bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulators of aerobic and anaerobic methane oxidation in two pristine temperate peatland types
Authors: Nweze Justus Amuche , Tláskal Vojtěch , Wutkowska Magdalena , Meador Travis B , Picek Tomáš , Urbanová Zuzana , Daebeler Anne 
Published: November 2024

Abstract
Despite covering &lt;5% of Earth's terrestrial area, peatlands are crucial for global carbon storage and are hot spots of methane cycling. This study examined the dynamics of aerobic and anaerobic methane oxidation in two undisturbed peatlands: a fen and a spruce swamp forest. Using microcosm incubations, we investigated the effect of ammonium addition, at a level similar to current N pollution processes, on aerobic methane oxidation. Our findings revealed higher methane consumption rates in fen compared to swamp peat, but no effect of ammonium amendment on methane consumption was found. Members of Methylocystis and Methylocella were the predominant methanotrophs in both peatlands. Furthermore, we explored the role of ferric iron and sulfate as electron acceptors for the anaerobic oxidation of methane (AOM). AOM occurred without the addition of an external electron acceptor in the fen, but not in the swamp peat. AOM was stimulated by sulfate and ferric iron addition in the swamp peat and inhibited by ferric iron in the fen. Our findings suggest that aerobic methane oxidizers are not N-limited in these peatlands and that there is an intrinsic potential for AOM in these environments, partially facilitated by ferric iron and sulfate acting as electron acceptors.
Efficacy of Janus Kinase Inhibitors (JAKi) in the treatment of biologic-naive and biologic-experienced patients with ulcerative colitis
Authors: Yeung K , Al-Zarrad D , Chana A , Dyall L , Kamperidis N , Arebi N 
Published: November 2024

Abstract

Introduction
Janus kinase inhibitors (JAKi) are an orally available treatment for patients with moderately to severe ulcerative colitis (UC). There are currently 3 JAKi for UC: tofacitinib, filgotinib and upadacitinib with variable selectivity to JAK-11. There is limited data comparing the outcomes between biologic-naive and biologic-experienced patients. This study describes the effectiveness of JAKi according to biologic exposure.

Aim
To investigate the effectiveness of 3 the JAKi’s, tofacitinib, filgotinib and upadacitinib according to biologic exposure.

Method
We undertook a retrospective study of UC patients treated with JAKi within a tertiary hospital. Clinical endpoints were assessed at week 8-12. Baseline disease activity, previous advanced therapies and use of corticosteroids were documented. Clinical response was defined as reduction in SCCAI score by ≥3 points from baseline or a sustained score of &lt;2.5. Clinical remission was defined as a SCCAI score of &lt; 2.5, and/ or a calprotectin level of &lt;250 mg/g with a CRP of &lt; 5mg/L.
Ethical approval has been granted by HRA and Health and Care Research Wales (HCRW) (REC ref: 24/HRA/1198)

Results
52 patients were reviewed at week 8-12 following their first dose. 15, 15 and 22 patients were on tofacitinib, filgotinib, and upadacitinib respectively. 3 (20%) of patient in the tofacitinib group were exposed to at least 3 biologics prior to initiating the JAK Inhibitor, followed by upadacitinib which was 3 (14%) of patients. In the tofacitinib group, most patients were exposed to 2 previous biologics (n=7, 47%), whereas majority of patients on filgotinib and upadacitinib had exposure to 1 previous biologic, 7 (47%) and 8 (36%) patients respectively. For the patient group exposed to 3 or more biologics (n=7, 14%), 100% patients on tofacitinib (n=3) and upadacitinib (n=3) achieved clinical remission by week 8-12, whereas none of the patients on filgotinib achieve clinical remission. In biologic naïve patients, filgotinib demonstrated the greatest improvement in calprotectin score with a reduction in 30% from baseline (n=2, 100%). In patients exposed to ≥3 biologics, upadacitinib achieved higher rates of improvement in faecal calprotectin score (n=2, 100%).

Conclusion
Our observations suggest that patients exposed to at least 3 biologics, tofacitinib and upadacitinib were the most effective, whereas filgotinib seems to be more effective in biologic naïve patients. Our patient cohort is small. We will continue to collect data and undertake further statistical analysis to examine the significance of the observations and factors associated with effectiveness.

Reference
1. Goetsch, A et al. Advances in pharmacotherapy for ulcerative colitis: a focus on JAK1 inhibitors. Expert Opinion on Pharmacotherapy, 2023, 24(7), 849–861.
New insights on extramedullary granulopoiesis and neutrophil heterogeneity in the spleen and its importance in disease
Authors: Guo Rongxia , Xie Xuemei , Ren Qian , Liew Pei Xiong 
Published: November 2024

Abstract
Neutrophils are traditionally viewed as uncomplicated exterminators that arrive quickly at sites of infection, kill pathogens, and then expire. However, recent studies employing modern transcriptomics coupled with novel imaging modalities have discovered that neutrophils exhibit significant heterogeneity within organs and have complex functional roles ranging from tissue homeostasis to cancer and chronic pathologies. This has revised the view that neutrophils are simplistic butchers, and there has been a resurgent interest in neutrophils. The spleen was described as a granulopoietic organ more than 4 decades ago, and studies indicate that neutrophils are briefly retained in the spleen before returning to circulation after proliferation. Transcriptomic studies have discovered that splenic neutrophils are heterogeneous and distinct compared with those in blood. This suggests that a unique hematopoietic niche exists in the splenic microenvironment, i.e., capable of programming neutrophils in the spleen. During severe systemic inflammation with an increased need of neutrophils, the spleen can adapt by producing neutrophils through emergency granulopoiesis. In this review, we describe the structure and microanatomy of the spleen and examine how cells within the splenic microenvironment help to regulate splenic granulopoiesis. A focus is placed on exploring the increase in splenic granulopoiesis to meet host needs during infection and inflammation. Emerging technologies such as single-cell RNA sequencing, which provide valuable insight into splenic neutrophil development and heterogeneity, are also discussed. Finally, we examine how tumors subvert this natural pathway in the spleen to generate granulocytic suppressor cells to promote tumor growth.
Association between glucagon-like peptide-1 receptor agonist use and progression of monoclonal gammopathy of uncertain significance to multiple myeloma among patients with diabetes
Authors: Grandhi Nikhil , Liu Lawrence , Wang Mei , Thomas Theodore , Schoen Martin , Sanfilippo Kristen , Gao Feng , Colditz Graham A , Carson Kenneth R , Janakiram Murali , Chang Su-Hsin 
Published: November 2024

Abstract

Background
In patients with diabetes and monoclonal gammopathy of uncertain significance (MGUS), the impact of glucagon-like peptide-1 (GLP-1) receptor agonists on the natural history of MGUS is unknown. We aimed to assess the association of GLP-1 receptor agonist use in the progression of MGUS to multiple myeloma in patients with diabetes.

Methods
This is a population-based cohort study of veterans diagnosed with MGUS from 2006 to 2021 with a prior diagnosis of diabetes. A validated natural language processing algorithm was used to confirm MGUS and progression to multiple myeloma. We performed 1:2 matching for individuals with and without GLP-1 receptor agonist exposure. The Gray test was performed to detect the difference in cumulative incidence functions for progression by GLP-1 receptor agonist use status. The association between time-varying GLP-1 receptor agonist use and progression was estimated through multivariable-adjusted hazard ratio using a stratified Fine-Gray distribution hazard model, with death as a competing event and stratum for the matched patient triad.

Results
Our matched cohort included 1097 individuals with MGUS who had ever used GLP-1 receptor agonists and the matched 2194 patients who had never used GLP-1 receptor agonists. Overall, 2.6% of individuals progressed in the GLP-1 receptor agonist ever use group compared with 5.0% in the GLP-1 receptor agonist never use group. Cumulative incidence functions were statistically significantly different between the exposed and unexposed groups (P = .02). GLP-1 receptor agonist use vs no use was associated with decreased progression to multiple myeloma (hazard ratio = 0.45, 95% confidence interval = 0.22 to 0.93, P = .03).

Conclusions
For patients with diabetes and MGUS, GLP-1 receptor agonist use is associated with a 55% reduction in risk of progression from MGUS to multiple myeloma compared with no use.
Systematic review and meta-analysis of combined cognitive-behavioral therapy and physical activity and exercise interventions for pediatric chronic disease
Authors: Black William R , von Klinggraeff Lauren , White David A ,   ACSM-CEP, Forseth Bethany , Jackson Jamie L , Bates Carolyn R , Pfledderer Christopher D , Dobbins Sidney , Hoskinson Kristen R , Gehred Alison , Davis Ann M 
Published: November 2024

Abstract

Objective
Cognitive-behavioral (CBT) interventions combined with either a physical activity (CBT+PA) or exercise intervention (CBT+Ex) are becoming more common in pediatric populations. Considering the independent effects of PA and exercise on health and psychological outcomes, it is unclear whether CBT alone differs from CBT+PA or CBT+Ex in efficacy. The main objective of this systematic review and meta-analysis of randomized clinical trials (RCTs) was to assess the efficacy of CBT+PA and CBT+Ex interventions in pediatric chronic disease.

Method
This review included RCTs in children (≤18 years) with a chronic condition, a CBT+Ex or CBT+PA intervention, and an objective measure of PA&Ex. Seven databases were searched using MeSH terms and key terms and included studies published before July 1, 2023. Abstracts were reviewed for inclusion by two independent reviewers, data was extracted by three independent reviewers. Risk of bias (RoB 2) and study quality were coded. Random effect meta-analyses of differences in between-group change in PA&Ex were conducted.

Results
Eligible studies (k = 5) reported outcomes for a combined 446 children. A small, nonsignificant overall effect was found (d = 0.10, 95% CI −0.16, 0.35) indicating intervention groups (CBT+PA or CBT+Ex) increased engagement in PA&Ex more than comparator groups (CBT). Additional analyses were inconclusive due to the small number of eligible studies.

Discussion
Additional RCTs are needed with integrated PA&Ex interventions targeting pediatric chronic disease. Future trials should report more detailed PA&Ex data. The full protocol for this analysis was prospectively registered in Open Science Framework (project ID: osf.io/m4wtc).
Breach of Confidence
Authors: Rushbrooke Justin , Speker Adam , Hamer Ben 
Published: November 2024

Abstract
Chapter 4 focuses on breach of confidence. Section B provides an overview of this cause of action through looking at its origins and development, juridical basis, and key components. The section also looks at the elements of ‘hybrid’ breach of confidence, the position of third parties who acquire information that is subject to a duty of confidence, defences, and remedies. Section C considers the four primary classes of information that are associated with breach of confidence, namely: trade secrets, personal confidences, government information, and artistic and literary confidences. Section D examines the criteria for identifying confidentiality in non-contractual matters as well as the factors negating confidentiality. Section E sets out the circumstances in which a duty of confidence will be imposed, the factors that amount to a breach of that duty, and who has a right to bring an action for breach of confidence.
Defamation
Authors: Speker Adam 
Published: November 2024

Abstract
Chapter 8 considers the relationship between defamation law and the protection of personal privacy. The introduction begins with an analysis of the impact of ZXC v Bloomberg LP [2022] UKSC 5 on the development of other causes of action to protect reputation. It then goes on to consider the relationship between defamation, privacy and confidentiality, the essential features of defamation and malicious falsehood, the value of reputation, and the value of freedom of expression. Section B sets out the various protections of privacy afforded by defamation law, including the test for determining what is defamatory, the pre-2013 defence of fair comment on a matter of public interest, the defence of publication on a matter of public interest (now found in s 4 Defamation Act 2013), the statutory privilege defences, and the principles relating to defamation damages. In Section C, the conflict between defamation and privacy is addressed by examining truth as an absolute defence in defamation, the rule against prior restraint, and the impact of Article 8 ECHR rights on the substantive defences in defamation.
Intrusion into Physical Privacy
Authors: Moreham N A , Hamer Clara 
Published: November 2024

Abstract
By contrast with informational privacy, which is protected in England and Wales primarily through the bespoke tort of misuse of private information, intrusions into people’s homes, space, or property are limited by a wide range of statutory and tortious actions, but no single specialized cause of action. This chapter is divided principally between statutory measures which protect physical privacy on the one hand (Section B), and protections deriving from the common law on the other (Section C). It ends in Section D with a brief overview of how physical privacy is preserved in other common law jurisdictions, often through legislation or torts specifically targeted at intrusion, and how it could be better protected in England and Wales.
Privacy, the Internet, and Social Media
Authors: Busuttil Godwin , McMahon Felicity , de Wilde Gervase 
Published: November 2024

Abstract
This chapter considers the legal means of protecting individuals against unwarranted infringements of privacy in the context of the ever-expanding media through which information is shared online. The Online Safety Act 2023 imposes significant new responsibilities on Internet Service Providers (ISPs), including apps and social media platforms, though the explanatory codes of practice to be produced by Ofcom as regulator are yet to be released. Without significant guidance or jurisprudence on the Act, the causes of action discussed elsewhere in this book remain the key means of legal redress. Section B offers practical advice on preliminary considerations when an online privacy breach is alleged, and Section C briefly discusses potential criminal liability for such breaches. Sections D to F consider questions about who bears responsibility for privacy-infringing material posted online, particularly, the novel means of republishing online (eg through hyperlinks), difficulties identifying anonymous online authors, and the extent of ISPs’ liability. Section G addresses statutory defences available in cases of online publication, particularly for web hosts and search engine operators under the e-Commerce Regulations 2002. Section H considers the key common law actions which protect online privacy, particularly harassment which is a flexible tool for addressing multi-faceted online abuse. Section I ends by describing the remedies available to online privacy claimants, including damages and injunctions.
Impact of survey spatial variability on galaxy redshift distributions and the cosmological 3 × 2-point statistics for the Rubin Legacy Survey of Space and Time (LSST)
Authors: Hang Qianjun , Joachimi Benjamin , Charles Eric , Crenshaw John Franklin , Larsen Patricia , Malz Alex I , Schmidt Sam , Yan Ziang , Zhang Tianqing ,   the LSST Dark Energy Science Collaboration, Leistedt Boris , Rau Markus , Bianco Federica , Burchat Pat , Hearin Andrew , Kovacs Eve , Lahav Ofer , Mandelbaum Rachel , Nicola Andrina , Yoachim Peter 
Published: November 2024

ABSTRACT
We investigate the impact of spatial survey non-uniformity on the galaxy redshift distributions for forthcoming data releases of the Rubin Observatory Legacy Survey of Space and Time (LSST). Specifically, we construct a mock photometry data set degraded by the Rubin OpSim observing conditions, and estimate photometric redshifts of the sample using a template-fitting photo-z estimator, BPZ, and a machine learning method, FlexZBoost. We select the Gold sample, defined as $i\lt 25.3$ for 10 yr LSST data, with an adjusted magnitude cut for each year and divide it into five tomographic redshift bins for the weak lensing lens and source samples. We quantify the change in the number of objects, mean redshift, and width of each tomographic bin as a function of the coadd i-band depth for 1-yr (Y1), 3-yr (Y3), and 5-yr (Y5) data. In particular, Y3 and Y5 have large non-uniformity due to the rolling cadence of LSST, hence provide a worst-case scenario of the impact from non-uniformity. We find that these quantities typically increase with depth, and the variation can be $10\!-\!40~{{\rm per\ cent}}$ at extreme depth values. Using Y3 as an example, we propagate the variable depth effect to the weak lensing $3\times 2$ pt analysis, and assess the impact on cosmological parameters via a Fisher forecast. We find that galaxy clustering is most susceptible to variable depth, and non-uniformity needs to be mitigated below 3 per cent to recover unbiased cosmological constraints. There is little impact on galaxy–shear and shear–shear power spectra, given the expected LSST Y3 noise.
Combination therapy as a new standard of care in diabetic and non-diabetic chronic kidney disease
Authors: Neuen Brendon L , Yeung Emily K , Rangaswami Janani , Vaduganathan Muthiah 
Published: November 2024

PLAIN ENGLISH SUMMARY

Combination therapy, involving the use of multiple medications together, is becoming a new standard of care for chronic kidney disease (CKD). For people with CKD, combination therapy offers the promise of preventing kidney failure and reducing the risk of heart problems. This approach is appealing because different drugs target distinct mechanisms involved in CKD progression. For instance, some target immune responses, others reduce kidney inflammation and scarring, while others improve blood pressure within the kidneys. Data from large clinical trials suggest that each treatment works effectively on its own, regardless of other medications people are taking. Combining therapies can also reduce the risk of side effects of individual medications. This review highlights the evidence for combination therapy in CKD, explores how to improve its use, and discusses how future studies may answer remaining questions.

ABSTRACT
A range of therapies now exists to reduce the risk of kidney failure and cardiovascular events in people with type 2 diabetes, including renin–angiotensin system blockade, sodium-glucose cotransporter 2 (SGLT2) inhibitors, non-steroidal mineralocorticoid receptor antagonists, and glucagon-like peptide-1 receptor agonists. With multiple clinical trials underway, it is likely that at least some of these therapies—as well as additional agents such as endothelin receptor antagonists—will further demonstrate kidney-protective effects in people with CKD who do not have diabetes in the near future. For conditions such as IgA nephropathy, several therapies have recently been approved or are being evaluated in late phase trials. Thus combination therapy is emerging as a new standard for diabetic and non-diabetic chronic kidney disease (CKD). This approach is supported by randomized data suggesting that each therapeutic class offers independent and additive benefits in diabetic kidney disease, regardless of background therapy. Notably, the reduction in hyperkalaemia and fluid retention with SGLT2 inhibitors may enhance the tolerability and safety of other treatments. In this review, we present the rationale for combination therapy with evidence-based kidney therapies in diabetic and non-diabetic CKD. We also summarize randomized evidence supporting a multi-medicine approach, address safety considerations, review ongoing trials, and propose frameworks for implementing treatments aligned with patient risk to optimize person-centred care and reduce long-term risks of kidney failure and related complications.
Dinor-12-oxo-phytodienoic acid conjugation with amino acids inhibits its phytohormone bioactivity in Marchantia polymorpha
Authors: Liang Wenting , Zamarreño Ángel M , Torres-Montilla Salvador , de la Torre Antonio , Totozafy Jean Chrisologue , Kaji Takuya , Ueda Minoru , Corso Massimiliano , García-Mina José M , Solano Roberto , Chini Andrea 
Published: November 2024

Abstract
Jasmonates (JAs) are important phytohormones that regulate plant tolerance to biotic and abiotic stresses, and developmental processes. Distinct JAs in different plant lineages activate a conserved signaling pathway that mediates these responses: dinor-12-oxo-phytodienoic acid (dn-OPDA) isomers in bryophytes and lycophytes, and JA-Ile in most vascular plants. In many cases, the final responses triggered by these phytohormones depend on the accumulation of specialized metabolites. To identify compounds regulated by the dn-OPDA pathway in the liverwort Marchantia polymorpha, untargeted metabolomic analyses were carried out in response to wounding, a stress that activates the dn-OPDA pathway. A previously unreported group of molecules was identified from these analyses: dn-OPDA-amino acid conjugates (dn-OPDA-aas). Their accumulation after wounding and herbivory was confirmed by targeted metabolic profiling in Marchantia and in all species in which we previously detected dn-iso-OPDA. Mutants in GRETCHEN-HAGEN 3A (MpGH3A) failed to accumulate dn-OPDA-aa conjugates and showed a constitutive activation of the OPDA pathway and increased resistance to herbivory. Our results show that dn-iso-OPDA bioactivity is reduced by amino acid conjugation. Therefore, JA conjugation in land plants plays dichotomous roles: jasmonic acid conjugation with isoleucine (Ile) produces the bioactive JA-Ile in tracheophytes, whereas conjugation of dn-iso-OPDA with different amino acids deactivates the phytohormone in bryophytes and lycophytes.