0.421) VCAM1 levels indicating elevated levels of systemic and intracranial VCAM1 are associated with reduced improvement of stroke severity based on NIHSS from admittance to discharge. STRING-generated analyses identified biologic functional descriptions as well as function-associated proteins from the predictive models of infarct and edema volume.

Conclusions
The current study provides novel data on systemic and intracranial VCAM1 in relation to stroke comorbidities, stroke severity, functional outcomes, and the role VCAM1 plays in complex protein-protein signaling pathways. These data will allow future studies to develop predictive biomarkers and proteomic targets for drug development to improve our ability to treat a devastating pathology.
Strategies to promote the implementation of Screening, Brief Intervention, and Referral to Treatment (SBIRT) in healthcare settings: a scoping review
Authors: Thoele Kelli , Moffat Laura , Konicek Stephanie , Lam-Chi Monika , Newkirk Erica , Fulton Janet , Newhouse Robin 
Published: May 2021

Abstract
Background
Screening, brief intervention, and referral to treatment (SBIRT), is an approach for the prevention and treatment of substance use disorders, but is often underutilized in healthcare settings. Although the implementation of SBIRT is challenging, the use of multi-faceted and higher intensity strategies are more likely to result in the successful incorporation of SBIRT into practice in primary care settings. SBIRT may be used in different healthcare settings, and the context for implementation and types of strategies used to support implementation may vary by setting. The purpose of this scoping review is to provide an overview regarding the use of strategies to support implementation of SBIRT in all healthcare settings and describe the associated outcomes.

Methods
A scoping review was conducted using CINAHL Complete, HealthBusiness FullTEXT, PsycINFO, PubMed, and Embase to search for articles published in English prior to September 2019. The search returned 462 citations, with 18 articles included in the review. Two independent reviewers extracted data from each article regarding the theory, design, timeline, location, setting, patient population, substance type, provider, sample size and type, implementation strategies, and implementation outcomes. The reviewers entered all extracted data entered into a table and then summarized the results.

Results
Most of the studies were conducted in the United States in primary care or emergency department settings, and the majority of studies focused on SBIRT to address alcohol use in adults. The most commonly used strategies to support implementation included training and educating stakeholders or developing stakeholder interrelationships. In contrast, only a few studies engaged patients or consumers in the implementation process. Efforts to support implementation often resulted in an increase in screening, but the evidence regarding the brief intervention is less clear, and most studies did not assess the reach or adoption of the referral to treatment.

Discussion
In addition to summarizing the strategies used to increase reach and adoption of SBIRT in healthcare settings, this scoping review identified multiple gaps in the literature. Two major gaps include implementation of SBIRT in acute care settings and the application of implementation theories to inform healthcare efforts to enable use of SBIRT.
How therapists and patients need to develop a clinical feedback system after 18 months of use in a practice-research network: a qualitative study
Authors: Moltu Christian , McAleavey Andrew A. , Helleseth Marianne M. , Møller Geir Helge , Nordberg Sam S. 
Published: May 2021

AbstractBackgroundA personalized computer-adaptive system for clinical feedback and routine outcome monitoring in mental health, Norse Feedback aims to bridge the needs for standardized and idiographic measures in ordinary practice.MethodsItem response theory analyses of completed treatment processes (n = 800) informed a qualitative study comprising individual in-depth interviews and focus groups with patients (n = 9) and clinicians (n = 10). The research question was: How do clinicians and patients contribute to developing a clinical feedback system in a continuous process aimed at refining its clinical usefulness?ResultsWe conducted thematic analyses and found five themes: 1. Added clinical needs, 2. Needs for re-organizing the clinician report, 3.Needs for differentiation of clinical content, 4. User-interface needs, and 5. Item level suggestions.ConclusionIn this article, we detail resulting needs for continuous adaptation to practice, and discuss implications of the concrete experiences with the Norse action research program for the larger field of ROM/CFS implementation.
Functional mapping of androgen receptor enhancer activity
Authors: Huang Chia-Chi Flora , Lingadahalli Shreyas , Morova Tunc , Ozturan Dogancan , Hu Eugene , Yu Ivan Pak Lok , Linder Simon , Hoogstraat Marlous , Stelloo Suzan , Sar Funda , van der Poel Henk , Altintas Umut Berkay , Saffarzadeh Mohammadali , Le Bihan Stephane , McConeghy Brian , Gokbayrak Bengul , Feng Felix Y. , Gleave Martin E. , Bergman Andries M. , Collins Colin , Hach Faraz , Zwart Wilbert , Emberly Eldon , Lack Nathan A. 
Published: May 2021

AbstractBackgroundAndrogen receptor (AR) is critical to the initiation, growth, and progression of prostate cancer. Once activated, the AR binds to cis-regulatory enhancer elements on DNA that drive gene expression. Yet, there are 10–100× more binding sites than differentially expressed genes. It is unclear how or if these excess binding sites impact gene transcription.ResultsTo characterize the regulatory logic of AR-mediated transcription, we generated a locus-specific map of enhancer activity by functionally testing all common clinical AR binding sites with Self-Transcribing Active Regulatory Regions sequencing (STARRseq). Only 7% of AR binding sites displayed androgen-dependent enhancer activity. Instead, the vast majority of AR binding sites were either inactive or constitutively active enhancers. These annotations strongly correlated with enhancer-associated features of both in vitro cell lines and clinical prostate cancer samples. Evaluating the effect of each enhancer class on transcription, we found that AR-regulated enhancers frequently interact with promoters and form central chromosomal loops that are required for transcription. Somatic mutations of these critical AR-regulated enhancers often impact enhancer activity.ConclusionsUsing a functional map of AR enhancer activity, we demonstrated that AR-regulated enhancers act as a regulatory hub that increases interactions with other AR binding sites and gene promoters.
Super-resolution visualization and modeling of human chromosomal regions reveals cohesin-dependent loop structures
Authors: Hao Xian , Parmar Jyotsana J. , Lelandais Benoît , Aristov Andrey , Ouyang Wei , Weber Christian , Zimmer Christophe 
Published: May 2021

Abstract
Background
The 3D organization of the chromatin fiber in cell nuclei plays a key role in the regulation of gene expression. Genome-wide techniques to score DNA-DNA contacts, such as Hi-C, reveal the partitioning of chromosomes into epigenetically defined active and repressed compartments and smaller “topologically associated” domains. These domains are often associated with chromatin loops, which largely disappear upon removal of cohesin. Because most Hi-C implementations average contact frequencies over millions of cells and do not provide direct spatial information, it remains unclear whether and how frequently chromatin domains and loops exist in single cells.

Results
We combine 3D single-molecule localization microscopy with a low-cost fluorescence labeling strategy that does not denature the DNA, to visualize large portions of single human chromosomes in situ at high resolution. In parallel, we develop multi-scale, whole nucleus polymer simulations, that predict chromatin structures at scales ranging from 5 kb up to entire chromosomes. We image chromosomes in G1 and M phase and examine the effect of cohesin on interphase chromatin structure. Depletion of cohesin leads to increased prevalence of loose chromatin stretches, increased gyration radii, and reduced smoothness of imaged chromatin regions. By comparison to model predictions, we estimate that 6–25 or more purely cohesin-dependent chromatin loops coexist per megabase of DNA in single cells, suggesting that the vast majority of the genome is enclosed in loops.

Conclusion
Our results provide new constraints on chromatin structure and showcase an affordable non-invasive approach to study genome organization in single cells.
Cellular and transcriptomic analyses reveal two-staged chloroplast biogenesis underpinning photosynthesis build-up in the wheat leaf
Authors: Loudya Naresh , Mishra Priyanka , Takahagi Kotaro , Uehara-Yamaguchi Yukiko , Inoue Komaki , Bogre Laszlo , Mochida Keiichi , López-Juez Enrique 
Published: May 2021

Abstract
Background
The developmental gradient in monocot leaves has been exploited to uncover leaf developmental gene expression programs and chloroplast biogenesis processes. However, the relationship between the two is barely understood, which limits the value of transcriptome data to understand the process of chloroplast development.

Results
Taking advantage of the developmental gradient in the bread wheat leaf, we provide a simultaneous quantitative analysis for the development of mesophyll cells and of chloroplasts as a cellular compartment. This allows us to generate the first biologically-informed gene expression map of this leaf, with the entire developmental gradient from meristematic to fully differentiated cells captured. We show that the first phase of plastid development begins with organelle proliferation, which extends well beyond cell proliferation, and continues with the establishment and then the build-up of the plastid genetic machinery. The second phase is marked by the development of photosynthetic chloroplasts which occupy the available cellular space. Using a network reconstruction algorithm, we predict that known chloroplast gene expression regulators are differentially involved across those developmental stages.

Conclusions
Our analysis generates both the first wheat leaf transcriptional map and one of the most comprehensive descriptions to date of the developmental history of chloroplasts in higher plants. It reveals functionally distinct plastid and chloroplast development stages, identifies processes occurring in each of them, and highlights our very limited knowledge of the earliest drivers of plastid biogenesis, while providing a basis for their future identification.
Serosurvey and associated risk factors of anti-Toxocara spp. antibodies in bovines from slaughterhouses of southeastern Brazil
Authors: Giudice Paula Andreia Fabris , Lescano Susana Angélica Zevallos , Gonzáles William Henry Roldan , Giuffrida Rogério , Bandeira Fernanda Nobre , Kmetiuk Louise Bach , Pires dos Santos Andrea , Biondo Alexander Welker , Santarém Vamilton Alvares 
Published: May 2021

Abstract
Background
Toxocariasis, caused by a nematode species of the genus Toxocara, has been described as one of the most prevalent zoonotic helminthiases worldwide. Human transmission may occur by ingesting Toxocara spp. larvae from raw or undercooked meat or organs; however, no comprehensive serosurvey study has been conducted to date investigating the role of cattle as paratenic hosts. The aim of the study reported here was to assess the prevalence of anti-Toxocara spp. antibodies and associated risk factors in bovines from two slaughterhouses located in Presidente Prudente, southeastern Brazil.

Methods
Blood samples were collected and tested by indirect enzyme-linked immunosorbent assay (ELISA). Cattle farmers voluntarily responded to an epidemiologic questionnaire.

Results
Overall, 213 of the 553 (38.5%) bovine samples were assessed as seropositive for anti-Toxocara spp. antibodies by indirect ELISA. Multivariate analysis revealed that the source of beef cattle and the presence of dogs or cats at the farm were associated with seropositivity. The use of feedlot systems was associated with lower likelihood of seropositivity.

Conclusions
These results indicate a high level of anti-Toxocara seropositivity in slaughterhouse cattle, with potentially contaminated meat posing an infection risk to humans. In addition, the presence of dogs and cats where the slaughtered beef cattle were raised was statistically associated with bovine seropositivity, probably due to the overlapping environment at the farm and the lack of pet deworming. The use of feedlot systems was a protective factor likely due to the absence of dog and cat contact, elevated feeding troughs that avoid contact with contaminated soil or grass, and younger age at slaughter of feedlot cattle. In summary, bovines may be used as environmental sentinels of Toxocara spp. contamination, and high seropositivity of slaughterhouse cattle may indicate a potential risk of human toxocariasis through the ingestion of raw or undercooked contaminated meat.

Graphical Abstract
Double anus in an Ixodes scapularis nymph, a medically important tick vector
Authors: Taank Vikas , Lattanzio Frank A. , Sultana Hameeda , Neelakanta Girish 
Published: May 2021

Abstract
Background
Ixodes scapularis ticks are medically important arthropod vectors that transmit several pathogens to humans. The observations of morphological abnormalities, including nanism, missing leg, extra leg, and gynandromorphism, have been reported in these ticks. In this study, we report the presence of two anuses in a laboratory-reared I. scapularis nymph.

Results
Larval ticks were allowed to feed on mice and to molt to nymphs. Two anuses were observed in one of the freshly molted nymphs. Stereo and scanning electron microscopy confirmed the presence of two anuses in one nymph within a single anal groove.

Conclusions
This report confirms the rare occurrence of double anus in I. scapularis.

Graphical Abstract