bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of thinning intensity and rotation length on albedo- and carbon stock-based radiative forcing in boreal Norway spruce stands
Authors: Kellomäki Seppo , Strandman Harri , Kirsikka-Aho Sara , Kirschbaum Miko U F , Peltola Heli 
Published: January 2023

AbstractWe investigated how thinning intensity and rotation length affect radiative forcing, and thus climate warming or cooling, through changes in albedo and carbon stocks in Norway spruce (Picea abies Kart. (L.)) stands. Forest ecosystem model simulations were conducted under the current climate on sub-mesic sites in central Finland (62oN). Even-aged management regime with a business-as-usual (baseline) thinning from below over an 80-year rotation length was used as the reference management regime with which others were compared. Other even-aged management regimes included baseline thinning with ±20 per cent changes in basal area thinning thresholds over rotation lengths of 80, 100 and 120 years. Additionally, we used as a comparison an uneven-aged management regime, with selective cuttings (from above) at ca. 15-year intervals, and no management regime, over the simulation periods of 80–120 years. Under even-aged management, a simultaneous decrease in thinning intensity and extension of rotation length from 80 to 120 years reduced total radiative forcing compared to the reference management regime. Thus, it had an overall net cooling effect. Under even-aged management with baseline thinning and/or higher thinning intensity with rotation lengths of 80–100 years, and under uneven-aged management, there was little net climatic effect. This was because the opposing effects of changes in albedo and ecosystem carbon stocks largely cancelled each other out. No management regime resulted in the highest net cooling effect but provided no harvest income for timber. Thus, proper incentives for forest owners would likely be required to promote such potential cooling effects in forest management.
Trans-dimensional Bayesian joint inversion of magnetotelluric and geomagnetic depth sounding responses to constrain mantle electrical discontinuities
Authors: Yao Hongbo , Ren Zhengyong , Tang Jingtian , Guo Rongwen , Yan Jiayong 
Published: January 2023

SUMMARYJoint inversion of magnetotelluric (MT) and geomagnetic depth sounding (GDS) responses can constrain the crustal and mantle conductivity structures. Previous studies typically use either deterministic inversion algorithms that provide limited information on model uncertainties or using stochastic inversion algorithms with a predetermined number of layers that is generally not known a priori. Here, we present a new open-source Bayesian framework for the joint inversion of MT and GDS responses to probe 1D layered Earth’s conductivity structures. Within this framework, model uncertainties can be accurately estimated by generating numerous models that fit the observed data. A trans-dimensional Markov Chain Monte Carlo (MCMC) method is employed to self-parametrize the model parameters, where the number of layers is treated as an inversion parameter that is determined automatically by the data. This adaptability can overcome the under or over-parametrization problem and may be able to automatically detect the conductivity discontinuities in the Earth’s interior. To accelerate the computations, a large number of Markov chains with different initial states can be run simultaneously using the MPI parallel technique. Synthetic data sets are used to validate the feasibility of our method and illustrate how separate and joint inversions, as well as various priors affect the posterior model distributions. The trans-dimensional MCMC algorithm is then applied to jointly invert the MT and GDS responses estimated at the Tucson geomagnetic observatory, North America. Our results not only contain model uncertainty estimates but also indicate two distinct conductivity discontinuities at around 85 and 440 km, which are likely related to the lithosphere-asthenosphere boundary and the upper interface of the mantle transition zone, respectively.
Biosynthesis of the O antigen of pathogenicEscherichia coliO157:H7. Characterization of α1,4-Fuc-transferase WbdO
Authors: Melamed Jacob , Brockhausen Inka 
Published: January 2023

AbstractThe O157:H7 strain of Escherichia coli is responsible for frequent outbreaks of hemorrhagic colitis worldwide. Its lipopolysaccharide is a virulence factor and contains an O antigen having repeating units with the tetrasaccharide structure [2-D-PerNAcα1-3-L-Fucα1-4-D-Glcβ1-3-D-GalNAcα1-]n. Genes encoding glycosyltransferases WbdN, WbdO, and WbdP are responsible for the biosynthesis of this repeating unit. We have previously characterized the second enzyme in the pathway, WbdN, which transfers Glc in β1-3 linkage to GalNAcα-O-PO3-PO3-(CH2)11-O-Ph (GalNAc-PP-PhU). In this work, Fuc-transferase WbdO from E. coli O157:H7 expressed in BL21 bacteria was characterized using the product of WbdN as the acceptor substrate. We showed that WbdO is specific for GDP-β-L-Fuc as the donor substrate. Compounds that contained terminal Glc or Glcβ1-3GalNAc structures but lacked the diphosphate group did not serve as acceptor substrates. The structure of the WbdO product was identified by mass spectrometry and Nuclear magnetic resonance (NMR) as L-Fucα1-4-D-Glcβ1-3-D-GalNAc PP-PhU. WbdO is an unusual bivalent metal ion-dependent Fuc-transferase classified as an inverting GT2 family enzyme that has 2 conserved sequences near the N-terminus. The Asp37 residue within the 36VDGGSTD42 sequence was found to be essential for catalysis. Mutation of Asp68 to Ala within the conserved 67YDAMNK72 sequence resulted in a 3-fold increase in activity. These studies show that WbdOO157 is a highly specific Fuc-transferase with little homology to other characterized Fuc-transferases.
What accounts for the different regional responses to COVID-19 in China? Exploring the role of institutional environment, governance capacity and legitimacy
Authors: Mao Yexin 
Published: January 2023

AbstractThe coronavirus disease 2019 (COVID-19) pandemic has brought enormous challenges for public health crisis management in China. Crisis responses vary greatly among provinces. Many studies focus on the role of the central government in crisis management. However, how regional governments respond to such pandemic crises is underexplored. The existing literature lacks extensive comparative studies explaining why different regions respond differently to the crisis and how different regional institutional environments affect crisis management. By proposing an analytical framework based on governance capacity and legitimacy theory, this article seeks to address these questions. This study mainly focuses on provincial governments because they play a crucial role in coordinating various organizations and different levels of government in response to the crisis. By comparing the different COVID-19 responses of Hubei and Zhejiang provinces, this study finds that different regional institutional environments based on the triangular linkage of government, business and society influence regional crisis management by shaping different governance capacities (coordination, analytical, regulation and delivery capacity) and legitimacy (input, throughput and output legitimacy). Regional governments with strong governance capacity can promote crisis management through cross-organizational collaboration, scientific analysis and timely decision-making and effective policy implementation. Promoting citizen participation and information disclosure in the policy process and enhancing citizens’ support can improve governance legitimacy, thereby facilitating crisis management. Governance capacity and legitimacy also affect each other. These findings contribute to the literature on public health crisis management. They also shed light on how regional governments in China and other countries with regional variation can effectively tackle public health crises under different institutional environments.
The utilization of systematic review evidence in formulating India’s National Health Programme guidelines between 2007 and 2021
Authors: Rajwar Eti , Pundir Prachi , Parsekar Shradha S , D S Anupama , D’Souza Sonia R B , Nayak Baby S , Noronha Judith Angelitta , D’Souza Preethy , Oliver Sandy 
Published: January 2023

AbstractEvidence-informed policymaking integrates the best available evidence on programme outcomes to guide decisions at all stages of the policy process and its importance becomes more pronounced in resource-constrained settings. In this paper, we have reviewed the use of systematic review evidence in framing National Health Programme (NHP) guidelines in India. We searched official websites of the different NHPs, linked to the main website of the Ministry of Health and Family Welfare (MoHFW), in December 2020 and January 2021. NHP guideline documents with systematic review evidence were identified and information on the use of this evidence was extracted. We classified the identified systematic review evidence according to its use in the guideline documents and analysed the data to provide information on the different factors and patterns linked to the use of systematic review evidence in these documents. Systematic reviews were mostly visible in guideline documents addressing maternal and newborn health, communicable diseases and immunization. These systematic reviews were cited in the guidelines to justify the need for action, to justify recommendations for action and opportunities for local adaptation, and to highlight implementation challenges and justify implementation strategies. Guideline documents addressing implementation cited systematic reviews about the problems and policy options more often than citing systematic reviews about implementation. Systematic reviews were linked directly to support statements in few guideline documents, and sometimes the reviews were not appropriately cited. Most of the systematic reviews providing information on the nature and scale of the policy problem included Indian data. It was seen that since 2014, India has been increasingly using systematic review evidence for public health policymaking, particularly for some of its high-priority NHPs. This complements the increasing investment in research synthesis centres and procedures to support evidence-informed decision making, demonstrating the continued evolution of India’s evidence policy system.
Accelerated epigenetic aging and DNA methylation alterations in Berardinelli–Seip congenital lipodystrophy
Authors: Qannan Abeer , Bejaoui Yosra , Izadi Mahmoud , Yousri Noha A , Razzaq Aleem , Christiansen Colette , Martin George M , Bell Jordana T , Horvath Steve , Oshima Junko , Megarbane Andre , Ericsson Johan , Pourkarimi Ehsan , El Hajj Nady 
Published: January 2023

Abstract
Berardinelli–Seip congenital lipodystrophy type 2 (CGL2) is a very rare human genetic disorder with potential significance to the understanding of the pathobiology of aging. CGL2 patients display characteristic progeroid features and suffer from type 2 diabetes, insulin resistance and fatty liver. In this study, we profiled genome-wide DNA methylation levels in CGL2 patients with BSCL2 mutations to study epigenetic age acceleration and DNA methylation alterations. This analysis revealed significant age acceleration in blood DNA of CGL2 patients using both first- and second-generation epigenetic clocks. We also observed a shortened lifespan of Caenorhabditis elegans following knockdown of the BSCL2 homolog seip-1 on a daf-16/forkhead box, class O mutant background. DNA methylation analysis revealed significant differentially methylated sites enriched for lyase activity, kinase regulator activity, protein kinase regulator activity and kinase activator activity. We could also observe significant hypomethylation in the promoter of the dual specificity phosphatase 22 gene when comparing CGL2 patients versus controls. We conclude that in line with the observed progeroid features, CGL2 patients exhibit significant epigenetic age acceleration and DNA methylation alterations that might affect pathways/genes of potential relevance to the disease.
Normal range CAG repeat size variations in the HTT gene are associated with an adverse lipoprotein profile partially mediated by body mass index
Authors: Faquih Tariq O , Aziz N Ahmad , Gardiner Sarah L , Li-Gao Ruifang , de Mutsert Renée , Milaneschi Yuri , Trompet Stella , Jukema J Wouter , Rosendaal Frits R , van Hylckama Vlieg Astrid , van Dijk Ko Willems , Mook-Kanamori Dennis O 
Published: January 2023

Abstract
Tandem cytosine-adenine-guanine (CAG) repeat sizes of 36 or more in the huntingtin gene (HTT) cause Huntington's disease (HD). Apart from neuropsychiatric complications, the disease is also accompanied by metabolic dysregulation and weight loss, which contribute to a progressive functional decline. Recent studies also reported an association between repeats below the pathogenic threshold (&lt;36) for HD and body mass index (BMI), suggesting that HTT repeat sizes in the non-pathogenic range are associated with metabolic dysregulation. In this study, we hypothesized that HTT repeat sizes &lt; 36 are associated with metabolite levels, possibly mediated through reduced BMI. We pooled data from three European cohorts (n = 10 228) with genotyped HTT CAG repeat size and metabolomic measurements. All 145 metabolites were measured on the same targeted platform in all studies. Multilevel mixed-effects analysis using the CAG repeat size in HTT identified 67 repeat size metabolite associations. Overall, the metabolomic profile associated with larger CAG repeat sizes in HTT were unfavorable—similar to those of higher risk of coronary artery disease and type 2 diabetes—and included elevated levels of amino acids, fatty acids, low-density lipoprotein (LDL)-, very low-density lipoprotein- and intermediate density lipoprotein (IDL)-related metabolites while with decreased levels of very large high-density lipoprotein (HDL)-related metabolites. Furthermore, the associations of 50 metabolites, in particular, specific very large HDL-related metabolites, were mediated by lower BMI. However, no mediation effect was found for 17 metabolites related to LDL and IDL. In conclusion, our findings indicate that large non-pathogenic CAG repeat sizes in HTT are associated with an unfavorable metabolomic profile despite their association with a lower BMI.
Efficacy, Effectiveness, and Safety of Ustekinumab for the Treatment of Ulcerative Colitis: A Systematic Review
Authors: Gisbert Javier P , Parody-Rúa Elizabeth , Chaparro María 
Published: January 2023

Abstract

Objective
This study aimed to evaluate ustekinumab efficacy, effectiveness, and safety as a treatment for ulcerative colitis in adult patients.

Methods
A systematic review of the efficacy, effectiveness, and safety of ustekinumab in ulcerative colitis was carried out. The search was conducted via PubMed, Embase, and the Cochrane library. Two reviewers independently assessed the quality of studies and extracted study data.

Results
Of the 892 studies identified, 17 were included: 1 randomized controlled trial (RCT), 3 long-term extensions, and 13 observational studies. In the randomized clinical trial evaluating efficacy at week 8, clinical remission was achieved in 16% of patients, whereas clinical response was achieved in 51% and 62% of patients who received intravenous ustekinumab at a dose of 130 mg and 6 mg/kg, respectively. At 3 years’ follow-up, symptomatic remission was achieved in 68% of patients. On the other hand, the effectiveness of ustekinumab was evaluated in 13 observational studies. In these studies, clinical remission at induction was achieved in 24% to 61% of cases, whereas clinical response at induction was achieved in 47% to 77% of cases. Moreover, clinical remission was achieved in 33% to 79% of cases at 52 weeks of follow-up. The adverse events ranged from 2.6% to 77% of all the studies that reported safety data. Adverse events leading to discontinuation ranged from 2.6% to 8.1%, and serious adverse events were uncommon and ranged from 3.7% to 6.0%.

Conclusions
Ustekinumab has demonstrated efficacy (in RCTs), effectiveness (in real clinical practice), and safety for the treatment of ulcerative colitis.
Dupuytren’s contracture-associated SNPs increase SFRP4 expression in non-immune cells including fibroblasts to enhance inflammation development
Authors: Kida Hiroaki , Jiang Jing-Jing , Matsui Yuichiro , Takahashi Ikuko , Hasebe Rie , Kawamura Daisuke , Endo Takeshi , Shibayama Hiroki , Kondo Makoto , Nishio Yasuhiko , Nishida Kinya , Matsuno Yoshihiro , Oikawa Tsukasa , Kubota Shimpei I , Hojyo Shintaro , Iwasaki Norimasa , Hashimoto Shigeru , Tanaka Yuki , Murakami Masaaki 
Published: January 2023

Abstract
Dupuytren’s contracture (DC) is an inflammatory fibrosis characterized by fibroproliferative disorders of the palmar aponeurosis, for which there is no effective treatment. Although several genome-wide association studies have identified risk alleles associated with DC, the functional linkage between these alleles and the pathogenesis remains elusive. We here focused on two single nucleotide polymorphisms (SNPs) associated with DC, rs16879765 and rs17171229, in secreted frizzled related protein 4 (SFRP4). We investigated the association of SRFP4 with the IL-6 amplifier, which amplifies the production of IL-6, growth factors and chemokines in non-immune cells and aggravates inflammatory diseases via NF-κB enhancement. Knockdown of SFRP4 suppressed activation of the IL-6 amplifier in vitro and in vivo, whereas the overexpression of SFRP4 induced the activation of NF-κB-mediated transcription activity. Mechanistically, SFRP4 induced NF-κB activation by directly binding to molecules of the ubiquitination SFC complex, such as IkBα and βTrCP, followed by IkBα degradation. Furthermore, SFRP4 expression was significantly increased in fibroblasts derived from DC patients bearing the risk alleles. Consistently, fibroblasts with the risk alleles enhanced activation of the IL-6 amplifier. These findings indicate that the IL-6 amplifier is involved in the pathogenesis of DC, particularly in patients harboring the SFRP4 risk alleles. Therefore, SFRP4 is a potential therapeutic target for various inflammatory diseases and disorders, including DC.
A historic religious sanctuary may have preserved ancestral genetics of Japanese sika deer (Cervus nippon)
Authors: Takagi Toshihito , Murakami Ryoko , Takano Ayako , Torii Harumi , Kaneko Shingo , Tamate Hidetoshi B 
Published: January 2023

AbstractDeer have been a major resource for human populations for thousands of years. Anthropogenic activities, such as hunting, have influenced the genetic structure and distribution of deer populations. In Japan, wild Japanese sika deer (Cervus nippon) have been hunted since ancient times but have also been historically protected as sacred animals in several sanctuaries. Sika deer have been protected for over a thousand years in the religious sanctuary around the Kasuga Taisha Shrine on the Kii Peninsula, located in the center of Japan. Here, we used short sequence repeats (SSR) and mitochondrial DNA (mtDNA) to investigate the genetic diversity, population structure, and demography of Japanese sika deer inhabiting the Kii Peninsula, Japan, and discuss possible anthropogenic influences. Using SSR, three distinct genetic groups were distinguished on the Kii Peninsula: an Eastern genetic group, a Western genetic group, and an isolated genetic group with individuals in the religious sanctuary of Kasuga Taisha Shrine in Nara city. The isolated genetic sanctuary group had only the mtDNA haplotype S4. The SSR genotype data suggested a newer divergence time of the genetic groups of the religious sanctuary than would have occurred as a result of Late Quaternary climate change. This time scale coincided with the establishment of the sanctuary with Kasuga Taisha Shrine. Thus, the religious protection conserved genetic variation over a thousand years.
A toolbox of different approaches to analyze and present PRO-CTCAE data in oncology studies
Authors: Regnault Antoine , Loubert Angély , Gorsh Boris , Davis Randy , Cardellino Anna , Creel Kristin , Quéré Stéphane , Sapra Sandhya , Nelsen Linda , Eliason Laurie 
Published: January 2023

AbstractBackgroundThe patient-reported outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) is used to assess symptomatic adverse events in oncology trials. Currently, no standard for PRO-CTCAE analysis exists.MethodsKey methods of descriptive analysis and longitudinal modeling using PRO-CTCAE data from an oncology clinical trial, DRiving Excellence in Approaches to Multiple Myeloma-2 (DREAMM-2), a phase II trial of belantamab mafodotin in multiple myeloma (NCT03525678), were explored. Descriptive methods included maximum postbaseline ratings, mean change over time, ratings above a predefined cutoff, line graphs, and stacked bar charts to illustrate patient-reported adverse events at one timepoint or dynamics over time. Analysis methods involving modeling over time included toxicity over time (ToxT) (repeated measurement model, time-to-event, area under the curve analyses), generalized estimating equations (GEE), and ordinal log-linear models (OLLMs).ResultsVisualizations of PRO-CTCAE data highlighted different aspects of the data. Selection of the appropriate visualization will depend on the audience and message to be conveyed. Consistent results were obtained by all modeling approaches; no difference was found between dose groups of the DREAMM-2 study in any PRO-CTCAE item by the ToxT approach or the more sophisticated GEE and OLLM methods. Interpretation of GEE results was the most challenging. OLLM supported the interval nature of the PRO-CTCAE response scale in the DREAMM-2 study. All modeling approaches account for multiple testing (driven by the number of items).ConclusionsDescriptive analyses and longitudinal modeling approaches are complementary approaches to presenting PRO-CTCAE data. In modeling, the ToxT approach may be a good compromise compared with more sophisticated analyses.
Detection of colon cancer recurrences during follow-up care by general practitioners vs surgeons
Authors: Vos Julien A M , Sert Edanur , Busschers Wim B , Duineveld Laura A M , Wieldraaijer Thijs , Wind Jan , Donkervoort Sandra C , Govaert Marc J P M , Beverdam Frédérique H , Smits Anke B , Bemelman Willem A , Heuff Gijsbert , van Weert Henk C P M , van Asselt Kristel M ,   I CARE study Group, van Geloven A A W , van de Ven A W H 
Published: January 2023

Abstract

Background
In the I CARE study, colon cancer patients were randomly assigned to receive follow-up care from either a general practitioner (GP) or a surgeon. Here, we address a secondary outcome, namely, detection of recurrences and effect on time to detection of transferring care from surgeon to GP.

Methods
Pattern, stage, and treatment of recurrences were described after 3 years. Time to event was defined as date of surgery, until date of recurrence or last follow-up, with death as competing event. Effects on time to recurrence and death were estimated as hazard ratios (HRs) using Cox regression. Restricted mean survival times were estimated.

Results
Of 303 patients, 141 were randomly assigned to the GP and 162 to the surgeon. Patients were male (67%) with a mean age of 68.0 (8.4) years. During follow-up, 46 recurrences were detected; 18 (13%) in the GP vs 28 (17%) in the surgeon group. Most recurrences were detected via abnormal follow-up tests (74%) and treated with curative intent (59%). Hazard ratio for recurrence was 0.75 (95% confidence interval [CI] = 0.41 to 1.36) in GP vs surgeon group. Patients in the GP group remained in the disease-free state slightly longer (2.76 vs 2.71 years). Of the patients, 38 died during follow-up; 15 (11%) in the GP vs 23 (14%) in the surgeon group. Of these, 21 (55%) deaths were related to colon cancer. There were no differences in overall deaths between the groups (HR = 0.76, 95% CI = 0.39 to 1.46).

Conclusion
Follow-up provided by GPs vs surgeons leads to similar detection of recurrences. Also, no differences in mortality were found.