bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epicardial adipose tissue and severe Coronavirus Disease 19
Authors: Bihan Hélène , Heidar Richard , Beloeuvre Aude , Allard Lucie , Ouedraogo Elise , Tatulashvili Sopio , Tandjaoui Yacine , Gaudry Stephane , Brillet Pierre-Yves , Cosson Emmanuel 
Published: July 2021

Abstract
Background
Both visceral adipose tissue and epicardial adipose tissue (EAT) have pro-inflammatory properties. The former is associated with Coronavirus Disease 19 (COVID-19) severity. We aimed to investigate whether an association also exists for EAT.

Material and methods
We retrospectively measured EAT volume using computed tomography (CT) scans (semi-automatic software) of inpatients with COVID-19 and analyzed the correlation between EAT volume and anthropometric characteristics and comorbidities. We then analyzed the clinicobiological and radiological parameters associated with severe COVID-19 (O2 $$\ge$$
≥
6 l/min), intensive care unit (ICU) admission or death, and 25% or more CT lung involvement, which are three key indicators of COVID-19 severity.

Results
We included 100 consecutive patients; 63% were men, mean age was 61.8 ± 16.2 years, 47% were obese, 54% had hypertension, 42% diabetes, and 17.2% a cardiovascular event history. Severe COVID-19 (n = 35, 35%) was associated with EAT volume (132 ± 62 vs 104 ± 40 cm3, p = 0.02), age, ferritinemia, and 25% or more CT lung involvement. ICU admission or death (n = 14, 14%) was associated with EAT volume (153 ± 67 vs 108 ± 45 cm3, p = 0.015), hypertension and 25% or more CT lung involvement. The association between EAT volume and severe COVID-19 remained after adjustment for sex, BMI, ferritinemia and lung involvement, but not after adjustment for age. Instead, the association between EAT volume and ICU admission or death remained after adjustment for all five of these parameters.

Conclusions
Our results suggest that measuring EAT volume on chest CT scans at hospital admission in patients diagnosed with COVID-19 might help to assess the risk of disease aggravation.
Tumor microenvironment: a prospective target of natural alkaloids for cancer treatment
Authors: Luo Yanming , Yin Shuangshuang , Lu Jia , Zhou Shiyue , Shao Yingying , Bao Xiaomei , Wang Tao , Qiu Yuling , Yu Haiyang 
Published: July 2021

AbstractMalignant tumor has become one of the major diseases that seriously endangers human health. Numerous studies have demonstrated that tumor microenvironment (TME) is closely associated with patient prognosis. Tumor growth and progression are strongly dependent on its surrounding tumor microenvironment, because the optimal conditions originated from stromal elements are required for cancer cell proliferation, invasion, metastasis and drug resistance. The tumor microenvironment is an environment rich in immune/inflammatory cells and accompanied by a continuous, gradient of hypoxia and pH. Overcoming immunosuppressive environment and boosting anti-tumor immunity may be the key to the prevention and treatment of cancer. Most traditional Chinese medicine have been proved to have good anti-tumor activity, and they have the advantages of better therapeutic effect and few side effects in the treatment of malignant tumors. An increasing number of studies are giving evidence that alkaloids extracted from traditional Chinese medicine possess a significant anticancer efficiency via regulating a variety of tumor-related genes, pathways and other mechanisms. This paper reviews the anti-tumor effect of alkaloids targeting tumor microenvironment, and further reveals its anti-tumor mechanism through the effects of alkaloids on different components in tumor microenvironment.
Health-related quality of life in amyotrophic lateral sclerosis using EQ-5D-5L
Authors: Wei Qian-Qian , Hou Yanbing , Chen Yongping , Ou Ruwei , Cao Bei , Zhang Lingyu , Yang Tianmi , Shang Huifang 
Published: July 2021

Abstract
Background
The study aimed to appraise the health-related quality of life (HRQoL) measured by the five-level EuroQol-5 dimensions (EQ-5D-5L) in amyotrophic lateral sclerosis (ALS), and to explore the associations between non-motor symptoms (mood changes, cognitive disturbances and sleep disturbances).

Methods
EQ-5D-5L descriptive scores were converted into a single aggregated “health utility” score. A calibrated visual analog scale (EQ-VAS) was used for self-rating of current health status. Multiple logistic regression analysis was used to explore the factors associated with HRQoL.

Results
Among the 547 enrolled ALS patients who were assessed using EQ-5D-5L, the highest frequency of reported problems was with usual activities (76.7%), followed by self-care (68.8%) and anxiety/depression (62.0%). The median health utility score was 0.78 and the median EQ-VAS score was 70. Clinical factors corresponding to differences in the EQ-5D-5L health utility score included age of onset, onset region, the ALS Functional Rating Scale-Revised (ALSFRS-R) score, and King’s College stages. Patients with depression, anxiety, and poor sleep had lower health utility scores. Patients with excessive daytime sleepiness and rapid eye movement sleep behavior disorder had lower EQ-VAS scores. Multivariate logistic analysis indicated that ALSFRS-R scores, depression, and anxiety were associated with health utility scores. After adjusting other parameters, ALSFRS-R score, stages, and depression were significantly associated with EQ-VAS scores (P < 0.05).

Conclusion
This study examined HRQoL in ALS patients using the Chinese version of the EQ-5D-5L scale across different stages of the disease. We found that HRQoL is related to disease severity and to mood disturbances. Management of non-motor symptoms may help improve HRQoL in ALS patients.
Role of α- and β-adrenergic signaling in phenotypic targeting: significance in benign and malignant urologic disease
Authors: Archer M. , Dogra N. , Dovey Z. , Ganta T. , Jang H.-S. , Khusid J. A. , Lantz A. , Mihalopoulos M. , Stockert J. A. , Zahalka A. , Björnebo L. , Gaglani S. , Noh M. R. , Kaplan S. A. , Mehrazin R. , Badani K. K. , Wiklund P. , Tsao K. , Lundon D. J. , Mohamed N. , Lucien F. , Padanilam B. , Gupta M. , Tewari A. K. , Kyprianou N. 
Published: July 2021

AbstractThe urinary tract is highly innervated by autonomic nerves which are essential in urinary tract development, the production of growth factors, and the control of homeostasis. These neural signals may become dysregulated in several genitourinary (GU) disease states, both benign and malignant. Accordingly, the autonomic nervous system is a therapeutic target for several genitourinary pathologies including cancer, voiding dysfunction, and obstructing nephrolithiasis. Adrenergic receptors (adrenoceptors) are G-Protein coupled-receptors that are distributed throughout the body. The major function of α1-adrenoceptors is signaling smooth muscle contractions through GPCR and intracellular calcium influx. Pharmacologic intervention of α-and β-adrenoceptors is routinely and successfully implemented in the treatment of benign urologic illnesses, through the use of α-adrenoceptor antagonists. Furthermore, cell-based evidence recently established the antitumor effect of α1-adrenoceptor antagonists in prostate, bladder and renal tumors by reducing neovascularity and impairing growth within the tumor microenvironment via regulation of the phenotypic epithelial-mesenchymal transition (EMT). There has been a significant focus on repurposing the routinely used, Food and Drug Administration-approved α1-adrenoceptor antagonists to inhibit GU tumor growth and angiogenesis in patients with advanced prostate, bladder, and renal cancer. In this review we discuss the current evidence on (a) the signaling events of the autonomic nervous system mediated by its cognate α- and β-adrenoceptors in regulating the phenotypic landscape (EMT) of genitourinary organs; and (b) the therapeutic significance of targeting this signaling pathway in benign and malignant urologic disease.
NLRP3 inhibition attenuates early brain injury and delayed cerebral vasospasm after subarachnoid hemorrhage
Authors: Dodd William S. , Noda Imaray , Martinez Melanie , Hosaka Koji , Hoh Brian L. 
Published: July 2021

Abstract
Background
The NLRP3 inflammasome is a critical mediator of several vascular diseases through positive regulation of proinflammatory pathways. In this study, we defined the role of NLRP3 in both the acute and delayed phases following subarachnoid hemorrhage (SAH). SAH is associated with devastating early brain injury (EBI) in the acute phase, and those that survive remain at risk for developing delayed cerebral ischemia (DCI) due to cerebral vasospasm. Current therapies are not effective in preventing the morbidity and mortality associated with EBI and DCI. NLRP3 activation is known to drive IL-1β production and stimulate microglia reactivity, both hallmarks of SAH pathology; thus, we hypothesized that inhibition of NLRP3 could alleviate SAH-induced vascular dysfunction and functional deficits.

Methods
We studied NLRP3 in an anterior circulation autologous blood injection model of SAH in mice. Mice were randomized to either sham surgery + vehicle, SAH + vehicle, or SAH + MCC950 (a selective NLRP3 inhibitor). The acute phase was studied at 1 day post-SAH and delayed phase at 5 days post-SAH.

Results
NLRP3 inhibition improved outcomes at both 1 and 5 days post-SAH. In the acute (1 day post-SAH) phase, NLRP3 inhibition attenuated cerebral edema, tight junction disruption, microthrombosis, and microglial reactive morphology shift. Further, we observed a decrease in apoptosis of neurons in mice treated with MCC950. NLRP3 inhibition also prevented middle cerebral artery vasospasm in the delayed (5 days post-SAH) phase and blunted SAH-induced sensorimotor deficits.

Conclusions
We demonstrate a novel association between NLRP3-mediated neuroinflammation and cerebrovascular dysfunction in both the early and delayed phases after SAH. MCC950 and other NLRP3 inhibitors could be promising tools in the development of therapeutics for EBI and DCI.
Contributions of economic growth, terrestrial sinks, and atmospheric transport to the increasing atmospheric CO2 concentrations over the Korean Peninsula
Authors: Yun Jeongmin , Jeong Sujong 
Published: July 2021

Abstract
Background
Understanding a carbon budget from a national perspective is essential for establishing effective plans to reduce atmospheric CO2 growth. The national characteristics of carbon budgets are reflected in atmospheric CO2 variations; however, separating regional influences on atmospheric signals is challenging owing to atmospheric CO2 transport. Therefore, in this study, we examined the characteristics of atmospheric CO2 variations over South and North Korea during 2000–2016 and unveiled the causes of their regional differences in the increasing rate of atmospheric CO2 concentrations by utilizing atmospheric transport modeling.

Results
The atmospheric CO2 concentration in South Korea is rising by 2.32 ppm year− 1, which is more than the globally-averaged increase rate of 2.05 ppm year− 1. Atmospheric transport modeling indicates that the increase in domestic fossil energy supply to support manufacturing export-led economic growth leads to an increase of 0.12 ppm year− 1 in atmospheric CO2 in South Korea. Although enhancements of terrestrial carbon uptake estimated from both inverse modeling and process-based models have decreased atmospheric CO2 by up to 0.02 ppm year− 1, this decrease is insufficient to offset anthropogenic CO2 increases. Meanwhile, atmospheric CO2 in North Korea is also increasing by 2.23 ppm year− 1, despite a decrease in national CO2 emissions close to carbon neutrality. The great increases estimated in both South Korea and North Korea are associated with changes in atmospheric transport, including increasing emitted and transported CO2 from China, which have increased the national atmospheric CO2 concentrations by 2.23 ppm year− 1 and 2.27 ppm year− 1, respectively.

Conclusions
This study discovered that economic activity is the determinant of regional differences in increasing atmospheric CO2 in the Korea Peninsula. However, from a global perspective, changes in transported CO2 are a major driver of rising atmospheric CO2 over this region, yielding an increase rate higher than the global mean value. Our findings suggest that accurately separating the contributions of atmospheric transport and regional sources to the increasing atmospheric CO2 concentrations is important for developing effective strategies to achieve carbon neutrality at the national level.
Safety of exercise training in multiple sclerosis: a protocol for an updated systematic review and meta-analysis
Authors: Learmonth Y. C. , Pilutti L. A. , Herring M. P. , Motl R. W. , Chan B. , Metse A. P. 
Published: July 2021

Abstract
Background
There has been an exponential growth in the number of clinical research studies regarding exercise training in multiple sclerosis, and literature reviews and meta-analyses have documented the many benefits of exercise training. This research further requires careful review for documenting the safety of exercise training in multiple sclerosis, as clarity on safety represents a major hurdle in the clinical prescription of exercise behaviour.

Objectives
To enhance understanding of the feasibility of exercise in multiple sclerosis, we (1) provide a protocol of a systematic review and meta-analysis that summarises rates and risks of clinical relapse, adverse events (i.e., an unfavourable outcome that occurs during the intervention delivery time period), and serious adverse events (i.e., an untoward occurrence that results in death or is life threatening, requires hospitalisation, or results in disability during the intervention delivery time period), as well as retention, adherence, and compliance, from randomised controlled trials of exercise training in persons with multiple sclerosis; and (2) identify moderators of relapse, adverse events, and serious adverse event rates.

Methods
Eight field-relevant databases will be searched electronically. Studies that involve a randomised controlled trial of exercise training (with non-exercise, non-pharmacological, comparator), report on safety outcomes, and include adults with multiple sclerosis will be included. Rates and relative risks of the three primary outcomes (relapse, adverse event, and serious adverse event) will be calculated and reported each with standard error and 95% confidence interval. Random-effects meta-analysis will estimate mean population relative risk for outcomes. Potential sources of variability, including participant characteristics, features of the exercise stimulus, and comparison condition, will be examined with random-effects meta-regression with maximum likelihood estimation.

Discussion
The results from this systematic review and meta-analysis will inform and guide healthcare practitioners, researchers, and policymakers on the safety of exercise training in persons with multiple sclerosis. Where possible, we will identify the impact of exercise type, exercise delivery style, participant disability level, and the prescription of exercise guidelines, on the safety of exercise training. The result will identify critical information on the safety of exercise in persons with multiple sclerosis, while also identifying gaps in research and setting priorities for future enquiries.

Systematic review registration
PROSPERO 2020 CRD42020190544
The causal influence of responsive parenting behaviour on academic readiness: a protocol for a systematic review and meta-analysis of randomized controlled trials
Authors: Prime Heather , Andrews Krysta , Gonzalez Andrea , Janus Magdalena , Tricco Andrea C. , Bennett Teresa , Atkinson Leslie 
Published: July 2021

Abstract
Background
Children’s academic readiness has important implications for subsequent achievement and psychosocial functioning. A growing number of studies are utilizing randomized controlled trials (RCT) to examine whether responsive parenting interventions lead to positive gains in children’s academic readiness. A synthesis of the extant literature is warranted to gain a precise estimate of the causal influence of responsive parenting on academic readiness, as well as to examine moderators that may serve to strengthen or weaken this effect. The main objective of this study will be to conduct a systematic review and meta-analysis of RCTs evaluating the use of responsive parenting interventions to target academic readiness: problem-solving/reasoning, language proficiency, executive functioning, and pre-academic skills (e.g., numeracy/literacy).

Methods
Studies that took place in the early childhood period (< 6 years at baseline), targeted responsive parenting behaviours using an RCT (with control group, waitlist, or treatment as usual as a comparator), and included an outcome assessment of academic readiness will be considered for eligibility. Children and/or parents with special needs and/or disabilities will be excluded. The primary outcome is the effect of responsive parenting interventions on academic readiness. Secondary outcomes include substantive and methodological moderators and parent-mediated effects on outcomes. We will search MEDLINE, PsycINFO, ERIC, and ProQuest Dissertations & Theses Global databases from their inception onwards and we will also conduct backward/forward searching of eligible studies. Published and unpublished works will be considered. Screening, full-text assessments, and data extraction will be completed by two independent reviewers. Risk of bias will be assessed using the CLARITY tool for RCTs. Effect sizes will be calculated based on study-level standardized differences between experimental and control groups and entered into random effects models to obtain a pooled effect (meta-analysis). Moderation will be examined through Q-statistics and meta-regression to study sources of between-study variation in effect sizes. A pooled path model of mediation will be used to study parent-mediated effects.

Discussion
Findings will illuminate causal relations between responsive parenting and academic readiness, with implications for developmental science. Findings will also guide decision making in policy and practice for supporting early childhood development and reducing social disparities in children prior to school-entry.

Systematic review registration
PROSPERO CRD42020222143.
Effect of continuous infusion of dexmedetomidine on blood loss in orthognathic surgery: a retrospective study
Authors: Jin Chenyu , Lv Xiang , Sun Yu , Jiang Hong 
Published: July 2021

Abstract
Background
Patients with maxillofacial deformities require orthognathic surgeries to correct occlusion. The surgical procedure may lead to massive bleeding, which is associated with haematoma, respiratory obstruction, and asphyxia. Dexmedetomidine has been used in controlled hypotension and may reduce blood loss in orthognathic surgery. We conducted a retrospective cohort study to evaluate the effect of dexmedetomidine on blood loss in orthognathic surgeries.

Methods
The primary outcome examined was blood loss, and secondary outcomes were postoperative haemoglobin level; intraoperative heart rate and blood pressure (T1: at incision; T2: 30 min after incision; T3: 60 min after incision; T4: 120 min after incision); dosage of fentanyl, remifentanil, urapidil, and esmolol; operation time; and incidence of allogeneic blood transfusion.

Results
A total of 1247 patients were included in this study, and 540 patient pairs were matched via propensity score matching. There were significant decreases in mean blood loss, heart rate at T1–T4, blood pressure at T1, and remifentanil and esmolol dosage in the dexmedetomidine group compared with those in the control group. There was also a significant increase in the postoperative haemoglobin level of the dexmedetomidine group.

Conclusions
Continuous infusion of dexmedetomidine can decrease blood loss in orthognathic surgery.
Trial registration: ChiCTR1800018794 (retrospectively registered)
Name of registry: Chinese Clinical Trial Registry
Date of registration: 2018/10/09
URL: www.chictr.org.cn/showproj.aspx?proj=30612
Genetic pathogenesis of immunoglobulin light chain amyloidosis: basic characteristics and clinical applications
Authors: Xu Linchun , Su Yongzhong 
Published: July 2021

AbstractImmunoglobulin light chain amyloidosis (AL) is an indolent plasma cell disorder characterized by free immunoglobulin light chain (FLC) misfolding and amyloid fibril deposition. The cytogenetic pattern of AL shows profound similarity with that of other plasma cell disorders but harbors distinct features. AL can be classified into two primary subtypes: non-hyperdiploidy and hyperdiploidy. Non-hyperdiploidy usually involves immunoglobulin heavy chain translocations, and t(11;14) is the hallmark of this disease. T(11;14) is associated with low plasma cell count but high FLC level and displays distinct response outcomes to different treatment modalities. Hyperdiploidy is associated with plasmacytosis and subclone formation, and it generally confers a neutral or inferior prognostic outcome. Other chromosome abnormalities and driver gene mutations are considered as secondary cytogenetic aberrations that occur during disease evolution. These genetic aberrations contribute to the proliferation of plasma cells, which secrete excess FLC for amyloid deposition. Other genetic factors, such as specific usage of immunoglobulin light chain germline genes and light chain somatic mutations, also play an essential role in amyloid fibril deposition in AL. This paper will propose a framework of AL classification based on genetic aberrations and discuss the amyloid formation of AL from a genetic aspect.
Vibrio vulnificus induces the death of a major bacterial species in the mouse gut via cyclo-Phe-Pro
Authors: Kim Jeong-A , Jang Bo-Ram , Kim Yu-Ra , Jung You-Chul , Kim Kun-Soo , Lee Kyu-Ho 
Published: July 2021

Abstract
Background
A foodborne pathogen, Vibrio vulnificus, encounters normal microflora inhabiting the gut environments prior to causing fatal septicemia or gastroenteritis and should overcome the barriers derived from the gut commensals for successful infection. Its interactions with gut commensals during the infection process, however, have not yet been understood. In the present study, the effect of V. vulnificus on the community structures of gut microbiota in mice was examined.

Results
Analyses of microbiota in the fecal samples of mice that died due to V. vulnificus infection revealed the decreased abundance of bacteria belonged to Bacteroidetes, notably, the species Bacteroides vulgatus. In vitro coculturing of the two bacterial species resulted in the decreased survival of B. vulgatus. The antagonistic effect of V. vulnificus against B. vulgatus was found to be mediated by cyclo-Phe-Pro (cFP), one of the major compounds secreted by V. vulnificus. cFP-treated B. vulgatus showed collapsed cellular morphology with an undulated cell surface, enlarged periplasmic space, and lysed membranes, suggesting the occurrence of membrane disruption. The degree of membrane disruption caused by cFP was dependent upon the cellular levels of ObgE in B. vulgatus. Recombinant ObgE exhibited a high affinity to cFP at a 1:1 ratio. When mice were orally injected with cFP, their feces contained significantly reduced B. vulgatus levels, and their susceptibility to V. vulnificus infection was considerably increased.

Conclusions
This study demonstrates that V. vulnificus-derived cFP modulates the abundance of the predominant species among gut commensals, which made V. vulnificus increase its pathogenicity in the hosts.