bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association ofHLA-class IIalleles with risk of relapse in myeloperoxidase-antineutrophil cytoplasmic antibody positive vasculitis in the Japanese population
Authors: Kawasaki Aya , Sada Ken-ei , Kusumawati Premita Ari , Hirano Fumio , Kobayashi Shigeto , Nagasaka Kenji , Sugihara Takahiko , Ono Nobuyuki , Fujimoto Takashi , Kusaoi Makio , Tamura Naoto , Kusanagi Yasuyoshi , Itoh Kenji , Sumida Takayuki , Yamagata Kunihiro , Hashimoto Hiroshi , Makino Hirofumi , Arimura Yoshihiro , Harigai Masayoshi , Tsuchiya Naoyuki 
Published: December 2022

AbstractBackgroundDisease relapse remains a major problem in the management of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). In European populations,HLA-DPB1*04:01is associated with both susceptibility and relapse risk in proteinase 3-ANCA positive AAV. In a Japanese population, we previously reported an association betweenHLA-DRB1*09:01andDQB1*03:03with susceptibility to, andDRB1*13:02with protection from, myeloperoxidase-ANCA positive AAV (MPO-AAV). Subsequently, the association ofDQA1*03:02, which is in strong linkage disequilibrium withDRB1*09:01andDQB1*03:03, with MPO-AAV susceptibility was reported in a Chinese population. However, an association between these alleles and risk of relapse has not yet been reported. Here, we examined whetherHLA-class IIis associated with the risk of relapse in MPO-AAV.MethodsFirst, the association ofHLA-DQA1*03:02with susceptibility to MPO-AAV and microscopic polyangiitis (MPA) and its relationship with previously reportedDRB1*09:01andDQB1*03:03were examined in 440 Japanese patients and 779 healthy controls. Next, the association with risk of relapse was analyzed in 199 MPO-ANCA positive, PR3-ANCA negative patients enrolled in previously reported cohort studies on remission induction therapy. Uncorrected P values (Puncorr) were corrected for multiple comparisons in each analysis using the false discovery rate method.ResultsThe association ofDQA1*03:02with susceptibility to MPO-AAV and MPA was confirmed in a Japanese population (MPO-AAV: Puncorr=5.8×10−7, odds ratio [OR] 1.74, 95% confidence interval [CI] 1.40–2.16, MPA: Puncorr=1.1×10−5, OR 1.71, 95%CI 1.34–2.17).DQA1*03:02was in strong linkage disequilibrium withDRB1*09:01andDQB1*03:03, and the causal allele could not be determined using conditional logistic regression analysis. Relapse-free survival was shorter with nominal significance in carriers ofDRB1*09:01(Puncorr=0.049, Q=0.42, hazard ratio [HR]:1.87),DQA1*03:02(Puncorr=0.020, Q=0.22, HR:2.11) andDQB1*03:03(Puncorr=0.043, Q=0.48, HR:1.91) than in non-carriers in the log-rank test. Conversely, serine carriers at position 13 of HLA-DRβ1 (HLA-DRβ1_13S), includingDRB1*13:02carriers, showed longer relapse-free survival with nominal significance (Puncorr=0.010, Q=0.42, HR:0.31). By combiningDQA1*03:02and HLA-DRβ1_13S, a significant difference was detected between groups with the highest and lowest risk for relapse (Puncorr=0.0055, Q=0.033, HR:4.02).ConclusionHLA-class IIis associated not only with susceptibility to MPO-AAV but also with risk of relapse in the Japanese population.
Cost-effectiveness of the second COVID-19 booster vaccination in the United States
Authors: Li Rui , Lu Pengyi , Fairley Christopher K , Pagán José A. , Hu Wenyi , Yang Qianqian , Zhuang Guihua , Shen Mingwang , Li Yan , Zhang Lei 
Published: December 2022

ABSTRACTBackgroundThe United States (US) authorized the second COVID-19 booster for individuals aged 50+ years on March 29, 2022. To date, the cost-effectiveness of the second booster strategy remains unassessed.MethodsWe developed a decision-analytic SEIR-Markov model by five age groups (0-4yrs, 5-11yrs 12-17yrs, 18-49yrs, and 50+yrs) and calibrated the model by actual mortality in each age group in the US. We conducted fives scenarios to evaluate the cost-effectiveness of the second booster strategy and incremental benefits if the strategy would expand to 18-49yrs and 12-17yrs, from a healthcare system perspective.FindingsImplementing the second booster strategy for those aged 50+yrs would cost $807 million but reduce direct medical costs by $1,128 million, corresponding to a benefit-cost ratio of 1.40. Moreover, the strategy would also result in a gain of 1,048 quality-adjusted life-years (QALYs) during the 180 days, indicating it was cost-saving. Further, vaccinating individuals aged 18-49yrs with the second booster would result in an additional gain of $1,566 million and 2,276 QALYs. Similarly, expanding vaccination to individuals aged 12-17yrs would result in an additional gain of $15 million and 89 QALYs. However, if social interaction between all age groups was severed, vaccination expansion to 18-49yrs and 12-17yrs would no longer be cost-effective.InterpretationThe second booster strategy was likely to be cost-effective in reducing the disease burden of the COVID-19 pandemic. Expanding the second booster strategy to 18-49yrs and 12-17yrs would remain cost-effective due to their social contacts with the older age group.FundingWorld Health Organization
Systemic effects of melanoma-secreted MIDKINE in the inhibition of dendritic cell differentiation and function
Authors: Catena Xavier , Contreras-Alcalde Marta , Cerezo-Wallis Daniela , Juan-Larrea Naiara , Olmeda David , Calvo Guadalupe G. , Mucientes Cynthia , Oterino Sergio , Soengas María S. 
Published: December 2022

ABSTRACTCutaneous melanomas are a prime example of potentially immunogenic tumors, and as such, ideal targets for immune therapy. These lesions have the largest mutational burden described to date, and accumulate a broad spectrum of post-transcriptional and translational alterations that could conceptually result in a plethora of neoantigens for immune recognition. However, a significant fraction of metastatic melanoma patients is or becomes resistant to current immunotherapeutic agents. How lesions that should represent an inherently hot milieu for immune attack shift into immunologically cold or irresponsive neoplasms is not well understood. Combining cellular systems, mouse models and clinical datasets, here we identify the growth factor Midkine (MDK) as a multipronged blocker of antigen presentation. Mechanistically, we found MDK to repress all main aspects of the maturation, activation and function of dendritic cells, particularly of conventional type 1 (cDC1). These roles of MDK were found to involve primary tumors and lymph nodes, and were traced back to suppressive effects on myeloid precursor cells in the bone marrow. Moreover, MDK shifted the transcriptional profile of DCs towards a tolerogenic state that prevented and bypassed CD8+T cell activation. Blocking MDK enhanced the response to DC-based vaccination and improved the response to immune checkpoint blockade.Together, these data provide insight into how melanomas overcome immune surveillance and support MDK as a target for therapeutic intervention.
Artificial intelligence for automated thoracic aorta diameter measurement using different computed tomography protocols
Authors: Portugal Maria Fernanda , Pinheiro Lucas Lembrança , Lee Henrique Min Ho , Vieira Henrique Cursino , de Oliveira Lariza Laura , del Valle Matheus , Miyoshi Newton Shydeo Brandão , Oliveira-Ciabati Livia , Barone Ronaldo , Szarf Gilberto , Wolosker Nelson 
Published: December 2022

AbstractIntroductionThoracic aortic aneurysm diameter determination is paramount for the decision-making process regarding surgical management. Studies focusing in asymptomatic patients have determined prevalence of 0.16 to 0.36% of TAAs in imaging studies. Several groups have proposed automated aortic measurement tools as propaedeutic and therapeutic instruments. In this study we developed and tested an automatic 3-dimensional (3D) segmentation method for the thoracic aorta, applicable on computed tomography angiography (CTA) acquired using low-dose and standard dose protocol, with and without contrast enhancement; and to accurately calculate the 3D diameter information of the arterial segments.Methodsa retrospective cohort of all CT scans acquired in our service between 2016 and 2021 led to the selection of 587 CT exams including low and standard-dose radiation, with and without contrast enhancement. 527 exams were used for neural network training of an algorithm capable of aptly measuring the aortic diameters, using manual measurements performed by three medical specialists as a baseline. Sixty exams were used for validation. The algorithm was developed both for use with the support of PyRadiomics and for a self-made approach.ResultsAortic measurement using the algorithm supported by PyRadiomics resulted in mean absolute error values under 2mm. For the self-made approach, mean absolute error values were under 5mm.ConclusionThis study presents an effective automated solution for thoracic aortic measurement with good results in sets of standard or low-radiation exams, as well as those acquired with or without contrast enhancement; presenting a possibility for an auxiliary tool for automation of the process of measuring the diameter of the thoracic aorta.
The P450 Sterol Side Chain Cleaving Enzyme (P450scc) for Digoxin Biosynthesis in the Foxglove Plant Belongs to the CYP87A Family
Authors: Carroll Emily , Gopal Baradwaj Ravi , Raghavan Indu , Wang Zhen Q. 
Published: December 2022

AbstractDigoxin from the foxglove plant is a commonly prescribed plant natural product for treating heart failure and atrial fibrillation. Despite its medicinal prominence, how foxglove synthesizes digoxin is largely unknown, especially the cytochrome P450 sterol side chain cleaving enzyme (P450scc), which catalyzes the first and rate-limiting step in this pathway. Here we report the identification of the foxglove P450scc, the gatekeeping enzyme that channels sterols to digoxin. This enzyme converts both cholesterol and campesterol to pregnenolone, thus explaining how pregnenolone is synthesized in plants. Phylogenetic analysis indicates that this enzyme arose from a duplicatedCYP87Agene and does not share clear homology with the mammalian P450scc. Identifying this long-speculated plant P450sccenzyme suggests that the digoxin biosynthetic pathway starts from both cholesterol and phytosterols, instead of just cholesterol as previously thought. The identification of this gatekeeping enzyme is a key step towards complete elucidation of digoxin biosynthesis and expanding the therapeutic applications of digoxin analogs in future work.
WITHDRAWN: Screening for Poverty And Related Social determinants to improve Knowledge of and links to resources (SPARK): development and cognitive testing of a tool for primary care
Authors: Adekoya Itunuoluwa , Delahunty-Pike Alannah , Howse Dana , Kosowan Leanne , Seshie Zita , Abaga Eunice , Cooney Jane , Robinson Marjeiry , Senior Dorothy , Zsager Alexander , Aubrey-Bassler Kris , Irwin Mandi , Jackson Lois , Katz Alan , Marshall Emily , Muhajarine Nazeem , Neudorf Cory , Pinto Andrew D. 
Published: December 2022

Withdrawal statement“The authors have withdrawn this manuscript owing to one of the authors, Lynn Thompson, no longer standing by her participation in this work. Therefore, the authors do not wish this work to be cited as reference for the project. The remaining authors have since published the work inBMC Primary Care:Adekoya, I., Delahunty-Pike, A., Howse, D. et al. Screening for poverty and related social determinants to improve knowledge of and links to resources (SPARK): development and cognitive testing of a tool for primary care.BMC Prim. Care24, 247 (2023).https://doi.org/10.1186/s12875-023-02173-8. If you have any questions, please contact the corresponding author.”
Decreased expression of mitochondrial aminoacyl-tRNA synthetases causes downregulation of mitochondrial OXPHOS subunits in type 2 diabetic skeletal muscle
Authors: López-Soldado Iliana , Torres Adrian Gabriel , Ventura Raúl , Martínez-Ruiz Inma , Díaz-Ramos Angels , Planet Evarist , Cooper Diane , Pazderska Agnieszka , Wanic Krzysztof , O’Hanlon Declan , O’Gorman Donal J. , Carbonell Teresa , de Pouplana Lluís Ribas , Nolan John J. , Hernández-Alvarez María Isabel 
Published: December 2022

AbstractType 2 diabetes mellitus (T2D) affects millions of people worldwide and is one of the leading causes of morbidity and mortality. The skeletal muscle (SKM) is the most important tissue involved in maintaining glucose homeostasis and substrate oxidation, and it undergoes insulin resistance in T2D. In this study, we identify the existence of alterations in the expression of mitochondrial aminoacyl-tRNA synthetases (mt-aaRSs) in skeletal muscle from two different forms of T2D: early-onset type 2 diabetes (YT2) (onset of the disease before 30 years of age) and the classical form of the disease (OT2). GSEA analysis from microarray studies revealed the repression of mitochondrial mt-aaRSs independently of age, which was validated by real-time PCR assays. In agreement with this, a reduced expression of several encoding mt-aaRSs was also detected in skeletal muscle from diabetic (db/db) mice but not in obese ob/ob mice. In addition, the expression of the mt-aaRSs proteins most relevant in the synthesis of mitochondrial proteins, threonyl-tRNA, and leucyl-tRNA synthetases (LARS2 and TARS2) were also repressed in muscle from db/db mice. It is likely that these alterations participate in the reduced expression of proteins synthesized in the mitochondria detected in db/db mice. Because it is known that, nitrosative stress inhibits aminoacylation of TARS2 and LARS2 activities, we noticed an increased protein expression of iNOS in isolated muscle mitochondria in diabetic mice.Our results indicate a reduced expression of mitochondrial mt-aaRSs in skeletal muscle from T2D patients, which may participate in the reduced expression of proteins synthesized in mitochondria. This may be due to an enhanced NO production secondary to enhanced iNOS expression in muscle under diabetic conditions.HighlightsMt-aaRSs are downregulated in the skeletal muscle of type 2 diabetic patients and diabetic mice.The downregulation of mt-aaRSs in the skeletal muscle of diabetic mice is affecting the synthesis of ND2 which is amitochondriallyencodedsubunitof complex I.Mitochondrial iNOS could be a target for reduced expression of mt-aaRSs in the skeletal muscle of diabetic mice.
Microbiome and breast cancer: A systematic review and meta-analysis
Authors: Thu May Soe , Chotirosniramit Korn , Nopsopon Tanawin , Hirankarn Nattiya , Pongpirul Krit 
Published: December 2022

AbstractBackgroundDysbiosis characterizes breast cancer (BC) through direct or indirect interference in a variety of biological pathways, therefore specific microbial patterns and diversity may be a biomarker for BC diagnosis and prognosis. However, there is still much to determine on the complex interplay of gut microbiome and BC.ObjectiveTo evaluate the microbial alteration in BC patients as compared with control subjects, to explore the gut microbial modification from a range of different BC treatments, and to identify the impact of microbiome patterns on the same treatment-receiving BC patients.MethodsA literature search was conducted using electronic databases such as PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) inThe Cochrane Libraryto April 2021. The search was limited to adult BC women and the English language. A prespecified subgroup analysis in BC patients was performed. The results were synthesized quantitatively and qualitatively using random-effects meta-analysis.ResultsA total of 33 studies were included in the review, accounting for 20 case-control, 8 cohort, and 5 non-randomized intervention studies. In the meta-analysis, the bacterial DNA load is reduced in the tumor compared with paired normal breast and healthy breast tissue, and interestingly, there is an inverse correlation of the bacterial load in different breast tumor stages. From the intervention studies, it revealed 41 species related to breast tumors with a predominance ofGemella haemolysansandStreptococcus mitis, and after chemotherapy, the number of species per patient was elevated by a mean of 2.6 (SD = 4.7, p = 0.052). Also, the tumor tissue showed a significant reduction of transcripts of microbial sensors such as TLR2, TLR5, and TLR9, cytoplasmic microbial sensors like NOD1 and NOD2, and the levels of BPI, MPO, and PRTN3. It found that the post-menopausal group has higher leucine-and valine-arylamidase, β-glucuronidase, and esterase-lipase activities in contrast to pre-menopausal and healthy groups.ConclusionsThis systematic review elucidates the complex network of the microbiome, BC, and the therapeutic options, expecting to provide a link for stronger research studies and toward personalized medicine to improve their quality of life.FundingNone.Registration IDPROSPERO 2021 CRD42021288186
Improving self-regulated learning competencies of service employees: roles of regulatory appraisals and supportive resources
Authors: Elmadag A. Banu , Okan Mehmet , Kurtuldu Ece 
Published: December 2022

PurposeIn the era of technological advancements such as artificial intelligence and robotics, the working environment of service employees is changing, and the need to self-regulate their learning efforts has reached a pinnacle. The purpose of this study is to investigate how supportive resources (organizational investments in social capital, supervisor support and favorable customer feedback) facilitate service employees' self-regulated learning competencies (SRLCs) and how individual factors (self-efficacy and goal orientation) regulate service employee performance outcomes (commitment to service quality and job performance).Design/methodology/approachDrawing on the social cognitive theory and social capital perspectives, a quantitative survey was implemented with 516 service employees of a corporation operating in Turkey in various service sectors (i.e. retailing, health and technology). The data are analyzed through a covariance-based structural equation model.FindingsResults showed that organizational, supervisory and customer-level supportive resources improved SRLCs and subsequently performance outcomes. Service employees' goal orientation and self-efficacy attenuate the relationship between supportive resources and SRLCs.Originality/valueThis paper enhances the current literature by investigating SRLCs of frontline service employees who need more dynamic and adaptive self-managed self-regulated learning rather than passive training activities. Moreover, the unexpected negative effect of regulatory mechanisms (goal orientation and self-efficacy) on the relationship between supportive resources and SRLCs opens new avenues for managers.
A homozygous loss‐of‐function variant in the MPO gene is associated with generalized pustular psoriasis
Authors: Onitsuka Mami , Farooq Muhammad , Iqbal Muhammad Nasir , Yasuno Shuichiro , Shimomura Yutaka 
Published: December 2022

AbstractGeneralized pustular psoriasis (GPP) is a rare form of psoriasis, which is characterized by sudden onset of repeated erythema and pustule formation with generalized inflammation. Recent advances in molecular genetics have led to the identification of several genes associated with GPP, including IL36RN, CARD14, AP1S3, SERPINA3, and MPO. Of these, only limited cases of GPP have been reported to carry mutations in the AP1S3, SERPINA3, or MPO to date. In the present study, we investigated a Japanese patient with GPP and found a homozygous missense mutation c.1769G>T (p.Arg590Leu) in the MPO gene. Structural analysis predicted that the mutant MPO protein would abolish its ability to bind with heme protein. In vitro studies using cultured cells revealed that the mutant MPO was stably expressed, but completely lost its myeloperoxidase activity. Immunohistochemistry (IHC) using an anti‐MPO antibody showed markedly reduced expression of MPO protein in the patient's skin, suggesting that the mutation would lead to an instability of the MPO protein in vivo. Finally, IHC with an anti‐citrullinated Histone H3 antibody demonstrated a sparse formation of neutrophil extracellular traps within a Kogoj's spongiform pustule of the patient's skin. Collectively, we conclude that the c.1769G>T (p.Arg590Leu) in the MPO is a complete loss‐of‐function mutation associated with GPP in the patient. Our data further underscore critical roles of the MPO gene in the pathogenesis of GPP.
An integrated animal tracking technology combining a GPS tracking system with a UAV
Authors: Jin Tinghao , Si Xingfeng , Liu Juan , Ding Ping 
Published: December 2022

Abstract

Global Position System (GPS) tags are widely used in animal tracking to address far‐ranging ecological, behavioural and conservation‐related questions. However, GPS tags with transmitting functions via Global System for Mobile communications (GSM) and long‐lasting batteries are too cumbersome for animals with small body sizes. In addition, GSM is expensive with strict signal limitations in remote areas. Downloading locations from small GPS tags also requires animal recapture, which can result in large workloads. Combined, these problems limit the use of GPS tags in tracking small animals.

To overcome these challenges, we present an integrated technology to pinpoint animal locations, especially those of medium‐ and small‐sized species. Our system consists of 3.7 g solar‐powered GPS tags (Nano), whose sampling frequency can be changed flexibly, and a combination of a receiver and an unmanned aerial vehicle (UAV) to retrieve data. The UAV carries the receiver that can retrieve data from Nanos via Bluetooth. Data are uploaded to a platform via GSM by the receiver and then downloaded by users in real time. Users can also directly download data from tags or the receiver via Bluetooth.

We conducted stationary and field tests to assess the system's performance in Thousand Island Lake, China. Stationary tests were conducted at eight sites near the buildings, in open fields and on an island. Nanos can transmit data to the receiver within distances of 600–1000 m and at speeds of 6–72 records/s. The mean accuracy was 10.44–23.32 m and the fix success rates (FSRs) were larger than 97%. In field tests, we captured and attached Nanos on six Eurasian jays Garrulus glandarius. The FSRs were larger than 98%. Using the UAV reduced the time spent in field.

Our system is labour‐saving and accurate in locating animals larger than 80 g as tested in a land‐bridge island system. Bluetooth transmission assisted by the UAV can overcome signal limitations and landscape blocks, and has the potential to be applied in inaccessible landscapes. The large memory of Nanos also allows for the retrieval of data from migratory species with strong site fidelity on their returns.