bluuebunny/crossref_metadata_2025 huggingface dataset:
Protein Phosphatase 2A Deficiency in Macrophages Increases Foam Cell Formation and Accelerates Atherosclerotic Lesion Development
Authors: Li Rui , Zhang Chao , Xie Fei , Zhou Xianming , Hu Xingjian , Shi Jiawei , Du Xinling , Lin Zhiyong , Dong Nianguo
Published: January 2022

Protein phosphatase 2A (PP2A), a crucial serine/threonine phosphatase, has recently been reported to play an important role in cardiovascular disease. Previous studies have hinted that PP2A is involved in atherosclerosis formation, but the associated mechanisms remain poorly understood. In this study, we investigate the role of PP2A in the pathogenesis of atherosclerosis. In human atherosclerotic coronary arteries, we found that the expression and activity of PP2A decreased significantly when compared to non-atherosclerotic arteries. Additional experiments demonstrated that pharmacological inhibition of PP2A aggravated atherosclerosis of ApoE−/− mice. Considering the central role of macrophages in atherosclerosis, mice with conditional knockout of the PP2A-Cα subunit in myeloid cells were produced to investigate the function of PP2A in macrophages. Results showed that PP2A deficiency in myeloid cells aggravated atherosclerotic lesions in mice. in vitro experiments indicated that PP2A-deficient macrophages had an enhanced ability of lipid uptake and foam cell formation. Mechanistically, the deficiency of the PP2A in macrophages led to an increase in the phosphorylation level of p38, which contributed to the elevated expression of scavenger receptor CD36, a key factor involved in lipoprotein uptake. Our data suggest that PP2A participates in the pathophysiological process of atherosclerosis. The decrease of PP2A expression and activity in macrophages is a crucial determinant for foam cell formation and the initiation of atherosclerosis. Our study may provide a potential novel approach for the treatment of atherosclerosis.
IL-6/STAT3 Signaling Promotes Cardiac Dysfunction by Upregulating FUNDC1-Dependent Mitochondria-Associated Endoplasmic Reticulum Membranes Formation in Sepsis Mice
Authors: Jiang Tao , Peng Dewei , Shi Wei , Guo Junyi , Huo Shengqi , Men Lintong , Zhang Cuntai , Li Sheng , Lv Jiagao , Lin Li
Published: January 2022

Aims

Cytokine storm is closely related to the initiation and progression of sepsis, and the level of IL-6 is positively correlated with mortality and organ dysfunction. Sepsis-induced myocardial dysfunction (SIMD) is one of the major complications. However, the role of the IL-6/STAT3 signaling in the SIMD remains unclear.

Methods and Results

Septic mice were induced by intraperitoneal injection of LPS (10 mg/kg). Echocardiography, cytokines detection, and histologic examination showed that sepsis mice developed cardiac systolic and diastolic dysfunction, increase of inflammatory cytokines in serum, activated STAT3 and TLR4/NFκB pathway in heart, and raised myocardial apoptosis, which were attenuated by IL-6/STAT3 inhibitor, Bazedoxifene.In vitro, we found that LPS decreased cell viability in a concentration-dependent manner and activated STAT3. Western blot and immunofluorescence results indicated that STAT3 phosphorylation induced by LPS was inhibited by Bazedoxifene. Bazedoxifene also suppressed LPS-induced IL-6 transcription. sIL-6R caused LPS-induced p-STAT3 firstly decreased and then significantly increased. More importantly, we found STAT3-knockdown suppressed LPS-induced expression of FUNDC1, a protein located in mitochondria-associated endoplasmic reticulum membranes (MAMs). Overexpression of STAT3 led to an increase in FUNDC1 expression. Dual-luciferase reporter assay was used to confirm that STAT3 was a potential transcription factor for FUNDC1. Moreover, we showed that LPS increased MAMs formation and intracellular Ca2+levels, enhanced the expression of Cav1.2 and RyR2, decreased mitochondrial membrane potential and intracellular ATP levels, and promoted mitochondrial fragmentation, the expression of mitophagy proteins and ROS production in H9c2 cells, which were reversed by knockdown of FUNDC1 and IL-6/STAT3 inhibitor including Bazedoxifene and Stattic.

Conclusions

IL-6/STAT3 pathway plays a key role in LPS-induced myocardial dysfunction, through regulating the FUNDC1-associated MAMs formation and interfering the function of ER and mitochondria. IL-6/STAT3/FUNDC1 signaling could be a new therapeutic target for SIMD.
Serum Chloride Level Is Associated With Abdominal Aortic Calcification
Authors: Hu Sheng , Lan Tian , Wang Silin , Su Lang , Zou Sheng , Ye Jiayue , Zhang Yang , Zhang Deyuan , Guo Qiang , Zhang Wenxiong , Yu Dongliang , Xu Jianjun , Wei Yiping , Peng Jinhua
Published: January 2022

Background

Abdominal aortic calcification is a potentially important independent risk factor for cardiovascular health. The aim of this study was to determine the relationship between serum chloride level and abdominal artery calcification.

Methods

We obtained the data of 3,018 individuals from the National Health and Nutrition Examination Survey database and analyzed the relationship between serum chloride and abdominal artery calcification. We performed stratified and single factor analysis, multiple equation regression analysis, smooth curve fitting, and threshold effect and saturation effect analysis. R and EmpowerStats were used for data analysis.

Results

Serum chloride is independently related to the AAC total 24 score (AAC-24). The smooth curves fitted were all inverted-U shaped. Below a cutoff value of 92 mmol/L, increase in serum chloride level was associated with increase in AAC-24; however, above that cutoff, increase in serum chloride level was associated with decrease in AAC-24.

Conclusions

At serum levels below 92 mmol/L, chloride is a risk factor for abdominal aortic calcification but levels above 92 mmol/L appear to protect against abdominal aortic calcification.
Analysis of Class II Intermaxillary Elastics Applied Forces: An in-vitro Study
Authors: Castroflorio Tommaso , Sedran Ambra , Spadaro Francesca , Rossini Gabriele , Cugliari Giovanni , Quinzi Vincenzo , Deregibus Andrea
Published: January 2022

Objectives

The aims of this study were: (1) to assess the average inter-arch distances characterizing Class II malocclusions, (2) to analyze the applied forces at those distances by different elastics, and (3) to compare measured forces with those declared by manufacturers, both in dry and wet environments.

Materials and Methods

Settings and sample population: Class II models of 167 adult subjects (96 women and 71 men, age: 28 ± 3 years) referred to the Orthodontic Department of the University of Turin, Turin, Italy, between January 2018 and January 2020, were collected. Distances between facial axes (FA) points of upper canines and lower first molars (A), upper first premolar and lower first molar (B), upper second premolar and lower first molar (C), upper canine and lower first premolar (D), and upper canine and lower second premolar (E), were measured using 3Shape Ortho® Viewer program. Different elastics' diameters and forces were tested at those distances. The MTS Insight® Electromechanical Testing System was used to measure the tensile forces of elastics. The applied forces were measured in dry (T0) and wet conditions, after 1 (T1), 6 (T2), and 12 h (T3).

Results

Average distances were calculated: A = 24.64 mm (SD 2.10), B = 16.3 mm (SD 1.94), C = 9.78 mm (SD 1.77), D = 9.8 mm (SD 1.88), and E = 15.99 mm (SD 2.06). Significant differences (p < 0.05) were highlighted between the measured force and the force declared by manufacturers, and all elastics had a significant force decay (p < 0.05).

Conclusion

The results showed that 3/16" 4.5 oz are the most reliable elastics in terms of applied force with respect to the declared one and in terms of force degradation.
Rock the Boat! Shaken by the COVID-19 Crisis: A Review on Teachers’ Competencies in ICT
Authors: Montiel Hugo , Gomez-Zermeño Marcela Georgina
Published: January 2022

The COVID-19 pandemic suddenly brought great challenges to the continuation of education. Institutions had to elect between pre-maturely ending their current school cycles or shifting to an online, flexible environment that had to deal with the digital divide in internet access. As part of its Sustainable Development Agenda, UNESCO developed the “Information and Communications Technology Competency Framework for Teachers” in 2018 to help institutions achieve digital literacy and reduce the digital divide. A systematic literature review (SLR) was conducted, identifying 23 studies on the use of ICT tools during COVID-19 educational disruptions in the database ProQuest Central and Google Scholar from August 2019 to August 2020. The results of this SLR showed that frameworks such as that of UNESCO could guide institutions to fast-track the development of educational strategies for post-crisis, COVID-19 implementation. Also, findings suggest an increase in the use of ICTs in learning environments, which will encourage organizations like UNESCO to develop plans and projects, such as the ICT framework further. Coping with the challenges of today’s learning environments is urgent; it is already time to “Rock the boat!” Introduction.
Tracking Flights to Investigate Seabird Mortality Induced by Artificial Lights
Authors: Rodríguez Airam , Rodríguez Beneharo , Acosta Yarci , Negro Juan J.
Published: January 2022

Light pollution causes attraction and/or disorientation of seabirds, leading to mortality events due to multiple threats. This is a poorly understood phenomenon, largely because of the challenge to track seabirds at night from their nests to the grounding light-polluted locations. New tracking technologies can inform about this phenomenon. Here, we used GPS transmitters with remote download to track the flights of Cory’s shearwaterCalonectris borealisfledglings from an inland experimental releasing site to the ocean. We released birds assigned to three experimental groups: GPS tagged, tape-labelled, and control birds. We assessed how both intrinsic (such as body mass, body condition, body size, and down abundance) and extrinsic (i.e., flight descriptors, such as distance, straightness, and flight duration, wind speed, or moon luminance) factors influenced light-induced groundings by using two datasets: one including the three groups and another including just the GPS tagged birds (as GPS devices provide unique information). We tested whether the probability of being grounded by artificial lights was related to intrinsic factors. With the use of the whole dataset, we found that birds with a higher down abundance had a higher probability of being grounded. GPS data revealed that the probability of being grounded was positively related to the tortuosity of flights and the overflown light pollution levels. Also, birds with slower flights were more likely to be grounded than birds with fast flights. Tortuosity increased with light pollution levels but decreased with the ambient light of the moon. GPSs with remote data download provided information on birds reaching the ocean, this being a substantial improvement to previous studies requiring recapture of the individuals to retrieve the data. GPS tracks of birds reaching the ocean allowed us to know that some birds overflew coastal urban areas so light-polluted as the landing sites of grounded birds. We provide novel scientific-based information to manage seabird mortality induced by artificial lights.
The Effectiveness of Financial Incentives for Addressing Mangrove Loss in Northern Vietnam
Authors: Pham Thu Thuy , Vu Tan Phuong , Hoang Tuan Long , Dao Thi Linh Chi , Nguyen Dinh Tien , Pham Duc Chien , Dao Le Huyen Trang , Nguyen Van Truong , Hoang Nguyen Viet Hoa
Published: January 2022

This paper analyzes the effectiveness of existing financial incentives for mangrove conservation in Vietnam. Current conservation programs and projects have created financial incentives for mangrove protection, but the effectiveness of these incentives in addressing mangrove loss in northern Vietnam has been mixed. While financial incentives have contributed to a larger area of planted mangroves, their effectiveness is hampered by contradictory national policies, which encourage mangrove conservation on the one hand, and aquaculture expansion in mangrove areas on the other, thus making it difficult to address mangrove deforestation and degradation effectively. Mangrove conservation in Vietnam is challenged further by inequitable distribution of power and benefits, difficulties accessing information, weak law enforcement, lack of compliance, low payments for protecting mangroves, lack of full recognition of local rights, discontinued funding after policies and projects end, and lack of participation by local people in policy and project design and implementation. Conservation policies and projects should aim to protect existing mangrove forests, restore degraded mangroves and plant new ones to enhance mangrove area, quality and biodiversity. Sustainable mangrove conservation not only requires effective and sustainable financial incentives, but other enabling conditions such as addressing the conflict between mangrove conservation and aquaculture expansion, and grounding mangrove conservation projects by building on local knowledge and leadership. As these drivers are often motivated by national development goals and other sectoral development needs with ministries competing for budgets and influence, holistic land-use planning needs to be coupled with effective coordination and clarification of responsibilities between government agencies, and coordinated and consistent policies concerning these natural resources. Addressing these underlying governance issues is far more important for mangrove conservation and restoration than merely offering financial incentives as various national and international projects have attempted.
Safety and Efficacy of Camrelizumab in Combination With Nab-Paclitaxel Plus S-1 for the Treatment of Gastric Cancer With Serosal Invasion
Authors: Lin Ju-Li , Lin Jian-Xian , Lin Jun Peng , Zheng Chao-Hui , Li Ping , Xie Jian-Wei , Wang Jia-bin , Lu Jun , Chen Qi-Yue , Huang Chang-Ming
Published: January 2022

Objective

To investigate the safety and efficacy of camrelizumab in combination with nab-paclitaxel plus S-1 for the treatment of gastric cancer with serosal invasion.

Method

Two hundred patients with gastric cancer with serosal invasion who received neoadjuvant therapy from January 2012 to December 2020 were retrospectively analyzed. According to the different neoadjuvant therapy regimens, the patients were divided into the following three groups: the SOX group (S-1 + oxaliplatin) (72 patients), SAP group (S-1 + nab-paclitaxel) (95 patients) and C-SAP group (camrelizumab + S-1 + nab-paclitaxel) (33 patients).

Result

The pathological response (TRG 1a/1b) in the C-SAP group (39.4%) was not significantly different from that in the SAP group (26.3%) and was significantly higher than that in the SOX group (18.1%). The rate of ypT0 in the C-SAP group (24.2%) was higher than that in the SAP group (6.3%) and the SOX group (5.6%). The rate of ypN0 in the C-SAP group (66.7%) was also higher than that in the SAP group (38.9%) and the SOX group (36.1%). The rate of pCR in the C-SAP group (21.2%) was higher than that in the SAP group (5.3%) and the SOX group (2.8%). The use of an anti-PD-1 monoclonal antibody was an independent protective factor for TRG grade (1a/1b). The use of camrelizumab did not increase postoperative complications or the adverse effects of neoadjuvant therapy.

Conclusion

Camrelizumab combined with nab-paclitaxel plus S-1 could significantly improve the rate of tumor regression grade (TRG 1a/1b) and the rate of pCR in gastric cancer with serosal invasion.
SARS-CoV-2-Specific T Cell Responses Are Stronger in Children With Multisystem Inflammatory Syndrome Compared to Children With Uncomplicated SARS-CoV-2 Infection
Authors: Conway Susan R. , Lazarski Christopher A. , Field Naomi E. , Jensen-Wachspress Mariah , Lang Haili , Kankate Vaishnavi , Durkee-Shock Jessica , Kinoshita Hannah , Suslovic William , Webber Kathleen , Smith Karen , Cohen Jeffrey I. , Burbelo Peter D. , Zhang Anqing , Teach Stephen J. , Ibeh Trisha , Delaney Meghan , DeBiasi Roberta L. , Keller Michael D. , Bollard Catherine M.
Published: January 2022

Background

Despite similar rates of infection, adults and children have markedly different morbidity and mortality related to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Compared to adults, children have infrequent severe manifestations of acute infection but are uniquely at risk for the rare and often severe Multisystem Inflammatory Syndrome in Children (MIS-C) following infection. We hypothesized that these differences in presentation are related to differences in the magnitude and/or antigen specificity of SARS-CoV-2-specific T cell (CST) responses between adults and children. We therefore set out to measure the CST response in convalescent adults versus children with and without MIS-C following SARS-CoV-2 infection.

Methods

CSTs were expanded from blood collected from convalescent children and adults post SARS-CoV-2 infection and evaluated by intracellular flow cytometry, surface markers, and cytokine production following stimulation with SARS-CoV-2-specific peptides. Presence of serum/plasma antibody to spike and nucleocapsid was measured using the luciferase immunoprecipitation systems (LIPS) assay.

Findings

Twenty-six of 27 MIS-C patients, 7 of 8 non-MIS-C convalescent children, and 13 of 14 adults were seropositive for spike and nucleocapsid antibody. CST responses in MIS-C patients were significantly higher than children with uncomplicated SARS-CoV-2 infection, but weaker than CST responses in convalescent adults.

Interpretation

Age-related differences in the magnitude of CST responses suggest differing post-infectious immunity to SARS-CoV-2 in children compared to adults post uncomplicated infection. Children with MIS-C have CST responses that are stronger than children with uncomplicated SARS-CoV-2 infection and weaker than convalescent adults, despite near uniform seropositivity.
The Role of miRNA in Tumor Immune Escape and miRNA-Based Therapeutic Strategies
Authors: Zhang Zhengjia , Huang Qingcai , Yu Liuchunyang , Zhu Dongjie , Li Yang , Xue Zeyu , Hua Zhenglai , Luo Xinyi , Song Zhiqian , Lu Cheng , Zhao Ting , Liu Yuanyan
Published: January 2022

Tumor immune escape is a critical step in the malignant progression of tumors and one of the major barriers to immunotherapy, making immunotherapy the most promising therapeutic approach against tumors today. Tumor cells evade immune surveillance by altering the structure of their own, or by causing abnormal gene and protein expression, allowing for unrestricted development and invasion. These genetic or epigenetic changes have been linked to microRNAs (miRNAs), which are important determinants of post-transcriptional regulation. Tumor cells perform tumor immune escape by abnormally expressing related miRNAs, which reduce the killing effect of immune cells, disrupt the immune response, and disrupt apoptotic pathways. Consequently, there is a strong trend toward thoroughly investigating the role of miRNAs in tumor immune escape and utilizing them in tumor treatment. However, because of the properties of miRNAs, there is an urgent need for a safe, targeted and easily crossed biofilm vehicle to protect and deliver them in vivo, and exosomes, with their excellent biological properties, have successfully beaten traditional vehicles to provide strong support for miRNA therapy. This review summarizes the multiple roles of miRNAs in tumor immune escape and discusses their potential applications as an anti-tumor therapy. Also, this work proposes exosomes as a new opportunity for miRNA therapy, to provide novel ideas for the development of more effective tumor-fighting therapeutic approaches based on miRNAs.
Response of Posidonia oceanica (L.) Delile and Its Associated N2 Fixers to Different Combinations of Temperature and Light Levels
Authors: García-Márquez Manuela Gertrudis , Fernández-Juárez Víctor , Rodríguez-Castañeda José Carlos , Agawin Nona S. R.
Published: January 2022

The increasing occurrence of heat waves and water turbidity are threats to the persistence of seagrass meadows. Their effects on the productivity of seagrasses and the functioning of their associated microorganisms have not been studied extensively. The purpose of this study is to assess the effects of different light levels and temperatures onPosidonia oceanica; the endemic seagrass species in the Mediterranean Sea, and their N2-fixing community, which contributes importantly to the nitrogen requirements and high productivity of the plants. Aquarium experiments were conducted in winter, when the plants are more vulnerable to changes in temperature, subjecting them to short-term exposures to an ambient (15.5°C) and elevated temperatures (ambient+5.5°C), and at limited (13 μmol photons m−2s−1) and saturating light conditions (124 μmol photons m−2s−1). Primary production, chlorophyll content, reactive oxygen species production, polyphenols content, thenifHgene expression, N2fixation, and alkaline phosphatase activities were measured in different plant tissues. Plants incubated at ambient temperature and high light exhibited an enhanced total chlorophyll production. Significantly higher gross and net primary production rates were also recorded under ambient temperature and high light conditions, which were approximately two-fold compared to the rest of the treatments. The oxidative stress analyses revealed an increased production of reactive oxygen species in young leaves incubated at ambient temperature and saturating light, while the polyphenols content in top leaves was considerably higher under elevated temperatures. In contrast, the N2fixation and alkaline phosphatase rates were significantly higher under elevated temperature and low light levels. The presence of the N2-fixing phylotypes UCYN-A, -B, and -C was detected through genetic analyses, with UCYN-B demonstrating the highestnifHgene transcription levels at elevated temperatures. These findings emphasize the significant role of irradiance on the productivity ofP. oceanicaand the temperature dependence of the N2fixation process in winter.
The Sandwich Structure of the Southern Yellow Sea Cold Water Mass and Yellow Sea Warm Current
Authors: Fei Yu , Qiang Ren , Xinyuan Diao , Chuanjie Wei , Yibo Hu
Published: January 2022

The southern Yellow Sea Cold Water Mass (YSCWM) and the Yellow Sea Warm Current (YSWC) are prominent features in the southern Yellow Sea. The traditional viewpoint is that the southern YSCWM exists in the warm half of the year and the YSWC exists in the cold half of the year; the most existing studies have regarded these features as independent ocean phenomenon. Through marine investigations conducted in the recent years in the southern Yellow Sea, the southern YSCWM was found to exist in the early winter in 2010, and the YSWC was observed in the early summer in 2013, 2014. For approximately half the year, the southern YSCWM and YSWC existed simultaneously, and the YSWC was located in a slightly high-temperature region in the middle of the southern YSCWM. A sandwich-shaped temperature structure formed in the middle of the southern Yellow Sea from spring to autumn. This article studies the seasonal variation characteristics of the three-dimensional southern YSCWM and YSWC structures using ocean survey data collected in the recent years. The new perspective of the seasonal variations in the southern YSCWM and YSWC obtained herein will promote the recognition of southern Yellow Sea water exchanges and support biogeochemical cycle research in the Yellow Sea.
Sporophyte Stage Genes Exhibit Stronger Selection Than Gametophyte Stage Genes in Haplodiplontic Giant Kelp
Authors: Molano Gary , Diesel Jose , Montecinos Gabriel J. , Alberto Filipe , Nuzhdin Sergey V.
Published: January 2022

Macrocystis pyrifera (giant kelp), a haplodiplontic brown macroalga that alternates between a macroscopic diploid (sporophyte) and a microscopic haploid (gametophyte) phase, provides an ideal system to investigate how ploidy background affects the evolutionary history of a gene. In M. pyrifera, the same genome is subjected to different selective pressures and environments as it alternates between haploid and diploid life stages. We assembled M. pyrifera gene models using available expression data and validated 8,292 genes models using the model alga Ectocarpus siliculosus. Differential expression analysis identified gene models expressed in either or both the haploid and diploid life stages while functional annotation identified processes enriched in each stage. Genes expressed preferentially or exclusively in the gametophyte stage were found to have higher nucleotide diversity (π = 2.3 × 10–3 and 2.8 × 10–3, respectively) than those for sporophytes (π = 1.1 × 10–3 and 1 × 10–3, respectively). While gametophyte-biased genes show faster sequence evolution, the sequence evolution exhibits less signatures of adaptations when compared to sporophyte-biased genes. Our findings contrast the standing masking hypothesis, which predicts higher standing genetic variation at the sporophyte stage, and support the strength of expression theory, which posits that genes expressed more strongly are expected to evolve slower. We argue that the sporophyte stage undergoes more stringent selection compared with the gametophyte stage, which carries a heavy genetic load associated with broadcast spawning. Furthermore, using whole-genome sequencing, we confirm the strong population structure in wild M. pyrifera populations previously established using microsatellite markers, and estimate population genetic parameters, such as pairwise genetic diversity and Tajima’s D, important for conservation and domestication of M. pyrifera.
Current Status of Acceptance of Disability and the Correlation With the Life Quality in Parkinson's Disease in Southwest China
Authors: Liang Yan , Chen Dezhi , Ou Ruwei , Zhao Bi , Song Wei , Yi Xiaojiang , Yang Rong , Chen Xueping
Published: January 2022

Background

Acceptance of disability (AOD) is a process that a patient must undergo to cope with altered abilities, but its effect in Parkinson's disease (PD) remains unclear. The present study aimed to determine the level of AOD, examine the influence of sociodemographic variables and disease characteristics on the AOD level, and evaluate the relation between AOD level and quality of life in a cohort of PD patients from Southwest of China.

Methods

A total of 336 PD patients were consecutively recruited from November 2018 to October 2020. At enrollment, demographic and clinical data were obtained using a questionnaire, and the Acceptance of Disability Scale-Revised (AODS-R) scale was used to measure the AOD level.

Results

The mean total score of AOD is 87.28, indicating a moderate level of disability acceptance in PD patients. Statistical analysis showed that understanding of PD, family support, and UPDRS-II score were major factors affecting AOD level, and patients with low AOD levels were more likely to have poorer quality of life.

Conclusion

AOD is a serious problem in PD patients in Southwest China, especially among individuals with insufficient family support and a lack of recognition of the disease. AOD was also associated with motor function and daily living ability, thus suggesting that evaluation of the AOD and promotion of the awareness may be helpful to improve the quality of life in patients with PD.
Hantavirus Induced Kidney Disease
Authors: Mir Sheema
Published: January 2022

Hantavirus induced hemorrhagic fever with renal syndrome (HFRS) is an emerging viral zoonosis affecting up to 200,000 humans annually worldwide. This review article is focused on recent advances in the mechanism, epidemiology, diagnosis, and treatment of hantavirus induced HFRS. The importance of interactions between viral and host factors in the design of therapeutic strategies is discussed. Hantavirus induced HFRS is characterized by thrombocytopenia and proteinuria of varying severities. The mechanism of kidney injury appears immunopathological with characteristic deterioration of endothelial cell function and compromised barrier functions of the vasculature. Although multidisciplinary research efforts have provided insights about the loss of cellular contact in the endothelium leading to increased permeability, the details of the molecular mechanisms remain poorly understood. The epidemiology of hantavirus induced renal failure is associated with viral species and the geographical location of the natural host of the virus. The development of vaccine and antiviral therapeutics is necessary to avoid potentially severe outbreaks of this zoonotic illness in the future. The recent groundbreaking approach to the SARS-CoV-2 mRNA vaccine has revolutionized the general field of vaccinology and has provided new directions for the use of this promising platform for widespread vaccine development, including the development of hantavirus mRNA vaccine. The combinational therapies specifically targeted to inhibit hantavirus replication and vascular permeability in infected patients will likely improve the disease outcome.
The Diagnostic Performance of an Extended Ultrasound Protocol in Patients With Clinically Suspected Giant Cell Arteritis
Authors: Skoog Johan , Svensson Christina , Eriksson Per , Sjöwall Christopher , Zachrisson Helene
Published: January 2022

Objective

To evaluate the diagnostic performance of an extended ultrasound protocol in patients referred under the suspicion of giant cell arteritis (GCA).

Methods

Consecutive patients with suspected GCA were examined with an extended color duplex ultrasound (CDU) protocol during a period of 2 years. The extended CDU protocol included temporal, axillary, subclavian, brachiocephalic, and carotid arteries. The reference was clinically diagnosed GCA, confirmed after ≥6-month follow-up. Hypo- or medium-echogenic, circumferential, homogenous wall thickening, and/or a positive compression sign in temporal arteries, were regarded as typical signs of arteritis.

Results

Of the eligible 201 patients, 83 (41%) received a clinical GCA diagnosis at follow-up ≥6 months post CDU examination. Among these cases, 48 (58%) demonstrated inflammation solely in temporal arteries, 8 (10%) showed abnormalities restricted to extra-cranial vessels, and 23 (28%) patients displayed inflammatory changes in both temporal and extra-cranial arteries. Color duplex ultrasound of temporal arteries yielded a diagnostic sensitivity and specificity [95% confidence intervals (CI)] of 86% (76–92%) and 99% (95–99%), respectively. By adding axillary artery examination, the sensitivity increased to 92% (83–97%) while the specificity remained unchanged. Further, inclusion of subclavian artery marginally increased the sensitivity by 1%. Finally, by also including brachiocephalic and common carotid arteries resulted in a sensitivity of 95% (88–99%) and a specificity of 98% (94–99%).

Conclusions

Color duplex ultrasound examination demonstrated a high accuracy in diagnosing patients both with cranial and extra-cranial GCA. Further examination of brachiocephalic and common carotid arteries can increase the sensitivity without affecting the specificity when temporal and axillary findings are indecisive. Finally, the extended CDU protocol allows measurement of the general burden of inflammation, which could be relevant for future monitoring purposes.
Case Report: “Methicillin-Resistant Staphylococcus aureus Endocarditis Overlying Calcified Mitral Annular Abscess Misdiagnosed as Klebsiella pneumoniae Endocarditis”
Authors: Yamamoto Hiroyuki , Hashimoto Katsuya , Yamada Hiroyuki , Ikeda Yoshihiko , Takahashi Takashi , Hashimoto Toru
Published: January 2022

Infective endocarditis (IE) involving mitral annular calcification (MAC) is a rare disease, but is potentially lethal due to frequent serious periannular complications, and therefore requires early diagnosis and prompt treatment. However, either reaching the correct diagnosis or the detection of periannular complications, even with conventional transesophageal echocardiography (TEE), remains challenging because calcium deposition obscures clear visualization of the area around the MAC. We describe a unique case of methicillin-resistant Staphylococcus aureus (MRSA) IE involving a calcified mitral annular abscess, which was initially misdiagnosed as Klebsiella pneumoniae IE. Accurate diagnosis of MAC-related IE as well as detection of the annular abscess were made possible by 4D TEE, leading to successful cardiac surgery, which confirmed MRSA IE pathologically, and the associated annular abscess. This case highlights the usefulness of 4D TEE for the accurate diagnosis and proper surgical planning. In addition, this case raises the limitations of the modified Duke criteria in cases of definite IE with dual bacteremia.
Effects of Herbal Tea Residue on Growth Performance, Meat Quality, Muscle Metabolome, and Rumen Microbiota Characteristics in Finishing Steers
Authors: Li Ling , Sun Xiaohong , Luo Junyi , Chen Ting , Xi Qianyun , Zhang Yongliang , Sun Jiajie
Published: January 2022

Herbal tea residue (HTR) contains various medicinal and nutritional components and is a potential high-quality unconventional source of roughage. In this study, a total of 30 healthy Simmental crossbred finishing steers were equally divided into two groups: CN (fed with a basic diet) and RE (HTR partly replaced Pennisetum purpureum). HTR did not alter the growth performance of steers but increased the net meat rate, tenderness, and water-holding capacity and increased the moisture content and oleic acid and linoleic acid concentrations in longissimus dorsi. It altered muscle metabolic pathways and improved rumen fermentation by increasing the propionic acid concentration and propionic acid-to-acetic acid ratio. We studied the steers’ rumen microbial community composition and determined their correlation with the tested parameters. Certain rumen microorganisms were closely associated with muscle glucolipid metabolites and rumen NH3-N and volatile fatty acid levels. Our findings suggest that, as a functional roughage source, HTR improved to a certain extent the meat quality of steers by altering the rumen microbial composition and affecting the rumen fatty acid composition and muscle glucolipid metabolism.
Epidemiology and Genetics of Mucopolysaccharidosis Type VI in Russia
Authors: Voskoboeva Elena , Semyachkina Alla , Miklyaev Ochir , Gamzatova Amina , Mikhaylova Svetlana , Vashakmadze Nato , Baydakova Galina , Omzar Olga , Pichkur Natalia , Zakharova Ekaterina , Kutsev Sergey
Published: January 2022

Mucopolysaccharidosis VI (MPS VI) is an autosomal recessive lysosomal storage disease caused by mutations in the arylsulfatase B gene (ARSB) and consequent deficient activity of ARSB, a lysosomal enzyme involved in the glycosaminoglycan (s) (GAGs) metabolism. Here, we present the results of the study of ARSB DNA analysis in MPS VI patients in the Russian Federation (RF) and other republics of the Former Soviet Union. In a cohort of 68 patients (57 families) with MPS VI, a total of 28 different pathogenic alleles were found. The most prevalent nucleotide changes included NM_000046.5:c.194C>T and NM_000046.5:c.454C>T. Five pathogenic alleles were novel, not previously reported (NM_000046.5:c.304C>G, NM_000046.5:c.533A>G, NM_000046.5:c.941T>C, NM_000046.5:c.447_456del10, and NM_000046.5:c.990_10003del14). The nucleotide variant NM_000045.6:c.454C>T was the prevalent allele among Slavic Russian patients. The nucleotide variant NM_000045.6:c.194C>T was found only in MPS VI families from the Republic of Dagestan. Based on the analysis of dry blood spots (DBSs) collected from newborns in this RF region, we showed the frequency of this mutant allele in the Republic of Dagestan to be 0.01 corresponding to the MPS VI frequency of nearly 1:10,000, which is one of the highest worldwide. This may eventually make the selective asymptomatic carrier test and newborn screening highly feasible in this region of the country.
Somatic Mutation Profiles Revealed by Next Generation Sequencing (NGS) in 39 Chinese Hepatocellular Carcinoma Patients
Authors: Ke Lixin , Shen Jianming , Feng Jikun , Chen Jialin , Shen Shunli , Li Shaoqiang , Kuang Ming , Liang Lijian , Lu Cuncun , Li Dongming , He Qiang , Peng Baogang , Hua Yunpeng
Published: January 2022

The features and significance of somatic mutation profiles in hepatocellular carcinoma (HCC) have not been completely elucidated to date. In this study, 39 tumor specimens from HCC patients were collected for gene variation analysis by next-generation sequencing (NGS), and a correlation analysis between mutated genes and clinical characteristics was also conducted. The results were compared with genome data from cBioPortal database. Our study found that T > G/A > C transversions (Tv) and C > T/G > A transitions (Ti) were dominant. The sequence variations of TP53, MUC16, MUC12, MUC4 and others, and the copy number variations (CNVs) of FGF3, TERT, and SOX2 were found to be more frequent in our cohort than in cBioPortal datasets, and they were highly enriched in pathways in cancer and participated in complex biological regulatory processes. The TP53 mutation was the key mutation (76.9%, 30/39), and the most common amino acid alteration and mutation types were p.R249S (23.5%) and missense mutation (82.3%) in the TP53 variation. Furthermore, TP53 had more co-mutations with MUC17, NBPF10, and AHNAK2. However, there were no significant differences in clinical characteristics between HCC patients with mutant TP53 and wild-type TP53, and the overall survival rate between treatment via precision medication guided by NGS and that via empirical medication (logrank p = 0.181). Therefore, the role of NGS in the guidance of personalized targeted therapy, solely based on NGS, may be limited. Multi-center, large sample, prospective studies are needed to further verify these results.
Role of Clathrin and Dynamin in Clathrin Mediated Endocytosis/Synaptic Vesicle Recycling and Implications in Neurological Diseases
Authors: Prichard Kate L. , O'Brien Nicholas S. , Murcia Sari R. , Baker Jennifer R. , McCluskey Adam
Published: January 2022

Endocytosis is a process essential to the health and well-being of cell. It is required for the internalisation and sorting of “cargo”—the macromolecules, proteins, receptors and lipids of cell signalling. Clathrin mediated endocytosis (CME) is one of the key processes required for cellular well-being and signalling pathway activation. CME is key role to the recycling of synaptic vesicles [synaptic vesicle recycling (SVR)] in the brain, it is pivotal to signalling across synapses enabling intracellular communication in the sensory and nervous systems. In this review we provide an overview of the general process of CME with a particular focus on two key proteins: clathrin and dynamin that have a central role to play in ensuing successful completion of CME. We examine these two proteins as they are the two endocytotic proteins for which small molecule inhibitors, often of known mechanism of action, have been identified. Inhibition of CME offers the potential to develop therapeutic interventions into conditions involving defects in CME. This review will discuss the roles and the current scope of inhibitors of clathrin and dynamin, providing an insight into how further developments could affect neurological disease treatments.
Cognitive Networks (Cognits) Process and Maintain Working Memory
Authors: Fuster Joaquín M.
Published: January 2022

Ever since it was discovered in the monkey’s prefrontal cortex, persistent neuronal activity during the delay period of delay tasks has been considered a phenomenon of working memory. Operationally, this interpretation is correct, because during that delay those tasks require the memorization of a sensory cue, commonly visual. What is incorrect is the assumption that the persistent activity during the delay is caused exclusively by the retention of the sensory cue. In this brief review, the author takes the position that the neural substrate of working memory is an array of long-term memory networks, that is, of cognitive networks (cognits), updated and orderly activated for the attainment of a behavioral goal. In the case of a behavioral task, that activated array of cognits has been previously formed in long-term memory (throughout this text, the expression “long-term memory” refers to all experiences acquired after birth, including habits and so-called procedural memory, such as the learning of a behavioral task). The learning of a task is the forming of synaptic associations between neural representations of three cognitive components of the task: perceptual, motor, and reward-related. Thereafter, when needed, the composite cognit of the task is activated in an orderly fashion to serve working memory in the perception-action cycle. To make his points on a complex issue, which has been the focus of his work, and to delineate a frontier for future research, the author refers to several of his own publications and previously published reviews.
Seizure Prediction in EEG Signals Using STFT and Domain Adaptation
Authors: Peng Peizhen , Song Yang , Yang Lu , Wei Haikun
Published: January 2022

Epileptic seizure prediction is one of the most used therapeutic adjuvant strategies for drug-resistant epilepsy. Conventional approaches commonly collect training and testing samples from the same patient due to inter-individual variability. However, the challenging problem of domain shift between various subjects remains unsolved, resulting in a low conversion rate to the clinic. In this work, a domain adaptation (DA)-based model is proposed to circumvent this issue. The short-time Fourier transform (STFT) is employed to extract the time-frequency features from raw EEG data, and an autoencoder is developed to map these features into high-dimensional space. By minimizing the inter-domain distance in the embedding space, this model learns the domain-invariant information, such that the generalization ability is improved by distribution alignment. Besides, to increase the feasibility of its application, this work mimics the data distribution under the clinical sampling situation and tests the model under this condition, which is the first study that adopts the assessment strategy. Experimental results on both intracranial and scalp EEG databases demonstrate that this method can minimize the domain gap effectively compared with previous approaches.
Bilateral Anterior Capsulotomy for the Treatment of Refractory Somatic Symptom Disorder: A Case Report
Authors: He Weibin , Shao Lingmin , Wang Huiling , Huang Huan , Zhang Shudi , Li Chenhui , Zhang Chencheng , Yi Wei
Published: January 2022

Somatic symptom disorder (SSD) is a form of mental illness that causes one or more distressing somatic symptoms leading to a significant disruption to everyday life, characterized by excessive thoughts, feelings, or behaviors related to these symptoms. While SSD is characterized by significant discomfort in some parts of the body, these symptoms are not related to any known medical condition and therefore it cannot be diagnosed using any medical instrument examination. Currently available treatments for SSD, including drug therapy and psychotherapy (such as cognitive behavioral therapy), usually improve psychiatric symptoms, but the results are often disappointing. Furthermore, SSD is often comorbid with anxiety and depression (75.1 and 65.7%, respectively). Importantly, interventions targeting the anterior limb of the internal capsule (ALIC; e.g., deep brain stimulation and thermal ablation) can effectively treat various mental disorders, such as refractory obsessive-compulsive disorder, depression, and eating disorders, suggesting that it may also be effective for treating the depressive symptoms associated with SSD comorbidity. In this report, a 65-year-old woman diagnosed with SSD accompanied with depression and anxiety underwent bilateral anterior capsulotomy. The patient complained of nausea and vomiting, swelling of the hilum of the liver for 14 years, weakness of the limbs for 13 years, and burning pain in the esophagus for 1 year. Psychiatric and neuropsychological assessments were conducted to record the severity of the patients' symptoms and the progression of postoperative symptoms. The patient's somatization, depression, and anxiety symptoms as well as quality of life improved significantly and steadily; thus, anti-depressive and anti-anxiety medication were stopped. However, the patient developed new somatization symptoms, including dizziness, headache, and sternal pain, 10 months after the operation. Therefore, the patient resumed taking flupentixol and melitracen in order to control the new symptoms. This study shows that bilateral anterior capsulotomy appears to be a complementary treatment for refractory SSD with depressive and anxiety symptoms. Furthermore, postoperative use of anxiolytic and antidepressant medications may be useful for controlling future somatization symptoms.
Biofortified Wheat Increases Dietary Zinc Intake: A Randomised Controlled Efficacy Study of Zincol-2016 in Rural Pakistan
Authors: Lowe Nicola M. , Zaman Mukhtiar , Khan Muhammad Jaffar , Brazier Anna K. M. , Shahzad Babar , Ullah Ubaid , Khobana Gul , Ohly Heather , Broadley Martin R. , Zia Munir H. , McArdle Harry J. , Joy Edward J. M. , Bailey Elizabeth H. , Young Scott D. , Suh Jung , King Janet C. , Sinclair Jonathan , Tishkovskaya Svetlana
Published: January 2022

A new variety of zinc biofortified wheat (Zincol-2016) was released in Pakistan in 2016. The primary aim of this study was to examine the effects of consuming Zincol-2016 wheat flour on biochemical and functional markers of zinc status in a population with widespread zinc deficiency. An individually-randomised, double-blind, placebo-controlled cross over design was used. Fifty households were recruited to participate in the study, with each household included at least one woman of reproductive age (16–49 years) who was neither pregnant nor breast feeding or currently taking nutritional supplements. All households were provided with control flour for an initial 2-week baseline period, followed by the intervention period where households were randomly allocated in a 1:1 ratio to receive biofortified flour (group A; n = 25) and control flour (group B; n = 25) for 8-weeks, then switched to the alternate flour for 8-weeks. The trial has been registered with the ISRCTN (https://www.isrctn.com), ID ISRCTN83678069. The primary outcome measure was plasma zinc concentration, and the secondary outcome measures were plasma selenium and copper concentrations, plasma copper:zinc ratio and fatty acid desaturase and elongase activity indices. Nutrient intake was assessed using 24-h dietary recall interviews. Mineral concentrations in plasma were measured using inductively coupled plasma mass spectrometry and free fatty acids and sphingolipids by mass spectrometry. Linear Mixed Model regression and General Linear Model with repeated measures were used to analyse the outcomes. Based on an average flour consumption of 224 g/day, Zincol-2016 flour provided an additional daily zinc intake of between 3.0 and 6.0 mg for white and whole grain flour, respectively. No serious adverse events were reported. This resulted in significant, increase in plasma zinc concentration after 4 weeks [mean difference 41.5 μg/L, 95% CI (6.9–76.1), p = 0.02]. This was not present after 8 weeks (p = 0.6). There were no consistent significant effects of the intervention on fatty acid desaturase and elongase activity indices. Regular consumption of Zincol-2016 flour increased the daily zinc intake of women of reproductive age by 30–60%, however this was not associated with a sustained improvement in indices of zinc status.