bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analyzing the demographic, spatial, and temporal factors influencing social contact patterns in U.S. and implications for infectious disease spread
Authors: Dorélien Audrey M. , Ramen Aparna , Swanson Isabella , Hill Rachelle 
Published: September 2021

Abstract
Background
Diseases such as COVID-19 are spread through social contact. Reducing social contacts is required to stop disease spread in pandemics for which vaccines have not yet been developed. However, existing data on social contact patterns in the United States (U.S.) is limited.

Method
We use American Time Use Survey data from 2003–2018 to describe and quantify the age-pattern of disease-relevant social contacts. For within-household contacts, we construct age-structured contact duration matrices (who spends time with whom, by age). For both within-household and non-household contacts, we also estimate the mean number and duration of contact by location. We estimate and test for differences in the age-pattern of social contacts based on demographic, temporal, and spatial characteristics.

Results
The mean number and duration of social contacts vary by age. The biggest gender differences in the age-pattern of social contacts are at home and at work; the former appears to be driven by caretaking responsibilities.
Non-Hispanic Blacks have a shorter duration of contact and fewer social contacts than non-Hispanic Whites. This difference is largely driven by fewer and shorter contacts at home. Pre-pandemic, non-Hispanic Blacks have shorter durations of work contacts. Their jobs are more likely to require close physical proximity, so their contacts are riskier than those of non-Hispanic Whites. Hispanics have the highest number of household contacts and are also more likely to work in jobs requiring close physical proximity than non-Hispanic Whites.
With the exceptions of work and school contacts, the duration of social contact is higher on weekends than on weekdays. Seasonal differences in the total duration of social contacts are driven by school-aged respondents who have significantly shorter contacts during the summer months. Contact patterns did not differ by metro status. Age patterns of social contacts were similar across regions.

Conclusion
Social contact patterns differ by age, race and ethnicity, and gender. Other factors besides contact patterns may be driving seasonal variation in disease incidence if school-aged individuals are not an important source of transmission. Pre-pandemic, there were no spatial differences in social contacts, but this finding has likely changed during the pandemic.
Spatial spillover and COVID-19 spread in the U.S.
Authors: Ulimwengu John , Kibonge Aziza 
Published: September 2021

AbstractBackgroundThis research estimates the effects of vulnerability on the spread of COVID-19 cases across U.S. counties. Vulnerability factors (Socioeconomic Status, Minority Status & Language, Housing type, Transportation, Household Composition & Disability, Epidemiological Factors, Healthcare system Factors, High-risk Environments, and Population density) do not only influence an individual’s likelihood of getting infected but also influence the likelihood of his/her neighbors getting infected. Thus, spatial interactions occurring among individuals are likely to lead to spillover effects which may cause further virus transmission.MethodsThis research uses the COVID-19 community index (CCVI), which defines communities likely vulnerable to the impact of the pandemic and captures the multi-dimensionality of vulnerability. The spatial Durbin model was used to estimate the spillover effects of vulnerability to COVID-19 in U.S. counties, from May 1 to December 15, 2020.ResultsThe findings confirm the existence of spatial spillover effects; with indirect effects (from neighboring counties) dominating the direct effects (from county-own vulnerability level). This not only validates social distancing as a strategy to contain the spread of the pandemic but also calls for comprehensive and coordinated approach to fight its effects. By keeping vulnerability factors constant but varying the number of reported infected cases every 2 weeks, we found that marginal effects of vulnerability vary significantly across counties. This might be the reflection of both the changing intensity of the pandemic itself but also the lack of consistency in the measures implemented to combat it.ConclusionOverall, the results indicate that high vulnerability in Minority, Epidemiological factors, Healthcare System Factors, and High-Risk Environments in each county and adjacent counties leads to an increase in COVID-19 confirmed cases.
Age-related increase in muscle stiffness is muscle length dependent and associated with muscle force in senior females
Authors: Xu Jingfei , Fu Siu Ngor , Hug François 
Published: September 2021

AbstractBackgroundIn aging, muscle stiffness is considered as one of the factors associated with the reduction of force generation capability. There have been inconsistent findings on age-related alteration in the passive stiffness of quadriceps muscle in the female adults. Thus, the aim of this study was to determine the effect of aging on the shear moduli of the superficial muscle heads of the quadriceps and to explore its relationship with knee extension force.MethodsPassive shear moduli of the rectus femoris (RF), vastus lateralis (VL), and vastus medialis (VM) were measured at rest using shear wave elastography in 20 young and 20 senior female adults. Measurements were repeated at four knee joint positions, that is, 30°, 60°, 90°, and 105° of knee flexion. Maximal isometric voluntary knee extension force was assessed at 30°, 60°, and 90° of knee flexion.ResultsAs per our findings, senior adults were determined to have significantly higher passive muscle shear moduli in the RF (by 34% – 68%; allp < 0.05) and the VL muscle heads (by 13%–16%, allp < 0.05) at and beyond 60° of knee flexion. Age-related increase in the VM was evident at 105° knee flexion (by11%,p = 0.020). The RF shear modulus was negatively correlated to the maximal isometric voluntary contraction force measured at 60° (r =  − 0.485,p = 0.030) in senior adults.ConclusionsSenior female adults had greater passive stiffness at the superficial muscle heads of the quadriceps muscles when measured at long muscle length. Among the senior female adults, the passive stiffness of RF has been determined to have a negative association with the knee extensor force only at 60° knee flexion. No significant association was noted for other angles and muscles.
Neuroligin-1 mediates presynaptic maturation through brain-derived neurotrophic factor signaling
Authors: Petkova-Tuffy Andonia , Gödecke Nina , Viotti Julio , Korte Martin , Dresbach Thomas 
Published: September 2021

Abstract
Background
Maturation is a process that allows synapses to acquire full functionality, optimizing their activity to diverse neural circuits, and defects in synaptic maturation may contribute to neurodevelopmental disorders. Neuroligin-1 (NL1) is a postsynaptic cell adhesion molecule essential for synapse maturation, a role typically attributed to binding to pre-synaptic ligands, the neurexins. However, the pathways underlying the action of NL1 in synaptic maturation are incompletely understood, and some of its previously observed effects seem reminiscent of those described for the neurotrophin brain-derived neurotrophic factor (BDNF). Here, we show that maturational increases in active zone stability and synaptic vesicle recycling rely on the joint action of NL1 and brain-derived neurotrophic factor (BDNF).

Results
Applying BDNF to hippocampal neurons in primary cultures or organotypical slice cultures mimicked the effects of overexpressing NL1 on both structural and functional maturation. Overexpressing a NL1 mutant deficient in neurexin binding still induced presynaptic maturation. Like NL1, BDNF increased synaptic vesicle recycling and the augmentation of transmitter release by phorbol esters, both hallmarks of presynaptic maturation. Mimicking the effects of NL1, BDNF also increased the half-life of the active zone marker bassoon at synapses, reflecting increased active zone stability. Overexpressing NL1 increased the expression and synaptic accumulation of BDNF. Inhibiting BDNF signaling pharmacologically or genetically prevented the effects of NL1 on presynaptic maturation. Applying BDNF to NL1-knockout mouse cultures rescued defective presynaptic maturation, indicating that BDNF acts downstream of NL1 and can restore presynaptic maturation at late stages of network development.

Conclusions
Our data introduce BDNF as a novel and essential component in a transsynaptic pathway linking NL1-mediated cell adhesion, neurotrophin action, and presynaptic maturation. Our findings connect synaptic cell adhesion and neurotrophin signaling and may provide a therapeutic approach to neurodevelopmental disorders by targeting synapse maturation.
p113 isoform encoded by CUX1 circular RNA drives tumor progression via facilitating ZRF1/BRD4 transactivation
Authors: Yang Feng , Hu Anpei , Guo Yanhua , Wang Jianqun , Li Dan , Wang Xiaojing , Jin Shikai , Yuan Boling , Cai Shuang , Zhou Yi , Li Qilan , Chen Guo , Gao Haiyang , Zheng Liduan , Tong Qiangsong 
Published: September 2021

AbstractBackgroundMetabolic reprogramming sustains tumorigenesis and aggressiveness of neuroblastoma (NB), the most common extracranial malignancy in childhood, while underlying mechanisms and therapeutic approaches still remain elusive.MethodsCircular RNAs (circRNAs) were validated by Sanger sequencing. Co-immunoprecipitation, mass spectrometry, chromatin immunoprecipitation (ChIP) sequencing, and RNA sequencing assays were applied to explore protein interaction and target genes. Gene expression regulation was observed by ChIP, dual-luciferase reporter, real-time quantitative RT-PCR, and western blot assays. Gain- and loss-of-function studies were performed to observe the impacts of circRNA-encoded protein and its partners on the lipid metabolism, mitochondrial activity, growth, invasion, and metastasis of NB cells.ResultsA novel 113-amino acid protein (p113) of CUT-like homeobox 1 (CUX1) was identified in NB cells treated by serum deprivation. Further validating studies revealed that nuclear p113 was encoded by circRNA ofCUX1, and promoted the lipid metabolic reprogramming, mitochondrial activity, proliferation, invasion, and metastasis of NB cells.Mechanistically, p113 interacted with Zuotin-related factor 1 (ZRF1) and bromodomain protein 4 (BRD4) to form a transcriptional regulatory complex, and mediated the transactivation of ZRF1/BRD4 in upregulatingALDH3A1,NDUFA1, andNDUFAF5essential for conversion of fatty aldehydes into fatty acids, fatty acid β-oxidation, and mitochondrial complex I activity. Administration of an inhibitory peptide blocking p113-ZRF1 interaction suppressed the tumorigenesis and aggressiveness of NB cells. In clinical NB cases, high expression ofp113,ZRF1, orBRD4was associated with poor survival of patients.ConclusionsThese results indicate that p113 isoform encoded byCUX1circular RNA drives tumor progression via facilitating ZRF1/BRD4 transactivation.
Co-delivery of nanoparticle and molecular drug by hollow mesoporous organosilica for tumor-activated and photothermal-augmented chemotherapy of breast cancer
Authors: Zhang Haixian , Song Feifei , Dong Caihong , Yu Luodan , Chang Cai , Chen Yu 
Published: September 2021

Abstract
Background
In comparison with traditional therapeutics, it is highly preferable to develop a combinatorial therapeutic modality for nanomedicine and photothermal hyperthermia to achieve safe, efficient, and localized delivery of chemotherapeutic drugs into tumor tissues and exert tumor-activated nanotherapy. Biocompatible organic–inorganic hybrid hollow mesoporous organosilica nanoparticles (HMONs) have shown high performance in molecular imaging and drug delivery as compared to other inorganic nanosystems. Disulfiram (DSF), an alcohol-abuse drug, can act as a chemotherapeutic agent according to its recently reported effectiveness for cancer chemotherapy, whose activity strongly depends on copper ions.

Results
In this work, a therapeutic construction with high biosafety and efficiency was proposed and developed for synergistic tumor-activated and photothermal-augmented chemotherapy in breast tumor eradication both in vitro and in vivo. The proposed strategy is based on the employment of HMONs to integrate ultrasmall photothermal CuS particles onto the surface of the organosilica and the molecular drug DSF inside the mesopores and hollow interior. The ultrasmall CuS acted as both photothermal agent under near-infrared (NIR) irradiation for photonic tumor hyperthermia and Cu2+ self-supplier in an acidic tumor microenvironment to activate the nontoxic DSF drug into a highly toxic diethyldithiocarbamate (DTC)-copper complex for enhanced DSF chemotherapy, which effectively achieved a remarkable synergistic in-situ anticancer outcome with minimal side effects.

Conclusion
This work provides a representative paradigm on the engineering of combinatorial therapeutic nanomedicine with both exogenous response for photonic tumor ablation and endogenous tumor microenvironment-responsive in-situ toxicity activation of a molecular drug (DSF) for augmented tumor chemotherapy.

Graphical abstract
Studying dietary intake in daily life through multilevel two-part modelling: a novel analytical approach and its practical application
Authors: Ruf Alea , Neubauer Andreas B. , Ebner-Priemer Ulrich , Reif Andreas , Matura Silke 
Published: September 2021

Abstract
Background
Understanding which factors influence dietary intake, particularly in daily life, is crucial given the impact diet has on physical as well as mental health. However, a factor might influence whether but not how much an individual eats and vice versa or a factor’s importance may differ across these two facets. Distinguishing between these two facets, hence, studying dietary intake as a dual process is conceptually promising and not only allows further insights, but also solves a statistical issue. When assessing the association between a predictor (e.g. momentary affect) and subsequent dietary intake in daily life through ecological momentary assessment (EMA), the outcome variable (e.g. energy intake within a predefined time-interval) is semicontinuous. That is, one part is equal to zero (i.e. no dietary intake occurred) and the other contains right-skewed positive values (i.e. dietary intake occurred, but often only small amounts are consumed). However, linear multilevel modelling which is commonly used for EMA data to account for repeated measures within individuals cannot be applied to semicontinuous outcomes. A highly informative statistical approach for semicontinuous outcomes is multilevel two-part modelling which treats the outcome as generated by a dual process, combining a multilevel logistic/probit regression for zeros and a multilevel (generalized) linear regression for nonzero values.

Methods
A multilevel two-part model combining a multilevel logistic regression to predict whether an individual eats and a multilevel gamma regression to predict how much is eaten, if an individual eats, is proposed. Its general implementation in R, a widely used and freely available statistical software, using the R-package brms is described. To illustrate its practical application, the analytical approach is applied exemplary to data from the Eat2beNICE-APPetite-study.

Results
Results highlight that the proposed multilevel two-part model reveals process-specific associations which cannot be detected through traditional multilevel modelling.

Conclusions
This paper is the first to introduce multilevel two-part modelling as a novel analytical approach to study dietary intake in daily life. Studying dietary intake through multilevel two-part modelling is conceptually as well as methodologically promising. Findings can be translated to tailored nutritional interventions targeting either the occurrence or the amount of dietary intake.
Molecular and epidemiological characterization of human adenoviruses infection among children with acute diarrhea in Shandong Province, China
Authors: Huang Deyu , Wang Zheng , Zhang Guanyou , Sai Lintao 
Published: September 2021

Abstract
Background
Human adenovirus (HAdV) had been recognized as one of the most common enteric viruses associated with acute diarrhea in children. The present study was carried out to demonstrate the molecular and epidemiological characterization of HAdV Infections among children in Shandong province in China between July 2017 and June 2018.

Methods
Fecal specimens were collected from children under 5 years old with acute diarrhea. DNA was extracted from the stool specimens and adenovirus DNA was detected by PCR amplification with specific primers. The amplification products were subjected to electrophoresis and visualized on a UV transilluminator. All positive RT-PCR amplification products were sequenced and the obtained sequences analyzed by MEGA (version 7.0). Demographic information and clinical manifestation data were also analyzed.

Results
In total, 656 fecal specimens were collected and the overall positive rate of HAdV was 7.47%. HAdV infections were detected in all age groups, in which children aged 13–24 months presented the highest positive rate. Seasonal pattern could be observed with a peak in December, January and February. Diarrhea, vomiting, dehydration and fever were the main clinical manifestations, in which vomiting was the most common accompanied symptom. By phylogenetic analysis, four species (A, B, C, and F) were detected and seven different serotypes were identified. HAdV-41 (48.98%, 24/49) was the most common serotype followed by HAdV-3 (18.37%, 9/49), HAdV-31 (14.29%, 7/49), HAdV-7 (8.16%, 4/49), HAdV-40 (4.08%, 2/49), HAdV-1 (4.08%, 2/49) and HAdV-2 (2.04%, 1/49).

Conclusion
This study indicated that HAdV infection was an important cause of acute diarrhea among children under 5 years old in Shandong province. The results will contribute to (a) increase understanding of the role of HAdV in diarrheal children and enhance identification of the predominant diarrhea pathogen for diagnosis; (b) avoid abuse of antibiotics; (c) monitor the change of prevalent HAdV serotypes and promote vaccine development and vaccination.
Risk factors of prolonged ventilation after thymectomy in thymoma myasthenia gravis patients
Authors: Du Anqi , Li Xiao , An Youzhong , Gao Zhancheng 
Published: September 2021

Abstract
Background
To explore the risk factors for prolonged ventilation after thymectomy in patients with thymoma associated with myasthenia gravis (TAMG).

Methods
We reviewed the records of 112 patients with TAMG after thymectomy between January 2010 and December 2019 in Peking University People’s Hospital. Demographic, pathological, preoperative data and the Anesthesia, surgery details were assessed with multivariable logistic regression analysis to predict the risk of prolonged ventilation after thymectomy. A nomogram to predict the probability of post-thymectomy ventilation was constructed with R software. Discrimination and calibration were employed to evaluate the performance of the nomogram.

Results
By multivariate analysis, male, low vital capacity (VC), Osserman classification (IIb, III, IV), total intravenous anesthesia, and long operation time were identified as the risk factors and entered into the nomogram. The nomogram showed a robust discrimination, with an area under the receiver operating characteristic curve (AUC) of 0. 835 (95% confidence interval [CI], 0.757–0.913). The calibration plot indicated that the nomogram-predicted probabilities compared very well with the actual probabilities (Hosmer–Lemeshow test: P = 0.921).

Conclusion
The nomogram is a valuable predictive tool for prolonged ventilation after thymectomy in patients with TAMG.
Robust inflammatory breast cancer gene signature using nonparametric random forest analysis
Authors: Zare Alaa , Postovit Lynne-Marie , Githaka John Maringa 
Published: September 2021

AbstractInflammatory breast cancer (IBC) is a rare, aggressive cancer found in all the molecular breast cancer subtypes. Despite extensive previous efforts to screen for transcriptional differences between IBC and non-IBC patients, a robust IBC-specific molecular signature has been elusive. We report a novel IBC-specific gene signature (59 genes; G59) that achieves 100% accuracy in discovery and validation samples (45/45 correct classification) and remarkably only misclassified one sample (60/61 correct classification) in an independent dataset. G59 is independent of ER/HER2 status, molecular subtypes and is specific to untreated IBC samples, with most of the genes being enriched for plasma membrane cellular component proteins, interleukin (IL), and chemokine signaling pathways. Our finding suggests the existence of an IBC-specific molecular signature, paving the way for the identification and validation of targetable genomic drivers of IBC.
High frequency of intron retention and clustered H3K4me3-marked nucleosomes in short first introns of human long non-coding RNAs
Authors: Dey Pinki , Mattick John S. 
Published: September 2021

Abstract
Background
It is established that protein-coding exons are preferentially localized in nucleosomes. To examine whether the same is true for non-coding exons, we analysed nucleosome occupancy in and adjacent to internal exons in genes encoding long non-coding RNAs (lncRNAs) in human CD4+ T cells and K562 cells.

Results
We confirmed that internal exons in lncRNAs are preferentially associated with nucleosomes, but also observed an elevated signal from H3K4me3-marked nucleosomes in the sequences upstream of these exons. Examination of 200 genomic lncRNA loci chosen at random across all chromosomes showed that high-density regions of H3K4me3-marked nucleosomes, which we term ‘slabs’, are associated with genomic regions exhibiting intron retention. These retained introns occur in over 50% of lncRNAs examined and are mostly first introns with an average length of just 354 bp, compared to the average length of all human introns of 6355 and 7987 bp in mRNAs and lncRNAs, respectively. Removal of short introns from the dataset abrogated the high upstream H3K4me3 signal, confirming that the association of slabs and short lncRNA introns with intron retention holds genome-wide. The high upstream H3K4me3 signal is also associated with alternatively spliced exons, known to be prominent in lncRNAs. This phenomenon was not observed with mRNAs.

Conclusions
There is widespread intron retention and clustered H3K4me3-marked nucleosomes in short first introns of human long non-coding RNAs, which raises intriguing questions about the relationship of IR to lncRNA function and chromatin organization.