bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extrachromosomal DNA in HPV-Mediated Oropharyngeal Cancer Drives Diverse Oncogene Transcription
Authors: Pang John , Nguyen Nam , Luebeck Jens , Ball Laurel , Finegersh Andrey , Ren Shuling , Nakagawa Takuya , Flagg Mitchell , Sadat Sayed , Mischel Paul S. , Xu Guorong , Fisch Kathleen , Guo Theresa , Cahill Gabrielle , Panuganti Bharat , Bafna Vineet , Califano Joseph 
Published: September 2021

Abstract

Purpose:
Human papillomavirus (HPV) plays a major role in oncogenesis and circular extrachromosomal DNA (ecDNA) is found in many cancers. However, the relationship between HPV and circular ecDNA in human cancer is not understood.

Experimental Design:
Forty-four primary tumor tissue samples were obtained from a cohort of patients with HPV-positive oropharynx squamous cell carcinoma (OPSCC). Twenty-eight additional HPV oropharyngeal cancer (HPVOPC) tumors from The Cancer Genome Atlas (TCGA) project were analyzed as a separate validation cohort. Genomic, transcriptomic, proteomic, computational, and functional analyses of HPVOPC were applied to these datasets.

Results:
Our analysis revealed circular, oncogenic DNA in nearly all HPVOPC, with circular human and human–viral hybrid ecDNA present in over a third of HPVOPC and viral circular DNA in remaining tumors. Hybrid ecDNA highly express fusion transcripts from HPV promoters and HPV oncogenes linked to downstream human transcripts that drive oncogenic transformation and immune evasion, and splice multiple, diverse human acceptors to a canonical SA880 viral donor site. HPVOPC have high E6*I expression with specific viral oncogene expression pattern related to viral or hybrid ecDNA composition.

Conclusions:
Nonchromosomal circular oncogenic DNA is a dominant feature of HPVOPC, revealing an unanticipated link between HPV and ecDNA that leverages the power of extrachromosomal inheritance to drive HPV and somatic oncogene expression.
Vitreous Noise on Optical Coherence Tomography as an Early Finding of Brolucizumab-Related Intraocular Inflammation
Authors: Yoshikawa Yuji , Kumagai Tomoyuki , Shinoda Kei 
Published: September 2021

We describe a case of brolucizumab-related intraocular inflammation (IOI) detected using vitreous haze on optical coherence tomography (OCT) at an early stage before the patient was aware of any symptom. A 69-year-old female presented with decreased right vision. The patient was diagnosed with pachychoroidal neovasculopathy and started intravitreal aflibercept (IVA) with a 3+ treat-and-extend strategy (TAE). Although the serous retinal detachment (SRD) disappeared after IVA treatment, the patient was managed with treatment every 4 weeks without extending the treatment interval To shorten the treatment interval, intravitreal brolucizumab (IVBr) was started 44 weeks after starting IVA treatment. After initiating IVBr treatment, the SRD completely disappeared. However, 16 weeks after starting IVBr, OCT showed noise in the vitreous cavity, which had not been seen before, and infrared images showed a black smoke-like shadow over the macula. Despite these findings, the patient had no subjective symptoms, and so IVBr was re-administered with an 8-week TAE interval. Five days after IVBr treatment, vitreous inflammatory cells were observed, and the noise in the vitreous cavity and the smoke-like shadow in the infrared image were further enhanced. We diagnosed the patient with brolucizumab-related IOI, and anti-inflammatory treatment was initiated. After extensive treatment, the vitreous opacity gradually disappeared, and the vitreous noise on OCT and the black smoke-like shadow on infrared images disappeared. IOI may have already been present 16 weeks after starting IVBr treatment, when we judged that there was no inflammation and IVBr was re-administered. When following patients receiving IVBr, IOI may be detected by OCT at an earlier stage by evaluating vitreous haze.
How Visual Expertise Changes Representational Geometry: A Behavioral and Neural Perspective
Authors: Duyck Stefanie , Martens Farah , Chen Chiu-Yueh , Op de Beeck Hans 
Published: September 2021

Abstract
Many people develop expertise in specific domains of interest, such as chess, microbiology, radiology, and, the case in point in our study: ornithology. It is poorly understood to what extent such expertise alters brain function. Previous neuroimaging studies of expertise have typically focused upon the category level, for example, selectivity for birds versus nonbird stimuli. We present a multivariate fMRI study focusing upon the representational similarity among objects of expertise at the subordinate level. We compare the neural representational spaces of experts and novices to behavioral judgments. At the behavioral level, ornithologists (n = 20) have more fine-grained and task-dependent representations of item similarity that are more consistent among experts compared to control participants. At the neural level, the neural patterns of item similarity are more distinct and consistent in experts than in novices, which is in line with the behavioral results. In addition, these neural patterns in experts show stronger correlations with behavior compared to novices. These findings were prominent in frontal regions, and some effects were also found in occipitotemporal regions. This study illustrates the potential of an analysis of representational geometry to understand to what extent expertise changes neural information processing.
Distinct clinical characteristics ofDUX4-andPAX5-altered childhood B-lymphoblastic leukemia
Authors: Li Zhenhua , Lee Shawn Hsien Ren , Chin Winnie Hui Ni , Lu Yi , Jiang Nan , Lim Evelyn Huizi , Coustan-Smith Elaine , Chiew Kean Hui , Oh Bernice Ling Zhi , Koh Grace Shimin , Chen Zhiwei , Kham Shirley Kow Yin , Quah Thuan Chong , Lin Hai Peng , Tan Ah Moy , Ariffin Hany , Yang Jun J. , Yeoh Allen Eng-Juh 
Published: September 2021

AbstractAmong the recently described subtypes in childhood B-lymphoblastic leukemia (B-ALL) were DUX4- and PAX5-altered (PAX5alt). By using whole transcriptome RNA sequencing in 377 children with B-ALL from the Malaysia-Singapore ALL 2003 (MS2003) and Malaysia-Singapore ALL 2010 (MS2010) studies, we found that, after hyperdiploid and ETV6-RUNX1, the third and fourth most common subtypes were DUX4 (n = 51; 14%) and PAX5alt (n = 36; 10%). DUX4 also formed the largest genetic subtype among patients with poor day-33 minimal residual disease (MRD; n = 12 of 44). But despite the poor MRD, outcome of DUX4 B-ALL was excellent (5-year cumulative risk of relapse [CIR], 8.9%; 95% confidence interval [CI], 2.8%-19.5% and 5-year overall survival, 97.8%; 95% CI, 85.3%-99.7%). In MS2003, 21% of patients with DUX4 B-ALL had poor peripheral blood response to prednisolone at day 8, higher than other subtypes (8%; P = .03). In MS2010, with vincristine at day 1, no day-8 poor peripheral blood response was observed in the DUX4 subtype (P = .03). The PAX5alt group had an intermediate risk of relapse (5-year CIR, 18.1%) but when IKZF1 was not deleted, outcome was excellent with no relapse among 23 patients. Compared with MS2003, outcome of PAX5alt B-ALL with IKZF1 codeletion was improved by treatment intensification in MS2010 (5-year CIR, 80.0% vs 0%; P = .05). In conclusion, despite its poor initial response, DUX4 B-ALL had a favorable overall outcome, and the prognosis of PAX5alt was strongly dependent on IKZF1 codeletion.
Concentration optimization of combinatorial drugs using Markov chain-based models
Authors: Ma Shuang , Dang Dan , Wang Wenxue , Wang Yuechao , Liu Lianqing 
Published: September 2021

AbstractBackgroundCombinatorial drug therapy for complex diseases, such as HSV infection and cancers, has a more significant efficacy than single-drug treatment. However, one key challenge is how to effectively and efficiently determine the optimal concentrations of combinatorial drugs because the number of drug combinations increases exponentially with the types of drugs.ResultsIn this study, a searching method based on Markov chain is presented to optimize the combinatorial drug concentrations. In this method, the searching process of the optimal drug concentrations is converted into a Markov chain process with state variables representing all possible combinations of discretized drug concentrations. The transition probability matrix is updated by comparing the drug responses of the adjacent states in the network of the Markov chain and the drug concentration optimization is turned to seek the state with maximum value in the stationary distribution vector. Its performance is compared with five stochastic optimization algorithms as benchmark methods by simulation and biological experiments. Both simulation results and experimental data demonstrate that the Markov chain-based approach is more reliable and efficient in seeking global optimum than the benchmark algorithms. Furthermore, the Markov chain-based approach allows parallel implementation of all drug testing experiments, and largely reduces the times in the biological experiments.ConclusionThis article provides a versatile method for combinatorial drug screening, which is of great significance for clinical drug combination therapy.
Spatio-temporal dynamics of bacterial communities in the shoreline of Laurentian great Lake Erie and Lake St. Clair’s large freshwater ecosystems
Authors: Shahraki Abdolrazagh Hashemi , Chaganti Subba Rao , Heath Daniel 
Published: September 2021

Abstract
Background
Long-term trends in freshwater bacterial community composition (BCC) and dynamics are not yet well characterized, particularly in large lake ecosystems. We addressed this gap by temporally (15 months) and spatially (6 sampling locations) characterizing BCC variation in lakes Erie and St. Clair; two connected ecosystems in the Laurentian Great Lakes.

Results
We found a spatial variation of the BCC between the two lakes and among the sampling locations (significant changes in the relative abundance of 16% of the identified OTUs at the sampling location level). We observed five distinct temporal clusters (UPGMA broad-scale temporal variation) corresponding to seasonal variation over the 15 months of sampling. Temporal variation among months was high, with significant variation in the relative abundance of 69% of the OTUs. We identified significant differences in taxonomic composition between summer months of 2016 and 2017, with a corresponding significant reduction in the diversity of BCC in summer 2017.

Conclusions
As bacteria play a key role in biogeochemical cycling, and hence in healthy ecosystem function our study defines the scope for temporal and spatial variation in large lake ecosystems. Our data also show that freshwater BCC could serve as an effective proxy and monitoring tool to access large lake health.
Relating outdoor play to sedentary behavior and physical activity in youth - results from a cohort study
Authors: Nigg Carina , Niessner Claudia , Nigg Claudio R. , Oriwol Doris , Schmidt Steffen C. E. , Woll Alexander 
Published: September 2021

Abstract
Background
Outdoor play, sedentary behavior (SB), and moderate-to-vigorous physical activity (MVPA) are related to youth’s health, however, there are research gaps regarding 1) associations between outdoor play, SB, and MVPA across a broad pediatric age range (6–17 years), and 2) longitudinal associations between outdoor play, SB, and MVPA across childhood and adolescence. Two studies were conducted to address those research gaps: Study 1 aimed to investigate relationships between outdoor play and accelerometer-assessed SB and MVPA in a cross-sectional nationwide sample of children and adolescents in Germany. Study 2 aimed to investigate prospective associations between outdoor play and self-reported screen-time SB and MVPA and in a sample of children with three measurement timepoints across 11 years.

Methods
Data were obtained of the German national representative Motorik-Modul (MoMo) Study and the German Health Interview and Examination Survey for Children and Adolescents (KiGGS). In Study 1, N = 2278 participants (6–17 years) were included with self-reported outdoor play and accelerometer-assessed SB and MVPA. Associations were examined via multiple linear regressions. In Study 2, N = 570 participants (baseline: 4–7 years) were included in the longitudinal analysis with follow-ups six and 11 years later. Screen-time SB (TV watching and PC/Gaming), MVPA, and outdoor play were self-reported. Associations were investigated through a path prediction model.

Results
Study 1 showed that compared to <1 h outdoor play, higher engagement in daily outdoor play was related to lower SB (1-2 h: − 9.75 min/day, P = 0.017; ≥2 h: − 17.78 min/day, P < 0.001) and higher MVPA (≥2 h: + 3.87 min/day, P = 0.001). The cross-sectional relationship between MVPA and outdoor play was moderated by sex (in favor of males) and age (in favor of younger children). Study 2 showed that outdoor play in early childhood negatively predicted PC use/Gaming in later childhood, but was unrelated to MVPA.

Conclusion
In Study 1, outdoor play was negatively related to SB cross-sectionally. In Study 2, outdoor play in early childhood was negatively related to PC and Gaming time in later childhood. Thus, providing outdoor play opportunities, especially during early childhood, has potential to prevent SB. Future research should investigate longitudinal relationships using device-based assessments for SB and MVPA.
Should the physiotherapy outcomes airway clearance, physical activity and fitness be recorded on the Australian Cystic Fibrosis Data Registry? A consensus approach
Authors: Potter Angela , Pancholi Bhavita , Smith Lahni , Maher Carol 
Published: September 2021

Abstract
Background
Physiotherapy is a cornerstone of cystic fibrosis (CF) management, yet the Australian CF Data Registry (ACFDR) currently does not record physiotherapy-related data. This study aimed to gather opinions from lead Australian CF physiotherapists regarding the importance and feasibility of collecting physiotherapy-related data on the ACFDR.

Methods
A three-round online Delphi survey was conducted to gather expert stakeholder opinion and consensus agreement. Lead physiotherapists from all 23 Australian CF centres were invited to participate. Round one explored the potential benefits, barriers and importance of recording three physiotherapy-related domains on the ACFDR: airway clearance, physical activity and fitness. Subsequent rounds were developed based on the findings from the previous round and sought consensus (80% agreement) for the inclusion of physiotherapy-related data on the ACFDR and for the most appropriate methods of collecting such data.

Results
The response rate was > 80% for all rounds. Participants agreed that collection of airway clearance, physical activity and fitness data on the ACFDR was important and feasible. Findings suggested that airway clearance and physical activity should be collected using self-reported questionnaires, while fitness should be measured using a field-based test.

Conclusions
Australian lead CF physiotherapists believe that collection of airway clearance, physical activity and fitness on the ACFDR is important and feasible. Future work is needed to pilot the data collection procedure to examine its feasibility in real-world clinical settings. This study demonstrates how Delphi methodology can provide a contemporary summary of expert clinicians’ opinion that may underpin nation-wide health service improvement.
Prospective study of dietary mushroom intake and risk of mortality: results from continuous National Health and Nutrition Examination Survey (NHANES) 2003-2014 and a meta-analysis
Authors: Ba Djibril M. , Gao Xiang , Al-Shaar Laila , Muscat Joshua , Chinchilli Vernon M. , Ssentongo Paddy , Zhang Xinyuan , Liu Guodong , Beelman Robert B. , Richie John P. 
Published: September 2021

Abstract
Background
Whether mushroom consumption, which is a rich source of potent antioxidants ergothioneine and glutathione, vitamins, and minerals (e.g., selenium & copper), is associated with a lower mortality risk is not well understood. This study aimed to examine the association between mushroom consumption and risk of mortality in a prospective cohort study and a meta-analysis of prospective cohort studies.

Methods
We followed 30,378 participants from the continuous National Health and Nutrition Examination Survey (NHANES) extant data (2003-2014). Dietary mushroom intake was assessed using up to two 24-h recalls. Mortality was evaluated in all participants linked to the National Death Index mortality data through December 31, 2015. We used Cox proportional hazards regression models to calculate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs). We also conducted a meta-analysis, including results from our present study and 4 other cohort studies.

Results
During a mean (SD) of 6.7 (3.4) years of follow-up, a total of 2855 death cases were documented among NHANES participants. In our analysis of continuous NHANES, we found a non-significant association between mushroom consumption and all-cause mortality (adjusted hazard ratio (HR) = 0.84; 95% CI: 0.67-1.06) after adjusting for demographic, major lifestyle factors, overall diet quality, and other dietary factors, including total energy. The meta-analysis of prospective cohort studies, including 601,893 individuals, showed that mushroom consumption was associated with a lower risk of all-cause mortality (pooled risk ratio: 0.94; 95% CI: 0.91, 0.98).

Conclusion
In a meta-analysis of prospective cohort studies, mushroom consumption was associated with a lower risk of all-cause mortality.
APOC3 genetic variation, serum triglycerides, and risk of coronary artery disease in Asian Indians, Europeans, and other ethnic groups
Authors: Goyal Shiwali , Tanigawa Yosuke , Zhang Weihua , Chai Jin-Fang , Almeida Marcio , Sim Xueling , Lerner Megan , Chainakul Juliane , Ramiu Jonathan Garcia , Seraphin Chanel , Apple Blair , Vaughan April , Muniu James , Peralta Juan , Lehman Donna M. , Ralhan Sarju , Wander Gurpreet S. , Singh Jai Rup , Mehra Narinder K. , Sidorov Evgeny , Peyton Marvin D. , Blackett Piers R. , Curran Joanne E. , Tai E. Shyong , van Dam Rob , Cheng Ching-Yu , Duggirala Ravindranath , Blangero John , Chambers John C. , Sabanayagam Charumathi , Kooner Jaspal S. , Rivas Manuel A. , Aston Christopher E. , Sanghera Dharambir K. 
Published: September 2021

Abstract
Background
Hypertriglyceridemia has emerged as a critical coronary artery disease (CAD) risk factor. Rare loss-of-function (LoF) variants in apolipoprotein C-III have been reported to reduce triglycerides (TG) and are cardioprotective in American Indians and Europeans. However, there is a lack of data in other Europeans and non-Europeans. Also, whether genetically increased plasma TG due to ApoC-III is causally associated with increased CAD risk is still unclear and inconsistent. The objectives of this study were to verify the cardioprotective role of earlier reported six LoF variants of APOC3 in South Asians and other multi-ethnic cohorts and to evaluate the causal association of TG raising common variants for increasing CAD risk.

Methods
We performed gene-centric and Mendelian randomization analyses and evaluated the role of genetic variation encompassing APOC3 for affecting circulating TG and the risk for developing CAD.

Results
One rare LoF variant (rs138326449) with a 37% reduction in TG was associated with lowered risk for CAD in Europeans (p = 0.007), but we could not confirm this association in Asian Indians (p = 0.641). Our data could not validate the cardioprotective role of other five LoF variants analysed. A common variant rs5128 in the APOC3 was strongly associated with elevated TG levels showing a p-value 2.8 × 10− 424. Measures of plasma ApoC-III in a small subset of Sikhs revealed a 37% increase in ApoC-III concentrations among homozygous mutant carriers than the wild-type carriers of rs5128. A genetically instrumented per 1SD increment of plasma TG level of 15 mg/dL would cause a mild increase (3%) in the risk for CAD (p = 0.042).

Conclusions
Our results highlight the challenges of inclusion of rare variant information in clinical risk assessment and the generalizability of implementation of ApoC-III inhibition for treating atherosclerotic disease. More studies would be needed to confirm whether genetically raised TG and ApoC-III concentrations would increase CAD risk.
Augmented feedback for manual wheelchair propulsion technique training in a virtual reality simulator
Authors: Yan Hui , Archambault Philippe S. 
Published: September 2021

Abstract
Background
Motor learning of appropriate manual wheelchair propulsion is critical, as incorrect technique elevates risk for upper extremity pain. Virtual reality simulators allow users to practice this complex task in a safe and realistic environment. Additionally, augmented feedback (AF) may be provided in order to optimize learning. The purpose of this study was to investigate the effects of providing AF with various delivery schedules on motor learning and transfer of this skill to over-ground propulsion.

Methods
Thirty healthy young adults were randomly assigned to three groups. During a virtual reality propulsion training session, the high-frequency AF group received AF in the form of knowledge of performance throughout all propulsion training; the faded AF group received this AF in a faded schedule (high relative frequency of AF early in practice, with relative frequency of AF provision diminishing throughout practice); and the control group underwent training with no AF. Propulsion assessments were performed at baseline and 48 h after practice in both virtual and real environments to measure retention and transfer, respectively.

Results
Compared to the control group, both feedback groups exhibited significant improvements in contact angle and push frequency in both environments after training. Small, non-significant between-group differences were also found between the high-frequency and faded feedback groups.

Conclusion
Virtual reality training is an effective learning intervention for acquisition, retention, and transfer of appropriate manual wheelchair propulsion technique when such training includes AF regarding propulsion biomechanics.