bluuebunny/crossref_metadata_2025 huggingface dataset:
Red Blood Cell Distribution Width: A Prognostic Marker in Patients With Type B Aortic Dissection Undergoing Endovascular Aortic Repair
Authors: Jiang Cheng , Liu Anbang , Huang Lei , Liu Quanjun , Liu Yuan , Geng Qingshan
Published: May 2022

Background

Red blood cell distribution width (RDW) is associated with cardiovascular mortality. However, the relationship between preoperative RDW and outcomes after thoracic endovascular aortic repair (TEVAR) in type B aortic dissection (TBAD) remains to be determined.

Methods

We review the records of 678 patients with TBAD and treated with TEVAR in three centers. Patients were divided into two groups according to the admission RDW cut-off by receiver operating characteristic curve analysis [≤13.5% (n = 278) and >13.5% (n = 400)]. The association between RDW and long-term mortality was evaluated using Cox survival analysis. Additionally, we used general additive models (GAM) with restricted cubic splines (RCS) to explore non-linear relationships between RDW and outcomes.

Results

Subjects with a high RDW had significantly higher in-hospital mortality rates (1.4 vs. 4.3%, P = 0.038). A total of 70 subjects died after a median follow-up period of 3.3 years. Kaplan–Meier analysis showed that subjects with an RDW >13.5% had worse survival rates than those with lower RDW values (P < 0.001). Multivariate Cox proportional hazard modeling revealed that an RDW >13.5% was an independent predictor of long-term mortality (adjusted HR = 2.27, P = 0.006). Also, we found that there was a non-linear relationship between RDW and mortality from RCS, and RDW of 13.5% might be an inflection point to distinguish the long-term mortality risk of TBAD patients.

Conclusion

As an inexpensive and routinely measured parameter, RDW holds promise as a novel prognostic marker in patients with TBAD receiving TEVAR. We found that an RDW >13.5% on admission was independently associated with increased long-term mortality.
The Role of Multimodality Imaging for Percutaneous Coronary Intervention in Patients With Chronic Total Occlusions
Authors: Melotti Eleonora , Belmonte Marta , Gigante Carlo , Mallia Vincenzo , Mushtaq Saima , Conte Edoardo , Neglia Danilo , Pontone Gianluca , Collet Carlos , Sonck Jeroen , Grancini Luca , Bartorelli Antonio L. , Andreini Daniele
Published: May 2022

Background

Percutaneous coronary intervention (PCI) of Chronic total occlusions (CTOs) has been traditionally considered a challenging procedure, with a lower success rate and a higher incidence of complications compared to non-CTO-PCI. An accurate and comprehensive evaluation of potential candidates for CTO-PCI is of great importance. Indeed, assessment of myocardial viability, left ventricular function, individual risk profile and coronary lesion complexity as well as detection of inducible ischemia are key information that should be integrated for a shared treatment decision and interventional strategy planning. In this regard, multimodality imaging can provide combined data that can be very useful for the decision-making algorithm and for planning percutaneous CTO recanalization.

Aims

The purpose of this article is to appraise the value and limitations of several non-invasive imaging tools to provide relevant information about the anatomical characteristics and functional impact of CTOs that may be useful for the pre-procedural assessment and follow-up of candidates for CTO-PCI. They include echocardiography, coronary computed tomography angiography (CCTA), nuclear imaging, and cardiac magnetic resonance (CMR). As an example, CCTA can accurately delineate CTO location and length, distal coronary bed, vessel tortuosity and calcifications that can predict PCI success, whereas stress CMR, nuclear imaging and stress-CT can provide functional evaluation in terms of myocardial ischemia and viability and perfusion defect extension.
Left Atrial Thrombus in Patients With Non-valvular Atrial Fibrillation: A Cross-Sectional Study in China
Authors: Shi Shaobo , Zhao Qingyan , Liu Tao , Zhang Shujuan , Liang Jinjun , Tang Yanhong , Yang Bo , Huang He , Huang Congxin
Published: May 2022

Background

Stroke is predominately attributed to left atrial thrombus (LAT) in patients with non-valvular atrial fibrillation (NVAF), however, its detection rate in real clinical practice has been few reported in China.

Objective

This study aimed to investigate the prevalence and associated factors of LAT in patients with NVAF in China.

Methods

All adult NVAF patients undergoing transesophageal echocardiography (TEE) in the China Atrial Fibrillation Center database from January 2017 to January 2022 were enrolled in this study. The prevalence of LAT was calculated, and associated factors were identified.

Results

A total of 36,007 NVAF inpatients from 602 hospitals in 30 provinces/autonomous regions/municipalities were included in the final analysis, with a median age of 66 years and 39.4% were female. LAT was present in 1,467 (4.1%) patients overall, 2.7, 5.7, and 6.8% in patients with paroxysmal, persistent, and long-standing persistent AF, respectively. In subgroup analysis, including age ≥ 65 years, CHA2DS2-VASC score ≥ 2, left atrial diameter (LAD) ≥ 50 mm, left ventricular ejection fraction (LVEF) < 50%, and anticoagulation, patients with paroxysmal AF always had the lowest LAT prevalence, followed by patients with persistent and long-standing persistent AF. Patients treated with anticoagulants had less prevalent LAT than those without anticoagulation (2.1 vs. 5.0%, p < 0.001). In multivariate analysis, AF pattern (both persistent AF and long-standing persistent AF), hypertension, chronic heart failure, coronary heart disease, transient ischemic attack/stroke, diabetes mellitus, and LAD (per 5 mm) were associated with an increased prevalence of LAT. However, LVEF (per 5%) and anticoagulation were associated with a reduced prevalence of LAT.

Conclusion

LAT was found in 4.1% of Chinese adult NVAF inpatients underwent TEE in real-world experience. The prevalence of LAT mainly associated with non-paroxysmal AF, cardiovascular diseases, diabetes mellitus, enlarged left atrium, lower LVEF, and lack of anticoagulation therapy.
Prognosis of Adults With Isolated Left Ventricular Non-Compaction: Results of a Prospective Multicentric Study
Authors: Gerard Hilla , Iline Nicolas , Martel Hélène , Nguyen Karine , Richard Pascale , Donal Erwan , Eicher Jean-Christophe , Huttin Olivier , Selton-Suty Christine , Raud-Raynier Pascale , Jondeau Guillaume , Mansencal Nicolas , Sawka Caroline , Ader Flavie , Pruny Jean-François , Casalta Anne-Claire , Michel Nicolas , Donghi Valeria , Faivre Laurence , Giorgi Roch , Charron Philippe , Habib Gilbert
Published: May 2022

Background

Whether left ventricular non-compaction (LVNC) bears a different prognosis than dilated cardiomyopathy (DCM) is still a matter of debate.

Methods

From a multicenter French prospective registry, we compared the outcomes of 98 patients with LVNC and 65 with DCM. The primary endpoint combined cardiovascular death, heart transplantation, and hospitalization for cardiovascular events. The two groups presented similar outcomes but different left ventricular ejection fractions (LVEF) (43.3% in LVNC vs. 35.95% in DCM, p = 0.001). For this reason, a subgroup analysis was performed comparing only patients with LVEF ≤ 45%, including 56 with LVNC and 49 with DCM.

Results

Among patients with LVEF≤ 45%, at 5-year follow-up, the primary endpoint occurred in 33 (58.9%) among 56 patients with LVNC and 18 (36.7%) among 49 patients with DCM (p = 0.02). Hospitalization for heart failure (18 [32.14%] vs. 5 [10.20%], p = 0.035) and heart transplantation were more frequent in the LVNC than in the DCM group. The incidences of rhythmic complications (24 [42.85%] vs. 12 [24.48%], p = 0.17), embolic events, and cardiovascular death were similar between LVNC and DCM cases. Among the 42 patients with LVNC and LVEF > 45%, the primary endpoints occurred in only 4 (9.52%) patients, including 2 hospitalizations for heart failure and 3 rhythmic complications, but no embolic events.

Conclusion

In this prospective cohort, patients with LVNC who have left ventricular dysfunction present a poorer prognosis than DCM patients. Heart failure events were especially more frequent, but embolic events were not. Patients with LVNC and preserved ejection fraction present very few events in 5 years.
Transiently Observed Trace Albuminuria on Urine Dipstick Test Is Associated With All-Cause Death, Cardiovascular Death, and Incident Chronic Kidney Disease: A National Health Insurance Service-National Sample Cohort in Korea
Authors: Park Samel , Woo Jiyoung , Leem Subeen , Heo Nam Hun , Cho Nam-Jun , Gil Hyowook , Kim Jae Heon , Lee Eun Young
Published: May 2022

Introduction

Albuminuria is a well-known risk factor for end-stage kidney disease, all-cause mortality, and cardiovascular mortality, even when the albumin-to-creatinine ratio is <30 mg/g. However, the association between transiently observed trace albuminuria and these major adverse outcomes has not yet been reported. This study aimed to examine the effect of transient albuminuria on these major adverse outcomes using the National Health Insurance Service data in Korea.

Methods and Results

The National Health Insurance Service-National Sample Cohort from Korea, followed from 2002 to 2015, consisted of 1,025,340 individuals, accounting for 2.2% of the total Korean population. We analyzed the effect of transient albuminuria on all-cause death, cardiovascular death, and incident chronic kidney disease (CKD) and compared it with the group without albuminuria. Among 1,025,340 individuals, 121,876 and 2,815 had transient albuminuria and no albuminuria, respectively. Adjusted hazard ratios of the transient albuminuria group for cardiovascular death and incident CKD were 1.76 (1.01–3.08) and 1.28 (1.15–1.43), respectively. There were significant differences in all-cause death, cardiovascular death, and incident CKD between the two groups after propensity score matching (p = 0.0037, p = 0.015, and p < 0.0001, respectively). Propensity score matching with bootstrapping showed that the hazard ratios of the transient albuminuria group for all-cause death and cardiovascular death were 1.39 (1.01–1.92) and 2.18 (1.08–5.98), respectively.

Conclusions

In this nationwide, large-scale, retrospective cohort study, transient albuminuria was associated with all-cause death, cardiovascular death, and incident CKD, suggesting that transient albuminuria could be a risk marker for adverse outcomes in the future, and that its own subclinical phenotype could play an important role during the course of CKD.
Emotional Wellbeing: The Impact of the COVID-19 Pandemic on Women Academics in South Africa
Authors: Ronnie Linda , Bam Armand , Walters Cyrill
Published: May 2022

After the World Health Organization declared COVID-19 a pandemic on 11 March 2020, countries around the world responded with state-mandated lockdowns. Emerging data on the adverse psychological impact of the lockdown shows that women as a whole are among the most vulnerable groups. This study explores the specific stressors manifesting for women academics during lockdown and their toll on emotional wellbeing. A qualitative interpretive analysis of responses from 2,029 women academics showed participants experienced frustration, weariness, anxiety, and being overwhelmed as the result of emotional taxation from three sources: home responsibilities, social milieu, and work environment. The work-life merge that occurred during lockdown seemed to have a concertina effect on emotional wellbeing as participants were pressured to manage an inordinate number of responsibilities at once. The specific consequences of the concertina effect found in this study highlight opportunities for the academy to better support the wellbeing of women academics.
Relationship Between Serum Testosterone Levels and Kidney Stones Prevalence in Men
Authors: Huang Fang , Li Yongchao , Cui Yu , Zhu Zewu , Chen Jinbo , Zeng Feng , Li Yang , Chen Zhiyong , Chen Hequn
Published: May 2022

Background

The role of serum testosterone levels in male renal stone formation remains controversial. This study aimed to evaluate the relationship between serum testosterone levels and kidney stone prevalence in males.

Methods

We conducted a cross-sectional study based on the data from the National Health and Nutrition Examination Survey 2011–2016, which included 6,633 male participants, to investigate the association between testosterone levels and the prevalence of kidney stones.

Results

In this study, using the highest quartile of serum testosterone as a reference, a logistic regression model adjusted for confounders in all participants showed that the first quartile (OR: 1.375, p = 0.016), the second quartile (OR: 1.348, p = 0.021), and the third quartile (OR: 1.472, p = 0.003) of testosterone significantly increased kidney stone risks. In the 41–60 age group, the ORs of kidney stone risk in the first, second, and third of serum testosterone were 1.904 (P = 0.005), 1.599 (P = 0.040), and 1.734 (P = 0.015), respectively. This trend can also be found in the 61–80-year group, except in the first quartile of serum testosterone (OR: 1.169, P = 0.436). Adjusted smoothed curves suggest a non-linear relationship between the 8 quantiles of serum testosterone and the risk of kidney stones in all participants and the 61–80 age group and a significant negative relationship in the 41–60 age group (OR: 0.921, P = 0.0193). But no correlation was seen in the 20–40 group.

Conclusions

Serum testosterone levels were significantly inversely associated with the prevalence of kidney stones in men over 40 years of age, but no correlation was seen in the 20–40 group. The role of testosterone in stone formation should be redefined, and its effect should be further verified.
Participants’ Engagement With Telephone Support Interventions to Promote Healthy Feeding Practices and Obesity-Protective Behaviours for Infant Obesity Prevention
Authors: Ekambareshwar Mahalakshmi , Xu Huilan , Rissel Chris , Baur Louise , Taki Sarah , Mihrshahi Seema , Wen Li Ming
Published: May 2022

Background

Participant engagement with program interventions is vital to support intended behaviour changes and outcomes. The aim of this research was to investigate participant engagement with the Communicating Healthy Beginnings Advice by Telephone (CHAT) program, an early childhood obesity prevention program that included interventions for promoting healthy infant feeding practices and obesity-protective behaviours via telephone, and whether engagement with the telephone support program varied by participants’ sociodemographic characteristics.

Methods

This study used de-identified CHAT program data of participants who received the interventions via telephone. Data analysed included 1) participant engagement in telephone support from late pregnancy to 12 months of child's age, 2) demographic characteristics collected at late pregnancy and 3) intervention providers’ observations and notes (qualitative data) for 10 participants from each engagement group (low, medium, high) to explore issues discussed during telephone support.

Results

Call completion rate by participants was above sixty percent for all six stages of the telephone support program with more than half of the participants (57%) demonstrating high level of engagement. We found that participants’ country of birth, employment status and annual household income were predictors of engagement with the telephone support provided in the CHAT program. The odds of participants’ engagement with the telephone support program were 1.68 times higher for Australian born (95% CI 1.07 – 2.62), 1.63 times higher for participants who were employed (95% CI 1.01 – 2.66) and 1.63 times higher for participants with annual household income ≥AUD$80,000 (95% CI 1.02 – 2.60).

Conclusions

Participant engagement with the program interventions was good. Participants’ engagement with the telephone support program was significantly associated with certain socio-demographic characteristics. Australian born participants, and participants associated with higher household income and employment engaged significantly more with the telephone support provided in the CHAT program. Additionally, the program engaged more participants older than 30 years of age and those who spoke English at home. The program provided unintended personal benefits to some participants with high engagement level due to their various psychosocial needs such as domestic violence, mental health and sleep related issues. Although not an intended benefit of the intervention, psychosocial needs of participants were met which was a likely factor for mothers’ engagement with the program. This is an important factor that needs to be considered while implementing future programs or scale up of this program.
Cluster Partition-Based Zonal Voltage Control for Distribution Networks With High Penetrated PVs
Authors: Zhao Xingyu , Xiao Chuanliang , Peng Ke , Chen Jiajia , Zhang Xinhui
Published: May 2022

With the high penetrated photovoltaics (PVs) accessing distribution networks (DNs) in the future, the overvoltage of distribution network will be more serious, and the voltage control will be more complex. To solve this problem, a cluster partition-based zonal voltage control method for DN is proposed in this study. First, a cluster partition method using a comprehensive performance index is proposed: in terms of DN structure, a global density quality function index is introduced to measure the coupling degree of nodes in clusters. In terms of cluster function, the inconsistency coefficient index is presented to reflect the PV output characteristics, and a node membership function index is presented to limit the scale of the cluster. Then, the DN cluster partition is carried out under the fast Newman (FN) algorithm. Second, a second-order cone programming (SOCP) model of voltage control is established to maximize the PV consumption in each cluster. To achieve the coordinated optimization of clusters, an iterative optimization strategy among clusters is proposed. Finally, the effectiveness and rationality of the proposed method are verified in a 10 kV actual feeder system in Zhejiang Province, China.
Gallium Oxides Photocatalysts Doped With Fe Ions for Discoloration of Rhodamine Under UV and Visible Light
Authors: Orozco S. , Rivero M. , Montiel E. , Espino Valencia J.
Published: May 2022

Heterogeneous photocatalysis is a highly efficient process for degrading recalcitrant and emerging pollutants. Rhodamine B (RhB) is a nonbiodegradable and highly refractory compound persistent in conventional processes. In this work, we investigate the photocatalytic activity of gallium-based catalysts undoped (GO) and doped with Fe ions (GOFe). Catalysts were synthesized by simple precipitation assisted with an ultrasonic transducer and subjected to thermal treatment at different temperatures (500, 650, 800 and 950°C). They were characterized by thermogravimetric analysis (TGA), Fourier transform infrared (ATR-FTIR) spectroscopy, and X-ray diffraction (XRD). Catalysts were tested in the discoloration of Rhodamine B dye. Experiments were carried out at different pH values (3.00, 5.00 and 9.00) in the presence of H2O2 and using Visible and Visible-UV light sources as study variables. Better discoloration results were observed for GO and GOFe under acid environments (pH = 3.00) for both light sources. GO and GOFe photocatalyst showed high effectiveness in the discoloration of RhB completing the process in 300  min, under a Visible-UV lamp at pH = 3.00. Incorporating Fe ions into the gallium oxides matrix decreases its bandgap, allowing it to activate under visible light. The discoloration process exhibited pseudo-zero-order apparent kinetics.
Causal Effects of Genetically Predicted Cystatin C on Osteoporosis: A Two-Sample Mendelian Randomization Study
Authors: Yuan Jiaqin , Peng Lipeng , Luan Fujun , Li Jie , Zhang Jinglin , Jiang Wei , Wang Wenting
Published: May 2022

Objectives: Although it has long been reported that high levels of cystatin C could contribute to the development of osteoporosis in some studies, no evidence has established a causal association between them thus far.

Methods: A Mendelian randomization (MR) study was conducted to determine the causal effect of cystatin C on osteoporosis based on public databases obtained from separately published genome-wide association studies (GWASs). The single-nucleotide polymorphisms (SNPs) for cystatin C were extracted from the MR-Base (CKDGen, 33,152 participants), and the SNPs for osteoporosis were extracted from the United Kingdom Biobank project (United Kingdom Biobank, including 5,266 osteoporosis cases and 331,893 controls). We defined the odds ratio (OR) of IVW methods as the primary outcome. In addition, weighted median and MR–Egger regressions were used in the sensitivity analysis.

Results: In IVW, we found that genetically predicted cystatin C was causally associated with the risk of osteoporosis with an OR of 1.02 [95% confidence interval (CI) = 1.003–1.025, p = 0.01]. In the further sensitivity analysis, weighted median regression also showed directionally similar estimates (OR = 1.02, 95% CI = 1.005–1.03, p = 0.005), and MR–Egger regression (OR = 1.02, 95% CI = 1.000–1.036, p = 0.15) revealed similar estimates but with lower precision. The funnel plot, MR–Egger intercept, and MR-PRESSO all indicate that no directional pleiotropic effect was observed.

Conclusion: In conclusion, our MR study showed evidence of a causal association between serum cystatin C levels and osteoporosis, which also needs to be verified by studies with larger sample sizes in the future. Early monitoring of cystatin C may enable us to prevent osteoporosis-related diseases.
Molecular Subtyping of Cancer Based on Distinguishing Co-Expression Modules and Machine Learning
Authors: Sun Peishuo , Wu Ying , Yin Chaoyi , Jiang Hongyang , Xu Ying , Sun Huiyan
Published: May 2022

Molecular subtyping of cancer is recognized as a critical and challenging step towards individualized therapy. Most existing computational methods solve this problem via multi-classification of gene-expressions of cancer samples. Although these methods, especially deep learning, perform well in data classification, they usually require large amounts of data for model training and have limitations in interpretability. Besides, as cancer is a complex systemic disease, the phenotypic difference between cancer samples can hardly be fully understood by only analyzing single molecules, and differential expression-based molecular subtyping methods are reportedly not conserved. To address the above issues, we present here a new framework for molecular subtyping of cancer through identifying a robust specific co-expression module for each subtype of cancer, generating network features for each sample by perturbing correlation levels of specific edges, and then training a deep neural network for multi-class classification. When applied to breast cancer (BRCA) and stomach adenocarcinoma (STAD) molecular subtyping, it has superior classification performance over existing methods. In addition to improving classification performance, we consider the specific co-expressed modules selected for subtyping to be biologically meaningful, which potentially offers new insight for diagnostic biomarker design, mechanistic studies of cancer, and individualized treatment plan selection.
MicroRNA-382 Promotes M2-Like Macrophage via the SIRP-α/STAT3 Signaling Pathway in Aristolochic Acid-Induced Renal Fibrosis
Authors: Wang Xiaoyan , Jia Ping , Ren Ting , Zou Zhouping , Xu Sujuan , Zhang Yunlu , Shi Yiqin , Bao Siyu , Li Yingxiang , Fang Yi , Ding Xiaoqiang
Published: May 2022

Aristolochic acid nephropathy (AAN) is a type of drug-induced nephropathy and is correlated with a potentially progression of kidney fibrosis. However, whether miR-382 is implicated in macrophage activation in AA-induced kidney fibrosis remains elusive. Here, cell-sorting experiments defined a significant miR-382 enrichment in renal macrophage after AAN 14 days. Then, we found that treatment of AA induced a significant switch in the phenotype of macrophage bothin vivoandin vitro. Furthermore, miR-382 knockout (KO) mice and miR-382-/-bone marrow-derived macrophage (BMDM) were subjected to AA induction. We found that both systemic KO and macrophage-specific miR-382 depletion notably suppressed M2-like macrophage activation as well as kidney interstitial fibrosis. Additionally, adoptive transfer of miR-382 overexpression BMDMs into mice promoted AA-induced kidney injury. Moreover, in cultured macrophage, upregulation of miR-382 promoted M2-related gene expression, accompanied by downregulation of signal regulatory protein α (SIRP-α) and activation of signal transducer and activator of transcription 3 (STAT3). The interaction between miR-382 and SIRP-α was evaluatedviadual-luciferase assay. Knockdown of SIRP-α upregulated phosphorylated STAT3 at S727 and Y705. Pharmacological inhibition of STAT3 was performed bothin vivoandin vitro. Inhibition of STAT3 attenuated AA-induced kidney fibrosis, in parallel to lesser macrophage M2 polarization. Coculture experiments further confirmed that overexpressed miR-382 in macrophage promoted injuries of tubular cells. Luminex bio-chip detection suggested that IL-4 and CCL-5 were critical in the cross talk between macrophages and tubular cells. Taken together, our data suggest that miR-382 is a critical mediator in M2-like macrophage polarization and can be a promising therapeutic target for kidney fibrosis.
Lysine Acetylation/Deacetylation Modification of Immune-Related Molecules in Cancer Immunotherapy
Authors: Ding Peng , Ma Zhiqiang , Liu Dong , Pan Minghong , Li Huizi , Feng Yingtong , Zhang Yimeng , Shao Changjian , Jiang Menglong , Lu Di , Han Jing , Wang Jinliang , Yan Xiaolong
Published: May 2022

As major post-translational modifications (PTMs), acetylation and deacetylation are significant factors in signal transmission and cellular metabolism, and are modulated by a dynamic process via two pivotal categories of enzymes, histone acetyltransferases (HATs) and histone deacetylases (HDACs). In previous studies, dysregulation of lysine acetylation and deacetylation has been reported to be associated with the genesis and development of malignancy. Scientists have recently explored acetylation/deacetylation patterns and prospective cancer therapy techniques, and the FDA has approved four HDAC inhibitors (HDACi) to be used in clinical treatment. In the present review, the most recent developments in the area of lysine acetylation/deacetylation alteration in cancer immunotherapy were investigated. Firstly, a brief explanation of the acetylation/deacetylation process and relevant indispensable enzymes that participate therein is provided. Subsequently, a multitude of specific immune-related molecules involved in the lysine acetylation/deacetylation process are listed in the context of cancer, in addition to several therapeutic strategies associated with lysine acetylation/deacetylation modification in cancer immunotherapy. Finally, a number of prospective research fields related to cancer immunotherapy concepts are offered with detailed analysis. Overall, the present review may provide a reference for researchers in the relevant field of study, with the aim of being instructive and meaningful to further research as well as the selection of potential targets and effective measures for future cancer immunotherapy strategies.
Elevated Nutrient Supply Caused by the Approaching Kuroshio to the Southern Coast of Japan
Authors: Durán Gómez Gloria Silvana , Nagai Takeyoshi
Published: May 2022

Although the Kuroshio Current has been well-known for being nutrient poor in its upper layers, it sustains a great biodiversity within its region, including the Kuroshio Extension. Previous studies reported that the Kuroshio carries a large amount of nutrients in its dark subsurface layers, yet, the mechanisms of how these nutrients are brought to sunlit layers remain unclear. In a previous observational study, it is shown that when the Kuroshio flows near the shelf break, very strong turbulence with dissipation rates of O (10 -7 W kg -1), caused by trapped near-inertial internal waves, leads to the generation of large diffusive nitrate fluxes of 1-10 mmol N m -2 day -1. Nevertheless, since these results were obtained from just one transect survey, questions remain, such as how long the enhanced turbulent diffusive nitrate flux extends downstream, and how the Kuroshio path modulations affect this nutrient injection. In this study, observed features were reproduced by using a high-resolution nested simulation coupled with a N2PZD2 ecosystem model. The results show that when the model Kuroshio flows closely to the coast, it hits a small bump in the upstream region of the Hyuganada Sea producing negative potential vorticity. At the same time, trapped near-inertial internal waves in a streak of lowered lowest internal wave frequencies are reproduced near the area with low PV values, generating strong vertical mixing similar to the observations. Since more nitrate is brought upward on the continental shelf when the Kuroshio approaches to the coast, the enhanced vertical mixing effectively diffuses up the nitrate from subsurface to surface layers at a rate of ~O(1 mmol N m -2 day -1) toward 50-100 km downstream along the Kuroshio. Further analyses on how the distance between the model Kuroshio and the southeastern coast of Kyushu affects the nutrient supply, suggest that when the Kuroshio flows closer to the coast, the internal wave kinetic energy, the nitrate concentration, its vertical gradients and vertical diffusive flux increase.
Impact of Microstructure on Solar Radiation Transfer Within Sea Ice During Summer in the Arctic: A Model Sensitivity Study
Authors: Yu Miao , Lu Peng , Cheng Bin , Leppäranta Matti , Li Zhijun
Published: May 2022

The recent rapid changes in Arctic sea ice have occurred not only in ice thickness and extent, but also in the microstructure of ice. To understand the role of microstructure on partitioning of incident solar shortwave radiation within the ice and upper ocean, this study investigated the sensitivity of the optical properties of summer sea ice on ice microstructures such as the volume fraction, size, and vertical distribution of gas bubbles, brine pockets, and particulate matter (PM). The results show that gas bubbles are the predominant scatterers within sea ice. Their effects on the scattering coefficient and ice albedo are 5 and 20 times stronger respectively than the effect of brine pockets. Albedo and transmittance of ice decrease with higher concentration and larger size of PM particles. A 4-cm top layer of ice with high PM concentration (50 g/m3) results in a 10% increase in radiation absorption. The role of ice microstructure in the partitioning of radiation transfer is more important for seasonal than for multiyear ice, and more important for ponded than for snow-covered ice. Varying ice microstructure can obviously alter solar radiation transfer in the ice-ocean system, even with a constant ice thickness. Our results suggest that numerical models should take the variable microstructure of sea ice into account to improve model accuracy and to understand the interaction between internal variations in Arctic sea ice and the ocean, especially in summer.
A New Staging System Based on the Dynamic Prognostic Nomogram for Elderly Patients With Primary Gastrointestinal Diffuse Large B-Cell Lymphoma
Authors: Wang Junmin , Ren Weirui , Zhang Chuang , Wang Xiaoya
Published: May 2022

Objective

The purpose of this study is to establish an accurate prognostic model based on important clinical parameters to predict the overall survival (OS) of elderly patients with primary gastrointestinal diffuse large B-cell lymphoma (EGI DLBCL).

Methods

The Cox regression analysis is based on data from the Surveillance, Epidemiology, and End Results (SEER) database.

Results

A total of 1,783 EGI DLBCL cases were eligible for the study [median (interquartile range, IQR) age, 75 (68–82) years; 974 (54.63%) males], of which 1,248 were randomly assigned to the development cohort, while 535 were into the validation cohort. A more accurate and convenient dynamic prognostic nomogram based on age, stage, radiation, and chemotherapy was developed and validated, of which the predictive performance was superior to that of the Ann Arbor staging system [C-index:0.69 (95% CI:0.67–0.71) vs. 56 (95%CI:0.54–0.58); P < 0.001]. The 3- and 5-year AUC values of ROC curves for 3-year OS and 5-year OS in the development cohort and the validation cohort were were alll above 0.7.

Conclusion

We establish and validate a more accurate and convenient dynamic prognostic nomogram for patients with EGI DLBCL, which can provide evidence for individual treatment and follow-up.
Epidemiological, Clinical, and Trichoscopic Features of Syphilitic Alopecia: A Retrospective Analysis and Systematic Review
Authors: Pomsoong Cherrin , Sukanjanapong Siriorn , Ratanapokasatit Yanisa , Suchonwanit Poonkiat
Published: May 2022

Background

Syphilitic alopecia (SA), which mimics other types of alopecia, is an uncommon manifestation of secondary syphilis. Trichoscopic features may facilitate its diagnosis. However, studies on SA and its trichoscopic characteristics remain limited.

Objective

To investigate the epidemiological, clinical, and trichoscopic findings and laboratory results, treatment, and outcomes of SA in Thai patients as well as to comprehensively summarize all trichoscopic features of SA through a systematic review.

Methods

Data on patients diagnosed with SA between December 2010 and December 2021 were obtained from their medical records and analyzed retrospectively. A systematic review of trichoscopic data, both from our institution and from studies registered in the PubMed, MEDLINE, and Embase databases, was conducted. A descriptive summarization was performed to comprehensively study the trichoscopic features of SA.

Results

Of the 205 patients with secondary syphilis, 23 patients with SA (symptomatic SA: 20, essential SA: 3) were included. The mean age was 27.6 ± 8.8 years, and male predominance was noted. The moth-eaten pattern was the most common SA presentation, and the parieto-occipital scalp was the most commonly affected area. All patients with SA achieved significant hair regrowth within 3 months of antibiotic therapy. Trichoscopic images were available for 20 patients with SA from our institute and were included in the systematic review. Fourteen articles provided information on 21 patients. Overall (N = 41), 26 (63.4%), 8 (19.5%), and 7 (17.1%) patients had moth-eaten alopecia, diffuse alopecia, and mixed alopecia, respectively. The most frequent trichoscopic finding was short regrowing hairs (78%), followed by decreased hair per follicular unit (75.6%), and empty follicles (51.2%). Unique features included flame hairs, bent tapering hairs, reddish-brown background, and brown rings around the perifollicular areas, each described in one case. However, the results were based only on case reports and small case series.

Conclusions

Given the progressively increasing frequency of SA, trichoscopic examination may be valuable when SA is suspected in patients with idiopathic alopecia; however, our findings are quite non-specific. The absence of exclamation mark hairs may help in the diagnosis of SA. Further comparative studies on other types of alopecia are required to determine the most useful diagnostic features.
Porous Scaffold-Hydrogel Composites Spatially Regulate 3D Cellular Mechanosensing
Authors: DiCerbo Matthew , Benmassaoud Mohammed Mehdi , Vega Sebastián L.
Published: May 2022

Cells encapsulated in 3D hydrogels exhibit differences in cellular mechanosensing based on their ability to remodel their surrounding hydrogel environment. Although cells in tissue interfaces feature a range of mechanosensitive states, it is challenging to recreate this in 3D biomaterials. Human mesenchymal stem cells (MSCs) encapsulated in methacrylated gelatin (GelMe) hydrogels remodel their local hydrogel environment in a time-dependent manner, with a significant increase in cell volume and nuclear Yes-associated protein (YAP) localization between 3 and 5 days in culture. A finite element analysis model of compression showed spatial differences in hydrogel stress of compressed GelMe hydrogels, and MSC-laden GelMe hydrogels were compressed (0–50%) for 3 days to evaluate the role of spatial differences in hydrogel stress on 3D cellular mechanosensing. MSCs in the edge (high stress) were significantly larger, less round, and had increased nuclear YAP in comparison to MSCs in the center (low stress) of 25% compressed GelMe hydrogels. At 50% compression, GelMe hydrogels were under high stress throughout, and this resulted in a consistent increase in MSC volume and nuclear YAP across the entire hydrogel. To recreate heterogeneous mechanical signals present in tissue interfaces, porous polycaprolactone (PCL) scaffolds were perfused with an MSC-laden GelMe hydrogel solution. MSCs in different pore diameter (~280–430 μm) constructs showed an increased range in morphology and nuclear YAP with increasing pore size. Hydrogel stress influences MSC mechanosensing, and porous scaffold-hydrogel composites that expose MSCs to diverse mechanical signals are a unique biomaterial for studying and designing tissue interfaces.
Herbivory Protection via Volatile Organic Compounds Is Influenced by Maize Genotype, Not Bacillus altitudinis-Enriched Bacterial Communities
Authors: Raglin Sierra S. , Kent Angela D. , Ngumbi Esther N.
Published: May 2022

Belowground, plants interact with beneficial soil microbes such as plant growth-promoting rhizobacteria (PGPR). PGPR are rhizosphere bacteria that colonize roots and elicit beneficial effects in plants such as improved plant growth, pathogen resistance, abiotic stress tolerance, and herbivore protection. Treatment of plants with PGPR has been shown to trigger the emission of volatile organic compounds (VOCs). Volatile emissions can also be triggered by herbivory, termed herbivore-induced plant volatiles (HIPV), with important ramifications for chemical-mediated plant and insect interactions. Much of our current understanding of PGPR and herbivore-induced volatiles is based on studies using one plant genotype, yet domestication and modern breeding has led to the development of diverse germplasm with altered phenotypes and chemistry. In this study, we investigated if volatile emissions triggered by PGPR colonization and herbivory varies by maize genotype and microbial community assemblages. Six maize genotypes representing three decades of crop breeding and two heterotic groups were used, with four microbiome treatments: live or sterilized soil, with or without a Bacillus inoculant. Soil sterilization was used to delay microbiome establishment, resulting in low-diversity treatments. At planting, maize seeds were inoculated with PGPR Bacillus altitudinis AP-283 and grown under greenhouse conditions. Four weeks post planting, plants were subjected to feeding by third instar Helicoverpa zea (Lepidoptera: Noctuidae) larvae. Volatiles were collected using solid phase microextraction and analyzed with gas chromatography-mass spectrometry. Illumina NovaSeq 16S rRNA amplicon sequencing was carried out to characterize the rhizosphere microbiome. Maize genotype significantly influenced total volatile emissions, and relative abundance of volatile classes. We did not document a strong influence of microbe treatment on plant VOC emissions. However, inoculating plants with PGPR improved plant growth under sterile conditions. Taken together, our results suggest that genotypic variation is the dominant driver in HIPV composition and individual HIPV abundances, and any bacterial-mediated benefit is genotype and HIPV-specific. Therefore, understanding the interplay of these factors is necessary to fully harness microbially-mediated benefits and improve agricultural sustainability.
Free Energy Profiles Relating With Conformational Transition of the Switch Domains Induced by G12 Mutations in GTP-Bound KRAS
Authors: Chen Jianzhong , Zhang Shaolong , Zeng Qingkai , Wang Wei , Zhang Qinggang , Liu Xinguo
Published: May 2022

Mutations of G12 in KRAS have been involved in different cancers. Multiple replica-Gaussian accelerated molecular dynamics (MR-GaMD) simulations are applied to investigate conformational changes of the switch domains caused by G12C, G12D and G12R. Free energy landscapes suggest that G12C, G12D and G12R induce more energetic states compared to the GTP-bound WT KRAS and make the conformations of the switch domains more disordered, which disturbs bindings of KRAS to effectors. Dynamics analyses based on MR-GaMD trajectory show that G12C, G12D and G12R not only change structural flexibility of the switch domains but also affect their motion behavior, indicating that these three mutations can be used to tune the activity of KRAS. The analyses of interaction networks verify that the instability in interactions of the GTP with the switch SⅠ plays an important role in the high disorder states of the switch domain. This work is expected to provide useful information for deeply understanding the function of KRAS.
Age-Dependent Alterations of Cognition, Mitochondrial Function, and Beta-Amyloid Deposition in a Murine Model of Alzheimer’s Disease—A Longitudinal Study
Authors: Reutzel Martina , Grewal Rekha , Joppe Aljoscha , Eckert Gunter P.
Published: May 2022

Aging is the main risk factor for sporadic Alzheimer’s disease (AD), which is characterized by the cerebral deposition of β-amyloid peptides (Aβ) and cognitive decline. Mitochondrial dysfunction is also characteristic of the disease and represents a hallmark of both, aging and neurodegeneration. We longitudinally followed Aβ levels, cognition, and mitochondrial function in the same cohort of Thy1-APP751SL mice representing a murine model of AD. In the course of time, changes were most prominent at an age of 13 months including the latency time in the passive avoidance test, the activity of complexes I and IV of the mitochondrial respiration chain, and expression of genes related to mitochondrial biogenesis and synaptic plasticity including Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1-α), CAMP responsive element binding protein 1 (CREB1), and Synaptophysin 1 (SYP1). These changes occurred in parallel with massively increasing cerebral Aβ levels. Other parameters were changed in younger mice including the alteration rate in the Y-maze test and the nesting score when Aβ levels were not changed yet. The results are consistent in the cohort described. However, previous, non-longitudinal studies reported divergent time points for the occurrence of the parameters studied. These findings are discussed in light of the current results.
Deep Reinforcement Learning Based Trajectory Planning Under Uncertain Constraints
Authors: Chen Lienhung , Jiang Zhongliang , Cheng Long , Knoll Alois C. , Zhou Mingchuan
Published: May 2022

With the advance in algorithms, deep reinforcement learning (DRL) offers solutions to trajectory planning under uncertain environments. Different from traditional trajectory planning which requires lots of effort to tackle complicated high-dimensional problems, the recently proposed DRL enables the robot manipulator to autonomously learn and discover optimal trajectory planning by interacting with the environment. In this article, we present state-of-the-art DRL-based collision-avoidance trajectory planning for uncertain environments such as a safe human coexistent environment. Since the robot manipulator operates in high dimensional continuous state-action spaces, model-free, policy gradient-based soft actor-critic (SAC), and deep deterministic policy gradient (DDPG) framework are adapted to our scenario for comparison. In order to assess our proposal, we simulate a 7-DOF Panda (Franka Emika) robot manipulator in the PyBullet physics engine and then evaluate its trajectory planning with reward, loss, safe rate, and accuracy. Finally, our final report shows the effectiveness of state-of-the-art DRL algorithms for trajectory planning under uncertain environments with zero collision after 5,000 episodes of training.
Cisplatin Neurotoxicity Targets Specific Subpopulations and K+ Channels in Tyrosine-Hydroxylase Positive Dorsal Root Ganglia Neurons
Authors: Finno Carrie J. , Chen Yingying , Park Seojin , Lee Jeong Han , Perez-Flores Maria Cristina , Choi Jinsil , Yamoah Ebenezer N.
Published: May 2022

Among the features of cisplatin chemotherapy-induced peripheral neuropathy are chronic pain and innocuous mechanical hypersensitivity. The complete etiology of the latter remains unknown. Here, we show that cisplatin targets a heterogeneous population of tyrosine hydroxylase-positive (TH+) primary afferent dorsal root ganglion neurons (DRGNs) in mice, determined using single-cell transcriptome and electrophysiological analyses. TH+ DRGNs regulate innocuous mechanical sensation through C-low threshold mechanoreceptors. A differential assessment of wild-type and vitamin E deficient TH+ DRGNs revealed heterogeneity and specific functional phenotypes. The TH+ DRGNs comprise; fast-adapting eliciting one action potential (AP; 1-AP), moderately-adapting (≥2-APs), in responses to square-pulse current injection, and spontaneously active (SA). Cisplatin increased the input resistance and AP frequency but reduced the temporal coding feature of 1-AP and ≥2-APs neurons. By contrast, cisplatin has no measurable effect on the SA neurons. Vitamin E reduced the cisplatin-mediated increased excitability but did not improve the TH+ neuron temporal coding properties. Cisplatin mediates its effect by targeting outward K+ current, likely carried through K2P18.1 (Kcnk18), discovered through the differential transcriptome studies and heterologous expression. Studies show a potential new cellular target for chemotherapy-induced peripheral neuropathy and implicate the possible neuroprotective effects of vitamin E in cisplatin chemotherapy.
Influence of T-Bar on Calcium Concentration Impacting Release Probability
Authors: Knodel Markus M. , Dutta Roy Ranjita , Wittum Gabriel
Published: May 2022

The relation of form and function, namely the impact of the synaptic anatomy on calcium dynamics in the presynaptic bouton, is a major challenge of present (computational) neuroscience at a cellular level. The Drosophila larval neuromuscular junction (NMJ) is a simple model system, which allows studying basic effects in a rather simple way. This synapse harbors several special structures. In particular, in opposite to standard vertebrate synapses, the presynaptic boutons are rather large, and they have several presynaptic zones. In these zones, different types of anatomical structures are present. Some of the zones bear a so-called T-bar, a particular anatomical structure. The geometric form of the T-bar resembles the shape of the letter “T” or a table with one leg. When an action potential arises, calcium influx is triggered. The probability of vesicle docking and neurotransmitter release is superlinearly proportional to the concentration of calcium close to the vesicular release site. It is tempting to assume that the T-bar causes some sort of calcium accumulation and hence triggers a higher release probability and thus enhances neurotransmitter exocytosis. In order to study this influence in a quantitative manner, we constructed a typical T-bar geometry and compared the calcium concentration close to the active zones (AZs). We compared the case of synapses with and without T-bars. Indeed, we found a substantial influence of the T-bar structure on the presynaptic calcium concentrations close to the AZs, indicating that this anatomical structure increases vesicle release probability. Therefore, our study reveals how the T-bar zone implies a strong relation between form and function. Our study answers the question of experimental studies (namely “Wichmann and Sigrist, Journal of neurogenetics 2010”) concerning the sense of the anatomical structure of the T-bar.