bluuebunny/crossref_metadata_2025_split huggingface dataset:
Statistical and bioinformatic analysis of hemimethylation patterns in non-small cell lung cancer
Authors: Sun Shuying , Zane Austin , Fulton Carolyn , Philipoom Jasmine 
Published: March 2021

AbstractBackgroundDNA methylation is an epigenetic event involving the addition of a methyl-group to a cytosine-guanine base pair (i.e., CpG site). It is associated with different cancers. Our research focuses on studying non-small cell lung cancer hemimethylation, which refers to methylation occurring on only one of the two DNA strands. Many studies often assume that methylation occurs on both DNA strands at a CpG site. However, recent publications show the existence of hemimethylation and its significant impact. Therefore, it is important to identify cancer hemimethylation patterns.MethodsIn this paper, we use the Wilcoxon signed rank test to identify hemimethylated CpG sites based on publicly available non-small cell lung cancer methylation sequencing data. We then identify two types of hemimethylated CpG clusters, regular and polarity clusters, and genes with large numbers of hemimethylated sites. Highly hemimethylated genes are then studied for their biological interactions using available bioinformatics tools.ResultsIn this paper, we have conducted the first-ever investigation of hemimethylation in lung cancer. Our results show that hemimethylation does exist in lung cells either as singletons or clusters. Most clusters contain only two or three CpG sites. Polarity clusters are much shorter than regular clusters and appear less frequently. The majority of clusters found in tumor samples have no overlap with clusters found in normal samples, and vice versa. Several genes that are known to be associated with cancer are hemimethylated differently between the cancerous and normal samples. Furthermore, highly hemimethylated genes exhibit many different interactions with other genes that may be associated with cancer. Hemimethylation has diverse patterns and frequencies that are comparable between normal and tumorous cells. Therefore, hemimethylation may be related to both normal and tumor cell development.ConclusionsOur research has identified CpG clusters and genes that are hemimethylated in normal and lung tumor samples. Due to the potential impact of hemimethylation on gene expression and cell function, these clusters and genes may be important to advance our understanding of the development and progression of non-small cell lung cancer.
Using a hybrid agent-based and equation based model to test school closure policies during a measles outbreak
Authors: Hunter Elizabeth , Kelleher John D. 
Published: March 2021

Abstract
Background
In order to be prepared for an infectious disease outbreak it is important to know what interventions will or will not have an impact on reducing the outbreak. While some interventions might have a greater effect in mitigating an outbreak, others might only have a minor effect but all interventions will have a cost in implementation. Estimating the effectiveness of an intervention can be done using computational modelling. In particular, comparing the results of model runs with an intervention in place to control runs where no interventions were used can help to determine what interventions will have the greatest effect on an outbreak.

Methods
To test the effects of a school closure policy on the spread of an infectious disease (in this case measles) we run simulations closing schools based on either the proximity of the town to the initial outbreak or the centrality of the town within the network of towns in the simulation. To do this we use a hybrid model that combines an agent-based model with an equation-based model. In our analysis, we use three measures to compare the effects of different intervention strategies: the total number of model runs leading to an outbreak, the total number of infected agents, and the geographic spread of outbreaks.

Results
Our results show that closing down the schools in the town where an outbreak begins and the town with the highest in degree centrality provides the largest reduction in percent of runs leading to an outbreak as well as a reduction in the geographic spread of the outbreak compared to only closing down the town where the outbreak begins. Although closing down schools in the town with the closest proximity to the town where the outbreak begins also provides a reduction in the chance of an outbreak, we do not find the reduction to be as large as when the schools in the high in degree centrality town are closed.

Conclusions
Thus we believe that focusing on high in degree centrality towns during an outbreak is important in reducing the overall size of an outbreak.
What do patients consulting in a free sexual health center know about HIV transmission and post-exposure prophylaxis?
Authors: Duteil Christelle , de La Rochebrochard Elise , Piron Prescillia , Segouin Christophe , Troude Pénélope 
Published: March 2021

AbstractBackgroundScreening, condom use and post-exposure prophylaxis (PEP) are among existing HIV prevention strategies. However, efficient use of these strategies requires that patients have an adequate knowledge of HIV transmission routes and awareness of risk behaviors. This study aimed to assess knowledge about HIV transmission among patients who attended a free HIV and sexually transmitted infection (STI) screening center in Paris, France, and to explore the patient profiles associated with HIV-related knowledge.MethodsThis observational cross-sectional study included 2002 patients who attended for STI testing from August 2017 through August 2018 and completed a self-administered electronic questionnaire. Based on incorrect answers regarding HIV transmission, two outcomes were assessed: lack of knowledge and false beliefs. Factors associated with these two outcomes were explored using univariate and multivariate logistic regressions.ResultsOnly 3.6% of patients did not know about HIV transmission through unprotected sexual intercourse and/or by sharing needles. More than one third of patients (36.4%) had at least one false belief, believing that HIV could be transmitted by sharing a drink (9.7%), kissing (17.6%) or using public toilets (27.5%). A low educational level and no previous HIV testing were associated in multivariate analyses with both lack of knowledge and false beliefs. Age and sexual orientation were also associated with false beliefs. Furthermore, 55.6% of patients did not know that post-exposure prophylaxis consists of taking emergency treatment as soon as possible after risky intercourse.ConclusionsAlthough the main HIV transmission routes are well known, false beliefs persist and knowledge regarding PEP needs to be improved. Prevention campaigns must focus on these themes which appear as a complementary strategy to pre-exposure prophylaxis to reduce HIV infection.
Cockroach exposure and perceived stress interact to predict clinical outcomes in childhood asthma
Authors: Rabito Felicia A. , Werthmann Derek , He Hua , Madkour Aubrey S. , Arroyave Whitney D. , Sever Michelle L. , LaVeist Thomas A. 
Published: March 2021

Abstract
Background
Nonpharmacologic interventions for asthma management rely on identification and mitigation of important asthma triggers. Cockroach exposure is strongly associated with asthma morbidity. It is also associated with stress, another risk factor for asthma. Despite high prevalence of both in vulnerable populations, the impact of joint exposure has not been examined.

Methods
Participants included 173 children with asthma in New Orleans, Louisiana. Cockroach exposure was based on visual inspection using standard protocols. Caregiver stress was measured using Cohen’s 4-item Perceived Stress Scale. Outcomes included unscheduled clinic or emergency department (ED) visits, hospitalization, and pulmonary function. Multivariable logistic regression was performed to assess independent effects of the exposure on the outcome and effect modification was examined in stratified analysis based on stress. Path analysis to explore the mediation effect by stress was performed using a probit link with parameters based on Bayes’ method with non-informative priors.

Results
Adjusting for stress and other covariates, cockroach exposure was associated with unscheduled clinic/ED visits (aOR = 6.2; 95% CI 1.8, 21.7). Positive associations were also found for hospitalization and FEV1 < 80%. High stress modified the relationship with unscheduled clinic/ED visits (high aOR = 7.7 95% CI 1.0, 60.2, versus normal aOR = 4.1 95% CI 0.8, 21.9). Path models identified direct and indirect effects (p = 0.05) indicating that a majority of the total effect on unscheduled clinic/ED visits is attributed directly to cockroach exposure.

Conclusion
The strong association between cockroach exposure and asthma morbidity is not due to uncontrolled confounding by stress. The combination of cockroach exposure and high stress, common in urban homes, are modifiable factors associated with poor asthma outcomes.
Does breaking up prolonged sitting improve cognitive functions in sedentary adults? A mapping review and hypothesis formulation on the potential physiological mechanisms
Authors: Chandrasekaran Baskaran , Pesola Arto J. , Rao Chythra R. , Arumugam Ashokan 
Published: March 2021

Abstract
Background
Prolonged (excessive) sitting is detrimentally associated with cardiovascular, metabolic and mental health. Moreover, prolonged sitting has been associated with poor executive function, memory, attention and visuospatial skills, which are important cognitive aspects of work performance. Breaking up prolonged sitting with standing or light-intensity exercises at the workplace is recognized as a potential measure in improving cognition. However, preliminary evidence, primarily from acute laboratory experiments, has enabled formulating hypothesis on the possible mechanistic pathways. Hence, the aim of this mapping review is to gather preliminary evidence and substantiate possible physiological mechanisms underpinning the putative effects of breaking prolonged sitting on improving cognitive function among sedentary office workers.

Mapping method
We searched four databases to identify relevant studies that explored the effects of uninterrupted sitting on cognitive function. First, we introduce how prolonged sitting increases the risks of hyperglycemia, autonomic stability, inflammation, adverse hormonal changes and restrictions in cerebral blood flow (CBF) and alters cognitive function. Second, we elucidate the direct and indirect effects of breaking up prolonged sitting time that may prevent a decline in cognitive performance by influencing glycaemic variability, autonomic stability, hormones (brain derived neurotrophic factor, dopamine, serotonin), vascular functions, and CBF. We highlight the importance of breaking up prolonged sitting on metabolic, vascular and endocrine functions, which in turn may improve cognitive functions and eventually foster work productivity. Improved synaptic transmission or neuroplasticity due to increased brain glucose and mitochondrial metabolism, increased endothelial shear and CBF, increased brain neurotrophic factors (dopamine) and accelerated anti-inflammatory functions are some of the hypothetical mechanisms underpinning improved cognitive functions.

Conclusion
We postulate that improving cognitive function by breaking up prolonged sitting periods is biologically plausible with the myriad of (suggested) physiological mechanisms. Future experimental studies to ascertain the aforementioned hypothetical mechanisms and clinical trials to break sedentary behavior and improve cognitive functions in sedentary office workers are warranted.
Locking plate combined with titanium cable for Neer type II distal clavicle fractures
Authors: Zhang Fan , Fu Qiang , Li Yongchuan , Lu Nan , Chen Aimin , Zhao Liangyu 
Published: March 2021

Abstract
Background
There is controversy about the optimal strategy treatment of unstable distal clavicle fractures. We explored use of a surgical strategy: combination of a distal clavicle locking plate and a titanium cable. The purpose of this retrospective case series study was to evaluate the clinical outcomes of this new strategy in treating Neer type II distal clavicle fractures.

Methods
Twenty-one patients with Neer type II distal clavicle fracture were treated with a distal clavicle locking plate and a titanium cable. All patients were followed for at least one year. We retrospectively collected and reviewed follow-up data. The clinical outcomes were assessed for union rate, functional score, and complication rate.

Results
All patients achieved bony union within 6 months. The average follow-up period was 20.6 months (range12–48 months). The mean Constant score at one-year follow-up was 94.6 ± 3.3 (range 84–98), and the mean UCLA (University of California, Los Angeles) score was 33.3 ± 2.6 (range 27–35). Only one complication (wound infection) was observed during follow-up. Two patients received another operation for implant removal due to local irritation.

Conclusions
Use of a distal clavicle locking plate in combination with a titanium cable for treatment of Neer type II fractures results in high union rate, a low complication rate, and good shoulder function. This combined surgical strategy can be considered an effective method for treating unstable distal clavicle fractures.
Increased frequency of β cells with abnormal NKX6.1 expression in type 2 diabetes but not in subjects with higher risk for type 2 diabetes
Authors: Liu Tengli , Sun Peng , Zou Jiaqi , Wang Le , Wang Guanqiao , Liu Na , Liu Yaojuan , Ding Xuejie , Zhang Boya , Liang Rui , Wang Shusen , Shen Zhongyang 
Published: March 2021

Abstract
Background
NKX6.1 is a transcription factor for insulin, as well as a marker for β cell maturity. Abnormal NKX6.1 expression in β cells, such as translocation from the nucleus to cytoplasm or lost expression, has been shown as a marker for β cell dedifferentiation.

Methods
We obtained pancreatic sections from organ donors and immunofluorescence staining with NKX6.1 and insulin was performed to characterize NKX6.1 expression in subjects with or without type 2 diabetes mellitus (T2DM).

Results
Our results showed that cells with insulin expression but no nucleic NKX6.1 expression (NKX6.1Nuc-Ins+), and cells with cytoplasmic NKX6.1 expression but no insulin expression (NKX6.1cytIns−) were significantly increased in T2DM subjects and positively correlated with glycated hemoglobin (HbA1c), indicating the elevated β cell dedifferentiation with NKX6.1 inactivation in T2DM. To investigate whether β cell dedifferentiation has initiated in subjects with higher risks for T2DM, we next analyzed the association between β-cell dedifferentiation level in ND subjects with different ages, body mass index, and HbA1c. The results showed the absolute number and percentage of dedifferentiated β cells with NKX6.1 inactivation did not significantly change in subjects with advanced aging, obesity, or modest hyperglycemia, indicating that the β cell dedifferentiation might mainly occur after T2DM was diagnosed.

Conclusion
Our results suggested that NKX6.1 expression in β cells was changed in type 2 diabetic subjects, evidenced by significantly increased NKX6.1Nuc-Ins+ and NKX6.1cytIns− cells. This abnormality did not occur more frequently in subjects with a higher risk for T2DM, suggesting that β cell dedifferentiation might be secondary to the pathological changes in T2DM.
Mortality due to primary brain tumours in China and detection rate in people with suspected symptoms: a nationally representative cross-sectional survey
Authors: Jiang Bin , Liu Hongmei , Sun Dongling , Sun Haixin , Ru Xiaojuan , Fu Jie , Ge Siqi , Wang Wenzhi 
Published: March 2021

Abstract
Background and purpose
Epidemiological data on primary brain tumours (PBTs) are lacking due to the difficulty in case ascertainment among the population. Thus, we aimed to estimate mortality due to PBTs in China nationwide and the detection rate in people with suspected symptoms.

Methods
A multistage, complex sampling survey regarding mortality due to PBTs in Chinese individuals was carried out by reviewing all causes of death within a year. The detection rates in people with suspected symptoms were estimated based on PBT symptom screening and neurologist reviews and compared between groups by logistic regression analysis.

Results
Weighted mortality due to PBT was 1.6 (0.8–3.3) per 100,000 population in Chinese individuals, 1.8 (0.7–4.6) per 100,000 population in men, and 1.5 (0.5–4.5) per 100,000 population in women. Among 14,990 people with suspected symptoms, the PBT detection rate was 306.9 (95% CI 224.7–409.3) per 100,000 population in the total population, 233.0 (95% CI 135.7–373.1) per 100,000 population in men, and 376.9 (95% CI 252.4–546.3) per 100,000 population in women. People with an unsteady gait (OR 2.46; 95% CI 1.09–5.51; P=0.029), visual anomalies (3.84; 1.88–7.85; P<0.001), and headache (2.06; 1.10–3.86; P=0.023) were more likely to have a brain tumour than those without corresponding symptoms, while people with dizziness/vertigo were less likely to have a brain tumour than those without corresponding symptoms (0.45; 0.23–0.87; P=0.017).

Conclusions
Mortality due to PBT in China was low, with a nationwide estimate of 21,215 (10,427–43,165) deaths attributable to PBTs annually. However, the detection rate of PBTs can be greatly improved based on symptom screening in the population.
Fluid proteomics of CSF and serum reveal important neuroinflammatory proteins in blood–brain barrier disruption and outcome prediction following severe traumatic brain injury: a prospective, observational study
Authors: Lindblad Caroline , Pin Elisa , Just David , Al Nimer Faiez , Nilsson Peter , Bellander Bo-Michael , Svensson Mikael , Piehl Fredrik , Thelin Eric Peter 
Published: March 2021

AbstractBackgroundSevere traumatic brain injury (TBI) is associated with blood–brain barrier (BBB) disruption and a subsequent neuroinflammatory process. We aimed to perform a multiplex screening of brain enriched and inflammatory proteins in blood and cerebrospinal fluid (CSF) in order to study their role in BBB disruption, neuroinflammation and long-term functional outcome in TBI patients and healthy controls.MethodsWe conducted a prospective, observational study on 90 severe TBI patients and 15 control subjects. Clinical outcome data, Glasgow Outcome Score, was collected after 6–12 months. We utilized a suspension bead antibody array analyzed on a FlexMap 3D Luminex platform to characterize 177 unique proteins in matched CSF and serum samples. In addition, we assessed BBB disruption using the CSF-serum albumin quotient (QA), and performed Apolipoprotein E-genotyping as the latter has been linked to BBB function in the absence of trauma. We employed pathway-, cluster-, and proportional odds regression analyses. Key findings were validated in blood samples from an independent TBI cohort.ResultsTBI patients had an upregulation of structural CNS and neuroinflammatory pathways in both CSF and serum. In total, 114 proteins correlated withQA, among which the top-correlated proteins were complement proteins. A cluster analysis revealed protein levels to be strongly associated with BBB integrity, but not carriage of the Apolipoprotein E4-variant. Among cluster-derived proteins, innate immune pathways were upregulated. Forty unique proteins emanated as novel independent predictors of clinical outcome, that individually explained ~ 10% additional model variance. Among proteins significantly different between TBI patients with intact or disrupted BBB, complement C9 in CSF (p = 0.014, ΔR2 = 7.4%) and complement factor B in serum (p = 0.003, ΔR2 = 9.2%) were independent outcome predictors also following step-down modelling.ConclusionsThis represents the largest concomitant CSF and serum proteomic profiling study so far reported in TBI, providing substantial support to the notion that neuroinflammatory markers, including complement activation, predicts BBB disruption and long-term outcome. Individual proteins identified here could potentially serve to refine current biomarker modelling or represent novel treatment targets in severe TBI.
Take one for the team: on the time efficiency of application-level buffer-aided relaying in edge cloud communication
Authors: Li Zheng , Millar-Bilbao Francisco , Rojas-Durán Gonzalo , Ladra Susana 
Published: March 2021

Abstract
Background
Adding buffers to networks is part of the fundamental advance in data communication. Since edge cloud computing is based on the heterogeneous collaboration network model in a federated environment, it is natural to consider buffer-aided data communication for edge cloud applications. However, the existing studies generally pursue the beneficial features of buffering at a cost of time, not to mention that many investigations are focused on lower-layer data packets rather than application-level communication transactions.

Aims
Driven by our argument against the claim that buffers “can introduce additional delay to the communication between the source and destination”, this research aims to investigate whether or not (and if yes, to what extent) the application-level buffering mechanism can improve the time efficiency in edge-cloud data transmissions.

Method
To collect empirical evidence for the theoretical discussion, we built up a testbed to simulate a remote health monitoring system, and conducted both experimental and modeling investigations into the first-in-first-served (FIFS) and buffer-aided data transmissions at a relay node in the system.

Results
An empirical inequality system is established for revealing the time efficiency of buffer-aided edge cloud communication. For example, given the reference of transmitting the 11th data entity in the FIFS manner, the inequality system suggests buffering up to 50 data entities into one transmission transaction on our testbed.

Conclusions
Despite the trade-off benefits (e.g., energy efficiency and fault tolerance) of buffering data, our investigation argues that the buffering mechanism can also speed up data transmission under certain circumstances, and thus it would be worth taking data buffering into account when designing and developing edge cloud applications even in the time-critical context.
Ultrasensitive assays for detection of plasma tau and phosphorylated tau 181 in Alzheimer’s disease: a systematic review and meta-analysis
Authors: Ding Xulong , Zhang Shuting , Jiang Lijun , Wang Lu , Li Tao , Lei Peng 
Published: March 2021

AbstractA lack of convenient and reliable biomarkers for diagnosis and prognosis is a common challenge for neurodegenerative diseases such as Alzheimer’s disease (AD). Recent advancement in ultrasensitive protein assays has allowed the quantification of tau and phosphorylated tau proteins in peripheral plasma. Here we identified 66 eligible studies reporting quantification of plasma tau and phosphorylated tau 181 (ptau181) using four ultrasensitive methods. Meta-analysis of these studies confirmed that the AD patients had significantly higher plasma tau and ptau181 levels compared with controls, and that the plasma tau and ptau181 could predict AD with high-accuracy area under curve of the Receiver Operating Characteristic. Therefore, plasma tau and plasma ptau181 can be considered as biomarkers for AD diagnosis.