bluuebunny/crossref_metadata_2025 huggingface dataset:
Lateral, Vertical, and Temporal Variability of Seawater Carbonate Chemistry at Hog Reef, Bermuda
Authors: Pezner Ariel K. , Courtney Travis A. , Page Heather N. , Giddings Sarah N. , Beatty Cory M. , DeGrandpre Michael D. , Andersson Andreas J.
Published: February 2021

Spatial and temporal carbonate chemistry variability on coral reefs is influenced by a combination of seawater hydrodynamics, geomorphology, and biogeochemical processes, though their relative influence varies by site. It is often assumed that the water column above most reefs is well-mixed with small to no gradients outside of the benthic boundary layer. However, few studies to date have explored the processes and properties controlling these multi-dimensional gradients. Here, we investigated the lateral, vertical, and temporal variability of seawater carbonate chemistry on a Bermudan rim reef using a combination of spatial seawater chemistry surveys and autonomous in situ sensors. Instruments were deployed at Hog Reef measuring current flow, seawater temperature, salinity, pHT, pCO2, dissolved oxygen (DO), and total alkalinity (TA) on the benthos, and temperature, salinity, DO, and pCO2 at the surface. Water samples from spatial surveys were collected from surface and bottom depths at 13 stations covering ∼3 km2 across 4 days. High frequency temporal variability in carbonate chemistry was driven by a combination of diel light and mixed semi-diurnal tidal cycles on the reef. Daytime gradients in DO between the surface and the benthos suggested significant water column production contributing to distinct diel trends in pHT, pCO2, and DO, but not TA. We hypothesize these differences reflect the differential effect of biogeochemical processes important in both the water column and benthos (organic carbon production/respiration) vs. processes mainly occurring on the benthos (calcium carbonate production/dissolution). Locally at Hog Reef, the relative magnitude of the diel variability of organic carbon production/respiration was 1.4–4.6 times larger than that of calcium carbonate production/dissolution, though estimates of net organic carbon production and calcification based on inshore-offshore chemical gradients revealed net heterotrophy (−118 ± 51 mmol m–2 day–1) and net calcification (150 ± 37 mmol CaCO3 m–2 day–1). These results reflect the important roles of time and space in assessing reef biogeochemical processes. The spatial variability in carbonate chemistry parameters was larger laterally than vertically and was generally observed in conjunction with depth gradients, but varied between sampling events, depending on time of day and modifications due to current flow.
Impact of Increased Nutrients and Lowered pH on Photosynthesis and Growth of Three Marine Phytoplankton Communities From the Coastal South West Atlantic (Patagonia, Argentina)
Authors: Masuda Takako , Prášil Ondřej , Villafañe Virginia E. , Valiñas Macarena S. , Inomura Keisuke , Helbling E. Walter
Published: February 2021

Effect of global change variables on the structure and photosynthesis of phytoplankton communities was evaluated in three different sites of the Patagonian coast of Argentina: enclosed bay (Puerto Madryn, PM), estuarine (Playa Unión, PU), and open waters (Isla Escondida, IE). We exposed samples to two contrasting scenarios: Present (nutrients atin situlevels) vs. Future (with lowered pH and higher nutrients inputs), and determined growth and photosynthetic responses after 2 days of acclimation. Under the Future condition phytoplankton growth was higher in the estuarine site compared to those in PM and IE. This effect was the most pronounced on large diatoms. While the increase of photosynthetic activity was not always observed in the Future scenario, the lower photosynthetic electron requirement for carbon fixation (Φe,C= ETR/PmB) in this scenario compared to the Present, suggests a more effective energy utilization. Long-term experiments were also conducted to assess the responses along a 4 days acclimation period in PU. Diatoms benefited from the Future conditions and had significantly higher growth rates than in the Present. In addition,Φe,Cwas lower after the acclimation period in the Future scenario, compared to the Present. Our results suggest that the availability, frequency and amount of nutrients play a key role when evaluating the effects of global change on natural phytoplankton communities. The observed changes in diatom growth under the Future scenario in PU and IE and photosynthesis may have implications in the local trophodynamics by bottom up control.
Reactive Solute Transport Through Two Contrasting Subterranean Estuary Exit Sites in the Ría de Vigo (NW Iberian Peninsula)
Authors: Calvo-Martin Elisa , Álvarez-Salgado Xosé Antón , Rocha Carlos , Ibánhez J. Severino Pino
Published: February 2021

Subterranean estuaries (STEs), where continental groundwaters and saltwaters meet, are zones of intense biogeochemical reactivity. As such, STEs significantly modify groundwater-borne nutrient fluxes to the coastal zone. Thus, evaluating their reactive role is crucial to anticipate impacts of submarine groundwater discharge (SGD) over coastal ecosystems. Here, we studied the nitrogen biogeochemistry of two STEs with contrasting wave-exposure and redox conditions in Panxón and Ladeira beaches (Ría de Vigo, NW Iberian Peninsula). Seasonal surveys were performed at the permanently saturated zone of both beaches during low tide in February, May, July, and October 2019. Sediment was sampled and porewater samples collected using push-pull piezometers. Salinity, 222Rn and 226Ra activities were used to trace water circulation inside each beach. Porewater nitrate, ammonium, nitrite and dissolved oxygen were used to evaluate the role of these STEs as reactive sinks or sources of inorganic nitrogen. Our results showed a marked seasonal variability of water circulation inside both beaches, with strong salinity gradients in February and May and weakened circulation in July and October. The presence of a gravel layer in Panxón beach completely altered the typical structure of STEs by increasing porewater transport and mixing through the beach interior. As a result, Panxón beach profiles were highly enriched in nitrate and oxygen. Conversely, suboxic, and anoxic conditions were prevalent in Ladeira beach during the study period, with ammonium being the prevailing inorganic nitrogen form. High nitrate concentrations occurred associated to the tidal circulation cell during February and May, being the only effective mechanism of sediment oxygenation in Ladeira beach. Although nitrate reduction and production were observed in both STEs, comparison with averaged conservative mixing porewater profiles showed that Ladeira beach acted as a net nitrogen sink whereas Panxón beach acted as a net nitrogen source. The presence of a gravel layer oxygenates the interior of Panxón beach, thus limiting nitrate reduction and promoting the amplification of groundwater-borne nitrogen fluxes to the coast.
Hybridization Effect on Crashworthiness Parameters of Natural Composite
Authors: Salim Hamza Sabah , Ismail Al Emran , Yuhazri M. Y. , Ariffin Ahmad Hamdan , Hameed Sultan Mohamed Thariq
Published: February 2021

The use of metallic materials in automotive industry leads to increasing fuel consumption and cost, so trends are starting to use lighter and cheaper materials. In automotive applications, fibers are used in composites because they are stronger, stiffer, and lighter than bulk materials, and they can achieve higher energy absorbing compared to metallic materials. The purpose of this work is to study the potential utilization of natural fibers in the crash energy absorbing applications. The experimental procedures (the principle of a combination of manual layup and vacuum bladder technique) were applied to search the influence of utilizing jute fiber mat on crashworthiness parameters of composite materials with other kinds of fibers such as woven glass fiber reinforced epoxy composites. The study involved corrugated composite tubes with three layers of jute and hybrid glass-jute/epoxy material have been tested in uniaxial quasi-static crush conditions at the speed 10 mm/min. The results exhibit that the tube of jute fiber was somewhat lower than synthetic fibers, but the substitution of one layer of jute fiber with one layer of glass fiber resulted in an improvement in the crashworthiness parameters. As hybrid jute-glass was used, the best result was obtained, where energy absorption and specific energy absorption are improved by 17.75% and 25.122%, respectively.
Sex Differences on Clinical Characteristics, Severity, and Mortality in Adult Patients With COVID-19: A Multicentre Retrospective Study
Authors: Sha Jing , Qie Guoqiang , Yao Qingchun , Sun Wenqing , Wang Cuiyan , Zhang Zhongfa , Wang Xingguang , Wang Peng , Jiang Jinjiao , Bai Xue , Chu Yufeng , Meng Mei
Published: February 2021

Background: Coronavirus disease-2019 (COVID-19) epidemic is spreading globally. Sex differences in the severity and mortality of COVID-19 emerged. This study aims to describe the impact of sex on outcomes in COVOD-19 with a special focus on the effect of estrogen.

Methods: We performed a retrospective cohort study which included 413 patients (230 males and 183 females) with COVID-19 from three designated hospitals in China with a follow up time from January 31, 2020, to April 17, 2020. Women over 55 were considered as postmenopausal patients according to the previous epidemiological data from China. The interaction between age and sex on in-hospital mortality was determined through Cox regression analysis. In addition, multivariate Cox regression models were performed to explore risk factors associated with in-hospital mortality of COVID-19.

Results: Age and sex had significant interaction for the in-hospital mortality (P < 0.001). Multivariate Cox regression showed that age (HR 1.041, 95% CI 1.009–1.073, P = 0.012), male sex (HR 2.033, 95% CI 1.007–2.098, P = 0.010), the interaction between age and sex (HR 1.118, 95% CI 1.003–1.232, P = 0.018), and comorbidities (HR 9.845, 95% CI 2.280–42.520, P = 0.002) were independently associated with in-hospital mortality of COVID-19 patients. In this multicentre study, female experienced a lower fatality for COVID-19 than male (4.4 vs. 10.0%, P = 0.031). Interestingly, stratification by age group revealed no difference in-hospital mortality was noted in women under 55 compared with women over 55 (3.8 vs. 5.2%, P = 0.144), as well as in women under 55 compared with the same age men (3.8 vs. 4.0%, P = 0.918). However, there was significantly difference in women over 55 with men of the same age group (5.2 vs. 21.0%, P = 0.007). Compared with male patients, female patients had higher lymphocyte (P < 0.001) and high-density lipoprotein (P < 0.001), lower high sensitive c reaction protein level (P < 0.001), and lower incidence rate of acute cardiac injury (6.6 vs. 13.5%, P = 0.022).

Conclusion: Male sex is an independent risk factor for COVID-19 in-hospital mortality. Although female mortality in COVID-19 is lower than male, it might not be directly related to the effect of estrogen. Further study is warranted to identify the sex difference in COVID-19 and mechanisms involved.
Genetics of Behçet's Disease: Functional Genetic Analysis and Estimating Disease Heritability
Authors: Ortiz-Fernández Lourdes , Sawalha Amr H.
Published: February 2021

Behçet's disease is a chronic multisystemic inflammatory disorder characterized by recurrent oral and genital ulcers. Although its etiology remains unclear, it is thought that both genetic and environmental factors contribute to the onset and progression of Behçet's disease. Here, we provide an updated view of the genetic landscape and architecture of Behçet's disease. Large-scale genetic studies performed to date revealed 21 genetic susceptibility loci associated with the disease at a GWAS level of significance (p-value = 5 × 10−8). We performed epigenetic pattern enrichment analysis in Behçet's disease associated loci, providing new insights into the molecular mechanisms underlying its pathophysiology. Our data suggest the crucial involvement of several immune cell types, including natural killer cells, monocytes, and B cells in the pathogenesis of the disease. Pathway enrichment analysis identified important biological processes involved. Using large-scale genetic data available from ~200 immune-related loci (Immunochip), we estimate Behçet's disease heritability to be at least 16%. We further used the same approach to estimate the heritability explained by the known Behçet's disease-associated loci, suggesting that they explain ~ 60% of the genetic component underlying Behçet's disease. These results indicate a significant role of non-genetic factors in causing Behçet's disease and that additional genetic variation influencing the risk of Behçet's disease remains to be identified. Finally, we calculated a cumulative genetic risk score across populations reinforcing the link between geographic variations in disease prevalence with its genetic component.
Early Diffusion of SARS-CoV-2 Infection in the Inner Area of the Italian Sardinia Island
Authors: Piras Giovanna , Grandi Nicole , Monne Maria , Asproni Rosanna , Fancello Tatiana , Fiamma Maura , Mameli Giuseppe , Casu Gavino , lo Maglio Iana , Palmas Angelo D. , Tramontano Enzo
Published: February 2021

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for the coronavirus disease 2019 (COVID-19) pandemic, which started as a severe pneumonia outbreak in Wuhan, China, in December 2019. Italy has been the first European country affected by the pandemic, registering a total of 300,363 cases and 35,741 deaths until September 24, 2020. The geographical distribution of SARS-CoV-2 in Italy during early 2020 has not been homogeneous, including regions severely affected as well as administrative areas being only slightly interested by the infection. Among the latter, Sardinia represents one of the lowest incidence areas likely due to its insular nature.

Methods

Next-generation sequencing of a small number of complete viral genomes from clinical samples and their virologic and phylogenetic characterization was performed.

Results

We provide a first overview of the SARS-CoV-2 genomic diversity in Sardinia in the early phase of the March–May 2020 pandemic based on viral genomes isolated in the most inner regional hospital of the island. Our analysis revealed a remarkable genetic diversity in local SARS-CoV-2 viral genomes, showing the presence of at least four different clusters that can be distinguished by specific amino acid substitutions. Based on epidemiological information, these sequences can be linked to at least eight different clusters of infection, four of which likely originates from imported cases. In addition, the presence of amino acid substitutions that were not previously reported in Italian patients has been observed, asking for further investigations in a wider population to assess their prevalence and dynamics of emergence during the pandemic.

Conclusion

The present study provides a snapshot of the initial phases of the SARS-CoV-2 infection in inner area of the Sardinia Island, showing an unexpected genomic diversity.
The Good, the Bad, and the Ugly: Mycotoxin Production During Postharvest Decay and Their Influence on Tritrophic Host–Pathogen–Microbe Interactions
Authors: Bartholomew Holly P. , Bradshaw Michael , Jurick Wayne M. , Fonseca Jorge M.
Published: February 2021

Mycotoxins are a prevalent problem for stored fruits, grains, and vegetables. Alternariol, aflatoxin, and patulin, produced by Alternaria spp., Aspergillus spp., and Penicillium spp., are the major mycotoxins that negatively affect human and animal health and reduce fruit and produce quality. Control strategies for these toxins are varied, but one method that is increasing in interest is through host microbiome manipulation, mirroring a biocontrol approach. While the majority of mycotoxins and other secondary metabolites (SM) produced by fungi impact host–fungal interactions, there is also an interplay between the various organisms within the host microbiome. In addition to SMs, these interactions involve compounds such as signaling molecules, plant defense and growth hormones, and metabolites produced by both the plants and microbial community. Therefore, studies to understand the impact of the various toxins impacting the beneficial and harmful microorganisms that reside within the microbiome is warranted, and could lead to identification of safe analogs for antimicrobial activity to reduce fruit decay. Additionally, exploring the composition of the microbial carposphere of host plants is likely to shed light on developing a microbial consortium to maintain quality during storage and abate mycotoxin contamination.
Screening and Identification of Key Common and Specific Genes and Their Prognostic Roles in Different Molecular Subtypes of Breast Cancer
Authors: Sun Na , Gao Pingping , Li Yanling , Yan Zexuan , Peng Zaihui , Zhang Yi , Han Fei , Qi Xiaowei
Published: February 2021

Breast cancer is one of the most common cancers. Although the present molecular classification improves the treatment effect and prognosis of breast cancer, the heterogeneity of the molecular subtype remains very complex, and the applicability and effectiveness of treatment methods are still limited leading to poorer patient prognosis than expected. Further identification of more refined molecular typing based on gene expression profile will yield better understanding of the heterogeneity, improving treatment effects and prolonging prognosis of patients. Here, we downloaded the mRNA expression profiles and corresponding clinical data of patients with breast cancer from public databases and performed typical molecular typing using PAM50 (Prediction Analysis of Microarray 50) method. Comparative analyses were performed to screen the common and specific differentially expressed genes (DEGs) between cancer and corresponding para-cancerous tissues in each breast cancer subtype. The GO and KEGG analyses of the DEGs were performed to enrich the common and specific functional progress and signaling pathway involved in breast cancer subtypes. A total of 38 key common and specific DEGs were identified and selected based on the validated results, GO/KEGG enrichments, and the priority of expression, including four common DEGs and 34 specific DEGs in different subtypes. The prognostic value of these key common and specific DEGs was further analyzed to obtain useful potential markers in clinic. Finally, the potential roles and the specific prognostic values of the common and specific DEGs were speculated and summarized in total breast cancer and different subtype breast cancer based on the results of these analyses. The findings of our study provide the basis of more refined molecular typing of breast cancer, potential new therapeutic targets and prognostic markers for different breast cancer subtypes
Potential Molecular Mechanism of TNF Superfamily-Related Genes in Glioblastoma Multiforme Based on Transcriptome and Epigenome
Authors: Xie Hui , Yuan Ce , Li Jin-jiang , Li Zhao-yang , Lu Wei-cheng
Published: February 2021

Objective:This study aimed to investigate the molecular mechanism of tumor necrosis factor (TNF) superfamily-related genes and potential therapeutic drugs for glioblastoma multiforme (GBM) patients based on transcriptome and epigenome.

Methods:Gene expression data, corresponding clinical data, and methylation data of GBM samples and normal samples in the TCGA-GBM and GTEx datasets were downloaded. The TNF-related genes were obtained, respectively, from two groups in the TCGA dataset. Then, the TNF-related differentially expressed genes (DEGs) were investigated between two groups, followed by enrichment analysis. Moreover, TNF superfamily-related gene expression and upstream methylation regulation were investigated to explore candidate genes and the prognostic model. Finally, the protein expression level of candidate genes was performed, followed by drug prediction analysis.

Results:A total of 41 DEGs including 4 ligands, 18 receptors, and 19 downstream signaling molecules were revealed between two groups. These DEGs were mainly enriched in pathways like TNF signaling and functions like response to TNF. A total of 5 methylation site-regulated prognosis-related genes including TNF Receptor Superfamily Member (TNFRSF) 12A, TNFRSF11B, and CD40 were explored. The prognosis model constructed by 5 genes showed a well-prediction effect on the current dataset and verification dataset. Finally, drug prediction analysis showed that zoledronic acid (ZA)-TNFRSF11B was the unique drug–gene relation in both two databases.

Conclusion:Methylation-driven gene TNFRSF12A might participate in the development of GBM via response to the TNF biological process and TNF signaling pathway and significantly associated with prognosis. ZA that targets TNFRSF11B expression might be a potential effective drug for clinical treatment of GBM.
Freedom From Seizures Might Be Key to Continuing Occupation After Epilepsy Surgery
Authors: Nozaki Toshiki , Fujimoto Ayataka , Yamazoe Tomohiro , Niimi Keiko , Baba Shimpei , Yamamoto Takamichi , Sato Keishiro , Enoki Hideo , Okanishi Tohru
Published: February 2021

Introduction: We hypothesized that epilepsy surgery for adult patients with temporal lobe epilepsy (TLE) who obtained freedom from seizures could provide opportunities for these patients to continue their occupation, and investigated continuity of occupation to test this postulation.

Methods: Data were obtained from patients who had undergone resective surgery for medically intractable TLE between October 2009 and April 2019 in our hospital. Inclusion criteria were as follows: (1) ≥16 years old at surgery; (2) post-operative follow-up ≥12 months; (3) seizure-free period ≥12 months. As a primary outcome, we evaluated employment status before and after surgery, classified into three categories as follows: Level 0, no job; Level 1, students or homemakers (financially supported by a family member); and Level 2, working. Neuropsychological status was also evaluated as a secondary outcome.

Results: Fifty-one (87.9%) of the 58 enrolled TLE patients who obtained freedom from seizures after surgery continued working as before or obtained a new job (employment status: Level 2). A significant difference in employment status was identified between before and after surgery (p = 0.007; Wilcoxon signed-rank test). Twenty-eight patients (48.3%) were evaluated for neuropsychological status both before and after surgery. Significant differences in Wechsler Adult Intelligence Scale-III scores were identified between before and after surgery (p < 0.05 each; paired t-test).

Conclusion: Seizure freedom could be a factor that facilitates job continuity, although additional data are needed to confirm that possibility. Further investigation of job continuity after epilepsy surgery warrants an international, multicenter study.
A Neurodisparity Index of Nationwide Access to Neurological Health Care in Northern Ireland
Authors: McCarron Mark O. , Clarke Mike , Burns Paul , McCormick Michael , McCarron Peter , Forbes Raeburn B. , McCarron Luke V. , Mullan Fiona , McVerry Ferghal
Published: February 2021

Nationwide disparities in managing neurological patients have rarely been reported. We compared neurological health care between the population who reside in a Health and Social Care Trust with a tertiary neuroscience center and those living in the four non-tertiary center Trusts in Northern Ireland. Using the tertiary center Trust population as reference, neurodisparity indices (NDIs) defined as the number of treated patients resident in each Trust per 100,000 residents compared to the same ratio in the tertiary center Trust for a fixed time period. NDIs were calculated for four neurological pathways—intravenous thrombolysis (iv-tPA) and mechanical thrombectomy (MT) for acute ischemic stroke (AIS), disease modifying treatment (DMT) in multiple sclerosis (MS) and admissions to a tertiary neurology ward. Neurological management was recorded in 3,026 patients. Patients resident in the tertiary center Trust were more likely to receive AIS treatments (iv-tPA and MT) and access to the neurology ward (p< 0.001) than patients residing in other Trusts. DMT use for patients with MS was higher in two non-tertiary center Trusts than in the tertiary center Trust. There was a geographical gradient for MT for AIS patients and ward admissions. Averaged NDIs for non-tertiary center Trusts were: 0.48 (95%CI 0.32–0.71) for patient admissions to the tertiary neurology ward, 0.50 (95%CI 0.38–0.66) for MT in AIS patients, 0.78 (95%CI 0.67–0.92) for iv-tPA in AIS patients, and 1.11 (95%CI 0.99–1.26) for DMT use in MS patients. There are important neurodisparities in Northern Ireland, particularly for MT and tertiary ward admissions. Neurologists and health service planners should be aware that geography and time-dependent management of neurological patients worsen neurodisparities.
Magnetic Resonance Imaging Findings in Childhood Epilepsy at a Tertiary Hospital in Kenya
Authors: Samia Pauline , Odero Nicholas , Njoroge Maureen , Ochieng Shem , Mavuti Jacqueline , Waa Sheila , Gwer Samson
Published: February 2021

Background: Neuroimaging is important for determining etiology and guiding care in early childhood epilepsy. However, access to appropriate imaging in sub-Saharan Africa is modest, and as a consequence, etiological descriptions of childhood epilepsy in the region have been limited. We sought to describe MRI findings in children with epilepsy presenting to a tertiary hospital in Nairobi, Kenya, over a 6-year period of routine care.

Materials and Methods: We undertook a retrospective review of MRI findings of children aged between 0 and 18 years with a diagnosis of epilepsy presenting to the pediatric neurology department of Aga Khan University Hospital in Nairobi, Kenya, between January 2014 and July 2020. Over this period, the hospital had 1.5T MRI machines (GE1.5T Signa Excite and GE 1.5T Signa Explorer) and a 3T MRI machine (Philips 3T Ingenia). MRI images were independently reviewed by two study radiologists, and the findings were summarized and categorized into a study database. Related clinical and electroencephalographic (EEG) details were extracted from patient records. Categorical data analysis methods were applied to investigate for relationships between clinically relevant neuroimaging findings and key clinical and EEG observations.

Results: Over the study period, 288 children with a confirmed diagnosis of epilepsy had an MRI. They were of median age of 6 [interquartile range (IQR) 2–11] years. Ninety-five (33%) children had abnormal findings on imaging. The most common findings were encephalomalacia related to chronic infarcts (n = 18: 6.3%), cerebral atrophy (n = 11: 3.8%), disorders of neuronal migration (n = 11: 3.8%), periventricular leukomalacia (n = 9: 3.1%), and hippocampal sclerosis (n = 8: 2.8%). Findings related to infectious etiology were only observed in four children. Clinical comorbidity and inter-ictal epileptiform activity on EEG were independently associated with abnormal findings on imaging.

Conclusion: Up to a third of the children who underwent an MRI had a positive yield for abnormal findings. Imaging findings related to infectious etiologies were little observed in our cohort, in contradistinction to etiology studies in similar settings. At the time of the study, comorbidity and inter-ictal epileptiform activity on EEG were associated with abnormal findings on imaging and should be considered in informing prioritization for imaging in childhood epilepsy in this setting.
Gait in Benign Paroxysmal Positional Vertigo
Authors: Lim Yong-Hyun , Kang Kyunghun , Lee Ho-Won , Kim Ji-Soo , Kim Sung-Hee
Published: February 2021

Purpose: Patients with benign paroxysmal positional vertigo (BPPV) experience gait unsteadiness not only during the attacks but also between the spells. This study aimed to measure gait changes in BPPV and determine whether these changes are associated with the involved canal or lesion side.

Methods: We recruited 33 patients with a diagnosis of unilateral BPPV. Patients with other vestibular or central nervous system disorders were excluded. Gait was assessed using the GAITRite™ system before and after canalith repositioning treatment (CRT).

Results: After CRT, improvements were observed in various gait parameters including velocity (p < 0.001), cadence (p < 0.001), functional ambulation profile (p = 0.011), and the coefficient of variation of stride time (p = 0.004). Exploration of the center of pressure (COP) distribution also revealed improved stabilization during locomotion after CRT. The spatiotemporal gait variables did not differ between the patients with horizontal- and posterior-canal BPPV, or between the ipsilesional and contralesional sides before CRT.

Conclusions: The gait parameters reflecting velocity and rhythmicity along with stability of COP distribution improved after the resolution of BPPV. Episodic overexcitation of semicircular canal may impair the vestibular information that is integrated with the other reference afferent systems and lead to impaired gait performance.
Case Report: Borrelia-DNA Revealed the Cause of Arthritis and Dermatitis During Treatment With Rituximab
Authors: Sjöwall Johanna , Xirotagaros Georgios , Anderson Chris D. , Sjöwall Christopher , Dahle Charlotte
Published: February 2021

Borrelia-specific antibodies in serum did not contribute to the diagnosis of Borrelia arthritis or Borrelia-associated dermatitis in a young woman with ongoing treatment with rituximab due to multiple sclerosis. The diagnosis was confirmed by the detection of Borrelia-DNA in a skin punch biopsy. The patient history did not reveal any tick exposure. She had suffered for several months from fluctuating pain and swelling of the right knee as well as skin involvement with redness and oedema around the ankle of the same leg. Monoarthritis was confirmed by a rheumatologist. Knee puncture was performed but the synovial fluid was only sufficient for microscopic examination of crystals. Neither monosodium urate crystals nor calcium pyrophosphate crystals were found. Borrelia serology in blood revealed borderline levels of immunoglobulin (Ig)M and IgG, respectively. Treatment with doxycycline resulted in resolution of the joint and skin manifestations within a month. This case highlights that Borrelia-specific antibody levels cannot be reliably interpreted in patients who have received B-cell depleting therapy. Under these circumstances, detection of the bacterial genome in different body fluids, such as in the skin, can be a useful complement to the diagnosis of Lyme disease. In this young female, the diagnosis would certainly have been further delayed without the detection of Borrelia-DNA in the skin.
Maternal Distress and Offspring Neurodevelopment: Challenges and Opportunities for Pre-clinical Research Models
Authors: Fitzgerald Eamon , Parent Carine , Kee Michelle Z. L. , Meaney Michael J.
Published: February 2021

Pre-natal exposure to acute maternal trauma or chronic maternal distress can confer increased risk for psychiatric disorders in later life. Acute maternal trauma is the result of unforeseen environmental or personal catastrophes, while chronic maternal distress is associated with anxiety or depression. Animal studies investigating the effects of pre-natal stress have largely used brief stress exposures during pregnancy to identify critical periods of fetal vulnerability, a paradigm which holds face validity to acute maternal trauma in humans. While understanding these effects is undoubtably important, the literature suggests maternal stress in humans is typically chronic and persistent from pre-conception through gestation. In this review, we provide evidence to this effect and suggest a realignment of current animal models to recapitulate this chronicity. We also consider candidate mediators, moderators and mechanisms of maternal distress, and suggest a wider breadth of research is needed, along with the incorporation of advanced -omics technologies, in order to understand the neurodevelopmental etiology of psychiatric risk.
A Study on the Effect of Mental Practice Using Motor Evoked Potential-Based Neurofeedback
Authors: Matsuda Daiki , Moriuchi Takefumi , Ikio Yuta , Mitsunaga Wataru , Fujiwara Kengo , Matsuo Moemi , Nakamura Jiro , Suzuki Tomotaka , Sugawara Kenichi , Higashi Toshio
Published: February 2021

This study aimed to investigate whether the effect of mental practice (motor imagery training) can be enhanced by providing neurofeedback based on transcranial magnetic stimulation (TMS)-induced motor evoked potentials (MEP). Twenty-four healthy, right-handed subjects were enrolled in this study. The subjects were randomly allocated into two groups: a group that was given correct TMS feedback (Real-FB group) and a group that was given randomized false TMS feedback (Sham-FB group). The subjects imagined pushing the switch with just timing, when the target circle overlapped a cross at the center of the computer monitor. In the Real-FB group, feedback was provided to the subjects based on the MEP amplitude measured in the trial immediately preceding motor imagery. In contrast, the subjects of the Sham-FB group were provided with a feedback value that was independent of the MEP amplitude. TMS was applied when the target, moving from right to left, overlapped the cross at the center of the screen, and the MEP amplitude was measured. The MEP was recorded in the right first dorsal interosseous muscle. We evaluated the pre-mental practice and post-mental practice motor performance in both groups. As a result, a significant difference was observed in the percentage change of error values between the Real-FB group and the Sham-FB group. Furthermore, the MEP was significantly different between the groups in the 4th and 5th sets. Therefore, it was suggested that TMS-induced MEP-based neurofeedback might enhance the effect of mental practice.
An Ontological Approach of the Cognitive and Affective Product Experience
Authors: Tavares David Ribeiro , Canciglieri Junior Osiris , Guimarães Lia Buarque de Macedo , Rudek Marcelo
Published: February 2021

The cognitive and affective design aims to attract consumers with products and new products that provide innovative experiences with the intense functional and “cognitive” impact such as ease of use, in addition to “affective” impact as the pleasure of consuming. However, it is difficult to anticipate the consumer's preferences and intentionality, because what happens inside his mind, brain, or subjective experience (wishes, needs, and preferences) is not accessible. This study's objective was to propose an ontological and multidisciplinary approach to the cognitive and affective product experience through an explanation framework and a conceptual model. The model was tested, and the preliminary results indicate that the proposal contributes positively to the advance of the explanation, evaluation and translation of the product experience.
Descriptive Analysis of Heavy Metals Content of Beef From Eastern Uganda and Their Safety for Public Consumption
Authors: Kasozi Keneth Iceland , Hamira Yunusu , Zirintunda Gerald , Alsharif Khalaf F. , Altalbawy Farag M. A. , Ekou Justine , Tamale Andrew , Matama Kevin , Ssempijja Fred , Muyinda Robert , Kawooya Francis , Pius Theophilus , Kisakye Hellen , Bogere Paul , Matovu Henry , Omadang Leonard , Etiang Patrick , Mbogua Joseph , Ochieng Juma John , Osuwat Lawrence Obado , Mujinya Regan , Batiha Gaber El-Saber , Otim Ochan
Published: February 2021

In this study, we initiated an effort to generate information about beef safety in Uganda. Our entry point was to assess by atomic absorption spectrophotometry the levels of essential elements copper (Cu), cobalt (Co), iron (Fe) and zinc (Zn), and non-essential elements lead (Pb), chromium (Cr), nickel (Ni), and cadmium (Cd) in 40 beef samples collected from within and around Soroti (Uganda). The information was used to evaluate the safety of consuming such beef against the World Health Organization (WHO) limits. The latter was accomplished by (i) estimating the daily intake (EDI) of each metal in the study area, (ii) modeling the non-cancer health risk using the target hazard quotient (THQ) and (iii) modeling the cancer risk using the incremental lifetime cancer risk (ILCR). The study finds that the mean concentrations (±95% CI) and EDI were in the order of Fe > Zn > Cr > Ni > Pb > Co > Cu > Cd. Cancer risk was found to be due to Ni > Cr > Cd > Pb and significantly higher in children than adults. The latter particularly demonstrates the importance of Ni poisoning in the study area. Overall, while essential elements in our beef samples were below WHO limits (hence no health risks), non-essential elements had high health and cancer risks due to higher levels of Cr and Ni.
Types of Nutrition Knowledge, Their Socio-Demographic Determinants and Their Association With Food Consumption: Results of the NEMONIT Study
Authors: Koch Franziska , Hoffmann Ingrid , Claupein Erika
Published: February 2021

Objectives: To investigate nutrition knowledge in the German population, its determinants and its association with food consumption.

Methods: Data were obtained from the NEMONIT study (2014/15, n = 1,505, participants' age: 22–80 years). Nutrition knowledge was measured using the consumer nutrition knowledge scale (CoNKS) in a computer-assisted telephone interview. Two 24-h recalls were conducted to assess food consumption, which was evaluated using the Healthy Eating Index-NVS II.

Results: Areas for knowledge enhancement were the understanding of health benefits of fruit and vegetable consumption, the concept of a balanced diet and saturated fatty acids. Nutrition knowledge was higher among females, younger and high socio-economic status participants. Correlations between nutrition knowledge and a favorable diet were significant but low. Analyses of types of nutrition knowledge yielded similar results for procedural knowledge and knowledge on nutrients but not for knowledge on calories.

Conclusions: Areas for knowledge enhancement were identified, but an increase in nutrition knowledge alone seems unlikely to result in large improvements of dietary behavior.
MicroRNAs and Long Non-Coding RNAs as Regulators of NANOG Expression in the Development of Oral Squamous Cell Carcinoma
Authors: Grubelnik Gašper , Boštjančič Emanuela , Aničin Aleksandar , Dovšak Tadej , Zidar Nina
Published: February 2021

NANOG is a stem cell transcription factor that is believed to play an important role in the development of oral squamous cell carcinoma (OSCC), but there is limited data regarding the role of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) in the regulation of NANOG expression. We therefore analyzed expression of NANOG, NANOG-regulating miRNAs and lncRNAs in OSCC cancerogenesis, using oral biopsy samples from 66 patients including normal mucosa, dysplasia, and OSCC. Expression analysis of NANOG, miR-34a, miR-145, RoR, SNHG1, AB209630, and TP53 was performed using qPCR and immunohistochemistry for NANOG protein detection. NANOG protein showed no staining in normal mucosa, very weak in low-grade dysplasia, and strong staining in high-grade dysplasia and OSCC. NANOG, miR-145, RoR, and SNHG1 showed up-regulation, TP53 and miR-34a showed down-regulation, and AB209630 showed variable expression during cancerogenesis. NANOG mRNA was up-regulated early in cancerogenesis, before strong protein expression can be detected. NANOG was in correlation with miR-145 and RoR. Our results suggest that miRNAs and lncRNAs, particularly miR-145 and RoR, might be important post-transcription regulatory mechanisms of NANOG in OSCC cancerogenesis. Furthermore, NANOG protein detection has a diagnostic potential for oral high-grade dysplasia, distinguishing it from low-grade dysplasia and non-neoplastic reactive lesions.
ITM2A as a Tumor Suppressor and Its Correlation With PD-L1 in Breast Cancer
Authors: Zhang Rui , Xu Tao , Xia Yu , Wang Zhi , Li Xingrui , Chen Wen
Published: February 2021

Background

High expression of integral membrane protein 2A (ITM2A) was reported to be associated with favorable prognosis in several solid tumors including breast cancer. This study aimed to investigate the role of ITM2A in breast cancer, especially in respect to tumor microenvironment.

Methods

ITM2A expression was evaluated based on qRT-PCR results on breast cancer specimens, as well as TCGA and GEO datasets. The influence of ITM2A expression on breast cancer cell proliferation and tumor growth were evaluated by CCK-8 assay, clonogenic assay, and murine xenograft models. Transwell assay was performed to observe the changes of invasion and migration capacity in breast cancer cells. To determine the biological functions of ITM2A, differentially expressed genes (DEGs) were screened based on RNA-sequencing data of MCF-7 cells overexpressed ITM2A. Then, functional annotation on DEGs was given by Gene Ontology and KEGG analysis. The stimulation on programmed cell death ligand 1 (PD-L1) expression when ITM2A overexpressed was determined by flow cytometry. Meanwhile, the correlation on expression levels between PD-L1 and ITM2A was tested via qRT-PCR on 24 breast cancer tissues, as well as public database.

Results

We demonstrated that ITM2A was frequently downregulated in breast cancer. Patients with high expression levels of ITM2A had longer overall survival and relapse free survival. Overexpression of ITM2A inhibited proliferation and impaired cells capacity of invasion and migration in vitro and in vivo. The DEGs in breast cancer cells overexpressed ITM2A were found to be associated with immunity responses. Moreover, ITM2A was found to facilitate breast cancer cells to express PD-L1. The correlation between PD-L1 and ITM2A was verified with both qRT-PCR assay and public database. Additionally, it was found that breast cancer had higher ITM2A expression frequently had more tumor-infiltrating lymphocytes (TILs).

Conclusion

In summary, we found that high expression of ITM2A reduced the aggressivity of breast cancer cells and had a favorable effect on outcomes of patients with breast cancer. Moreover, ITM2A induced PD-L1 expression in breast cancer cells was accompanied with higher TILs numbers in tumor microenvironment.
SH3KBP1 Promotes Glioblastoma Tumorigenesis by Activating EGFR Signaling
Authors: Song Hai , Wang Yanpei , Shi Chaojia , Lu Jianxiang , Yuan Tian , Wang Xiangpeng
Published: February 2021

Glioblastoma (GBM) is the most common and aggressive brain tumor in adults. Overexpression or activation of epidermal growth factor receptor (EGFR) occurs commonly in multiple human cancers and promotes tumorigenesis. However, the underlying molecular mechanism of EGFR aberrant activation and the downstream signaling pathways remains largely unknown. In this study, we report that both SH3-domain kinase binding protein 1 (SH3KBP1) mRNA and protein levels are highly expressed in GBM and its high expression is associated with worse survival of glioma patients. In addition, we provide evidence that SH3KBP1 is prominently expressed in GBM stem cells (GSCs) and have potential to serve as a novel GSCs marker. Moreover, silencing SH3KBP1 dramatically impairs GBM cell proliferation, migration and GSCs self-renewal ability in vitro and xenograft tumors growth in vivo. Most importantly, we found that SH3KBP1 directly interacts with EGFR and may act as an adaptor protein to transduce EGFR signaling. Together, our work uncovers SH3KBP1 as a novel regulator of oncogenic EGFR signaling and also as a potential therapeutic target for GBM patients with EGFR activation.
Biomarkers of Checkpoint Inhibitor Induced Immune-Related Adverse Events—A Comprehensive Review
Authors: Hommes Josefien W. , Verheijden Rik J. , Suijkerbuijk Karijn P. M. , Hamann Dörte
Published: February 2021

Immune checkpoint inhibitors (ICIs) have substantially improved the prognosis of patients with different types of cancer. Through blockade of cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1), negative feedback mechanisms of the immune system are inhibited, potentially resulting in very durable anti-tumor responses. Despite their promise, ICIs can also elicit auto-immune toxicities. These immune-related adverse events (irAEs) can be severe and sometimes even fatal. Therefore, being able to predict severe irAEs in patients would be of added value in clinical decision making. A search was performed using “adverse events”, “immune checkpoint inhibitor”, “biomarker”, and synonyms in PubMed, yielding 3580 search results. After screening title and abstract on the relevance to the review question, statistical significance of reported potential biomarkers, and evaluation of the remaining full papers, 35 articles were included. Five additional reports were obtained by means of citations and by using the similar article function on PubMed. The current knowledge is presented in comprehensive tables summarizing blood-based, immunogenetic and microbial biomarkers predicting irAEs prior to and during ICI therapy. Until now, no single biomarker has proven to be sufficiently predictive for irAE development. Recommendations for further research on this topic are presented.
Regulatory Effects of Circular RNAs on Host Genes in Human Cancer
Authors: Wang Xiong , Li Huijun , Lu Yanjun , Cheng Liming
Published: February 2021

Circular RNAs (circRNAs) are a class of single-stranded, covalent closed-loop RNAs with tissue-/development-specific expression patterns. circRNAs are stable and play oncogenic or tumor suppressive roles in various aspects of cancer, including tumorigenesis, proliferation, apoptosis, metastasis, invasion, chemo-therapeutic resistance, and prognosis. circRNAs act as miRNA/protein sponges, protein scaffold, or template for translation. Increasing evidence shows circRNAs contribute to cancer progression via modulating the expression or function of their host genes. In this review, we summarize the latest progress in the regulation of host genes by circRNAs in human cancer. The works on circRNAs mediated regulation of host genes enhance us to understand the interaction between circRNAs and their host genes in human cancer.
Chemoradiotherapy for Inoperable Carotid Body Leiomyosarcoma: A Case Report and Review of Literature
Authors: Liu Cheng-Sheng , Tsai Jia-Ruey , Kao Yi-Tzu , Lu Long-Sheng , Chen Yin-Ju , Burnouf Thierry , Wang Peng-Yuan , Chiou Jeng-Fong , Ting Lai-Lei
Published: February 2021

Vascular leiomyosarcoma is an extremely rare tumor and is associated with poor prognosis among leiomyosarcoma. Surgical resection remains the main treatment option. But outcome of definitive treatment with chemoradiotherapy in inoperable patients is not clear. Here, we report treatment and outcome of definitive chemoradiotherapy in a case of vascular leiomyosarcoma. A 64-year-old man with the initial presentation of pulsatile right neck mass was diagnosed with right carotid body leiomyosarcoma. He refused surgical intervention due to risk of carotid body injury and ischemic stroke. Successful tumor control was achieved with carboplatin-based concurrent chemoradiotherapy. Investigational liquid biopsy for circulating sarcoma cells was also performed to analyze drug sensitivity profile of this rare tumor. One year after treatment, the disease remained well controlled and there was no evidence of baroreflex failure or treatment-related late toxicities. To our best knowledge, this is the first case report of right carotid body leiomyosarcoma controlled with definitive concurrent chemoradiotherapy. The approach of personalized multi-modality treatment will be a focus of our future investigation.