bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Occupational Noise on Hypertension Risk: A Case-Control Study in Automobile Factory Personnel
Authors: Wu Xiaomei , Li Chaoxiu , Zhang Xiaohong , Song Yumeng , Zhao Dan , Lan YueYan , Zhou Bo
Published: February 2022

Background

Many epidemiological studies have investigated the relationship between occupational noise and hypertension, but with conflicting findings. This study aimed to assess the relationship between occupational noise exposure and the risk of hypertension.

Methods

A case-control study was conducted to explore hypertension predictors, and then sensitivity analysis was performed based on propensity score matching (PSM). Data were collected from participants' annual physical examinations and occupational noise exposure measurements. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression analysis. A restricted cubic spline (RCS) function was used to fit the dose-effect relationship.

Results

500 cases and 4,356 controls were included in the study. Multivariate logistic regression showed that an increase in the level of occupational noise [range 68–102 dB(A)] of 1 dB(A), corresponded to an increase in hypertension risk of 8.3% (OR: 1.083, 95% CI: 1.058–1.109). Compared to the first quartile, the risk of hypertension in the fourth quartile was 1.742 (95% CI: 1.313–2.310). After applying PSM to minimize bias, we obtained a population of 500 cases and 1,000 controls. Noise level was significantly associated with the risk of hypertension. In addition, the RCS curve showed the risk of hypertension was relatively stable until a predicted noise level of around 80 dB(A) and then started to increase rapidly afterward (Pnonlinear = 0.002).

Conclusions

Occupational noise exposure was significantly associated with hypertension risk and there was a positively correlated dose-response relationship.
Diabetes and Its Cardiovascular Complications: Comprehensive Network and Systematic Analyses
Authors: Wu Hao , Norton Vikram , Cui Kui , Zhu Bo , Bhattacharjee Sudarshan , Lu Yao Wei , Wang Beibei , Shan Dan , Wong Scott , Dong Yunzhou , Chan Siu-Lung , Cowan Douglas , Xu Jian , Bielenberg Diane R. , Zhou Changcheng , Chen Hong
Published: February 2022

Diabetes mellitus is a worldwide health problem that usually comes with severe complications. There is no cure for diabetes yet and the threat of these complications is what keeps researchers investigating mechanisms and treatments for diabetes mellitus. Due to advancements in genomics, epigenomics, proteomics, and single-cell multiomics research, considerable progress has been made toward understanding the mechanisms of diabetes mellitus. In addition, investigation of the association between diabetes and other physiological systems revealed potentially novel pathways and targets involved in the initiation and progress of diabetes. This review focuses on current advancements in studying the mechanisms of diabetes by using genomic, epigenomic, proteomic, and single-cell multiomic analysis methods. It will also focus on recent findings pertaining to the relationship between diabetes and other biological processes, and new findings on the contribution of diabetes to several pathological conditions.
A Nomogram to Predict Regrowth After Ultrasound-Guided Radiofrequency Ablation for Benign Thyroid Nodules
Authors: Yan Lin , Zhang Mingbo , Li Xinyang , Li YingYing , Luo Yukun
Published: February 2022

Objective

To develop and validate a nomogram to predict regrowth for patients with benign thyroid nodules undergoing radiofrequency ablation (RFA).

Methods

A total of 200 patients with 220 benign thyroid nodules who underwent RFA were included in this respective study. After RFA, patients were followed up at 1, 3, 6, and 12 months, and every 12 months thereafter. Regrowth was defined as an increase in nodule volume 50% over the previously recorded smallest volume. A nomogram was developed based on the variables identified by multivariate logistic regression and the model performance was evaluated by discrimination(concordance index) and calibration curves.

Results

The incidence of regrowth was 13.64% (30/220) after a mean follow-up period of 27.43 ± 17.99 months. Multivariate logistic regression revealed initial volume (OR = 1.047, 95%CI 1.020–1.075), vascularity (OR = 2.037, 95%CI 1.218–3.404), and location close to critical structure (OR = 4.713, 95%CI 1.817–12.223) were independent factors associated with regrowth. The prognostic nomogram incorporating these three factors achieved good calibration and discriminatory abilities with a concordance index of 0.779 (95%CI 0.686–0.872).

Conclusions

A prognostic nomogram was successfully developed to predict nodule regrowth after RFA, which might guide physician in stratifying patients and provide precise guidance for individualized treatment protocols.
Levothyroxine Supplementation in Euthyroid Pregnant Women With Positive Autoantibodies: A Systematic Review and Meta-Analysis
Authors: Di Girolamo Raffaella , Liberati Marco , Silvi Claudia , D’Antonio Francesco
Published: February 2022

Objectives

To explore the role of levothyroxine (LT4) supplementation in affecting the outcome of pregnant euthyroid women with thyroperoxidase (TPO) antibodies.

Methods

MEDLINE, EMBASE, Google Scholar, and the Web of Science databases were searched. The primary outcome was pre-term birth (PTB), defined as live birth before 37 weeks of gestation; secondary outcomes were gestational hypertension, pre-eclampsia (PE), placental abruption, miscarriage, intra-uterine death (IUD), and admission to neonatal intensive care unit (NICU). All these outcomes were explored in euthyroid women with TPO antibodies receiving compared to those not receiving LT4 supplementation in pregnancy. Random-effect meta-analyses were used to analyze the data and results reported as pooled odds ratios (OR) with their 95% confidence intervals (CI).

Results

The risk of PTB was lower in women with TPO antibodies receiving compared to those not receiving LT4 supplementation (OR of 0.60 (95% CI 0.4-0.9). However, this association came mainly from observational studies (OR: 0.29, 95% CI 0.1-0), while RCTs did not show any beneficial effect of LT4 supplementation in affecting such outcomes. Conversely, there was no difference in the risk of gestational hypertension, preeclampsia, placental abruption, miscarriage, and admission to NICU between the two groups.

Conclusions

LT4 supplementation in TPO euthyroid women is not associated with a reduced risk of PTB in TPO-positive women with normal thyroid function.
Diabetes and COVID-19; A Bidirectional Interplay
Authors: Kazakou Paraskevi , Lambadiari Vaia , Ikonomidis Ignatios , Kountouri Aikaterini , Panagopoulos Georgios , Athanasopoulos Stavros , Korompoki Eleni , Kalomenidis Ioannis , Dimopoulos Meletios A. , Mitrakou Asimina
Published: February 2022

There seems to be a bidirectional interplay between Diabetes mellitus (DM) and coronavirus disease 2019 (COVID-19). On the one hand, people with diabetes are at higher risk of fatal or critical care unit-treated COVID-19 as well as COVID-19 related health complications compared to individuals without diabetes. On the other hand, clinical data so far suggest that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may result in metabolic dysregulation and in impaired glucose homeostasis. In addition, emerging data on new onset DM in previously infected with SARS-CoV-2 patients, reinforce the hypothesis of a direct effect of SARS-CoV-2 on glucose metabolism. Attempting to find the culprit, we currently know that the pancreas and the endothelium have been found to express Angiotensin-converting enzyme 2 (ACE2) receptors, the main binding site of the virus. To move from bench to bedside, understanding the effects of COVID-19 on metabolism and glucose homeostasis is crucial to prevent and manage complications related to COVID-19 and support recovering patients. In this article we review the potential underlying pathophysiological mechanisms between COVID-19 and glucose dysregulation as well as the effects of antidiabetic treatment in patients with diabetes and COVID-19.
Consequences and Drivers of Differentiated Environmental Regulation Policies on Hog Production in China: A Spatial Econometrics Approach
Authors: Zeng Fang , Yan Lingxiao , Tan Ying
Published: February 2022

Using a spatial econometric approach and national prefecture-level hog inventory data, this paper analyzes the extent to which environmental regulation policies influence hog production in China, and obtained the following research results: 1) During the 12th Five-Year Plan period, environmental regulation policies will significantly reduce the output of the hog industry in highly regulated areas. 2) The specific policy commands from the central government targeting on livestock sector and a high share of agriculture in the economy will increase the stringency of the environmental regulation policies on hog production. 3) The COD emission reduction requirements also have a significant negative impact on major hog farming provinces, the results obtained from the main model are verified again. The results highlight the importance of a more flexible environmental decentralization regime in China and other developing countries for future reforms.
Progress and Challenges Toward Generation and Maintenance of Long-Lived Memory T Lymphocyte Responses During COVID-19
Authors: Kumar Swatantra , Saxena Shailendra K. , Maurya Vimal K. , Tripathi Anil K.
Published: February 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing the coronavirus disease 2019 (COVID-19) pandemic is a serious global threat until we identify the effective preventive and therapeutic strategies. SARS-CoV-2 infection is characterized by various immunopathological consequences including lymphocyte activation and dysfunction, lymphopenia, cytokine storm, increased level of neutrophils, and depletion and exhaustion of lymphocytes. Considering the low level of antibody-mediated protection during coronavirus infection, understanding the role of T cell for long-term protection is decisive. Both CD4+ and CD8+ T cell response is imperative for cell-mediated immune response during COVID-19. However, the level of CD8+ T cell response reduced to almost half as compared to CD4+ after 6 months of infection. The long-term protection is mediated via generation of immunological memory response during COVID-19. The presence of memory CD4+ T cells in all the severely infected and recovered individuals shows that the memory response is predominated by CD4+ T cells. Prominently, the antigen-specific CD4+ and CD8+ T cells are specifically observed during day 0 to day 28 in COVID-19-vaccinated individuals. However, level of antigen-specific T memory cells in COVID-19-vaccinated individuals defines the long-term protection against forthcoming outbreaks of SARS-CoV-2.
A Deep Insight Into Regulatory T Cell Metabolism in Renal Disease: Facts and Perspectives
Authors: Han Zhongyu , Ma Kuai , Tao Hongxia , Liu Hongli , Zhang Jiong , Sai Xiyalatu , Li Yunlong , Chi Mingxuan , Nian Qing , Song Linjiang , Liu Chi
Published: February 2022

Kidney disease encompasses a complex set of diseases that can aggravate or start systemic pathophysiological processes through their complex metabolic mechanisms and effects on body homoeostasis. The prevalence of kidney disease has increased dramatically over the last two decades. CD4+CD25+ regulatory T (Treg) cells that express the transcription factor forkhead box protein 3 (Foxp3) are critical for maintaining immune homeostasis and preventing autoimmune disease and tissue damage caused by excessive or unnecessary immune activation, including autoimmune kidney diseases. Recent studies have highlighted the critical role of metabolic reprogramming in controlling the plasticity, stability, and function of Treg cells. They are also likely to play a vital role in limiting kidney transplant rejection and potentially promoting transplant tolerance. Metabolic pathways, such as mitochondrial function, glycolysis, lipid synthesis, glutaminolysis, and mammalian target of rapamycin (mTOR) activation, are involved in the development of renal diseases by modulating the function and proliferation of Treg cells. Targeting metabolic pathways to alter Treg cells can offer a promising method for renal disease therapy. In this review, we provide a new perspective on the role of Treg cell metabolism in renal diseases by presenting the renal microenvironment、relevant metabolites of Treg cell metabolism, and the role of Treg cell metabolism in various kidney diseases.
Tumor Immune Microenvironment and Immunotherapy in Brain Metastasis From Non-Small Cell Lung Cancer
Authors: Wang Yuchang , Chen Rui , Wa Yue , Ding Shikuan , Yang Yijian , Liao Junbo , Tong Lei , Xiao Gelei
Published: February 2022

Brain metastasis (BM), a devastating complication of advanced malignancy, has a high incidence in non-small cell lung cancer (NSCLC). As novel systemic treatment drugs and improved, more sensitive imaging investigations are performed, more patients will be diagnosed with BM. However, the main treatment methods face a high risk of complications at present. Therefore, based on immunotherapy of tumor immune microenvironment has been proposed. The development of NSCLC and its BM is closely related to the tumor microenvironment, the surrounding microenvironment where tumor cells live. In the event of BM, the metastatic tumor microenvironment in BM is composed of extracellular matrix, tissue-resident cells that change with tumor colonization and blood-derived immune cells. Immune-related cells and chemicals in the NSCLC brain metastasis microenvironment are targeted by BM immunotherapy, with immune checkpoint inhibition therapy being the most important. Blocking cancer immunosuppression by targeting immune checkpoints provides a suitable strategy for immunotherapy in patients with advanced cancers. In the past few years, several therapeutic advances in immunotherapy have changed the outlook for the treatment of BM from NSCLC. According to emerging evidence, immunotherapy plays an essential role in treating BM, with a more significant safety profile than others. This article discusses recent advances in the biology of BM from NSCLC, reviews novel mechanisms in diverse tumor metastatic stages, and emphasizes the role of the tumor immune microenvironment in metastasis. In addition, clinical advances in immunotherapy for this disease are mentioned.
Regulation of Pattern-Recognition Receptor Signaling by HBX During Hepatitis B Virus Infection
Authors: You Hongjuan , Qin Suping , Zhang Fulong , Hu Wei , Li Xiaocui , Liu Dongsheng , Kong Fanyun , Pan Xiucheng , Zheng Kuiyang , Tang Renxian
Published: February 2022

As a small DNA virus, hepatitis B virus (HBV) plays a pivotal role in the development of various liver diseases, including hepatitis, cirrhosis, and liver cancer. Among the molecules encoded by this virus, the HBV X protein (HBX) is a viral transactivator that plays a vital role in HBV replication and virus-associated diseases. Accumulating evidence so far indicates that pattern recognition receptors (PRRs) are at the front-line of the host defense responses to restrict the virus by inducing the expression of interferons and various inflammatory factors. However, depending on HBX, the virus can control PRR signaling by modulating the expression and activity of essential molecules involved in the toll-like receptor (TLR), retinoic acid inducible gene I (RIG-I)-like receptor (RLR), and NOD-like receptor (NLR) signaling pathways, to not only facilitate HBV replication, but also promote the development of viral diseases. In this review, we provide an overview of the mechanisms that are linked to the regulation of PRR signaling mediated by HBX to inhibit innate immunity, regulation of viral propagation, virus-induced inflammation, and hepatocarcinogenesis. Given the importance of PRRs in the control of HBV replication, we propose that a comprehensive understanding of the modulation of cellular factors involved in PRR signaling induced by the viral protein may open new avenues for the treatment of HBV infection.
Leukocytes in Cerebral Thrombus Respond to Large-Vessel Occlusion in a Time-Dependent Manner and the Association of NETs With Collateral Flow
Authors: Chen Xi , Wang Li , Jiang Meiling , Lin Lin , Ba Zhaojing , Tian Hao , Li Guangjian , Chen Lin , Liu Qu , Hou Xianhua , Wu Min , Liu Lu , Ju Wenying , Zeng Wen , Zhou Zhenhua
Published: February 2022

Thrombus components are dynamically influenced by local blood flow and blood immune cells. After a large-vessel occlusion stroke, changes in the cerebral thrombus are unclear. Here we assessed a total of 206 cerebral thrombi from patients with ischemic stroke undergoing endovascular thrombectomy. The thrombi were categorized by time to reperfusion of <4 h (T4), 4–8 h (T4–8), and >8 h (T8). The cellular compositions in thrombus were analyzed, and relevant clinical features were compared. Both white blood cells and neutrophils were increased and then decreased in thrombus with time to reperfusion, which were positively correlated with those in peripheral blood. The neutrophil extracellular trap (NET) content in thrombus was correlated with the degree of neurological impairment of patients. Moreover, with prolonged time to reperfusion, the patients showed a trend of better collateral grade, which was associated with a lower NET content in the thrombus. In conclusion, the present results reveal the relationship between time-related endovascular immune response and clinical symptoms post-stroke from the perspective of thrombus and peripheral blood. The time-related pathological changes of cerebral thrombus may not be the direct cause for the difficulty in thrombolysis and thrombectomy. A low NET content in thrombi indicates excellent collateral flow, which suggests that treatments targeting NETs in thrombi might be beneficial for early neurological protection.
Disrupted Peyer’s Patch Microanatomy in COVID-19 Including Germinal Centre Atrophy Independent of Local Virus
Authors: Trevelin Silvia C. , Pickering Suzanne , Todd Katrina , Bishop Cynthia , Pitcher Michael , Garrido Mesa Jose , Montorsi Lucia , Spada Filomena , Petrov Nedyalko , Green Anna , Shankar-Hari Manu , Neil Stuart J.D. , Spencer Jo
Published: February 2022

Confirmed SARS-coronavirus-2 infection with gastrointestinal symptoms and changes in microbiota associated with coronavirus disease 2019 (COVID-19) severity have been previously reported, but the disease impact on the architecture and cellularity of ileal Peyer’s patches (PP) remains unknown. Here we analysed post-mortem tissues from throughout the gastrointestinal (GI) tract of patients who died with COVID-19. When virus was detected by PCR in the GI tract, immunohistochemistry identified virus in epithelium and lamina propria macrophages, but not in lymphoid tissues. Immunohistochemistry and imaging mass cytometry (IMC) analysis of ileal PP revealed depletion of germinal centres (GC), disruption of B cell/T cell zonation and decreased potential B and T cell interaction and lower nuclear density in COVID-19 patients. This occurred independent of the local viral levels. The changes in PP demonstrate that the ability to mount an intestinal immune response is compromised in severe COVID-19, which could contribute to observed dysbiosis.
Using Geographical Overlaps to Track Temporal Changes in Species Interactions and Community Coexistence Instability
Authors: Lai Yin-Zheng , Tu Chih-Wei , Hsieh Chih-hao , Ko Chia-Ying
Published: February 2022

Environmental and climatic changes are expected to redistribute species, altering the strengths of species interaction networks; however, long-term and large-scale evaluations remain elusive. One way to infer species interaction networks is by analyzing their geographical overlaps, which provides indices of species interdependence, such as mean spatial robustness (MSR), which represents the geographical impact of a species on other species, and mean spatial sensitivity (MSS), which indicates how a species is influenced by other species. Integrating MSR and MSS further allows us to assess community coexistence stability and structure, with a stronger negative relationship between MSR and MSS (i.e., species are unequally dependent on each other) within a community at a given time suggesting a more stable community. Here, we assessed multidecadal changes in adult marine fish communities using bottom trawl datasets across latitudes from 1982 to 2011 in the Eastern US Continental Shelf, North Sea, and Eastern Bering Sea. Consistent, significant long-term increasing temporal trends of MSR and MSS were found in all three large marine communities. MSR exhibited strong correlations with species’ range sizes, especially in high-latitude communities, while MSS was strongly positively correlated with species’ median proportion of overlap with interacting species. The relationships between MSR and MSS were generally negative, indicating stably coexisting fish communities. However, the negative relationships weakened over time, implying that the coexisting fish communities gradually became unstable. Our findings provide an assessment of changes in spatially geographical aspects of multiple species, for decades and at mid- to high latitudes, to allow the detection of global ecological changes in marine systems by alternative estimation of geographic overlaps of species interaction networks. Such species co-occurrence estimation can help stay vigilant of strategies for accelerating climate change mitigation particularly at coarser spatial scales.
Promising Antiproliferative Compound From the Green Microalga Dunaliella tertiolecta Against Human Cancer Cells
Authors: Martínez Kevin A. , Saide Assunta , Crespo Gloria , Martín Jesús , Romano Giovanna , Reyes Fernando , Lauritano Chiara , Ianora Adrianna
Published: February 2022

Dunaliella tertiolecta is a green flagellated microalga with a high tolerance to salinity and high production of pigments such as zeaxanthin, a xanthophyll carotenoid present in higher plants known for its antioxidant potential. In the current study, the antiproliferative activity of raw extracts and fractions of D. tertiolecta (clone CCMP 1320) was evaluated against four different human cancer cell lines: melanoma, hepatocellular liver carcinoma, and two lung adenocarcinoma cell lines. In addition, a normal cell line (lung fibroblast) was used as toxicity control. The activity was evaluated by treatment with the extracts/fractions following the MTT colorimetric assay procedures. HPLC-UV-HRMS based dereplication helped to identify the bioactive metabolites. A glycoglycerolipid was identified in the active fraction, being involved in the bioactivity of this microalga. This compound, glycerol 1-(9Z,12Z,15Z-octadecatrienoate)-2-(4Z,7Z,10Z,13Z-hexadecatetraenoate)-3-O-β-D-galactopyranoside (1), was purified and its antiproliferative activity was confirmed. This work gives new insights on the antiproliferative activity of the green alga D. tertiolecta and its potential industrial applications.
Sea Wave Data Reconstruction Using Micro-Seismic Measurements and Machine Learning Methods
Authors: Iafolla Lorenzo , Fiorenza Emiliano , Chiappini Massimo , Carmisciano Cosmo , Iafolla Valerio Antonio
Published: February 2022

Sea wave monitoring is key in many applications in oceanography such as the validation of weather and wave models. Conventional in situ solutions are based on moored buoys whose measurements are often recognized as a standard. However, being exposed to a harsh environment, they are not reliable, need frequent maintenance, and the datasets feature many gaps. To overcome the previous limitations, we propose a system including a buoy, a micro-seismic measuring station, and a machine learning algorithm. The working principle is based on measuring the micro-seismic signals generated by the sea waves. Thus, the machine learning algorithm will be trained to reconstruct the missing buoy data from the micro-seismic data. As the micro-seismic station can be installed indoor, it assures high reliability while the machine learning algorithm provides accurate reconstruction of the missing buoy data. In this work, we present the methods to process the data, develop and train the machine learning algorithm, and assess the reconstruction accuracy. As a case of study, we used experimental data collected in 2014 from the Northern Tyrrhenian Sea demonstrating that the data reconstruction can be done both for significant wave height and wave period. The proposed approach was inspired from Data Science, whose methods were the foundation for the new solutions presented in this work. For example, estimating the period of the sea waves, often not discussed in previous works, was relatively simple with machine learning. In conclusion, the experimental results demonstrated that the new system can overcome the reliability issues of the buoy keeping the same accuracy.
Distribution, Diversity, and Abundance of Nitrite Oxidizing Bacteria in the Subterranean Estuary of the Daya Bay
Authors: Sun Wei , Jiao Lijing , Wu Jiapeng , Wei Mingken , Hong Yiguo
Published: February 2022

The oxidation of nitrite to nitrate as the second step of nitrification is vital for the global nitrogen cycle, and the genus Nitrospira is the most widespread nitrite-oxidizing bacteria (NOB) in diverse natural ecosystems. However, our understanding of Nitrospira distribution and their response to dynamic environmental parameters is still limited in the subterranean estuary (STE), a special environment of the mixed zone between land and sea. In this study, Nitrospira communities were collected within 5–10 cm depth intervals of sediments with the physiochemical gradients along the transections of the Daya Bay (DYB) from the landward member to the seaward member. The abundance, community structure of Nitrospira, and their potentially influencing environmental factors were investigated using Q-PCR, the high throughput sequencing targeting Nitrospira nxrB gene, and biostatistics analyses. The abundance of Nitrospira showed uniform distribution along the transections, but significantly decreasing variations were observed from the surface (<20 cm) to the bottom (>20 cm) of sediments. The community diversity and structure of Nitrospira also displayed a remarkable vertical distribution in the DYB (STE), although no significant differences were observed along the transections of STE. Nitrospira marina (N. marina) predominated in the sediments, Candidatus Nitrospira bockiana (Ca. N. bockiana), and Candidatus Nitrospira defluvii (Ca. N. defluvii) were the main Nitrospira species, and Candidatus Nitrospira lenta (Ca. N. lenta) and Nitrospira japonica (N. japonica) also existed with relatively low abundance in the DYB (STE). These findings revealed that Nitrospira species (Ca. N. defluvii, Ca. N. lenta, and N. japonica) derived from activated sludge was also widespread in natural habitats and deduced that the STE may be affected by the pollution derived from terrigenous human activities. The statistical analysis combined with the STE dynamic variation indicated that dissolved organic carbon (DOC), salinity, and ammonium along the sediment depths attributed to the vertical community distribution of the Nitrospira species. In summary, the vertical distribution of Nitrospira and their response to the dynamic physicochemical parameters imply their important role in the nitrite oxidation of the STE and provide insights into the niche differentiation and diversely physiologic metabolism of NOB.
Surface Warming Slowdown With Continued Subsurface Warming in the East Sea (Japan Sea) Over Recent Decades (2000–2014)
Authors: Jeong Yubeen , Nam SungHyun , Kwon Jae-Il , Uppara Umakanth , Jo Young-Heon
Published: February 2022

The long-term surface warming trend in the East Sea (Japan Sea; ES hereafter) stalled from 2000 to 2014 (−0.05°C yr−1, surface warming slowdown), while the subsurface (100–300°m) warming trend continued (+0.03°C yr−1). To address the processes underlying these contrasting trends in surface and subsurface temperature change, the trends in sea-level anomaly, isopycnal depth, and wind pattern were analyzed using monthly mean ocean reanalysis system 4 (ORAS4) data. During this period, the strengthened northwesterly/northerly wind in the central part of ES is supposed to contribute to a negative (positive) wind stress curl to its west (east), corresponding to an anticyclonic (cyclonic) circulation in the west (east). Furthermore, the induced negative wind stress in the west appears to enhance the northward penetration of East Korean Warm Current (EKWC), the slowdown in its eastward meandering around 38° N from the Korea coast, resulting in warm water accumulation in the west with peak warm anomaly at relatively greater depth compared to peak cold anomaly in the east. Overall, these wind-driven changes in transport from west to east, wind stress curl induced horizontal divergence (convergence) and the associated upwelling (downwelling), causes surface warming to slow and subsurface warming to persist during 2000 to 2014.
Evaluation of the PLAC8 Gene in Mexican Women With and Without Preeclampsia and Obesity
Authors: Barragán-Zúñiga Laura Jazel , Marchat Laurence A. , Carrasco-Wong Ivo , Blanco-Castaneda Ricardo , Salas-Pacheco José M. , Simental-Mendia Luis Ernesto , Correa-Ramírez Miguel Mauricio , Sosa-Macías Martha , Gutiérrez Jaime , Galaviz-Hernandez Carlos
Published: February 2022

Preeclampsia (PE) is a leading cause of maternal-fetal mortality worldwide, and obesity is an important risk factor. Genes associated with pathophysiological events common to preeclampsia and obesity, such as PLAC8, remain to be studied; therefore, the aim of the present study was to evaluate this gene in the placentas of women affected with preeclampsia and healthy pregnant women. This case-controlled study included 71 healthy and 64 preeclampsia pregnancies. Gene expression was evaluated in primary human cytotrophoblasts (PHCT) from six normal and six preeclampsia pregnancies, and protein expression was verified in placentas from five healthy and six preeclampsia pregnancies. The whole coding and 5′ regions of the PLAC8 gene were sequenced from healthy (n = 10) and preeclamptic (n = 10) pregnancies. The presence of the observed nucleotide variations was analyzed by RT-PCR in the total population. Statistical analyses were performed accordingly. Obesity was associated with severe preeclampsia (SPE) (OR = 3.34; CI 95% 1.3–8.2, p < 0.01). Significantly higher mRNA and protein expression was observed in preeclamptic vs. healthy placentas (p < 0.05). After sequencing, a single nucleotide variation was identified in 10 cases and one control (p < 0.01), which was then evaluated in the total population showing no association with preeclampsia. This preliminary study confirms the association of SPE with obesity and suggests higher expression of PLAC8 mRNA and protein in placentas from preeclampsia. No differences in nucleotide variations between cases and controls of the whole population were observed. Further research is required to evaluate the implications of higher gene/protein expression in preeclampsia and the causes of such variation.
Genetic Predisposition to Coronavirus Disease 2019 in Relation to Ten Cardiovascular Conditions: A Two-Sample Mendelian Randomization Study
Authors: Jia Min , Chen He-Jia , Jia Ling-Mei , Chen Ya-Li
Published: February 2022

Background

The long-term health consequences of coronavirus disease 2019 (COVID-19) remain largely unclear. This study aimed to apply the Mendelian randomization (MR) design to estimate the causal associations between COVID-19 and ten cardiovascular conditions.

Methods

Single-nucleotide polymorphisms (SNPs) associated with COVID-19 were used as instrumental variables to estimate the causal effect of COVID-19 on ten cardiovascular conditions. The random-effects inverse-variance weighted (IVW) method was conducted for the main analyses with a complementary analysis of the weighted median and MR-Egger approaches.

Results

In the IVW analysis, genetically predicted COVID-19 was suggestively associated with major coronary heart disease events (OR 1.081; 95% CI 1.007–1.16; P = 0.045) and heart failure (OR 1.049; 95% CI 1.001–1.1; P = 0.045) with similar estimates in weighted median regressions. No directional pleiotropic effects were observed in both funnel plots and MR-Egger intercepts.

Conclusions

Our findings provide direct evidence that patients infected with COVID-19 are causally associated with increased risk of cardiovascular disease, especially for major coronary heart disease events and heart failure.
Dysregulation of the Nitric Oxide/Dimethylarginine Pathway in Hypoxic Pulmonary Vasoconstriction—Molecular Mechanisms and Clinical Significance
Authors: Hannemann Juliane , Böger Rainer
Published: February 2022

The pulmonary circulation responds to hypoxia with vasoconstriction, a mechanism that helps to adapt to short-lived hypoxic episodes. When sustained, hypoxic pulmonary vasoconstriction (HPV) may become deleterious, causing right ventricular hypertrophy and failure, and contributing to morbidity and mortality in the late stages of several chronic pulmonary diseases. Nitric oxide (NO) is an important endothelial vasodilator. Its release is regulated, amongst other mechanisms, by the presence of endogenous inhibitors like asymmetric dimethylarginine (ADMA). Evidence has accumulated in recent years that elevated ADMA may be implicated in the pathogenesis of HPV and in its clinical sequelae, like pulmonary arterial hypertension (PAH). PAH is one phenotypic trait in experimental models with disrupted ADMA metabolism. In high altitude, elevation of ADMA occurs during long-term exposure to chronic or chronic intermittent hypobaric hypoxia; ADMA is significantly associated with high altitude pulmonary hypertension. High ADMA concentration was also reported in patients with chronic obstructive lung disease, obstructive sleep apnoea syndrome, and overlap syndrome, suggesting a pathophysiological role for ADMA-mediated impairment of endothelium-dependent, NO-mediated pulmonary vasodilation in these clinically relevant conditions. Improved understanding of the molecular (dys-)regulation of pathways controlling ADMA concentration may help to dissect the pathophysiology and find novel therapeutic options for these diseases.
Optimization of the SARS-CoV-2 ARTIC Network V4 Primers and Whole Genome Sequencing Protocol
Authors: Lambisia Arnold W. , Mohammed Khadija S. , Makori Timothy O. , Ndwiga Leonard , Mburu Maureen W. , Morobe John M. , Moraa Edidah O. , Musyoki Jennifer , Murunga Nickson , Mwangi Jane N. , Nokes D. James , Agoti Charles N. , Ochola-Oyier Lynette Isabella , Githinji George
Published: February 2022

Introduction

The ARTIC Network's primer set and amplicon-based protocol is one of the most widely used SARS-CoV-2 sequencing protocol. An update to the V3 primer set was released on 18th June 2021 to address amplicon drop-off observed among the Delta variant of concern. Here, we report on an in-house optimization of a modified version of the ARTIC Network V4 protocol that improves SARS-CoV-2 genome recovery in instances where the original V4 pooling strategy was characterized by amplicon drop-offs.

Methods

We utilized a matched set of 43 clinical samples and serially diluted positive controls that were amplified by ARTIC V3, V4 and optimized V4 primers and sequenced using GridION from the Oxford Nanopore Technologies'.

Results

We observed a 0.5% to 46% increase in genome recovery in 67% of the samples when using the original V4 pooling strategy compared to the V3 primers. Amplicon drop-offs at primer positions 23 and 90 were observed for all variants and positive controls. When using the optimized protocol, we observed a 60% improvement in genome recovery across all samples and an increase in the average depth in amplicon 23 and 90. Consequently, ≥95% of the genome was recovered in 72% (n = 31) of the samples. However, only 60–70% of the genomes could be recovered in samples that had <28% genome coverage with the ARTIC V3 primers. There was no statistically significant (p > 0.05) correlation between Ct value and genome recovery.

Conclusion

Utilizing the ARTIC V4 primers, while increasing the primer concentrations for amplicons with drop-offs or low average read-depth, greatly improves genome recovery of Alpha, Beta, Delta, Eta and non-VOC/non-VOI SARS-CoV-2 variants.
Highlights of Strategies Targeting Fibroblasts for Novel Therapies for Rheumatoid Arthritis
Authors: Chu Cong-Qiu
Published: February 2022

Synovial fibroblasts of rheumatoid arthritis (RA) play a critical role in perpetuation of chronic inflammation by interaction with immune and inflammatory cells and in cartilage and bone invasion, but current therapies for RA are not directly targeted fibroblasts. Selectively fibroblast targeted therapy has been hampered because of lack of fibroblast specific molecular signature. Recent advancement in technology enabled us to gain insightful information concerning RA synovial fibroblast subpopulations and functions. Exploring fibroblast targeted therapies have been focused on inducing cell death via fibroblast associated proteins; interrupting fibroblast binding to matrix protein; blocking intercellular signaling between fibroblasts and endothelial cells; inhibiting fibroblast proliferation and invasion; promoting cell apoptosis and inducing cellular senescence, and modulating fibroblast glucose metabolism. Translation into clinical studies of these fibroblast targeted strategies is required for evaluation for their clinical application, in particular for combination therapy with current immune component targeted therapies. Here, several strategies of fibroblast targeted therapy are highlighted.
iCn3D: From Web-Based 3D Viewer to Structural Analysis Tool in Batch Mode
Authors: Wang Jiyao , Youkharibache Philippe , Marchler-Bauer Aron , Lanczycki Christopher , Zhang Dachuan , Lu Shennan , Madej Thomas , Marchler Gabriele H. , Cheng Tiejun , Chong Li Chuin , Zhao Sarah , Yang Kevin , Lin Jack , Cheng Zhiyu , Dunn Rachel , Malkaram Sridhar Acharya , Tai Chin-Hsien , Enoma David , Busby Ben , Johnson Nicholas L. , Tabaro Francesco , Song Guangfeng , Ge Yuchen
Published: February 2022

iCn3D was initially developed as a web-based 3D molecular viewer. It then evolved from visualization into a full-featured interactive structural analysis software. It became a collaborative research instrument through the sharing of permanent, shortened URLs that encapsulate not only annotated visual molecular scenes, but also all underlying data and analysis scripts in a FAIR manner. More recently, with the growth of structural databases, the need to analyze large structural datasets systematically led us to use Python scripts and convert the code to be used in Node. js scripts. We showed a few examples of Python scripts at https://github.com/ncbi/icn3d/tree/master/icn3dpython to export secondary structures or PNG images from iCn3D. Users just need to replace the URL in the Python scripts to export other annotations from iCn3D. Furthermore, any interactive iCn3D feature can be converted into a Node. js script to be run in batch mode, enabling an interactive analysis performed on one or a handful of protein complexes to be scaled up to analysis features of large ensembles of structures. Currently available Node. js analysis scripts examples are available at https://github.com/ncbi/icn3d/tree/master/icn3dnode. This development will enable ensemble analyses on growing structural databases such as AlphaFold or RoseTTAFold on one hand and Electron Microscopy on the other. In this paper, we also review new features such as DelPhi electrostatic potential, 3D view of mutations, alignment of multiple chains, assembly of multiple structures by realignment, dynamic symmetry calculation, 2D cartoons at different levels, interactive contact maps, and use of iCn3D in Jupyter Notebook as described at https://pypi.org/project/icn3dpy.
High Estimated Glomerular Filtration Rate Is Associated With Worse Cognitive Performance in the Hypertensive Population: Results From the China H-Type Hypertension Registry Study
Authors: Li Junpei , Yu Shichao , Tan Ziheng , Yu Yun , Luo Linfei , Zhou Wei , Zhu Linjuan , Wang Tao , Cao Tianyu , Tu Jianglong , Bao Huihui , Huang Xiao , Cheng Xiaoshu
Published: February 2022

Background

Increasing studies have focused on the predictive value of high estimated glomerular filtration rate (eGFR) on cardiovascular diseases and mortality; however, the association between high eGFR with cognitive function is still not established. Thus, this study aimed to determine the co-relationship between high eGFR and cognitive performance in the hypertensive population.

Methods

We conducted a baseline cross-sectional study using data from the China H-type Hypertension Registry study. Mini-Mental State Examination (MMSE) assessment was performed to evaluate the cognitive function scale, and serum creatinine was collected to estimate eGFR level. Different MMSE cutoff values were applied in participants with the various educational background to define dementia: <24 in participants with secondary school and above education setting, <20 in those with primary school, and <17 in illiterate participants.

Results

A total of 9,527 hypertensive adults with mean age 63.7 ± 9.8 years and 67% female gender were analyzed. The eGFR cutoff value of 71.52 ml/min/1.73 m2 was found after adjusting for potential covariates in a threshold effect analysis. The MMSE increased significantly with the increment of eGFR (β, 0.27; 95% CI: 0.12–0.41) in participants with eGFR < 71.52 ml/min/1.73 m2 and decreased (β, −0.28; 95% CI: −0.39 to −0.17) in participants with eGFR ≥ 71.52 ml/min/1.73 m2. Individuals with eGFR ≥ 85 ml/min/1.73 m2 have an elevated risk of cognitive impairment than those with eGFR of 65–75 ml/min/1.73 m2. Subgroup analysis showed that a greater reduction degree of MMSE was observed in female individuals and those who had body mass index (BMI) ≥ 24 kg/m2 among participants with eGFR ≥ 71.52 ml/min/1.73 m2.

Conclusion

Our findings observed an inverted U-shaped relationship between eGFR and cognitive function. Both the low and high levels of eGFR were independently associated with worse cognitive assessment in the hypertensive population.
Clinical Imaging-Derived Metrics of Corticospinal Tract Structural Integrity Are Associated With Post-stroke Motor Outcomes: A Retrospective Study
Authors: Saltão da Silva Mary Alice , Baune Nathan Allen , Belagaje Samir , Borich Michael R.
Published: February 2022

Objective

The primary objective of this study was to retrospectively investigate associations between clinical magnetic resonance imaging-based (MRI) metrics of corticospinal tract (CST) status and paretic upper extremity (PUE) motor recovery in patients that completed acute inpatient rehabilitation (AR) post-stroke.

Methods

We conducted a longitudinal chart review of patients post-stroke who received care in the Emory University Hospital system during acute hospitalization, AR, and outpatient therapy. We extracted demographic information, stroke characteristics, and longitudinal documentation of post-stroke motor function from institutional electronic medical records. Serial assessments of paretic shoulder abduction and finger extension were estimated (E-SAFE) and an estimated Action Research Arm Test (E-ARAT) score was used to quantify 3-month PUE motor function outcome. Clinically-diagnostic MRI were used to create lesion masks that were spatially normalized and overlaid onto a white matter tract atlas delineating CST contributions emanating from six cortical seed regions to obtain the percentage of CST lesion overlap. Metric associations were investigated with correlation and cluster analyses, Kruskal-Wallis tests, classification and regression tree analysis.

Results

Thirty-four patients met study eligibility criteria. All CST overlap percentages were correlated with E-ARAT however, ventral premotor tract (PMv) overlap was the only tract that remained significantly correlated after multiple comparisons adjustment. Lesion overlap percentage in CST contributions from all seed regions was significantly different between outcome categories. Using MRI metrics alone, dorsal premotor (PMd) and PMv tracts classified recovery outcome category with 79.4% accuracy. When clinical and MRI metrics were combined, AR E-SAFE, patient age, and overall CST lesion overlap classified patients with 88.2% accuracy.

Conclusions

Study findings revealed clinical MRI-derived CST lesion overlap was associated with PUE motor outcome post-stroke and that cortical projections within the CST, particularly those emanating from non-M1 cortical areas, prominently ventral premotor (PMv) and dorsal premotor (PMd) cortices, distinguished between PUE outcome groups. Exploratory predictive models using clinical MRI metrics, either alone or in combination with clinical measures, were able to accurately identify recovery outcome category for the study cohort during both the acute and early subacute phases of post-stroke recovery. Prospective studies are recommended to determine the predictive utility of including clinical imaging-based biomarkers of white matter tract structural integrity in predictive models of post-stroke recovery.
Gut Microbiota and Targeted Biomarkers Analysis in Patients With Cognitive Impairment
Authors: Lu Shourong , Yang Ying , Xu Qiao , Wang Shuqiang , Yu Jie , Zhang Bingshan , Wang Zhuo , Zhang Yunyun , Lu Wenwei , Hong Kan
Published: February 2022

Gut microbial alteration is closely associated with brain disorders including cognitive impairment (CI). Gut microbes have the potential to predicate the development of diseases. However, the gut microbial markers for CI remain to be elucidated. In this study, the gut microbial alterations were assessed using16S rRNA sequencing, and identified the gut microbial markers using a random forest model. The results showed that there were significant gut microbial differences between the control and CI groups based on beta diversity (p < 0.002). Patients with CI had higher abundances of Actinobacteria and Proteobacteria but lower proportions of Bcateroidetes and Firmicutes vs. that in the control group. Patients had 39 special genera and the control subjects had 11 special genera. Furthermore, 11 genera such as Blautia, Roseburia, and Lactococcus and 18 genera such as Lactobacillus, Ruminococcus 2, and Akkermansia were the differential taxa in the control and CI groups, respectively. Gene functions related to nutrient metabolisms were upregulated in patients with CI. This suggested that the huge differences in gut microbes between the two groups and gut microbiota had the potential to predicate the development of CI. Based on machine learning results, 15 genera such as Lactobacillus, Bifidobacterium, and Akkermansia were selected as the optimal marker set to predicate CI with an area under curve (AUC) value of 78.4%. The results revealed the gut microbial markers for CI and provided a potential diagnosis tool to prevent the development of CI in the elderly.