bluuebunny/crossref_metadata_2025 huggingface dataset:
Habitat models and assessment of habitat partitioning for Kemp’s ridley and loggerhead marine turtles foraging in Chesapeake Bay (USA)
Authors: DiMatteo A , Lockhart G , Barco S
Published: November 2021

Understanding the spatial distribution of a species is required to enact effective conservation. Complications to effective conservation can arise when the distributions of multiple target species are non-overlapping. Conservation efforts meant to protect one species may shift threats into the distribution of another species. Two species of marine turtle, loggerhead Caretta caretta and Kemp’s ridley Lepidochelys kempii, are common seasonally in Chesapeake Bay, a large estuary on the US east coast. Both species are protected under the US Endangered Species Act and face spatially complex threats in the region. We created habitat suitability models for these 2 species to inform conservation efforts in the region and explore the extent of overlap between their distributions. Argos satellite tags were deployed on 24 Kemp’s ridley and 10 loggerhead turtles to record animal locations within the Bay. Boosted regression tree models were created for each species using presence-only animal locations, predicting suitable habitat within the Bay. Habitat for Kemp’s ridley turtles was predicted in shallow, coastal areas of the southern Bay as well as in brackish areas of rivers. Loggerhead turtle habitat was predicted to extend farther north than Kemp’s ridley habitat and was generally found in deeper areas of the middle Bay. There is some evidence that these 2 species are partitioning habitat. Any conservation measures adopted to conserve marine turtles in the Chesapeake Bay should consider the habitat of both species holistically to avoid shifting impacts from one species to another.
Evaluation of The Ethmoid Bone Using by Cone Beam Computed Tomography In Turkish Subpopulation
Authors: AKTUNA BELGİN Ceren , BAYRAK Seval , ORHAN Kaan
Published: November 2021

Objective: The objective of this retrospective study was to determine the prevalence of the data obtained from anatomical structures of ethmoid bone evaluated morphometrically on cone beam computed tomography (CBCT) images in a Turkish subpopulation.

Methods: The CBCT images of 200 patients which met the study criteria were selected from the digital database of our university. The medial ethmoid roof height (MERH), cribriform plate height (CP), the height of the lateral lamella of the cribriform plate (LLCP) were evaluated retrospectively using. All the data were grouped by age, side and gender.

Results: For MERH; the mean length for left and the right side was 25.55 ± 3.00 mm and 25.24 ± 3.01 mm, respectively. The mean LLCP heights in right and left side were 4.98±2.12 mm and 4.49 ±1.64 mm, respectively. In the female, the mean of right and left LLCP height were 5.07±2.07 mm and 4.48±1.63 mm, respectively. In the male, the mean of right and left LLCP height were 4.83±2.21 and 4.50±1.66 mm, respectively. It was found that LLCP height did not have a statistically significant correlation with gender (p>0.05). There was a statistically significant negative correlation between LLCP and CP (p
The Effect of High Body Mass Index on Self-Esteem and Sexual Functions in Obese Females Admitted to The Plastic Reconstructive and Aesthetic Surgery Department
Authors: AHMEDOV Anvar , AHMEDOV Yeşim
Published: November 2021

Objective: Obesity can be defined as body weight above the desired level. Obesity has gone beyond being a cosmetic problem and is now referred to as a disease, and there is a currently significantly increasing number of studies examining the relationship between the obesity and psychopathology. The psychological and social effects of obesity also affect the self-confidence of the individual and the behavioral orientation at the onset of sexual intercourse and avoidance. The aim of this study was to determine whether high body mass index has an effect on selfesteem and sexual functions in obese women who were referred to an obesity center.

Methods: This descriptive study was conducted between 1.11.2018 and 15.01.2020. A total of 202 patients referred from the plastic surgery department to the obesity centre were included in the study. All the patients were assessed twice within a 7-month period with the Rosenberg Self-Esteem Scale, Body Perception Scale and Arizona Sexual Experiences Scale.

Results: Of the 202 women evaluated, 66.3% were in the 51-70 years age range, and 52% had a body mass index in the range of 35-39.9. Evaluation of the two applications of the scales showed a significant positive relationship between the first scale and the second scale scores seven months after weight loss.

Conclusion: The results of this study showed that a decrease in body weight had a positive effect on body perception and on sexual satisfaction.
Surgery Nurses’ Awareness on SBAR Communication Model and SBAR Training
Authors: VATAN Merve , YILDIZ Tülin
Published: November 2021

Objective: The study has been carried out to analyze surgery nurses’ awareness on SBAR communication model and to measure the effectiveness of SBAR training on it. SBAR communication model, which abbreviates “situation, background, assessment and recommendation”, undertakes a significant role to provide patient safety.

Methods: It was undertaken between 1 March 2019 – 30 April 2019 with a sample consisting of 138 nurses serving in surgical units of the hospital involved in the study. A session of 45-minute training, which has been delivered to surgery nurses, consisted of example scenarios and practices based on SBAR communication model as well as the user guide and some video shots related to communication settings in compliance with SBAR Model. The data were collected during pre-training, immediately after post-training and one-month after the posttraining sessions via face-to face interviews conducted with surgery nurses.

Results: Mean values of nurses’ SBAR communication model awareness have been calculated for all 18 questions in the form. Those mean values have been displayed as 62.76±28.52 during pre-training, 95.05±7.56 during immediate post-training and 90.90±13.89 during a-monthlater session of post-training. Comparisons of pre-training and post-training scores have displayed a statistically significant increase in mean values, both after the training and one month later (p
The Effect of Helfer Skin Tap Technique and ShotBlocker Application on Pain in Deltoid Muscle Injection
Authors: KARABEY Tuba , KARAGÖZOĞLU Şerife
Published: November 2021

Objective: This study was performed experimentally and single-blind randomized controlled trial to compare the effects of Helfer Skin Tap technique and Shot Blocker application on pain in the intramuscular injection application to the deltoid muscle.
Methods: The study was designed as a prospective, single-blind randomized controlled trial. The research was conducted in accordance with the Consolidated Standards of Reporting Trials (CONSORT) Checklist guide. The study was conducted in a family health center in Sivas Province between 05.10.2020-30.12.2020. Individuals who received Hepatitis B vaccine injection were included in the sample of the study. All intramuscular injections were made by the same nurse, and the approaches to reducing pain were made by the researcher. A total of 120 patients including the Helfer Skin Tap Technique (n=40), the standard application (n=40) and the ShotBlocker technique (n=40) were included. Mann Whitney U and Kruskal Wallis tests were used to evaluate the data.
Results: In our study, 75% (n=30) of the Helfer Skin Tap group, 82.50% (n=33) of the standard administration group and 75% (n=30) of the ShotBlocker group reported that they had no fear of injection. When the distribution of post-injection pain scores of the individuals according to different injection methods was examined, the difference between the average pain scores of the different methods used to provide pain control was found to be significant and statistically significant (p=0.001).
Conclusion: In line with the findings of our study, it was concluded that the use of ShotBlocker in intramuscular injection application of individuals was more effective in reducing pain due to injection compared to Helfer Skin Tap and standard application, and the Helfer Skin Tap technique was more successful in pain control than standard practice. All health professionals’, especially nurses’, awareness of the effectiveness of different methods in reducing pain during IM injection should be raised. To ensure pain control during IM injection, Shotblocker and Helfer Skin Tap Technique should be preferred since they are easy to apply and cost effective.
The Effect of Foot Massage on Pain and Anxiety Levels after Laparoscopic Cholecystectomy: A Randomized-Controlled Trial
Authors: ABDULLAYEV Ayşegül
Published: November 2021

Objective: This study was conducted to determine the effect of foot reflexology massage performed on patients after laparoscopic cholecystectomy on pain levels, analgesic use and anxiety levels.

Methods: This prospective, experimental and randomized-controlled study was conducted with patients who underwent cholecystectomy. Ninety patients in total were divided into the experiment (n = 30), control (n = 30) and placebo (n = 30) groups. Foot reflexology massage was performed on the patients in the experiment group two times after surgery. Placebo massage was performed on the patients in the placebo group at the same times. Only routine treatment and care were given to the patients in the control group. The patients’ pain and anxiety levels and their amounts of analgesic use within 24 hours were monitored.

Results: The patients’ state anxiety scores decreased significantly from the preoperative to the postoperative measurements, and the degree of decrease did not differ between the groups (p>0.05). The pain scores of the patients decreased after the first and second massage applications in all groups in comparison to their pre-massage scores, and the pain in the experiment group felt after the second massage was lower than that in the patients in the placebo group (p0.05).

Conclusion: As a result, it may be stated that using reflexology with effectiveness of pain treatment and the quality of nursing care.
Automatic Behavior and Posture Detection of Sows in Loose Farrowing Pens Based on 2D-Video Images
Authors: Küster Steffen , Nolte Philipp , Meckbach Cornelia , Stock Bernd , Traulsen Imke
Published: November 2021

The monitoring of farm animals and the automatic recognition of deviant behavior have recently become increasingly important in farm animal science research and in practical agriculture. The aim of this study was to develop an approach to automatically predict behavior and posture of sows by using a 2D image-based deep neural network (DNN) for the detection and localization of relevant sow and pen features, followed by a hierarchical conditional statement based on human expert knowledge for behavior/posture classification. The automatic detection of sow body parts and pen equipment was trained using an object detection algorithm (YOLO V3). The algorithm achieved an Average Precision (AP) of 0.97 (straw rack), 0.97 (head), 0.95 (feeding trough), 0.86 (jute bag), 0.78 (tail), 0.75 (legs) and 0.66 (teats). The conditional statement, which classifies and automatically generates a posture or behavior of the sow under consideration of context, temporal and geometric values of the detected features, classified 59.6% of the postures (lying lateral, lying ventral, standing, sitting) and behaviors (interaction with pen equipment) correctly. In conclusion, the results indicate the potential of DNN toward automatic behavior classification from 2D videos as potential basis for an automatic farrowing monitoring system.
A Tool for Segmentation of Secondary Structures in 3D Cryo-EM Density Map Components Using Deep Convolutional Neural Networks
Authors: Mu Yongcheng , Sazzed Salim , Alshammari Maytha , Sun Jiangwen , He Jing
Published: November 2021

Although cryo-electron microscopy (cryo-EM) has been successfully used to derive atomic structures for many proteins, it is still challenging to derive atomic structures when the resolution of cryo-EM density maps is in the medium resolution range, such as 5–10 Å. Detection of protein secondary structures, such as helices and β-sheets, from cryo-EM density maps provides constraints for deriving atomic structures from such maps. As more deep learning methodologies are being developed for solving various molecular problems, effective tools are needed for users to access them. We have developed an effective software bundle, DeepSSETracer, for the detection of protein secondary structure from cryo-EM component maps in medium resolution. The bundle contains the network architecture and a U-Net model trained with a curriculum and gradient of episodic memory (GEM). The bundle integrates the deep neural network with the visualization capacity provided in ChimeraX. Using a Linux server that is remotely accessed by Windows users, it takes about 6 s on one CPU and one GPU for the trained deep neural network to detect secondary structures in a cryo-EM component map containing 446 amino acids. A test using 28 chain components of cryo-EM maps shows overall residue-level F1 scores of 0.72 and 0.65 to detect helices and β-sheets, respectively. Although deep learning applications are built on software frameworks, such as PyTorch and Tensorflow, our pioneer work here shows that integration of deep learning applications with ChimeraX is a promising and effective approach. Our experiments show that the F1 score measured at the residue level is an effective evaluation of secondary structure detection for individual classes. The test using 28 cryo-EM component maps shows that DeepSSETracer detects β-sheets more accurately than Emap2sec+, with a weighted average residue-level F1 score of 0.65 and 0.42, respectively. It also shows that Emap2sec+ detects helices more accurately than DeepSSETracer with a weighted average residue-level F1 score of 0.77 and 0.72 respectively.
T Cell Immunity Evaluation and Immunodominant Epitope T Cell Receptor Identification of Severe Acute Respiratory Syndrome Coronavirus 2 Spike Glycoprotein in COVID-19 Convalescent Patients
Authors: Li Luo , Chen Qian , Han Xiaojian , Shen Meiying , Hu Chao , Chen Siyin , Zhang Jing , Wang Yingming , Li Tingting , Huang Jingjing , Li Shenglong , Hao Yanan , Jin Aishun
Published: November 2021

A better understanding of the role of T cells in the immune response to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is helpful not only for vaccine development but also for the treatment of COVID-19 patients. In this study, we determined the existence of SARS-CoV-2-specific T cells in the blood of COVID-19 convalescents. Meanwhile, the specific T cell response in the non-RBD region was stronger than in the RBD region. We also found that SARS-CoV-2 S-specific reactive CD4+ T cells exhibited higher frequency than CD8+ T cells in recovered COVID-19 patients, with greater number of corresponding epitopes presented. Importantly, we isolated the SARS-CoV-2-specific CD4+ T cell receptors (TCRs) and inserted the TCRs into allogenic CD4+ T cells. These TCR-T cells can be activated by SARS-CoV-2 spike peptide and produce IFN-γ in vitro. These results might provide valuable information for the development of vaccines and new therapies against COVID-19.
Antioxidant/Pro-Oxidant Actions of Polyphenols From Grapevine and Wine By-Products-Base for Complementary Therapy in Ischemic Heart Diseases
Authors: Chedea Veronica Sanda , Tomoiagǎ Liliana Lucia , Macovei Ştefan Octavian , Mǎgureanu Dan Claudiu , Iliescu Maria Lucia , Bocsan Ioana Corina , Buzoianu Anca Dana , Voşloban Crinuţa Maria , Pop Raluca Maria
Published: November 2021

Grape pomace and grape seeds, by-products of the wine industry, and grapevine cane resulting from grapevine pruning are cheap matrices containing important amounts of polyphenols. While there is a continuous need of introducing new ways of these by-products valorization, we propose their use as a source of bioactive polyphenols for complementary therapy in ischemic heart diseases. As oxidative stress plays an important role in these diseases, by their antioxidant/pro-oxidant properties, these compounds, mainly flavan-3-ols, procyanidins, and resveratrol may counteract the damage of the oxidative stress. For instance, to some extent, the grape seed extract, considered as an antioxidant nutritive supplement, may have pro-oxidant activity as well, depending on dose, duration of administration, and other dietary components.In vitrostudies confirm that the antioxidant activity of this extract might be mediated by pro-oxidanto-quinones and oxidation products of the polyphenols from grape and winery byproducts, indicating that quinones, as oxidation products, are involved in the modulation of the antioxidant/pro-oxidant balance at the cellular level in the case of catechin-type compounds, in the absence or presence of oxidative stress inducers.In vivo, studies indicate that a grape pomace-rich diet results in a significant increase of the total antioxidant status in the plasma, liver, spleen, and kidneys. Also, the administration of grape pomace shows antioxidant activity with positive effects on health. In this context, the present review aims to present the most recent research focused on the antioxidant/pro-oxidant actions of the bioactive polyphenols from grapevine and wine byproducts, in conditions of ischemic heart diseases as assessedin vitroorin vivo.
A2 Adenosine Receptor Subtypes Overproduction in Atria of Perioperative Atrial Fibrillation Patients Undergoing Cardiac Surgery: A Pilot Study
Authors: Maille Baptiste , Fromonot Julien , Guiol Claire , Marlinge Marion , Baptiste Florian , Lim Suzy , Colombani Charlotte , Chaptal Marie Charlotte , Chefrour Mohamed , Gastaldi Marguerite , Franceschi Frederic , Deharo Jean-Claude , Gariboldi Vlad , Ruf Jean , Mottola Giovanna , Guieu Régis
Published: November 2021

Objective: Although atrial fibrillation is a common cardiac arrhythmia in humans, the mechanism that leads to the onset of this condition is poorly elucidated. Adenosine is suspected to be implicated in the trigger of atrial fibrillation (AF) through the activation of its membrane receptors, mainly adenosine receptor (AR) subtypes A1R and A2R. In this study, we compared blood adenosine concentration (BAC), and A1R, A2AR, and A2BR production in right (RA) and left atrium (LA), and on peripheral blood mononuclear cells (PBMCs) in patients with underlying structural heart disease undergoing cardiac surgery with or without peri-operative AF (PeOpAF).

Methods: The study group consisted of 39 patients (30 men and 9 women, mean age, range 65 [40–82] years) undergoing cardiac surgery and 20 healthy patients (8 women and 12 men; mean age, range 60 [39–72] years) as controls were included. Among patients, 15 exhibited PeOpAF.

Results: Blood adenosine concentration was higher in patients with PeOpAF than others. A2AR and A2BR production was higher in PBMCs of patients compared with controls and was higher in PeOpAF patients than other patients. In LA and RA, the production of A2AR and A2BR was higher in patients with PeOpAF than in other patients. Both A2AR and A2BR production were higher in LA vs. RA. A1R production was unchanged in all situations. Finally, we observed a correlation between A1R, A2AR, and A2BR production evaluated on PBMCs and those evaluated in LA and RA.

Conclusions: Perioperative AF was associated with high BAC and high A2AR and A2BR expression, especially in the LA, after cardiac surgery in patients with underlying structural heart disease. Whether these increases the favor in triggering the AF in this patient population needs further investigation.
Economic Evaluation of Digital Health Interventions in Palliative Care: A Systematic Review of the Literature
Authors: Naoum Panagiota , Pavi Elpida , Athanasakis Kostas
Published: November 2021

Introduction:Digital health interventions can facilitate the provision of palliative care. However, the economic evaluation of such interventions has not yet been a standard practice. The present study aimed to identify the existing literature on the particular subject.

Methods:A systematic search was conducted in six literature databases between 2010 and 2021: PubMed, Scopus, DARE, NHS EED, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials. Methodological quality was assessed with the Drummond Checklist.

Results:The search identified 423 publications, 66 of which were removed as duplicates, resulting in 357 records to be screened by title and abstract. Ten studies were subjected to full-text review and 3 were included in the analysis. The interventions of these studies referred to video consultations and eHealth interventions for symptom management. Overall, the digital health interventions incurred lower costs compared with usual care or no intervention and were considered cost saving and cost-effective. The methodological quality of the studies was considered good.

Conclusion:The results of this systematic review indicate that the use of digital health interventions has the potential to be cost-effective in palliative care. However, applicability and generalizability of the evidence is uncertain, mainly due to methodological heterogeneity and scarcity of research.
High-Resolution WRF Simulation of Extreme Heat Events in Eastern China: Large Sensitivity to Land Surface Schemes
Authors: Hua Wenjian , Dong Xuan , Liu Qingyuan , Zhou Liming , Chen Haishan , Sun Shanlei
Published: November 2021

Regional climate models with high-resolution simulation are particularly useful for providing a detailed representation of land surface processes, and for studying the relationship between land surface processes and heat events. However, large differences and uncertainties exist among different land surface schemes (LSSs). This study comprehensively assesses the sensitivity to different LSSs based on two extreme heat events in eastern China using the Weather Research and Forecasting (WRF) model. Among the five LSSs (i.e., 5TD, CLM4, Noah, Noah-MP and RUC), Noah is closest to observations in reproducing the temperatures and energy fluxes for both two heat events. The modeled warm biases result mainly from the underestimation of evapotranspirative cooling. Our results show that how each LSS partitions the evapotranspiration (ET) and sensible heat largely determines the relationship between the temperature and turbulent fluxes. Although the simulated two extreme heat events manifest similar biases in the temperatures and energy fluxes, the land surface responses (ET and soil moisture) are different.
Quercetin Modulates IGF-I and IGF-II Levels After Eccentric Exercise-Induced Muscle-Damage: A Placebo-Controlled Study
Authors: Sgrò Paolo , Ceci Roberta , Lista Marco , Patrizio Federica , Sabatini Stefania , Felici Francesco , Sacchetti Massimo , Bazzucchi Ilenia , Duranti Guglielmo , Di Luigi Luigi
Published: November 2021

Background

Prolonged or unaccustomed eccentric exercise may cause muscle damage and depending from its extent, this event negatively affects physical performance.

Objectives

The aim of the present investigation was to evaluate, in humans, the effect of the flavonoid quercetin on circulating levels of the anabolic insulin-like growth factor 1 (IGF-I) and insulin-like growth factor 2 (IGF-II), produced during the recovery period after an eccentric-induced muscle damage (EIMD).

Methods

A randomized, double-blind, crossover study has been performed; twelve young men ingested quercetin (1 g/day) or placebo for 14 days and then underwent an eccentric-induced muscle damaging protocol. Blood samples were collected, and cell damage markers [creatine kinase (CK), lactate dehydrogenase (LDH) and myoglobin (Mb)], the inflammatory responsive interleukin 6 (IL-6), IGF-I and IGF-II levels were evaluated before the exercise and at different recovery times from 24 hours to 7 days after EIMD.

Results

We found that, in placebo treatment the increase in IGF-I (72 h) preceded IGF-II increase (7 d). After Q supplementation there was a more marked increase in IGF-I levels and notably, the IGF-II peak was found earlier, compared to placebo, at the same time of IGF-I (72 h). Quercetin significantly reduced plasma markers of cell damage [CK (p<0.005), LDH (p<0.001) and Mb (p<0.05)] and the interleukin 6 level [IL-6 (p<0.05)] during recovery period following EIMD compared to placebo.

Conclusions

Our data are encouraging about the use of quercetin as dietary supplementation strategy to adopt in order to mitigate and promote a faster recovery after eccentric exercise as suggested by the increase in plasma levels of the anabolic factors IGF-I and IGF-II.
Sestrin2 as a Potential Target for Regulating Metabolic-Related Diseases
Authors: Gong Linan , Wang Zanzan , Wang Zhenggui , Zhang Zhiguo
Published: November 2021

Sestrin2 is a highly conserved protein that can be induced under a variety of stress conditions, including DNA damage, oxidative stress, endoplasmic reticulum (ER) stress, and metabolic stress. Numerous studies have shown that the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway has a crucial role in the regulation of metabolism. Sestrin2 regulates metabolismviaa number of pathways, including activation of AMPK, inhibition of the mTOR complex 1 (mTORC1), activation of mTOR complex 2 (mTORC2), inhibition of ER stress, and promotion of autophagy. Therefore, modulation of Sestrin2 activity may provide a potential therapeutic target for the prevention of metabolic diseases such as insulin resistance, diabetes, obesity, non-alcoholic fatty liver disease, and myocardial ischemia/reperfusion injury. In this review, we examined the regulatory relationship between Sestrin2 and the AMPK/mTOR signaling pathway and the effects of Sestrin2 on energy metabolism.
Oral Antidiabetics and Sleep Among Type 2 Diabetes Patients: Data From the UK Biobank
Authors: Xue Pei , Wu Jiafei , Tang Xiangdong , Tan Xiao , Benedict Christian
Published: November 2021

Previous small-scale studies have found that oral antidiabetic therapy is associated with sleep difficulties among patients with type 2 diabetes (T2D). Here, we used data from 11 806 T2D patients from the UK Biobank baseline investigation to examine the association of oral antidiabetic therapy with self-reported difficulty falling and staying asleep and daily sleep duration. As shown by logistic regression adjusted for, e.g., age, T2D duration, and HbA1c, patients on non-metformin therapy (N=815; 86% were treated with sulphonylureas) had a 1.24-fold higher odds ratio of reporting regular difficulty falling and staying asleep at night compared to those without antidiabetic medication use (N=5 366, P<0.05) or those on metformin monotherapy (N=5 625, P<0.05). Non-metformin patients reported about 8 to 10 minutes longer daily sleep duration than the other groups (P<0.05). We did not find significant differences in sleep outcomes between untreated and metformin patients. Our findings suggest that non-metformin therapy may result in sleep initiation and maintenance difficulties, accompanied by a small but significant sleep extension. The results of the present study must be replicated in future studies using objective measures of sleep duration and validated questionnaires for insomnia. Considering that most T2D patients utilize multiple therapies to manage their glycemic control in the long term, it may also be worth investigating possible interactions of antidiabetic drugs on sleep.
Optimal Balancing of Wind Parks with Virtual Power Plants
Authors: Omelčenko Vadim , Manokhin Valery
Published: November 2021

In this paper, we explore the optimization of virtual power plants (VPP), consisting of a portfolio of biogas power plants and a battery whose goal is to balance a wind park while maximizing their revenues. We operate under price and wind production uncertainty and in order to handle it, methods of machine learning are employed. For price modeling, we take into account the latest trends in the field and the most up-to-date events affecting the day-ahead and intra-day prices. The performance of our price models is demonstrated by both statistical methods and improvements in the profits of the virtual power plant. Optimization methods will take price and imbalance forecasts as input and conduct parallelization, decomposition, and splitting methods in order to handle sufficiently large numbers of assets in a VPP. The main focus is on the speed of computing optimal solutions of large-scale mixed-integer linear programming problems, and the best speed-up is in two orders of magnitude enabled by our method which we called Gradual Increase.
Ferroptosis-Related Gene Signature Predicts the Prognosis of Skin Cutaneous Melanoma and Response to Immunotherapy
Authors: Xu Ziqian , Xie Yihui , Mao Yaqi , Huang Juntao , Mei Xingyu , Song Jun , Sun Yue , Yao Zhixian , Shi Weimin
Published: November 2021

Ferroptosis is a non-apoptotic regulated cell death process, and much research has indicated that ferroptosis can induce the non-apoptotic death of tumor cells. Ferroptosis-related genes are expected to become a biological target for cancer treatment. However, the regulation of ferroptosis-related genes in skin cutaneous melanoma (SKCM) has not been well studied. In the present study, we conducted a systematic analysis of SKCM based on RNA sequencing data and clinical data obtained from The Cancer Genome Atlas (TCGA) database and the FerrD database. SKCM patients from the GSE78220 and MSKCC cohorts were used for external validation. Applying consensus clustering on RNA sequencing data from TCGA the generated ferroptosis subclasses of SKCM, which were analyzed based on the set of differentially expressed ferroptosis-related genes. Then, a least absolute shrinkage and selection operator (LASSO)-Cox regression was used to construct an eight gene survival-related linear signature. The median cut-off risk score was used to divide patients into high- and low-risk groups. The time-dependent receiver operating characteristic curve was used to examine the predictive power of the model. The areas under the curve of the signature at 1, 3, and 5 years were 0.673, 0.716, and 0.746, respectively. Kaplan-Meier survival analysis showed that the prognosis of high-risk patients was worse than that of low-risk patients. Univariate and multivariate Cox regression analyses showed that the risk signature was a robust independent prognostic indicator. By incorporating risk scores with tumor staging, a nomogram was constructed to predict prognostic outcomes for SKCM patients. In addition, the immunological analysis showed different immune cell infiltration patterns. Programmed-death-1 (PD-1) immunotherapy showed more significant benefits in the low-risk group than in the high-risk group. In summary, a model based on ferroptosis-related genes can predict the prognosis of SKCM and could have a potential role in guiding targeted therapy of SKCM.
Accumulation of Senescent Neural Cells in Murine Lupus With Depression-Like Behavior
Authors: Saito Yuki , Miyajima Maki , Yamamoto Sena , Sato Tsukasa , Miura Norihiro , Fujimiya Mineko , Chikenji Takako S.
Published: November 2021

Neuropsychiatric manifestations targeting the central, peripheral, and autonomic nervous system are common in systemic lupus erythematosus (SLE); collectively, these symptoms are termed neuropsychiatric SLE (NPSLE). Among a wide variety of neuropsychiatric symptoms, depression is observed in about 24-39% of SLE patients. Several cytokines and chemokines have been identified as biomarkers or therapeutic targets of NPSLE; in particular, the levels of type 1 interferons, TNFs, and IL-6 are elevated in SLE patient’s cerebrospinal fluid (CSF), and these factors contribute to the pathology of depression. Here, we show that senescent neural cells accumulate in the hippocampal cornu ammonis 3 (CA3) region in MRL/lpr SLE model mice with depressive behavior. Furthermore, oral administration of fisetin, a senolytic drug, reduced the number of senescent neural cells and reduced depressive behavior in the MRL/lpr mice. In addition, transcription of several senescence and senescence-associated secretory phenotype (SASP) factors in the hippocampal region also decreased after fisetin treatment in the MRL/lpr mice. These results indicate that the accumulation of senescent neural cells in the hippocampus plays a role in NPSLE pathogenesis, and therapies targeting senescent cells may represent a candidate approach to treat NPSLE.
Targeting the CCL2/CCR2 Axis in Cancer Immunotherapy: One Stone, Three Birds?
Authors: Fei Liyang , Ren Xiaochen , Yu Haijia , Zhan Yifan
Published: November 2021

CCR2 is predominantly expressed by monocytes/macrophages with strong proinflammatory functions, prompting the development of CCR2 antagonists to dampen unwanted immune responses in inflammatory and autoimmune diseases. Paradoxically, CCR2-expressing monocytes/macrophages, particularly in tumor microenvironments, can be strongly immunosuppressive. Thus, targeting the recruitment of immunosuppressive monocytes/macrophages to tumors by CCR2 antagonism has recently been investigated as a strategy to modify the tumor microenvironment and enhance anti-tumor immunity. We present here that beneficial effects of CCR2 antagonism in the tumor setting extend beyond blocking chemotaxis of suppressive myeloid cells. Signaling within the CCL2/CCR2 axis shows underappreciated effects on myeloid cell survival and function polarization. Apart from myeloid cells, T cells are also known to express CCR2. Nevertheless, tissue homing of Treg cells among T cell populations is preferentially affected by CCR2 deficiency. Further, CCR2 signaling also directly enhances Treg functional potency. Thus, although Tregs are not the sole type of T cells expressing CCR2, the net outcome of CCR2 antagonism in T cells favors the anti-tumor arm of immune responses. Finally, the CCL2/CCR2 axis directly contributes to survival/growth and invasion/metastasis of many types of tumors bearing CCR2. Together, CCR2 links to two main types of suppressive immune cells by multiple mechanisms. Such a CCR2-assoicated immunosuppressive network is further entangled with paracrine and autocrine CCR2 signaling of tumor cells. Strategies to target CCL2/CCR2 axis as cancer therapy in the view of three types of CCR2-expessing cells in tumor microenvironment are discussed.
Comparative Analysis of Chloroplast Genomes of Seven Chaetoceros Species Revealed Variation Hotspots and Speciation Time
Authors: Xu Qing , Cui Zongmei , Chen Nansheng
Published: November 2021

Chaetoceros is a species-rich diatom genus with broad distribution and plays an important role in global carbon cycle and aquatic ecosystems. However, genomic information of Chaetoceros species is limited, hindering advanced researches on Chaetoceros biodiversity and their differential impact on ecology. In this study, we constructed full-length chloroplast genomes (cpDNAs) for seven Chaetoceros species, including C. costatus, C. curvisetus, C. laevisporus, C. muelleri, C. pseudo-curvisetus, C. socialis, and C. tenuissimus. All of these cpDNAs displayed a typical quadripartite structure with conserved genome arrangement and specific divergence. The sizes of these cpDNAs were similar, ranging from 116,421 to 119,034 bp in size, and these cpDNAs also displayed similar GC content, ranging from 30.26 to 32.10%. Despite extensive synteny conservation, discrete regions showed high variations. Divergence time estimation revealed that the common ancestor of Chaetoceros species, which formed a monophyletic clade at approximately 58 million years ago (Mya), split from Acanthoceras zachariasii at about 70 Mya. The availability of cpDNAs of multiple Chaetoceros species provided valuable reference sequences for studying evolutionary relationship among Chaetoceros species, as well as between Chaetoceros species and other diatom species.
3D Interaction Homology: Computational Titration of Aspartic Acid, Glutamic Acid and Histidine Can Create pH-Tunable Hydropathic Environment Maps
Authors: Herrington Noah B. , Kellogg Glen E.
Published: November 2021

Aspartic acid, glutamic acid and histidine are ionizable residues occupying various protein environments and perform many different functions in structures. Their roles are tied to their acid/base equilibria, solvent exposure, and backbone conformations. We propose that the number of unique environments for ASP, GLU and HIS is quite limited. We generated maps of these residue's environments using a hydropathic scoring function to record the type and magnitude of interactions for each residue in a 2703-protein structural dataset. These maps are backbone-dependent and suggest the existence of new structural motifs for each residue type. Additionally, we developed an algorithm for tuning these maps to any pH, a potentially useful element for protein design and structure building. Here, we elucidate the complex interplay between secondary structure, relative solvent accessibility, and residue ionization states: the degree of protonation for ionizable residues increases with solvent accessibility, which in turn is notably dependent on backbone structure.
Longitudinal Analysis of Brain-Predicted Age in Amnestic and Non-amnestic Sporadic Early-Onset Alzheimer's Disease
Authors: Gautherot Morgan , Kuchcinski Grégory , Bordier Cécile , Sillaire Adeline Rollin , Delbeuck Xavier , Leroy Mélanie , Leclerc Xavier , Pruvo Jean-Pierre , Pasquier Florence , Lopes Renaud
Published: November 2021

Objective:Predicted age difference (PAD) is a score computed by subtracting chronological age from “brain” age, which is estimated using neuroimaging data. The goal of this study was to evaluate the PAD as a marker of phenotypic heterogeneity and severity among early-onset Alzheimer's disease (EOAD) patients.

Methods:We first used 3D T1-weighted (3D-T1) magnetic resonance images (MRI) of 3,227 healthy subjects aged between 18 and 85 years to train, optimize, and evaluate the brain age model. A total of 123 participants who met the criteria for early-onset (<65 years) sporadic form of probable Alzheimer's disease (AD) and presented with two distinctive clinical presentations [an amnestic form (n= 74) and a non-amnestic form (n= 49)] were included at baseline and followed-up for a maximum period of 4 years. All the participants underwent a work-up at baseline and every year during the follow-up period, which included clinical examination, neuropsychological testing and genotyping, and structural MRI. In addition, cerebrospinal fluid biomarker assay was recorded at baseline. PAD score was calculated by applying brain age model to 3D-T1 images of the EOAD patients and healthy controls, who were matched based on age and sex. At baseline, between-group differences for neuropsychological and PAD scores were assessed using linear models. Regarding longitudinal analysis of neuropsychological and PAD scores, differences between amnestic and non-amnestic participants were analyzed using linear mixed-effects modeling.

Results:PAD score was significantly higher for non-amnestic patients (2.35 ± 0.91) when compared to amnestic patients (2.09 ± 0.74) and controls (0.00 ± 1). Moreover, PAD score was linearly correlated with the Mini-Mental State Examination (MMSE) and the Clinical Dementia Rating Sum of Boxes (CDR-SB), for both amnestic and non-amnestic sporadic forms. Longitudinal analyses showed that the gradual development of the disease in patients was accompanied by a significant increase in PAD score over time, for both amnestic and non-amnestic patients.

Conclusion:PAD score was able to separate amnestic and non-amnestic sporadic forms. Regardless of the clinical presentation, as PAD score was a way of quantifying an early brain age acceleration, it was an appropriate method to detect the development of AD and follow the evolution of the disease as a marker of severity as MMSE and CDR-SB.
Neurodegenerative Diseases and Cholesterol: Seeing the Field Through the Players
Authors: Pfrieger Frank W.
Published: November 2021

Neurodegenerative diseases, namely Alzheimer’s (AD), Parkinson’s (PD), and Huntington’s disease (HD) together with amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS), devastate millions of lives per year worldwide and impose an increasing socio-economic burden across nations. Consequently, these diseases occupy a considerable portion of biomedical research aiming to understand mechanisms of neurodegeneration and to develop efficient treatments. A potential culprit is cholesterol serving as an essential component of cellular membranes, as a cofactor of signaling pathways, and as a precursor for oxysterols and hormones. This article uncovers the workforce studying research on neurodegeneration and cholesterol using the TeamTree analysis. This new bibliometric approach reveals the history and dynamics of the teams and exposes key players based on citation-independent metrics. The team-centered view reveals the players on an important field of biomedical research.
Robust Torque Predictions From Electromyography Across Multiple Levels of Active Exoskeleton Assistance Despite Non-linear Reorganization of Locomotor Output
Authors: George Jacob A. , Gunnell Andrew J. , Archangeli Dante , Hunt Grace , Ishmael Marshall , Foreman K. Bo , Lenzi Tommaso
Published: November 2021

Robotic exoskeletons can assist humans with walking by providing supplemental torque in proportion to the user's joint torque. Electromyographic (EMG) control algorithms can estimate a user's joint torque directly using real-time EMG recordings from the muscles that generate the torque. However, EMG signals change as a result of supplemental torque from an exoskeleton, resulting in unreliable estimates of the user's joint torque during active exoskeleton assistance. Here, we present an EMG control framework for robotic exoskeletons that provides consistent joint torque predictions across varying levels of assistance. Experiments with three healthy human participants showed that using diverse training data (from different levels of assistance) enables robust torque predictions, and that a convolutional neural network (CNN), but not a Kalman filter (KF), can capture the non-linear transformations in EMG due to exoskeleton assistance. With diverse training, the CNN could reliably predict joint torque from EMG during zero, low, medium, and high levels of exoskeleton assistance [root mean squared error (RMSE) below 0.096 N-m/kg]. In contrast, without diverse training, RMSE of the CNN ranged from 0.106 to 0.144 N-m/kg. RMSE of the KF ranged from 0.137 to 0.182 N-m/kg without diverse training, and did not improve with diverse training. When participant time is limited, training data should emphasize the highest levels of assistance first and utilize at least 35 full gait cycles for the CNN. The results presented here constitute an important step toward adaptive and robust human augmentation via robotic exoskeletons. This work also highlights the non-linear reorganization of locomotor output when using assistive exoskeletons; significant reductions in EMG activity were observed for the soleus and gastrocnemius, and a significant increase in EMG activity was observed for the erector spinae. Control algorithms that can accommodate spatiotemporal changes in muscle activity have broad implications for exoskeleton-based assistance and rehabilitation following neuromuscular injury.
Virtual Flow-T Stenting for Two Patient-Specific Bifurcation Aneurysms
Authors: Lyu Mengzhe , Ventikos Yiannis , Peach Thomas W. , Makalanda Levansri , Bhogal Pervinder
Published: November 2021

The effective treatment of wide necked cerebral aneurysms located at vessel bifurcations (WNBAs) remains a significant challenge. Such aneurysm geometries have typically been approached with Y or T stenting configurations of stents and/or flow diverters, often with the addition of endovascular coils. In this study, two WNBAs were virtually treated by a novel T-stenting technique (Flow-T) with a number of braided stents and flow-diverter devices. Multiple possible device deployment configurations with varying device compression levels were tested, using fast-deployment algorithms, before a steady state computational hemodynamic simulation was conducted to examine the efficacy and performance of each scenario. The virtual fast deployment algorithm based on a linear and torsional spring analogy is used to accurately deploy nine stents in two WNBAs geometries. The devices expand from the distal to proximal side of the devices with respect to aneurysm sac. In the WNBAs modelled, all configurations of Flow-T device placement were shown to reduce factors linked with increased aneurysm rupture risk including aneurysm inflow jets and high aneurysm velocity, along with areas of flow impingement and elevated wall shear stress (WSS). The relative position of the flow-diverting device in the secondary daughter vessel in the Flow-T approach was found to have a negligible effect on overall effectiveness of the procedure in the two geometries considered. The level of interventionalist-applied compression in the braised stent that forms the other arm of the Flow-T approach was shown to impact the aneurysm inflow reduction and aneurysm flow pattern more substantially. In the Flow-T approach the relative position of the secondary daughter vessel flow-diverter device (the SVB) was found to have a negligible effect on inflow reduction, aneurysm flow pattern, or WSS distribution in both aneurysm geometries. This suggests that the device placement in this vessel may be of secondary importance. By contrast, substantially more variation in inflow reduction and aneurysm flow pattern was seen due to variations in braided stent (LVIS EVO or Baby Leo) compression at the aneurysm neck. As such we conclude that the success of a Flow-T procedure is primarily dictated by the level of compression that the interventionalist applies to the braided stent. Similar computationally predicted outcomes for both aneurysm geometries studied suggest that adjunct coiling approach taken in the clinical intervention of the second geometry may have been unnecessary for successful aneurysm isolation. Finally, the computational modelling framework proposed offers an effective planning platform for complex endovascular techniques, such as Flow-T, where the scope of device choice and combination is large and selecting the best strategy and device combination from several candidates is vital.
U-Shaped Association of Aspect Ratio and Single Intracranial Aneurysm Rupture in Chinese Patients: A Cross-Sectional Study
Authors: Yin Jia-He , Su Shi-Xing , Zhang Xin , Bi Yi-Ming , Duan Chuan-Zhi , Huang Wei-mei , Wang Xi-Long
Published: November 2021

Background: Previous studies have analyzed the association of aspect ratio (AR) on the ruptured intracranial aneurysm (IA), but the findings are inconclusive and controversial. Therefore, the study aimed to derive a more detailed estimation of this association between AR and ruptured IA in Chinese IA patients.

Methods: The present work was a cross-sectional study. We retrospectively collected 1,588 Chinese patients with a single IA from January 2010 to November 2017. The relationship was examined between AR at diagnosis and ruptured IA. Covariates included data of demographics, morphological parameters, lifestyle habits, clinical features, and comorbidities. Binary logistic regression and two-piecewise linear models were used to analyze independent associations of AR with ruptured IA.

Results: The results suggest that the association between AR and IA rupture was U-shaped. In the AR range of 1.08–1.99, the prevalence of IA rupture was 13% lower for each 0.1-unit increment in AR [odds ratio 0.87, 95% confidence interval (CI) 0.80–0.98]. Conversely, for every 0.1-unit increase in AR, the prevalence of IA rupture increased by ~3% (odds ratio 1.03, 95% CI 1.01–1.06) in the AR range of 3.42–4.08.

Conclusion: The relationship between AR and ruptured IA was U-shaped, with the negative association at AR of 1.08–1.99 and positive association at AR of 3.42–4.08.