bluuebunny/crossref_metadata_2025 huggingface dataset:
Not Just for Dancing? A Content Analysis of Concussion and Head Injury Videos on TikTok
Authors: Carter Peyton N. , Hall Eric E. , Ketcham Caroline J. , Ahmed Osman H.
Published: October 2021

Social media platforms are an accessible and increasingly used way for the public to gather healthcare-related information, including on sports injuries. “TikTok” is currently one of the fastest-growing social media platforms worldwide, and it is especially popular amongst adolescents and young adults. The widespread use and popularity of TikTok suggests that this platform has potential to be a source for healthcare information for younger individuals. The aim of this study was to gain a preliminary understanding of the concussion/head injury-related information on TikTok, and to gauge if TikTok could serve as a platform for concussion education. This exploratory study used a systematic search strategy to understand more about how concussion is being portrayed through TikTok videos. Using the keywords “concussion” and “head injury,” 200 videos were downloaded from TikTok and 43 videos were excluded. Of the 92 videos retrieved using the keyword “concussion,” 95% (n = 88) had more than 100,000 views and 6% (n = 10) had been viewed more than 10 million times. Over half, 54% (n = 50) of the “concussion” videos depicted individuals “playing around” and getting hit in the head, whilst only 1% (n = 1) of the TikTok videos were categorized as “explaining concussion facts.” The large numbers of views of concussion-related TikTok videos demonstrates the popularity of this platform and indicates that healthcare organizations should consider TikTok as a potential means for concussion education amongst younger individuals.
Improving Food Systems: A Participatory Consultation Exercise to Determine Priority Research and Action Areas in Viet Nam
Authors: Nguyen Trang , van den Berg Marrit , Raneri Jessica E. , Huynh Tuyen
Published: October 2021

With increased burden of malnutrition on global health, there is a need to set clear and transparent priorities for action in food systems at a global and local level. While priority settings methods are available for several adjacent domains, such as nutrition and health policies, setting priorities for food system research has not been documented and streamlined. The challenges involve food systems' multisector, multi-stakeholder and multi-outcome nature. Where data exists, it is not easy to aggregate data from across food system dimensions and stakeholders to make an informed analysis of the overall picture of the food system, as well as current and potential food system trade-offs to inform research and policy. Once research priorities are set, they risk staying on paper and never make their ways to concrete outputs and outcomes. In this paper, we documented and assessed the inclusive process of setting research priorities for a local food system, taking Vietnamese food systems as a case study. From this exercise, we examined how priority setting for food systems research could learn from and improve upon earlier priority setting research practices in other domains. We discussed the lessons for research and policies in local food systems, such as the need for a concrete follow-up plan accompanying the priority setting process.
Nomogram Predicting Parametrial Involvement Based on the Radical Hysterectomy Specimens in the Early-Stage Cervical Cancer
Authors: Li Chunbo , Yang Shimin , Hua Keqin
Published: October 2021

Objective: Radical hysterectomy (RH) is the surgical standard for the treatment of the early-stage cervical cancer (CC). However, this procedure is associated with a high rate of adverse impact on the quality of the life of the patient. Since the rate of parametrial involvement (PI) is low for the patients with the early-stage CC, some authors believe that the patients with the early-stage CC may benefit from the less radical surgery. This study aims to estimate the incidence of the PI in the patients with the early-stage CC and establish a simple nomogram to identify a cohort of the patients with low risk of the PI who may benefit from the less radical surgery.

Methods: All the patients who underwent the RH and pelvic lymphadenectomy were included from 2013 to 2018. The significant independent predictors were identified through the Cox regression analysis and then incorporated into a nomogram to predicate the PI. The calibration plots and receiver operating characteristic (ROC) curves were used to assess the predictive accuracy of the nomogram.

Results: A total of 4,533 patients met the inclusion criteria and 441 women (9.7%) had the PI. The positive PI rate in the ≤2 cm group (1.2%) was significantly lower compared to >2– ≤4 cm (6.2%) or >4 cm (22.4%) groups. The multivariate analyses revealed that tumor size (p = 0.002), lymphovascular space invasion (LVSI) (p = 0.001), vaginal involvement (VI) (p < 0.001), status of the pelvic lymph nodes (PLNs) (p = 0.001), and depth of stromal invasion (DSI) (p < 0.001) were the independent prognostic factors of the PI. Finally, the five variables were combined to construct the nomogram model. The concordance indexes (C-indexes) of the PI were 0.756 (95% CI 0.726–0.786) for the internal validation and 0.729 (95% CI 0.678–0.780) for the external validation. The calibration plots further showed good consistency between the nomogram prediction and the actual observation.

Conclusion: This study confirmed that the patients with tumor size 2 cm or smaller were at very low risk for the PI. If other variables such as negative LVSI, DSI <50%, no VI, and negative PLN were limited, the risk would reduce significantly. Meanwhile, a simple nomogram based on the significant clinicopathological characteristics could be used as a tool for the clinicians to predict the PI among the patients with the early-stage CC, who might benefit from a less radical surgery.
Environmental Impacts of Pig and Poultry Production: Insights From a Systematic Review
Authors: Andretta Ines , Hickmann Felipe M. W. , Remus Aline , Franceschi Carolina H. , Mariani Alexandre B. , Orso Catiane , Kipper Marcos , Létourneau-Montminy Marie-Pierre , Pomar Candido
Published: October 2021

Pig and poultry production systems have reached high-performance levels over the last few decades. However, there is still room for improvement when it comes to their environmental sustainability. This issue is even more relevant due to the growing demand for food demand since this surplus food production needs to be met at an affordable cost with minimum impact on the environment. This study presents a systematic review of peer-reviewed manuscripts that investigated the environmental impacts associated with pig and poultry production. For this purpose, independent reviews were performed and two databases were constructed, one for each production system. Previous studies published in peer-reviewed journals were considered for the databases if the method of life cycle assessment (LCA) was applied to pig (pork meat) or poultry (broiler meat or table eggs) production to estimate at least the potential effects of climate change, measured as CO2-eq. Studies considering the cradle-to-farm gate were considered, as well as those evaluating processes up to the slaughterhouse or processor gate. The pig database comprised 55 studies, while 30 publications were selected for the poultry database. These studies confirmed feeding (which includes the crop cultivation phase, manufacturing processes, and transportation) as the main contributor to the environmental impact associated with pig and poultry production systems. Several studies evaluated feeding strategies, which were indicated as viable alternatives to mitigate the environmental footprint associated with both production chains. In this study, precision feeding techniques are highlighted given their applicability to modern pig and poultry farming. These novel feeding strategies are good examples of innovative strategies needed to break paradigms, improve resource-use efficiency, and effectively move the current productive scenario toward more sustainable livestock systems.
Predicting the Photosynthetic Rate of Chinese Brassica Using Deep Learning Methods
Authors: Gao Peng , Xie Jiaxing , Yang Mingxin , Zhou Ping , Liang Gaotian , Chen Yufeng , Sun Daozong , Han Xiongzhe , Wang Weixing
Published: October 2021

Water stress is a significant element impacting photosynthesis, which is one of the major physiological activities governing crop growth and development. In this study, the photosynthetic rate of Brassica chinensis L. var. parachinensis (Bailey) (referred to as Chinese Brassica hereafter) was predicted using the deep learning method. Five sets of Chinese Brassica were created, each with a different water stress gradient. Air temperature (Ta), relative humidity (RH), canopy temperature (Tc), transpiration rate (Tr), photosynthetic rate (Pn), and photosynthetically available radiation (PAR) were measured in different growth stages. The upper limit and lower limit equations were built using the non-water-stress baseline (NWSB) and hierarchical density-based spatial clustering of applications with noise (HDBSCAN) methods. The crop water stress index (CWSI) was then calculated using these built equations. The multivariate long short-term memory (MLSTM) model was proposed to predict Pn based on CWSI and other parameters. At the same time, the support vector regression (SVR) method was applied to provide a comparison to the MSLTM model. The results show that water stress had an important effect on the growth of Chinese Brassica. The more serious the water stress, the lower the growth range (GR). The HDBSCAN method had a lower root mean square error (RMSE) in calculating CWSI. Furthermore, the CWSI had a significant effect on predicting Pn. The regression fitting between measured Pn and predicted Pn showed that the determination coefficient (R2) and RMSE were 0.899 and 0.108 μmol·m−2·s−1, respectively. In this study, we successfully developed a method for the reliable prediction of Pn in Chinese Brassica, which can serve as a useful reference for application in water saving.
Update on Paraneoplastic Cerebellar Degeneration
Authors: Loehrer Philipp Alexander , Zieger Lara , Simon Ole J.
Published: October 2021

Purpose of review: To provide an update on paraneoplastic cerebellar degeneration (PCD), the involved antibodies and tumors, as well as management strategies. Recent findings: PCD represents the second most common presentation of the recently established class of immune mediated cerebellar ataxias (IMCAs). Although rare in general, PCD is one of the most frequent paraneoplastic presentations and characterized clinically by a rapidly progressive cerebellar syndrome. In recent years, several antibodies have been described in association with the clinical syndrome related to PCD; their clinical significance, however, has yet to be determined. The 2021 updated diagnostic criteria for paraneoplastic neurologic symptoms help to establish the diagnosis of PCD, direct cancer screening, and to evaluate the presence of these newly identified antibodies. Recognition of the clinical syndrome and prompt identification of a specific antibody are essential for early detection of an underlying malignancy and initiation of an appropriate treatment, which represents the best opportunity to modulate the course of the disease. As clinical symptoms can precede tumor diagnosis by years, co-occurrence of specific symptoms and antibodies should prompt continuous surveillance of the patient. Summary: We provide an in-depth overview on PCD, summarize recent findings related to PCD, and highlight the transformed diagnostic approach.
CBFB Break-Apart FISH Testing: An Analysis of 1629 AML Cases with a Focus on Atypical Findings and Their Implications in Clinical Diagnosis and Management
Authors: Yang Richard K. , Toruner Gokce A. , Wang Wei , Fang Hong , Issa Ghayas C. , Wang Lulu , Quesada Andrés E. , Thakral Beenu , Patel Keyur P. , Peng Guang , Liu Shujuan , Yin C. Cameron , Borthakur Gautam , Tang Zhenya , Wang Sa A. , Miranda Roberto N. , Khoury Joseph D. , Medeiros L. Jeffrey , Tang Guilin
Published: October 2021

Fluorescence in situ hybridization (FISH) is a confirmatory test to establish a diagnosis of inv(16)/t(16;16) AML. However, incidental findings and their clinical diagnostic implication have not been systemically studied. We studied 1629 CBFB FISH cases performed in our institution, 262 (16.1%), 1234 (75.7%), and 133 (8.2%) were reported as positive, normal, and abnormal, respectively. The last included CBFB copy number changes (n = 120) and atypical findings such as 3′CBFB deletion (n = 11), 5′CBFB deletion (n = 1), and 5′CBFB gain (n = 1). Correlating with CBFB-MYH11 RT-PCR results, totally 271 CBFB rearrangement cases were identified, including five with discrepancies between FISH and RT-PCR due to new partner genes (n = 3), insertion (n = 1), or rare CBFB-MYH11 variant (n = 1) and eight with 3′CBFB deletion. All cases with atypical findings and/or discrepancies presented clinical diagnostic challenges. Correlating FISH signal patterns and karyotypes, additional chromosome 16 aberrations (AC16As) show impacts on the re-definition of a complex karyotype and prognostic prediction. The CBFB rearrangement but not all AC16As will be detected by NGS-based methods. Therefore, FISH testing is currently still needed to provide a quick and straightforward confirmatory inv(16)/t(16;16) AML diagnosis and additional information related to clinical management.
Expression Levels of RAD51 Inversely Correlate with Survival of Glioblastoma Patients
Authors: Morrison Christopher , Weterings Eric , Mahadevan Daruka , Sanan Abhay , Weinand Martin , Stea Baldassarre
Published: October 2021

Treatment failures of glioblastoma (GBM) occur within high-dose radiation fields. We hypothesized that this is due to increased capacity for DNA damage repair in GBM. We identified 24 adult GBM patients treated with maximal safe resection followed by radiation with concurrent and adjuvant temozolomide. The mRNA from patients was quantified using NanoString Technologies’ nCounter platform and compared with 12 non-neoplastic temporal lobe tissue samples as a control. Differential expression analysis identified seven DNA repair genes significantly upregulated in GBM tissues relative to controls (>4-fold difference, adjusted p values < 0.001). Among these seven genes, Cox proportional hazards models identified RAD51 to be associated with an increased risk of death (HR = 3.49; p = 0.03). Kaplan–Meier (KM) analysis showed that patients with high RAD51 expression had significantly shorter OS compared to low levels (median OS of 10.6 mo. vs 20.1 mo.; log-rank p = 0.03). Our findings were validated in a larger external dataset of 162 patients using publicly available gene expression data quantified by the same NanoString technology (median OS of 13.8 mo. vs. 17.4 mo; log-rank p = 0.006). Within this uniformly treated GBM population, RAD51, in the homologous recombination pathway, was overexpressed (vs. normal brain) and inversely correlated with OS. High RAD51 expression may be a prognostic biomarker and a therapeutic target in GBM.
TP53 Mutation Is a Prognostic Factor in Lower Grade Glioma and May Influence Chemotherapy Efficacy
Authors: Noor Humaira , Briggs Nancy E. , McDonald Kerrie L. , Holst Jeff , Vittorio Orazio
Published: October 2021

Background: Identification of prognostic biomarkers in cancers is a crucial step to improve overall survival (OS). Although mutations in tumour protein 53 (TP53) is prevalent in astrocytoma, the prognostic effects of TP53 mutation are unclear. Methods: In this retrospective study, we sequenced TP53 exons 1 to 10 in a cohort of 102 lower-grade glioma (LGG) subtypes and determined the prognostic effects of TP53 mutation in astrocytoma and oligodendroglioma. Publicly available datasets were analysed to confirm the findings. Results: In astrocytoma, mutations in TP53 codon 273 were associated with a significantly increased OS compared to the TP53 wild-type (HR (95% CI): 0.169 (0.036–0.766), p = 0.021). Public datasets confirmed these findings. TP53 codon 273 mutant astrocytomas were significantly more chemosensitive than TP53 wild-type astrocytomas (HR (95% CI): 0.344 (0.13–0.88), p = 0.0148). Post-chemotherapy, a significant correlation between TP53 and YAP1 mRNA was found (p = 0.01). In O (6)-methylguanine methyltransferase (MGMT) unmethylated chemotherapy-treated astrocytoma, both TP53 codon 273 and YAP1 mRNA were significant prognostic markers. In oligodendroglioma, TP53 mutations were associated with significantly decreased OS. Conclusions: Based on these findings, we propose that certain TP53 mutant astrocytomas are chemosensitive through the involvement of YAP1, and we outline a potential mechanism. Thus, TP53 mutations may be key drivers of astrocytoma therapeutic efficacy and influence survival outcomes.
Enhancing T Cell Chemotaxis and Infiltration in Glioblastoma
Authors: Singh Kirit , Hotchkiss Kelly M. , Patel Kisha K. , Wilkinson Daniel S. , Mohan Aditya A. , Cook Sarah L. , Sampson John H.
Published: October 2021

Glioblastoma is an immunologically ‘cold’ tumor, which are characterized by absent or minimal numbers of tumor-infiltrating lymphocytes (TILs). For those tumors that have been invaded by lymphocytes, they are profoundly exhausted and ineffective. While many immunotherapy approaches seek to reinvigorate immune cells at the tumor, this requires TILs to be present. Therefore, to unleash the full potential of immunotherapy in glioblastoma, the trafficking of lymphocytes to the tumor is highly desirable. However, the process of T cell recruitment into the central nervous system (CNS) is tightly regulated. Naïve T cells may undergo an initial licensing process to enter the migratory phenotype necessary to enter the CNS. T cells then must express appropriate integrins and selectin ligands to interact with transmembrane proteins at the blood–brain barrier (BBB). Finally, they must interact with antigen-presenting cells and undergo further licensing to enter the parenchyma. These T cells must then navigate the tumor microenvironment, which is rich in immunosuppressive factors. Altered tumoral metabolism also interferes with T cell motility. In this review, we will describe these processes and their mediators, along with potential therapeutic approaches to enhance trafficking. We also discuss safety considerations for such approaches as well as potential counteragents.
Breast Invasive Ductal Carcinoma Classification on Whole Slide Images with Weakly-Supervised and Transfer Learning
Authors: Kanavati Fahdi , Tsuneki Masayuki
Published: October 2021

Invasive ductal carcinoma (IDC) is the most common form of breast cancer. For the non-operative diagnosis of breast carcinoma, core needle biopsy has been widely used in recent years for the evaluation of histopathological features, as it can provide a definitive diagnosis between IDC and benign lesion (e.g., fibroadenoma), and it is cost effective. Due to its widespread use, it could potentially benefit from the use of AI-based tools to aid pathologists in their pathological diagnosis workflows. In this paper, we trained invasive ductal carcinoma (IDC) whole slide image (WSI) classification models using transfer learning and weakly-supervised learning. We evaluated the models on a core needle biopsy (n = 522) test set as well as three surgical test sets (n = 1129) obtaining ROC AUCs in the range of 0.95–0.98. The promising results demonstrate the potential of applying such models as diagnostic aid tools for pathologists in clinical practice.
Update on Novel Therapeutics for Primary CNS Lymphoma
Authors: Schaff Lauren R. , Grommes Christian
Published: October 2021

Primary central nervous system lymphoma (PCNSL) is a rare lymphoma isolated to the central nervous system or vitreoretinal space. Standard treatment consists of cytotoxic methotrexate-based chemotherapy, with or without radiation. Despite high rates of response, relapse is common, highlighting the need for novel therapeutic approaches. Recent advances in the understanding of PCNSL have elucidated mechanisms of pathogenesis and resistance including activation of the B-cell receptor and mammalian target of rapamycin pathways. Novel treatment strategies such as the Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib, phosphatidylinositol-3 kinase (PI3K) inhibitors, and immunomodulatory drugs are promising. Increasingly, evidence suggests immune evasion plays a role in PCNSL pathogenesis and several immunotherapeutic strategies including checkpoint inhibition and targeted chimeric antigen receptor T (CAR-T) cells are under investigation. This review provides a discussion on the challenges in development of targeted therapeutic strategies, an update on recent treatment advances, and offers a look toward ongoing clinical studies.
Nonlinear Topological Effects in Optical Coupled Hexagonal Lattice
Authors: Li Fude , Xue Kang , Yi Xuexi
Published: October 2021

Topological physics in optical lattices have attracted much attention in recent years. The nonlinear effects on such optical systems remain well-explored and a large amount of progress has been achieved. In this paper, under the mean-field approximation for a nonlinearly optical coupled boson–hexagonal lattice system, we calculate the nonlinear Dirac cone and discuss its dependence on the parameters of the system. Due to the special structure of the cone, the Berry phase (two-dimensional Zak phase) acquired around these Dirac cones is quantized, and the critical value can be modulated by interactions between different lattices sites. We numerically calculate the overall Aharonov-Bohm (AB) phase and find that it is also quantized, which provides a possible topological number by which we can characterize the quantum phases. Furthermore, we find that topological phase transition occurs when the band gap closes at the nonlinear Dirac points. This is different from linear systems, in which the transition happens when the band gap closes and reopens at the Dirac points.
Entropy and Ergodicity of Boole-Type Transformations
Authors: Blackmore Denis , Balinsky Alexander A. , Kycia Radoslaw , Prykarpatski Anatolij K.
Published: October 2021

We review some analytic, measure-theoretic and topological techniques for studying ergodicity and entropy of discrete dynamical systems, with a focus on Boole-type transformations and their generalizations. In particular, we present a new proof of the ergodicity of the 1-dimensional Boole map and prove that a certain 2-dimensional generalization is also ergodic. Moreover, we compute and demonstrate the equivalence of metric and topological entropies of the 1-dimensional Boole map employing “compactified”representations and well-known formulas. Several examples are included to illustrate the results. We also introduce new multidimensional Boole-type transformations invariant with respect to higher dimensional Lebesgue measures and investigate their ergodicity and metric and topological entropies.
Exploring the Migration to a Digitalised Curriculum at UKZN
Authors: Khoza Simon Bheki.
Published: October 2021

The COVID-19 revolution has demanded that higher education institutions (HEIs) in South Africa, as in most other countries globally, migrate to a digitalised curriculum (DC). The DC is a plan for or of digital technology-driven education. The COVID-19 revolution compelled the University of KwaZulu-Natal (UKZN) to migrate to a DC in order to complete the 2020 academic year or calendar. Pragmatism, critical discourse analysis (CDA), and community of inquiry (CoI) with natural identity (NI) framed the document analysis used to generate data for this study. Purposive convenience sampling was used to select the published documents that carry information on the migration to a DC at UKZN. It was for this reason that this study explored and understood the migration to a DC at UKZN through the use of digital resources. Findings suggested that, while the UKZN had the professional identity of migration through engaging Moodle, it began the migration through the use of WhatsApp, Facebook, Skype, and Zoom video conferencing technology (ZVCT), promoting societal identity. The migration seemed to miss the personal or pragmatic identity as an important ingredient of a DC, which addresses individual personal needs. Consequently, this study recommends a DC that balances performance-based, competence-based, and pragmatic/personal identities in order to address professional, societal, and personal needs, respectively, for natural identity realisation.
Experimental Study on the Effect of Temperature on the Mechanical Properties of Unconsolidated Silty Sandstones
Authors: Arias-Buitrago Juan Alejandro , Alzate-Espinosa Guillermo A. , Arbelaez-Londoño Alejandra , Zambrano-Narvaez Gonzalo , Chalaturnyk Rick
Published: October 2021

Hydrocarbon reservoirs can be subjected to temperature changes due to different processes during production. Heat injection has become an advantageous method to produce heavy oils in Canada and Venezuela because it increases oil recovery. The heat reduces oil viscosity and oil flows easily. Colombia has significant heavy oil reserves in unconsolidated silty sandstones. It is important to understand the mechanical behavior of these reservoirs in thermal recovery conditions (temperature and effective stress). The reconstituted samples from a Colombian heavy oil outcrop were evaluated using a high-temperature and high-pressure triaxial cell. Twelve isotropically consolidated drained triaxial tests were conducted at three different effective stresses (0.4, 4.0, and 8.2 MPa) and a temperature range from 50 to 230 °C to represent the initial and thermal recovery conditions, and obtain parameters, such as Young’s and Bulk moduli, internal friction angle, and cohesion. The samples at higher confining stress (4.0 and 8.2 MPa) were under contraction, while samples at lower confining stress (0.4 MPa) were under dilation. The stiffness increased as the confining stress increased and decreased as temperature increased, and the strength properties significantly decreased as temperature increased. Finally, the Colombian samples exhibited low friction angles when compared to clean sandstones as Canadian sands.
Evaluation of Primary User Power Impact for Joint Optimization of Energy Efficiency in Cognitive Radio Networks
Authors: Yang Tian , Esseghir Moez , Khoukhi Lyes , Pan Su
Published: October 2021

Energy efficiency (EE) is of great concern in cognitive radio networks since the throughput and energy consumption of secondary users (SUs) vary with the sensing time. However, the conditions of the detection probability and false alarm probability should be respected to better protect primary users (PUs) and to improve the sensing performance of SUs. Additionally, the PUs’ minimum averaged power provision should also be regarded as a key problem of interactive linking to SUs. Therefore, an integrated design between the PU and SUs is desired for the coordination of the whole cognitive radio system, especially regarding the satisfaction of EE and performance metrics. This study formulates sensing constraints in a unified way and calculates the minimum SNR of SUs, based on which the essential PU power provision is computed. Furthermore, EE is proved as a decreasing function with the PU’s active ratio, where the maximum EE is obtained corresponding to the minimum QoS requirements of the sensing process. Hence, a bisection-based method is proposed to maximize EE, which is considered as a concave function of SUs’ sensing time and has only one unique optimum. EE’s optimization was analyzed under different fusion rules for diverse SNR conditions. The optimum was also studied with sensing performance targets for various cases of PU power provision.
Trisomy of Human Chromosome 21 Orthologs Mapping to Mouse Chromosome 10 Cause Age and Sex-Specific Learning Differences: Relevance to Down Syndrome
Authors: Minter Ross , Gardiner Katheleen J.
Published: October 2021

Down syndrome (DS), trisomy of human chromosome 21 (Hsa21), is the most common genetic cause of intellectual disability. The Dp10(1)Yey (Dp10) is a mouse model of DS that is trisomic for orthologs of 25% of the Hsa21 protein-coding genes, the entirety of the Hsa21 syntenic region on mouse chromosome 10. Trisomic genes include several involved in brain development and function, two that modify and regulate the activities of sex hormones, and two that produce sex-specific phenotypes as null mutants. These last four are the only Hsa21 genes with known sexually dimorphic properties. Relatively little is known about the potential contributions to the DS phenotype of segmental trisomy of Mmu10 orthologs. Here, we have tested separate cohorts of female and male Dp10 mice, at 3 and 9 months of age, in an open field elevated zero maze, rotarod, and balance beam, plus the learning and memory tasks, spontaneous alternation, puzzle box, double-H maze, context fear conditioning, and acoustic startle/prepulse inhibition, that depend upon the function of the prefrontal cortex, striatum, hippocampus, and cerebellum. We show that there are age and sex-specific differences in strengths and weaknesses, suggesting that genes within the telomere proximal region of Hsa21 influence the DS phenotype.
Epigenetic Mechanisms of ART-Related Imprinting Disorders: Lessons From iPSC and Mouse Models
Authors: Horánszky Alex , Becker Jessica L. , Zana Melinda , Ferguson-Smith Anne C. , Dinnyés András
Published: October 2021

The rising frequency of ART-conceived births is accompanied by the need for an improved understanding of the implications of ART on gametes and embryos. Increasing evidence from mouse models and human epidemiological data suggests that ART procedures may play a role in the pathophysiology of certain imprinting disorders (IDs), including Beckwith-Wiedemann syndrome, Silver-Russell syndrome, Prader-Willi syndrome, and Angelman syndrome. The underlying molecular basis of this association, however, requires further elucidation. In this review, we discuss the epigenetic and imprinting alterations of in vivo mouse models and human iPSC models of ART. Mouse models have demonstrated aberrant regulation of imprinted genes involved with ART-related IDs. In the past decade, iPSC technology has provided a platform for patient-specific cellular models of culture-associated perturbed imprinting. However, despite ongoing efforts, a deeper understanding of the susceptibility of iPSCs to epigenetic perturbation is required if they are to be reliably used for modelling ART-associated IDs. Comparing the patterns of susceptibility of imprinted genes in mouse models and IPSCs in culture improves the current understanding of the underlying mechanisms of ART-linked IDs with implications for our understanding of the influence of environmental factors such as culture and hormone treatments on epigenetically important regions of the genome such as imprints.
Numerical Investigation of the Effectiveness of Vegetation-Embankment Hybrid Structures for Tsunami Mitigation Introduced after the 2011 Tsunami
Authors: Tanaka Norio , Igarashi Yoshiya , Zaha Takehito
Published: October 2021

As a mitigation measure against a tsunami inundation, vegetation-embankment hybrid structures received attention after the 2011 Great East Japan Tsunami, and some structures have already been constructed or are under construction in Japan. The present study conducted a series of numerical simulations using a hybrid system comprised of an artificial structure (an embankment, moat) and a natural component (vegetation) that was experimentally proposed in previous studies as an effective structure for tsunami mitigation. After validating the numerical model using published data, this study investigated differences in the performance of the hybrid system by changing the tsunami period and height characteristics of the tsunami-like surge-type flow. As a result, the delay in tsunami arrival time (ΔT) was not affected by the tsunami wave period for the investigated hybrid structures. Among the investigated structures, Case Ve40ME (where Ve40, M, and E represent vegetation, moat, and embankment, respectively, in that order from seaward) showed the maximum performance of ΔT. The reductions of overflow volume (ΔQ), fluid force index (RFI), and moment index (RMI) declined during the tsunami period. The tsunami mitigation effect is closely related to the relationship between the development times of backwater rise, hydraulic jump, and the tsunami period. Case Ve40ME was effective for ΔT, ΔQ, and RMI. Case EMVe40 was especially effective for RFI. When the tsunami period is short, the water level at the shoreline starts to decrease before full development of the hydraulic jump generated in the hybrid system. Thus, overflow volume to landward decreases, and the mitigation effects increase. When the tsunami period is long, the receding phenomenon at the peak water level does not affect the maximum values, thus the mitigation effects become smaller compared with the short period. However, the superiority to other structures is maintained in Case Ve40ME and Case EMVe40 with seaward vegetation and landward vegetation, respectively.
Occupational and Leisure-Time Physical Activity Related to Job Stress and Job Satisfaction: Correspondence Analysis on a Population-Based Study
Authors: de-Pedro-Jiménez Domingo , Meneses-Monroy Alfonso , de Diego-Cordero Rocío , Hernández-Martín Marta María , Moreno-Pimentel Antonio Gabriel , Romero-Saldaña Manuel
Published: October 2021

Background: Leisure-time physical activity (LTPA) is not the same as occupational activity. Various factors influence both forms of physical activity, including job stress and job satisfaction, but the associations found are weak, and the need for new studies in large populations is emphasized. The objective was to study the relationship between job stress and job satisfaction, and the relationship between these and occupational and leisure-time physical activity according to the National Survey of Health 2017. Methods: A population-based study of 8716 workers between 18 and 65 years of age. The variables age, sex, leisure, and occupational-time physical activity (OTPA), educational level, type of occupation, job stress level, and job satisfaction were collected. A simple and multiple correspondence analysis was performed between the variables that reached statistical significance. Results: 4621 cases (53.02%) correspond to men with a mean age of 44.83 years (SD 10.22) and 4095 cases to women with a mean age of 44.55 years (SD 10.23). Women had higher percentages of higher education (p < 0.001), intermediate to high occupations and unskilled (p < 0.001), job stress (p < 0.001), covered the most extreme levels of satisfaction (p = 0.003), and do less LTPA (p < 0.001) and OTPA (p < 0.001). Also, in women a relationship was found between job stress and LTPA (p = 0.024), as well as between satisfaction and both forms of physical activity (OTPA p = 0.013 and LTPA p < 0.001). In men, significance was only reached in the relationship between job stress and OTPA (p <0.001). Conclusions. The higher the job stress, the less the job satisfaction, but the relationship is reversed in the intermediate categories. For both sexes, job stress is related to a sedentary lifestyle and higher employment and education levels. Higher levels of satisfaction correspond to higher levels of occupancy. The relationship between job satisfaction and educational level is direct in women but inverse in men. In women, there is a relationship between sedentary occupations and job satisfaction. In addition, intense physical activity at work is related to higher levels of job stress, lower satisfaction levels, and less physical activity in leisure-time.
Educating Medical Students for Practice in a Changing Landscape: An Analysis of Public Health Topics within Current Indonesian Medical Programs
Authors: Kadir Nurhira Abdul , Schütze Heike , Weston Kathryn M.
Published: October 2021

Medical curricula need to prepare doctors for emerging health issues and increased public health roles. With medical schools spread over a vast geographical region of Indonesia, ensuring that all schools meet appropriate standards in the quality of subjects, course delivery, and performance is challenging. This paper explores the inclusion of public health subjects in medical education across the country. A search of all subjects (n = 388) who were taught in 28 representative medical schools was undertaken and categorized by geographical region, accreditation grade, and according to the Indonesian National Standard of Medical Competency. Basic biomedicine subjects had the highest representation in the curricula (49.2 ± 8.7%) and public health was generally well represented (14.3 ± 5.0%). All medical schools complied with the minimum of 144 credits required for the bachelor stage. No statistically significant difference was found between school accreditation grades, or when an overall comparison of programs in Eastern and Western regions was undertaken. The Indonesian medical schools included have relatively good curriculum transparency, and public health is an important feature in their curricula. Further research is critical to identify the materials taught, the relevance and the applicability of the specific public health content, and the assessment of public health competency of graduates.
Societal Narratives on Caregivers in Asia
Authors: Ng Reuben , Indran Nicole
Published: October 2021

Although there has been an increase in awareness of the struggles experienced by caregivers, discourse on caregiving remains confined mostly to academia, policy circles or the family unit. There have been suggestions that public discourse on informal caregiving dwells overwhelmingly on the outsize toll it takes on the health of caregivers. However, few studies have examined societal narratives on caregivers—a gap our study aims to fill. We leveraged an online media database of 12 billion words collated from over 30 million articles to explore societal narratives on caregivers in six Asian countries. Computational linguistics and statistical analysis were applied to study the content of narratives on caregivers. The prevalence of societal narratives on caregivers was highest in Singapore—five times higher than Sri Lanka, which evidenced the lowest prevalence. Findings reveal that the inadequacies of institutional care as well as the need to train and empower caregivers are pressing issues that need to be prioritized on the policy agenda in Asia. Of broader significance, the diverse capabilities across Asia present opportunities for cross-country learning and capacity-building.
Relationship of the Use of Short Footwear with the Development of Hallux Valgus in a Sample of Andalusian Schoolchildren
Authors: González-Elena María Luisa , Castro-Méndez Aurora , Coheña-Jiménez Manuel , Córdoba-Fernández Antonio
Published: October 2021

Background: Several studies have shown the relationship between poor footwear fit and the risk of feet deformities. The available evidence seems to show that the development of hallux valgus deformity in the feet of schoolchildren may be related to the use of shoes that are poorly fitting in length. The objective of this cross-sectional study was to analyze the relationship between poor footwear fit in length and risk of developing hallux valgus. Methods: Using an instrument that was designed and calibrated for this purpose, maximum foot length was obtained and compared to the inner length of the shoe in 187 schoolchildren. Hallux valgus angle (HVA) was measured on weight-bearing podogram image obtained from the longest foot in 188 schoolchildren. Results: By default, the footwear was poorly fitting in length (too short or close-fitting) in 38.5% of the schoolchildren, with boys having the worst footwear fit; though no significant differences stood out. (p = 0.276). Regarding the HVA, no significant differences were recorded according to age or gender (p = 0.573). A strong correlation was observed between too-short footwear and the increase in HVA in 10-year-old boys (r = 0.817; p = 0.025) and in 9-year-old girls (r = 0.705; p = 0.005). Conclusions: Inadequate footwear fit in length may be a predisposing extrinsic risk factor for the development of hallux valgus in schoolchildren of both sexes. Results of the present study demonstrate the need to adapt the sizes of footwear to the rapid increase in foot-length that occur at puberty to avoid the risk of developing hallux valgus, especially at the ages of onset pubertal foot growth.
Sleep, Distressed Appearance, and Quality of Life Relate to Satisfaction with Orthognathic Surgery
Authors: Huang Yu-Shu , Chin Wei-Chih , Yao Chuan-Fong , Chen Ying-An , Tang I , Chen Yu-Ray , Lin Cheng-Hui
Published: October 2021

Background: In this study, we aimed to identify factors correlating with satisfaction with orthognathic surgery in order to improve its outcome. Methods: We recruited 77 participants who had received orthognathic surgery and 32 age- and gender-matched normal-controls. Questionnaires that included devised questions for family support, Big Five Inventory, Derriford Appearance Score, Pittsburgh Sleep Quality Index, Hospital Anxiety and Depression Scale, 36-Item Short-Form Health Survey, and a visual analogy scale for satisfaction, were completed before and one month and nine months after the surgery. The statistical analysis methods included descriptive statistics, t-test, and Pearson correlation. Results: All participants received the preoperative and one-month follow-up, while 28 also completed the nine-month follow-up. Satisfaction was not significantly related to demographic data, but long-term satisfaction was related to an extraverted personality. The preoperative and postoperative results of the Derriford Appearance Scale were related to short-term and long-term satisfaction. Furthermore, both the preoperative and one-month postoperative Pittsburgh Sleep Quality Index findings were significantly related to short-term satisfaction. The postoperative 36-Item Short-Form Health Survey was significantly related to short-term and long-term satisfaction. Conclusions: Not only subjective distress and dysfunction of appearance but also sleep problems and quality of life were correlated to satisfaction with orthognathic surgery. In the future, relevant interventions can be developed to further improve patient’s satisfaction and their physical and mental health.
Mouse Models of CMML
Authors: Belotserkovskaya Ekaterina , Demidov Oleg
Published: October 2021

Chronic myelomonocytic leukemia (CMML) is a rare and challenging type of myeloproliferative neoplasm. Poor prognosis and high mortality, associated predominantly with progression to secondary acute myeloid leukemia (sAML), is still an unsolved problem. Despite a growing body of knowledge about the molecular repertoire of this disease, at present, the prognostic significance of CMML-associated mutations is controversial. The absence of available CMML cell lines and the small number of patients with CMML make pre-clinical testing and clinical trials complicated. Currently, specific therapy for CMML has not been approved; most of the currently available therapeutic approaches are based on myelodysplastic syndrome (MDS) and other myeloproliferative neoplasm (MNP) studies. In this regard, the development of the robust CMML animal models is currently the focus of interest. This review describes important studies concerning animal models of CMML, examples of methodological approaches, and the obtained hematologic phenotypes.
Immune Synapse Residency of Orai1 Alters Ca2+ Response of T Cells
Authors: Voros Orsolya , Panyi György , Hajdu Péter
Published: October 2021

CRAC, which plays important role in Ca2+-dependent T-lymphocyte activation, is composed of the ER-resident STIM1 and the plasma membrane Orai1 pore-forming subunit. Both accumulate at the immunological synapse (IS) between a T cell and an antigen-presenting cell (APC). We hypothesized that adapter/interacting proteins regulate Orai1 residence in the IS. We could show that mGFP-tagged Orai1-Full channels expressed in Jurkat cells had a biphasic IS-accumulation kinetics peaked at 15 min. To understand the background of Orai1 IS-redistribution we knocked down STIM1 and SAP97 (adaptor protein with a short IS-residency (15 min) and ability to bind Orai1 N-terminus): the mGFP-Orai1-Full channels kept on accumulating in the IS up to the 60th minute in the STIM1- and SAP97-lacking Jurkat cells. Deletion of Orai1 N terminus (mGFP-Orai1-Δ72) resulted in the same time course as described for STIM1/SAP97 knock-down cells. Ca2+-imaging of IS-engaged T-cells revealed that of Orai1 residency modifies the Ca2+-response: cells expressing mGFP-Orai1-Δ72 construct or mGFP-Orai1-Full in SAP-97 knock-down cells showed higher number of Ca2+-oscillation up to the 90th minute after IS formation. Overall, these data suggest that SAP97 may contribute to the short-lived IS-residency of Orai1 and binding of STIM1 to Orai1 N-terminus is necessary for SAP97-Orai1 interaction.
Functional Availability of ON-Bipolar Cells in the Degenerated Retina: Timing and Longevity of an Optogenetic Gene Therapy
Authors: Kralik Jakub , Kleinlogel Sonja
Published: October 2021

Degenerative diseases of the retina are responsible for the death of photoreceptors and subsequent loss of vision in patients. Nevertheless, the inner retinal layers remain intact over an extended period of time, enabling the restoration of light sensitivity in blind retinas via the expression of optogenetic tools in the remaining retinal cells. The chimeric Opto-mGluR6 protein represents such a tool. With exclusive ON-bipolar cell expression, it combines the light-sensitive domains of melanopsin and the intracellular domains of the metabotropic glutamate receptor 6 (mGluR6), which naturally mediates light responses in these cells. Albeit vision restoration in blind mice by Opto-mGluR6 delivery was previously shown, much is left to be explored in regard to the effects of the timing of the treatment in the degenerated retina. We performed a functional evaluation of Opto-mGluR6-treated murine blind retinas using multi-electrode arrays (MEAs) and observed long-term functional preservation in the treated retinas, as well as successful therapeutical intervention in later stages of degeneration. Moreover, the treatment decreased the inherent retinal hyperactivity of the degenerated retinas to levels undistinguishable from healthy controls. Finally, we observed for the first time micro electroretinograms (mERGs) in optogenetically treated animals, corroborating the origin of Opto-mGluR6 signalling at the level of mGluR6 of ON-bipolar cells.