bluuebunny/crossref_metadata_2025 huggingface dataset:
Altered Default Mode Network Functional Connectivity in Parkinson’s Disease: A Resting-State Functional Magnetic Resonance Imaging Study
Authors: Chen Lu , Huang Ting , Ma Di , Chen Yu-Chen
Published: June 2022

Purpose

Whether the intrinsic functional connectivity pattern of the default mode network (DMN) is involved in the progression of cognitive decline in Parkinson’s disease (PD) remains unclear. This study aimed to investigate the intrinsic functional connectivity (FC) pattern of the DMN anchored on the posterior cingulate cortex (PCC) in patients with PD by resting-state functional magnetic resonance imaging (fMRI).

Methods

Fifty patients with PD and 50 healthy controls (HCs) were included for resting-state fMRI scanning. A seed-based FC method was used to reveal FC patterns in the DMN with region of interest (ROI) in the PCC. Relationships between FC patterns and disease severity (UPDRS-III) were detected.

Results

Compared with the HCs, the patients with PD showed increased FC between the PCC and the right precuneus, left cuneus, and right angular gyrus. In the PD group, the increased FC values in the right precuneus were significantly and positively correlated with motor severity as assessed with UPDRS-III scores (rho = 0.337, p = 0.02).

Conclusion

Our result highlights that the patients with PD showed increased FC between the PCC and the right precuneus, left cuneus, and right angular gyrus in the DMN. The altered connectivity pattern in the DMN may play a crucial role in the neurophysiological mechanism of cognitive decline in patients with PD. These findings might provide new insights into neural mechanisms of cognitive decline in PD.
Genetic Variation of PD-L1 Gene Affects its Expression and Is Related to Clinical Outcome in Epithelial Ovarian Cancer
Authors: Sun Haiyan , Li Yan , Si Wengang , Hua Tian , Chen Juan , Kang Shan
Published: June 2022

Objective

This study aims to investigate the effect of polymorphisms of programmed cell death-ligand 1 (PD-L1) on the risk and patient’s outcomes of epithelial ovarian cancer (EOC).

Methods

Totally, 568 patients and 532 healthy women were included. Three polymorphisms in the PD-L1 gene, rs2297136, rs4143815 and rs4742098, were genotyped by the polymerase chain reaction/ligase detection reaction (PCR-LDR). Survival analysis was performed in 234 patients (received primary debulking surgery followed by platinum-based chemotherapy).

Results

Patients with the rs2297136 AG + GG genotypes had shorter progression-free survival (PFS) (hazard ratio (HR)=1.44, 95% CI=1.03-2.01) and overall survival (OS) (HR=1.55, 95% CI=1.06-2.27) than those with the AA genotype. Moreover, the mRNA and protein expression levels of PD-L1 in EOC tissues with the rs2297136 AG + GG genotypes were remarkably higher than those with the AA genotype (P=0.032 and P=0.047, respectively). Survival analysis showed that high expression of PD-L1 mRNA was remarkably associated with worse 10-year PFS (HR=1.55, 95% CI=1.28-1.88) and OS (HR=1.51, 95% CI=1.00-2.28) in EOC patients.

Conclusions

The rs2297136 may not only effectively influence the expression of PD-L1, but also is significantly associated with EOC patients’ outcomes.
Could Metabolic Syndrome Be a Predictor of Survival Outcomes in Upper Tract Urothelial Carcinoma? A Propensity Score Matching Study in a Large Chinese Center
Authors: Dai Xiang , Wang Fei , Du Yiqing , Qin Caipeng , Lai Shicong , Song Yuxuan , Huang Zixiong , Han Songchen , Zhang Xiaopeng , Xu Tao
Published: June 2022

Purpose

To evaluate the prognostic value of metabolic syndrome (MetS) in upper tract urothelial carcinoma (UTUC) patients based on propensity score matching (PSM) analysis.

Patients and Methods

A total of 573 patients with UTUC after radical nephroureterectomy were included at Peking University People’s Hospital from January 2007 to April 2021. MetS was diagnosed according to the criteria of Chinese Diabetes Society and was defined as the presence of 3 or more of the following 4 conditions (obesity, hyperglycemia, hypertension, high triglycerides and/or low high-density lipoprotein-cholesterol). Patients were divided into two groups based on whether they had MetS, whose variables were adjusted using 1:1 PSM analysis with a caliber of 0.02 to minimize selection bias. Univariate and multivariate Cox regression analysis were used to evaluate the association of MetS and its components with pathological outcomes after adjusting preoperative confounders by propensity score matching. The Kaplan-Meier method was used to estimate overall survival (OS), cancer-specific survival (CSS), and intravesical recurrence-free survival (IVRFS) after surgery.

Results

MetS was significantly correlated with older age, a history of coronary heart disease, high Charlson Comorbidity Index, low estimated Glomerular filtration rate, and low aspartate/alanine aminotransferase ratio (all P<0.05). Multivariate Cox regression analysis and Kaplan-Meier curves demonstrated that MetS showed no statistical correlation with lower OS or IVRFS and approaching significance with lower CSS (P=0.063) before PSM. After PSM, the 5-year OS, CSS, and IVRFS were 64.1%, 74.7%, and 77.2%, respectively, in the MetS group, compared with 67.4%, 78.8%, and 77.2%, respectively, in non-MetS group. Univariate Cox regression analyses showed that MetS and its components were not associated with decreased OS, CSS, or IVRFS (all P>0.05).

Conclusion

In our study, no statistical difference was found between MetS and survival outcomes in UTUC, except a marginal association with lower CSS. Further studies are needed to evaluate the role of MetS and its each single component on UTUC.
Endoscopic Endonasal Supraoptic and Infraoptic Approaches for Complex “Parasuprasellar” Lesions: Surgical Anatomy, Technique Nuances, and Case Series
Authors: Bao YouYuan , Yang YouQing , Zhou Lin , Xie ShenHao , Wu Xiao , Ding Han , Wu Jie , Xiao Limin , Yang Le , Tang Bin , Hong Tao
Published: June 2022

Objective

The surgical management of lesions involving the lateral area of the suprasellar region, including the lateral aspect of the planum sphenoidale and the tight junction region of the optic canal (OC), anterior clinoid process (ACP), and internal carotid artery (ICA) and its dural rings, is extremely challenging. Here, these regions, namely, the “parasuprasellar” area, are described from the endonasal perspective. Moreover, the authors introduce two novels endoscopic endonasal supraoptic (EESO) and endoscopic endonasal infraoptic (EEIO) approaches to access the parasuprasellar area.

Methods

Surgical simulation of the EESO and EEIO approaches to the parasuprasellar area was conducted in 5 silicon-injected specimens. The same techniques were applied in 12 patients with lesions involving the parasuprasellar area.

Results

The EESO approach provided excellent surgical access to the lateral region of the planum sphenoidale, which corresponds to the orbital gyrus of the frontal lobe. With stepwise bone (OC, optic strut and ACP) removal, dissociation of the ophthalmic artery (OA) and optic nerve (ON), the EEIO approach enables access to the lateral region of the supraclinoidal ICA. These approaches can be used independently or in combination, but are more often employed as a complement to the endoscopic endonasal midline and transcavernous approaches. In clinical application, the EESO and EEIO approaches were successfully performed in 12 patients harboring tumors as well as multiple aneurysms involving the parasuprasellar area. Gross total and subtotal tumor resection were achieved in 9 patients and 1 patient, respectively. For two patients with multiple aneurysms, the lesions were clipped selectively according to location and size. Visual acuity improved in 7 patients, remained stable in 4, and deteriorated in only 1. No postoperative intracranial infection or ICA injury occurred in this series.

Conclusions

The EESO and EEIO approaches offer original treatment options for well-selected lesions involving the parasuprasellar area. They can be combined with the endoscopic endonasal midline and transcavernous approaches to remove extensive pathologies involving the intrasellar, suprasellar, sphenoid, and cavernous sinuses and even the bifurcation of the ICA. This work for the first time pushes the boundary of the endoscopic endonasal approach lateral to the supraclinoidal ICA and ON.
The Effect of Complications on Oncological Outcomes of Colorectal Cancer Patients After Primary Surgery: A Propensity Score Matching Analysis
Authors: Liu Xiao-Yu , Zhang Bin , Kang Bing , Cheng Yu-Xi , Yuan Chao , Tao Wei , Wei Zheng-Qiang , Peng Dong
Published: June 2022

Purpose

The purpose of this study is to explore the oncologic outcomes of complications on colorectal cancer (CRC) patients who underwent primary surgery using a propensity score matching (PSM) analysis.

Methods

A retrospective study was conducted from Jan 2011 to Jan 2020 in a clinical center. The overall survival (OS) and disease-free survival (DFS) were compared among the no complications group, the major complications group and the minor complications group.

Results

A total of 4250 CRC patients who underwent radical primary surgery were included in the current study. Among them, 927 (21.8%) patients suffered complications. After 1:1 ratio PSM, there were 98 patients in the major complications group and in the minor complications group, and 911 patients in the overall complications group and in the no complications group. There was no significant difference in terms of baseline information after PSM (p>0.05). Complications were independent predictors of OS (p=0.000, HR=1.693, 95% CI=1.476-1.941) and DFS (p=0.000, HR=1.555, 95% CI=1.367-1.768). In terms of specific tumor stage, the no complications group had better OS on all stages (p=0.006) and stage III (p=0.003) CRC than the complications group after PSM. Furthermore, the no complications group had better DFS on all stages (p=0.005) and stage III (p=0.021) CRC than the complications group after PSM. However, there was no significant difference between the minor complications group and the major complications group in different tumor stages (p>0.05).

Conclusion

Complications were associated with poor prognosis of CRC and surgeons should be cautious of the adverse events.
Biomarking and Induction of Apoptosis in Ovarian Cancer Using Bifunctional Polyethyleneimine-Caged Platinum Nanoclusters
Authors: Zhang Mengjun , Yue Haodi , Liu Yuan , Li Hao , Yin Yue , Sun Zhenxing , Cui Ping , Li Fei , Chen Xiuwei , Huang Xin
Published: June 2022

According to the 2020 GLOBOCAN Global Cancer Women’s Cancer Data, ovarian cancer is the eighth most common tumor in humans. Still, its mortality rate ranks first among all gynecological tumors, with a 5-year survival rate of 30% to 50%. Widespread clinical use of platinum-based drugs has improved survival outcomes in patients with ovarian cancer, but organ toxicity and drug resistance hinder their anticancer effects. In particular, the resistance to platinum drugs is an important reason for ovarian cancer’s high recurrence rate and mortality. With the development of chemotherapeutic drugs synthesized by nanomaterials in the biomedical field, we developed bifunctional ultrafine polyethyleneimine caged platinum nanoclusters (PEI-Pt NCs) to improve the dilemma of platinum drugs. This study aimed to elucidate the antitumor effect of PEI-Pt NCs in OC. First, as observed by confocal microscopy, Pt NCs entered OC cells in a dose-dependent manner and accumulated on the surface of the nuclear membrane and in the nucleus. Subsequently, through cck8, ki-67 immunofluorescence, wound healing assay, transwell assay, clone formation assay, flow cytometry, tunel staining, and western blotting assay, it was confirmed that PEI-Pt NCs could inhibit the proliferation and migration and induce the apoptosis of ovarian cancer cells. PEI-Pt NCs can be used as fluorescent markers for systemic bioimaging of ovarian cancer, showing great potential in diagnosing and treating ovarian cancer, and making a specific contribution to solving the dilemma of platinum-based drug therapy for OC.
Occurrence of Thromboembolism in Paediatric Patients With Inflammatory Bowel Disease: Data From the CEDATA-GPGE Registry
Authors: De Laffolie Jan , Ballauff Antje , Wirth Stefan , Blueml Carolin , Rommel Frank Risto , Claßen Martin , Laaß Martin , Lang Thomas , Hauer Almuthe Christina ,   the CEDATA-GPGE Study Group
Published: June 2022

Objective

Among patients with inflammatory bowel disease (IBD), the risk of thromboembolism (TE) is increased, representing a relevant cause of morbidity and mortality. In contrast to other extraintestinal IBD manifestations, TE receives much less attention because of its low incidence, estimated at merely 0.4–0.9% in hospitalised children with IBD.

Methods

Cases with TE, as documented in the German-Austrian Paediatric IBD registry gesellschaft für pädiatrische gastroenterologie und ernährung – large paediatric patient registry (CEDATA-GPGE), were analyzed retrospectively. For all patients with signs of TE, a questionnaire was filled in by the treating paediatric gastroenterologist.

Results

Over 10 years, 4,153 paediatric patients with IBD (0–18 years) were registered in the registry, and 12 of them identified with TE. Eight patients were diagnosed with ulcerative colitis (UC), three with Crohn’s disease (CD), and one with IBD-unclassified. The median age at IBD diagnosis was 10 years and at the manifestation of TE 13 years, respectively, with a median latency to TE of 2 years. Prevalence of TE was 0.3%, with a significantly higher risk for patients with UC than CD (OR 5.9, CI 1.56–22.33, p = 0.008). More girls than boys were affected (f:m = 7:5) without reaching significance. Approximately 90% of patients experienced TE during active disease, with relevant cerebral and limb involvement in 6/12 patients. Various risk factors, e.g., hospitalisation, coagulopathy, or anaemia were identified. TE management included intensive care and surgery. Among the 12 patients, 11 recovered fully, in which one patient has focal epilepsy as a sequela.

Conclusion

Paediatric patients with IBD have a substantially increased risk for TE. Risk factors, such as those identified should be considered when managing paediatric IBD and preventive measures for those hospitalised taken routinely. Initiating pharmacological thromboprophylaxis is challenging for the lack of published trials on efficacy and safety in paediatric IBD but should be considered carefully in each case.
HSP90 Inhibitor Ganetespib Enhances the Sensitivity of Mantle Cell Lymphoma to Bruton’s Tyrosine Kinase Inhibitor Ibrutinib
Authors: Lu Ziwen , Wang Zhixin , Tu Zhigang , Liu Hanqing
Published: June 2022

Mantle cell lymphoma (MCL) is a highly aggressive and heterogeneous B-cell lymphoma. Though Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib has shown great efficacy as a single agent for MCL treatment, the real-world use of ibrutinib is still subject to limitations. Our previous study has shown the treatment with HSP90 inhibitor ganetespib can attack major targets of MCL, luckily complementary to ibrutinib’s targets. In this study, transient ganetespib treatment sensitizes MCL cells to ibrutinib as manifested by the significant decrease of IC50 values, percentages of EdU (5-Ethynyl-2′-deoxyuridine) positive cells, and levels of p-AKT and NF-κB after combinational treatment. Additionally, pretreatment with ganetespib enhanced cell cycle arrest induced by ibrutinib at G0/G1 phase and significantly decreased levels of cell cycle promoting proteins CDK2, 4, and 6. Pretreatment with ganetespib also enhanced cell apoptosis induced by ibrutinib through the upregulation of cleaved-caspase 9 and downregulation of BCL-2 in MCL cells at the molecular level. The sequential administration of ganetespib and ibrutinib had similar effects on increasing DNA damage as the transient treatment with ganetespib as demonstrated by the improved percentage of γH2AX and 53BP1 foci. Furthermore, ganetespib significantly increased inhibition of tumor growth mediated by ibrutinib in vivo, confirmed by the changes of the expression levels of Ki-67 and BCL-2 through immunohistochemistry assays. This study indicates that HSP90 inhibitor ganetespib maybe ideal for the combinational use with BTK inhibitor ibrutinib to target major pathogenesis-associated signaling pathways for MCL treatment which may help identify new possibilities for clinical trials.
Itraconazole Reverts ABCB1-Mediated Docetaxel Resistance in Prostate Cancer
Authors: Lima Thiago S. , Souza Luciano O. , Iglesias-Gato Diego , Elversang Johanna , Jørgensen Flemming Steen , Kallunki Tuula , Røder Martin A. , Brasso Klaus , Moreira José M.A.
Published: June 2022

Docetaxel (DTX) was the first chemotherapeutic agent to demonstrate significant efficacy in the treatment of men with metastatic castration-resistant prostate cancer. However, response to DTX is generally short-lived, and relapse eventually occurs due to emergence of drug-resistance. We previously established two DTX-resistant prostate cancer cell lines, LNCaPR and C4-2BR, derived from the androgen‐dependent LNCaP cell line, and from the LNCaP lineage-derived androgen-independent C4-2B sub-line, respectively. Using an unbiased drug screen, we identify itraconazole (ITZ), an oral antifungal drug, as a compound that can efficiently re-sensitize drug-resistant LNCaPR and C4-2BR prostate cancer cells to DTX treatment. ITZ can re-sensitize multiple DTX-resistant cell models, not only in prostate cancer derived cells, such as PC-3 and DU145, but also in docetaxel-resistant breast cancer cells. This effect is dependent on expression of ATP-binding cassette (ABC) transporter protein ABCB1, also known as P-glycoprotein (P-gp). Molecular modeling of ITZ bound to ABCB1, indicates that ITZ binds tightly to the inward-facing form of ABCB1 thereby inhibiting the transport of DTX. Our results suggest that ITZ may provide a feasible approach to re-sensitization of DTX resistant cells, which would add to the life-prolonging effects of DTX in men with metastatic castration-resistant prostate cancer.
Use of Complementary and Alternative Medicine and Adherence to Medication Therapy Among Stroke Patients: A Meta-analysis and Systematic Review
Authors: Rajahthurai Sareneya Dashni , Farrukh Muhammad Junaid , Makmor-Bakry Mohd , Tan Hui Jan , Fatokun Omotayo , Mohd Saffian Shamin , Ramatillah Diana Laila
Published: June 2022

Purpose: To identify the use patterns of complementary and alternative medicine (CAM) and its impact on medication adherence among patients with stroke.

Method: A systematic search through Science Direct, Google Scholar, and PubMed was performed to identify potential studies up to June 2021.The primary outcome was CAM use, and the secondary outcome was medication adherence among patients with stroke. Articles included in the review met the following criteria: 1) patients with stroke ≥18 years old on prescribed medications, and 2) medication adherence reported status. Meta-analyses were conducted to estimate the pooled prevalence of complementary and alternative medicine and adherence in stroke patients using a random-effects model.

Results: A total of 1,330 studies were screened, of which 22 were included in the final analysis. The type of studies included were cross-sectional surveys, cohort studies, retrospective studies and prospective survey. The pooled prevalence of CAM usage was at 38% (29–48% CI) and medication non-adherence among stroke patients was at 29% (20–48% CI). The most common reason for inadequate stroke therapy and higher dependence on CAM was the patients’ lack of knowledge and the regimen complexity of the medication. Other factors for medication non-adherence were forgetfulness, side effects, cost, and lack of doctor-patient communication.

Conclusion: A low prevalence of CAM usage and non-adherence to medications was observed among patients with stroke. Studies investigating the association between CAM usage and medication adherence among patients with stroke are scarce and future researches are needed to explore the influence of CAM use on stroke medication adherence.
12-Deoxyphorbol-13-Hexadecanoate Abrogates OVX-Induced Bone Loss in Mice and Osteoclastogenesis via Inhibiting ROS Level and Regulating RANKL-Mediated NFATc1 Activation
Authors: He Qi , Yang Junzheng , Chen Delong , Li Yejia , Gong Dawei , Ge Hui , Wang Zihao , Wang Haibin , Chen Peng
Published: June 2022

Osteoporosis is a major health problem in the elderly. Almost every bone can fracture due to the increased bone fragility in osteoporosis, posing a major challenge to public health. 12-Deoxyphorbol-13-hexadecanoate (DHD), one of the main bioactive components of Stellera chamaejasme L. (Lang Du), is considered to have antitumor, antibacterial, and antifungal properties. However, the role of DHD in osteoporosis is still elusive. In this study, we demonstrated for the first time that DHD inhibits the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis and bone resorption in a dose- and time-dependent manner without exhibiting cytotoxicity in vitro. Mechanistically, we found that DHD not only represses the expression of osteoclasts marker genes by suppressing RANKL-induced mitogen-activated protein kinase (MAPK) and calcium signaling pathways but also scavenges reactive oxygen species (ROS) through enhancing cytoprotective enzymes expression. Furthermore, DHD inhibits the activation of nuclear factor of activated T cells 1 (NFATc1) during RANKL-induced osteoclasts formation. Preclinical studies revealed that DHD protects against bone loss in ovariectomy (OVX) mice. In sum, our data confirmed that DHD could potentially inhibit osteoclastogenesis by abrogating RANKL-induced MAPK, calcium, and NFATc1 signaling pathways and promoting the expression of ROS scavenging enzymes, thereby preventing OVX-induced bone loss. Thus, DHD may act as a novel therapeutic agent to manage osteoporosis.
Engaging Patients via Online Healthcare Fora: Three Pharmacovigilance Use Cases
Authors: Powell Greg , Kara Vijay , Painter Jeffery L. , Schifano Lorrie , Merico Erin , Bate Andrew
Published: June 2022

Increasingly, patient-generated safety insights are shared online, via general social media platforms or dedicated healthcare fora which give patients the opportunity to discuss their disease and treatment options. We evaluated three areas of potential interest for the use of social media in pharmacovigilance. To evaluate how social media may complement existing safety signal detection capabilities, we identified two use cases (drug/adverse event [AE] pairs) and then evaluated the frequency of AE discussions across a range of social media channels. Changes in frequency over time were noted in social media, then compared to frequency changes in Food and Drug Administration Adverse Event Reporting System (FAERS) data over the same time period using a traditional disproportionality method. Although both data sources showed increasing frequencies of AE discussions over time, the increase in frequency was greater in the FAERS data as compared to social media. To demonstrate the robustness of medical/AE insights of linked posts we manually reviewed 2,817 threads containing 21,313 individual posts from 3,601 unique authors. Posts from the same authors were linked together. We used a quality scoring algorithm to determine the groups of linked posts with the highest quality and manually evaluated the top 16 groups of posts. Most linked posts (12/16; 75%) contained all seven relevant medical insights assessed compared to only one (of 1,672) individual post. To test the capability of actively engage patients via social media to obtain follow-up AE information we identified and sent consents for follow-up to 39 individuals (through a third party). We sent target follow-up questions (identified by pharmacovigilance experts as critical for causality assessment) to those who consented. The number of people consenting to follow-up was low (20%), but receipt of follow-up was high (75%). We observed completeness of responses (37 out of 37 questions answered) and short average time required to receive the follow-up (1.8 days). Our findings indicate a limited use of social media data for safety signal detection. However, our research highlights two areas of potential value to pharmacovigilance: obtaining more complete medical/AE insights via longitudinal post linking and actively obtaining rapid follow-up information on AEs.
God (≡ Elohim), The First Small World Network
Authors: Ausloos Marcel
Published: June 2022

In this article, the approach of network mapping of words in literary texts is extended to “textual factors”: the network nodes are defined as “concepts”; the links are “community connexions.” Thereafter, the text network properties are investigated along modern statistical physics approaches of networks, thereby relating network topology and algebraic properties to literary text contents. As a practical illustration, the first chapter of Genesis in the Bible is mapped into a 10-node network, as in the Kabbalah approach, mentioning God (≡ Elohim). The characteristics of the network are studied starting from its adjacency matrix and the corresponding Laplacian matrix. Triplets of nodes are particularly examined in order to emphasize the “textual (community) connexions” of each agent “emanation,” through the so-called clustering coefficients and the overlap index, hence measuring the “semantic flow” between the different nodes. It is concluded that this graph is a small world network and weakly dis-assortative, because its average local clustering coefficient is significantly higher than a random graph constructed on the same vertex set.
Effect of Parkinson’s Disease on Cardio-postural Coupling During Orthostatic Challenge
Authors: Fadil Rabie , Huether Asenath X. A. , Verma Ajay K. , Brunnemer Robert , Blaber Andrew P. , Lou Jau-Shin , Tavakolian Kouhyar
Published: June 2022

Cardiac baroreflex and leg muscles activation are two important mechanisms for blood pressure regulation, failure of which could result in syncope and falls. Parkinson’s disease is known to be associated with cardiac baroreflex impairment and skeletal muscle dysfunction contributing to falls. However, the mechanical effect of leg muscles contractions on blood pressure (muscle-pump) and the baroreflex-like responses of leg muscles to blood pressure changes is yet to be comprehensively investigated. In this study, we examined the involvement of the cardiac baroreflex and this hypothesized reflex muscle-pump function (cardio-postural coupling) to maintain blood pressure in Parkinson’s patients and healthy controls during an orthostatic challenge induced via a head-up tilt test. We also studied the mechanical effect of the heart and leg muscles contractions on blood pressure. We recorded electrocardiogram, blood pressure and electromyogram from 21 patients with Parkinson’s disease and 18 age-matched healthy controls during supine, head-up tilt at 70°, and standing positions with eyes open. The interaction and bidirectional causalities between the cardiovascular and musculoskeletal signals were studied using wavelet transform coherence and convergent cross mapping techniques, respectively. Parkinson’s patients displayed an impaired cardiac baroreflex and a reduced mechanical effect of the heart on blood pressure during supine, tilt and standing positions. However, the effectiveness of the cardiac baroreflex decreased in both Parkinson’s patients and healthy controls during standing as compared to supine. In addition, Parkinson’s patients demonstrated cardio-postural coupling impairment along with a mechanical muscle pump dysfunction which both could lead to dizziness and falls. Moreover, the cardiac baroreflex had a limited effect on blood pressure during standing while lower limb muscles continued to contract and maintain blood pressure via the muscle-pump mechanism. The study findings highlighted altered bidirectional coupling between heart rate and blood pressure, as well as between muscle activity and blood pressure in Parkinson’s disease. The outcomes of this study could assist in the development of appropriate physical exercise programs to reduce falls in Parkinson’s disease by monitoring the cardiac baroreflex and cardio-postural coupling effect on maintaining blood pressure.
A Convolutional Neural Network Based on Ultrasound Images of Primary Breast Masses: Prediction of Lymph-Node Metastasis in Collaboration With Classification of Benign and Malignant Tumors
Authors: Li Chunxiao , Guo Yuanfan , Jia Liqiong , Yao Minghua , Shao Sihui , Chen Jing , Xu Yi , Wu Rong
Published: June 2022

Purpose: A convolutional neural network (CNN) can perform well in either of two independent tasks [classification and axillary lymph-node metastasis (ALNM) prediction] based on breast ultrasound (US) images. This study is aimed to investigate the feasibility of performing the two tasks simultaneously.

Methods: We developed a multi-task CNN model based on a self-built dataset containing 5911 breast US images from 2131 patients. A hierarchical loss (HL) function was designed to relate the two tasks. Sensitivity, specificity, accuracy, precision, F1-score, and analyses of receiver operating characteristic (ROC) curves and heatmaps were calculated. A radiomics model was built by the PyRadiomics package.

Results: The sensitivity, specificity and area under the ROC curve (AUC) of our CNN model for classification and ALNM tasks were 83.5%, 71.6%, 0.878 and 76.9%, 78.3%, 0.836, respectively. The inconsistency error of ALNM prediction corrected by HL function decreased from 7.5% to 4.2%. Predictive ability of the CNN model for ALNM burden (≥3 or ≥4) was 77.3%, 62.7%, and 0.752, and 66.6%, 76.8%, and 0.768, respectively, for sensitivity, specificity and AUC.

Conclusion: The proposed multi-task CNN model highlights its novelty in simultaneously distinguishing breast lesions and indicating nodal burden through US, which is valuable for “personalized” treatment.
Species-Specific Gene Expansion of the Cellulose synthase Gene Superfamily in the Orchidaceae Family and Functional Divergence of Mannan Synthesis-Related Genes in Dendrobium officinale
Authors: Wang Yunzhu , Zhao Kunkun , Chen Yue , Wei Qingzhen , Chen Xiaoyang , Wan Hongjian , Sun Chongbo
Published: June 2022

Plant Cellulose synthase genes constitute a supergene family that includes the Cellulose synthase (CesA) family and nine Cellulose synthase-like (Csl) families, the members of which are widely involved in the biosynthesis of cellulose and hemicellulose. However, little is known about the Cellulose synthase superfamily in the family Orchidaceae, one of the largest families of angiosperms. In the present study, we identified and systematically analyzed the CesA/Csl family members in three fully sequenced Orchidaceae species, i.e., Dendrobium officinale, Phalaenopsis equestris, and Apostasia shenzhenica. A total of 125 Cellulose synthase superfamily genes were identified in the three orchid species and classified into one CesA family and six Csl families: CslA, CslC, CslD, CslE, CslG, and CslH according to phylogenetic analysis involving nine representative plant species. We found species-specific expansion of certain gene families, such as the CslAs in D. officinale (19 members). The CesA/Csl families exhibited sequence divergence and conservation in terms of gene structure, phylogeny, and deduced protein sequence, indicating multiple origins via different evolutionary processes. The distribution of the DofCesA/DofCsl genes was investigated, and 14 tandemly duplicated genes were detected, implying that the expansion of DofCesA/DofCsl genes may have originated via gene duplication. Furthermore, the expression profiles of the DofCesA/DofCsl genes were investigated using transcriptome sequencing and quantitative Real-time PCR (qRT-PCR) analysis, which revealed functional divergence in different tissues and during different developmental stages of D. officinale. Three DofCesAs were highly expressed in the flower, whereas DofCslD and DofCslC family genes exhibited low expression levels in all tissues and at all developmental stages. The 19 DofCslAs were differentially expressed in the D. officinale stems at different developmental stages, among which six DofCslAs were expressed at low levels or not at all. Notably, two DofCslAs (DofCslA14 and DofCslA15) showed significantly high expression in the stems of D. officinale, indicating a vital role in mannan synthesis. These results indicate the functional redundancy and specialization of DofCslAs with respect to polysaccharide accumulation. In conclusion, our results provide insights into the evolution, structure, and expression patterns of CesA/Csl genes and provide a foundation for further gene functional analysis in Orchidaceae and other plant species.
Identification of Golovinomyces artemisiae Causing Powdery Mildew, Changes in Chlorophyll Fluorescence Parameters, and Antioxidant Levels in Artemisia selengensis
Authors: Guo Zhixin , Sun Xiaoyang , Qin Ligang , Dong Lili , Xiong Liangbing , Xie Fuchun , Qin Dong , Chen Yajun
Published: June 2022

Artemisia selengensis Turcz. is a valuable edible and medicinal vegetable crop widely cultivated in Northeast China. Powdery mildew (PM) disease occurs during field and greenhouse cultivation, resulting in production losses and quality deterioration. The pathogen in A. selengensis was Golovinomyces artemisiae identified using optical microscopic and scanning electron microscopic observations, morphological identification, and molecular biological analyses. Parameters of chlorophyll fluorescence (ChlF) and antioxidant system responses as well as callose and lignin contents in A. selengensis were analyzed with inoculating G. artemisiae. Obvious of PM-infected leaves were confirmed with significantly lower values in electron transport rate (ETR), non-photochemical quenching (NPQ), photochemical quenching (qP), and actual photochemical efficiency [Y(II)], but higher values in non-adjusting energy dissipation yield [Y(NO)], supposed that maximal photosystem II quantum yield (Fv/Fm) value and images could be used to monitor PM degree on infectedA. selengensis. In addition, malondialdehyde (MDA), superoxide anion (O2–), callose, lignin contents, and peroxidase (POD) activity increased, while superoxide dismutase (SOD) activity, catalase (CAT) activity, and ascorbic acid (AsA) content decreased significantly in infected leaves compared to mock-inoculated leaves, indicated that lignin and protective enzymes are the key indicators for detecting PM resistant in A. selengensis. These results suggest that PM caused by G. artemisiae disrupted the photosynthetic capacity and induced imbalance of antioxidant system inA. selengensis. The findings were of great significance for designing a feasible approach to effectively prevent and control the PM disease in A. selengensis as well as in other vegetable crops.
HSP90 Contributes to chs3-2D-Mediated Autoimmunity
Authors: Lu Junxing , Liang Wanwan , Zhang Nanbing , van Wersch Solveig , Li Xin
Published: June 2022

Plants employ multi-layered immune system to fight against pathogen infections. Different receptors are able to detect the invasion activities of pathogens, transduce signals to downstream components, and activate defense responses. Among those receptors, nucleotide-binding domain leucine-rich repeat containing proteins (NLRs) are the major intracellular ones. CHILLING SENSITIVE 3 (CHS3) is an Arabidopsis NLR with an additional Lin-11, Isl-1 and Mec-3 (LIM) domain at its C terminus. The gain-of-function mutant, chs3-2D, exhibiting severe dwarfism and constitutively activated defense responses, was selected as a genetic background in this study for a forward genetic screen. A mutant allele of hsp90.2 was isolated as a partial suppressor of chs3-2D, suggesting that HSP90 is required for CHS3-mediated defense signaling. In addition, HSP90 is also required for the autoimmunity of the Dominant Negative (DN)-SNIPER1 and gain-of-function ADR1-L2 D484V transgenic lines, suggesting a broad role for HSP90 in NLR-mediated defense. Overall, our work indicates a larger contribution of HSP90 not only at the sensor, but also the helper NLR levels.
Low Temperature Stress Tolerance: An Insight Into the Omics Approaches for Legume Crops
Authors: Bhat Kaisar Ahmad , Mahajan Reetika , Pakhtoon Mohammad Maqbool , Urwat Uneeb , Bashir Zaffar , Shah Ali Asghar , Agrawal Ankit , Bhat Basharat , Sofi Parvaze A. , Masi Antonio , Zargar Sajad Majeed
Published: June 2022

The change in climatic conditions is the major cause for decline in crop production worldwide. Decreasing crop productivity will further lead to increase in global hunger rate. Climate change results in environmental stress which has negative impact on plant-like deficiencies in growth, crop yield, permanent damage, or death if the plant remains in the stress conditions for prolonged period. Cold stress is one of the main abiotic stresses which have already affected the global crop production. Cold stress adversely affects the plants leading to necrosis, chlorosis, and growth retardation. Various physiological, biochemical, and molecular responses under cold stress have revealed that the cold resistance is more complex than perceived which involves multiple pathways. Like other crops, legumes are also affected by cold stress and therefore, an effective technique to mitigate cold-mediated damage is critical for long-term legume production. Earlier, crop improvement for any stress was challenging for scientific community as conventional breeding approaches like inter-specific or inter-generic hybridization had limited success in crop improvement. The availability of genome sequence, transcriptome, and proteome data provides in-depth sight into different complex mechanisms under cold stress. Identification of QTLs, genes, and proteins responsible for cold stress tolerance will help in improving or developing stress-tolerant legume crop. Cold stress can alter gene expression which further leads to increases in stress protecting metabolites to cope up the plant against the temperature fluctuations. Moreover, genetic engineering can help in development of new cold stress-tolerant varieties of legume crop. This paper provides a general insight into the “omics” approaches for cold stress in legume crops.
The Influence of Trait Emotion and Spatial Distance on Risky Choice Under the Framework of Gain and Loss
Authors: Xu Fuming , Huang Long
Published: June 2022

In the time of the COVID-19 pandemic, people are often faced with uncertain risky choice. Risky choice will be affected by different descriptions of the event’s gain or loss framework, this phenomenon is known as the framing effect. With the continuous expansion and in-depth study of frame effects in the field of risky choice, researchers have found that the are quite different in different situations. People have different interpretations of the same event at different psychological distances, and will also be affected by their own emotions. Therefore, the current study examines the common influence of task frame, spatial distance, and trait emotion on risky choice through two studies. Study 1 used a 2 (framework: gain vs. loss) × 2 (trait sentiment: high vs. low) inter-subject design, and the dependent variable is the choice of the rescue plan for the classic “Asian disease” problem. The results revealed that trait anger did not predict individuals’ risky choice preferences, and high trait anxiety led individuals to be more risk-averse. The framing effect exists in risky choice, and individuals prefer risk seeking in the loss frame. Study 2 used a 2 (spatial distance: distant vs. proximal) × 2 (framework: gain vs. loss) × 2 (trait sentiment: high vs. low) three-factor inter-subject design in which the dependent variable is the choice of rescue plan. The results indicate that the framing effect also exists in risky choice, and individuals prefer risk seeking in a loss frame. High trait anxiety lead individuals to be more risk-averse, while trait anger has no significant predictive effect on risk preference. Distant spatial distance lead individuals to increase their preference for risk-seeking under the gain frame, which leads to the disappearance of the framing effect. In conclusion, trait anxiety and spatial distance have a certain degree of influence on risky choice under the framework of gain and loss.
Moderating Effects of Striving to Avoid Inferiority on Income and Mental Health
Authors: Nagae Asa , Asano Kenichi , Kotera Yasuhiro
Published: June 2022

Many people experience feelings of inferiority in their life. The concept of striving to avoid inferiority is a belief associated with the unwanted fear of being overlooked, missing out on opportunities for advancement, and active rejection. This study examined the effect of striving to avoid inferiority on mental health and well-being. We hypothesized that striving to avoid inferiority would modify the relationship among socioeconomic status, mental health, and well-being, therefore examined the effect of striving to avoid inferiority on the relationship between annual income, mental health, and well-being. The participants were 491 adults (241 men and 250 women). The results indicated that insecure striving (IS) in competition with others positively correlated with depression, anxiety, and stress, whereas secure non-striving (SNS) in acceptance of inferiority positively correlated with the satisfaction with life and negatively correlated with depression. The effect of striving to avoid inferiority on the relationship among annual income, mental health, and well-being indicated that SNS affected the relationships between annual income and well-being, annual income and depression, income and anxiety, and the interaction between IS and SNS. Moreover, the relationship between income and stress was influenced by SNS and the interaction between IS and SNS. These results indicated that SNS or the interaction between IS and SNS were the only variables regulating the relationship among annual income, mental health, and well-being. These findings suggested that accepting feelings of inferiority or striving to avoid inferiority influences the mental health and well-being of people.
Burnout Among School Teachers During the COVID-19 Pandemic in Jazan Region, Saudi Arabia
Authors: Alqassim Ahmad Y. , Shami Mohammed O. , Ageeli Ahmed A. , Ageeli Mohssen H. , Doweri Abrar A. , Melaisi Zakaria I. , Wafi Ahmed M. , Muaddi Mohammed A. , El-Setouhy Maged
Published: June 2022

Background

Burnout is a syndrome that results from stressors in the work environment that have not been successfully managed. The prevalence of burnout among schoolteachers was always controversial. COVID-19 pandemic added more stressors to teachers since they had to change their working styles in response to the pandemic lockdowns or curfews. In Saudi Arabia, the prevalence and determinants of burnout among school teachers were not measured by any other group during the COVID-19 pandemic stressors.

Methods

A cross-sectional survey was conducted among 879 teachers in the Jazan region, Saudi Arabia, using the Maslach Burnout Inventory (MBI), during April 2021. Multistage cluster random sampling was used.

Results

The mean age of the participants was 41.4 (±6.9) years. Male teachers represented 52.6% of the participants while females represented 47.4%. Most teachers showed burnout symptoms (69.6%). Consequences of burnout were observed, such as using psychotropic medications (4.6%), absenteeism (45.6%), lack of job satisfaction (7.7%), and changing schools (15.8%). Using the MBI scale, most teachers showed medium or high emotional exhaustion (57.6%), low depersonalization (62.2%), and low personal accomplishment (51.4%).

Conclusion

Most teachers showed symptoms of burnout during the COVID-19 pandemic. Being an expert and ability to adapt to technology during the COVID-19 pandemic proved to effectively reduce burnout symptoms. Increasing incentives, early detection, and improving the work environment is recommended to diminish burnout consequences.
Relationship Between Teachers’ Teaching Modes and Students’ Temperament and Learning Motivation in Confucian Culture During the COVID-19 Pandemic
Authors: Mo Chuan-Yu , Jin Jiyang , Jin Peiqi
Published: June 2022

Because of the coronavirus disease 2019 (COVID-19) pandemic, the traditional didactic teaching method that is practiced in Confucian culture, an Eastern cultural model, is being challenged by multiple alternative teaching modes. In Western cultures, the teaching behavior of teachers is dependent on their ability to influence the temperament of students; in contrast, teachers in Eastern cultures are influenced by changes in external environment (i.e., social policy). This phenomenon can mainly be explained by the tendency of students in Eastern cultures to adopt a passive learning style because of Confucianism. On the basis of Confucian culture and literature review, we conducted a Chinese-language questionnaire survey of temperament scales and learning motivation, and 724 effective questionnaires were collected and used to explore the relationship between students’ temperament and learning motivation under three teaching modes, namely, online teaching, traditional offline classroom teaching, and online–offline mixed teaching. Conclusions drawn were as follows. (1) In a Chinese Confucian cultural system, the passive learning style of students and its relationship with the surrounding collective culture creates the temperament characteristics of sanguinity and phlegmatism. (2) Influenced by the traditional Confucian values of benevolence and honesty, students with a melancholic temperament do not focus on their learning motivations. Furthermore, changes in external information, to which such students are sensitive, cause them to give up opportunities easily. (3) Similarly, students with a choleric temperament are sensitive and prone to fluctuating emotions, and they tend to be affected by changes in their external environment. (4) Although students have a strong learning motivation under the traditional offline teaching mode, a paradox in individual cognition exists because of differences between Chinese and Western cultures. Therefore, students generally prefer the online–offline mixed teaching mode to the traditional single teaching mode. This study explored factors that influence students’ learning motivation, namely, individual temperament and educational environment (e.g., teaching modes), and provides a reference for the future development of post epidemic education.
Sense of Relationship Entitlement of Aging Parents Toward Their Offspring (SRE-ao)—A New Concept and Measurement Tool
Authors: Tolmacz Rami , Lev-Ari Lilac , Bachner-Melman Rachel , Palgi Yuval , Bodner Ehud , Feldman Darya , Chakir Ron , Ben-David Boaz
Published: June 2022

Our sense of entitlement influences our interactions and attitudes in a range of specific relational contexts, one of them being aging parents’ relationships with their adult children. This study aimed to examine the factor structure of the Sense of Relational Entitlement—aging parents toward their offspring (SRE-ao), an 11-item questionnaire that assesses aging people’s sense of relational entitlement toward their children, and examine the associations of its subscales with related personality and mental health constructs. One thousand and six participants (24.6% men), aged 65–99, with at least one child, completed the SRE-ao, Brief Symptom Inventory, Loneliness Scale, and General Belongingness scale. The SRE-ao demonstrated good construct structure using confirmatory factor analysis. Both SRE-ao subscales (restricted and inflated sense of entitlement) were significantly and positively associated with anxiety, depression, somatization and sense of loneliness and negatively with sense of belonging. When all variables were entered into a regression model, age, anxiety, and low sense of belonging, but not sense of loneliness, positively predicted both restricted and inflated sense of entitlement. Somatization negatively predicted inflated sense of entitlement. The SRE-ao is a reliable and valid scale that can be used in clinical practice and research to enhance our understanding of parent–child relationships throughout the lifespan.