bluuebunny/crossref_metadata_2025_split huggingface dataset:
MICAL1 facilitates pancreatic cancer proliferation, migration, and invasion by activating WNT/β-catenin pathway
Authors: Cai Kun , Deng Lu , Zheng Dijie , Li Lin , He Zhiwei , Yu Chao 
Published: November 2022

AbstractBackgroundMICAL1 is involved in the malignant processes of several types of cancer; however, the role of MICAL1 in pancreatic cancer (PC) has not been well-characterized. This study aimed to investigate the expression and function of MICAL1 in PC.MethodsRT-qPCR and immunohistochemistry were used to detect MICAL1 expression in PC and adjacent nontumor tissues. Cell Counting Kit-8, EdU, clone formation, wound healing, and Transwell assays as well as animal models were used to investigate the effects of overexpression or inhibition of MICAL1 expression on the proliferation, invasion, and metastasis of PC cells. RNA-seq was used to explore the main pathway underlying the functions of MICAL1. Proteomics, mass spectrometry, and co-immunoprecipitation assays were used to investigate the interaction of proteins with MICAL1. Rescue experiments were conducted to validate these findings.ResultsBoth MICAL1 mRNA and protein levels were upregulated in PC tissues compared with matched adjacent nontumor tissues. The expression level of MICAL1 was associated with the proliferative and metastatic status of PC. Repression of MICAL1 significantly inhibited PC cell growth, migration, and invasion in vitro and in vivo. RNA sequencing analysis indicated that MICAL1 was closely correlated with the WNT pathway. Overexpression of MICAL1 (1) promoted the phosphorylation of TBC1D1 at the Ser660 site, (2) facilitated the distribution of FZD7 on the cytomembrane, (3) inhibited the degradation of FZD7 in the lysosome, and (4) activated the WNT pathway.ConclusionsMICAL1 was upregulated in PC and involved in stimulating the progression of PC cells by activating the WNT/β-catenin signaling pathway. Therefore, MICAL1 is a potential therapeutic target for PC.
Systemic lupus of pediatric onset in Afro-Caribbean children: a cohort study in the French West Indies and French Guiana
Authors: Felix Arthur , Delion Frederique , Suzon Benoit , Martin Elise , Ogrizek Anais , Mohamed Sahnoun M’hamed , Hospice Claudia , Armougon Aurelie , Cuadro Emma , Elenga Narcisse , Dramé Moustapha , Bader-Meunier Brigitte , Deligny Christophe , Hatchuel Yves 
Published: November 2022

Abstract
Background
Systemic diseases of pediatric onset are more frequent in the Afro-Caribbean population. We performed a study of patients followed in the French overseas departments of America (FOAD) for pediatric systemic lupus erythematosus (pSLE). The aims were to describe the clinical and biological specificities during childhood in this population.

Methods
A retrospective study was conducted between January 2000 and September 2021. Patients with pSLE were identified from multiple sources: computerized hospital archives, registry of referring pediatricians, adult specialists in internal medicine and the French National Registry for rare diseases. We studied SLE with pediatric onset defined by international criteria.

Results
Overall, 2148 patients were identified, of whom 54 were included. The average follow-up was 8.3 years (range: 0.3—25 years). We observed an increase in new diagnoses over time. At onset, pSLE patients had a median of 10 SLICC criteria (range: 4–12), and the median EULAR/ACR 2019 score was 38 (12—54). At onset, one third of patients had renal involvement, 15% had neurolupus and 41% cardiac involvement. During childhood, 54% had renal involvement, and 26% suffered from neurolupus. Patients suffered a median of 3 flares during childhood, and 26% had more than 5 flares. Patients with younger age at onset had worse outcomes than those who were older at diagnosis, i.e., more flares (median 5, p = 0.02) and requiring an average of 4 background therapies (p = 0.04).

Conclusion
The outcomes of Afro-Caribbean patients were similar to those in Western population, but with worse disease activity at onset. Further studies should be performed to identify the genetic and environmental factors in this population.
Patenting and patent challenges in South Korea after introducing a patent linkage system
Authors: Son Kyung-Bok 
Published: November 2022

Abstract
Background
South Korea introduced the patent linkage system in 2015 as part of the implementation of free trade agreements with the United States. This study assessed trends in brand-name drug patenting and generic patent challenges in South Korea after the introduction of the system.

Methods
From 2012–19, we constructed a novel dataset that combines information about listed patents with their corresponding brand-name drugs and patent challenges against these brand-name drugs. We analyzed brand-name drug patenting and generic patent challenges and elucidated factors in timely patent challenges using event history analysis.

Results
During the study period, 659 brand-name drugs listed their patents in the K-Orange Book and patent challenges against 95 brand-name drugs were initiated. The number of listed patents and their nominal patent term varied by the characteristics of the brand-name drugs. Patent challenges of generic drugs were marginal in South Korea even though the surge of patent challenges of generics were noticed right after the introduction of the patent linkage system.

Conclusions
Patenting and patent challenges are critical factors when introducing generic drugs into the market under the patent linkage system. However, the impact of the patent linkage system on patenting and patent challenges could be varied by the specific form of the patent linkage system and the contexts of pharmaceutical markets.
Growth pattern in children with X-linked hypophosphatemia treated with burosumab and growth hormone
Authors: Ertl Diana-Alexandra , Le Lorier Justin , Gleiss Andreas , Trabado Séverine , Bensignor Candace , Audrain Christelle , Zhukouskaya Volha , Coutant Régis , Berkenou Jugurtha , Rothenbuhler Anya , Haeusler Gabriele , Linglart Agnès 
Published: November 2022

Abstract
Background
X-linked hypophosphatemia (XLH) is characterized by increased serum concentrations of fibroblast growth factor 23 (FGF23), hypophosphatemia and insufficient endogenous synthesis of calcitriol. Beside rickets, odonto- and osteomalacia, disproportionate short stature is seen in most affected individuals. Vitamin D analogs and phosphate supplements, i.e., conventional therapy, can improve growth especially when started early in life. Recombinant human growth hormone (rhGH) therapy in XLH children with short stature has positive effects, although few reports are available. Newly available treatment (burosumab) targeting increased FGF23 signaling leads to minimal improvement of growth in XLH children. So far, we lack data on the growth of XLH children treated with concomitant rhGH and burosumab therapies.

Results
Thirty-six patients received burosumab for at least 1 year after switching from conventional therapy. Of these, 23 received burosumab alone, while the others continued rhGH therapy after switching to burosumab. Children treated with burosumab alone showed a minimal change in height SDS after 1 year (mean ± SD 0.0 ± 0.3 prepubertal vs. 0.1 ± 0.3 pubertal participants). In contrast, rhGH clearly improved height during the first year of treatment before initiating burosumab (mean ± SD of height gain 1.0 ± 0.4); patients continued to gain height during the year of combined burosumab and rhGH therapies (mean ± SD height gain 0.2 ± 0.1). As expected, phosphate serum levels normalized upon burosumab therapy. No change in serum calcium levels, urinary calcium excretion, or 25-OHD levels was seen, though 1,25-(OH)2D increased dramatically under burosumab therapy.

Conclusion
To our knowledge, this is the first study on growth under concomitant rhGH and burosumab treatments. We did not observe any safety issue in this cohort of patients which is one of the largest in Europe. Our data suggest that continuing treatment with rhGH after switching from conventional therapy to burosumab, if the height prognosis is compromised, might be beneficial for the final height.
Efficacy of belimumab combined with rituximab in severe systemic lupus erythematosus: study protocol for the phase 3, multicenter, randomized, open-label Synbiose 2 trial
Authors: van Schaik Mieke , Arends Eline J. , Soonawala Darius , van Ommen Ellen , de Leeuw Karina , Limper Maarten , van Paassen Pieter , Huizinga Tom W. J. , Toes René E. M. , van Kooten Cees , Rotmans Joris I. , Rabelink Ton J. , Teng Y. K. Onno 
Published: November 2022

AbstractBackgroundBelimumab, an anti-B-cell activating factor antibody, is approved for the treatment of auto-antibody positive systemic lupus erythematosus with a high degree of disease activity. Anti-CD20 B cell depletion with rituximab is used in refractory SLE as well, although with variable responses. We hypothesized that incomplete B cell depletion, related to a surge in BAFF levels following rituximab treatment, can cause ongoing disease activity and flares. The Synbiose 1 study primarily focused on immunological effects and shows the preliminary clinical benefit of combined rituximab and belimumab in SLE. The Synbiose 2 study will evaluate the clinical efficacy of combining belimumab with rituximab in patients with severe SLE, allowing the tapering of prednisolone and mycophenolate.MethodsSynbiose 2 is a phase 3, multicenter, randomized, controlled, open-label 2-year clinical trial. Seventy adults with severe SLE including lupus nephritis will be randomized 1:1 to receive either standard of care consisting of prednisolone and mycophenolate as induction and maintenance treatment, or belimumab and rituximab combined with standard of care as induction treatment, followed by prednisolone and belimumab as maintenance treatment. The primary objective is to assess whether combined B cell therapy will lead to a reduction of treatment failure. Secondary endpoints are complete and partial clinical and renal response and the improvement of SLE-specific autoimmune phenomena. Safety endpoints include the incidence of adverse events, with a special interest in infections.DiscussionThe Synbiose 2 trial is the first multicenter phase 3 clinical trial investigating combined B cell targeted therapy in SLE, including lupus nephritis. The outcome of this study will provide further evidence for the clinical efficacy of this new treatment strategy in severe SLE.Trial registrationClinicalTrials.govNCT03747159. Registered on 20 November 2018.
Kinetics study of anodic electrophoretic deposition for polytetrafluoroethylene (PTFE) coatings on AZ31 magnesium alloy
Authors: Xiang Qing , Qin Jiyao , Qin Taihong , Chen Lu , Zhang Daixiong 
Published: November 2022

AbstractElectrophoretic deposition (EPD) coating has become a hot topic due to its simple experiment, wide application, and wide material range. In this study, the PTFE coating was successfully prepared by electrophoretic deposition through the systematic study of electrophoretic deposition kinetics. In particular, in the dispersion system with ethanol as solvent, Nafion and NaOH were simultaneously added as additives to obtain a beneficial synergistic effect on PTFE electrophoretic deposition. And the best additive scheme is: when the concentration of PTFE was 6 g·L− 1 and the deposition time was increased to 20 min, adding 0.10 g·L− 1 Nafion and 0.10 mM NaOH simultaneously. Compared with the scheme with Nafion being only additive, the addition of NaOH can improve the deposition rate from 0.16 mg·cm− 2 to 0.98 mg·cm− 2, and the deposition rate increases by about 6 times. According to electrophoretic deposition kinetics, there is an obvious critical transition time between linear and parabolic regions in the preparation of the coating. Prolonging the arrival of critical transition time is beneficial to effectively achieve stable growth of the coating in a longer time. It is found that a more ideal additive can not only increase the deposition rate of coating, but also significantly accelerate the arrival of critical transition time. Meanwhile, the deposition voltage also has an important influence on the critical transition time. Increasing the voltage can improve the deposition speed but shorten the critical transition time. Therefore, the application of deposition voltage needs to strike a balance between deposition rate and critical time point. The optimal deposition conditions proposed in this work are: deposition voltage 60 V, deposition time 20 min, additive 0.10 g·L− 1 Nafion and 0.10 mM NaOH.
The oviposition cue indole inhibits animal host attraction in Aedes aegypti (Diptera: Culicidae) mosquitoes
Authors: Dekel Amir , Sar-Shalom Evyatar , Vainer Yuri , Yakir Esther , Bohbot Jonathan D. 
Published: November 2022

AbstractBackgroundMosquitoes are responsible for disease transmission worldwide. They possess the ability to discriminate between different ecological resources, including nectar sources, animal hosts and oviposition sites, a feature mediated by their olfactory system. Insect repellents, such asN,N-diethyl-meta-toluamide (also called DEET), have been shown to activate and inhibit mosquito odorant receptors, resulting in behavioral modulation. This and other repellents currently available for personal protection against mosquitoes are topically applied to the skin and operate at a short range. In our search for potential long-range inhibitors of attractants to human hosts, we have hypothesized that the shared chemical similarities between indole and DEET may confer the former with the ability to block odorant receptor function and inhibit human host attraction in a similar way as DEET.MethodsWe used the two-electrode voltage clamp system to assayXenopus laevisoocytes as a platform to compare the pharmacological effect of commercially available insect repellents and indole on theAedes aegypti(R)-1-octen-3-ol receptor, OR8, a receptor involved in the decision-making of female mosquitoes to identify human hosts. We also conducted arm-in-a-cage and wind-tunnel bioassays to explore the effect of indole on human host-seeking femaleAedes aegyptimosquitoes.ResultsOur results demonstrate that indole inhibited theAedes aegypti(R)-1-octen-3-ol receptor OR8. In our arm-in-a-cage assay, 1 M of DEET reduced mosquito visits on average by 69.3% while the same indole concentration achieved 97.8% inhibition. This effect of indole on flight visits was dose-dependent and disappeared at 1 μM. In the flight tunnel, indole elicited on average 27.5% lower speed, 42.3% lower upwind velocity and 30.4% higher tortuosity compared to the control.ConclusionsIndole significantly inhibits OR8 activation by (R)-1-octen-3-ol, mosquito visits to a human hand and long-range human host-seeking. The volatility of indole may be leveraged to develop a novel insect repellent in the context of personal mosquito protection.Graphical abstract
Investigating pathological epigenetic aberrations by epi-proteomics
Authors: Robusti Giulia , Vai Alessandro , Bonaldi Tiziana , Noberini Roberta 
Published: November 2022

AbstractEpigenetics includes a complex set of processes that alter gene activity without modifying the DNA sequence, which ultimately determines how the genetic information common to all the cells of an organism is used to generate different cell types. Dysregulation in the deposition and maintenance of epigenetic features, which include histone posttranslational modifications (PTMs) and histone variants, can result in the inappropriate expression or silencing of genes, often leading to diseased states, including cancer. The investigation of histone PTMs and variants in the context of clinical samples has highlighted their importance as biomarkers for patient stratification and as key players in aberrant epigenetic mechanisms potentially targetable for therapy. Mass spectrometry (MS) has emerged as the most powerful and versatile tool for the comprehensive, unbiased and quantitative analysis of histone proteoforms. In recent years, these approaches—which we refer to as “epi-proteomics”—have demonstrated their usefulness for the investigation of epigenetic mechanisms in pathological conditions, offering a number of advantages compared with the antibody-based methods traditionally used to profile clinical samples. In this review article, we will provide a critical overview of the MS-based approaches that can be employed to study histone PTMs and variants in clinical samples, with a strong focus on the latest advances in this area, such as the analysis of uncommon modifications and the integration of epi-proteomics data into multi-OMICs approaches, as well as the challenges to be addressed to fully exploit the potential of this novel field of research.
Performance of a fully-automated Lumipulse plasma phospho-tau181 assay for Alzheimer’s disease
Authors: Wilson Edward N. , Young Christina B. , Ramos Benitez Javier , Swarovski Michelle S. , Feinstein Igor , Vandijck Manu , Le Guen Yann , Kasireddy Nandita M. , Shahid Marian , Corso Nicole K. , Wang Qian , Kennedy Gabriel , Trelle Alexandra N. , Lind Betty , Channappa Divya , Belnap Malia , Ramirez Veronica , Skylar-Scott Irina , Younes Kyan , Yutsis Maya V. , Le Bastard Nathalie , Quinn Joseph F. , van Dyck Christopher H. , Nairn Angus , Fredericks Carolyn A. , Tian Lu , Kerchner Geoffrey A. , Montine Thomas J. , Sha Sharon J. , Davidzon Guido , Henderson Victor W. , Longo Frank M. , Greicius Michael D. , Wagner Anthony D. , Wyss-Coray Tony , Poston Kathleen L. , Mormino Elizabeth C. , Andreasson Katrin I. 
Published: November 2022

Abstract
Background
The recent promise of disease-modifying therapies for Alzheimer’s disease (AD) has reinforced the need for accurate biomarkers for early disease detection, diagnosis and treatment monitoring. Advances in the development of novel blood-based biomarkers for AD have revealed that plasma levels of tau phosphorylated at various residues are specific and sensitive to AD dementia. However, the currently available tests have shortcomings in access, throughput, and scalability that limit widespread implementation.

Methods
We evaluated the diagnostic and prognostic performance of a high-throughput and fully-automated Lumipulse plasma p-tau181 assay for the detection of AD. Plasma from older clinically unimpaired individuals (CU, n = 463) and patients with mild cognitive impairment (MCI, n = 107) or AD dementia (n = 78) were obtained from the longitudinal Stanford University Alzheimer’s Disease Research Center (ADRC) and the Stanford Aging and Memory Study (SAMS) cohorts. We evaluated the discriminative accuracy of plasma p-tau181 for clinical AD diagnosis, association with amyloid β peptides and p-tau181 concentrations in CSF, association with amyloid positron emission tomography (PET), and ability to predict longitudinal cognitive and functional change.

Results
The assay showed robust performance in differentiating AD from control participants (AUC 0.959, CI: 0.912 to 0.990), and was strongly associated with CSF p-tau181, CSF Aβ42/Aβ40 ratio, and amyloid-PET global SUVRs. Associations between plasma p-tau181 with CSF biomarkers were significant when examined separately in Aβ+ and Aβ− groups. Plasma p-tau181 significantly increased over time in CU and AD diagnostic groups. After controlling for clinical diagnosis, age, sex, and education, baseline plasma p-tau181 predicted change in MoCA overall and change in CDR Sum of Boxes in the AD group over follow-up of up to 5 years.

Conclusions
This fully-automated and available blood-based biomarker assay therefore may be useful for early detection, diagnosis, prognosis, and treatment monitoring of AD.
Fibrosing mediastinitis in a child with Mendelian susceptibility to mycobacterial disease possibly due to Bacillus Calmette-Guérin
Authors: Sharifinejad Niusha , Mahdaviani Seyed Alireza , Fallah Shahrzad , Fard Nasrin Khakbazan , Norouzi Alireza , Jamee Mahnaz , Sadeghi-Shabestari Mahnaz , Marjani Majid , Malekshoar Mehran , Farnia Parisa , Velayati Ali Akbar 
Published: November 2022

Abstract
Background
Mendelian susceptibility to mycobacterial disease (MSMD) is an uncommon disorder with increased susceptibility to less virulent mycobacteria including bacillus Calmette-Guérin (BCG). Fibrosing mediastinitis (FM) is also a rare condition defined by excessive fibrotic reactions in the mediastinum. So far, some infectious organisms and autoimmune diseases have been introduced as possible etiologies of FM. However, no study has ever discussed the possible association of BCG infection and FM.

Case presentation
In this study, we report a 3-year-old female presenting with persistent fever, weakness, and bloody diarrhea in addition to mediastinal lymphadenopathy, hepatosplenomegaly, and pleural and pericardial effusion. Further examinations established a diagnosis of MSMD based on her clinical condition, immunologic data, positive tests for mycobacterial species, positive family history, and genetic study (IL12RB1 gene, c.G1193C, p.W398S). A year and a half later, she was referred with submandibular lymphadenitis and underwent immunologic work-up which revealed high inflammatory indices, a slight reduction in numbers of CD3 + and CD4 + cells as well as elevated CD16/56 + cell count and hyperimmunoglobulinemia. Purified protein derivative (PPD), QuantiFERON, and gastric washing test were all negative. Her chest computed tomography (CT) scan revealed suspicious para-aortic soft tissue and her echocardiography was indicative of strictures in superior vena cava and pulmonary veins. She further underwent chest CT angiography which confirmed FM development. Meanwhile, she has been treated with anti-mycobacterial agents and subcutaneous IFN-γ.

Conclusion
In summary, we described a novel case of MSMD in a child presenting with granulomatous FM possibly following BCG infection. This is the first report introducing aberrant BCG infection as the underlying cause of FM. This result could assist physicians in identifying early-onset FM in suspicious cases with MSMD. However, more studies are required to support this matter.
Impact of Moringa oleifera on rumen fermentation and methane emission under in vitro condition
Authors: Leitanthem Vandana Kumari , Chaudhary Parul , Bhakat Mukesh , Mohini Madhu , Mondal Goutam 
Published: November 2022

AbstractExploring innovative methods to provide essential nutrients and reducing ruminant greenhouse gas emission is crucial for animal production and diminishing global warming. This study was conducted to examine the efficacy ofMoringa oleiferaleaves (ML) in ruminants at 0%, 5%, 10%, 15%, 20%, 30% and 40% level in different roughage (R) and concentrate (C) (80R:20C, 70R:30C and 60R:40C) under in vitro conditions. Chemical composition of ML, concentrate mixture and berseem were estimated. Rumen fermentation parameters of male goat kids viz., total gas production, CH4, true dry matter digestibility (TDMD), organic matter digestibility (TOMD), partial fraction (PF), microbial biomass (MBP), ammonia (N), acetate, propionate, butyrate and acetate propionate ratio were observed under in vitro conditions. Results revealed that crude protein, organic matter and ethyl ether content were higher in ML as compared to concentrate mixture and berseem. Magnesium and iron content were also higher in ML as compared to concentrate and berseem. Total gas production, digestibility of DM and OM, MBP, acetate and propionate level were improved (P < 0.05) upto 10–20% replacement. In contrast, decreased in CH4(%) and CH4(mL/100 mg dDM) was noted with increased levels of ML incorporation. There was no change observed in ammonia, acetate: propionate ratios at all the three planes of nutrition. In this study, it is concluded that mixingMoringa oleiferaleaves in feed can be used as protein supplement and reduce the methane emission without causing any effect on digestibility and rumen fermentation parameters. However, ML can be suggested for widespread practice to attain the sustainable animal production (10–20%) and to alleviate the global warming.