bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular subtypes based on cuproptosis-related genes and tumor microenvironment infiltration characterization in ovarian cancer
Authors: Zhang Jingjing , Lu Miao , Xu Haoya , Ren Fang , Zhu Liancheng
Published: October 2022

Background

Cuproptosis (copper death) is a recently found cell death type produced by copper iron; nonetheless, the properties of cuproptosis molecular subtypes and possible involvement of cuproptosis-related genes (CRGs) in the tumor microenvironment (TME) in ovarian cancer (OC) remain unknown.

Methods

CRG changes were characterized at the genomic and transcriptional levels in 656 OC samples, and their expression patterns were investigated using three different datasets.

Results

We identified three distinct molecular subtypes, and discovered that variations in molecular subtypes were linked to patient prognosis, TME cell infiltration characteristics, malignancy, and immune-related pathways. Then, in order to predict overall survival (OS), we created a risk score and tested its predictive potential in OC patients. As a result, we created a very accurate nomogram to increase risk score clinical applicability. Better OS, younger age, early stage, and immune activity were all associated with a low risk score. The hallmarks of a high-risk score are older age, advanced stage, immunosuppression, and a bad prognosis. Furthermore, risk score was linked to immune checkpoint expression (including PD-L1, CTLA4), targeted therapy gene expression (PARP, PDGFRA), cancer stem cell (CSC), chemotherapy and targeted medication sensitivity.

Conclusions

Our comprehensive analysis of CRGs in OC showed their potential role in TME, clinicopathological characteristics, chemotherapy and targeted drug screening and prognosis. These discoveries could help us better understand CRGs in OC, as well as pave the path for novel ways to assess prognosis and design more effective immunotherapy strategies.
Molecular surveillance for anti-malarial drug resistance and genetic diversity of Plasmodium falciparum after chloroquine and sulfadoxine-pyrimethamine withdrawal in Quibdo, Colombia, 2018
Authors: Guerra Angela Patricia , Olivera Mario Javier , Cortés Liliana Jazmín , Chenet Stella M. , Macedo de Oliveira Alexandre , Lucchi Naomi W.
Published: October 2022

Background

Resistance to anti-malarial drugs is associated with polymorphisms in target genes and surveillance for these molecular markers is important to detect the emergence of mutations associated with drug resistance and signal recovering sensitivity to anti-malarials previously used.

Methods

The presence of polymorphisms in genes associated with Plasmodium falciparum resistance to chloroquine and sulfadoxine-pyrimethamine was evaluated by Sanger sequencing, in 85 P. falciparum day of enrollment samples from a therapeutic efficacy study of artemether–lumefantrine conducted in 2018–2019 in Quibdo, Colombia. Samples were genotyped to assess mutations in pfcrt (codons 72–76), pfdhfr (codons 51, 59, 108, and 164), and pfdhps genes (codons 436, 437, 540, and 581). Further, the genetic diversity of infections using seven neutral microsatellites (NMSs) (C2M34, C3M69, Poly α, TA1, TA109, 2490, and PfPK2) was assessed.

Results

All isolates carried mutant alleles for pfcrt (K76T and N75E), and for pfdhfr (N51I and S108N), while for pfdhps, mutations were observed only for codon A437G (32/73, 43.8%). Fifty samples (58.8%) showed a complete neutral microsatellites (NMS) profile. The low mean number of alleles (2 ± 0.57) per locus and mean expected heterozygosity (0.17 ± 0.03) showed a reduced genetic diversity. NMS multilocus genotypes (MMG) were built and nine MMG were identified.

Conclusions

Overall, these findings confirm the fixation of chloroquine and pyrimethamine-resistant alleles already described in the literature, implying that these drugs are not currently appropriate for use in Colombia. In contrast, mutations in the pfdhps gene were only observed at codon 437, an indication that full resistance to sulfadoxine has not been achieved in Choco. MMGs found matched the clonal lineage E variant 1 previously reported in northwestern Colombia.
New insight into the role of lipid metabolism-related proteins in rheumatic heart valve disease
Authors: Xie Ting , Chen Xuan , Liu Cong , Cai Xingjiu , Xiang Mei , Liu Shiwu , Li Ruzheng , Lin Zhichuan , Liu Debing , Dong Ming , Chen Xinzhong , Zou Minghui , Qiao Ping
Published: October 2022

Purpose

The aim of this study was to determine the expression of lipid metabolism-related proteins in rheumatic heart valve disease (RHVD).

Methods

This retrospective study involved a total of 20 cases of moderate or severe rheumatic mitral valve stenosis and 4 cases of mitral regurgitation due to secondary causes from September 2018 to September 2021. The patients enrolled included 12 males and 12 females who underwent surgical excision of the mitral valve at the cardiac surgery department of Hainan General Hospital. The samples of mitral valve were collected during surgery treatment as the study group, and mitral valves collected from patients with ischemic heart disease were allocated into the control group. Hematoxylin–eosin (HE), oil red staining and immunohistochemical (IHC) staining were conducted to compare the expression of lipid metabolism-related proteins (ATP-binding cassette transporter A1 and acyl-coenzyme A: cholesterol acyltransferase-1), and real-time polymerase chain reaction (RT–PCR) was applied to compare the mRNA levels of ABCA1, ACAT1, and the inflammatory cytokines TNF-α, IL-10, and MCP-1.

Results

In general, the rheumatic mitral valve showed leaflet thickening along with border adhesions and visible yellow fats. Oil red O staining also revealed the abovementioned results as well as fat cells. Both ABCA1 and ACAT1 were expressed in the rheumatic mitral valve via IHC, whereas only ACAT1 showed a faint level of expression in the ischemic mitral valve with no expression of ABCA1. In addition, compared with the ischemic mitral valve, RT-PCT showed increased mRNA expression levels of ABCA1, ACAT1, and the inflammatory cytokines TNF-α, IL-10, and MCP-1 (P < 0.05). After dividing the RMs into two groups for RT–PCR, we found that the higher the expression of ABCA1 and ACAT1 was, the lower the relative expression of inflammatory factors.

Conclusion

This study showed that adipose tissue, adipose cells, and lipid transport-related proteins were expressed strongly in the rheumatic mitral valve, suggesting that adipose tissue formation might be one of the important pathways in the pathology of rheumatic heart disease. In addition, adipose tissue and adipocytes were also involved in the inflammatory process. These data provide new insight into pathological mechanisms in rheumatic heart disease.
MICALL2 as a substrate of ubiquitinase TRIM21 regulates tumorigenesis of colorectal cancer
Authors: Wen Pushuai , Wang Huade , Li Yi , Sui Xinyao , Hou Zhijuan , Guo Xiaoyan , Xue Wanying , Liu Dahua , Wang Yu , Gao Jing
Published: October 2022

Background

Molecule interacting with CasL-like protein 2 (MICALL2) is believed to regulate cytoskeleton dynamics, tight junction formation, and neurite outgrowth. However, its biological role and the underlying mechanism in colorectal cancer (CRC) remain largely elusive.

Methods

qRT-PCR, Western blotting and immunohistochemistry assays were used to detect the expression levels of different genes. Next, mass spectrometry, co-immunoprecipitation and immunofluorescence staining were used to detect the interactions of proteins. Furthermore, MTT assay, colony formation assay, wound-healing assays and xenograft tumor models were performed to demonstrate the functions of MICALL2 in CRC. In addition, transcriptome sequencing and Western blotting were conducted to verify the mechanism of MICALL2 in CRC.

Results

We found that both mRNA and protein levels of MICALL2 are up-regulated in colorectal cancer tissues compared with non-tumor tissues and that its overexpression is closely correlated with poor prognosis. Ubiquitin E3 ligase Tripartite motif-containing protein 21 (TRIM21) mediated MICALL2 ubiquitination and proteasome-dependent degradation, negatively correlated with MICALL2 levels, and reversely regulated the tumorigenic activity of MICALL2 in CRC. Functional studies confirmed that MICALL2 promoted colorectal cancer cell growth and migration via the Wnt/β-catenin signaling pathway.

Conclusions

As a substrate of ubiquitinase TRIM21, MICALL2 enhances the growth and migration of colorectal cancer cells and activates the Wnt/β-catenin signaling pathway.
ANCA-associated vasculitis with cardiac valve vegetations in two teenage males: two case reports and a literature review
Authors: Theisen Alexandra , Phillips Carrie L. , Rodriguez Martha
Published: October 2022

Background

Anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis is a term used to describe systemic vasculitides that affect small and medium-sized blood vessels. Granulomatosis with Polyangiitis (GPA), a type of ANCA-associated vasculitis (AAV), is rare in children with an estimated prevalence of 3–4 per million, and even more rare is the manifestation of cardiac abnormalities secondary to ANCA-associated vasculitis in the pediatric population.

Case presentation

We discuss the cases of two teenage males who presented with cardiac valvular lesions secondary to GPA in addition to sinus, pulmonary, renal, and cutaneous involvement. These findings of cardiac valvular abnormalities in GPA have rarely been described in the literature in pediatrics. Both patients were treated with rituximab, high-dose methylprednisolone, and therapeutic plasma exchange and showed improvement in their disease manifestations.

Conclusions

A review of the literature revealed only five pediatric cases of ANCA-associated vasculitis with cardiac manifestations, and interestingly, three of the five had valvular involvement. Subsequent valvular involvement makes obtaining the diagnosis of ANCA-Associated Vasculitis difficult due to concern for underlying infectious endocarditis and can lead to misdiagnosis given the rarity of cardiac involvement in ANCA-associated vasculitis. Routine echocardiogram is not always completed in newly diagnosed AAV, yet cardiac involvement can lead to severe consequences as was seen with our first patient in the form of thromboembolic stroke. We discuss the importance of keeping AAV on the differential when cardiac lesions are present as well as the importance of regular cardiac screening in newly diagnosed patients with AAV, as it is a major factor of cardiac morbidity and mortality in the adult population and can contribute substantially to management decisions.
Targeted medical examinations for workers exposed to fumigants
Authors: Aribou Zeenathnisa Mougammadou , Ng Wee Tong
Published: October 2022

Fumigants are gaseous pesticides or biocides which eradicate pests by suffocation or poisoning. Worker exposure to fumigants is mainly via inhalation, followed by dermal contact and ingestion, leading to various acute and chronic health effects. Implementation of appropriate workplace controls such as adequate ventilation, training and personal protective equipment ensure that exposure to fumigants are kept to the lowest level as practically possible. In addition, routine medical examinations also allow for doctors to identify and manage possible exposure to fumigants and ascertain workers’ fitness to work.

While management guidelines after an acute exposure to such fumigants is clear and consistent, the guidelines on routine medical examination for fumigators is sparse. Components of the medical examinations vary according to the fumigant, workers are exposed to and its chronic health effects. Hence, this paper highlights the health hazards of commonly utilised fumigants; Methyl Bromide, Hydrogen Cyanide, Hydrogen Phosphide and Sulfuryl Fluoride; and outlines the guidance for routine medical examinations for exposed fumigators.
A safety study of intraoperative radiation therapy following stereotactic body radiation therapy and multi-agent chemotherapy in the treatment of localized pancreatic adenocarcinoma: study protocol of a phase I trial
Authors: Reddy Abhinav V. , Hill Colin S. , Zheng Lei , He Jin , Narang Amol K.
Published: October 2022

Background

Localized pancreatic adenocarcinoma carries a poor prognosis even after aggressive therapy. Up to 40% of patients may develop locoregional disease as the first site of failure. As such, there may be a role for intensification of local therapy such as radiation therapy. Radiation dose escalation for pancreatic cancer is limited by proximity of the tumor to the duodenum. However, the duodenum is removed during Whipple procedure, allowing the opportunity to dose escalate with intraoperative radiation therapy (IORT). Although prior studies have shown potential benefit of IORT in pancreatic cancer, these studies did not utilize ablative doses (biologically effective dose [BED10] > 100 Gy). Furthermore, the optimal radiation target volume in this setting is unclear. There has been increased interest in a “Triangle Volume” (TV), bordered by the celiac axis, superior mesenteric artery, common hepatic artery, portal vein, and superior mesenteric vein. Dissection of this area, has been advocated for by surgeons from Heidelberg as it contains extra-pancreatic perineural and lymphatic tracts, which may harbor microscopic disease at risk of mediating local failure. Interestingly, a recent analysis from our institution indicated that nearly all local failures occur in the TV. Therefore, the purpose of this protocol is to evaluate the safety of delivering an ablative radiation dose to the TV with IORT following neoadjuvant chemotherapy and stereotactic body radiation therapy (SBRT).

Methods

Patients with non-metastatic pancreatic adenocarcinoma centered in the head or neck of the pancreas will be enrolled. Following treatment with multi-agent neoadjuvant chemotherapy, patients will undergo SBRT (40 Gy/5 fractions) followed by IORT (15 Gy/1 fraction) to the TV during the Whipple procedure. The primary objective is acute (< 90 days) toxicity after IORT measured by Clavien-Dindo classification. Secondary objectives include late (> 90 days) toxicity after IORT measured by Clavien-Dindo classification, overall survival, local progression-free survival, distant metastasis-free survival, and progression-free survival.

Discussion

If the results show that delivering an ablative radiation dose to the TV with IORT after neoadjuvant chemotherapy and SBRT is safe and feasible, it warrants further investigation in a phase II trial to evaluate efficacy of this approach.

Trial Registration This study was registered at ClinicalTrials.gov on 12/2/2021 (NCT05141513). https://clinicaltrials.gov/ct2/show/NCT05141513
Alterations of bacteriome, mycobiome and metabolome characteristics in PCOS patients with normal/overweight individuals
Authors: Yin Guoshu , Chen Fu , Chen Guishan , Yang Xiaoping , Huang Qingxia , Chen Lan , Chen Minjie , Zhang Weichun , Ou Miaoqiong , Cao Man , Lin Hong , Chen Man , Xu Hongzhi , Ren Jianlin , Chen Yongsong , Chen Zhangran
Published: October 2022

To characterize the gut bacteriome, mycobiome and serum metabolome profiles in polycystic ovary syndrome (PCOS) patients with normal/overweight individuals and evaluate a potential microbiota-related diagnostic method development for PCOS, 16S rRNA and ITS2 gene sequencing using 88 fecal samples and 87 metabolome analysis from serum samples are conducted and PCOS classifiers based on multiomics markers are constructed. There are significant bacterial, fungal community and metabolite differences among PCOS patients and healthy volunteers with normal/overweight individuals. Healthy individuals with overweight/obesity display less abnormal metabolism than PCOS patients and uniquely higher abundance of the fungal genus Mortierella. Nine bacterial genera, 4 predicted pathways, 11 fungal genera and top 30 metabolites are screened out which distinguish PCOS from healthy controls, with AUCs of 0.84, 0.64, 0.85 and 1, respectively. The metabolite-derived model is more accurate than the microbe-based model in discriminating normal BMI PCOS (PCOS-LB) from normal BMI healthy (Healthy-LB), PCOS-HB from Healthy-HB. Featured bacteria, fungi, predicted pathways and serum metabolites display higher associations with free androgen index (FAI) in the cooccurrence network. In conclusion, our data reveal that hyperandrogenemia plays a central role in the dysbiosis of intestinal microecology and the change in metabolic status in patients with PCOS and that its effect exceeds the role of BMI. Healthy women with high BMI showed unique microbiota and metabolic features.The priority of predictive models in discriminating PCOS from healthy status in this study were serum metabolites, fungal taxa and bacterial taxa.
scTAM-seq enables targeted high-confidence analysis of DNA methylation in single cells
Authors: Bianchi Agostina , Scherer Michael , Zaurin Roser , Quililan Kimberly , Velten Lars , Beekman Renée
Published: October 2022

Single-cell DNA methylation profiling currently suffers from excessive noise and/or limited cellular throughput. We developed scTAM-seq, a targeted bisulfite-free method for profiling up to 650 CpGs in up to 10,000 cells per experiment, with a dropout rate as low as 7%. We demonstrate that scTAM-seq can resolve DNA methylation dynamics across B-cell differentiation in blood and bone marrow, identifying intermediate differentiation states that were previously masked. scTAM-seq additionally queries surface-protein expression, thus enabling integration of single-cell DNA methylation information with cell atlas data. In summary, scTAM-seq is a high-throughput, high-confidence method for analyzing DNA methylation at single-CpG resolution across thousands of single cells.
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

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

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

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

Peste 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

Background

Corpora 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.

Results

We 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.

Conclusions

The 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

Background

Indigenous 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.

Methods

The 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.

Discussion

The 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

The 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

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

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

Myasthenia 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.
Prediction of the indoor climate in cultural heritage buildings through machine learning: first results from two field tests
Authors: Boesgaard Christian , Hansen Birgit Vinther , Kejser Ulla Bøgvad , Mollerup Søren Højlund , Ryhl-Svendsen Morten , Torp-Smith Noah
Published: October 2022

Control of temperature and relative humidity in storage areas and exhibitions is crucial for long-term preservation of cultural heritage objects. This paper explores the possibilities for developing a proactive system, based on a machine-learning model (XGBoost), for predicting the occurrence of unwanted indoor environmental conditions: either a too high or a too low relative humidity, within the forthcoming 24 h. The features used in the model were hourly indoor and outdoor climate recordings, and it was applied to two indoor heritage environments; a storage facility and a church building. The test accuracy (f1-score) of the model was good (0.93 for high RH; 0.93 for low RH) when applied to the storage building, but only 0.78; 0.62 (high RH; low RH) for the church building test. Challenges encountered include difficulties in obtaining good historical climate data sets for training and testing the model, and the dependency of external IT systems, which, if they fail, inactivates the model without a warning. Several issues call for more research: A desirable improvement of the model would be predictions for periods longer than 24 h ahead, still maintaining a high test accuracy. Further perspectives of using machine learning for indoor environmental forecasting could be for indoor air pollution, or energy consumption due to climate control.
Prevalences and excretion levels of Lawsonia intracellularis, Brachyspira pilosicoli and Escherichia coli F4 and F18 in fecal sock samples from Danish weaner and finisher pig batches and the association with diarrhea
Authors: Musse Susanne Leth , Nielsen Gitte Blach , Stege Helle , Weber Nicolai Rosager , Houe Hans
Published: October 2022

Background

Bacterial enteritis in growing pigs is a matter of concern in Danish pig production challenging herd health as well as production economy, and antimicrobial usage. The aim of this observational study using fecal sock samples was to determine the prevalence and excretion level of Lawsonia intracellularis(LI), Brachyspira pilosicoli(BP),Escherichia coli F4(F4) andF18(F18) and to investigate associations between prevalence or excretion levels of the bacteria and diarrhea. The study was performed in the late weaner and the early finisher period in herds with a history of diarrhea. Every weaner and finisher herd contributed with one sample each.

Results

In total, 47 weaner and 59 finisher herds were sampled. The overall prevalence and excretion levels (median and range in log(10) copies/gram of feces) were for LI 84.0% (median 6.2; range 3.0–7.7), for BP 45.2% (median 5.6; range 3.0–6.6), for F18 20.8% (median 5.7; range 4.7–7.7), and for F4 4.7% (median 5.5; range 5.2–6.0). In both diarrheic and non-diarrheic samples, the most prevalent bacteria were either LI alone or LI and BP in combination. In general, no association was found between increasing total bacterial excretion levels and diarrhea, but prevalence (p = 0.04) and excretion (p < 0.01) level of F18 was found to be significantly higher in diarrheic samples. Further, a significant association was found between low LI excretion level and lack of diarrhea in weaner herds (p = 0.03). A significant positive correlation was found between excretion levels of LI and BP in diarrheic weaner herd samples (p = 0.02).

Conclusion

Enteric pathogens were prevalent in a wide range of bacterial excretion levels in both diarrheic and non-diarrheic samples. Especially LI and BP were frequently found and with a positive correlation between excretion levels. Even in the absence of diarrhea, high prevalence and excretion levels of LI and BP were detected, thus making the status of diarrhea an insufficient tool for assessing the severity of their infections.
Identification of tumor-associated antigens and immune subtypes of lower-grade glioma and glioblastoma for mRNA vaccine development
Authors: Wang Zhi-liang , Huang Ruo-yu , Han Bo , Wu Fan , Sun Zhi-yan , Li Guan-zhang , Zhang Wei , Zhao Zheng , Liu Xing
Published: October 2022

Background

mRNA became a promising therapeutic approach in many diseases. This study aimed to identify the tumor antigens specifically expressed in tumor cells for lower-grade glioma (LGG) and glioblastoma (GBM) patients.

Methods

In this work, the mRNA microarray expression profile and clinical data were obtained from 301 samples in the Chinese Glioma Genome Atlas (CGGA) database, the mRNA sequencing data and clinical data of 701 samples were downloaded from The Cancer Genome Atlas (TCGA) database. Genetic alterations profiles were extracted from CGGA and cBioPortal datasets. R language and GraphPad Prism software were applied for the statistical analysis and graph work.

Results

PTBP1 and SLC39A1, which were overexpressed and indicated poor prognosis in LGG patients, were selected as tumor-specific antigens for LGG patients. Meanwhile, MMP9 and SLC16A3, the negative prognostic factors overexpressed in GBM, were identified as tumor-specific antigens for GBM patients. Besides, three immune subtypes (LGG1-LGG3) and eight WGCNA modules were identified in LGG patients. Meanwhile, two immune subtypes (GBM1–GBM2) and 10 WGCNA modules were selected in GBM. The immune characteristics and potential functions between different subtypes were diversity. LGG2 and GBM1 immune subtype were associated with longer overall survival than other subtypes.

Conclusion

In this study, PTBP1 and SLC39A1 are promising antigens for mRNA vaccines development in LGG, and MMP9 and SLC16A3 were potential antigens in GBM. Our analyses indicated that mRNA vaccine immunotherapy was more suitable for LGG2 and GBM1 subtypes. This study was helpful for the development of glioma immunotherapies.
The AYA Care Plan: Initial Evaluation of a Web-Based Psychosocial Intervention
Authors: Markwardt Haley S. , Taghavi Sarah E. , Williams Addison P. , Olivares Matthew N. , McDuffee Peyton R. , Al Achkar Morhaf , Hall Brittany C.
Published: October 2022

PURPOSE

Adolescents and young adults (AYA) with cancer do not fit neatly into pediatric or older adult oncology care settings. Recent efforts have led to the development of psychosocial interventions for AYAs, but studies show AYAs demonstrate low levels of engagement in psychosocial services. The AYA Care Plan is one of the only web-based tools providing a personalized, psychosocial resource that addresses unmet needs for AYAs in active treatment and post-treatment survivorship. The current study aims to assess the usability and utility of the AYA Care Plan and identify opportunities for improvement.

METHODS

Clinic staff administered an online distress and needs assessment to AYA patients with cancer at outpatient oncology clinics. Personalized care plans were sent to participants on the basis of their responses. A total of 11 AYAs between the ages 18 and 39 years, with a mean age of 31.64 years, then completed qualitative interviews about their experiences. Thematic analysis was used to identify themes on the AYA Care Plan.

RESULTS

A majority of participants reported positive usability features. Half of the participants reported using their care plan to make health care decisions. One person indicated not finding the resources helpful, and the other half of participants reported not engaging with the care plan. Participants also offered suggestions for improvement.

CONCLUSION

The AYA Care Plan appears to be a useful psychosocial intervention for some AYAs with cancer. Future research should continue to examine the AYA Care Plan's usability and utility, and specify when, how, and for whom the AYA Care Plan is useful.