bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-definition transcranial direct current stimulation (HD-tDCS) as augmentation therapy in late-life depression (LLD) with suboptimal response to treatment—a study protocol for a double-blinded randomized sham-controlled trial
Authors: Ngan Sze Ting Joanna , Chan Lap Kei , Chan Wai Chi , Lam Linda Chiu Wa , Li Wan Kei , Lim Kelvin , Or Ego , Pang Pui Fai , Poon Ting Keung , Wong Mei Cheung Mimi , Wu Ying King Anna , Cheng Pak Wing Calvin 
Published: October 2022

Abstract

Background

Late-life depression (LLD) has a poorer prognosis and higher relapse rate than younger adults, with up to one third of patients with LLD showing suboptimal response to antidepressant therapy. LLD has been associated with significant impairment in cognition and daily functioning. Few studies have evaluated the therapeutic effects of high-definition transcranial direct current stimulation (HD-tDCS) on depressive and cognitive symptoms of LLD. The current randomized controlled trial assesses the efficacy of HD-tDCS as an augmentation therapy with antidepressants compared to sham-control in subjects with LLD.

Methods
Fifty-eight patients with LLD will be recruited and randomly assigned to the active HD-tDCS or sham HD-tDCS group. In both groups, patients will receive the active or sham intervention in addition to their pre-existing antidepressant therapy, for 2 weeks with 5 sessions per week, each lasting 30 min. The primary outcome measures will be the change of depressive symptoms, clinical response and the remission rate as measured with the Hamilton Depression Rating scale (HAMD-17) before and after the intervention, and at the 4th and 12th week after the completed intervention. Secondary outcome measures include cognitive symptoms, anxiety symptoms, daily functioning and adverse effects.

Discussion
Older adults with depression are associated with poorer outcomes or unsatisfactory responses to antidepressant therapy, and significant cognitive decline. Therefore, a new effective treatment option is needed. This randomized control trial aims at assessing the efficacy of HD-tDCS on ameliorating the depressive, cognitive and anxiety symptoms, and improving the daily functioning of subjects with LLD.

Trial registration
ClinicalTrials.gov NCT05322863. Registered on 11 April 2022.
Association between osteocalcin, a pivotal marker of bone metabolism, and secretory function of islet beta cells and alpha cells in Chinese patients with type 2 diabetes mellitus: an observational study
Authors: Lei Haiyan , Liu Jun , Wang Wei , Yang Xinyi , Feng Zhouqin , Zang Pu , Lu Bin , Shao Jiaqing 
Published: October 2022

Abstract
Background
Several recent studies have found that Osteocalcin (OCN), a multifunctional protein secreted exclusively by osteoblasts, is beneficial to glucose metabolism and type 2 diabetes mellitus (T2DM). However, the effects of OCN on islets function especially islet ɑ cells function in patients with type 2 diabetes mellitus characterized by a bi-hormonal disease are still unclear. The purpose of this cross-sectional study was to investigate the relationship between serum OCN and the secretion of islet β cells and ɑ cells in Chinese patients with type 2 diabetes mellitus.

Methods
204 patients with T2DM were enrolled. Blood glucose (FBG, PBG0.5h, PBG1h, PBG2h, PBG3h), insulin (FINS, INS0.5h, INS1h, INS2h, INS3h), C-peptide (FCP, CP0.5h, CP1h, CP2h, CP3h), and glucagon (GLA0, GLA0.5 h, GLA1h, GLA2h, GLA3h) levels were measured on 0 h, 0.5 h, 1 h, 2 h, and 3 h after a 100 g standard bread meal load. Early postprandial secretion function of islet β cells was calculated as Δcp0.5h = CP0.5-FCP. The patients were divided into low, medium and high groups (T1, T2 and T3) according to tertiles of OCN. Comparison of parameters among three groups was studied. Correlation analysis confirmed the relationship between OCN and pancreatic secretion. Multiple regression analysis showed independent contributors to pancreatic secretion.

Main results
FBG, and PBG2h were the lowest while Δcp0.5h was the highest in the highest tertile group (respectively, p < 0.05). INS3h, area under the curve of insulin (AUCins3h) in T3 Group were significantly lower than T1 Group (respectively, p < 0.05). GLA1h in T3 group was lower than T1 group (p < 0.05), and GLA0.5 h in T3 group was lower than T2 and T1 groups (p < 0.05). Correlation analysis showed OCN was inversely correlated with Homeostatic model of insulin resistance (HOMA-IR), INS3h, AUCins3h (p < 0.05), and was still inversely correlated with FCP, GLA0.5 h, GLA1h, area under the curve of glucagon (AUCgla3h) (respectively, p < 0.05) after adjustment for body mass index (BMI) and alanine aminotransferase (ALT). The multiple regression analysis showed that OCN was independent contributor to Δcp0.5h, GLA0.5h and GLA1h (respectively, p < 0.05).

Conclusions
Higher serum OCN level is closely related to better blood glucose control, higher insulin sensitivity, increased early-phase insulin secretion of islet β cells and appropriate inhibition of postprandial glucagon secretion of islet ɑ cells in adult patients with type 2 diabetes mellitus.
Why the estrous cycle matters for neuroscience
Authors: Rocks Devin , Cham Heining , Kundakovic Marija 
Published: October 2022

Abstract
Background
Ovarian hormone fluctuations over the rodent estrous cycle and the human menstrual cycle are known to significantly impact brain physiology and disease risk, yet this variable is largely ignored in preclinical neuroscience research, clinical studies, and psychiatric practice.

Methods
To assess the importance of the estrous cycle information for the analysis of sex differences in neuroscience research, we re-analyzed our previously published data with or without the estrous cycle information, giving a side-by-side comparison of the analyses of behavior, brain structure, gene expression, and 3D genome organization in female and male mice. We also examined and compared the variance of female and male groups across all neurobehavioral measures.

Results
We show that accounting for the estrous cycle significantly increases the resolution of the neuroscience studies and allows for: (a) identification of masked sex differences; (b) mechanistic insight(s) into the identified sex differences, across different neurobehavioral outcomes, from behavior to molecular phenotypes. We confirm previous findings that female data from either mixed- or staged-female groups are, on average, not more variable than that of males. However, we show that female variability is not, at all, predictive of whether the estrous cycle plays an important role in regulating the outcome of interest.

Conclusions
We argue that “bringing back” the estrous cycle variable to the main stage is important in order to enhance the resolution and quality of the data, to advance the health of women and other menstruators, and to make research more gender-inclusive. We strongly encourage the neuroscience community to incorporate the estrous cycle information in their study design and data analysis, whenever possible, and we debunk some myths that tend to de-emphasize the importance and discourage the inclusion of this critically important biological variable.
Highlights

Ovarian hormone fluctuation impacts brain physiology and is a major psychiatric risk factor, yet this variable has been overlooked in neuroscience research and psychiatric practice.

From rodent behavior to gene regulation, accounting for the estrous cycle increases the resolution of the neuroscience data, allowing identification and mechanistic insight(s) into sex differences.

Female variability does not equal (and is not predictive of) the estrous cycle effect and should not be used as a proxy for the effects of ovarian hormones on the outcome of interest.

Neuroscience researchers are advised to incorporate the estrous cycle information in their studies to foster more equitable, female- and gender-inclusive research.

Studies of the ovarian cycle are especially important for improving women’s mental health.
Long noncoding RNA IRF1-AS is associated with peste des petits ruminants infection
Authors: Wen Bo , Qi Xuefeng , Lv Daiyue , Yang Lulu , Tang Pan , Chang Wenchi , Han Shuizhong , Yu Shengmeng , Wei Shaopeng , Xue Qinghong , Wang Jingyu 
Published: October 2022

AbstractPeste des petits ruminants (PPR) is an acute and highly contagious disease and has long been a significant threat to small ruminant productivity worldwide. However, the molecular mechanism underlying host-PPRV interactions remains unclear and the long noncoding RNAs (lncRNAs) regulation of PPR virus (PPRV) infection has rarely been reported so far. Here, we first demonstrated that PPRV infection can induce an obvious innate immune response in caprine endometrial epithelial cells (EECs) at 48 h post-infection (hpi) with an MOI of 3. Subsequently, we determined that PPRV infection is associated with 191 significantly differentially expressed (SDE) lncRNAs, namely, 137 upregulated and 54 downregulated lncRNAs, in caprine EECs compared with mock control cells at 48 hpi by using deep sequencing technology. Importantly, bioinformatics preliminarily analyses revealed that these DE lncRNAs were closely related to the immune response. Furthermore, we identified a system of lncRNAs related to the immune response and focused on the role of lncRNA 10636385 (IRF1-AS) in regulating the innate immune response. Interestingly, we found that IRF1-AS was a potent positive regulator of IFN-β and ISG production, which can significantly inhibit PPRV replication in host cells. In addition, our data revealed that IRF1-AS was positively correlated with its potential target gene, IRF1, which enhanced the activation of IRF3 and the expression of ISGs and interacted with IRF3. This study suggests that IRF1-AS could be a new host factor target for developing antiviral therapies against PPRV infection.
Wasteosomes (corpora amylacea) of human brain can be phagocytosed and digested by macrophages
Authors: Riba Marta , Campo-Sabariz Joan , Tena Iraida , Molina-Porcel Laura , Ximelis Teresa , Calvo Maria , Ferrer Ruth , Martín-Venegas Raquel , del Valle Jaume , Vilaplana Jordi , Pelegrí Carme 
Published: October 2022

AbstractBackgroundCorpora amylaceaof human brain, recently renamed as wasteosomes, are granular structures that appear during aging and also accumulate in specific areas of the brain in neurodegenerative conditions. Acting as waste containers, wasteosomes are formed by polyglucosan aggregates that entrap and isolate toxic and waste substances of different origins. They are expelled from the brain to the cerebrospinal fluid (CSF), and can be phagocytosed by macrophages. In the present study, we analyze the phagocytosis of wasteosomes and the mechanisms involved in this process. Accordingly, we purified wasteosomes from post-mortem extracted human CSF and incubated them with THP-1 macrophages. Immunofluorescence staining and time-lapse recording techniques were performed to evaluate the phagocytosis. We also immunostained human hippocampal sections to study possible interactions between wasteosomes and macrophages at central nervous system interfaces.ResultsWe observed that the wasteosomes obtained from post-mortem extracted CSF are opsonized by MBL and the C3b complement protein. Moreover, we observed that CD206 and CD35 receptors may be involved in the phagocytosis of these wasteosomes by THP-1 macrophages. Once phagocytosed, wasteosomes become degraded and some of the resulting fractions can be exposed on the surface of macrophages and interchanged between different macrophages. However, brain tissue studies show that, in physiological conditions, CD206 but not CD35 receptors may be involved in the phagocytosis of wasteosomes.ConclusionsThe present study indicates that macrophages have the machinery required to process and degrade wasteosomes, and that macrophages can interact in different ways with wasteosomes. In physiological conditions, the main mechanism involve CD206 receptors and M2 macrophages, which trigger the phagocytosis of wasteosomes without inducing inflammatory responses, thus avoiding tissue damage. However, altered wasteosomes like those obtained from post-mortem extracted CSF, which may exhibit waste elements, become opsonized by MBL and C3b, and so CD35 receptors constitute another possible mechanism of phagocytosis, leading in this case to inflammatory responses.
A methodological protocol for conducting a scoping review of health research on/by/with Indigenous women in North America
Authors: Loukes Keira A. , Ferreira Celeste , Gaudet Janice Cindy , McGuire-Adams Tricia 
Published: October 2022

AbstractBackgroundIndigenous women in North America experience multiple inequities in terms of health and well-being when compared to non-Indigenous women and Indigenous men. In an effort to understand these health disparities, there has been a surge of research in the field of Indigenous women’s health and well-being over the last 20 years. The objective of this study is to conduct a scoping review of the most current research in this field to determine which theoretical frameworks are being used to study which topics in Indigenous women’s health and well-being in North America.MethodsThe scoping review protocol used was designed to follow an iterative six-step process as laid out by Arksey and O’Malley. Peer-reviewed, academic articles from the following databases were identified: Academic Search Complete, Native Health Database, Web of Science, Google Scholar, Bibliography of Native North America, Sociological Abstracts, Gender Watch, and Indigenous Peoples of North America. Two team members subsequently conducted two screens of titles and abstracts to include articles which focused exclusively on Indigenous women’s health and well-being published between 2011 and 2021. The literature considered focused on Indigenous women’s health and well-being and explicitly states their use of critical theoretical frameworks (e.g., Indigenous feminist, intersectionality, Indigenous resurgence, feminist, critical race) or community-based participatory research (CBPR). Data analysis will involve quantitative and qualitative descriptions.DiscussionThe results of our scoping review (in progress) will map out the current field of Indigenous women’s health research. Our findings will highlight the theoretical frameworks operationalized in research on Indigenous women’s health, identify gaps therein, and provide a basis for understanding how these theoretical lenses shape questions, methodologies, analysis, and implications of academic research.
Mobility-aware hierarchical fog computing framework for Industrial Internet of Things (IIoT)
Authors: Qayyum Tariq , Trabelsi Zouheir , Waqar Malik Asad , Hayawi Kadhim 
Published: October 2022

AbstractThe Industrial Internet of Things (IIoTs) is an emerging area that forms the collaborative environment for devices to share resources. In IIoT, many sensors, actuators, and other devices are used to improve industrial efficiency. As most of the devices are mobile; therefore, the impact of mobility can be seen in terms of low-device utilization. Thus, most of the time, the available resources are underutilized. Therefore, the inception of the fog computing model in IIoT has reduced the communication delay in executing complex tasks. However, it is not feasible to cover the entire region through fog nodes; therefore, fog node selection and placement is still the challenging task. This paper proposes a multi-level hierarchical fog node deployment model for the industrial environment. Moreover, the scheme utilized the IoT devices as a fog node; however, the selection depends on energy, path/location, network properties, storage, and available computing resources. Therefore, the scheme used the location-aware module before engaging the device for task computation. The framework is evaluated in terms of memory, CPU, scalability, and system efficiency; also compared with the existing approach in terms of task acceptance rate. The scheme is compared with xFogSim framework that is capable to handle workload upto 1000 devices. However, the task acceptance ratio is higher in the proposed framework due to its multi-tier model. The workload acceptance ratio is 85% reported with 3000 devices; whereas, in xFogsim the ratio is reduced to approx. 68%. The primary reason for high workload acceptation is that the proposed solution utilizes the unused resources of the user devices for computations.
Myocardial infarction size as an independent predictor of intramyocardial haemorrhage in acute reperfused myocardial ischaemic rats
Authors: Xia Rui , Zhu Tong , Zhang Yu , He Bo , Chen Yushu , Wang Lei , Zhou Yang , Liao Jichun , Zheng Jie , Li Yongmei , Lv Fajin , Gao Fabao 
Published: October 2022

Abstract
Background
In previous studies, haemorrhage occurred only with large infarct sizes, and studies found a moderate correlation between the extent of necrosis and haemorrhage, but the extent of infarction size in these studies was limited. This study aimed to find the correlations between intramyocardial haemorrhage (IMH), myocardial infarction (MI), and myocardial oedema (ME) from small to large sizes of MI in a 7.0-T MR scanner.

Methods
Different sizes of myocardial infarction were induced by occluding different sections of the proximal left anterior descending coronary artery (1–3 mm under the left auricle). T2*-mapping, T2-mapping and late gadolinium enhancement (LGE) sequences were performed on a 7.0 T MR system at Days 2 and 7. T2*- and T2-maps were calculated using custom-made software. All areas were expressed as a percentage of the entire myocardial tissue of the left ventricle. The rats were divided into two groups based on the T2* results and pathological findings; MI with IMH was referred to as the + IMH group, while MI without IMH was referred to as the –IMH group.

Results
The final experimental sample consisted of 25 rats in the + IMH group and 10 rats in the –IMH group. For the + IMH group on Day 2, there was a significant positive correlation between IMH size and MI size (r = 0.677, P < 0.01) and a positive correlation between IMH size and ME size (r = 0.552, P < 0.01). On Day 7, there was a significant positive correlation between IMH size and MI size (r = 0.711, P < 0.01), while no correlation was found between IMH size and ME size (r = 0.429, P = 0.097). The MI sizes of the + IMH group were larger than those of the –IMH group (P < 0.01).

Conclusions
Infarction size prior to reperfusion is a critical factor in determining IMH size in rats.
Transcriptome analysis of sputum cells reveals two distinct molecular phenotypes of “asthma and chronic obstructive pulmonary disease overlap” in the elderly
Authors: Lee Suh-Young , Lee Hyun-Seung , Park Heung-Woo 
Published: October 2022

Abstract
Background
Little is known about the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD) overlap (ACO). This study examined the molecular phenotypes of ACO in the elderly.

Methods
A genome-wide investigation of gene expression in sputum cells from the elderly with asthma, ACO, or COPD was performed using gene set variation analysis (GSVA) with predefined asthma- or COPD-specific gene signatures. We then performed a subsequent cluster analysis using enrichment scores (ESs) to identify molecular clusters in the elderly with ACO. Finally, a second GSVA was conducted with curated gene signatures to gain insight into the pathogenesis of ACO associated with the identified molecular clusters.

Results
Seventy elderly individuals were enrolled (17 with asthma, 41 with ACO, and 12 with COPD). Two distinct molecular clusters of ACO were identified. Clinically, ACO cluster 1 (N = 23) was characterized by male and smoker dominance, more obstructive lung function, and higher proportions of both neutrophil and eosinophil in induced sputum compared to ACO cluster 2 (N = 18). ACO cluster 1 had molecular features similar to both asthma and COPD, with mitochondria and peroxisome dysfunction as important mechanisms in the pathogenesis of these diseases. The molecular features of ACO cluster 2 differed from those of asthma and COPD, with enhanced innate immune reactions to microorganisms identified as being important in the pathogenesis of this form of ACO.

Conclusion
Recognition of the unique biological pathways associated with the two distinct molecular phenotypes of ACO will deepen our understanding of ACO in the elderly.
Reemergence of pathogenic, autoantibody-producing B cell clones in myasthenia gravis following B cell depletion therapy
Authors: Fichtner Miriam L. , Hoehn Kenneth B. , Ford Easton E. , Mane-Damas Marina , Oh Sangwook , Waters Patrick , Payne Aimee S. , Smith Melissa L. , Watson Corey T. , Losen Mario , Martinez-Martinez Pilar , Nowak Richard J. , Kleinstein Steven H. , O’Connor Kevin C. 
Published: October 2022

AbstractMyasthenia gravis (MG) is an autoantibody-mediated autoimmune disorder of the neuromuscular junction. A small subset of patients (<10%) with MG, have autoantibodies targeting muscle-specific tyrosine kinase (MuSK). MuSK MG patients respond well to CD20-mediated B cell depletion therapy (BCDT); most achieve complete stable remission. However, relapse often occurs. To further understand the immunomechanisms underlying relapse, we studied autoantibody-producing B cells over the course of BCDT. We developed a fluorescently labeled antigen to enrich for MuSK-specific B cells, which was validated with a novel Nalm6 cell line engineered to express a human MuSK-specific B cell receptor. B cells (≅ 2.6 million) from 12 different samples collected from nine MuSK MG patients were screened for MuSK specificity. We successfully isolated two MuSK-specific IgG4 subclass-expressing plasmablasts from two of these patients, who were experiencing a relapse after a BCDT-induced remission. Human recombinant MuSK mAbs were then generated to validate binding specificity and characterize their molecular properties. Both mAbs were strong MuSK binders, they recognized the Ig1-like domain of MuSK, and showed pathogenic capacity when tested in an acetylcholine receptor (AChR) clustering assay. The presence of persistent clonal relatives of these MuSK-specific B cell clones was investigated through B cell receptor repertoire tracing of 63,977 unique clones derived from longitudinal samples collected from these two patients. Clonal variants were detected at multiple timepoints spanning more than five years and reemerged after BCDT-mediated remission, predating disease relapse by several months. These findings demonstrate that a reservoir of rare pathogenic MuSK autoantibody-expressing B cell clones survive BCDT and reemerge into circulation prior to manifestation of clinical relapse. Overall, this study provides both a mechanistic understanding of MuSK MG relapse and a valuable candidate biomarker for relapse prediction.