bluuebunny/crossref_metadata_2025 huggingface dataset:
Resting-State Electroencephalography Functional Connectivity Networks Relate to Pre- and Postoperative Language Functioning in Low-Grade Glioma and Meningioma Patients
Authors: Wolthuis Nienke , Satoer Djaina , Veenstra Wencke , Smits Marion , Wagemakers Michiel , Vincent Arnaud , Bastiaanse Roelien , Cherian Perumpillichira J. , Bosma Ingeborg
Published: December 2021

Introduction: Preservation of language functioning in patients undergoing brain tumor surgery is essential because language impairments negatively impact the quality of life. Brain tumor patients have alterations in functional connectivity (FC), the extent to which brain areas functionally interact. We studied FC networks in relation to language functioning in glioma and meningioma patients.

Method: Patients with a low-grade glioma (N = 15) or meningioma (N = 10) infiltrating into/pressing on the language-dominant hemisphere underwent extensive language testing before and 1 year after surgery. Resting-state EEG was registered preoperatively, postoperatively (glioma patients only), and once in healthy individuals. After analyzing FC in theta and alpha frequency bands, weighted networks and Minimum Spanning Trees were quantified by various network measures.

Results: Pre-operative FC network characteristics did not differ between glioma patients and healthy individuals. However, hub presence and higher local and global FC are associated with poorer language functioning before surgery in glioma patients and predict worse language performance at 1 year after surgery. For meningioma patients, a greater small worldness was related to worse language performance and hub presence; better average clustering and global integration were predictive of worse outcome on language function 1 year after surgery. The average eccentricity, diameter and tree hierarchy seem to be the network metrics with the more pronounced relation to language performance.

Discussion: In this exploratory study, we demonstrated that preoperative FC networks are informative for pre- and postoperative language functioning in glioma patients and to a lesser extent in meningioma patients.
Adjuvant Corticosteroids With Surgery for Chronic Subdural Hematoma: A Systematic Review and Meta-Analysis
Authors: Shi Min , Xiao Ling-fei , Zhang Ting-bao , Tang Qing-wen , Zhao Wen-yuan
Published: December 2021

The use of adjuvant corticosteroids with surgery for chronic subdural hematoma (CSDH) has received considerable attention in recent years. However, there is no conclusive evidence regarding its effectiveness and safety for CSDH. Therefore, we performed a meta-analysis and systematic review to evaluate the effectiveness and safety of corticosteroids as an adjuvant treatment for the treatment of CSDH. We comprehensively searched electronic databases (PubMed, EMBASE, Cochrane Library, and Web of Science) to identify relevant trials that investigated the efficacy and safety of adjuvant corticosteroids with surgery for CSDH, published from inception until May 2021. Outcome measures included recurrence rate, all-cause mortality, good functional outcome, length of hospitalization, and adverse events. We used the Cochrane risk of bias method to evaluate the quality of randomized controlled trials (RCTs), and the Newcastle Ottawa Scale to evaluate the quality of observational studies. We included nine studies, consisting of three RCTs and six observational studies, that compared corticosteroids as an adjuvant treatment to surgery with surgery alone. Pooled results revealed that the risk of recurrence was significantly reduced in patients who received adjuvant corticosteroids with surgery compared to those who underwent surgery alone (relative risk [RR] = 0.52, 95% confidence interval [CI] = 0.39–0.69, p < 0.00001). However, no statistically significant difference was observed between these groups in all-cause mortality (RR = 0.91, 95% CI = 0.37–2.23, p = 0.83), good functional outcome (RR = 1.03, 95% CI = 0.96–1.10, p = 0.47), length of hospitalization (MD = 0.35, 95% CI = –2.23 to 1.67, p = 0.83), and infection rates (RR = 0.99, 95% CI = 0.64–1.53, p = 0.95). Adjuvant corticosteroids with surgery reduce the risk of recurrence of CDSH, but do not improve the all-cause mortality or functional outcome, as compared to surgery alone. These findings support the use of adjuvant corticosteroids with surgery for CSDH patients. Further high-quality RCTs are required to confirm the efficacy and safety of adjuvant corticosteroids in the treatment of CSDH patients.
Musculoskeletal Modeling and Inverse Dynamic Analysis of Precision Grip in the Japanese Macaque
Authors: Saito Tsuyoshi , Ogihara Naomichi , Takei Tomohiko , Seki Kazuhiko
Published: December 2021

Toward clarifying the biomechanics and neural mechanisms underlying coordinated control of the complex hand musculoskeletal system, we constructed an anatomically based musculoskeletal model of the Japanese macaque (Macaca fuscata) hand, and then estimated the muscle force of all the hand muscles during a precision grip task using inverse dynamic calculation. The musculoskeletal model was constructed from a computed tomography scan of one adult male macaque cadaver. The hand skeleton was modeled as a chain of rigid links connected by revolute joints. The path of each muscle was defined as a series of points connected by line segments. Using this anatomical model and a model-based matching technique, we constructed 3D hand kinematics during the precision grip task from five simultaneous video recordings. Specifically, we collected electromyographic and kinematic data from one adult male Japanese macaque during the precision grip task and two sequences of the precision grip task were analyzed based on inverse dynamics. Our estimated muscular force patterns were generally in agreement with simultaneously measured electromyographic data. Direct measurement of muscle activations for all the muscles involved in the precision grip task is not feasible, but the present inverse dynamic approach allows estimation for all the hand muscles. Although some methodological limitations certainly exist, the constructed model analysis framework has potential in clarifying the biomechanics and neural control of manual dexterity in macaques and humans.
Associations of Dietary and Circulating Vitamin E Level With Metabolic Syndrome. A Meta-Analysis of Observational Studies
Authors: Zhang Yi , Ding Jun , Guo Hongbin , Liu Ze , Liu Qi , Li Yusheng , Zhang Dianzhong , Liang Jieyu
Published: December 2021

Objective:The associations of dietary and circulating vitamin E level with metabolic syndrome (MetS) remains conflicting. This meta-analysis of observational study was therefore employed to investigate the issue above.

Methods:The PubMed, Web of Science and Embase database were searched up to April 2021. The observational studies on the associations of dietary and circulating vitamin E level with MetS were specified. The pooled relative risk (RR) of MetS for the highest vs. lowest dietary and circulating vitamin E level, and the standard mean difference (SMD) of dietary and circulating vitamin E level for MetS vs. control subjects, were calculated.

Results:A total of 25 observational studies with 51,276 participants, were included in this meta-analysis. The overall multi-variable adjusted RR demonstrated that the dietary vitamin E level was inversely associated with MetS (RR = 0.92, 95%CI: 0.85–1.00;P= 0.044). In addition, the dietary vitamin E level in MetS was also lower than that in control subjects according to the overall combined SMD (SMD = −0.08, 95%CI: −0.14 to −0.02;P= 0.024). On the other hand, the overall multi-variable adjusted RR showed no significant relationship between the circulating vitamin E level and MetS (RR = 1.46, 95%CI: 0.85–2.48;P= 0.17). However, the circulating vitamin E level in MetS was lower than that in control subjects according to the overall combined SMD (SMD = −0.58, 95%CI: −1.04 to −0.13;P= 0.013).

Conclusions:The results of this meta-analysis suggest that the dietary vitamin E level is inversely associated with MetS. On the other hand, current evidence is still insufficient to conclude a relationship between the circulating vitamin E level and MetS. More well-designed prospective cohort studies are needed to address the issues further.
Expanded Transsphenoidal Trans-Lamina Terminalis Approach to Tumors Extending Into the Third Ventricle: Technique Notes and a Single Institute Experience
Authors: Cao Lei , Wu Wentao , Kang Jie , Qiao Hui , Yang Xiaocui , Bai Jiwei , Zhu Haibo , Zhang Yazhuo , Gui Songbai
Published: December 2021

Object

The trans lamina terminalis approach (TLTA) has been described as a way to remove third ventricular tumors. The aim of this paper was to analyze the feasible outcomes of TLTA applied to tumors extending into the third ventricle in our institute.

Methods

Suprasellar tumors (n = 149) were treated by the extended endonasal approach from September 2019 to December 2020 in Beijing Tiantan Hospital. Eleven of the tumors were treated by TLTA or TLTA via the trans-chiasm-pituitary corridor (TCPC). The surgical technique notes of TLTA were described and indications and outcomes of the approach were analyzed.

Results

There were 11 patients enrolled in the study, six with papillary craniopharyngiomas, two with adamantinomatous craniopharyngiomas, one with a germinal cell tumor (GCT), one with cavernous malformation and one with chordoid glioma. Four of the patients received a radical resection by TLTA alone, while seven of them received TLTA via the TCPC. Gross total resection was achieved in eight patients (72.7%), and partial resection in three patients (27.3%). Visual function was improved in four of the 11 patients (36.4%), was unchanged in five patients (45.5%), and deteriorated in two patients (18.2%). New-onset hypopituitarism occurred in seven patients (63.3%) and new-onset diabetes insipidus occurred in two patients (18.2%). Electrocyte imbalance were observed in six patients (54.5%) at post-operative week 2. There were no surgery-related deaths or cerebrospinal fluid leaks. Postoperative intracranial infection was observed in one patient (9.1%), and during the follow-up period, tumor recurrence occurred in one patient (9.1%).

Conclusion

The expanded TLTA provides a feasible suprachiasm corridor to remove tumors extending into the third ventricle, especially for craniopharyngiomas. Sound understanding of the major strengths and limitations of this approach, as well as strategies for complication avoidance, is necessary for its safe and effective application.
Integration of a Geriatric Assessment With Intervention in the Care of Older Adults With Hematologic Malignancies
Authors: Wall Sarah A. , Huang Ying , Keiter Ashleigh , Funderburg Allesia , Kloock Colin , Yuhasz Nicholas , Gure Tanya R. , Folefac Edmund , Stevens Erin , Presley Carolyn J. , Williams Nicole O. , Krok-Schoen Jessica L. , Naughton Michelle J. , Rosko Ashley E.
Published: December 2021

The incidence of hematologic malignancies (HMs) is highest in the seventh decade of life and coincides with increasing occult, age-related vulnerabilities. Identification of frailty is useful in prognostication and treatment decision-making for older adults with HMs. This real-world analysis describes 311 older adults with HMs evaluated in a multidisciplinary oncogeriatric clinic. The accumulation of geriatric conditions [1-unit increase, hazards ratio (HR) = 1.13, 95% CI 1.00–1.27, p = 0.04] and frailty assessed by the Rockwood Clinical Frailty Scale (CFS, mild/moderate/severe frailty vs. very fit/well, HR = 2.59, 95% CI 1.41–4.78, p = 0.002) were predictive of worse overall survival. In multivariate analysis, HM type [acute leukemia, HR = 3.84, 95% CI 1.60–9.22, p = 0.003; myelodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN)/bone marrow failure, HR = 2.65, 95% CI 1.10–6.35, p = 0.03], age (per 5-year increase, HR = 1.46, 95% CI 1.21–1.76, p < 0.001), hemoglobin (per 1 g/dl decrease, HR = 1.21, 95% CI 1.05–1.40, p = 0.009), deficit in activities of daily living (HR = 2.20, 95% CI 1.11–4.34, p = 0.02), and Mini Nutrition Assessment score (at-risk of malnutrition vs. normal, HR = 2.00, 95% CI 1.07–3.73, p = 0.03) were independently associated with risk of death. The most commonly prescribed geriatric interventions were in the domains of audiology (56%) and pharmacy (54%). The Rockwood CFS correlated with prescribed interventions in nutrition (p = 0.01) and physical function (p < 0.001) domains. Geriatric assessment with geriatric intervention can be practically integrated into the routine care of older adults with HMs.
The Role of Immune Checkpoint Blockade in the Hepatocellular Carcinoma: A Review of Clinical Trials
Authors: Ozer Muhammet , George Andrew , Goksu Suleyman Yasin , George Thomas J. , Sahin Ilyas
Published: December 2021

The prevalence of primary liver cancer is rapidly rising all around the world. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Unfortunately, the traditional treatment methods to cure HCC showed poor efficacy in patients who are not candidates for liver transplantation. Until recently, tyrosine kinase inhibitors (TKIs) were the front-line treatment for unresectable liver cancer. However, rapidly emerging new data has drastically changed the landscape of HCC treatment. The combination treatment of atezolizumab plus bevacizumab (immunotherapy plus anti-VEGF) was shown to provide superior outcomes and has become the new standard first-line treatment for unresectable or metastatic HCC. Currently, ongoing clinical trials with immune checkpoint blockade (ICB) have focused on assessing the benefit of antibodies against programmed cell death 1 (PD-1), programmed cell death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte- associated antigen 4 (CTLA-4) as monotherapies or combination therapies in patients with HCC. In this review, we briefly discuss the mechanisms underlying various novel immune checkpoint blockade therapies and combination modalities along with recent/ongoing clinical trials which may generate innovative new treatment approaches with potential new FDA approvals for HCC treatment in the near future.
Keratinocyte Biomarkers Distinguish Painful Diabetic Peripheral Neuropathy Patients and Correlate With Topical Lidocaine Responsiveness
Authors: Albrecht Phillip J. , Houk George , Ruggiero Elizabeth , Dockum Marilyn , Czerwinski Margaret , Betts Joseph , Wymer James P. , Argoff Charles E. , Rice Frank L.
Published: December 2021

This study investigated quantifiable measures of cutaneous innervation and algesic keratinocyte biomarkers to determine correlations with clinical measures of patient pain perception, with the intent to better discriminate between diabetic patients with painful diabetic peripheral neuropathy (PDPN) compared to patients with low-pain diabetic peripheral neuropathy (lpDPN) or healthy control subjects. A secondary objective was to determine if topical treatment with a 5% lidocaine patch resulted in correlative changes among the quantifiable biomarkers and clinical measures of pain perception, indicative of potential PDPN pain relief. This open-label proof-of-principle clinical research study consisted of a pre-treatment skin biopsy, a 4-week topical 5% lidocaine patch treatment regimen for all patients and controls, and a post-treatment skin biopsy. Clinical measures of pain and functional interference were used to monitor patient symptoms and response for correlation with quantitative skin biopsy biomarkers of innervation (PGP9.5 and CGRP), and epidermal keratinocyte biomarkers (Nav1.6, Nav1.7, CGRP). Importantly, comparable significant losses of epidermal neural innervation (intraepidermal nerve fibers; IENF) and dermal innervation were observed among PDPN and lpDPN patients compared with control subjects, indicating that innervation loss alone may not be the driver of pain in diabetic neuropathy. In pre-treatment biopsies, keratinocyte Nav1.6, Nav1.7, and CGRP immunolabeling were all significantly increased among PDPN patients compared with control subjects. Importantly, no keratinocyte biomarkers were significantly increased among the lpDPN group compared with control. In post-treatment biopsies, the keratinocyte Nav1.6, Nav1.7, and CGRP immunolabeling intensities were no longer different between control, lpDPN, or PDPN cohorts, indicating that lidocaine treatment modified the PDPN-related keratinocyte increases. Analysis of the PDPN responder population demonstrated that increased pretreatment keratinocyte biomarker immunolabeling for Nav1.6, Nav1.7, and CGRP correlated with positive outcomes to topical lidocaine treatment. Epidermal keratinocytes modulate the signaling of IENF, and several analgesic and algesic signaling systems have been identified. These results further implicate epidermal signaling mechanisms as modulators of neuropathic pain conditions, highlight a novel potential mode of action for topical treatments, and demonstrate the utility of comprehensive skin biopsy evaluation to identify novel biomarkers in clinical pain studies.
Ethical Development of Artificial Amniotic Sac and Placenta Technology: A Roadmap
Authors: Verweij E. J. , De Proost Lien , van Laar Judith O. E. H. , Frank Lily , Obermann-Borstn Sylvia A. , Vermeulen Marijn J. , van Baalen Sophie , van der Hout-van der Jagt M. Beatrijs , Kingma Elselijn
Published: December 2021

In this paper we present an initial roadmap for the ethical development and eventual implementation of artificial amniotic sac and placenta technology in clinical practice. We consider four elements of attention: (1) framing and societal dialogue; (2) value sensitive design, (3) research ethics and (4) ethical and legal research resulting in the development of an adequate moral and legal framework. Attention to all elements is a necessary requirement for ethically responsible development of this technology. The first element concerns the importance of framing and societal dialogue. This should involve all relevant stakeholders as well as the general public. We also identify the need to consider carefully the use of terminology and how this influences the understanding of the technology. Second, we elaborate on value sensitive design: the technology should be designed based upon the principles and values that emerge in the first step: societal dialogue. Third, research ethics deserves attention: for proceeding with first-in-human research with the technology, the process of recruiting and counseling eventual study participants and assuring their informed consent deserves careful attention. Fourth, ethical and legal research should concern the status of the subject in the AAPT. An eventual robust moral and legal framework for developing and implementing the technology in a research setting should combine all previous elements. With this roadmap, we emphasize the importance of stakeholder engagement throughout the process of developing and implementing the technology; this will contribute to ethically and responsibly innovating health care.
Development of a Network-Based Signal Detection Tool: The COVID-19 Adversome in the FDA Adverse Event Reporting System
Authors: Fusaroli Michele , Raschi Emanuel , Gatti Milo , De Ponti Fabrizio , Poluzzi Elisabetta
Published: December 2021

Introduction: The analysis of pharmacovigilance databases is crucial for the safety profiling of new and repurposed drugs, especially in the COVID-19 era. Traditional pharmacovigilance analyses–based on disproportionality approaches–cannot usually account for the complexity of spontaneous reports often with multiple concomitant drugs and events. We propose a network-based approach on co-reported events to help assessing disproportionalities and to effectively and timely identify disease-, comorbidity- and drug-related syndromes, especially in a rapidly changing low-resources environment such as that of COVID-19.

Materials and Methods: Reports on medications administered for COVID-19 were extracted from the FDA Adverse Event Reporting System quarterly data (January–September 2020) and queried for disproportionalities (Reporting Odds Ratio corrected for multiple comparisons). A network (the Adversome) was estimated considering events as nodes and conditional co-reporting as links. Communities of significantly co-reported events were identified. All data and scripts employed are available in a public repository.

Results: Among the 7,082 COVID-19 reports extracted, the seven most frequently suspected drugs (remdesivir, hydroxychloroquine, azithromycin, tocilizumab, lopinavir/ritonavir, sarilumab, and ethanol) have shown disproportionalities with 54 events. Of interest, myasthenia gravis with hydroxychloroquine, and cerebrovascular vein thrombosis with azithromycin. Automatic clustering identified 13 communities, including a methanol-related neurotoxicity associated with alcohol-based hand-sanitizers and a long QT/hepatotoxicity cluster associated with azithromycin, hydroxychloroquine and lopinavir-ritonavir interactions.

Conclusion: Findings from the Adversome detect plausible new signals and iatrogenic syndromes. Our network approach complements traditional pharmacovigilance analyses, and may represent a more effective signal detection technique to guide clinical recommendations by regulators and specific follow-up confirmatory studies.
Isolation and Identification of Andrographis paniculata (Chuanxinlian) and Its Biologically Active Constituents Inhibited Enterovirus 71-Induced Cell Apoptosis
Authors: Chao Wen-Wan , Kuo Yueh-Hsiung , Lin Bi-Fong
Published: December 2021

Aim:Andrographis paniculata (Burm. f.) Nees (also known as Chuanxinlian in Chinese) of Acanthaceae family is one of the Chinese herbs reputed to be effective in the treatment of inflammation, infection, cold, and fever. Enterovirus 71 (EV71) is one of the most important enteroviruses that cause hand, foot, and mouth disease (HFMD) accompanied with neurological complication.

Methods: To explore an anti-infective Chinese herb medicine, pure compounds isolated or synthesized analogues from A. paniculata (AP) ethyl acetate (EtOAc) extract are used to explore their anti-EV71-induced cytotoxicity. The antiviral activity was determined by cytopathic effect (CPE) reduction, and sub-G1 assays were used for measuring lysis and apoptosis of EV71-infected rhabdomyosarcoma (RD) cells. IFNγ-driven luciferase reporter assay was used to evaluate their potential roles in activation of immune responses.

Results: Our data showed that EV71-induced sub-G1 phase of RD cells was dose dependently increased. Highly apoptotic EV71-infected RD cells were reduced by AP extract treatment. Ergosterol peroxide (4) has the most anti-apoptotic effect among these seven compounds. In addition, 3,19-O-acetyl-14-deoxy-11,12-didehydroandrographolide (8) synthesized from acetylation of compound 7 showed significantly better antiviral activity and the lowest sub-G1 phase of 6%–18%. Further investigation of IFNγ-inducer activity of these compounds showed that compounds 3, 6, 10, 11, and 12 had significantly higher IFNγ luciferase activities, suggesting their potential to promote IFNγ expression and thus activate immune responses for antivirus function.

Conclusion: Our study demonstrated that bioactive compounds of AP and its derivatives either protecting EV71-infected RD cells from sub-G1 arrest or possessing IFNγ-inducer activity might be feasible for the development of anti-EV71 agents.
The Na+/Ca2+ Exchanger 3 Is Functionally Coupled With the NaV1.6 Voltage-Gated Channel and Promotes an Endoplasmic Reticulum Ca2+ Refilling in a Transgenic Model of Alzheimer’s Disease
Authors: Piccialli Ilaria , Ciccone Roselia , Secondo Agnese , Boscia Francesca , Tedeschi Valentina , de Rosa Valeria , Cepparulo Pasquale , Annunziato Lucio , Pannaccione Anna
Published: December 2021

The remodelling of neuronal ionic homeostasis by altered channels and transporters is a critical feature of the Alzheimer’s disease (AD) pathogenesis. Different reports converge on the concept that the Na+/Ca2+ exchanger (NCX), as one of the main regulators of Na+ and Ca2+ concentrations and signalling, could exert a neuroprotective role in AD. The activity of NCX has been found to be increased in AD brains, where it seemed to correlate with an increased neuronal survival. Moreover, the enhancement of the NCX3 currents (INCX) in primary neurons treated with the neurotoxic amyloid β 1–42 (Aβ1–42) oligomers prevented the endoplasmic reticulum (ER) stress and neuronal death. The present study has been designed to investigate any possible modulation of the INCX, the functional interaction between NCX and the NaV1.6 channel, and their impact on the Ca2+ homeostasis in a transgenic in vitro model of AD, the primary hippocampal neurons from the Tg2576 mouse, which overproduce the Aβ1–42 peptide. Electrophysiological studies, carried in the presence of siRNA and the isoform-selective NCX inhibitor KB-R7943, showed that the activity of a specific NCX isoform, NCX3, was upregulated in its reverse, Ca2+ influx mode of operation in the Tg2576 neurons. The enhanced NCX activity contributed, in turn, to increase the ER Ca2+ content, without affecting the cytosolic Ca2+ concentrations of the Tg2576 neurons. Interestingly, our experiments have also uncovered a functional coupling between NCX3 and the voltage-gated NaV1.6 channels. In particular, the increased NaV1.6 currents appeared to be responsible for the upregulation of the reverse mode of NCX3, since both TTX and the Streptomyces griseolus antibiotic anisomycin, by reducing the NaV1.6 currents, counteracted the increase of the INCX in the Tg2576 neurons. In agreement, our immunofluorescence analyses revealed that the NCX3/NaV1.6 co-expression was increased in the Tg2576 hippocampal neurons in comparison with the WT neurons. Collectively, these findings indicate that NCX3 might intervene in the Ca2+ remodelling occurring in the Tg2576 primary neurons thus emerging as a molecular target with a neuroprotective potential, and provide a new outcome of the NaV1.6 upregulation related to the modulation of the intracellular Ca2+ concentrations in AD neurons.
Unique Pharmacological Properties of α-Conotoxin OmIA at α7 nAChRs
Authors: Ho Thao N.T. , Abraham Nikita , Lewis Richard J.
Published: December 2021

OmIA, isolated from Conus omaria venom, is a potent antagonist at α7 nAChRs. We determined the co-crystal structure of OmIA with Lymnae stagnalis acetylcholine binding protein (Ls-AChBP) that identified His5, Val10 and Asn11 as key determinants for the high potency of OmIA at α7 nAChRs. Remarkably, despite a competitive binding mode observed in the co-crystal structure, OmIA and analogues displayed functional insurmountable antagonism at α7 and α3β4 nAChRs, except OmIA analogues having long side chain at position 10 ([V10Q]OmIA and [V10L]OmIA), which were partial insurmountable antagonist at α7 nAChRs in the presence of type II positive allosteric modulators (PAMs). A “two-state, two-step” model was used to explain these observations, with [V10Q]OmIA and [V10L]OmIA co-existing in a fast reversible/surmountable as well as a tight binding/insurmountable state. OmIA and analogues also showed biphasic-inhibition at α7 nAChRs in the presence of PNU120596, with a preference for the high-affinity binding site following prolonged exposure. The molecular basis of binding and complex pharmacological profile of OmIA at α7 nAChRs presented in here expands on the potential of α-conotoxins to probe the pharmacological properties of nAChRs and may help guide the development novel α7 modulators.
Exposure to Dibutyl Phthalate and Reproductive-Related Outcomes in Animal Models: Evidence From Rodents Study
Authors: Wang Jiawei , Zhang Xi , Li Yang , Liu Yingqing , Tao Lingsong
Published: December 2021

Background: Dibutyl phthalate (DBP) was an endocrine disruptor, which may lead to cancer and affects reproductive function when accumulated in the body. But the precise role of DBP in the reproductive system remained controversial.

Objective: We employed the meta-analysis to explore the relationship between DBP and reproductive-related outcomes.

Methods: We searched relevant literature in PubMed, EMBASE, and Web of Science databases. The standardized mean differences (SMDs) and their 95% CIs were measured by random-effects models. Funnel plots and Egger’s regression test were applied to assess publication bias.

Results: Finally, 19 literatures were included in this research. The outcomes revealed that DBP was negatively correlated with reproductive organs weight (testis weight: SMD: −0.59; 95% Cl: −1.23, −0.23; seminal vesicles weight: SMD: −0.74; 95% Cl: −1.21, −0.27; prostate weight: SMD: −0.46; 95% Cl: −0.76, −0.16) and sperm parameters (sperm morphology: SMD: 1.29; 95% Cl: 0.63, 1.94; sperm count: SMD: −1.81; 95% Cl: −2.39, −1.23; sperm motility: SMD: −1.92; 95% Cl: −2.62, −1.23).

Conclusion: Our research demonstrated that DBP may be negatively associated with reproductive-related indicators, especially at Gestation exposure period and middle dose (100–500 mg/kg/day).
Evidence of Ventricular Arrhythmogenicity and Cardiac Sympathetic Hyperinnervation in Early Cirrhotic Cardiomyopathy
Authors: Liu Shin-Huei , Lo Li-Wei , Chou Yu-Hui , Lin Wei-Lun , Tsai Tsung-Ying , Cheng Wen-Han , Lin Yenn-Jiang , Chang Shih-Lin , Hu Yu-Feng , Chung Fa-Po , Huang Hui-Chun , Chen Shih-Ann
Published: December 2021

Cirrhotic cardiomyopathy (CMP) is associated with altered cardiac electrophysiological (EP) properties, which leads to the risk of ventricular arrhythmias (VAs). We aimed to evaluate the EP properties, autonomic, and structural remodeling in a rabbit model with early liver cirrhosis (LC). Twelve rabbits were assigned to the sham and LC groups. The early-stage LC was induced by the ligation of the common bile duct. All rabbits received an EP study, VA inducibility test, myocardial, and liver histology staining. Western blot analyses of protein expression and tyrosine hydroxylase stain for sympathetic nerves were performed. The effective refractory period the LC group was significantly longer than the sham group [i.e., left ventricle (LV) 205.56 ± 40.30 vs. 131.36 ± 7.94 ms; right ventricle (RV) 206.78 ± 33.07 vs. 136.79 ± 15.15 ms; left atrium (LA) 140.56 ± 28.75 vs. 67.71 ± 14.29 ms; and right atrium (RA) 133.78 ± 40.58 vs. 65.43 ± 19.49 ms, all p < 0.01], respectively. The VA inducibility was elevated in the LC group when compared with the sham group (i.e., 21.53 ± 7.71 vs. 7.76 ± 2.44%, p = 0.013). Sympathetic innervation (102/μm2/mm2) was increased in all cardiac chambers of the LC group compared with the sham group (i.e., LV 9.11 ± 4.86 vs. 0.17 ± 0.15, p < 0.01; RV 4.36 ± 4.95 vs. 0.18 ± 0.12, p = 0.026; LA 6.79 ± 1.02 vs. 0.44 ± 0.20, p = 0.018; and RA 15.18 ± 5.12 vs. 0.10 ± 0.07, p = 0.014), respectively. Early LC is presented with an increased ventricular vulnerability, structural heterogeneity, and sympathetic innervation. Close monitoring for fatal arrhythmias is warranted in patients with early stages of LC.
Estimation of Pulmonary Arterial Wave Reflection by Echo-Doppler: A Preliminary Study in Dogs With Experimentally-Induced Acute Pulmonary Embolism
Authors: Yoshida Tomohiko , Uejima Tokuhisa , Komeda Syunta , Matsuura Katsuhiro , Uemura Akiko , Hayama Hiromasa , Yamashita Takeshi , Yilmaz Zeki , Tanaka Ryou
Published: December 2021

Background: Pulmonary arterial (PA) wave reflection provides additional information for assessing right ventricular afterload, but its applications is hampered by the need for invasive pressure and flow measurements. We tested the hypothesis that PA pressure and flow waveforms estimated by Doppler echocardiography could be used to quantify PA wave reflection.

Methods: Doppler echocardiographic images of tricuspid regurgitation and right ventricular outflow tract flow used to estimate PA pressure and flow waveforms were acquired simultaneously with direct measurements with a dual sensor-tipped catheter under various hemodynamic conditions in a canine model of pulmonary hypertension (n = 8). Wave separation analysis was performed on echo-Doppler derived as well as catheter derived waveforms to separate PA pressure into forward (Pf) and backward (Pb) pressures and derive wave reflection coefficient (RC) defined as the ratio of peak Pb to peak Pf.

Results: Wave reflection indices by echo-Doppler agreed well with corresponding indices by catheter (Pb: mean difference = 0.4 mmHg, 95% limits of agreement = −4.3 to 5.0 mmHg; RC: bias = 0.13, 95% limits of agreement = −0.25 to 0.26). RC correlated negatively with PA compliance.

Conclusion: This echo-Doppler method yields reasonable measurement of reflected wave in the pulmonary circulation, paving the way to a more integrative assessment of pulmonary hemodynamics in the clinical setting.
Functional Characterization of Cotton C-Repeat Binding Factor Genes Reveal Their Potential Role in Cold Stress Tolerance
Authors: Liu Jiangna , Magwanga Richard Odongo , Xu Yanchao , Wei Tingting , Kirungu Joy Nyangasi , Zheng Jie , Hou Yuqing , Wang Yuhong , Agong Stephen Gaya , Okuto Erick , Wang Kunbo , Zhou Zhongli , Cai Xiaoyan , Liu Fang
Published: December 2021

Low temperature is a common biological abiotic stress in major cotton-growing areas. Cold stress significantly affects the growth, yield, and yield quality of cotton. Therefore, it is important to develop more robust and cold stress-resilient cotton germplasms. In response to climate change and erratic weather conditions, plants have evolved various survival mechanisms, one of which involves the induction of various stress responsive transcript factors, of which the C-repeat-binding factors (CBFs) have a positive effect in enhancing plants response to cold stress. In this study, genomewide identification and functional characterization of the cotton CBFs were carried out. A total of 29, 28, 25, 21, 30, 26, and 15 proteins encoded by the CBF genes were identified in seven Gossypium species. A phylogenetic evaluation revealed seven clades, with Clades 1 and 6 being the largest. Moreover, the majority of the proteins encoded by the genes were predicted to be located within the nucleus, while some were distributed in other parts of the cell. Based on the transcriptome and RT-qPCR analysis, Gthu17439 (GthCBF4) was highly upregulated and was further validated through forward genetics. The Gthu17439 (GthCBF4) overexpressed plants exhibited significantly higher tolerance to cold stress, as evidenced by the higher germination rate, increased root growth, and high-induction levels of stress-responsive genes. Furthermore, the overexpressed plants under cold stress had significantly reduced oxidative damage due to a reduction in hydrogen peroxide (H2O2) production. Moreover, the overexpressed plants under cold stress had minimal cell damage compared to the wild types, as evidenced by the Trypan and 3,3′-Diaminobenzidine (DAB) staining effect. The results showed that the Gthu17439 (GthCBF4) could be playing a significant role in enhancing cold stress tolerance in cotton and can be further exploited in developing cotton germplasm with improved cold-stress tolerance.
Six Newly Sequenced Chloroplast Genomes From Trentepohliales: The Inflated Genomes, Alternative Genetic Code and Dynamic Evolution
Authors: Fang Jiao , Liu Benwen , Liu Guoxiang , Verbruggen Heroen , Zhu Huan
Published: December 2021

Cephaleuros is often known as an algal pathogen with 19 taxonomically valid species, some of which are responsible for red rust and algal spot diseases in vascular plants. No chloroplast genomes have yet been reported in this genus, and the limited genetic information is an obstacle to understanding the evolution of this genus. In this study, we sequenced six new Trentepohliales chloroplast genomes, including four Cephaleuros and two Trentepohlia. The chloroplast genomes of Trentepohliales are large compared to most green algae, ranging from 216 to 408 kbp. They encode between 93 and 98 genes and have a GC content of 26–36%. All new chloroplast genomes were circular-mapping and lacked a quadripartite structure, in contrast to the previously sequenced Trentepohlia odorata, which does have an inverted repeat. The duplicated trnD-GTC, petD, and atpA genes in C. karstenii may be remnants of the IR region and shed light on its reduction. Chloroplast genes of Trentepohliales show elevated rates of evolution, strong rearrangement dynamics and several genes display an alternative genetic code with reassignment of the UGA/UAG codon presumably coding for arginine. Our results present the first whole chloroplast genome of the genus Cephaleuros and enrich the chloroplast genome resources of Trentepohliales.
Teaching and Learning in COVID-19 Lockdown in Scotland: Teachers’ Engaged Pedagogy
Authors: Colville Tracey , Hulme Sarah , Kerr Claire , Mercieca Daniela , Mercieca Duncan P.
Published: December 2021

This paper reports on a study of teachers’ perceptions of teaching and learning in Scotland during the COVID-19 pandemic through the lens of engaged pedagogy and the ideas of bell hooks. It aimed to explore the different ways that teachers experienced teaching and learning during this time and the impact this may have had on teacher identity. Sixty teachers and head teachers were interviewed using MS Teams in the period April-June, 2020. For this paper, 18 transcripts were analyzed by members of the research team. Four key themes emerged from the interview data: Working from home, parental engagement, teacher identity, and changes in pedagogy. Each of these themes were discussed in terms of concepts such as engaged pedagogy, agency, self-actualization, recognition and boundary transgression situated in the work of bell hooks. The idea of boundaries wove itself throughout our data as teachers expressed how the transgression of boundaries was occurring in multiple, and often contradictory, ways in pedagogical, professional, institutional and personal spaces and systems. We see in our data evidence of a shift in practice not just in the way teachers are ‘doing’ education but also, perhaps, in the way that teachers are ‘being’ as educators as they adapt to different ways of knowing. This study provides a unique exploration of a time and space in Scotland during 2020. However, the themes and understandings that emerged are of relevance to educators internationally. Schools across the world were impacted by various lockdowns imposed by the Covid-19 pandemic and teachers faced a common set of challenges that were resolved via re-negotiation and recognition of individual and collective agency to create new pedagogies.
Reliability and Validity of the Chinese Nine-Item Basic Psychological Need Satisfaction Scale Based on Self-Determination Theory With Older Adults
Authors: Yang Yuting , Yao Miao , Yang Yongwei , Ye Qiong , Lin Ting
Published: December 2021

Background: Self-determination theory distinguishes three basic human psychological needs: competence, relatedness, and autonomy. The measurement of these needs in populations of older adults has been limited and inadequate. Yet, results from such an assessment are likely to be valuable in policymaking, specifically toward the goal of healthy aging.

Aim: The objective of this study was to test the reliability and validity of the Chinese version of the Basic Psychological Need Satisfaction Scale (BPNS) based on self-determination theory with older adults.

Methods: A total of 809 older adults were invited to participate in this study. We examined the item analysis, internal reliability, factorial validity, criterion validity, and measurement invariance across sex of a Chinese translation of the BPNS.

Results: The findings demonstrated that the scale had a good factorial validity, criterion validity, and satisfactory internal reliability. All the items were qualified according to item analysis (p < 0.001). The Cronbach’s α coefficient for the total scale was 0.877. The coefficients of three subscales were 0.826 (autonomy), 0.807 (competence), and 0.847 (relatedness). Exploratory factor analysis indicated three factors that explained 75.12% of the total variance. Confirmatory factor analysis showed measurement fit exceeded the recommended criteria in all the cases. Measurement invariance analysis manifested that the factor loadings, factor variances and covariances, and residuals to measurement structure were invariant across the male and female participants.

Conclusion: The Chinese version of the BPNS based on self-determination theory was proven to be reliable and valid. The usability of the scale to assess the satisfaction of the basic psychological needs of older adults in China was demonstrated.
How Gig Worker Responds to Negative Customer Treatment: The Effects of Work Meaningfulness and Traits of Psychological Resilience
Authors: Xiongtao He , Wenzhu Lu , Haibin Luo , Shanshi Liu
Published: December 2021

The negative interpersonal interaction between customers and platform gig workers has become a problem for platform owners and government. This study investigates the role of negative customer treatment in the context of gig work and its impact on gig workers’ sabotage behavior. A questionnaire survey approach was used in the study, collected three-wave survey data from 258 Chinese gig workers including food-deliver platform workers and app-based ride-hailing drivers. Both effects of the mediation and moderation were tested, all of which find support, using hierarchical multiple regression by SPSS22.0. Results indicate that negative customer treatment can also predict gig workers’ service sabotage through work meaningfulness. Furthermore, positive customer treatment acted as an effective safeguard against the effects of negative customer treatment on employee service sabotage. Trait psychological resilience can also mitigate the effects of a low level of work meaningfulness. The manuscript’s focus provides an interesting angle to the previous research, especially the inclusion of work meaningfulness and trait resilience, on negative customer treatment in the context of gig work. This study contributes to further broaden the perspective of conservation of resource (COR) theory for individual intrinsic motivation analysis. Practical implications for platform management and government governance have also been discussed in this manuscript.
Pre-pandemic Predictors of Loneliness in Adult Men During COVID-19
Authors: Mansour Kayla A. , Greenwood Christopher J. , Biden Ebony J. , Francis Lauren M. , Olsson Craig A. , Macdonald Jacqui A.
Published: December 2021

Loneliness is a major public health issue, with its prevalence rising during COVID-19 pandemic lockdowns and mandated “social distancing” practices. A 2020 global study (n = 46,054) found that, in comparison to women, men experienced the greatest levels of loneliness. Although research on predictors of loneliness during COVID-19 is increasing, little is known about the characteristics of men who may be particularly vulnerable. Studies using prospective data are needed to inform preventative measures to support men at risk of loneliness. The current study draws on rare longitudinal data from an Australian cohort of men in young to mid-adulthood (n = 283; aged M = 34.6, SD = 1.38 years) to examine 25 pre-pandemic psychosocial predictors of loneliness during COVID-19 social restrictions (March–September 2020). Adjusted linear regressions identified 22 pre-pandemic predictors of loneliness across a range of trait-based, relational, career/home and mental health variables. Given the extensive set of predictors, we then conducted penalized regression models (LASSO), a machine learning approach, allowing us to identify the best fitting multivariable set of predictors of loneliness during the pandemic. In these models, men's sense of pre-pandemic environmental mastery emerged as the strongest predictor of loneliness. Depression, neuroticism and social support also remained key predictors of pandemic loneliness (R2 = 26, including covariates). Our findings suggest that men's loneliness can be detected prospectively and under varying levels of social restriction, presenting possible targets for prevention efforts for those most vulnerable.
Adults With Opioid and Methamphetamine Co-use Have Lower Odds of Completing Short-Term Residential Treatment Than Other Opioid Co-use Groups: A Retrospective Health Services Study
Authors: Ware Orrin D. , Manuel Jennifer I. , Huhn Andrew S.
Published: December 2021

Objective: There is an increase in persons entering substance use treatment who co-use opioids and methamphetamines in recent years. Co-using these substances may negatively impact treatment retention in the residential setting. We explored predictors of adults completing short-term residential treatment among persons with primary opioid use disorder (OUD) who co-use either alcohol, benzodiazepines, cocaine, or methamphetamines.

Methods: This study used the 2019 de-identified, publicly available Treatment Episode Dataset-Discharges. The sample included adults discharged from short-term residential treatment with primary OUD who co-used either alcohol, benzodiazepines, cocaine, or methamphetamines. The final sample size included 24,120 treatment episodes. Univariate statistics were used to describe the sample. Two logistic regression models were used to predict completing treatment. The first logistic regression model included the co-use groups as predictors and the second model added other demographic and treatment-relevant covariates.

Results: A slight majority (51.4%) of the sample prematurely discharged from treatment. Compared to the other three co-use groups, the opioid and methamphetamine co-use group had the highest proportion of individuals who were women (45.0%), unemployed (62.5%), current injection drug use (76.0%), living in the Midwest (35.9%), living in the south (33.5%), and living in the west (15.5%). The opioid and methamphetamine co-use group also had the highest proportion of individuals not receiving medications for OUD (84.9%), not having a prior treatment episode (28.7%), and not completing treatment (57.4%). In the final logistic regression model, which included covariates, the opioid and alcohol (OR = 1.18, 95% CI = 1.080–1.287, p < 0.001), opioid and benzodiazepine (OR = 1.33, 95% CI = 1.213–1.455, p < 0.001), and opioid and cocaine (OR = 1.16, 95% CI = 1.075–1.240, p < 0.001) co-use groups had higher odds of completing treatment than the opioid and methamphetamine co-use group.

Conclusions: Opioid and methamphetamine co-use may complicate short-term residential treatment retention. Future work should identify effective strategies to retain persons who co-use opioids and methamphetamines in treatment.