bluuebunny/crossref_metadata_2025_split huggingface dataset:
The roles of DNA methylation on the promotor of the Epstein–Barr virus (EBV) gene and the genome in patients with EBV-associated diseases
Authors: Zhang Linlin , Wang Ran , Xie Zhengde 
Published: June 2022

Abstract
Epstein–Barr virus (EBV) is an oncogenic virus that is closely associated with several malignant and lymphoproliferative diseases. Studies have shown that the typical characteristic of EBV-associated diseases is aberrant methylation of viral DNA and the host genome. EBV gene methylation helps EBV escape from immune monitoring and persist in host cells. EBV controls viral gene promoter methylation by hijacking host epigenetic machinery to regulate the expression of viral genes. EBV proteins also interact with host epigenetic regulatory factors to mediate the methylation of the host’s important tumour suppressor gene promoters, thereby participating in the occurrence of tumorigenesis. Since epigenetic modifications, including DNA methylation, are reversible in nature, drugs that target DNA methylation can be developed for epigenetic therapy against EBV-associated tumours. Various methylation modes in the host and EBV genomes may also be of diagnostic and prognostic value. This review summarizes the regulatory roles of DNA methylation on the promotor of EBV gene and host genome in EBV-associated diseases, proposes the application prospect of DNA methylation in early clinical diagnosis and treatment, and provides insight into methylation-based strategies against EBV-associated diseases.

Key points
• Methylation of both the host and EBV genomes plays an important role in EBV-associateddiseases.
• The functions of methylation of the host and EBV genomes in the occurrence and development of EBV-associated diseases are diverse.
• Methylation may be a therapeutic target or biomarker in EBV-associated diseases.
Diagnostic Rechallenge with 18F‐FCH PET/CT Often Allows Minimally Invasive Parathyroidectomy While Maintaining Exceptional Cure Rates
Authors: Goren Shani , Paladino Nunzia Cinzia , Laks Shachar , Cuny Thomas , Vaillant‐Lombard Josiane , Mennetrey Clément , Assaf Dan , Hindié Elif , Guerin Carole , Fargette Christelle , Taïeb David , Sebag Fréderic 
Published: June 2022

AbstractBackgroundMinimally invasive parathyroidectomy (MIP) has gained acceptance as the preferred surgical procedure for management of primary hyperparathyroidism (pHPT). Appropriate selection of patients for a MIP is a crucial step in its utilization. The aim of the study was to evaluate the role of 18F‐FCH PET/CT as second‐line imaging for accurately directing MIP.
MethodsThis is a retrospective single‐center study. Seventy‐two patients with biochemical evidence of pHPT and a non‐conclusive or negative first‐line imaging (ultrasound and dual isotope subtraction scintigraphy) received 18F‐FCH PET/CT between January 2018 and February 2020. All imaging studies were performed at our institution. Assessment of therapeutic changes and outcomes was performed.Resultsof the 72 patients imaged with 18F‐FCH PET/CT, 54 subsequently underwent parathyroidectomy. When considering the ability of 18F‐FCH PET/CT alone to predict a uniglandular disease, the sensitivity, specificity, PPV and NPV were 92.7% (95%CI: 80.1—98.5), 46.2% (19.2–74.9), PPV 87.3% (80.5—92) and NPV 61.2% (31.4—84.5), respectively. When we combined the data provided by 18F‐FCH PET/CT with the data already collected from 1st line imaging we were able to complete a minimally invasive surgery in 38 of the 41 (92%) patients with a uniglandular disease. Thirteen patients (24%) had a multiglandular disease, all of them except one underwent bilateral neck exploration based on the data collected by all imaging modalities combined. Overall, cure was achieved in 53 (98%) patients.Conclusion18F‐FCH PET/CT, interpreted along with first‐line imaging results in selected patients, can better facilitate utilization of MIS while maintaining exceptional cure rates.
Patient Follow‐up After Orthopaedic Outreach Trips – Do We Know Whether Patients are Improving?
Authors: Leversedge Chelsea , Castro Samuel , Appiani Luis Miguel Castro , Kamal Robin , Shapiro Lauren 
Published: June 2022

AbstractBackgroundThe burden of traumatic musculoskeletal injuries falls greatest on low‐ and middle‐income countries (LMICs). To help address this burden, organizations host over 6,000 outreach trips annually, 20% of which are orthopaedic. Monitoring post‐surgical outcomes is critical to ensuring care quality; however, the implementation of such monitoring is unknown. The purpose of this review is to identify published follow‐up practices of short‐term orthopaedic surgery outreach trips to LMICs.MethodsWe completed a systematic review of Pubmed, Web of Science, EMBASE, and ProQuest following PRISMA guidelines. Follow‐up method, rate, duration, and types of outcomes measured along with barriers to follow‐up were collected and reported.ResultsThe initial search yielded 1,452 articles, 18 of which were eligible. The mean follow‐up time was 5.4 months (range: 15 days‐7 years). The mean follow‐up rate was 65.8% (range: 22%‐100%), the weighted rate was 57.5%. Fifteen studies reported follow‐up at or after 3 months while eight studies reported follow‐up at or after 9 months. Fifteen studies reported follow‐up in person, three reported follow‐up via phone call or SMS. Outcome reporting varied among mortality, complications, and patient‐reported outcomes. The majority (75%) outlined barriers to follow‐up, most commonly noting transportation and costs of follow‐up to the patient.ConclusionsThere is minimal and heterogeneous public reporting of patient outcomes and follow‐up after outreach trips to LMICs, limiting quality assessment and improvement. Future work should address the design and implementation of tools and guidelines to improve follow‐up as well as outcome measurement to ensure provision of high‐quality care.
Non-invasive auditory brainstem responses to FM sweeps in awake big brown bats
Authors: Simmons Andrea Megela , Tuninetti Amaro , Yeoh Brandon M. , Simmons James A. 
Published: June 2022

AbstractWe introduce two EEG techniques, one based on conventional monopolar electrodes and one based on a novel tripolar electrode, to record for the first time auditory brainstem responses (ABRs) from the scalp of unanesthetized, unrestrained big brown bats. Stimuli were frequency-modulated (FM) sweeps varying in sweep direction, sweep duration, and harmonic structure. As expected from previous invasive ABR recordings, upward-sweeping FM signals evoked larger amplitude responses (peak-to-trough amplitude in the latency range of 3–5 ms post-stimulus onset) than downward-sweeping FM signals. Scalp-recorded responses displayed amplitude-latency trading effects as expected from invasive recordings. These two findings validate the reliability of our noninvasive recording techniques. The feasibility of recording noninvasively in unanesthetized, unrestrained bats will energize future research uncovering electrophysiological signatures of perceptual and cognitive processing of biosonar signals in these animals, and allows for better comparison with ABR data from echolocating cetaceans, where invasive experiments are heavily restricted.
Structure and Complexity of 2-Intersection Graphs of 3-Hypergraphs
Authors: Di Marco Niccoló , Frosini Andrea , Kocay William Lawrence , Pergola Elisa , Tarsissi Lama 
Published: June 2022

AbstractGiven a 3-uniform hypergraph H having a set V of vertices, and a set of hyperedges $$T\subset \mathcal {P}(V)$$

T
⊂
P
(
V
)

, whose elements have cardinality three each, a null labelling is an assignment of $$\pm 1$$

±
1

to the hyperedges such that each vertex belongs to the same number of hyperedges labelled $$+1$$

+
1

and $$-1$$

-
1

. A sufficient condition for the existence of a null labelling of H (proved in Di Marco et al. Lect Notes Comput Sci 12757:282–294, 2021) is a Hamiltonian cycle in its 2-intersection graph. The notion of 2-intersection graph generalizes that of intersection graph of an (hyper)graph and extends its effectiveness. The present study first shows that this sufficient condition for the existence of a null labelling in H can not be weakened by requiring only the connectedness of the 2-intersection graph. Then some interesting properties related to their clique configurations are proved. Finally, the main result is proved, the NP-completeness of this characterization and, as a consequence, of the construction of the related 3-hypergraphs.
Generating polycrystalline microstructures with prescribed tensorial texture coefficients
Authors: Kuhn Jannick , Schneider Matti , Sonnweber-Ribic Petra , Böhlke Thomas 
Published: June 2022

AbstractThis work is concerned with synthetic microstructure models of polycrystalline materials. Once a representation of the microstructure is generated, the individual grains need to be furnished with suitable crystal orientations, matching a specific crystal orientation distribution. We introduce a novel method for this task, which permits to prescribe the orientations based on tensorial Fourier coefficients. This compact representation gives rise to the texture coefficient optimization for prescribing orientations method, enabling the determination of representative orientations for digital polycrystalline microstructures. We compare the proposed method to established and dedicated algorithms in terms of the linear elastic as well as the non-linear plastic behavior of a polycrystalline material.
Bayesian time-varying occupancy model for West Nile virus in Ontario, Canada
Authors: Temple Seth D. , Manore Carrie A. , Kaufeld Kimberly A. 
Published: June 2022

AbstractOccupancy models determine the true presence or absence of a species by adjusting for imperfect detection in surveys. They often assume that species presences can be detected only if sites are occupied during a sampling season. We extended these models to estimate occupancy rates that vary throughout a sampling season as well as account for spatial dependence among sites. For these methods, we constructed a fast Gibbs sampler with the Pólya-Gamma augmentation strategy to conduct inference on covariate effects. We applied these methods to evaluate how environmental conditions and surveillance practices are associated with the presence of West Nile virus in mosquito traps across Ontario, Canada from 2002 to 2017. We found that urban land cover and warm temperatures drove viral occupancy, whereas viral testing on pools with higher proportions of Culex mosquitoes was more likely to result in a positive test for West Nile virus. Models with time-varying occupancy effects achieved much lower Watanabe-Akaike information criteria than models without such effects. Our final model had strong predictive performance on test data that included some of the most extreme seasons, demonstrating the promise of these methods in the study of pathogens spread by mosquito vectors.
Impact of time to first relapse on long-term outcome in adult retroperitoneal sarcoma patients after radical resection
Authors: Guan Huajie , Liu Mengmeng , Cai Shaohui , Ou Biyi , Guan Yuanxiang , Liang Yao 
Published: June 2022

Abstract
Background
Local recurrence of primary retroperitoneal sarcoma (RPS) is one of the major causes of treatment failure and death. We attempted to assess the effects of time to local recurrence (TLR) on the survival after recurrence (SAR) and overall survival (OS) of RPS.

Methods
Included in this study were 224 patients who underwent R0 resection for primary RPS at our institution between January 2000 and December 2020, 118 of whom had local recurrence. Based on the median TLR (19.8 months), patients were divided into two groups: early local recurrence (ELR < 20 months) and late local recurrence (LLR > 20 months). The Kaplan–Meier method was employed to calculate the local recurrence-free survival (LRFS), SAR and OS. Univariate and multivariate analyses were conducted to explore the prognostic value of TLR.

Results
The median follow-up time was 60.5 months for the entire cohort and 58.5 months for the recurrence cohort. There were 60 (50.8%) patients in the ELR group and 58 (49.2%) in the LLR group. The ELR group exhibited a worse SAR (29.2 months vs. 73.4 months, P < 0.001), OS (41.8 months vs. 120.9 months, P < 0.001), and a lower 5-year OS rate (35.9% vs. 73.2%, P = 0.004) than the LLR group. Furthermore, multivariate analysis indicated that TLR was an independent prognostic indicator for SAR (P = 0.014) and OS (P < 0.001).

Conclusions
In patients with RPS, ELR after R0 resection presents adverse effects on OS and SAR than those with LLR, and TLR could serve as a promising predictor for OS and SAR.
Religiosity and Risk of Parkinson’s Disease in England and the USA
Authors: Otaiku Abidemi I. 
Published: June 2022

AbstractParkinson’s disease (PD) is associated with low religiosity cross-sectionally. Whether low religiosity might be associated with an increased risk for developing PD is unknown. This study investigated whether low religiosity in adulthood is associated with increased risk for developing PD. A population-based prospective cohort study was conducted. Participants from the English Longitudinal Study of Aging and the Midlife in the United States study who were free from PD at baseline (2004–2011) and completed questionnaires on self-reported religiosity, were included in a pooled analysis. Incident PD was based on self-report. Multivariable logistic regression was used to estimate odds ratios (OR) for developing PD according to baseline religiosity, with adjustment for sociodemographic characteristics, health and lifestyle factors and engagement in religious practices. Among 9,796 participants in the pooled dataset, 74 (0.8%) cases of incident PD were identified during a median follow-up of 8.1 years. In the fully adjusted model, compared with participants who considered religion very important in their lives at baseline, it was found that participants who considered religion “not at all important” in their lives had a tenfold risk of developing PD during follow-up (OR, 9.99; 95% CI 3.28–30.36). Moreover, there was a dose–response relationship between decreasing religiosity and increasing PD risk (P < 0.001 for trend). These associations were similar when adjusting for religious upbringing and when cases occurring within the first two years of follow-up were excluded from the analysis. The association was somewhat attenuated when religious practices were removed from the model as covariates, though it remained statistically significant (OR for “not at all important” vs. “very important”, 2.26; 95% CI 1.03–4.95) (P < 0.029 for trend). This longitudinal study provides evidence for the first time that low religiosity in adulthood may be a strong risk factor for developing PD.
Multi-neighborhood simulated annealing for the sports timetabling competition ITC2021
Authors: Rosati Roberto Maria , Petris Matteo , Di Gaspero Luca , Schaerf Andrea 
Published: June 2022

AbstractWe describe the solver that we developed for the Sports Timetabling Competition ITC2021, a three-stage simulated annealing approach, that makes use of a portfolio of six different neighborhoods. Five of these neighborhoods are taken from the literature on round-robin tournament scheduling, whereas the last one, denoted as PartialSwapTeamsPhased, is a novel contribution and it is specifically designed for the phased version of the problem. We perform a comprehensive and statistically principled tuning procedure to find the best combination of parameters for the competition instances. We dedicate specific focus to evaluate the contribution given by the new neighborhood PartialSwapTeamsPhased, which yielded better results on most phased instances. Overall, the final outcome is that the three-stage simulated annealing solver is able to find a feasible solution on 44 out of 45 instances and ranked second in both the first competition milestone and the final round. We also propose an Integer Linear Programming model implemented in CPLEX, which, unfortunately, did not produce significant results on the instances of the competition.
Effects of an intermittent exercise protocol on ankle control during a single-legged landing
Authors: Ayalath Lakshmi R. , Bini Rodrigo , Wundersitz Daniel W. T. , Weerakkody Nivan , de Noronha Marcos 
Published: June 2022

Abstract
Purpose
To identify the effects of fatigue from an exercise protocol (similar to a soccer match) on ankle motion and forces during single-legged drop landing.

Methods
Seventeen males aged (mean ± SD) 22.2 ± 2.0 years participated in this repeated measures study. A 90-min intermittent exercise protocol with a 15-min rest at halftime was performed. Before, at halftime and after the exercise, participants were tested via a single-legged drop landing task onto a force platform whilst wearing a three-dimensional inertial measurement system (Xsens). Ankle angles (plantarflexion/dorsiflexion and inversion/eversion) were analysed before landing and at peak ground reaction force after landing, and center of pressure was analysed at peak ground reaction force.

Results
No significant differences were found for the outcomes between pre-, halftime and post-exercise (p > 0.05).

Conclusions
Findings suggest that exercises simulating a soccer match (regarding exertion) do not necessarily lead to significant changes in ankle motion or forces around the ankle.
Enhancement of antitumor immune response by radiation therapy combined with dual immune checkpoint inhibitor in a metastatic model of HER2-positive murine tumor
Authors: Misaki Sayaka , Murata Satoshi , Shimoji Miyuki , Iwai Takayasu , Sihombing Andreas Michael , Aoki Ken , Takahashi Yutaka , Watanabe Yoshiyuki 
Published: June 2022

Abstract
Purpose
Treatments for metastatic human epidermal growth factor receptor 2 (HER2)-positive tumors are improving but remain inadequate. We investigated activating antitumor immune response by combining radiation therapy with immune checkpoint inhibitors using mouse tumors overexpressing HER2, a pivotal driver oncogenic antigen, to develop new immunotherapies for metastatic HER2-positive tumors.

Materials and methods
NT2.5 cells were inoculated into the two mammary fat pads of FVB/N mice, which were divided into four groups: no treatment (Non), anti-PD-1 and anti-CTLA4 antibodies (P1C4), irradiation of the large tumor (Rad), and combination (R + P1C4) groups. Tumor growth, immunostaining of tumor-infiltrating lymphocytes, and the proportion of HER2-tumor antigen-specific CD8-positive T cells in the spleen and tumor-infiltrating lymphocytes were analyzed.

Results
In the Rad group, unirradiated and irradiated tumors shrank after treatment. Besides the directly irradiated tumors, the unirradiated tumors in the R + P1C4 group shrank the most. In the unirradiated tumors, CD8-positive T cells and FOXP3-positive T cells accumulated significantly more in the R + P1C4 group than in the P1C4 and the Rad groups (all p < 0.001). CD4-positive helper T cells accumulated significantly more in the R + P1C4 group than in the Rad group (p < 0.05), but this was not significantly different from the P1C4 group. HER2-specific CD8-positive T cells in the spleen and tumor-infiltrating lymphocytes were significantly increased in the R + P1C4 group compared to the P1C4 and Rad groups (all p < 0.0001).

Conclusion
Irradiation of HER2-positive tumors induced an antitumor immune effect against the unirradiated tumor, which was enhanced by the combined use of immune checkpoint inhibitors and was mediated by enhanced recruitment of HER2-tumor antigen-specific cytotoxic T lymphocytes at the tumor site in an HER2-positive mouse tumor model. Harnessing the distant antitumor immune response induced by the combination of radiation therapy and immune checkpoint inhibitors could be a promising treatment strategy for metastatic HER2-positive tumors.
Hazards from lakes and reservoirs: new interpretation of the Vaiont disaster
Authors: Dykes Alan P. , Bromhead Edward N. 
Published: June 2022

AbstractHazards in reservoirs and lakes arising from subaerial landslides causing impact waves (or ‘lake tsunamis’) are now well known, with several recent examples having been investigated in detail. The potential scale of such hazards was not widely known at the time of the Vaiont dam project in the 1950s and early 1960s, although a small wave triggered by a landslide at another new reservoir nearby in the Dolomites (northern Italy) drew the possible hazard to the attention of the Vaiont project’s managers. The Vaiont disaster in 1963 arose from a combination of disparate and seemingly unrelated factors and circumstances that led to an occurrence that could not have been imagined at that time. The ultimate cause was a very large landslide moving very rapidly into a reservoir and displacing the water. The resulting wave overtopped the dam to a height of around 175 m and around 2000 people were killed. This paper identifies and examines all of the issues surrounding the Vaiont dam and landslide in order to identify causal factors, contributory factors (including aggravating factors) and underlying factors. In doing so, it demonstrates that the disaster arose from the Vaiont dam project and cannot be attributed simply to the landslide. Underlying geological factors gave rise to the high speed of the landslide, which would have occurred anyway at some time. However, without the contributory factors that account for the presence of the reservoir, i.e. the choice of location for the project and management of the project with respect to a possible landslide hazard, there would have been no disaster. Indeed, the disaster could have been avoided if the reservoir could have been emptied pending further ground investigations. Understanding of this case provides many lessons for future dam projects in mountainous locations but also highlights an ongoing and perhaps under-appreciated risk from similar events involving other water bodies including geologically recent lakes formed behind natural landslide dams.
A Global Perspective on Sustainable Show Cave Tourism
Authors: Chiarini Veronica , Duckeck Jochen , De Waele Jo 
Published: June 2022

AbstractCaves are among the most visited geological features in the world, attracting over 70 million people every year in more than 1,200 caves worldwide, and amounting up to 800 million Euros in entrance fees alone. The global business of show caves employs roughly 25,000 people directly (management, guides), and at least 100 times more people if we consider the connected tourist activities (souvenir shops, local transport, travel agencies, restaurants, and bars). It is estimated that the whole show cave business has a global commercial value of roughly 2 billion Euros, a number that is increasing constantly. Show caves are generally fragile ecosystems, and care should be taken in their management to safeguard their value for future generations. The international scientific (speleological) community has issued international guidelines for the sustainable development and management of show caves eight years ago, but their application is still far from being applied globally, especially in developing and least developed countries. Cave tourism is expected to increase, especially in countries where caves are abundant but not yet considered as tourist attractions, and where economic and political instability slow down the development of tourism. There are still a lot of possibilities for the opening of new show caves, especially in countries with low Gross Domestic Income (GDI), but their management needs to be sustainable, so that caves become a means of sustaining local economies, educating people on these fragile geo- and ecosystems, and protecting contemporarily their scientific and cultural heritage for future generations.