bluuebunny/crossref_metadata_2025 huggingface dataset:
Distinct profile of CD34+ cells and plasma-derived extracellular vesicles from triple-negative patients with Myelofibrosis reveals potential markers of aggressive disease
Authors: Forte Dorian , Barone Martina , Morsiani Cristina , Simonetti Giorgia , Fabbri Francesco , Bruno Samantha , Bandini Erika , Sollazzo Daria , Collura Salvatore , Deregibus Maria Chiara , Auteri Giuseppe , Ottaviani Emanuela , Vianelli Nicola , Camussi Giovanni , Franceschi Claudio , Capri Miriam , Palandri Francesca , Cavo Michele , Catani Lucia
Published: February 2021

Background

Myelofibrosis (MF) is a clonal disorder of hemopoietic stem/progenitor cells (HSPCs) with high prevalence in elderly patients and mutations in three driver genes (JAK2, MPL, or CALR). Around 10–15% of patients are triple-negative (TN) for the three driver mutations and display significantly worse survival. Circulating extracellular vesicles (EVs) play a role in intercellular signaling and are increased in inflammation and cancer. To identify a biomolecular signature of TN patients, we comparatively evaluated the circulating HSPCs and their functional interplay with the microenvironment focusing on EV analysis.

Methods

Peripheral blood was collected from MF patients (n = 29; JAK2V617F mutation, n = 23; TN, n = 6) and healthy donors (HD, n = 10). Immunomagnetically isolated CD34+ cells were characterized by gene expression profiling analysis (GEP), survival, migration, and clonogenic ability. EVs were purified from platelet-poor plasma by ultracentrifugation, quantified using the Nanosight technology and phenotypically characterized by flow cytometry together with microRNA expression. Migration and survival of CD34+ cells from patients were also analyzed after in vitro treatments with selected inflammatory factors, i.e. (Interleukin (IL)-1β, Tumor Necrosis Factor (TNF)-α, IL6) or after co-culture with EVs from MF patients/HD.

Results

The absolute numbers of circulating CD34+ cells were massively increased in TN patients. We found that TN CD34+ cells show in vitro defective functions and are unresponsive to the inflammatory microenvironment. Of note, the plasma levels of crucial inflammatory cytokines are mostly within the normal range in TN patients. Compared to JAK2V617F-mutated patients, the GEP of TN CD34+ cells revealed distinct signatures in key pathways such as survival, cell adhesion, and inflammation. Importantly, we observed the presence of mitochondrial components within plasma EVs and a distinct phenotype in TN-derived EVs compared to the JAK2V617F-mutated MF patients and HD counterparts. Notably, TN EVs promoted the survival of TN CD34+ cells. Along with a specific microRNA signature, the circulating EVs from TN patients are enriched with miR-361-5p.

Conclusions

Distinct EV-driven signals from the microenvironment are capable to promote the TN malignant hemopoiesis and their further investigation paves the way toward novel therapeutic approaches for rare MF.
Overexpression of NELFE contributes to gastric cancer progression via Wnt/β-catenin signaling-mediated activation of CSNK2B expression
Authors: Yu Shijun , Li Li , Cai Hui , He Bin , Gao Yong , Li Yandong
Published: February 2021

Background

Accumulating evidence has highlighted the importance of negative elongation factor complex member E (NELFE) in tumorigenesis. However, the relationship between NELFE and gastric cancer (GC) remains unclear. This study aimed to explore the expression pattern and specific function of NELFE in GC.

Methods

NELFE expression was evaluated by immunohistochemistry and qRT-PCR in GC tissues, respectively. Cell proliferation, migration and invasion were measured by CCK-8, colony formation, transwell assays, and nude mice model. Bioinformatics analysis was performed to search potential target genes of NELFE, and a Cignal Finder 10-Pathway Reporter Array was used to explore potential signaling pathways regulated by NELFE. Dual-luciferase reporter assays, qRT-PCR and western blotting were conducted to verify their regulatory relationship. The expression correlations among NELFE, β-catenin and CSNK2B were further explored by immunohistochemistry on consecutive resections.

Results

NELFE was significantly overexpressed in GC tissues both in protein and mRNA level and negatively correlated with the prognosis of GC patients. Gain- and loss-of-function experiments showed that NELFE potentiated GC cell proliferation and metastasis in vitro and in vivo. CSNK2B was identified as a downstream effector of NELFE. Wnt/β-catenin signaling may mediate the regulation of CSNK2B by NELFE. In addition, NELFE, β-catenin and CSNK2B were all remarkably upregulated in tumor tissues compared with adjacent normal tissues, and their expression levels in GC were positively correlated with each other.

Conclusion

Our findings reveal a new NELFE-Wnt/β-catenin-CSNK2B axis to promote GC progression and provide new candidate targets against this disease.
Alternative polyadenylation: methods, mechanism, function, and role in cancer
Authors: Zhang Yi , Liu Lian , Qiu Qiongzi , Zhou Qing , Ding Jinwang , Lu Yan , Liu Pengyuan
Published: February 2021

Occurring in over 60% of human genes, alternative polyadenylation (APA) results in numerous transcripts with differing 3’ends, thus greatly expanding the diversity of mRNAs and of proteins derived from a single gene. As a key molecular mechanism, APA is involved in various gene regulation steps including mRNA maturation, mRNA stability, cellular RNA decay, and protein diversification. APA is frequently dysregulated in cancers leading to changes in oncogenes and tumor suppressor gene expressions. Recent studies have revealed various APA regulatory mechanisms that promote the development and progression of a number of human diseases, including cancer. Here, we provide an overview of four types of APA and their impacts on gene regulation. We focus particularly on the interaction of APA with microRNAs, RNA binding proteins and other related factors, the core pre-mRNA 3’end processing complex, and 3’UTR length change. We also describe next-generation sequencing methods and computational tools for use in poly(A) signal detection and APA repositories and databases. Finally, we summarize the current understanding of APA in cancer and provide our vision for future APA related research.
MiR-144-3p-mediated dysregulation of EIF4G2 contributes to the development of hepatocellular carcinoma through the ERK pathway
Authors: Li Shuangshuang , Shao Jiajia , Lou Guohua , Wu Chao , Liu Yanning , Zheng Min
Published: February 2021

Background

Hepatocellular carcinoma (HCC) is one of the most common cancers with high incidence and mortality. However, the underlying mechanisms of HCC still remain unclear. Eukaryotic translation initiation factors (eIFs) have a substantial effect on tumor development. In this study, we were aimed to investigate the role of eukaryotic translation initiation factor 4 gamma 2 (EIF4G2) in HCC.

Methods

Western blot (WB) of 30 paired HCC tissues and tissue microarrays (TMAs) conducted by immunohistochemistry (IHC) in 89 paired HCC samples were performed to assess EIF4G2 expression. Clone formation, real-time cell analysis (RTCA), wound healing and transwell assays were adopted to evaluate the role of EIF4G2 on HCC cell proliferation, migration and invasion abilities. The function of EIF4G2 in HCC tumor growth was assessed in a xenograft nude mouse model in vivo. The regulation of EIF4G2 by miR-144-3p was performed by luciferase reporter assay and WB.

Results

The EIF4G2 protein was clearly upregulated in HCC tissues, and high EIF4G2 expression was closely related to HCC prognosis. EIF4G2 silencing could inhibit HCC cell growth and metastasis in vitro, and suppress tumorigenesis in vivo by repressing the ERK signaling pathway. The results of luciferase reporter assays, WB and IHC staining verified that EIF4G2 was negatively regulated by miR-144. And re-expression of EIF4G2 could partially reverse the inhibiting effect of miR-144 in HCC.

Conclusion

In summary, our study revealed the role of EIF4G2 in HCC development via the activation of the ERK pathway. We also found that EIF4G2 could be negatively regulated by the tumor suppressor miR-144. Our investigations indicated that EIF4G2 might be a promising therapeutic target in HCC.
Analgesia in adult trauma patients in physician-staffed Austrian helicopter rescue: a 12-year registry analysis
Authors: Rugg Christopher , Woyke Simon , Voelckel Wolfgang , Paal Peter , Ströhle Mathias
Published: February 2021

Background

Sufficient analgesia is an obligation, but oligoanalgesia (NRS> 3) is frequently observed prehospitally. Potent analgesics may cause severe adverse events. Thus, analgesia in the helicopter emergency medical service (HEMS) setting is challenging. Adequacy, efficacy and administration safety of potent analgesics pertaining to injured patients in HEMS were analysed.

Methods

Observational study evaluating data from 14 year-round physician-staffed helicopter bases in Austria in a 12-year timeframe.

Results

Overall, 47,985 (34.3%) patients received analgesics, 26,059 of whom were adult patients, injured and not mechanically ventilated on site. Main drugs administered were opioids (n=20,051; 76.9%), esketamine (n=9082; 34.9%), metamizole (n=798; 3.1%) and NSAIDs (n=483; 1.9%). Monotherapy with opioids or esketamine was the most common regimen (n=21,743; 83.4%), while opioids together with esketamine (n= 3591; 13.8%) or metamizole (n=369; 1.4%) were the most common combinations. Females received opioids less frequently than did males (n=6038; 74.5% vs. n=14,013; 78.1%; p< 0.001). Pain relief was often sufficient (> 95%), but females more often had moderate to severe pain on arrival in hospital (n=34; 5.0% vs. n=59; 3.2%; p=0.043). Administration of potent analgesics was safe, as indicated by MEES, SpO2 and respiratory rates. On 10% of all missions, clinical patient assessment was deemed sufficient by HEMS physicians and monitoring was spared.

Conclusions

Opioids and esketamine alone or in combination were the analgesics of choice in physician-staffed HEMS in Austria. Analgesia was often sufficient, but females more than males suffered from oligoanalgesia on hospital arrival. Administration safety was high, justifying liberal use of potent analgesics in physician-staffed HEMS.
Low-carbohydrate dietary pattern on glycemic outcomes trial (ADEPT) among individuals with elevated hemoglobin A1c: study protocol for a randomized controlled trial
Authors: Dorans Kirsten S. , Bazzano Lydia A. , Qi Lu , He Hua , Appel Lawrence J. , Samet Jonathan M. , Chen Jing , Mills Katherine T. , Nguyen Bernadette T. , O’Brien Matthew J. , Uwaifo Gabriel I. , He Jiang
Published: February 2021

Background

Type 2 diabetes mellitus (T2DM) is a major cause of morbidity and mortality globally. Strong evidence supports the importance of diet and other lifestyle factors in preventing T2DM. Among individuals with T2DM, low-carbohydrate diets lead to decreases in hemoglobin A1c (HbA1c). However, research on the effects of low-carbohydrate diets on glycemic outcomes among individuals not currently on glucose-lowering medications who have elevated HbA1c is limited.

Methods

The objective of this randomized controlled trial is to study the effect of a healthy low-carbohydrate diet achieved through behavioral intervention and key food supplementation compared with usual diet on HbA1c and other metabolic risk factors among individuals with HbA1c from 6.0 to 6.9% who are not on glucose-lowering medications. In this parallel trial, 150 participants will be randomized to the intervention or control group for 6 months. The healthy low-carbohydrate diet target is < 40 g of net carbohydrates during the first 3 months and < 40 to 60 net grams for months 3 to 6. This diet is characterized by abundant unsaturated fat and protein, high-fiber foods such as non-starchy vegetables and nuts, and minimal refined carbohydrates. The primary outcome is the difference in HbA1c change from baseline to 6 months in the intervention compared with usual diet group. Secondary outcomes include differences between groups in 6-month changes in fasting glucose, systolic blood pressure, total-to-high-density lipoprotein (HDL) cholesterol ratio, and body weight. Exploratory outcomes include differences in 6-month changes in fasting insulin, homeostasis model assessment of insulin resistance, diastolic blood pressure, waist circumference, and 10-year cardiovascular disease risk. An intention-to-treat analysis will be used.

Discussion

We expect that the results from this study will lead to new approaches for developing and implementing dietary approaches (other than the most commonly used reduced fat diet) that will substantially reduce risk of cardiometabolic disease among adults with or at high risk of T2DM. The study intervention involves behavioral counseling and promotes consumption of dietary components thought to reduce risk of cardiometabolic disease and has expected applicability in clinical practice.

Trial registration

ClinicalTrials.gov NCT03675360. Registered on September 18, 2018 (prior to enrolment of the first participant).
Sequential occurrence of microscopic polyangiitis and anti-glomerular basement membrane disease in a patient with small cell lung cancer: a case report
Authors: Hayashi Yusuke , Katayama Yuko , Sakuragi Minoru , Hayashi Ayano , Kakita Hiroko , Uyama Michihiro , Marumo Satoshi , Fukui Motonari
Published: February 2021

Background

The association between a preceding malignancy and the onset of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) has been reported in several studies. While the co-existence of ANCA and anti-glomerular basement membrane (GBM) antibodies in an individual patient is not a common occurrence, this double-positive disease currently has no optimal treatment method. Herein, we report a case of a double-positive disease involving the sequential development of acute kidney injury (AKI) and diffuse alveolar hemorrhage (DAH) in a patient with small cell lung cancer (SCLC).

Case presentation

A 75-year-old Japanese woman was diagnosed with small cell lung cancer (cT3N2M1b cStage IV) and received chemotherapy. After one cycle of chemotherapy, she experienced fever and malaise. Her serum creatinine level rapidly increased, and she tested positive for myeloperoxidase (MPO)-ANCA and anti-GBM antibody. She was diagnosed with AKI due to microscopic polyangiitis (MPA) based on renal biopsy. Corticosteroid therapy was initiated, which improved her renal dysfunction. Eight days after she was discharged from the hospital, she complained of dyspnea and bloody sputum, and her condition rapidly progressed to respiratory failure. Upon chest imaging, ground-glass opacities were seen in her bilateral lower lungs. Laboratory examinations after admission revealed a lower MPO-ANCA titer and an elevated anti-GBM antibody titer compared to her previous admission. We diagnosed her with DAH due to an anti-GBM disease. After corticosteroid pulse therapy, plasma exchange was performed five times; her oxygen saturation and chest radiologic findings improved gradually. Following five cycles of plasma exchange, her oxygen saturation recovered to 95% in room air.

Conclusions

To our knowledge, this is the first reported case of vasculitis caused by MPA and anti-GBM disease leading to the development of AKI and DAH during treatment of SCLC. SCLC, MPA, and anti-GBM disease may occur sequentially. A double-positive disease might have a worse prognosis; therefore, intensive therapy is more likely to achieve a better outcome.
Strategy drives implementation: COVID vaccination in Israel
Authors: Glied Sherry
Published: February 2021

This commentary on Rosen, Waitzberg, and Israeli’s assessment of Israel’s COVID response points to differences in the coherence of each national government’s strategy as the key factor influencing the effectiveness of the vaccine drive. The strengths of the Israeli healthcare system facilitated implementation of the roll-out, but the government’s unambiguous prioritization of vaccination drove implementation success.
Precipitation cloud identification based on faster-RCNN for Doppler weather radar
Authors: Ran Yuanbo , Wang Haijiang , Tian Li , Wu Jiang , Li Xiaohong
Published: February 2021

Precipitation clouds are visible aggregates of hydrometeor in the air that floating in the atmosphere after condensation, which can be divided into stratiform cloud and convective cloud. Different precipitation clouds often accompany different precipitation processes. Accurate identification of precipitation clouds is significant for the prediction of severe precipitation processes. Traditional identification methods mostly depend on the differences of radar reflectivity distribution morphology between stratiform and convective precipitation clouds in three-dimensional space. However, all of them have a common shortcoming that the radial velocity data detected by Doppler Weather Radar has not been applied to the identification of precipitation clouds because it is insensitive to the convective movement in the vertical direction. This paper proposes a new method for precipitation clouds identification based on deep learning algorithm, which is according the distribution morphology of multiple radar data. It mainly includes three parts, which are Constant Altitude Plan Position Indicator data (CAPPI) interpolation for radar reflectivity, Radial projection of the ground horizontal wind field by using radial velocity data, and the precipitation clouds identification based on Faster-RCNN. The testing result shows that the method proposed in this paper performs better than the traditional methods in terms of precision. Moreover, this method boasts great advantages in running time and adaptive ability.
Technology-based health solutions for cancer caregivers to better shoulder the impact of COVID-19: a systematic review protocol
Authors: Su Zhaohui , McDonnell Dean , Liang Bin , Kue Jennifer , Li Xiaoshan , Šegalo Sabina , Advani Shailesh , Flores Bertha E. , Wang Jing
Published: February 2021

Background

Cancer patients are particularly vulnerable to COVID-19, partially owing to their compromised immune systems and curbed or cut cancer healthcare services caused by the pandemic. As a result, cancer caregivers may have to shoulder triple crises: the COVID-19 pandemic, pronounced healthcare needs from the patient, and elevated need for care from within. While technology-based health interventions have the potential to address unique challenges cancer caregivers face amid COVID-19, limited insights are available. Thus, to bridge this gap, we aim to identify technology-based interventions designed for cancer caregivers and report the characteristics and effects of these interventions concerning cancer caregivers' distinctive challenges amid COVID-19.

Methods

A systematic search of the literature will be conducted in PubMed, PsycINFO, CINAHL, and Scopus from the database inception to the end of March 2021. Articles that center on technology-based interventions for cancer caregivers will be included in the review. The search strategy will be developed in consultation with an academic librarian who is experienced in systematic review studies. Titles, abstracts, and full-text articles will be screened against eligibility criteria developed a priori. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses procedures will be followed for the reporting process.

Conclusions

COVID-19 has upended cancer care as we know it. Findings of this study can shed light on evidence-based and practical solutions cancer caregivers can utilize to mitigate the unique challenges they face amid COVID-19. Furthermore, results of this study will also offer valuable insights for researchers who aim to develop interventions for cancer caregivers in the context of COVID-19. In addition, we also expect to be able to identify areas for improvement that need to be addressed in order for health experts to more adequately help cancer caregivers weather the storm of global health crises like COVID-19 and beyond.

Systematic review registration

PROSPEROCRD42020196301
Use of magnetic resonance imaging-guided radiotherapy for breast cancer: a scoping review protocol
Authors: Elliott Sarah , Berlangieri Alexandra , Wasiak Jason , Chao Michael , Foroudi Farshad
Published: February 2021

Background

In recent years, we have seen the incorporation of magnetic resonance imaging (MRI) simulators into radiotherapy centres and the emergence of the new technology of MR linacs. However, the significant health care resources associated with this advanced technology impact immediate widespread use and availability. There are currently limited studies to demonstrate the clinical effectiveness and inform decision-making on the use of MRI in radiotherapy. The objective of this scoping review is to identify and map the existing evidence surrounding the clinical implementation of MRI-guided radiotherapy in patients with breast cancer. It also aims to identify challenges and knowledge gaps in the literature.

Methods

We will perform a comprehensive search in MEDLINE and EMBASE databases from January 2010 onwards. Grey literature sources will include the WHO International Clinical Trials Registry Platform. We will include systematic reviews, randomised and non-randomised controlled studies published in English. Literature should examine the use of magnetic resonance imaging-guided radiotherapy in adults with breast cancer, regardless of cancer stage or severity. Two reviewers will independently screen all titles, abstracts and full-text reports. Data will be extracted and summarised using qualitative (e.g. content and thematic analysis) methods and presented in tables.

Discussion

The results from this review will consolidate the evidence surrounding MRI-guided radiotherapy for breast cancer, contributing to the development and optimisation of patient selection, simulation, planning, treatment delivery, quality assurance and research, to help improve patient outcomes, cancer care and treatment for women with breast cancer.

Systematic review registration

The protocol is available on Open Science Framework at DOI 10.17605/OSF.IO/8TEV6
Cutibacterium avidum resists surgical skin antisepsis in the groin—a potential risk factor for periprosthetic joint infection: a quality control study
Authors: Maurer Steven M. , Kursawe Laura , Rahm Stefan , Prinz Julia , Zinkernagel Annelies S. , Moter Annette , Kuster Stefan P. , Zbinden Reinhard , Zingg Patrick O. , Achermann Yvonne
Published: February 2021

Background

The skin commensal Cutibacterium avidum has been recognized as an emerging pathogen for periprosthetic joint infections (PJI). One currently assumes that the early occurring PJIs are a consequence of skin commensals contaminating the peri-implant tissue during surgery. We addressed whether standard skin antisepsis with povidone-iodine/alcohol before total hip arthroplasty (THA) is effective to eliminate colonizing bacteria with focus on C. avidum.

Methods

In a single-center, prospective study, we screened all patients for skin colonizing C. avidum in the groin before THA. Only in the patients positive for C. avidum, we preoperatively repeated skin swabs after the first and third skin antisepsis and antibiotic prophylaxis. We also obtained dermis biopsies for microbiology and fluorescence in situ hybridization (FISH).

Results

Fifty-one out of 60 patients (85%) were colonized on the skin with various bacteria, in particular with C. avidum in 12 out of 60. Skin antisepsis eliminated C. avidum in eight of ten (20%) colonized patients undergoing THA. Deeper skin (dermis) biopsies were all culture negative, but FISH detected single positive ribosome-rich C. avidum in one case near sweat glands.

Conclusion

Standard skin antisepsis was not effective to completely eliminate colonizing C. avidum on the skin in the groin of patients undergoing THA. Colonizing with C. avidum might pose an increased risk for PJI when considering a THA. Novel more effective antisepsis strategies are needed.

Trial registration No clinical trial
Advances in retina imaging as potential biomarkers for early diagnosis of Alzheimer’s disease
Authors: Zhang Ying , Wang Yanjiang , Shi Ce , Shen Meixiao , Lu Fan
Published: February 2021

As the most common form of dementia, Alzheimer’s disease (AD) is characterized by progressive cognitive impairments and constitutes a major social burden. Currently, the invasiveness and high costs of tests have limited the early detection and intervention of the disease. As a unique window of the brain, retinal changes can reflect the pathology of the brain. In this review, we summarize current understanding of retinal structures in AD, mild cognitive impairment (MCI) and preclinical AD, focusing on neurodegeneration and microvascular changes measured using optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) technologies. The literature suggests that the impairment of retinal microvascular network and neural microstructure exists in AD, MCI and even preclinical AD. These findings provide valuable insights into a better understanding of disease pathogenesis and demonstrate that retinal changes are potential biomarkers for early diagnosis of AD and monitoring of disease progression.
A post-GWAS confirming the genetic effects and functional polymorphisms of AGPAT3 gene on milk fatty acids in dairy cattle
Authors: Shi Lijun , Wu Xin , Yang Yuze , Ma Zhu , Lv Xiaoqing , Liu Lin , Li Yanhua , Zhao Feng , Han Bo , Sun Dongxiao
Published: February 2021

Background

People are paying more attention to the healthy and balanced diet with the improvement of their living standards. Milk fatty acids (FAs) have been reported that they were related to some atherosclerosis and coronary heart diseases in human. In our previous genome-wide association study (GWAS) on milk FAs in dairy cattle, 83 genome-wide significant single nucleotide polymorphisms (SNPs) were detected. Among them, two SNPs, ARS-BFGL-NGS-109493 and BTA-56389-no-rs associated with C18index (P = 0.0459), were located in the upstream of 1-acylglycerol-3-phosphate O-acyltransferase 3 (AGPAT3) gene. AGPAT3 is involved in glycerol-lipid, glycerol-phospholipid metabolism and phospholipase D signaling pathways. Hence, it was inferred as a candidate gene for milk FAs. The aim of this study was to further confirm the genetic effects of the AGPAT3 gene on milk FA traits in dairy cattle.

Results

Through re-sequencing the complete coding region, and 3000 bp of 5′ and 3′ regulatory regions of the AGPAT3 gene, a total of 17 SNPs were identified, including four in 5′ regulatory region, one in 5′ untranslated region (UTR), three in introns, one in 3′ UTR, and eight in 3′ regulatory region. By the linkage disequilibrium (LD) analysis with Haploview4.1 software, two haplotype blocks were observed that were formed by four and 12 identified SNPs, respectively. Using SAS9.2, we performed single locus-based and haplotype-based association analysis on 24 milk FAs in 1065 Chinese Holstein cows, and discovered that all the SNPs and the haplotype blocks were significantly associated with C6:0, C8:0 and C10:0 (P < 0.0001–0.0384). Further, with Genomatix, we predicted that four SNPs in 5′ regulatory region (g.146702957G > A, g.146704373A > G, g.146704618A > G and g.146704699G > A) changed the transcription factor binding sites (TFBSs) for transcription factors SMARCA3, REX1, VMYB, BRACH, NKX26, ZBED4, SP1, USF1, ARNT and FOXA1. Out of them, two SNPs were validated to impact transcriptional activity by performing luciferase assay that the alleles A of both SNPs, g.146704373A > G and g.146704618A > G, increased the transcriptional activities of AGPAT3 promoter compared with alleles G (P = 0.0004).

Conclusions

In conclusion, our findings first demonstrated the significant genetic associations of the AGPAT3 gene with milk FAs in dairy cattle, and two potential causal mutations were detected.
Considerations for mosquito microbiome research from the Mosquito Microbiome Consortium
Authors: Dada Nsa , Jupatanakul Natapong , Minard Guillaume , Short Sarah M. , Akorli Jewelna , Villegas Luis Martinez
Published: February 2021

In the past decade, there has been increasing interest in mosquito microbiome research, leading to large amounts of data on different mosquito species, with various underlying physiological characteristics, and from diverse geographical locations. However, guidelines and standardized methods for conducting mosquito microbiome research are lacking. To streamline methods in mosquito microbiome research and optimize data quality, reproducibility, and comparability, as well as facilitate data curation in a centralized location, we are establishing the Mosquito Microbiome Consortium, a collaborative initiative for the advancement of mosquito microbiome research. Our overall goal is to collectively work on unraveling the role of the mosquito microbiome in mosquito biology, while critically evaluating its potential for mosquito-borne disease control. This perspective serves to introduce the consortium and invite broader participation. It highlights the issues we view as most pressing to the community and proposes guidelines for conducting mosquito microbiome research. We focus on four broad areas in this piece: (1) sampling/experimental design for field, semi-field, or laboratory studies; (2) metadata collection; (3) sample processing, sequencing, and use of appropriate controls; and (4) data handling and analysis. We finally summarize current challenges and highlight future directions in mosquito microbiome research. We hope that this piece will spark discussions around this area of disease vector biology, as well as encourage careful considerations in the design and implementation of mosquito microbiome research.
VirSorter2: a multi-classifier, expert-guided approach to detect diverse DNA and RNA viruses
Authors: Guo Jiarong , Bolduc Ben , Zayed Ahmed A. , Varsani Arvind , Dominguez-Huerta Guillermo , Delmont Tom O. , Pratama Akbar Adjie , Gazitúa M. Consuelo , Vik Dean , Sullivan Matthew B. , Roux Simon
Published: February 2021

Background

Viruses are a significant player in many biosphere and human ecosystems, but most signals remain “hidden” in metagenomic/metatranscriptomic sequence datasets due to the lack of universal gene markers, database representatives, and insufficiently advanced identification tools.

Results

Here, we introduce VirSorter2, a DNA and RNA virus identification tool that leverages genome-informed database advances across a collection of customized automatic classifiers to improve the accuracy and range of virus sequence detection. When benchmarked against genomes from both isolated and uncultivated viruses, VirSorter2 uniquely performed consistently with high accuracy (F1-score > 0.8) across viral diversity, while all other tools under-detected viruses outside of the group most represented in reference databases (i.e., those in the orderCaudovirales). Among the tools evaluated, VirSorter2 was also uniquely able to minimize errors associated with atypical cellular sequences including eukaryotic genomes and plasmids. Finally, as the virosphere exploration unravels novel viral sequences, VirSorter2’s modular design makes it inherently able to expand to new types of viruses via the design of new classifiers to maintain maximal sensitivity and specificity.

Conclusion

With multi-classifier and modular design, VirSorter2 demonstrates higher overall accuracy across major viral groups and will advance our knowledge of virus evolution, diversity, and virus-microbe interaction in various ecosystems. Source code of VirSorter2 is freely available (https://bitbucket.org/MAVERICLab/virsorter2), and VirSorter2 is also available both on bioconda and as an iVirus app on CyVerse (https://de.cyverse.org/de).
Respiratory infections during lithium and valproate medication: a within-individual prospective study of 50,000 patients with bipolar disorder
Authors: Landén Mikael , Larsson Henrik , Lichtenstein Paul , Westin Johan , Song Jie
Published: February 2021

Background

In vitro studies have demonstrated that lithium has antiviral properties, but evidence from human studies is scarce. Lithium is used as a mood stabilizer to treat patients with bipolar disorder. Here, the aim was to investigate the association between lithium use and the risk of respiratory infections in patients with bipolar disorder. To rule out the possibility that a potential association could be due to lithium’s effect on psychiatric symptoms, we also studied the effect of valproate, which is an alternative to lithium used to prevent mood episodes in bipolar disorder.

Method

We followed 51,509 individuals diagnosed with bipolar disorder in the Swedish Patient register 2005–2013. We applied a within-individual design using stratified Cox regression to estimate the hazard ratios (HRs) of respiratory infections during treated periods compared with untreated periods.

Results

During follow-up, 5,760 respiratory infections were documented in the Swedish Patient Register. The incidence rate was 28% lower during lithium treatment (HR 0.73, 95% CI 0.61–0.86) and 35% higher during valproate treatment (HR 1.35, 95% CI 1.06–1.73) compared with periods off treatment.

Conclusions

This study provides real-world evidence that lithium is associated with decreased risk for respiratory infections and suggests that the repurposing potential of lithium for potential antiviral or antibacterial effects is worthy of investigation.
Blood pressure in bipolar disorder: evidence of elevated pulse pressure and associations between mean pressure and mood instability
Authors: McGowan Niall M. , Nichols Molly , Bilderbeck Amy C. , Goodwin Guy M. , Saunders Kate E. A.
Published: February 2021

Background

Bipolar disorder (BD) is associated with excess and premature cardiovascular mortality. Elevated blood pressure (BP) is a leading contributor to cardiovascular risk. However, few studies have examined BP in BD in comparison to other psychiatric disorders. Furthermore, the association between BP and mood instability is not presently clear despite increasing interest in repurposing existing antihypertensive medications as possible novel BD treatments. Thus we examined BP differences between BD and borderline personality disorder (BPD), a disorder with a similar symptom profile through chronic mood instability.

Methods

A total of 106 adults (38 BD, 25 BPD, and 43 healthy controls), evaluated in the Automated Monitoring of Symptom Severity (AMoSS) study, completed a week-long home blood pressure monitoring assessment and ecological momentary assessment of mood. We examined group-wise differences in mean BP and BP variability and their association with mood instability.

Results

BD individuals had a significantly wider resting pulse pressure (40.8 ± 7.4, mmHg) compared to BPD (35.7 ± 5.3, mmHg, P = 0.03) and control participants (37.3 ± 6.3, mmHg, P = 0.036). Systolic BP was negatively associated with sad mood instability, and all measures of mean BP (systolic, diastolic, and mean arterial pressure) were negatively associated with positive mood instability.

Conclusions

This study demonstrates BP differences between BD and healthy and clinical controls that are within a normotensive range. Early pulse pressure widening may be a modifiable pathophysiological feature of BD that confers later cardiovascular risk. BP may be an important transdiagnostic predictor of mood instability and a potential explicit treatment target.
Role of endogenous ouabain in the etiology of bipolar disorder
Authors: El-Mallakh Rif S. , Gao Yonglin , You Pan
Published: February 2021

Background

Bipolar disorder is a severe psychiatric illness with poor prognosis and problematic and suboptimal treatments. Understanding the pathoetiologic mechanisms may improve treatment and outcomes.

Discussion

Dysregulation of cationic homeostasis is the most reproducible aspect of bipolar pathophysiology. Correction of ionic balance is the universal mechanism of action of all mood stabilizing medications. Recent discoveries of the role of endogenous sodium pump modulators (which include ‘endogenous ouabain’) in regulation of sodium and potassium distribution, inflammation, and activation of key cellular second messenger systems that are important in cell survival, and the demonstration that these stress-responsive chemicals may be dysregulated in bipolar patients, suggest that these compounds may be candidates for the coupling of environmental stressors and illness onset. Specifically, individuals with bipolar disorder appear to be unable to upregulate endogenous ouabain under conditions that require it, and therefore may experience a relative deficiency of this important regulatory hormone. In the absence of elevated endogenous ouabain, neurons are unable to maintain their normal resting potential, become relatively depolarized, and are then susceptible to inappropriate activation. Furthermore, sodium pump activity appears to be necessary to prevent inflammatory signals within the central nervous system. Nearly all available data currently support this model, but additional studies are required to solidify the role of this system.

Conclusion

Endogenous ouabain dysregulation appears to be a reasonable candidate for understanding the pathophysiology of bipolar disorder.
Maternal overprotection predicts consistent improvement of self-compassion during mindfulness-based intervention and existential approach: a secondary analysis of the EXMIND study
Authors: Kawano Nobuko , Terao Takeshi , Sakai Akari , Akase Mari , Hatano Koji , Shirahama Masanao , Hirakawa Hirofumi , Kohno Kentaro , Ishii Nobuyoshi
Published: February 2021

Background

Recently, we showed that 4-week mindfulness-based intervention (MBI) followed by 4-week existential approach (EXMIND) was as effective for developing self-compassion as 8-week MBI. This study aims to identify the predictors to EXMIND.

Methods

Of the 63 participants who completed the EXMIND group, 60 participants had baseline, 4-week, and 8-week total scores of the Self-Compassion Scale (SCS). Of the participants, 49 were female and 11 were male, with a mean age of 48.4 years. We investigated the participants’ intervention response patterns, then used analysis of variance to compared those patterns by age, gender, and the baseline scores of the Temperament Evaluation of Memphis, Pisa and San Diego Auto-questionnaire, the Temperament and Character Inventory, Mini-Mental State Examination, the Japanese Adult Reading Test, Young Mania Rating Scale, Hamilton Rating Scale for Depression, the Parental Bonding Instrument, and the Purpose in Life Test. In addition, multivariate logistic regression analysis was performed to identify any response pattern predictors.

Results

Participants were divided into 4 groups based on response patterns in the changes of total SCS scores of the EXMIND group. The first group consisted of 15 participants who responded positively to MBI, but negatively to the existential approach (A group). The second group consisted of 23 participants who responded negatively to MBI, but positively to the existential approach (B group). The third group consisted of 20 participants who responded positively to both MBI and the existential approach (C group). The fourth group consisted of only 2 participants who responded negatively to both MBI and the existential approach (D group). Participants who responded positively to both MBI and the existential approach (C group) reported more maternal overprotectiveness than the other participants (groups A, B, and D).

Conclusions

The present findings suggest that maternal overprotection may predict consistent improvement of self-compassion during EXMIND therapy.
Neuroligin-1 in brain and CSF of neurodegenerative disorders: investigation for synaptic biomarkers
Authors: Camporesi Elena , Lashley Tammaryn , Gobom Johan , Lantero-Rodriguez Juan , Hansson Oskar , Zetterberg Henrik , Blennow Kaj , Becker Bruno
Published: February 2021

Synaptic pathology is a central event in Alzheimer’s disease (AD) and other neurodegenerative conditions, and investigation of synaptic proteins can provide valuable tools to follow synaptic dysfunction and loss in these diseases. Neuroligin-1 (Nlgn1) is a postsynaptic cell adhesion protein, important for synapse stabilization and formation. Nlgn1 has been connected to cognitive disorders, and specifically to AD, as target of the synaptotoxic effect of amyloid-β (Aβ) oligomers and Aβ fibrils. To address changes in Nlgn1 expression in human brain, brain regions in different neurological disorders were examined by Western blot and mass spectrometry. Brain specimens from AD (n = 23), progressive supranuclear palsy (PSP, n = 11), corticobasal degeneration (CBD, n = 10), and Pick’s disease (PiD, n = 9) were included. Additionally, cerebrospinal fluid (CSF) samples of AD patients (n = 43) and non-demented controls (n = 42) were analysed. We found decreased levels of Nlgn1 in temporal and parietal cortex (~ 50–60% reductions) in AD brains compared with controls. In frontal grey matter the reduction was not seen for AD patients; however, in the same region, marked reduction was found for PiD (~ 77%), CBD (~ 66%) and to a lesser extent for PSP (~ 43%), which could clearly separate these tauopathies from controls. The Nlgn1 level was reduced in CSF from AD patients compared to controls, but with considerable overlap. The dramatic reduction of Nlgn1 seen in the brain extracts of tauopathies warrants further investigation regarding the potential use of Nlgn1 as a biomarker for these neurodegenerative diseases.
Psychosocial stress increases testosterone in patients with borderline personality disorder, post-traumatic stress disorder and healthy participants
Authors: Deuter Christian E. , Duesenberg Moritz , Hellmann-Regen Julian , Metz Sophie , Roepke Stefan , Wolf Oliver T. , Otte Christian , Wingenfeld Katja
Published: February 2021

Background

The gonadal hormone testosterone not only regulates sexual behavior but is also involved in social behavior and cognition in both sexes. Changes in testosterone secretion in response to stress have been reported. In addition, stress associated mental disorders such as borderline personality disorder (BPD) and posttraumatic stress disorder (PTSD) are characterized by alterations in basal testosterone metabolism. However, testosterone changes to stress have not been investigated in mental disorders such as BPD and PTSD so far.

Methods

In the study described, we investigated testosterone reactivity to an acute psychosocial stressor, the Trier Social Stress Test (TSST). Our sample consisted of young adult women with BPD (n = 28), PTSD (n = 22) or both disorders (n = 22), and healthy control (n = 51). Based on previous studies on basal testosterone secretion in these disorders, we expected the stress-associated testosterone reactivity to be higher in the BPD group and lower in the PTSD group, when compared to the healthy control group.

Results

The study could demonstrate an increase in testosterone after acute stress exposure across all groups and independent of BPD or PTSD status. Different possible explanations for the absence of a group effect are discussed.

Conclusions

From the results of this study, we conclude that stress-related changes in testosterone release are not affected by BPD or PTSD status in a female patient population. This study expands the knowledge about changes in gonadal hormones and stress reactivity in these disorders.
High blood pressure readings on in-store machines: a qualitative study of the perspective of pharmacy staff
Authors: Mostarac Ivona , Atzema Clare L.
Published: February 2021

Objectives

Emergency department (ED) visits for high blood pressure are on the rise. Yet the majority of these patients are discharged home after their ED evaluation, particularly those who present following an elevated reading on an in-store pharmacy machine. We aimed to gain insight on the practice and referral patterns of pharmacy staff who encounter a patient with an elevated in-store blood pressure (BP) reading.

Methods

We conducted a qualitative study using semi-structured interviews with pharmacy staff (pharmacists and pharmacy technicians/assistants) from California, United States and Ontario, Canada. Interview questions were designed to examine the practice and referral patterns of pharmacy staff for patients with elevated in-store BP readings. Standard descriptive content analysis techniques were used to analyze the data and to develop themes for current practice and referral patterns.

Results

Twenty-four interviews were completed: six with pharmacy technicians/assistants and 18 with pharmacists. Canadian pharmacy staff (83%) reported being approached frequently (defined as from weekly up to multiple times per day) by patients concerned about an elevated BP reading on an in-store machine, versus 50% reported by American participants. Participant definition of an elevated BP varied, with systolic values ranging from 120 to 150 mmHg and diastolic values from 60 to 90 mmHg. Participants emphasized the need to converse with and assess their patients prior to providing advice. The most frequently reported advice was to seek referral from an outside health care provider: ED, urgent care, or a primary care practitioner. Severity of the BP reading and symptomatology were reported as determining factors for referring patients to the ED. Pharmacists (92%) reported a lack of corporate and/or governing body policy for managing patients with in-store markedly elevated BP readings.

Conclusions

Managing patients with an elevated BP reading in the community pharmacy setting is complex and not standardized. Referral to an external health care provider, including the ED, was a common theme. The development of a pharmacy referral tool/algorithm may be helpful to refer in-store patients with elevated BP readings to the most appropriate healthcare resources.
Characteristics and patterns of older adult homicides in the United States
Authors: Shawon Riffat Ara , Adhia Avanti , DeCou Christopher , Rowhani-Rahbar Ali
Published: February 2021

Background

Nearly 1800 homicides were reported in 2018 among individuals aged 60 years or older in the US. The characteristics and circumstances of these homicides are understudied. We investigated the trends of homicides over time and compared victim, perpetrator, and incident characteristics by mechanism (firearm vs. non-firearm) among adults aged 60 years or older.

Methods

We examined cross-sectional restricted-access data from the National Violent Death Reporting System from 2003 to 2017. Fatal Injury Data by CDC provided age-adjusted homicide rates. We quantitatively summarized victim, perpetrator, and incident characteristics for firearm and non-firearm homicides. We also reviewed 150 qualitative narratives to better understand the context of older adult homicides perpetrated by firearms. All data were analyzed in February 2020.

Results

Overall and firearm-specific older adult homicide rates increased between 2014 and 2017. Of the 6188 victims, 62% were male. The majority of victims (68%) were killed at home. Firearms (44%), sharp (19%) and blunt weapons (15%) were common mechanisms used in older adult homicides. The perpetrator was an intimate partner in 39% of firearm homicides and 12% of non-firearm homicides (prevalence difference = 27%; 95% CI: 25, 30%). Similarly, homicide-suicides (prevalence difference = 21%; 95% CI: 19, 22%) and multiple-victim incidents (prevalence difference = 7%; 95% CI: 5, 8%) were more common in firearm (23 and 13%, respectively) than in non-firearm (2 and 6%, respectively) homicides. Common contexts of firearm homicides were familial/intimate partner problems, robbery/burglary, argument, and illness.

Conclusions

A substantial number of older adults were killed with firearms and by their intimate partners. Further research to identify violence victimization prevention strategies in this group, especially those that limit access to firearms by potential perpetrators, is warranted.