bluuebunny/crossref_metadata_2025 huggingface dataset:
MMS22L Expression as a Predictive Biomarker for the Efficacy of Neoadjuvant Chemoradiotherapy in Oesophageal Squamous Cell Carcinoma
Authors: Luo Qiyu , He Wenwu , Mao Tianqin , Leng Xuefeng , Wu Hong , Li Wen , Deng Xuyang , Zhao Tingci , Shi Ming , Xu Chuan , Han Yongtao
Published: September 2021

Long-term survival in oesophageal squamous cell carcinoma (ESCC) is related with pathological response after neoadjuvant chemoradiotherapy (NCRT) followed by surgery. However, effective biomarkers to predict the pathologic response are still lacking. Therefore, a systematic analysis focusing on genes associated with the efficacy of chemoradiotherapy in ESCC will provide valuable insights into the regulation of molecular processes. By screening publications deposited in PubMed, we collected genes associated with the efficacy of chemoradiotherapy. A specific subnetwork was constructed using the Steiner minimum tree algorithm. Survival analysis in Kaplan-Meier Plotter online resources was performed to explore the relationship between gene mRNA expression and the prognosis of patients with ESCC. Quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemical staining (IHC) were used to evaluate the expression of key genes in cell lines and human samples. The areas under the receiver operating characteristic (ROC) curves (AUCs) were used to describe performance and accuracy. Transwell assays assessed cell migration, and cell viability was detected using the Cytotoxicity Assay. Finally, we identified 101 genes associated with efficacy of chemoradiotherapy. Additionally, specific molecular networks included some potential related genes, such as CUL3, MUC13, MMS22L, MME, UBC, VAPA, CYP1B1, and UGDH. The MMS22L mRNA expression level showed the most significant association with the ESCC patient outcome (p < 0.01). Furthermore, MMS22L was downregulated at both the mRNA (p < 0.001) and protein levels in tumour tissues compared with that in normal tissues. Lymph node metastasis was significantly associated with low MMS22L expression (p < 0.01). MMS22L levels were inversely correlated with the NCRT response in ESCC (p < 0.01). The resulting area under the ROC curve was 0.847 (95% CI: 0.7232 to 0.9703; p < 0.01). In conclusion, low expression of MMS22L is associated with poor response to NCRT, worse survival, lymph node metastasis, and enhanced migration of tumour cells in ESCC.
Status Quo and Research Trends of Craniopharyngioma Research: A 10-Year Bibliometric Analyses (From 2011 to 2020)
Authors: Li Tianhua , Yang Anming , Liu Guangjie , Zou Shisheng , Chen Yiguang , Ni Bowen , Liu Yi , Fan Jun
Published: September 2021

Background

Craniopharyngioma (CP) is a challenging intracranial tumor due to its special hypothalamus-pituitary location. Each patient with CP should be evaluated and treated separately. Exploring novel methods of automatized analysis of data for gaining knowledge on any medical field is an encouraging task, particularly in such an extremely challenging tumor as CP. We aim to summary the situations, investigate the research trends and evaluate research hotspots using bibliometric analysis for the CP research.

Methods

We extracted all the CP-related literatures from 2011 to 2020 from the Web of Science database. An Online analysis platform of literature metrology (Bibliometric), BICOMB, gCLUTO and CiteSpace softwares were used to do bibliometric analysis. As a supplement, we also analyzed the top 100 cited case reports with particular and certainly infrequent information to improve the analysis.

Results

According to our retrieval strategy, we found a total of 1262 CP-related literatures. The United States has maintained a leading position in global CP research, followed by China and Germany. Among institutions, Capital Med Univ, St Jude Childrens Res Hosp and Southern Med Univ rank in the top 3 in terms of the number of articles published. “WORLD NEUROSURGERY” is the most popular journal for CP-related research. Moreover, MULLER HL, MERCHANT TE, QI ST and others have made great achievements in the study of CP. Finally, we did biclustering analysis on keywords and identified 4 CP research hotspot clusters.

Conclusions

Our research provides a comprehensive analysis of the scientific progress of CP in the past 10 years, and insight into the development of CP research field, highlight research trends over time, and help identify valuable future directions.
Biomarkers in Acute Myeloid Leukemia: Leveraging Next Generation Sequencing Data for Optimal Therapeutic Strategies
Authors: El Achi Hanadi , Kanagal-Shamanna Rashmi
Published: September 2021

Next generation sequencing (NGS) is routinely used for mutation profiling of acute myeloid leukemia. The extensive application of NGS in hematologic malignancies, and its significant association with the outcomes in multiple large cohorts constituted a proof of concept that AML phenotype is driven by underlying mutational signature and is amenable for targeted therapies. These findings urged incorporation of molecular results into the latest World Health Organization (WHO) sub-classification and integration into risk-stratification and treatment guidelines by the European Leukemia Net. NGS mutation profiling provides a large amount of information that guides diagnosis and management, dependent on the type and number of gene mutations, variant allele frequency and amenability to targeted therapeutics. Hence, molecular mutational profiling is an integral component for work-up of AML and multiple leukemic entities. In addition, there is a vast amount of informative data that can be obtained from routine clinical NGS sequencing beyond diagnosis, prognostication and therapeutic targeting. These include identification of evidence regarding the ontogeny of the disease, underlying germline predisposition and clonal hematopoiesis, serial monitoring to assess the effectiveness of therapy and resistance mutations, which have broader implications for management. In this review, using a few prototypic genes in AML, we will summarize the clinical applications of NGS generated data for optimal AML management, with emphasis on the recently described entities and Food and Drug Administration approved target therapies.
TIM-3 in Leukemia; Immune Response and Beyond
Authors: Rezaei Mahnaz , Tan Jiaxiong , Zeng Chengwu , Li Yangqiu , Ganjalikhani-Hakemi Mazdak
Published: September 2021

T cell immunoglobulin and mucin domain 3 (TIM-3) expression on malignant cells has been reported in some leukemias. In myelodysplastic syndrome (MDS), increased TIM-3 expression on TH1 cells, regulatory T cells, CD8+ T cells, and hematopoietic stem cells (HSCs), which play a role in the proliferation of blasts and induction of immune escape, has been reported. In AML, several studies have reported overexpression of TIM-3 on leukemia stem cells (LSCs) but not on healthy HSCs. Overexpression of TIM-3 on exhausted CD4+ and CD8+ T cells and leukemic cells in CML, ALL, and CLL patients could be a prognostic risk factor for poor therapeutic response and relapse in patients. Currently, several TIM-3 inhibitors are used in clinical trials for leukemias, and some have shown encouraging response rates for MDS and AML treatment. For AML immunotherapy, blockade TIM-3 may have dual effects: directly inhibiting AML cell proliferation and restoring T cell function. However, blockade of PD-1 and TIM-3 fails to restore the function of exhausted CD8+ T cells in the early clinical stages of CLL, indicating that the effects of TIM-3 blockade may be different in AML and other leukemias. Thus, further studies are required to evaluate the efficacy of TIM-3 inhibitors in different types and stages of leukemia. In this review, we summarize the biological functions of TIM-3 and its contribution as it relates to leukemias. We also discuss the effects of TIM-3 blockade in hematological malignancies and clinical trials of TIM-3 for leukemia therapy.
Long Non-Coding RNA GRIK1-AS1 Inhibits the Proliferation and Invasion of Gastric Cancer Cells by Regulating the miR-375/IFIT2 Axis
Authors: Zhou Qi , Li Yuan , Chen Lujun , Zheng Xiao , Jiang Tianwei , Liu Juan , Fu Yuanyuan , Guan Liping , Ju Jingfang , Wu Changping
Published: September 2021

Long non-coding RNAs (lncRNAs) play important roles in various biological processes and human diseases, including cancer. In this study, we demonstrated a regulatory relationship between lncRNA GRIK1-AS1 and miR-375/IFIT2 axis in gastric cancer. Our results show a decreased expression of GRIK1-AS1 in gastric cancer tissues compared to adjacent normal gastric tissues. Gastric cell lines also have reduced levels of GRIK1-AS1 compared to gastric epithelial cell line GES-1. Ectopic expression of GRIK1-AS1 in gastric cancer cell lines significantly inhibits cellular viability, migration, and invasion. RNA-pull down and the luciferase activity assays show that GRIK1-AS1 mainly interacts specifically with miR-375. We further demonstrate a negatively regulatory relationship between lncRNA GRIK1-AS1 and miR-375. We discovered that IFIT2 was one of the direct key downstream target genes of miR-375, and established the important role of the GRIK1-AS1/miR-375/IFIT2 axis in the progression of gastric cancer. Taken together, our results revealed a novel mechanism of GRIK1-AS1 as a sponge to miR-375 that impacts gastric cancer progression via modulating target mRNA IFIT2 translation, and as a result, opens a new strategy to future GRIK1-AS1 based therapeutic development.
Availability and Utilization of Automated External Defibrillators in New York State Schools
Authors: Arabadjian Milla , Serrato Stephanie , Sherrid Mark V.
Published: September 2021

Background: Use of automated external defibrillators (AEDs) in out-of-hospital cardiac arrests (OHCAs) improve survival. Professional health organizations recommend that AEDs be available in crowded places, including schools but currently only 18 US states require them. Sudden cardiac arrest (SCA) research in the school-age population has largely focused on school sub-groups, leaving out the majority of US students and adults working in schools. New York State (NYS) has one of the largest student populations in the US. Our objective was to gain epidemiologic data on SCA across a variety of school levels and examine the availability and utilization of AEDs in a state that requires them.

Methods: This was an observational, cross-sectional study utilizing an electronic survey. We included NYS school nurses and collected electronic surveys in January-March, 2018. We analyzed demographic data of school characteristics, SCA occurrences and AED use and availability.

Results: Of 876 respondents (36.1% response rate), 71 (8.2%) reported SCAs, with 41 occurring in adults. AEDs were deployed in 59 of 71 (84.3%) events, 40 individuals had long-term survival. Most SCAs occurred in middle-schools. School size or number of AEDs/school had no bearing on short-term or long-term survival. AEDs were widely available in private schools, though this was not required by state law.

Conclusions: Our data suggest a need for more comprehensive examination of SCA in US schools. Research comparing the availability and utilization of school AEDs between states that do and do not require them is needed and may have important clinical and policy implications for SCA emergency preparedness in US schools.
Prediction of Coronary Artery Aneurysms in Children With Kawasaki Disease Before Starting Initial Treatment
Authors: Huang Ching-Ying , Chiu Nan-Chang , Huang Fu-Yuan , Chao Yen-Chun , Chi Hsin
Published: September 2021

Background:Precisely predicting coronary artery aneurysms (CAAs) remains a clinical challenge. We aimed to investigate whether coronary dimensions adjusted for body surface area (Z scores) on baseline echocardiography and clinical variables before primary treatment could predict the presence of late CAAs.

Methods:We conducted a retrospective study including children hospitalized for Kawasaki disease and received intravenous immunoglobulin within 10 days of illness. We defined late CAAs as a maximum Z score (Zmax) ≥2.5 of the left main, right, or left anterior descending coronary artery at 11–60 days of illness. Associations between late CAAs and clinical parameters and baseline maximum Z scores were analyzed.

Results:Among the 314 included children, 31 (9.9%) had late CAAs. Male, higher C-reactive protein, and higher baseline Zmax were risk factors of late CAAs. Late CAAs were significantly associated with baseline Zmax ≥2.0 vs. <2.0 (25 [32.5%] vs. 6 [2.5%],P< 0.001). The odds ratio for late CAAs among the patients with baseline Zmax ≥2.0 vs. <2.0 was 18.5 (95% confidence interval, 7.23 to 47.41,P< 0.001). The sensitivity, specificity, positive predictive value, and negative predictive value of baseline Zmax ≥2.0 for the presence of later CAAs were 80.6, 81.6, 32.5, and 97.5%, respectively.

Conclusions:Findings from this study suggest that Zmax ≥2.0 of coronary arteries on baseline echocardiography may be used to predict children at a high risk of late CAAs and allow for targeted early intensification therapy.
Case Report: Transcatheter Closure of Ruptured Sinus of Valsalva With Ventricular Septal Defect Occluder in a 3-Year-Old Child After Repair of Ventricular Septal Defect
Authors: Gong Xueyang , Wang Jundao , Wei Luyao , Zhao Tianli , Hu Shijun
Published: September 2021

Sinus of Valsalva aneurysm (SVA) is a rare cardiac anomaly that can undergo spontaneous rupture into other cardiac chambers or the pericardial space. A ruptured SVA has a very poor prognosis with high morbidity and mortality. These aneurysms often present as a rupture from the right coronary sinus into the right ventricle. Transcatheter closure has become an effective alternative to surgical treatment. However, it has been rarely reported in patients after ventricular defect repair in the past. We here describe a 3-year-and-3-month-old boy who was found to have a ruptured sinus of Valsalva. He underwent surgical closure of a ventricular septal defect at the age of 2 months, which occurred in the non-coronary sinus (NCS) and ruptured into the right atrium. We successfully occluded the ruptured sinus of Valsalva with a ventricular septal occluder.
Neuromodulatory Support for Breathing and Cardiovascular Action During Development
Authors: Harper Ronald M. , Kesavan Kalpashri
Published: September 2021

Neonatal survival requires precise control of breathing and cardiovascular action, with fatal consequences or severe injury without support. Prematurity presents multiple opportunities to disrupt cardiorespiratory regulation, leading to expressions of apnea of prematurity, periodic breathing, and inappropriate cardiovascular responses to apnea. Failed breathing control can result from altered breathing drives, typically arising from untimely development of sensory or motor coordination processes. Some drives, such as temperature, are a special concern in neonates with low body mass, enhancing susceptibility to rapid body cooling. Chemical drives, such as pH or CO2 or O2, may be inadequately developed; in some conditions, such as congenital central hypoventilation syndrome (CCHS), breathing responses to CO2 or low O2 may be reduced or absent, and coupling of cardiovascular responses to breathing changes are abolished. Sleep states exert profound influences on both chemical and temperature drives, with rapid eye movement (REM) sleep potentially modifying descending temperature influences, and state transitions significantly altering respiratory responses to chemical stimuli. In addition, neonates spend the majority of time in REM sleep, a state which induces a generalized inhibition of skeletal muscle activity that abolishes muscle tone to upper airway and thoracic wall muscles, enhancing the likelihood for obstructive sleep apnea. Although disrupted regulatory drives can often be replaced by positive (or negative) pressure ventilation, such as continuous positive airway pressure or enhanced by manipulating neurotransmitter action via caffeine, those approaches may exert negative consequences in the long term; the lungs of neonates, especially premature infants, are fragile, and easily injured by positive pressure. The consequences of caffeine use, acting directly on neural receptors, although seemingly innocuous in the near-term, may have long-term concerns and disrupts the integrity of sleep. The developmental breathing field needs improved means to support ventilation when one or more drives to respiration fail, and when the cardiovascular system, depending heavily on interactions with breathing, is compromised. Neuromodulatory procedures which manipulate the vestibular system to stabilize breathing or use tactile or proprioceptive stimuli to activate long-established reflexive mechanisms coupling limb movement with respiratory efforts can provide support for central and obstructive apnea, as well as for periodic breathing and cardiovascular action, particularly during sleep.
Intermittent Fasting Inhibits High-Fat Diet–Induced Atherosclerosis by Ameliorating Hypercholesterolemia and Reducing Monocyte Chemoattraction
Authors: Chen Yuanli , Su Jiamin , Yan Yali , Zhao Qian , Ma Jialing , Zhu Mengmeng , He Xiaoyu , Zhang Baotong , Xu Hongmei , Yang Xiaoxiao , Duan Yajun , Han Jihong
Published: September 2021

Atherosclerosis is a major pathology for cardiovascular diseases (CVDs). Clinically, the intermittent fasting (IF) has been observed to reduce the risk of CVDs. However, the effect of IF on the development of atherosclerosis has not been fully elucidated. Herein, we determined the protection of IF against high-fat diet–induced atherosclerosis in pro-atherogenic low-density lipoprotein receptor deficient (LDLR-/-) mice and the potentially involved mechanisms. The LDLR-/- mice were scheduled intermittent fasting cycles of 3-day HFD feeding ad libitum and 1 day fasting, while the mice in the control group were continuously fed HFD. The treatment was lasted for 7 weeks (∼12 cycles) or 14 weeks (∼24 cycles). Associated with the reduced total HFD intake, IF substantially reduced lesions in the en face aorta and aortic root sinus. It also increased plaque stability by increasing the smooth muscle cell (SMC)/collagen content and fibrotic cap thickness while reducing macrophage accumulation and necrotic core areas. Mechanistically, IF reduced serum total and LDL cholesterol levels by inhibiting cholesterol synthesis in the liver. Meanwhile, HFD-induced hepatic lipid accumulation was attenuated by IF. Interestingly, circulating Ly6Chigh monocytes but not T cells and serum c-c motif chemokine ligand 2 levels were significantly reduced by IF. Functionally, adhesion of monocytes to the aortic endothelium was decreased by IF via inhibiting VCAM-1 and ICAM-1 expression. Taken together, our study indicates that IF reduces atherosclerosis in LDLR-/- mice by reducing monocyte chemoattraction/adhesion and ameliorating hypercholesterolemia and suggests its potential application for atherosclerosis treatment.
Hydroxysafflor Yellow A and Anhydrosafflor Yellow B Protect Against Cerebral Ischemia/Reperfusion Injury by Attenuating Oxidative Stress and Apoptosis via the Silent Information Regulator 1 Signaling Pathway
Authors: Fangma Yijia , Zhou Huifen , Shao Chongyu , Yu Li , Yang Jiehong , Wan Haitong , He Yu
Published: September 2021

Hydroxysafflor yellow A (HSYA) and anhydrosafflor yellow B (AHSYB) are the main water-soluble compounds in Carthamus tinctorius L. However, studies on the effect of AHSYB on cerebral ischemia/reperfusion (I/R) injury and the therapeutic effect of HSYA by regulating silent information regulator 1 (SIRT1) pathway remain obscure. In this study, we investigated whether the neuroprotective effects of HSYA and AHSYB on oxygen-glucose deprivation/reoxygenation in primary-cultured hippocampal neuronal cells and the middle cerebral artery occlusion and reperfusion model in rats are associated with the regulation of the SIRT1 pathway. In vitro, HSYA and AHSYB increased cell viability, depressed oxidation properties, and reduced neuronal cell apoptosis. In vivo results showed that HSYA and AHSYB effectively reduced infarct volume, improved neurological function, suppressed apoptosis, and decreased the oxidative stress reaction. Besides, RT-PCR and Western blot analysis showed that HSYA and AHSYB increased the mRNA and protein expressions of the main factors in the SIRT1 pathway, including SIRT1, forkhead box O (FOXO) 1, and peroxisome proliferator–activated receptor coactivator 1α (PGC1α), decreased the expression of Bax, and increased the expression of Bcl-2. The results from immunohistochemistry also showed that the expressions of SIRT1, FOXO1, and PGC1α were increased after treatment with HSYA and AHSYB. Furthermore, the neuroprotective effects of HSYA and AHSYB were abolished by EX527 (SIRT1–specific inhibitor). These results indicated that HSYA and AHSYB should be developed into potential drugs for treating cerebral I/R injury via the SIRT1 pathway. Although HSYA and AHSYB have different chemical structures, both of them exert similar neuroprotective properties against I/R injury in vitro and in vivo, which means that AHSYB is also a non-negligible component in safflower.
Magnetic Skyrmion Generation by Reflective Spin Wave Focusing
Authors: Yao Xianglong , Wang Zhenyu , Deng Menghua , Li Z.-X. , Zhang Zhizhi , Cao Yunshan , Yan Peng
Published: September 2021

We propose a method to generate magnetic skyrmions by focusing spin waves totally reflected by a curved film edge. The edge contour is derived to be parabolic and frequency-independent based on the identical magnonic path length principle. We performed micromagnetic simulations to verify our theoretical design. Under proper conditions, the reflected spin waves first converge at the focal point with the enhanced intensity leading to the emergence of magnetic droplets, which are then converted to magnetic skyrmion accompanied by a change in the topological charge. We numerically obtain the phase diagram of skyrmion generation with respect to the amplitude and frequency of the driving field. Our finding would be helpful for the design of spintronic devices combining the advantage of skyrmionics and magnonics.
MicroRNA-195-5p Downregulation Inhibits Endothelial Mesenchymal Transition and Myocardial Fibrosis in Diabetic Cardiomyopathy by Targeting Smad7 and Inhibiting Transforming Growth Factor Beta 1-Smads-Snail Pathway
Authors: Ding Huaisheng , Yao Jianhui , Xie Hongxiang , Wang Chengyu , Chen Jing , Wei Kaiyong , Ji Yangyang , Liu Lihong
Published: September 2021

Diabetic cardiomyopathy (DCM) is a complication of diabetes mellitus, which is associated with fibrosis and microRNAs (miRs). This study estimated the mechanism of miR-195-5p in endothelial mesenchymal transition (EndMT) and myocardial fibrosis in DCM. After the establishment of DCM rat models, miR-195-5p was silenced by miR-195-5p antagomir. The cardiac function-related indexes diastolic left ventricular anterior wall (LVAW, d), systolic LVAW (d), diastolic left ventricular posterior wall (LVPW, d), systolic LVPW (d), left ventricular ejection fraction (LVEF), and fractional shortening (FS) were measured and miR-195-5p expression in myocardial tissue was detected. Myocardial fibrosis, collagen deposition, and levels of fibrosis markers were detected. Human umbilical vein endothelial cells (HUVECs) were exposed to high glucose (HG) and miR-195-5p was silenced. The levels of fibrosis proteins, endothelial markers, fibrosis markers, EndMT markers, and transforming growth factor beta 1 (TGF-β1)/Smads pathway-related proteins were measured in HUVECs. The interaction between miR-195-5p and Smad7 was verified. In vivo, miR-195-5p was highly expressed in the myocardium of DCM rats. Diastolic and systolic LVAW, diastolic and systolic LVPW were increased and LVEF and FS were decreased. Inhibition of miR-195-5p reduced cardiac dysfunction, myocardial fibrosis, collagen deposition, and EndMT, promoted CD31 and VE-cadehrin expressions, and inhibited α-SMA and vimentin expressions. In vitro, HG-induced high expression of miR-195-5p and the expression changes of endothelial markers CD31, VE-cadehrin and fibrosis markers α-SMA and vimentin were consistent with those in vivo after silencing miR-195-5p. In mechanism, miR-195-5p downregulation blocked EndMT by inhibiting TGF-β1-smads pathway. Smad7 was the direct target of miR-195-5p and silencing miR-195-5p inhibited EndMT by promoting Smad7 expression. Collectively, silencing miR-195-5p inhibits TGF-β1-smads-snail pathway by targeting Smad7, thus inhibiting EndMT and alleviating myocardial fibrosis in DCM.
A Comparison of the Effects of Foam Rolling and Stretching on Physical Performance. A Systematic Review and Meta-Analysis
Authors: Konrad Andreas , Tilp Markus , Nakamura Masatoshi
Published: September 2021

Foam rolling and stretching with its various techniques are frequently used as a warm-up routine to increase the range of motion of a joint. While the magnitude of the changes in range of motion between foam rolling and stretching (static and dynamic techniques) is similar, it is not clear if this also holds true for performance parameters (e.g., strength, jump height). The purpose of this meta-analysis was to compare the effects of an acute bout of foam rolling (with and without vibration) with an acute bout of stretching (with all techniques included) on performance parameters in healthy participants. We assessed the results from 13 studies and 35 effect sizes by applying a random-effect meta-analysis. Moreover, by applying a mixed-effect model, we performed subgroup analyses with the stretching technique, type of foam rolling, tested muscle, treatment duration, and type of task. We found no significant overall effect, and the analysis revealed only a trend of the performance parameters in favor of foam rolling when compared to stretching (when considering all techniques). Significantly favorable effects of foam rolling on performance were detected with subgroup analyses when compared to static stretching, when applied to some muscles (e.g., quadriceps) or some tasks (e.g., strength), when applied for longer than 60 s, or when the foam rolling included vibration. When foam rolling was compared to dynamic stretching or applied in the non-vibration mode, the same magnitude of effect was observed. While the present meta-analysis revealed no significantly different effect between foam rolling and stretching (including all techniques) prior to exercise, differences could be observed under specific conditions.
Discovering Myeloid Cell Heterogeneity in Mandibular Bone – Cell by Cell Analysis
Authors: Kwack Kyu Hwan , Lamb Natalie A. , Bard Jonathan E. , Kramer Elliot D. , Zhang Lixia , Abrams Scott I. , Kirkwood Keith L.
Published: September 2021

The myeloid-derived bone marrow progenitor populations from different anatomical locations are known to have diverse osteoclastogenesis potential. Specifically, myeloid progenitors from the tibia and femur have increased osteoclast differentiation potential compared to myeloid progenitors from the alveolar process. In this study, we explored the differences in the myeloid lineage progenitor cell populations in alveolar (mandibular) bone versus long (femur) bone using flow cytometry and high-throughput single cell RNA sequencing (scRNA-seq) to provide a comprehensive transcriptional landscape. Results indicate that mandibular bone marrow-derived cells exhibit consistent deficits in myeloid differentiation, including significantly fewer myeloid-derived suppressor cell (MDSC)-like populations (CD11b+Ly6C+, CD11b+Ly6G+), as well as macrophages (CD11b+F4/80+). Although significantly fewer in number, MDSCs from mandibular bone exhibited increased immunosuppressive activity compared to MDSCs isolated from long bone. Using flow cytometry panels specific for bone marrow progenitors, analysis of hematopoietic stem cells showed no defects in mandibular bone marrow in LSK (Lin–Sca1+cKit+) cell and LK (Lin–Sca1–cKit+) cell populations. While there was no significant difference in granulocyte progenitors, the granulocyte-monocyte progenitors and monocyte progenitor population were significantly decreased in the mandibular bone marrow. T-lymphocyte subsets were not significantly different between mandibular and femoral bone, except for CD4+CD25+Foxp3+ regulatory T lymphocytes, which were significantly increased in the mandible. In addition, B lymphocytes were significantly increased in mandible. Single cell RNA sequencing from mandible and femur BM revealed distinct differences in transcriptomic profiles in myeloid populations establishing previously unappreciated aspects of mandibular bone marrow populations. These analyses reveal site-specific differences in the myeloid progenitor cellular composition and transcriptional programs providing a deeper appreciation of the complex differences in myeloid cell heterogeneity from different anatomical bone marrow sites.
Ulk1, Not Ulk2, Is Required for Exercise Training-Induced Improvement of Insulin Response in Skeletal Muscle
Authors: Drake Joshua C. , Wilson Rebecca J. , Cui Di , Guan Yuntian , Kundu Mondira , Zhang Mei , Yan Zhen
Published: September 2021

Unc51 like autophagy activating kinase 1 (Ulk1), the primary autophagy regulator, has been linked to metabolic adaptation in skeletal muscle to exercise training. Here we compared the roles of Ulk1 and homologous Ulk2 in skeletal muscle insulin action following exercise training to gain more mechanistic insights. Inducible, skeletal muscle-specific Ulk1 knock-out (Ulk1-iMKO) mice and global Ulk2 knock-out (Ulk2–/–) mice were subjected to voluntary wheel running for 6 weeks followed by assessment of exercise capacity, glucose tolerance, and insulin signaling in skeletal muscle after a bolus injection of insulin. Both Ulk1-iMKO and Ulk2–/– mice had improved endurance exercise capacity post-exercise. Ulk1-iMKO did not improve glucose clearance during glucose tolerance test, while Ulk2–/– had only marginal improvement. However, exercise training-induced improvement of insulin action in skeletal muscle, indicated by Akt-S473 phosphorylation, was only impaired in Ulk1-iMKO. These data suggest that Ulk1, but not Ulk2, is required for exercise training-induced improvement of insulin action in skeletal muscle, implicating crosstalk between catabolic and anabolic signaling as integral to metabolic adaptation to energetic stress.
Uncertainty Quantification of Regional Cardiac Tissue Properties in Arrhythmogenic Cardiomyopathy Using Adaptive Multiple Importance Sampling
Authors: van Osta Nick , Kirkels Feddo P. , van Loon Tim , Koopsen Tijmen , Lyon Aurore , Meiburg Roel , Huberts Wouter , Cramer Maarten J. , Delhaas Tammo , Haugaa Kristina H. , Teske Arco J. , Lumens Joost
Published: September 2021

Introduction: Computational models of the cardiovascular system are widely used to simulate cardiac (dys)function. Personalization of such models for patient-specific simulation of cardiac function remains challenging. Measurement uncertainty affects accuracy of parameter estimations. In this study, we present a methodology for patient-specific estimation and uncertainty quantification of parameters in the closed-loop CircAdapt model of the human heart and circulation using echocardiographic deformation imaging. Based on patient-specific estimated parameters we aim to reveal the mechanical substrate underlying deformation abnormalities in patients with arrhythmogenic cardiomyopathy (AC).

Methods: We used adaptive multiple importance sampling to estimate the posterior distribution of regional myocardial tissue properties. This methodology is implemented in the CircAdapt cardiovascular modeling platform and applied to estimate active and passive tissue properties underlying regional deformation patterns, left ventricular volumes, and right ventricular diameter. First, we tested the accuracy of this method and its inter- and intraobserver variability using nine datasets obtained in AC patients. Second, we tested the trueness of the estimation using nine in silico generated virtual patient datasets representative for various stages of AC. Finally, we applied this method to two longitudinal series of echocardiograms of two pathogenic mutation carriers without established myocardial disease at baseline.

Results: Tissue characteristics of virtual patients were accurately estimated with a highest density interval containing the true parameter value of 9% (95% CI [0–79]). Variances of estimated posterior distributions in patient data and virtual data were comparable, supporting the reliability of the patient estimations. Estimations were highly reproducible with an overlap in posterior distributions of 89.9% (95% CI [60.1–95.9]). Clinically measured deformation, ejection fraction, and end-diastolic volume were accurately simulated. In presence of worsening of deformation over time, estimated tissue properties also revealed functional deterioration.

Conclusion: This method facilitates patient-specific simulation-based estimation of regional ventricular tissue properties from non-invasive imaging data, taking into account both measurement and model uncertainties. Two proof-of-principle case studies suggested that this cardiac digital twin technology enables quantitative monitoring of AC disease progression in early stages of disease.
Iron Is Filtered by the Kidney and Is Reabsorbed by the Proximal Tubule
Authors: Wareing Mark , Smith Craig P.
Published: September 2021

The aim of this study was to determine the iron (Fe) concentration profile within the lumen of the S2 renal proximal convoluted tubule (PCT) and to resolve whether this nephron segment transported Fe. To do this, we performed in vivo renal micropuncture on Wistar rats, collected PCT tubular fluid from superficial nephrons, and measured Fe concentration. The Fe concentration profile along the S2 PCT suggested significant Fe reabsorption. Proximal tubules were also microperfused in vivo with physiological solutions containing Fe and Zn, Cu, Mn, or Cd. PCTs perfused with 12μmol.l−1 55FeCl3 reabsorbed 105.2±12.7 fmol.mm−1.min−1 Fe, 435±52pmol.mm-1.min−1 Na, and 2.7±0.2nl.mm−1.min−1 water (mean ± SEM; n=19). Addition of ascorbate (1mmol.l−1) to the perfusate did not significantly alter Fe, Na, or water reabsorption. Supplementing the control perfusate with 60μmol.l−1 FeSO4 significantly decreased 55Fe uptake. Recalculating for the altered molar activity following addition of unlabeled Fe revealed a three-fold increase in Fe flux. Addition to the perfusate 12μmol.l−1 CuSO4, MnSO4, CdSO4, or ZnSO4 did not affect Fe, Na, or water flux. In conclusion, (1) in vivo, S2 PCTs of rat reabsorb Fe and (2) Fe is reabsorbed along the PCT via a pathway that is insensitive to Cu, Mn, Cd, or Zn. Together, these data demonstrate for the first time the hitherto speculated process of renal Fe filtration and subsequent tubular Fe reabsorption in a living mammal.
Uniform Water Potential Induced by Salt, Alkali, and Drought Stresses Has Different Impacts on the Seedling of Hordeum jubatum: From Growth, Photosynthesis, and Chlorophyll Fluorescence
Authors: Shi Congcong , Yang Fan , Liu Zihao , Li Yueming , Di Xiaolin , Wang Jinghong , Lin Jixiang
Published: September 2021

Hordeum jubatum is a halophyte ornamental plant wildly distributed in the Northeast of China, where the low water potential induced by various abiotic stresses is a major factor limiting plant growth and development. However, little is known about the comparative effects of salt, alkali, and drought stresses at uniform water potential on the plants. In the present study, the growth, gas exchange parameters, photosynthetic pigments, and chlorophyll fluorescence in the seedlings of H. jubatum under three low water potentials were measured. The results showed that the growth and photosynthetic parameters under these stresses were all decreased except for carotenoid (Car) with the increasing of stress concentration, and alkali stress caused the most damaging effects on the seedlings. The decreased net photosynthetic rate (Pn), stomatal conductance (Gs), and intercellular CO2 concentrations (Ci) values under salt stress were mainly attributed to stomatal factors, while non-stomatal factors were dominate under drought and alkali stresses. The reduced chlorophyll and slightly increased Car contents occurred under these stresses, and most significant changed under alkali stress. In addition, the maximum photochemical efficiency (Fv/Fm), actual photochemical efficiency (ΦPSII), and photochemical quenching coefficient (qP) under the stresses were all decreased, indicating that salt, alkali, and drought stresses all increased susceptibility of PSII to photoinhibition, reduced the photosynthetic activity by the declined absorption of light for photochemistry, and increased PSII active reaction centers. Moreover, the non-photochemical quenching coefficient (NPQ) of alkali stress was different from salt and drought stresses, showing that the high pH of alkali stress caused more damaging effects on the photoprotection mechanism depending on the xanthophyll cycle. The above results suggest that the H. jubatum has stronger tolerance of salt than drought and alkali stresses, and the negative effects of alkali stress on the growth and photosynthetic performance of this species was most serious.
Perspectives on Drought Preconditioning Treatments With a Case Study Using Western Larch
Authors: Moler Ehren Reid Von , Nelson Andrew Steven
Published: September 2021

As the demand for drought hardy tree seedlings rises alongside global temperatures, there is a need to optimize nursery drought preconditioning methods to improve field performance of planted seedlings. This perspective article advocates for a more holistic approach to drought preconditioning research that considers the moderating role of plant developmental stage on the effects of drought preconditioning. We identify discrepancies in past studies of root growth potential (RGP) responses to drought preconditioning and highlight studies that suggest such discrepancies may result from inconsistencies among studies in the timing of drought preconditioning implementation. We then illustrate our perspective by presenting original research from an aeroponic RGP trial of 1st-year western larch (Larix occidentalis Nutt.) seedlings exposed to three soil moisture contents for 6months. We evaluated whether drought preconditioning could be used to increase the ratio of root: foliar tissue mass or enhance seedling physiological vigor during a subsequent growth period. Drought preconditioning was found to increase the ratio of root: foliar tissue mass and enhance seedling physiological vigor. Specifically, soil moisture content related negatively with new root biomass, positively with new foliar biomass, and negatively with the length and number of new roots (p<0.001). Meanwhile, the mass of lateral root production following drought preconditioning, but prior to aeroponic growth, correlated weakly to the mass, count, and length of new roots produced during aeroponic growth. We propose that evaluating the importance of the timing of drought preconditioning treatments constitutes an important research frontier in plant science.
Transitivity Violations Undermine Rating Scales in Motivation Research
Authors: Tyumeneva Yulia , Vergeles Kseniya
Published: September 2021

Measures of psychological attributes, such as motivation, typically involve rating scales, assuming that an attribute can be ordered. If an attribute has an ordinal structure, its levels stand in ordinal relations to one another, and these must be transitive. We tested if transitivity is preserved when people compare different motives in terms of their importance to learning. We found transitivity violations in both strict (Study 1) and non-strict (Study 2) orderings in about half of the participants. Nevertheless, based on the distribution of such violations, we conclude that an ordinal structure of motivation can be found, but only when levels of motives differ noticeably. As the levels become subjectively similar, transitivity is not preserved, and the ordinal structure cannot be justified even in non-strict ordering. The findings question the mainstream practice of measuring psychological attributes before their structure is properly explored.
A New Routine for Analyzing Brief Symptom Inventory Profiles in Chronic Pain Patients to Evaluate Psychological Comorbidity
Authors: Franke Gabriele Helga , Jagla-Franke Melanie , Küch Dieter , Petrowski Katja
Published: September 2021

Question: Comorbidity, i.e., additional psychological distress in patients already suffering from chronic somatic diseases (e.g., orthopedic conditions) is of growing importance. The quality of analyzing and interpreting the often used Brief Symptom Inventory (BSI) used with orthopedic patients should improve by employing a new “case definition” of four groups (instead of two) of differentially psychologically distressed patients instead of two groups as before.

Methods: Four groups with the different psychological distress definitions of “no,” “mild,” “remarkable,” and “severe” were to be analyzed from a group of 639 orthopedic patients in inpatient rehabilitation clinics. The BSI is transformed into T values (M=50, SD=10). There is “no” distress if no T [two scales] is ≥60 and “mild” distress if T [two scales] and/or T [GSI] is ≥60 and <63. If T [two scales] and/or T [GSI] is ≥63 and <70, it is “remarkable,” and if T [two scales] and/or T [GSI] ≥70, it speaks for “severe” psychological distress.

Results: The new tool for analyzing psychological distress based on the T-scores of the BSI resulted in the following four groups: No psychological distress (41.9%): unspecific health-related information stands for a useful intervention. About 13.3% demonstrated low psychological distress: shorter diagnostic interviews and a few more diagnostic examinations led to a low-level outpatient group program to improve health and well-being in a preventive sense; one repeated measurement in 4weeks is advised. Remarkable psychological distress (26%): in-depth exploration using interviews, tests, and questionnaires to choose specific interventions in a single and/or group setting, outpatient or inpatient treatment; repeated measurements and process control. About 18.8% reported severe psychological distress: in-depth exploration led to specific interventions in a single and/or group setting, almost an inpatient setting; immediately crisis intervention and high-frequent process control.

Conclusion: The new evaluation strategy of the BSI should improve practice and research; further investigation is necessary.
The Relationship Between Reactive Agility and Change of Direction Speed in Professional Female Basketball and Handball Players
Authors: Popowczak Marek , Cichy Ireneusz , Rokita Andrzej , Domaradzki Jarosław
Published: September 2021

Assessing the physical ability of players to perform change of direction and the cognitive and motor abilities revealed in reactive agility (RA) is necessary to understand the physical requirements and capabilities of professional players in handball and basketball. The main aim of this study was to determine the differences between professional female basketball and handball players in terms of anthropometric features, change of direction speed (CODS), and the RA task. Moreover, the relationships among anthropometric features, agility, and parameters of perception were determined. Two scenarios of the Five-Time Shuttle Run to Gates test (planned and unplanned) were used to evaluate the CODS and RA. The response time (RT) was also measured in the unplanned scenario. Additionally, the index of reactivity (REAC-INDEX) was specified as the difference between the RA test result and the measurement of CODS. There was a significant difference found in terms of body height, with basketball players being taller than handball players (p = 0.032). Professional female handball players achieved better results than professional female basketball players with regard to RA tasks (p = 0.01) and CODS (p = 0.041). Significant simple correlations between each anthropometric feature (body height, body mass) and values for CODS and RA were observed (r = 0.49–0.53). Applying partial correlation allowed for the assessment of actual relationships among CODS, RA, RT, and REAC-INDEX, without a confounding variable. Detaching the anthropometric parameters from the rest of the relationships resulted in maintenance or changes in r-values and an increased significance in the relationships between each pair: RA vs. RT, RA vs. REAC-INDEX, and RT vs. REAC-INDEX. The strongest associations were related to RT vs. REAC-INDEX (r = 0.97 at detaching body height or body mass, p < 0.001) and CODS vs. RA (r = 0.66 at detaching body height and r = −0.67 at detaching body mass, p < 0.001). It is recommended to use partial correlations in subsequent studies, as simple correlations are not reliable and may not reveal the apparent relationships between the variables. In addition, when determining the CODS and RA, it is suggested to take anthropometric and perception variables into account, such as reaction time or REAC-INDEX.
Emotional and Behavioral Changes in Older Adults With High Risk of Cognitive Impairment During the COVID-19 Pandemic
Authors: Fu Jiangning , Liu Xiaomei , Li Jing , Ma Zhuoya , Li Juan
Published: September 2021

COVID-19 is not only a threat to physical health but also a stressor to mental health, particularly for older adults. Previous studies have indicated that healthy older adults have resilience to cope with such stressful event through emotional and behavioral effort. However, very few have investigated the coping ability of older adults with High Risk of Cognitive Impairment (HRCI), as they are characterized with risk factors that can make them more vulnerable to COVID-19 in both physical and mental aspects. To examine whether older adults with HRCI were able to cope with and recover from the outbreak of COVID-19, we investigated the changes of their self-reported emotional states and intentions of taking protective behaviors between the outbreak period (data collected from February 17th to 24th, 2020) and the remission period (data collected from April 7th to 20th, 2020). The results showed that compared with the outbreak period, older adults with HRCI showed better emotional states and higher levels of intention to take more protective behaviors during the remission period. Subgroup analysis showed that even those who showed relatively poor coping abilities during the outbreak period could gradually improve their emotional states and intend to take more protective behaviors later on in the remission period. Therefore, these results suggested that older adults with HRCI were able to cope with and recover from the pandemic outbreak.
Leadership and Job Demands-Resources Theory: A Systematic Review
Authors: Tummers Lars G. , Bakker Arnold B.
Published: September 2021

The purpose of this article is to provide a systematic review of leadership and Job Demands-Resources (JD-R) theory. We have analyzed 139 studies that study the relationship between leadership and Job Demands-Resources (JD-R) theory. Based on our analysis, we highlight ways forward. First, research designs can be improved by eliminating endogeneity problems. Regarding leadership concepts, proper measurements should be used. Furthermore, we point toward new theory building by highlighting three main ways in which leadership may affect employees, namely by: (1) directly influencing job demands and resources, (2) influencing the impact of job demands and resources on well-being; and (3) influencing job crafting and self-undermining. We hope this review helps researchers and practitioners analyze how leadership and JD-R theory can be connected, ultimately leading to improved employee well-being and organizational performance.