bluuebunny/crossref_metadata_2025 huggingface dataset:
Strong Expansion of Human Regulatory T Cells for Adoptive Cell Therapy Results in Epigenetic Changes Which May Impact Their Survival and Function
Authors: Ou Kristy , Hamo Dania , Schulze Anne , Roemhild Andy , Kaiser Daniel , Gasparoni Gilles , Salhab Abdulrahman , Zarrinrad Ghazaleh , Amini Leila , Schlickeiser Stephan , Streitz Mathias , Walter Jörn , Volk Hans-Dieter , Schmueck-Henneresse Michael , Reinke Petra , Polansky Julia K.
Published: November 2021

Adoptive transfer of regulatory T cells (Treg) is a promising new therapeutic option to treat detrimental inflammatory conditions after transplantation and during autoimmune disease. To reach sufficient cell yield for treatment,ex vivoisolated autologous or allogenic Tregs need to be expanded extensivelyin vitroduring manufacturing of the Treg product. However, repetitive cycles of restimulation and prolonged culture have been shown to impact T cell phenotypes, functionality and fitness. It is therefore critical to scrutinize the molecular changes which occur during T cell product generation, and reexamine current manufacturing practices. We performed genome-wide DNA methylation profiling of cells throughout the manufacturing process of a polyclonal Treg product that has proven safety and hints of therapeutic efficacy in kidney transplant patients. We found progressive DNA methylation changes over the duration of culture, which were donor-independent and reproducible between manufacturing runs. Differentially methylated regions (DMRs) in the final products were significantly enriched at promoters and enhancers of genes implicated in T cell activation. Additionally, significant hypomethylation did also occur in promoters of genes implicated in functional exhaustion in conventional T cells, some of which, however, have been reported to strengthen immunosuppressive effector function in Tregs. At the same time, a set of reported Treg-specific demethylated regions increased methylation levels with culture, indicating a possible destabilization of Treg identity during manufacturing, which was independent of the purity of the starting material. Together, our results indicate that the repetitive TCR-mediated stimulation lead to epigenetic changes that might impact functionality of Treg products in multiple ways, by possibly shifting to an effector Treg phenotype with enhanced functional activity or by risking destabilization of Treg identity and impaired TCR activation. Our analyses also illustrate the value of epigenetic profiling for the evaluation of T cell product manufacturing pipelines, which might open new avenues for the improvement of current adoptive Treg therapies with relevance for conventional effector T cell products.
The Beta-Tubulin Isotype TUBB6 Controls Microtubule and Actin Dynamics in Osteoclasts
Authors: Maurin Justine , Morel Anne , Guérit David , Cau Julien , Urbach Serge , Blangy Anne , Bompard Guillaume
Published: November 2021

Osteoclasts are bone resorbing cells that participate in the maintenance of bone health. Pathological increase in osteoclast activity causes bone loss, eventually resulting in osteoporosis. Actin cytoskeleton of osteoclasts organizes into a belt of podosomes, which sustains the bone resorption apparatus and is maintained by microtubules. Better understanding of the molecular mechanisms regulating osteoclast cytoskeleton is key to understand the mechanisms of bone resorption, in particular to propose new strategies against osteoporosis. We reported recently that β-tubulin isotype TUBB6 is key for cytoskeleton organization in osteoclasts and for bone resorption. Here, using an osteoclast model CRISPR/Cas9 KO for Tubb6, we show that TUBB6 controls both microtubule and actin dynamics in osteoclasts. Osteoclasts KO for Tubb6 have reduced microtubule growth speed with longer growth life time, higher levels of acetylation, and smaller EB1-caps. On the other hand, lack of TUBB6 increases podosome life time while the belt of podosomes is destabilized. Finally, we performed proteomic analyses of osteoclast microtubule-associated protein enriched fractions. This highlighted ARHGAP10 as a new microtubule-associated protein, which binding to microtubules appears to be negatively regulated by TUBB6. ARHGAP10 is a negative regulator of CDC42 activity, which participates in actin organization in osteoclasts. Our results suggest that TUBB6 plays a key role in the control of microtubule and actin cytoskeleton dynamics in osteoclasts. Moreover, by controlling ARHGAP10 association with microtubules, TUBB6 may participate in the local control of CDC42 activity to ensure efficient bone resorption.
Altered Fecal Microbiota Correlated With Systemic Inflammation in Male Subjects With Methamphetamine Use Disorder
Authors: Deng Di , Su Hang , Song Yuehong , Chen Tianzhen , Sun Qianqian , Jiang Haifeng , Zhao Min
Published: November 2021

Methamphetamine use disorder (MUD) is a major public health problem worldwide with limited effective treatment options. Previous studies have reported methamphetamine-associated alterations in gut microbiota. A potential role of gut microbiota in regulating methamphetamine-induced brain dysfunction through interactions with the host immune system has been proposed, but evidence for this hypothesis is limited. The present study aimed to investigate the alterations in the fecal microbiota and explore its relationship with systemic inflammation in MUD. Fecal samples were obtained from 26 male subjects with MUD and 17 sex- and age- matched healthy controls. Fecal microbial profiles were analyzed by 16S rRNA sequencing. Plasma inflammatory markers were measured using enzyme-linked immunosorbent assay. Associations between fecal microbiota, systemic inflammatory markers and clinical characteristics were examined by Spearman partial correlation analysis while controlling for possible confounders. Compared with healthy controls, individuals with MUD showed no difference in fecal microbial diversity, but exhibited differences in the relative abundance of several microbial taxa. At the genus level, a higher abundance of Collinsella, Odoribacter and Megasphaera and lower levels of Faecalibacterium, Blautia, Dorea and Streptococcus were detected in subjects with MUD. More importantly, altered fecal microbiota was found to be correlated with plasma levels of CRP, IL-2, IL-6 and IL-10. The order Lactobacillales, exhibiting lower abundance in participants with MUD, was positively related to the duration of methamphetamine abstinence and the plasma level of anti-inflammatory cytokine IL-10. This study is the first to provide evidence for a link between altered fecal microbiota and systemic inflammation in MUD. Further elucidation of interactions between gut microbiota and the host immune system may be beneficial for the development of novel therapeutic approaches for MUD.
Systems Approaches to Combating Wildlife Trafficking: Expanding Existing Frameworks to Facilitate Cross-Disciplinary Collaboration
Authors: Browne Christine , Ronis Emily M. , Miller Jennifer R. B. , Kapetanakos Yula , Gibbs Samantha , Hendrix Tatiana , Carlson Bremer Daphne
Published: November 2021

Wildlife trafficking is a complex conservation issue that threatens thousands of species around the world and, in turn, negatively affects biodiversity and human well-being. It occurs in varied social-ecological contexts; includes numerous and diverse actors along the source-transit-destination trade chain, who are involved in illicit and often covert human behaviors driven by interacting social, economic, cultural, and political factors; and involves numerous stakeholders comprising multiple sectors and disciplines. Such wicked problems can be difficult to define and usually lack simple, clear solutions. Systems thinking is a way to understand and address complex issues such as wildlife trafficking and requires multisectoral, cross-disciplinary collaboration to comprehensively understand today's increasingly complex problems and develop holistic and novel solutions. We review methods utilized to date to combat wildlife trafficking and discuss their strengths and limitations. Next, we describe the continuum of cross-disciplinarity and present two frameworks for understanding complex environmental issues, including the illegal trade in wildlife, that can facilitate collaboration across sectors and disciplines. The Open Standards for the Practice of Conservation provides guidance and tools for defining complex social-ecological systems and identifying strategic points of intervention. One Health focuses on the nexus of human, wildlife, and environmental health, and can provide a framework to address concerns around human-wildlife interactions, including those associated with the illegal wildlife trade. Finally, we provide recommendations for expanding these and similar frameworks to better support communication, learning, and collaboration in cross-disciplinary efforts aimed at addressing international wildlife trafficking and its intersections with other complex, global conservation issues.
The Association Between Time-Varying Wall Shear Stress and the Development of Plaque Ulcerations in Carotid Arteries From the Plaque at Risk Study
Authors: Dilba Kristine , van Dam-Nolen Dianne H. K. , Korteland Suze-Anne , van der Kolk Anja G. , Kassem Mohamed , Bos Daniel , Koudstaal Peter J. , Nederkoorn Paul J. , Hendrikse Jeroen , Kooi M. Eline , Gijsen Frank J. H. , van der Steen Anton F. W. , van der Lugt Aad , Wentzel Jolanda J.
Published: November 2021

Background and Purpose: Shear stress (WSS) is involved in the pathophysiology of atherosclerotic disease and might affect plaque ulceration. In this case-control study, we compared carotid plaques that developed a new ulcer during follow-up and plaques that remained silent for their exposure to time-dependent oscillatory shear stress parameters at baseline.

Materials and Methods: Eighteen patients who underwent CTA and MRI of their carotid arteries at baseline and 2 years follow-up were included. These 18 patients consisted of six patients who demonstrated a new ulcer and 12 control patients selected from a larger cohort with similar MRI-based plaque characteristics as the ulcer group. (Oscillatory) WSS parameters [time average WSS, oscillatory shear index (OSI), and relative residence time (RRT)] were calculated using computational fluid dynamics applying the MRI-based geometry of the carotid arteries and compared among plaques (wall thickness>2 mm) with and without ulceration (Mann–Whitney U test) and ulcer-site vs. non-ulcer-site within the plaque (Wilcoxon signed rank test). More detailed analysis on ulcer cases was performed and the predictive value of oscillatory WSS parameters was calculated using linear and logistic mixed-effect regression models.

Results: The ulcer group demonstrated no difference in maximum WSS [9.9 (6.6–18.5) vs. 13.6 (9.7–17.7) Pa, p = 0.349], a lower maximum OSI [0.04 (0.01–0.10) vs. 0.12 (0.06–0.20) p = 0.019] and lower maximum RRT [1.25 (0.78–2.03) Pa−1 vs. 2.93 (2.03–5.28) Pa−1, p = 0.011] compared to controls. The location of the ulcer (ulcer-site) within the plaque was not always at the maximal WSS, but demonstrated higher average WSS, lower average RRT and OSI at the ulcer-site compared to the non-ulcer-sites. High WSS (WSS>4.3 Pa) and low RRT (RRT < 0.25 Pa) were associated with ulceration with an odds ratio of 3.6 [CI 2.1–6.3] and 2.6 [CI 1.54–4.44] respectively, which remained significant after adjustment for wall thickness.

Conclusion: In this explorative study, ulcers were not exclusively located at plaque regions exposed to the highest WSS, OSI, or RRT, but high WSS and low RRT regions had a significantly higher odds to present ulceration within the plaque even after adjustment for wall thickness.
Pre-operative Cerebral Small Vessel Disease on MR Imaging Is Associated With Cerebral Hyperperfusion After Carotid Endarterectomy
Authors: Fan Xiaoyuan , Lai Zhichao , Lin Tianye , You Hui , Wei Juan , Li Mingli , Liu Changwei , Feng Feng
Published: November 2021

Objectives: To determine whether pre-operative cerebral small vessel disease is associated with cerebral hyperperfusion (CH) after carotid endarterectomy (CEA).

Methods: Seventy-seven patients (mean age of 66 years and 58% male) undergoing CEA for carotid stenosis were investigated using brain MRI before and after surgery. CH was defined as an increase in cerebral blood flow > 100% compared with pre-operative values on arterial spin labeling MR images. The grade or the number of four cerebral small vessel disease markers (white matter hyperintensities, lacunes, perivascular spaces, and cerebral microbleeds) were evaluated based on pre-operative MRI. Cerebral small vessel disease markers were correlated with CH by using multivariate logistic regression analysis. The cutoff values of cerebral small vessel disease markers for predicting CH were assessed by receiver-operating characteristic curve analysis.

Results: CH after CEA was observed in 16 patients (20.78%). Logistic regression analysis revealed that white matter hyperintensities (OR 3.09, 95% CI 1.72–5.54; p < 0.001) and lacunes (OR 1.37, 95% CI 1.06–1.76; p = 0.014) were independently associated with post-operative CH. Receiver-operating characteristic curve analysis showed that Fazekas score of white matter hyperintensities ≥3 points [area under the curve (AUC) = 0.84, sensitivity = 81.3%, specificity = 73.8%, positive predictive value (PPV) = 44.8% and negative predictive value (NPV) = 93.8%] and number of lacunes ≥ 2 (AUC = 0.73, sensitivity = 68.8%, specificity = 78.7%, PPV = 45.8% and NPV = 90.6%) were the optimal cutoff values for predicting CH.

Conclusion: In patients with carotid stenosis, white matter hyperintensities and lacunes adversely affect CH after CEA. Based on the NPVs, pre-operative MR imaging can help identify patients who are not at risk of CH.
The Predictive Value of Myoglobin for COVID-19-Related Adverse Outcomes: A Systematic Review and Meta-Analysis
Authors: Ma Chaoqun , Tu Dingyuan , Gu Jiawei , Xu Qiang , Hou Pan , Wu Hong , Guo Zhifu , Bai Yuan , Zhao Xianxian , Li Pan
Published: November 2021

Objective: Cardiac injury is detected in numerous patients with coronavirus disease 2019 (COVID-19) and has been demonstrated to be closely related to poor outcomes. However, an optimal cardiac biomarker for predicting COVID-19 prognosis has not been identified.

Methods: The PubMed, Web of Science, and Embase databases were searched for published articles between December 1, 2019 and September 8, 2021. Eligible studies that examined the anomalies of different cardiac biomarkers in patients with COVID-19 were included. The prevalence and odds ratios (ORs) were extracted. Summary estimates and the corresponding 95% confidence intervals (95% CIs) were obtained through meta-analyses.

Results: A total of 63 studies, with 64,319 patients with COVID-19, were enrolled in this meta-analysis. The prevalence of elevated cardiac troponin I (cTnI) and myoglobin (Mb) in the general population with COVID-19 was 22.9 (19–27%) and 13.5% (10.6–16.4%), respectively. However, the presence of elevated Mb was more common than elevated cTnI in patients with severe COVID-19 [37.7 (23.3–52.1%) vs.30.7% (24.7–37.1%)]. Moreover, compared with cTnI, the elevation of Mb also demonstrated tendency of higher correlation with case-severity rate (Mb, r = 13.9 vs. cTnI, r = 3.93) and case-fatality rate (Mb, r = 15.42 vs. cTnI, r = 3.04). Notably, elevated Mb level was also associated with higher odds of severe illness [Mb, OR = 13.75 (10.2–18.54) vs. cTnI, OR = 7.06 (3.94–12.65)] and mortality [Mb, OR = 13.49 (9.3–19.58) vs. cTnI, OR = 7.75 (4.4–13.66)] than cTnI.

Conclusions: Patients with COVID-19 and elevated Mb levels are at significantly higher risk of severe disease and mortality. Elevation of Mb may serve as a marker for predicting COVID-19-related adverse outcomes.

Prospero Registration Number:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020175133, CRD42020175133.
Cryoballoon Ablation Strategy in Persistent Atrial Fibrillation
Authors: Straube Florian , Pongratz Janis , Kosmalla Alexander , Brueck Benedikt , Riess Lukas , Hartl Stefan , Tesche Christian , Ebersberger Ullrich , Wankerl Michael , Dorwarth Uwe , Hoffmann Ellen
Published: November 2021

Background: Cryoballoon ablation is established for pulmonary vein isolation (PVI) in paroxysmal atrial fibrillation (AF). The objective was to evaluate CBA strategy in consecutive patients with persistent AF in the initial AF ablation procedure.

Material and Methods: Prospectively, patients with symptomatic persistent AF scheduled for AF ablation all underwent cryoballoon PVI. Technical enhancements, laboratory management, safety, single-procedure outcome, predictors of recurrence, and durability of PVI were evaluated.

Results: From 2007 to 2020, a total of 1,140 patients with persistent AF, median age 68 years, underwent cryoballoon ablation (CBA). Median left atrial (LA) diameter was 45 mm (interquantile range, IQR, 8), and Congestive heart failure, Hypertension, Age ≥75 years (doubled), Diabetes mellitus, prior Stroke or TIA or thromboembolism (doubled), Vascular disease, Age 65 to 74 years, Sex category (CHA2DS2-VASc) score was 3. Acute isolation was achieved in 99.6% of the pulmonary veins by CBA. Median LA time and median dose area product decreased significantly over time (p < 0.001). Major complications occurred in 17 (1.5%) patients including 2 (0.2%) stroke/transitory ischemic attack (TIA), 1 (0.1%) tamponade, relevant groin complications, 1 (0.1%) significant ASD, and 4 (0.4%) persistent phrenic nerve palsy (PNP). Transient PNP occurred in 66 (5.5%) patients. No atrio-esophageal fistula was documented. Five deaths (0.4%), unrelated to the procedure, occurred very late during follow-up. After initial CBA, arrhythmia recurrences occurred in 46.6% of the patients. Freedom from atrial arrhythmias at 1-, and 2-year was 81.8 and 61.7%, respectively. Independent predictors of recurrence were LA diameter, female sex, and use of the first cryoballoon generation. Repeat ablations due to recurrences were performed in 268 (23.5%) of the 1,140 patients. No pulmonary vein (PV) reconduction was found in 49.6% of the patients and 73.5% of PVs. This rate increased to 66.4% of the patients and 88% of PVs if an advanced cryoballoon was used in the first AF ablation procedure.

Conclusion: Cryoballoon ablation for symptomatic persistent AF is a reasonable strategy in the initial AF ablation procedure.
Integrated Care of Atrial Fibrillation Using the ABC (Atrial fibrillation Better Care) Pathway Improves Clinical Outcomes in Chinese Population: An Analysis From the Chinese Atrial Fibrillation Registry
Authors: Wang Yu-Feng , Jiang Chao , He Liu , Du Xin , Sang Cai-Hua , Long De-Yong , Tang Ri-Bo , Dong Jian-Zeng , Lip Gregory Y. H. , Ma Chang-Sheng
Published: November 2021

Background: “Atrial fibrillation Better Care” (ABC) pathway has been proposed to improve the management of patients suffered from atrial fibrillation (AF). This integrated or holistic management approach comprise of three aspects, including “A” Avoid stroke or Anticoagulation; “B” Better symptom control with rate or rhythm control strategies; “C” Cardiovascular risk factor and Concomitant diseases management. We aimed to confirm the beneficial evidence of ABC pathway compliance in a Chinese AF cohort.

Method and Results: From the Chinese Atrial Fibrillation registry (CAFR) dataset, a total of 19,187 non-valvular AF patients were enrolled, of which 4.365 (22.8%) were ABC pathway compliant (ABC compliance group). During a median follow-up of 4.1 ± 1.8 years, The incident rate of all-cause death in ABC compliance group and non-ABC compliance group is 2.7 and 1.1 per 100 person-year (p < 0.001), the incident rate of ischemic stroke is 1.3 and 0.8% per 100 person-year (p < 0.001), the incident rate of composite outcome, which consist of all-cause death, ischemic stroke and intracranial hemorrhage, is 3.8 and 1.9 per 100 person-year (p < 0.001). On Cox multivariable analysis, ABC pathway shows an independently association with reduction of all-cause death [hazard ratio (HR) = 0.82; 95% confidence interval (CI) = 0.70–0.95] and the composite outcome (HR 0.86, 95% CI 0.76–0.96). The increasingly components of ABC integrated care compliance is associated with lower risk of all-cause death and composite events.

Conclusion: In a large cohort of Chinese AF patients, ABC pathway compliance shows an independently association with reduction of all-cause death and composite outcome of all-cause death, ischemic stroke and intracranial hemorrhage. Better compliance of ABC integrated care contributes to lower HR for adverse events.
Case Report: Simultaneous Ascending Aortic Dissection and Pulmonary Artery Dissection Combined by Aortopulmonary Fistula After Aortic Valve Replacement
Authors: Song Lihui , Xiong Sizheng , Li Jun
Published: November 2021

Aortopulmonary fistula with/without pulmonary artery dissection is an extremely rare and fatal complication of acute aortic dissection and is often discovered postmortem. We present a case with a simultaneous ascending aortic dissection and pulmonary artery dissection combined by aortopulmonary fistula after aortic valve surgery. However, the patient died of postoperative complications after surgery. Herein, the anatomical basis for this rare entity and its outcome is explored with an emphasis.
Association Between Menstrual Patterns and Adverse Pregnancy Outcomes in Patients With Polycystic Ovary Syndrome
Authors: Yu Ting , Wu Di , Cao Yurong , Zhai Jun
Published: November 2021

Objective

To investigate the results of in vitro fertilization among polycystic ovary syndrome (PCOS) patients using the long-acting long protocol regarding the relationship between menstrual patterns and adverse pregnancy outcomes.

Design

Retrospective cohort study.

Setting

University-affiliated reproductive medical center.

Background

The menstrual patterns of patients with PCOS is considered related to metabolism; however, no study has analyzed the outcome of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) in patients with PCOS who have different menstrual patterns. This study aimed to observe the outcomes of IVF/ICSI in patients with PCOS with different menstrual patterns who used the long-acting long protocol.

Methods

This was a retrospective analysis in the first cycle of IVF/ICSI at the Reproductive Medicine Center of the First Affiliated Hospital of Zhengzhou University from January 2017 to December 2019. In total, 1834 patients with PCOS were classified into the regular menstruation group (n=214), the oligomenorrhea group (n=1402), and the amenorrhea group (n=218).

Results

PCOS patients who used the long-acting long protocol of IVF/ICSI had similar clinical pregnancy rates and live birth rates despite having different menstrual patterns. The overall incidence of adverse pregnancy outcomes, including abortion, spontaneous preterm birth (sPTB), gestational diabetes(GDM), hypertensive disorder inpregnancy (HDP), and premature rupture of membranes(PROM, was significantly higher in the amenorrhea group than in the regular menstrual and oligomenorrhea groups (25.88% vs. 30.41% vs. 43.69%; P = 0.013). Additionally, the rates of GDM (2.35% vs. 6.10% vs. 13.79%; P=0.015) and macrosomia (5.26% vs. 10.94% vs. 18.39%; P=0.026) in the amenorrhea group were significantly higher than those in the other two groups. Correction for confounding factors showed that menstrual patterns are related to the occurrence of adverse pregnancy outcomes. Amenorrhea is an independent risk factor for adverse pregnancy outcome (OR [odds ratio]: 2.039, 95% CI [confidence interval]: 1.087-3.822), GDM (OR: 5.023, 95% CI: 1.083–23.289), and macrosomia (OR: 4.918, 95% CI: 1.516–15.954).

Conclusions

IVF/ICSI can achieve similar pregnancy and live birth rates in PCOS patients with different menstrual patterns. However, the overall incidence of adverse pregnancy outcomes in PCOS patients with amenorrhea is higher than that in patients with regular menstruation or oligomenorrhea.
Postoperative GH and Degree of Reduction in IGF-1 Predicts Postoperative Hormonal Remission in Acromegaly
Authors: Cardinal Tyler , Collet Casey , Wedemeyer Michelle , Singer Peter A. , Weiss Martin , Zada Gabriel , Carmichael John D.
Published: November 2021

Purpose

Determine predictive factors for long-term remission of acromegaly after transsphenoidal resection of growth hormone (GH)-secreting pituitary adenomas.

Methods

We identified 94 patients who had undergone transsphenoidal resection of GH-secreting pituitary adenomas for treatment of acromegaly at the USC Pituitary Center from 1999-2019 to determine the predictive value of postoperative endocrine lab values.

Results

Patients underwent direct endoscopic endonasal (60%), microscopic transsphenoidal (38%), and extended endoscopic approaches (2%). The cohort was 63% female and 37% male, with average age of 48.9 years. Patients presented with acral enlargement (72, 77%), macroglossia (40, 43%), excessive sweating (39, 42%), prognathism (38, 40%) and frontal bossing (35, 37%). Seventy-five (80%) were macroadenomas and 19 (20%) were microadenomas. Cavernous sinus invasion was present in 45%. Available immunohistochemical data demonstrated GH staining in 88 (94%) and prolactin in 44 (47%). Available postoperative MRI demonstrated gross total resection in 63% of patients and subtotal resection in 37%. Most patients (66%) exhibited hormonal remission at 12 weeks postoperatively. Receiver operating characteristic (ROC) curves demonstrated postoperative day 1 (POD1) GH levels ≥1.55ng/mL predicted failure to remit from surgical resection alone (59% specificity, 75% sensitivity). A second ROC curve showed decrease in corrected insulin-like growth factor-1 (IGF-1) levels of at least 37% prognosticated biochemical control (90% sensitivity, 80% specificity).

Conclusion

POD1 GH and short-term postoperative IGF-1 levels can be used to successfully predict immediate and long-term hormonal remission respectively. A POD1 GH cutoff can identify patients likely to require adjuvant therapy to emphasize clinical follow-up.
Stochastic Time-Varying Model Predictive Control for Trajectory Tracking of a Wheeled Mobile Robot
Authors: Zheng Weijiang , Zhu Bing
Published: November 2021

In this paper, a stochastic model predictive control (MPC) is proposed for the wheeled mobile robot to track a reference trajectory within a finite task horizon. The wheeled mobile robot is supposed to subject to additive stochastic disturbance with known probability distribution. It is also supposed that the mobile robot is subject to soft probability constraints on states and control inputs. The nonlinear mobile robot model is linearized and discretized into a discrete linear time-varying model, such that the linear time-varying MPC can be applied to forecast and control its future behavior. In the proposed stochastic MPC, the cost function is designed to penalize its tracking error and energy consumption. Based on quantile techniques, a learning-based approach is applied to transform the probability constraints to deterministic constraints, and to calculate the terminal constraint to guarantee recursive feasibility. It is proved that, with the proposed stochastic MPC, the tracking error of the closed-loop system is asymptotically average bounded. A simulation example is provided to support the theoretical result.
Reliability in Distribution Modeling—A Synthesis and Step-by-Step Guidelines for Improved Practice
Authors: Bryn Anders , Bekkby Trine , Rinde Eli , Gundersen Hege , Halvorsen Rune
Published: November 2021

Information about the distribution of a study object (e.g., species or habitat) is essential in face of increasing pressure from land or sea use, and climate change. Distribution models are instrumental for acquiring such information, but also encumbered by uncertainties caused by different sources of error, bias and inaccuracy that need to be dealt with. In this paper we identify the most common sources of uncertainties and link them to different phases in the modeling process. Our aim is to outline the implications of these uncertainties for the reliability of distribution models and to summarize the precautions needed to be taken. We performed a step-by-step assessment of errors, biases and inaccuracies related to the five main steps in a standard distribution modeling process: (1) ecological understanding, assumptions and problem formulation; (2) data collection and preparation; (3) choice of modeling method, model tuning and parameterization; (4) evaluation of models; and, finally, (5) implementation and use. Our synthesis highlights the need to consider the entire distribution modeling process when the reliability and applicability of the models are assessed. A key recommendation is to evaluate the model properly by use of a dataset that is collected independently of the training data. We support initiatives to establish international protocols and open geodatabases for distribution models.
Annual Population Dynamics and Their Influencing Factors for an Endangered Submerged Macrophyte (Ottelia cordata)
Authors: Shen Yichun , Lei Jinrui , Song Xiqiang , Ren Mingxun
Published: November 2021

Due to wetland loss, Ottelia cordata (O. cordata, Wallich) Dandy has been categorized as an endangered species on the List of Key Protected Wild Plants in China. Quantifying the relative importance of demographic (i.e., growth, survival, and reproduction) and habitat preference traits on the population dynamics (abundance) of O. cordata could guide how to develop the best recovery strategies of O. cordata, yet currently, there are no studies that investigate this. By monitoring monthly changes in O. cordata abundance and demographic traits (plant height, leaf area, flower sex ratio, and seed number) that were highly correlated with growth rate, photosynthetic rate, and water depth, we identified several relationships. Linear mixed-effect models and variance partition quantified the specific effects of four demographic traits and water depth on O. cordata abundance in three habitat types (paddyfield, stream, and spring). The linear mixed-effect models indicate that among the four demographic traits, height could be significantly positively correlated to abundance in all three habitat types. In contrast, other three traits (leaf area, sex ratio, and seed numbers) were non-significantly associated with abundance across each habitat. Height was determined by water depth, so water depth rather than photosynthetic rate and reproduction rate may promote the development and recovery of O. cordata populations. Variance partition results showed that water depth mediated the positive influence of growth rate on the abundance of O. cordata in the living habitats (paddyfield and spring). In contrast, water depth but not growth rate determined the abundance of O. cordata in the living habitat (stream). However, water depth had a significantly negative impact on the abundance of O. cordata in stream habitats, likely because all of the streams were shallow. Altogether, in the short term for avoiding the potential harm or even extinction of O. cordata, keeping appropriate water depth or transplanting O. cordata to spring should be an effective strategy because the water is not only deep enough but also clear in spring habitats. Additionally, water turbidity was shown to affect the density of O. cordata growth, wherein O. cordata was sparsely distributed when turbidity was high. Therefore, in the long run, to make the population gradually recovery, it will be necessary to restore the degraded wetland. This could be accomplished by reducing water pollution and removing sludge to reduce turbidity and increase hydrological connectivity.
Behavioral Attributes of Social Groups Determine the Strength and Direction of Selection on Neural Investment
Authors: Caponera Virginia , Avilés Leticia , Barrett Meghan , O’Donnell Sean
Published: November 2021

The evolution of social systems can place novel selective forces on investment in expensive neural tissue by changing cognitive demands. Previous hypotheses about the impact of sociality on neural investment have received equivocal support when tested across diverse taxonomic groups and social structures. We suggest previous models for social behavior-brain relationships have overlooked important variation in social groups. Social groups vary significantly in structure and function, and the specific attributes of a social group may be more relevant to setting cognitive demands than sociality in general. We have identified intragroup competition, relationship differentiation, information sharing, dominance hierarchies, and task specialization and redundancy as attributes of social behavior which may impact selection for neural investment, and outline how variation in these attributes can result in increased or decreased neural investment with transitions to sociality in different taxa. Finally, we test some of the predictions generated using this framework in a phylogenetic comparison of neural tissue investment in Anelosimus social spiders. Social Anelosimus spiders engage in cooperative prey capture and brood care, which allows for individual redundancy in the completion of these tasks. We hypothesized that in social spider species, the presence of redundancy would reduce selection for individual neural investment relative to subsocial species. We found that social species had significantly decreased investment in the arcuate body, the cognitive center of the spider brain, supporting our predictions. Future comparative tests of brain evolution in social species should account for the special behavioral characteristics that accompany social groups in the subject taxa.
Influence of Olfaction in Host-Selection Behavior of the Cassava Whitefly Bemisia tabaci
Authors: Mrisho Latifa M. , Maeda Daniel G. , Ortiz Zaide M. , Ghanavi Hamid R. , Legg James P. , Stensmyr Marcus C.
Published: November 2021

Cassava is a vital food-security crop in Sub-Saharan Africa. Cassava crops are, however, severely affected by viral diseases transmitted by members of the whitefly species complexBemisia tabaci. We have here investigated the role of olfaction in host selection behavior of the cassava whiteflyB. tabaciSSA-ESA biotype. Surprisingly, we find that the whiteflies appear to make little use of olfaction to find their favored host. The cassava whitely shows a highly reduced olfactory system, both at the morphological and molecular level. Whitefly antennae possess only 15 sensilla with possible olfactory function, and from the genome we identified just a handful of candidate chemoreceptors, including nine tuning odorant receptors, which would afford the whitefly with one of the smallest olfactomes identified from any insect to date. Behavioral experiments with host and non-host plants, as well as with identified specific volatiles from these sources, suggest that the few input channels present are primarily tuned toward the identification of unwanted features, rather than favored ones, a strategy quite unlike most other insects. The demonstrated repellence effect of specific volatile chemicals produced by certain plants unflavored by whiteflies suggests that intercropping with these plants could be a viable strategy to reduce whitefly infestations in cassava fields.
Specialization on Ficus Supported by Genetic Divergence and Morphometrics in Sympatric Host-Populations of the Camellia Aphid, Aphis aurantii
Authors: Li Qiang , Chen Cui , Wu Yangxue , Siddiqui Junaid Ali , Lu Congcong , Cheng Zhentao , Li Yonghui , Liu Qian , Huang Xiaolei
Published: November 2021

Adaptation to different host plants is considered to be an important driver of the divergence and speciation of herbivorous insects. The application of molecular data and integrated taxonomic practices in recent years may contribute to our understanding of population divergence and speciation, especially for herbivorous insects considered to be polyphagous. Aphis aurantii is an important agricultural and forestry pest with a broad range of host plants. In this study, samples of A. aurantii feeding on different host plants in the same geographical area were collected, and their population genetic divergence and morphological difference were analyzed. Phylogenetic analysis and haplotype network analysis based on five genes revealed that the population on Ficus exhibited significantly genetic divergence from populations on other host plants, which was also supported by the statistical analysis based on measurements of 38 morphological characters. Our results suggest that A. aurantii has undergone specialized evolution on Ficus, and the Ficus population may represent a lineage that is experiencing ongoing sympatric speciation.
Insilico Functional Analysis of Genome-Wide Dataset From 17,000 Individuals Identifies Candidate Malaria Resistance Genes Enriched in Malaria Pathogenic Pathways
Authors: Damena Delesa , Agamah Francis E. , Kimathi Peter O. , Kabongo Ntumba E. , Girma Hundaol , Choga Wonderful T. , Golassa Lemu , Chimusa Emile R.
Published: November 2021

Recent genome-wide association studies (GWASs) of severe malaria have identified several association variants. However, much about the underlying biological functions are yet to be discovered. Here, we systematically predicted plausible candidate genes and pathways from functional analysis of severe malaria resistance GWAS summary statistics (N = 17,000) meta-analysed across 11 populations in malaria endemic regions. We applied positional mapping, expression quantitative trait locus (eQTL), chromatin interaction mapping, and gene-based association analyses to identify candidate severe malaria resistance genes. We further applied rare variant analysis to raw GWAS datasets (N = 11,000) of three malaria endemic populations including Kenya, Malawi, and Gambia and performed various population genetic structures of the identified genes in the three populations and global populations. We performed network and pathway analyses to investigate their shared biological functions. Our functional mapping analysis identified 57 genes located in the known malaria genomic loci, while our gene-based GWAS analysis identified additional 125 genes across the genome. The identified genes were significantly enriched in malaria pathogenic pathways including multiple overlapping pathways in erythrocyte-related functions, blood coagulations, ion channels, adhesion molecules, membrane signalling elements, and neuronal systems. Our population genetic analysis revealed that the minor allele frequencies (MAF) of the single nucleotide polymorphisms (SNPs) residing in the identified genes are generally higher in the three malaria endemic populations compared to global populations. Overall, our results suggest that severe malaria resistance trait is attributed to multiple genes, highlighting the possibility of harnessing new malaria therapeutics that can simultaneously target multiple malaria protective host molecular pathways.
FMixFN: A Fast Big Data-Oriented Genomic Selection Model Based on an Iterative Conditional Expectation algorithm
Authors: Xu Wenwu , Liu Xiaodong , Liao Mingfu , Xiao Shijun , Zheng Min , Yao Tianxiong , Chen Zuoquan , Huang Lusheng , Zhang Zhiyan
Published: November 2021

Genomic selection is an approach to select elite breeding stock based on the use of dense genetic markers and that has led to the development of various models to derive a predictive equation. However, the current genomic selection software faces several issues such as low prediction accuracy, low computational efficiency, or an inability to handle large-scale sample data. We report the development of a genomic prediction model named FMixFN with four zero-mean normal distributions as the prior distributions to optimize the predictive ability and computing efficiency. The variance of the prior distributions in our model is precisely determined based on an F2 population, and genomic estimated breeding values (GEBV) can be obtained accurately and quickly in combination with an iterative conditional expectation algorithm. We demonstrated that FMixFN improves computational efficiency and predictive ability compared to other methods, such as GBLUP, SSgblup, MIX, BayesR, BayesA, and BayesB. Most importantly, FMixFN may handle large-scale sample data, and thus should be able to meet the needs of large breeding companies or combined breeding schedules. Our study developed a Bayes genomic selection model called FMixFN, which combines stable predictive ability and high computational efficiency, and is a big data-oriented genomic selection model that has potential in the future. The FMixFN method can be freely accessed at https://zenodo.org/record/5560913 (DOI: 10.5281/zenodo.5560913).
Addressing Iron and Zinc Micronutrient Malnutrition Through Nutrigenomics in Pearl Millet: Advances and Prospects
Authors: Srivastava Rakesh K. , Satyavathi C. Tara , Mahendrakar Mahesh D. , Singh Ram B. , Kumar Sushil , Govindaraj Mahalingam , Ghazi Irfan A.
Published: November 2021

Iron (Fe) and zinc (Zn) micronutrient deficiencies are significant health concerns, particularly among the underprivileged and resource-poor people in the semi-arid tropics globally. Pearl millet is regarded as a climate-smart crop with low water and energy footprints. It thrives well under adverse agro-ecologies such as high temperatures and limited rainfall. Pearl millet is regarded as a nutri-cereal owing to health-promoting traits such as high grain Fe and Zn content, metabolizable energy, high antioxidant and polyphenols, high proportion of slowly digestible starches, dietary fibers, and favorable essential amino acid profile compared to many cereals. Higher genetic variability for grain Fe and Zn content has facilitated considerable progress in mapping and mining QTLs, alleles and genes underlying micronutrient metabolism. This has been made possible by developing efficient genetic and genomic resources in pearl millet over the last decade. These include genetic stocks such as bi-parental RIL mapping populations, association mapping panels, chromosome segment substitution lines (CSSLs) and TILLING populations. On the genomics side, considerable progress has been made in generating genomic markers, such as SSR marker repository development. This was followed by the development of a next-generation sequencing-based genome-wide SNP repository. The circa 1,000 genomes re-sequencing project played a significant role. A high-quality reference genome was made available by re-sequencing of world diversity panel, mapping population parents and hybrid parental lines. This mini-review attempts to provide information on the current developments on mapping Fe and Zn content in pearl millet and future outlook.
Characterisation and Molecular Analysis of an Unusual Chimeric Methicillin Resistant Staphylococcus Aureus Strain and its Bacteriophages
Authors: Burgold-Voigt Sindy , Monecke Stefan , Simbeck Alexandra , Holzmann Thomas , Kieninger Bärbel , Liebler-Tenorio Elisabeth M. , Braun Sascha D. , Collatz Maximilian , Diezel Celia , Müller Elke , Schneider-Brachert Wulf , Ehricht Ralf
Published: November 2021

In the context of microarray-based epidemiological typing of the clonal organism Staphylococcus aureus/MRSA, a strain was identified that did not belong to known clonal complexes. The molecular analysis by microarray-based typing yielded signals suggesting that it was a mosaic or hybrid strain of two lineages. To verify this result, the isolate was sequenced with both, short-read Illumina and long-read Nanopore technologies and analysed in detail. This supported the hypothesis that the genome of this strain, ST6610-MRSA-IVg comprised of segments originating from two different clonal complexes (CC). While the backbone of the strain’s genome, i.e., roughly 2 megabases, belongs to CC8, a continuous insert of 894 kb (approx. 30% of the genome) originated from CC140. Beside core genomic markers in the normal succession and orientation, this insert also included the mecA gene, coding for PbP2a and causing methicillin resistance, localised on an SCCmec IVg element. This particular SCCmec type was also previously observed in CC140 MRSA from African countries. A second conspicuous observation was the presence of the trimethoprim resistance gene dfrG within on a prophage that occupied an attachment site normally used by Panton-Valentine Leucocidin phages. This observation could indicate a role of large-scale chromosomal recombination in the evolution of S. aureus as well as a role of phages in the dissemination of antibiotic resistance genes.
Matrix Metalloproteinases in Relation to Bone Mineral Density: A Two-Sample Mendelian Randomization Study
Authors: Lv Xin , Wu Pengfei , Xiao Shipeng , Zhang Wan , Li Yawei , Ren Bolin , Li Zhihong , Xia Kun , Wang Bing
Published: November 2021

Background: We aimed at investigating causal associations between matrix metalloproteinases (MMPs) and bone mineral density (BMD) by the Mendelian randomization (MR) analysis.

Methods: From genome-wide association studies of European ancestry, we selected instrumental variables for MMP-1, MMP-3, MMP-7, MMP-8, MMP-10, and MMP-12. Accordingly, we retrieved summary statistics of three site-specific BMD, namely, forearm, femoral neck, and lumbar spine. We conducted an inverse variance weighted MR as the primary method to compute overall effects from multiple instruments, while additional MR approaches and sensitivity analyses were implemented. Bonferroni-adjusted significance threshold was set at p < 0.05/18 = 0.003.

Results: Totally, there was no evidence for causal effects of genetically-predicted levels of MMPs on BMD measurement at three common sites. MR results indicated that there were no causal associations of circulating MMPs with forearm BMD (all p ≥ 0.023) by the inverse variance weighted method. Similarly, there were no causal effects of MMPs on femoral neck BMD (all p ≥ 0.120) and MR results did not support causal relationships between MMPs and lumbar spine BMD (all p ≥ 0.017). Multiple sensitivity analyses suggested the robustness of MR results, which were less likely to be biased by unbalanced pleiotropy or evident heterogeneity.

Conclusion: We found no evidence for the causal relationship between MMPs and BMD in the European population.
Association Analysis of WNT3, HLA-DRB5 and IL1R2 Polymorphisms in Chinese Patients With Parkinson’s Disease and Multiple System Atrophy
Authors: Su Wei-Ming , Gu Xiao-Jing , Hou Yan-Bing , Zhang Ling-Yu , Cao Bei , Ou Ru-Wei , Wu Ying , Chen Xue-Ping , Song Wei , Zhao Bi , Shang Hui-Fang , Chen Yong-Ping
Published: November 2021

Background: The association between inflammation and neurodegeneration has long been observed in parkinson’s disease (PD) and multiple system atrophy (MSA). Previous genome-wide association studies (GWAS) and meta-analyses have identified several risk loci in inflammation-associated genes associated with PD.

Objective: To investigate whether polymorphisms in some inflammation-associated genes could modulate the risk of developing PD and MSA in a Southwest Chinese population.

Methods: A total of 2,706 Chinese subjects comprising 1340 PD, 483 MSA and 883 healthy controls were recruited in the study. Three polymorphisms (rs2074404 GG/GT/TT, rs17425622 CC/CT/TT, rs34043159 CC/CT/TT) in genes linked to inflammation in all the subjects were genotyped by using the Sequenom iPLEX Assay.

Results: The allele G of WNT3 rs2074404 can increase risk on PD (OR: 1.048, 95% CI: 1.182–1.333, p = 0.006), exclusively in the LOPD subgroup (OR: 1.166, 95% CI:1.025–1.327, p = 0.019), but not in EOPD or MSA. And the recessive model analysis also demonstrated an increased PD risk in GG genotype of this locus (OR = 1.331, p = 0.007). However, no significant differences were observed in the genotype distributions and alleles of HLA-DRB5 rs17425622 and IL1R2 rs34043159 between the PD patients and controls, between the MSA patients and controls, or between subgroups of PD or MSA and controls.

Conclusion: Our results suggested the allele G of WNT3 rs2074404 have an adverse effect on PD and particularly, on the LOPD subgroup among a Chinese population.