bluuebunny/crossref_metadata_2025_split huggingface dataset:
Secondary motor areas for response inhibition: an epicortical recording and stimulation study
Authors: Takeyama Hirofumi , Matsumoto Riki , Usami Kiyohide , Nakae Takuro , Shimotake Akihiro , Kikuchi Takayuki , Yoshida Kazumichi , Kunieda Takeharu , Miyamoto Susumu , Takahashi Ryosuke , Ikeda Akio 
Published: August 2022

Abstract
The areas that directly inhibit motor responses in the human brain remain not fully clarified, although the pre-supplementary motor area and lateral premotor areas have been implicated. The objective of the present study was to delineate the critical areas for response inhibition and the associated functional organization of the executive action control system in the frontal lobe. The subjects were eight intractable focal epilepsy patients with chronic subdural or depth electrode implantation for presurgical evaluation covering the frontal lobe (five for left hemisphere, three for right). We recorded event-related potentials to a Go/No-Go task. We then applied a brief 50 Hz electrical stimulation to investigate the effect of the intervention on the task. Brief stimulation was given to the cortical areas generating discrete event-related potentials specific for the No-Go trials (1–3 stimulation sites/patient, a total of 12 stimulation sites). We compared the locations of event-related potentials with the results of electrical cortical stimulation for clinical mapping. We also compared the behavioural changes induced by another brief stimulation with electrical cortical stimulation mapping. As the results, anatomically, No-Go-specific event-related potentials with relatively high amplitude, named ‘large No-Go event-related potentials’, were observed predominantly in the secondary motor areas, made up of the supplementary motor area proper, the pre-supplementary motor area, and the lateral premotor areas. Functionally, large No-Go event-related potentials in the frontal lobe were located at or around the negative motor areas or language-related areas. Brief stimulation prolonged Go reaction time at most stimulation sites (66.7%) [P &lt; 0.0001, effect size (d) = 0.30, Wilcoxon rank sum test], and increased No-Go error at some stimulation sites (25.0%: left posterior middle frontal gyrus and left pre-supplementary motor area). The stimulation sites we adopted for brief stimulation were most frequently labelled ‘negative motor area’ (63.6%), followed by ‘language-related area’ (18.2%) by the electrical cortical stimulation mapping. The stimulation sites where the brief stimulation increased No-Go errors tended to be labelled ‘language-related area’ more frequently than ‘negative motor area’ [P = 0.0833, Fisher’s exact test (two-sided)] and were located more anteriorly than were those without a No-Go error increase. By integrating the methods of different modality, namely, event-related potentials combined with brief stimulation and clinical electrical cortical stimulation mapping, we conducted a novel neuroscientific approach, providing direct evidence that secondary motor areas, especially the pre-supplementary motor area and posterior middle frontal gyrus, play an important role in response inhibition.
Malek’s Programmatic Secularism? A Dissent
Authors: Moyse Ashley 
Published: August 2022

AbstractProgrammatic secularism aims to secure public reason from rival rationalities, notably those from religious experience and education. The gathering of knowledge in clinical ethics into a concrete array of consensus claims and consensus-derived principles are thought by Janet Malek to secure such public reason—an essential tool for clinical ethics consultants to execute their professional role. The author compares this gathering of knowledge to an understanding of what technology is. Accordingly, the following interrogates Malek’s programmatic secularism, which is a moral technique (technology) that not only homogenizes moral dialogue but also dehumanizes persons as it tyrannizes the creative freedom for moral conversation and genuine encounter. Thus, the reader is encouraged to dissent of such a vision for delimiting the role of clinical ethics consultants according to the rule and measure of technology, the ontology of our age.
Rethinking sustainability: recalibrating the global SDGs to align with local principles for Buen Vivir
Authors: Chassagne Natasha 
Published: August 2022

AbstractThe Sustainable Development Goals (SDGs) were developed as a post-2015 response to growing global climate change and social justice issues, but the little progress made has been thrown off course by the COVID-19 pandemic. To achieve environmental and social transformation, we must recalibrate the global approach to include a contextual, bottom-up and wellbeing-oriented alternative to development that embraces holistic visions of wellbeing. This article advocates Buen Vivir as a localized approach to social and environmental wellbeing, but one that can plurally cooperate with other knowledges and frameworks such as the SDGs. It examines how the global SDGs can align with locally implemented principles for Buen Vivir to achieve effective and timely transformative change for communities and nature.
British Society for Immunology and United Kingdom Primary Immunodeficiency Network (UKPIN) consensus guideline for the management of immunoglobulin replacement therapy
Authors: Grigoriadou S , Clubbe R , Garcez T , Huissoon A , Grosse-Kreul D , Jolles S , Henderson K , Edmonds J , Lowe D , Bethune C 
Published: August 2022

Summary
Currently, there is no guideline to support the use of immunoglobulin replacement therapy (IgRT) in primary and secondary immunodeficiency disorders in UK. The UK Primary Immunodeficiency Network (UK-PIN) and the British Society of Immunology (BSI) joined forces to address this need. Given the paucity of evidence, a modified Delphi approach was used covering statements for the initiation, monitoring, discontinuation of IgRT as well as home therapy programme. A group of six consultant immunologists and three nurse specialists created the statements, reviewed responses and feedback and agreed on final recommendations. This guideline includes 22 statements for initiation, 22 statements for monitoring, 11 statement for home therapy, and 19 statements for discontinuation of IgRT. Further areas of research are proposed to improve future delivery of care.
Adalimumab Is Associated With Lower Healthcare Resource and Steroid Use Versus Vedolizumab in Biologic-Naive Crohn’s Disease: A Retrospective Claims Database Analysis
Authors: Ungaro Ryan C , Griffith Jenny , Garcia-Horton Viviana , Wang Aolin , Cross Raymond K 
Published: August 2022

Abstract

Background
We compared real-world healthcare resource utilization (HRU), Crohn’s disease (CD)-related complications, and time to systemic corticosteroid discontinuation between patients with CD treated with adalimumab versus vedolizumab as initial biologic.

Methods
Biologic-naïve adults with CD and ≥2 claims between 05/20/2014 and 09/30/2019 for adalimumab or vedolizumab were identified in the IBM MarketScan research database. Patient characteristics were assessed during the 6-month baseline period before biologic initiation (index date). Adalimumab- and vedolizumab-treated patients were propensity score-matched 1:1 on demographics, disease characteristics, and comorbidities with ≥10% prevalence that differed significantly between groups. Categorical, continuous, and time-to-event outcomes between groups during the 12-month follow-up on/after index were compared with chi-square tests, Wilcoxon rank-sum tests, and Kaplan–Meier analyses, respectively.

Results
Adalimumab- and vedolizumab-treated patients were matched (n = 461 per group) and baseline characteristics balanced. Significantly fewer adalimumab- versus vedolizumab-treated patients had a CD-related emergency room visit (12-month proportion: 14.5% vs 21.0%; log-rank P &lt; 0.01) or inpatient admission (14.9% vs 20.2%; log-rank P &lt; 0.05). Rates of CD-related surgeries were similar (9.3% vs 11.5%; log-rank P = 0.282). Among patients without internal/perianal abscess or fistula or intestinal stricture at baseline (NADA = 360, NVDZ = 364), numerically but not significantly fewer adalimumab- versus vedolizumab-treated patients had CD-related complications at 12 months (18.3% vs 22.3%; P = 0.171). Among patients with corticosteroid use at index (NADA = 143, NVDZ = 139), significantly more adalimumab- versus vedolizumab-treated patients discontinued corticosteroids (12-month proportion: 90.2% vs 76.3%; log-rank P &lt; 0.001).

Conclusions
Patients with CD treated with adalimumab as their first biologic experienced significantly lower CD-related HRU and were more likely to discontinue corticosteroids compared to vedolizumab-treated patients.
WTO Rulings and the Veil of Anonymity
Authors: Pauwelyn Joost , Pelc Krzysztof 
Published: August 2022

Abstract
Despite a general push for greater transparency, opacity continues to play an important function in international tribunals. The World Trade Organization (WTO) is a case in point. While it has done much to increase its openness, the very design of its dispute settlement body is premised on anonymity in some essential respects. We examine two such instances, each dealing with the authorship of dispute rulings. First, we use text analysis tools to demonstrate that the WTO’s panel reports appear to be largely drafted by WTO Secretariat staff rather than the panellists themselves. This appears especially true for the WTO’s most systemically important disputes. Second, we show that the formal anonymity of dissenting opinions, which is required by the WTO’s rules, is a thin veil. Using the most recent Appellate Body’s dissent for demonstration, we use text analysis to pinpoint its likely author. In both these instances, we argue that anonymity exists by design: it serves to strike a balance between judicial autonomy and political control. Yet, in both settings, due to increased scrutiny and widespread access to text analysis tools, the equilibrium relying on anonymity is likely to be upset, with implications for the institution’s future design. We argue that the ultimate result may be a beneficial one and offer a menu of reform options.
Geomagnetic field behaviour during the early Cretaceous Normal Superchron from palaeomagnetic analysis of the Ramon Volcanics, Israel
Authors: Dembo Neta , Kraus Erez , Seliverstov Irina , Weissman Gal , Granot Roi 
Published: August 2022

SUMMARY
Unravelling the long-term behaviour of the geomagnetic field is crucial for understanding the dynamics of the deep Earth. Yet, obtaining an accurate measure of geomagnetic palaeosecular variations (PSV) is difficult, partly because of tectonically induced rotations that overprint the original palaeomagnetic signal. We present a detailed palaeomagnetic investigation based on 99 sampling sites collected from the 119 to 112.6 Ma Ramon Volcanics exposed near the dormant Ramon Fault, southern Israel. These basaltic rocks were emplaced at equatorial palaeolatitudes during the beginning of the Cretaceous Normal Superchron (CNS; 123.4–83.6 Ma), during which there were no polarity reversals. Structurally corrected remanence directions consistently vary across the investigated area, whereby the sites found near a sharp bend of the Ramon Fault are clockwise rotated, whereas the other sites show no obvious rotational pattern. Elasto-plastic modelling suggests that the rotations were induced by up to 1.5 km of dextral horizontal slip accommodated by the fault, consistent with previous geological and geophysical estimations. Considering the remanence directions obtained from sites that were not influenced by the fault, we calculated an SB value of $13.3_{ - 1.3}^{ + 1.9 \circ }$ (95 percent confidence, 46 sites), which corresponds to previous SB estimations from pre- and early-CNS volcanic bodies emplaced at low palaeolatitudes (λ &lt; 20°). This observation suggests that the emergence of the superchron was not accompanied by a change in the behaviour of the geomagnetic PSV. Finally, our results, together with previous palaeo-equatorial observations, show that the middle part of the superchron had lower angular dispersion (i.e. lower SB) compared to the scatter that prevailed during the beginning of the superchron. This observation suggests that the geomagnetic field transitioned into a more axial dipole dominance state towards the middle part of the superchron. Altogether, our analysis indicates that the superchron cannot be treated as a period characterized by a steady-state field behaviour.
N-glycolylated carbohydrates in nature
Authors: Awofiranye Adeola E , Dhar Chirag , He Peng , Varki Ajit , Koffas Mattheos A G , Linhardt Robert J 
Published: August 2022

Abstract
N-glycolylated carbohydrates are amino sugars with an N-glycolyl amide group. These glycans have not been well studied due to their surprising rarity in nature in comparison with N-acetylated carbohydrates. Recently, however, there has been increasing interest in N-glycolylated sugars because the non-human sialic acid N-glycolylneuraminic acid (Neu5Gc), apparently the only source of all N-glycolylated sugars in deuterostomes, appears to be involved in xenosialitis (inflammation associated with consumption of Neu5Gc-rich red meats). Xenosialitis has been implicated in cancers as well as other diseases including atherosclerosis. Furthermore, metabolites of Neu5Gc have been shown to be incorporated into glycosaminoglycans (GAGs), resulting in N-glycolylated GAGs. These N-glycolylated GAGs have important potential applications, such as dating the loss of the Neu5Gc-generating CMAH gene in humans and being explored as a xenosialitis biomarker and/or estimate of the body burden of diet-derived Neu5Gc, to understand the risks associated with the consumption of red meats. This review explores N-glycolylated carbohydrates, how they are metabolized to N-glycolylglucosamine and N-glycolylgalactosamine, and how these metabolites can be incorporated into N-glycolylated GAGs in human tissues. We also discuss other sources of N-glycolylated sugars, such as recombinant production from microorganisms using metabolic engineering as well as chemical synthesis.
A genome-wide association study for rheumatoid arthritis replicates previous HLA and non-HLA associations in a cohort from South Africa
Authors: Mathebula Evans M , Sengupta Dhriti , Govind Nimmisha , Laufer Vincent A , Bridges Jr S Louis , Tikly Mohammed , Ramsay Michèle , Choudhury Ananyo 
Published: August 2022

Abstract
The complex pathogenesis of rheumatoid arthritis (RA) is not fully understood, with few studies exploring the genomic contribution to RA in patients from Africa. We report a genome-wide association study (GWAS) of South-Eastern Bantu-Speaking South Africans (SEBSSAs) with seropositive RA (n = 531) and population controls (n = 2653). Association testing was performed using PLINK (logistic regression assuming an additive model) with sex, age, smoking and the first three principal components as covariates. The strong association with the Human Leukocyte Antigen (HLA) region, indexed by rs602457 (near HLA-DRB1), was replicated. An additional independent signal in the HLA region represented by the lead SNP rs2523593 (near the HLA-B gene; Conditional P-value = 6.4 × 10−10) was detected. Although none of the non-HLA signals reached genome-wide significance (P &lt; 5 × 10−8), 17 genomic regions showed suggestive association (P &lt; 5 × 10−6). The GWAS replicated two known non-HLA associations with MMEL1 (rs2843401) and ANKRD55 (rs7731626) at a threshold of P &lt; 5 × 10−3 providing, for the first time, evidence for replication of non-HLA signals for RA in sub-Saharan African populations. Meta-analysis with summary statistics from an African-American cohort (CLEAR study) replicated three additional non-HLA signals (rs11571302, rs2558210 and rs2422345 around KRT18P39-NPM1P33, CTLA4-ICOS and AL645568.1, respectively). Analysis based on genomic regions (200 kb windows) further replicated previously reported non-HLA signals around PADI4, CD28 and LIMK1. Although allele frequencies were overall strongly correlated between the SEBSSA and the CLEAR cohort, we observed some differences in effect size estimates for associated loci. The study highlights the need for conducting larger association studies across diverse African populations to inform precision medicine-based approaches for RA in Africa.
Nesprin-1 LINC complexes recruit microtubule cytoskeleton proteins and drive pathology inLmna-mutant striated muscle
Authors: Leong Ei Leen , Khaing Nyein Thet , Cadot Bruno , Hong Wei Liang , Kozlov Serguei , Werner Hendrikje , Wong Esther Sook Miin , Stewart Colin L , Burke Brian , Lee Yin Loon 
Published: August 2022

AbstractMutations in LMNA, the gene encoding A-type lamins, cause laminopathies—diseases of striated muscle and other tissues. The aetiology of laminopathies has been attributed to perturbation of chromatin organization or structural weakening of the nuclear envelope (NE) such that the nucleus becomes more prone to mechanical damage. The latter model requires a conduit for force transmission to the nucleus. NE-associated Linker of Nucleoskeleton and Cytoskeleton (LINC) complexes are one such pathway. Using clustered regularly interspaced short palindromic repeats to disrupt the Nesprin-1 KASH (Klarsicht, ANC-1, Syne Homology) domain, we identified this LINC complex protein as the predominant NE anchor for microtubule cytoskeleton components, including nucleation activities and motor complexes, in mouse cardiomyocytes. Loss of Nesprin-1 LINC complexes resulted in loss of microtubule cytoskeleton proteins at the nucleus and changes in nuclear morphology and positioning in striated muscle cells, but with no overt physiological defects. Disrupting the KASH domain of Nesprin-1 suppresses Lmna-linked cardiac pathology, likely by reducing microtubule cytoskeleton activities at the nucleus. Nesprin-1 LINC complexes thus represent a potential therapeutic target for striated muscle laminopathies.
DNA methylation dynamics during stress response in woodland strawberry (Fragaria vesca)
Authors: López María-Estefanía , Roquis David , Becker Claude , Denoyes Béatrice , Bucher Etienne 
Published: August 2022

Summary
Environmental stresses can result in a wide range of physiological and molecular responses in plants. These responses can also impact epigenetic information in genomes, especially at the level of DNA methylation (5-methylcytosine). DNA methylation is the hallmark heritable epigenetic modification and plays a key role in silencing transposable elements (TEs). Although DNA methylation is an essential epigenetic mechanism, fundamental aspects of its contribution to stress responses and adaptation remain obscure.
We investigated epigenome dynamics of wild strawberry (Fragaria vesca) in response to variable ecologically relevant environmental conditions at the DNA methylation level. F. vesca methylome responded with great plasticity to ecologically relevant abiotic and hormonal stresses. Thermal stress resulted in substantial genome-wide loss of DNA methylation. Notably, all tested stress conditions resulted in marked hot spots of differential DNA methylation near centromeric or pericentromeric regions, particularly in the non-symmetrical DNA methylation context. Additionally, we identified differentially methylated regions (DMRs) within promoter regions of transcription factor (TF) superfamilies involved in plant stress-response and assessed the effects of these changes on gene expression.
These findings improve our understanding on stress-response at the epigenome level by highlighting the correlation between DNA methylation, TEs and gene expression regulation in plants subjected to a broad range of environmental stresses.
The high-quality genome of pummelo provides insights into the tissue-specific regulation of citric acid and anthocyanin during domestication
Authors: Lu Zhihao , Huang Yue , Mao Sangyin , Wu Fangfang , Liu Yong , Mao Xiangqing , Adhikari Prakash Babu , Xu Yuantao , Wang Lun , Zuo Hao , Rao Muhammad Junaid , Xu Qiang 
Published: August 2022

Abstract
Citric acid and anthocyanin contents were co-selected during Citrus domestication. Pummelo is a founding species in the Citrus genus, but the domestication of pummelo has not been well studied. Here, we compared the citric acid and anthocyanin contents of a low citric acid pummelo (Citrus maxima LCA) and its high citric acid variety (HCA) from the same cultivation area in China. Our study revealed that, unlike the LCA type, the HCA variety accumulated anthocyanin in the pericarp early in fruit development. To investigate the genetic basis of acid and anthocyanin enrichment in HCA pulp and pericarp, respectively, we generated a chromosome-scale HCA genome using long-read sequence reads and Hi-C sequencing data. Transcriptome analysis and transient overexpression assays showed that the accumulation of citric acid and anthocyanin was associated with high expression of CgANTHOCYANIN1 (CgAN1), and two different MYBs transcription factors (CgPH4 and CgRuby1), respectively. Moreover, the CgAN1 promoter was more methylated in the LCA pulp than in the HCA pulp. Treatment with a DNA methylation inhibitor, 5-azacytidine, alleviated the CgAN1 promoter hypermethylation in the LCA pulp, leading to increased CgAN1 expression and citric acid content. This study provides a new high-quality pummelo genome and insight into the molecular mechanism behind the change in tissue-specific citric acid and anthocyanin accumulation during pummelo domestication and provides a conceptual basis for precise genetic manipulation in fruit flavor breeding.
Social inequalities in all-cause mortality among adults with multimorbidity: a 10-year prospective study of 0.5 million Chinese adults
Authors: Zou Siyu , Wang Zhicheng , Tang Kun 
Published: August 2022

AbstractBackgroundChinese individuals face an increase in multimorbidity, but little is known about the mortality gradients of multimorbid people in different socio-economic groups. This study measures relative and absolute socio-economic inequality in mortality among multimorbid Chinese.MethodsFor this study, the prospective China Kadoorie Biobank (CKB) enrolled 512 712 participants ages 30–79 y from 10 areas of China between 25 June 2004 and 15 July 2008. All-cause mortality was accessed with a mean follow-up period of 10 y (to 31 December 2016). Associations between multimorbidity and mortality were assessed using Cox proportional hazards models, with the relative index of inequality (RII) and slope index of inequality (SII) in mortality calculated to measure disparities.ResultsMortality risk was highest for those who had not attended formal school and with four or more long-term conditions (LTCs) (hazard ratio 3.11 [95% confidence interval {CI} 2.75 to 3.51]). Relative educational inequality was lower in participants with four or more LTCs (RII 1.92 [95% CI 1.60 to 2.30]), especially in rural areas. Absolute disparities were greater in adults with more LTCs (SII 0.18 [95% CI 0.14 to 0.21] for rural participants with three LTCs).ConclusionsWhereas the relative inequality in all-cause mortality was lower among multimorbid people, absolute inequality was greater among multimorbid men, especially in rural areas.