bluuebunny/crossref_metadata_2025 huggingface dataset:
New Perspectives on the Immunopathogenesis and Treatment of Uveitis Associated With Vogt-Koyanagi-Harada Disease
Authors: Abu El-Asrar Ahmed M. , Van Damme Jo , Struyf Sofie , Opdenakker Ghislain
Published: November 2021

Uveitis associated with Vogt-Koyanagi-Harada (VKH) disease is a bilateral, chronic, granulomatous autoimmune disease associated with vitiligo, poliosis, alopecia, and meningeal and auditory manifestations. The disease affects pigmented races with a predisposing genetic background. Evidence has been provided that the clinical manifestations are caused by a T-lymphocyte-mediated autoimmune response directed against antigens associated with melanocytes in the target organs. Alongside of T lymphocytes, autoreactive B cells play a central role in the development and propagation of several autoimmune diseases. The potential role of B lymphocytes in the pathogenesis of granulomatous uveitis associated with VKH disease is exemplified within several studies. The early initial-onset acute uveitic phase typically exhibits granulomatous choroiditis with secondary exudative retinal detachment and optic disc hyperemia and swelling, subsequently involving the anterior segment if not adequately treated. The disease eventually progresses to chronic recurrent granulomatous anterior uveitis with progressive posterior segment depigmentation resulting in “sunset glow fundus” appearance and chorioretinal atrophy if not properly controlled. Chronically evolving disease is more refractory to treatment and, consequently, vision-threatening complications have been recognized to occur in the chronic recurrent phase of the disease. Conventional treatment with early high-dose systemic corticosteroids is not sufficient to prevent chronic evolution. Addition of immunomodulatory therapy with mycophenolate mofetil as first-line therapy combined with systemic corticosteroids in patients with acute initial-onset disease prevents progression to chronic evolution, late complications, vitiligo, and poliosis. Furthermore, patients under such combined therapy were able to discontinue treatment without relapse of inflammation. These findings suggest that there is a therapeutic window of opportunity for highly successful treatment during the early initial-onset acute uveitic phases, likely because the underlying disease process is not fully matured. It is hypothesized that early and aggressive immunosuppressive therapy will prevent remnant epitope generation in the initiation of the autoimmune process, the so-called primary response. B cell depleting therapy with the anti-CD20 monoclonal antibody rituximab is effective in patients with refractory chronic recurrent granulomatous uveitis. The good response after rituximab therapy reinforces the idea of an important role of B cells in the pathogenesis or progression of chronic recurrent uveitis associated with VKH disease.
Process Evaluation of Internet-Based Cognitive Behavioral Therapy Intervention for Informal Caregivers
Authors: Biliunaite Ieva , Kazlauskas Evaldas , Sanderman Robbert , Andersson Gerhard
Published: November 2021

Background: Informal caregivers are individuals who provide care for ill, frail, or otherwise dependent family members, siblings, or friends. Due to the caregiving demands, informal caregivers are known to experience negative mental health symptoms, such as stress or anxiety. Interventions based on Internet-based Cognitive Behavioral Therapy (ICBT) principles have been previously found to be effective for different populations and could also be considered as a plausible support option for informal caregivers. However, findings regarding effectiveness alone might not be sufficient for informing about the overall feasibility of the intervention.

Objective: The aim of this process evaluation study was to evaluate the feasibility of a previously developed ICBT intervention for informal caregivers in Lithuania. More specifically, we evaluated the suitability of the intervention in relation to its content and delivery mode.

Methods: Two studies were conducted. Study 1 consisted of participant evaluations of an 8-week, 8-module long therapist supported ICBT intervention. Evaluations for the Study 1 were retrieved from previously unused data, obtained from pilot testing of the intervention in which 63 informal caregivers took part. The evaluations contained of qualitative data (participant comments), as well as quantitative data (evaluations of each of the sessions). The Study 2 was an online stakeholder focus-group discussion conducted via Zoom. Eight stakeholders took part in the discussion, among whom there were social workers, medical professionals as well as individuals with caregiving experience themselves. Data were analyzed using descriptive statistics, thematic analysis, and data coding.

Results: Results of the Study 1 showed that most of the pilot randomized controlled trial participants evaluated content and format of the intervention positively. These results were complemented by the findings in the Study 2, in which stakeholders evaluated the intervention as suitable and promising. In addition, stakeholders made certain suggestions for improving the intervention's usability for the informal caregivers. This included improving the instructions, providing with more guidance, and considering personalization options.

Conclusion: The process evaluation helped to evaluate the feasibility of the ICBT intervention for informal caregivers in Lithuania from the two perspectives: users and stakeholders. Our findings suggest that the intervention is suitable for the target population.
18F-FDG PET/CT in a Patient With Malignant Pheochromocytoma Recurrence and Bone Metastasis After Operation—Case Report and Review of the Literature
Authors: Feng Bei , Chen Maojia , Jiang Yanghongyan , Hui Yongfeng , Zhao Qian
Published: November 2021

Introduction: Bone metastasis of malignant pheochromocytoma is a rare disease. We report a patient with a 10-year history who underwent 18F-FDG PET/CT to detect bone metastasis and receive radiotherapy and chemotherapy with complete response for bilateral iliac pain.

Case presentation: A 48-year-old male patient complained of dizziness, hypertension, and bilateral iliac pain for 2 months. The patient had a history of resection of bilateral malignant adrenal pheochromocytoma 10 years earlier, and all complaints were relieved immediately after operation. 18F-FDGPET/CT showed abdominal lymph node uptake and multiple bone uptake, as well as multiple brown fat uptake. A biopsy of the left ilium confirms the metastasis of malignant pheochromocytoma.

Discussion: In our literature review, we discuss the metastasis of pheochromocytoma reported by some scholars, and the role of radionuclides such as 18F-FDG PET/CT, 18F-DOPA PET/CT, I-123MIBG, and 68Ga-DOTATATE PET, in the diagnosis of malignant pheochromocytoma. The patient above is a good case for clinicians in the diagnosis and treatment of metastatic pheochromocytoma, especially in some hospitals with only 18F-FDG imaging agents.

Conclusion: A review of this case and similar rare cases in the literature illustrates the importance of 18F-FDG PET/CT in the diagnosis of malignant pheochromocytoma.
Development and Validation of a Predictive Scoring System for In-hospital Death in Patients With Intra-Abdominal Infection: A Single-Center 10-Year Retrospective Study
Authors: Xue Gaici , Liang Hongyi , Ye Jiasheng , Ji Jingjing , Chen Jianyu , Ji Bo , Liu Zhifeng
Published: November 2021

Objective: To develop and validate a scoring system to predict the risk of in-hospital death in patients with intra-abdominal infection (IAI).

Materials and Methods: Patients with IAI (n = 417) treated at our hospital between June 2010 and May 2020 were retrospectively reviewed. Risk factors for in-hospital death were identified by logistic regression analysis. The regression coefficients of each risk factor were re-assigned using the mathematical transformation principle to establish a convenient predictive scoring system. The scoring system was internally validated by bootstrapping sample method.

Results: Fifty-three (53/417, 12.7%) patients died during hospitalization. On logistic regression analysis, high APACHE II score (P = 0.012), pneumonia (P = 0.002), abdominal surgery (P = 0.001), hypoproteinemia (P = 0.025), and chronic renal insufficiency (P = 0.001) were independent risk factors for in-hospital death. On receiver operating characteristic curve analysis, the composite index combining these five risk factors showed a 62.3% sensitivity and 80.2% specificity for predicting in-hospital death (area under the curve: 0.778; 95% confidence interval: 0.711–0.845, P < 0.001). The predictive ability of the composite index was better than that of each independent risk factor. A scoring system (0–14 points) was established by re-assigning each risk factor based on the logistic regression coefficient: APACHE II score (10–15 score, 1 point; >15 score, 4 points); pneumonia (2 points), abdominal surgery (2 points), hypoproteinemia (2 points), and chronic renal insufficiency (4 points). Internal validation by 1,000 bootstrapping sample showed relatively high discriminative ability of the scoring system (C-index = 0.756, 95% confidence interval: 0.753–0.758).

Conclusions: The predictive scoring system based on APACHE II score, pneumonia, abdominal surgery, hypoproteinemia, and chronic renal insufficiency can help predict the risk of in-hospital death in patients with IAI.
Juvenile Idiopathic Arthritis and COVID-19 Pandemic: Good Compliance With Treatment, Reluctance to Return to School
Authors: Quéré Baptiste , Lemelle Irene , Lohse Anne , Pillet Pascal , Molimard Julie , Richer Olivier , Sordet Christelle , Despert Véronique , Rossi-Semerano Linda , Borocco Charlotte , Kone-Paut Isabelle , Gervais Elisabeth , Guellec Dewi , Devauchelle-Pensec Valérie
Published: November 2021

Objective: The SARS-CoV-2 pandemic has induced an exceptional sanitary crisis, potentially having an impact on treatment continuation, for juvenile idiopathic arthritis (JIA) patients receiving immunosuppressive therapies. After national lockdowns, many patients were also concerned about their safety at school. We evaluated the impact of the pandemic on the optimal continuation of treatment and on the return to school in JIA patients.

Methods: JIA patients under 18 years of age, usually treated with disease-modifying anti-rheumatic drugs (DMARDs) were prospectively included during their outpatient visit and completed a standardized questionnaire. The primary outcome was DMARD treatment modification in relation to the context of the pandemic but we also evaluated the pandemic's impact on the schooling.

Results: One hundred and seventy three patients from 8 different expert centers were included between May and August 2020. Their mean age was 11.6 years (± 4.1 years), and most of them 31.2% (54/173) had a rheumatoid factor-negative polyarticular JIA. Fifty percent (86/172) were treated with methotrexate, and 72.5% (124/171) were treated with bDMARDs. DMARD treatment modification in relation to the pandemic was observed in 4.0% (7/173) of participants. 49.1% (81/165) of the patients did not return to school due to a personal/parental decision in 69.9% (55/81) of cases. Two patients were diagnosed positive for SARS-CoV-2 infection.

Conclusion: This study suggests that JIA patients treated with DMARDs continued their treatment during the pandemic and were rarely affected by symptomatic COVID-19. In contrast, parents' reluctance was a major obstacle for returning to school. Therefore, more solidified school reopening strategies should be developed.
Tools Are Needed to Promote Sedation Practices for Mechanically Ventilated Patients
Authors: Wang Tao , Zhou Dongxu , Zhang Zhongheng , Ma Penglin
Published: November 2021

Suboptimal sedation practices continue to be frequent, although the updated guidelines for management of pain, agitation, and delirium in mechanically ventilated (MV) patients have been published for several years. Causes of low adherence to the recommended minimal sedation protocol are multifactorial. However, the barriers to translation of these protocols into standard care for MV patients have yet to be analyzed. In our view, it is necessary to develop fresh insights into the interaction between the patients' responses to nociceptive stimuli and individualized regulation of patients' tolerance when using analgesics and sedatives. By better understanding this interaction, development of novel tools to assess patient pain tolerance and to define and predict oversedation or delirium may promote better sedation practices in the future.
Artificial Cornea: Past, Current, and Future Directions
Authors: Holland Gráinne , Pandit Abhay , Sánchez-Abella Laura , Haiek Andrea , Loinaz Iraida , Dupin Damien , Gonzalez Maria , Larra Eva , Bidaguren Aritz , Lagali Neil , Moloney Elizabeth B. , Ritter Thomas
Published: November 2021

Corneal diseases are a leading cause of blindness with an estimated 10 million patients diagnosed with bilateral corneal blindness worldwide. Corneal transplantation is highly successful in low-risk patients with corneal blindness but often fails those with high-risk indications such as recurrent or chronic inflammatory disorders, history of glaucoma and herpetic infections, and those with neovascularisation of the host bed. Moreover, the need for donor corneas greatly exceeds the supply, especially in disadvantaged countries. Therefore, artificial and bio-mimetic corneas have been investigated for patients with indications that result in keratoplasty failure. Two long-lasting keratoprostheses with different indications, the Boston type-1 keratoprostheses and osteo-odonto-keratoprostheses have been adapted to minimise complications that have arisen over time. However, both utilise either autologous tissue or an allograft cornea to increase biointegration. To step away from the need for donor material, synthetic keratoprostheses with soft skirts have been introduced to increase biointegration between the device and native tissue. The AlphaCor™, a synthetic polymer (PHEMA) hydrogel, addressed certain complications of the previous versions of keratoprostheses but resulted in stromal melting and optic deposition. Efforts are being made towards creating synthetic keratoprostheses that emulate native corneas by the inclusion of biomolecules that support enhanced biointegration of the implant while reducing stromal melting and optic deposition. The field continues to shift towards more advanced bioengineering approaches to form replacement corneas. Certain biomolecules such as collagen are being investigated to create corneal substitutes, which can be used as the basis for bio-inks in 3D corneal bioprinting. Alternatively, decellularised corneas from mammalian sources have shown potential in replicating both the corneal composition and fibril architecture. This review will discuss the limitations of keratoplasty, milestones in the history of artificial corneal development, advancements in current artificial corneas, and future possibilities in this field.
Systematic Characterization of High-Power Short-Duration Ablation: Insight From an Advanced Virtual Model
Authors: Petras Argyrios , Moreno Weidmann Zoraida , Leoni Massimiliano , Gerardo-Giorda Luca , Guerra Jose M.
Published: November 2021

Background: High-power short-duration (HPSD) recently emerged as a new approach to radiofrequency (RF) catheter ablation. However, basic and clinical data supporting its effectiveness and safety is still scarce.

Objective: We aim to characterize HPSD with an advanced virtual model, able to assess lesion dimensions and complications in multiple conditions and compare it to standard protocols.

Methods: We evaluate, on both atrium and ventricle, three HPSD protocols (70 W/8 s, 80 W/6 s, and 90 W/4 s) through a realistic 3D computational model of power-controlled RF ablation, varying catheter tip design (spherical/cylindrical), contact force (CF), blood flow, and saline irrigation. Lesions are defined by the 50°C isotherm contour. Ablations are deemed safe or complicated by pop (tissue temperature >97°C) or charring (blood temperature >80°C). We compared HPSD with standards protocols (30–40 W/30 s). We analyzed the effect of a second HPSD application.

Results: We simulated 432 applications. Most (79%) associated a complication, especially in the atrium. The three HPSD protocols performed similarly in the atrium, while 90 W/4 s appeared the safest in the ventricle. Low irrigation rate led frequently to charring (72%). High-power short-duration lesions were 40–60% shallower and smaller in volume compared to standards, although featuring similar width. A second HPSD application increased lesions to a size comparable to standards.

Conclusion: High-power short-duration lesions are smaller in volume and more superficial than standards but comparable in width, which can be advantageous in the atrium. A second application can produce lesions similar to standards in a shorter time. Despite its narrow safety margin, HPSD seems a valuable new clinical approach.
Viable Severe Acute Respiratory Syndrome Coronavirus 2 Isolates Exhibit Higher Correlation With Rapid Antigen Assays Than Subgenomic RNA or Genomic RNA
Authors: Tariq Misbah , Kim Dong-Min , Kim Choon-Mee , Bang Mi-Seon , Lee You Mi , Seo Jun-Won , Kim Da Young , Yun Na Ra
Published: November 2021

Background: Rapid identification and effective isolation are crucial for curbing the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To meet this requirement, antigen-detection rapid diagnostic tests (Ag-RDTs) are essential.

Methods: Between February 2020 and August 2020 we performed a cohort study of patients with confirmed COVID-19. The clinical performance of Ag rapid fluorescence immunoassay (FIA) and Ag Gold was evaluated and compared in parallel with genomic and subgenomic real-time reverse transcription-polymerase chain reaction (rRT-PCR) and cell culture-based assays.

Results: In total, 150 samples were tested. Of these, 63 serial samples were obtained from 11 patients with SARS-CoV-2 and 87 from negative controls. Serial respiratory samples were obtained 2 days prior to symptom onset (-2) up to 25 days post-symptom onset. Overall, for rRT-PCR-positive samples (n = 51), the detection sensitivity of Ag rapid FIA and Ag Gold was 74.5% and 53.49%, respectively, with a specificity of 100%; however, for samples with low cycle threshold (Ct) values, Ag rapid FIA and Ag Gold exhibited a sensitivity of 82.61% (Ct ≤ 30, 5.6 log10RNA copies/mL) and 80% (Ct ≤ 25, 6.9 log10RNA copies/mL), respectively. Despite low analytical sensitivity, both Ag-RDTs detected 100% infection in cell culture-positive samples (n = 15) and were highly effective in distinguishing viable samples from those with subgenomic RNA (66.66%). For both Ag-RDTs, all samples that yielded discordant results (rRT-PCR + ve/Ag-RDT -ve) were also negative by culture.

Conclusion: The data suggest that Ag-RDTs reliably detect viable SARS-CoV-2; thus, they may serve as an important tool for rapid detection of potentially infectious individuals.
Combating Drug-Resistant Bacteria Using Photothermally Active Nanomaterials: A Perspective Review
Authors: Kaur Kawaljeet , Reddy Sagar , Barathe Pramod , Shriram Varsha , Anand Uttpal , Proćków Jarosław , Kumar Vinay
Published: November 2021

Injudicious use of antibiotics has been the main driver of severe bacterial non-susceptibility to commonly available antibiotics (known as drug resistance or antimicrobial resistance), a global threat to human health and healthcare. There is an increase in the incidence and levels of resistance to antibacterial drugs not only in nosocomial settings but also in community ones. The drying pipeline of new and effective antibiotics has further worsened the situation and is leading to a potentially “post-antibiotic era.” This requires novel and effective therapies and therapeutic agents for combating drug-resistant pathogenic microbes. Nanomaterials are emerging as potent antimicrobial agents with both bactericidal and potentiating effects reported against drug-resistant microbes. Among them, the photothermally active nanomaterials (PANs) are gaining attention for their broad-spectrum antibacterial potencies driven mainly by the photothermal effect, which is characterized by the conversion of absorbed photon energy into heat energy by the PANs. The current review capitalizes on the importance of using PANs as an effective approach for overcoming bacterial resistance to drugs. Various PANs leveraging broad-spectrum therapeutic antibacterial (both bactericidal and synergistic) potentials against drug-resistant pathogens have been discussed. The review also provides deeper mechanistic insights into the mechanisms of the action of PANs against a variety of drug-resistant pathogens with a critical evaluation of efflux pumps, cell membrane permeability, biofilm, and quorum sensing inhibition. We also discuss the use of PANs as drug carriers. This review also discusses possible cytotoxicities related to the therapeutic use of PANs and effective strategies to overcome this. Recent developments, success stories, challenges, and prospects are also presented.
Metabarcoding Reveals Lacustrine Picocyanobacteria Respond to Environmental Change Through Adaptive Community Structuring
Authors: Schallenberg Lena A. , Pearman John K. , Burns Carolyn W. , Wood Susanna A.
Published: November 2021

Picocyanobacteria (Pcy) are important yet understudied components of lake foodwebs. While phylogenetic studies of isolated strains reveal a high diversity of freshwater genotypes, little is known about abiotic drivers associated with Pcy in different lakes. Due to methodological limitations, most previous studies assess potential drivers using total cell abundances as a response, with often conflicting and inconsistent results. In the present study, we explored how picocyanobacterial communities respond to environmental change using a combination of epifluorescence microscopy and community data determined using 16S rRNA gene metabarcoding. Temporal shifts in picocyanobacterial abundance, diversity and community dynamics were assessed in relation to potential environmental drivers in five contrasting lakes over 1year. Cell abundances alone were not consistently related to environmental variables across lakes. However, the addition of metabarcoding data revealed diverse picocyanobacterial communities that differed significantly between lakes, driven by environmental variables related to trophic state. Within each lake, communities were temporally dynamic and certain amplicon sequence variants (ASVs) were strongly associated with specific environmental drivers. Rapid shifts in community structure and composition were often related to environmental changes, indicating that lacustrine Pcy can persist at high abundances through collective community adaptation. These results demonstrate that a combination of microscopy and metabarcoding enables an in-depth characterisation of picocyanobacterial communities and reveals strain-specific drivers. We recommend that future studies cease referring to picocyanobacterial as one functional group and take strain specific variability into consideration.
Identification of Volatile Organic Compounds in Extremophilic Bacteria and Their Effective Use in Biocontrol of Postharvest Fungal Phytopathogens
Authors: Toral Laura , Rodríguez Miguel , Martínez-Checa Fernando , Montaño Alfredo , Cortés-Delgado Amparo , Smolinska Agnieszka , Llamas Inmaculada , Sampedro Inmaculada
Published: November 2021

Phytopathogenic fungal growth in postharvest fruits and vegetables is responsible for 20–25% of production losses. Volatile organic compounds (VOCs) have been gaining importance in the food industry as a safe and ecofriendly alternative to pesticides for combating these phytopathogenic fungi. In this study, we analysed the ability of some VOCs produced by strains of the generaBacillus,Peribacillus,Pseudomonas,PsychrobacillusandStaphylococcusto inhibit the growth ofAlternaria alternata,Botrytis cinerea,Fusarium oxysporum,Fusarium solani,Monilinia fructicola,Monilinia laxaandSclerotinia sclerotiorum,in vitroandin vivo. We analysed bacterial VOCs by using GC/MS and 87 volatile compounds were identified, in particular acetoin, acetic acid, 2,3-butanediol, isopentanol, dimethyl disulphide and isopentyl isobutanoate.In vitrogrowth inhibition assays andin vivoexperiments using cherry fruits showed that the best producers of VOCs,Bacillus atrophaeusL193,Bacillus velezensisXT1 andPsychrobacillus vulpisZ8, exhibited the highest antifungal activity againstB. cinerea,M. fructicolaandM. laxa, which highlights the potential of these strains to control postharvest diseases. Transmission electron microscopy micrographs of bacterial VOC-treated fungi clearly showed antifungal activity which led to an intense degeneration of cellular components of mycelium and cell death.
Therapeutic Targeting of Nonalcoholic Fatty Liver Disease by Downregulating SREBP-1C Expression via AMPK-KLF10 Axis
Authors: Chen Yu-Chi , Chen Rong-Jane , Peng Szu-Yuan , Yu Winston C. Y. , Chang Vincent Hung-Shu
Published: November 2021

Krüppel-like factor 10 (KLF10) is a phospho-regulated transcriptional factor involved in many biological processes including lipogenesis; however, the transcriptional regulation on lipogenesis by KLF10 remains largely unclear. Lipogenesis is important in the development of nonalcoholic fatty liver disease (NAFLD) which was known regulated mainly by AMP-activated protein kinase (AMPK) and sterol regulatory element-binding protein (SREBP-1C). Interesting, our previous study using phosphorylated site prediction suggested a regulation of AMPK on KLF10. Therefore, we aimed to study the protein–protein interactions of AMPK on the regulation of KLF10, and to delineate the mechanisms of phosphorylated KLF10 in the regulation of NAFLD through SREBP-1C. We performed in vitro and in vivo assays that identified AMPK phosphorylates KLF10 at Thr189 and subsequently modulates the steady state level of KLF10. Meanwhile, a chromatin immunoprecipitation–chip assay revealed the novel target genes and signaling cascades of corresponding to phosphorylated KLF10. SREBP-1C was identified as a target gene suppressed by phosphorylated KLF10 through promoter binding. We further performed high-fat-diet-induced NAFLD models using hepatic-specific KLF10 knockout mice and wild-type mice and revealed that KLF10 knockout markedly led to more severe NAFLD than that in wild-type mice. Taken together, our findings revealed for the first time that AMPK activates and stabilizes the KLF10 protein via phosphorylation at Thr189, thereby repressing the expression of SREBP-1C and subsequent lipogenesis pathways along with metabolic disorders. We suggested that the targeted manipulation of liver metabolism, particularly through increased KLF10 expression, is a potential alternative solution for treating NAFLD.
Alternation in Effective Connectivity With Cognitive Aging: A Longitudinal Study of Elderly Populations
Authors: Cao Xingxing , Liu Tao , Jiang Jiyang , Liu Hao , Zhang Jing , Kochan Nicole A. , Niu Haijun , Brodaty Henry , Sachdev Perminder S. , Wen Wei
Published: November 2021

In this research, we investigated the alterations in the directionality and strength of regional interactions within functionally changed brain networks and their relationship to cognitive decline during the aging process in normal elderly individuals. Thirty-seven cognitively normal elderly people received resting-state fMRI scans and cognitive assessments at baseline (age = 78.65 ± 3.56 years) and at 4-year follow-up. Functional connectivity analyses were used to identify networks containing brain regions whose functions changed with age as regions of interest. The spectral dynamic causal modeling (spDCM) method was used to estimate the causal interactions within networks in subjects at different time points and in subjects with different cognitive levels to explore the alterations with cognitive aging. The results showed that, at both time points, all the networks, except the frontal-parietal network (FPN) at baseline, had mutual interactions between each pair of nodes. Furthermore, when the subjects were divided with global cognition level, lost connections were only found in the subgroup with better performance. These indicated that elderly people appeared to need more interaction pathways between brain areas with cognitive decline. We also observed that the strength of the flow of information from the left angular gyrus to the precuneus, which is associated with activation of memory retrieval and the functional hub involved in various cognitive domains, was predictive of declines in executive function with the aging process, making it a potential predictor of such situation.
Age Matching Is Essential for the Study of Cerebrospinal Fluid sTREM2 Levels and Alzheimer’s Disease Risk: A Meta-Analysis
Authors: Hu Shimin , Pan Na , Liu Chunyan , Wang Yuping , Zhang Tingting
Published: November 2021

Background: Both the genetic and pathological studies link Alzheimer’s disease (AD) to the triggering receptor expressed on myeloid cells 2 (TREM2). A large number of studies have explored the value of cerebrospinal fluid (CSF) soluble TREM2 (sTREM2) levels as a biomarker for the diagnosis and prediction of AD; however, the findings are inconsistent. We aimed to review the studies that investigated the association of CSF sTREM2 levels and AD risk, and to provide the recommendations for future research.

Methods and Results: A systematic literature search was performed using the MEDLINE, EMBASE, and Web of Science (all databases) databases. The meta-analysis for the association between the CSF sTREM2 levels and AD risk included 15 studies (17 comparisons) with a total of 1,153 cases and 1,626 controls. The total results showed that the higher CSF sTREM2 levels and AD risk were associated [standardized mean difference (SMD) = 0.428, 95% CI (0.213, 0.643), I2 = 81.1%]. However, the analysis of the subgroup of “age difference ≤ 2 years” indicated that sTREM2 was not associated with AD [SMD = 0.090, 95% CI (−0.092, 0.272), I2 = 27.4%] and had a significantly lower heterogeneity. Combining the results of the “age difference of 5–10 years” [SMD = 0.497, 95% CI (0.139, 0.855), I2 = 82.5%] and “age difference > 10 years” [SMD = 0.747, 95% CI (0.472, 1.023), I2 = 50.0%] subgroups showed that the difference in CSF sTREM2 between the AD and control groups was positively correlated with the age difference. A meta-regression analysis showed that the age difference can explain 33.4% of the between-study variance. By conducting further subgroup analyses of the five age-matched studies (495 cases and 364 controls) according to the measurement method, and whether inclusion criteria containing the requirement for pathological evidence of AD, no changes were observed in the corresponding pooled SMD or in the significance of the results. The meta-analysis result of “age difference ≤ 2 years” group was robust in the sensitivity analysis.

Conclusion: The available high-quality evidence does not yet support an association between the CSF sTREM2 levels and AD risk. Age matching between the patients with AD and cognitively unimpaired controls was a major influencing factor in the results.
Screening Computed Tomography Angiography to Identify Patients at Low Risk for Delayed Cerebral Ischemia Following Aneurysmal Subarachnoid Hemorrhage
Authors: Nguyen Andrew M. , Williamson Craig A. , Pandey Aditya S. , Sheehan Kyle M. , Rajajee Venkatakrishna
Published: November 2021

Introduction: Delayed cerebral ischemia (DCI) occurs during a risk period of 3–21 days following aneurysmal subarachnoid hemorrhage (aSAH) and is associated with worse outcomes. The identification of patients at low risk for DCI might permit triage to less intense monitoring and management. While large-vessel vasospasm (LVV) is a distinct clinical entity from DCI, the presence of moderate-to-severe LVV is associated with a higher risk of DCI. Our hypothesis was that the absence of moderate-to-severe LVV on screening computed tomographic angiography (CTA) performed within the first few days of the DCI risk period will accurately identify patients at low risk for subsequent DCI.

Methods: This was a retrospective cohort study. Our institutional SAH outcomes registry was queried for all aSAH patients admitted in 2016–2019 who underwent screening CTA brain between days 4 and 8 following ictus. We excluded patients diagnosed with DCI prior to the first CTA performed during this time period. All variables are prospectively entered into the registry, and outcomes including DCI and LVV are prospectively adjudicated. We evaluated the predictive value and accuracy of moderate-to-severe LVV on CTA performed 4–8 days following ictus for the prediction of subsequent DCI.

Results: A total of 243 aSAH patients were admitted during the study timeframe. Of the 54 patients meeting the eligibility criteria, 11 (20%) had moderate-to-severe LVV on the screening CTA study performed during the risk period. Seven of the 11 (64%) patients with moderate-to-severe LVV on the days 4–8 screening CTA vs. six of 43 (14%) patients without, subsequently developed DCI. On multivariate analysis, the presence of LVV on days 4–8 screening CTA was an independent predictor of DCI (odds ratio 10.26, 95% CI 1.69–62.24, p = 0.011). NPV for the subsequent development of DCI was 86% (95% CI 77–92%). Sensitivity was 54% (25–81%), specificity 90% (77–97%), and positive predictive value 64% (38–83%).

Conclusions: The presence of moderate-to-severe LVV on screening CTA performed between days 4 and 8 following aSAH was an independent predictor of DCI, but achieved only moderate diagnostic accuracy, with NPV 86% and sensitivity 54%. Complementary risk-stratification strategies are likely necessary.
After-Effects of Intermittent Theta-Burst Stimulation Are Differentially and Phase-Dependently Suppressed by α- and β-Frequency Transcranial Alternating Current Stimulation
Authors: Ogata Katsuya , Nakazono Hisato , Ikeda Takuro , Oka Shin-ichiro , Goto Yoshinobu , Tobimatsu Shozo
Published: November 2021

Intermittent theta-burst stimulation (iTBS) using transcranial magnetic stimulation (TMS) is known to produce excitatory after-effects over the primary motor cortex (M1). Recently, transcranial alternating current stimulation (tACS) at 10 Hz (α) and 20 Hz (β) have been shown to modulate M1 excitability in a phase-dependent manner. Therefore, we hypothesized that tACS would modulate the after-effects of iTBS depending on the stimulation frequency and phase. To test our hypothesis, we examined the effects of α- and β-tACS on iTBS using motor evoked potentials (MEPs). Eighteen and thirteen healthy participants were recruited for α and β tACS conditions, respectively. tACS electrodes were attached over the left M1 and Pz. iTBS over left M1 was performed concurrently with tACS. The first pulse of the triple-pulse burst of iTBS was controlled to match the peak (90°) or trough (270°) phase of the tACS. A sham tACS condition was used as a control in which iTBS was administered without tACS. Thus, each participant was tested in three conditions: the peak and trough of the tACS phases and sham tACS. As a result, MEPs were enhanced after iTBS without tACS (sham condition), as observed in previous studies. α-tACS suppressed iTBS effects at the peak phase but not at the trough phase, while β-tACS suppressed the effects at both phases. Thus, although both types of tACS inhibited the facilitatory effects of iTBS, only α-tACS did so in a phase-dependent manner. Phase-dependent inhibition by α-tACS is analogous to our previous finding in which α-tACS inhibited MEPs online at the peak condition. Conversely, β-tACS reduced the effects of iTBS irrespective of its phase. The coupling of brain oscillations and tACS rhythms is considered important in the generation of spike-timing-dependent plasticity. Additionally, the coupling of θ and γ oscillations is assumed to be important for iTBS induction through long-term potentiation (LTP). Therefore, excessive coupling between β oscillations induced by tACS and γ or θ oscillations induced by iTBS might disturb the coupling of θ and γ oscillations during iTBS. To conclude, the action of iTBS is differentially modulated by neuronal oscillations depending on whether α- or β-tACS is applied.
Associations of the BDNF Val66Met Polymorphism With Body Composition, Cardiometabolic Risk Factors, and Energy Intake in Youth With Obesity: Findings From the HEARTY Study
Authors: Goldfield Gary S. , Walsh Jeremy , Sigal Ronald J. , Kenny Glen P. , Hadjiyannakis Stasia , De Lisio Michael , Ngu Mathew , Prud’homme Denis , Alberga Angela S. , Doucette Steve , Goldfield Diana B. , Cameron Jameason D.
Published: November 2021

The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is functionally related to BDNF, and is associated with obesity and metabolic complications in adults, but limited research exists among adolescents. This study comparatively examined carriers and non-carriers of the BDNF Val66Met polymorphism on body composition, energy intake, and cardiometabolic profile among adolescents with obesity. The sample consisted of 187 adolescents with obesity; 99 were carriers of the homozygous Val (G/G) alleles and 88 were carriers of the Val/Met (G/A) or Met (A/A) alleles. Cardiometabolic profile and DNA were quantified from fasted blood samples. Body composition was assessed by magnetic resonance imaging (MRI). Compared to carriers of the homozygous Val (G/G) allele, carriers of the Val/Met (G/A) or Met/Met (A/A) variants exhibited significantly higher protein (p = 0.01) and fat (p = 0.05) intake, C-Reactive protein (p = 0.05), and a trend toward higher overall energy intake (p = 0.07), fat-free mass (p = 0.07), and lower HDL-C (p = 0.07) Results showed for the first time that among youth with obesity, carriers of the Val66Met BDNF Met-alleles exhibited significantly higher C-reactive protein and energy intake in the form of fat and protein compared to Val-allele carriers, thereby providing support for the possible role of BDNF in appetite, weight, and metabolic regulation during adolescence.

Clinical Trial Registration:http://clinicaltrials.gov/, identifier NCT00195858.
Mitochondrial Quality Control Strategies: Potential Therapeutic Targets for Neurodegenerative Diseases?
Authors: Hu Di , Liu Zunren , Qi Xin
Published: November 2021

Many lines of evidence have indicated the therapeutic potential of rescuing mitochondrial integrity by targeting specific mitochondrial quality control pathways in neurodegenerative diseases, such as Parkinson’s disease, Huntington’s disease, and Alzheimer’s disease. In addition to ATP synthesis, mitochondria are critical regulators of ROS production, lipid metabolism, calcium buffering, and cell death. The mitochondrial unfolded protein response, mitochondrial dynamics, and mitophagy are the three main quality control mechanisms responsible for maintaining mitochondrial proteostasis and bioenergetics. The proper functioning of these complex processes is necessary to surveil and restore mitochondrial homeostasis and the healthy pool of mitochondria in cells. Mitochondrial dysfunction occurs early and causally in disease pathogenesis. A significant accumulation of mitochondrial damage resulting from compromised quality control pathways leads to the development of neuropathology. Moreover, genetic or pharmaceutical manipulation targeting the mitochondrial quality control mechanisms can sufficiently rescue mitochondrial integrity and ameliorate disease progression. Thus, therapies that can improve mitochondrial quality control have great promise for the treatment of neurodegenerative diseases. In this review, we summarize recent progress in the field that underscores the essential role of impaired mitochondrial quality control pathways in the pathogenesis of neurodegenerative diseases. We also discuss the translational approaches targeting mitochondrial function, with a focus on the restoration of mitochondrial integrity, including mitochondrial dynamics, mitophagy, and mitochondrial proteostasis.
Style Features in Communication of the Crews With Mission Control
Authors: Yusupova Anna , Shved Dmitry , Gushin Vadim , Chekalina Angelina , Supolkina Natalia
Published: November 2021

In “Content,” an International Space Station (ISS) Russian segment space experiment, features of communication between the cosmonauts and the Mission Control Center (MCC) were studied using content analysis. The method is based on the concept of stress copings by Lazarus and Folkman. Differences found in the communication of cosmonauts led to assumptions about the existence of individual communication styles in routine communication between the cosmonauts and the MCC. The differences found were defined using V. Satir's classical model of communication types. The pre-dominance of three main communication styles (“computing,” “blaming,” and “placating,” as per Satir) was found. Manifestations and features of styles are discussed, considering the effectiveness of the “computing” style for ISS-MCC communication. Cosmonauts with a pre-dominance of this communication style, mostly are stable and with good self-control. An increase of the “blaming” and the “placating” style features in the communication of cosmonauts may require adaptation of the MCC communication and additional psychological support for the cosmonauts.
Effects of Mental Training Through Imagery on the Competitive Anxiety of Adolescent Tennis Players Fasting During Ramadan: A Randomized, Controlled Experimental Study
Authors: Fekih Sofien , Zguira Mohamed Sami , Koubaa Abdessalem , Bettaieb Anouar , Hajji Jamel , Bragazzi Nicola Luigi , Jarraya Mohamed
Published: November 2021

This study aimed to analyze the effects of mental training through imagery on the competitive anxiety of adolescent tennis players fasting during Ramadan. This is an experimental study conducted with 38 male tennis players, randomly allocated to two groups: an experimental group (EG, n = 18), aged 16.9 ± 0.6 years, and a control group (CG, n = 20), aged 16.7 ± 0.8 years. The study was designed as a randomized, controlled experimental trial (registration code PACTR 202006847771700). CG watched historical videos of the Olympics, while EG performed mental training. The competitive anxiety state assessment was recorded four times. The first measurement was carried out 1 week before Ramadan, the second measurement during the first week of the month, the third measurement at the end of the second week, and, finally, the fourth measurement during the fourth week of Ramadan. Our results revealed a significant interaction (time × groups) for all competitive anxiety subscales. Higher intensity and direction scores for the cognitive and somatic anxiety subscales during Ramadan compared with before Ramadan for both groups could be reported at P < 0.001. Higher intensity and direction scores for the cognitive and somatic anxiety subscales during Ramadan compared with pre-Ramadan for both groups could be found at P < 0.01. This increase in scores was greater for the CG than for the EG in the middle and at the end of Ramadan at P < 0.001. Finally, for the self-confidence subscale score, results revealed that intensity and direction scores were lower during Ramadan compared with pre-Ramadan for the two groups at P < 0.01. The score for the intensity of self-confidence was higher for the EG compared with the CG at the end of Ramadan at P < 0.001. It was concluded that mental imagery training was effective in reducing anxiety (cognitive and somatic) and increasing self-confidence in the intensity dimension of adolescent tennis players who fast during Ramadan.
Adverse Effects and Toxicity of Immune Checkpoint Inhibitors For Patients With Urothelial Carcinoma
Authors: Wang Di , Sun Kai , Wang Tianqi , Zhang Dongxu , Sun Fengze , Cui Yuanshan , Zhao Hongwei , Wu Jitao
Published: November 2021

Urothelial carcinoma (UC) occupies a high incidence among all the genitourinary malignancies. Immune checkpoint inhibitors (ICIs), as alternative treatments of metastatic urothelial carcinoma (mUC), have been applied in the treatment of mUC after chemotherapy failure, with comparable efficacy and safety. ICIs can enhance anti-tumor T cell reactivity and promote immune control over the cancerous cells by blocking cytotoxic T-lymphocyte antigen 4 (CTLA-4) or the combination of PD-1 and PD-L1. In the treatment of urothelial carcinoma, ICIs show obvious advantage and can enhance survival rates. However, their adverse effects are gradually manifested with increasing clinical applications. Therefore, we review the adverse effects and toxicity of ICIs in patients with UC, aiming to provide sound theoretical references and therapeutic strategies for their clinical application.
Cannabinoid Drugs-Related Neuroprotection as a Potential Therapeutic Tool Against Chemotherapy-Induced Cognitive Impairment
Authors: Boullon Laura , Abalo Raquel , Llorente-Berzal Álvaro
Published: November 2021

In recent years, and particularly associated with the increase of cancer patients’ life expectancy, the occurrence of cancer treatment sequelae, including cognitive impairments, has received considerable attention. Chemotherapy-induced cognitive impairments (CICI) can be observed not only during pharmacological treatment of the disease but also long after cessation of this therapy. The lack of effective tools for its diagnosis together with the limited treatments currently available for alleviation of the side-effects induced by chemotherapeutic agents, demonstrates the need of a better understanding of the mechanisms underlying the pathology. This review focuses on the comprehensive appraisal of two main processes associated with the development of CICI: neuroinflammation and oxidative stress, and proposes the endogenous cannabinoid system (ECS) as a new therapeutic target against CICI. The neuroprotective role of the ECS, well described in other cognitive-related neuropathologies, seems to be able to reduce the activation of pro-inflammatory cytokines involved in the neuroinflammatory supraspinal processes underlying CICI. This review also provides evidence supporting the role of cannabinoid-based drugs in the modulation of oxidative stress processes that underpin cognitive impairments, and warrant the investigation of endocannabinoid components, still unknown, that may mediate the molecular mechanism behind this neuroprotective activity. Finally, this review points forward the urgent need of research focused on the understanding of CICI and the investigation of new therapeutic targets.