bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selective inhibition of adenylyl cyclase subtype 1 reduces inflammatory pain in chicken of gouty arthritis
Authors: Liu Ren-Hao , Shi Wantong , Zhang Yu-Xiang , Zhuo Min , Li Xu-Hui 
Published: November 2021

Lack of uricase leads to the high incidence of gout in humans and poultry, which is different from rodents. Therefore, chicken is considered to be one of the ideal animal models for the study of gout. Gout-related pain caused by the accumulation of urate in joints is one type of inflammatory pain, which causes damage to joint function. Our previous studies have demonstrated the crucial role of calcium-stimulated adenylyl cyclase subtype 1 (AC1) in inflammatory pain in rodents; however, there is no study in poultry. In the present study, we injected mono-sodium urate (MSU) into the left ankle joint of the chicken to establish a gouty arthritis model, and tested the effect of AC1 inhibitor NB001 on gouty arthritis in chickens. We found that MSU successfully induced spontaneous pain behaviors including sitting, standing on one leg, and limping after 1–3 h of injection into the left ankle of chickens. In addition, edema and mechanical pain hypersensitivity also occurred in the left ankle of chickens with gouty arthritis. After peroral administration of NB001 on chickens with gouty arthritis, both the spontaneous pain behaviors and the mechanical pain hypersensitivity were effectively relieved. The MSU-induced edema in the left ankle of chickens was not affected by NB001, suggesting a central effect of NB001. Our results provide a strong evidence that AC1 is involved in the regulation of inflammatory pain in poultry. A selective AC1 inhibitor NB001 produces an analgesic effect (not anti-inflammatory effect) on gouty pain and may be used for future treatment of gouty pain in both humans and poultry.
Efficacy and safety of immunosuppressive therapy in myelin oligodendrocyte glycoprotein antibody–associated disease: a systematic review and meta-analysis
Authors: Lai Qi-Lun , Zhang Yin-Xi , Cai Meng-Ting , Zheng Yang , Qiao Song , Fang Gao-Li , Shen Chun-Hong 
Published: November 2021

Background: A considerable number of patients with myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD) will experience a relapse, but the effect of maintenance therapies on re-attack rates is currently unknown. Objective: To investigate the efficacy and safety of immunosuppressive therapy for preventing disease relapses in patients with MOGAD, including rituximab (RTX), mycophenolate mofetil (MMF), and azathioprine (AZA). Methods: English-language studies published prior to August 31, 2020, were searched in the NCBI (PubMed), ISI Web of Science, and the Cochrane Library databases. Patient characteristics, treatment regimens, outcome measures, and adverse effects were retrieved. Results: We enrolled 11 studies in the final meta-analysis, including 346 patients with MOGAD. RTX therapy was demonstrated to result in reduced mean annualized relapse rate (ARR) by 1.35 (95% confidence interval (CI): 0.85–1.85) and reduced mean Expanded Disability Status Scale score by 0.80 (95% CI: 0.53–1.08) in patients with MOGAD. MMF therapy was associated with the mean ARR decreasing by 0.83 (95% CI: 0.31–1.35), and AZA was related to the mean ARR decreasing by 1.71 (95% CI: 0.83–2.58). The reported discontinuation rates of RTX, MMF, and AZA therapy due to adverse effects were 3/197 (1.52%), 3/39 (7.69%), and 4/37 (10.81%), respectively. Conclusion: The study provided evidence to support the efficacy of RTX, MMF, and AZA on the preventive treatment in patients with MOGAD. However, large randomized controlled trials are still needed in the future.
Sociodemographic Factors Associated With Decreased Compliance to Prescribed Rehabilitation After Surgical Treatment of Knee Injuries in Pediatric Patients
Authors: Metz Allan K. , Hart-Johnson Tami , Blackwood R. Alexander , Crawford Eileen A. 
Published: November 2021

Background: Rehabilitation is an important component of care in postsurgical knee patients, especially as it pertains to return to preinjury activity level. Despite the established significance of rehabilitation in improving outcomes after certain surgical procedures, there is a lack of investigation into compliance rates and factors that affect compliance in pediatric patients. Purpose/Hypothesis: The purpose of this study was to evaluate sociodemographic factors associated with noncompliance in pediatric patients after knee surgery to characterize health disparities in this population. Our hypothesis was that certain sociodemographic factors would be associated with decreased compliance. Study Design: Cross-sectional study; Level of evidence, 3. Methods: A retrospective review of medical records was used to gather data on compliance rate, demographics, and socioeconomic factors for pediatric patients undergoing rehabilitation after knee surgery. Compliance rate was determined by counting the total scheduled appointments, cancellations, and no-shows (defined as visits for which patients did not show up and did not provide notification of cancellation). Various types of knee injuries were included in this study. Data were evaluated using bivariate analyses in addition to hierarchical linear and binary logistic regression to assess for associations between sociodemographic factors and compliance rate. Results: Our total sample size was 186 patients. When compared with patients from non–single-parent households, patients from single-parent households were found to have a lower rate of physical therapy compliance (72.2% vs 80.1%; P < .001), were less likely to reach the 85% compliance threshold (9.1% vs 42.4%; P < .001), and had an increased amount of cancellations and no-shows (16.7 vs 11.7 visits; P = .02). Although a small sample size, Hispanic/Latino patients were shown to have a lower achievement of the 85% compliance threshold compared with non-Hispanic/Latino patients (0% vs 38.2%; P = .04). Increased distance from the rehabilitation clinic was associated with lower achievement of the 85% compliance threshold ( P = .033). Conclusion: Overall, there were several significant demographic and socioeconomic variables associated with rehabilitation compliance, specifically single-parent status, distance to rehabilitation clinic, and ethnicity. These results suggest potential predictors of decreased compliance that warrant prospective investigation.
Primary cutaneous lymphoma: recommendations for clinical trial design and staging update from the ISCL, USCLC, and EORTC
Authors: Olsen Elise A. , Whittaker Sean , Willemze Rein , Pinter-Brown Lauren , Foss Francine , Geskin Larisa , Schwartz Lawrence , Horwitz Steven , Guitart Joan , Zic John , Kim Youn H. , Wood Gary S. , Duvic Madeleine , Ai Wei , Girardi Michael , Gru Alejandro , Guenova Emmanuella , Hodak Emmilia , Hoppe Richard , Kempf Werner , Kim Ellen , Lechowicz Mary Jo , Ortiz-Romero Pablo , Papadavid Evangelia , Quaglino Pietro , Pittelkow Mark , Prince H. Miles , Sanches Jose Antonio , Sugaya Makoto , Vermeer Maarten , Zain Jasmine , Knobler Robert , Stadler Rudolf , Bagot Martine , Scarisbrick Julia 
Published: November 2021

Abstract
The number of patients with primary cutaneous lymphoma (PCL) relative to other non-Hodgkin lymphomas (NHLs) is small and the number of subtypes large. Although clinical trial guidelines have been published for mycosis fungoides/Sézary syndrome, the most common type of PCL, none exist for the other PCLs. In addition, staging of the PCLs has been evolving based on new data on potential prognostic factors, diagnosis, and assessment methods of both skin and extracutaneous disease and a desire to align the latter with the Lugano guidelines for all NHLs. The International Society for Cutaneous Lymphomas (ISCL), the United States Cutaneous LymphomaConsortium (USCLC), and the Cutaneous Lymphoma Task Force of the European Organization for the Research and Treatment of Cancer (EORTC) now propose updated staging and guidelines for the study design, assessment, endpoints, and response criteria in clinical trials for all the PCLs in alignment with that of the Lugano guidelines. These recommendations provide standardized methodology that should facilitate planning and regulatory approval of new treatments for these lymphomas worldwide, encourage cooperative investigator-initiated trials, and help to assess the comparative efficacy of therapeutic agents tested across sites and studies.
The psychometric properties of the King's Brief Interstitial Lung Disease questionnaire and thresholds for meaningful treatment response in patients with progressive fibrosing interstitial lung diseases
Authors: Birring Surinder S. , Bushnell Donald M. , Baldwin Michael , Mueller Heiko , Male Natalia , Rohr Klaus B. , Inoue Yoshikazu 
Published: November 2021

BackgroundThere is a lack of fully validated patient-reported outcome measures for progressive fibrosing interstitial lung disease (ILD). We aimed to validate the King's Brief Interstitial Lung Disease (K-BILD) questionnaire for measuring health-related quality of life (HRQoL) in these patients. We also aimed to estimate the meaningful change threshold for interpreting stabilisation of HRQoL as a clinical end-point in progressive fibrosing ILD, where the current goal of treatment is disease stability and slowing progression.MethodsThis analysis evaluated data from 663 patients with progressive fibrosing ILD other than idiopathic pulmonary fibrosis from the INBUILD trial. Validation of the measurement properties was assessed for internal consistency, test–retest reliability, construct validity, known-groups validity and responsiveness. We calculated meaningful change thresholds for treatment response using anchor-based (within-patient) and distribution-based methods.ResultsK-BILD had strong internal consistency (Cronbach's α was 0.94 for total score, 0.88 for breathlessness and activities, 0.91 for psychological, and 0.79 for chest symptoms). The test–retest reliability intraclass correlation coefficient was 0.74 for K-BILD total score. K-BILD demonstrated weak correlations with forced vital capacity (FVC) percent predicted. Known-groups validity showed significant differences in K-BILD scores for patient groups with different disease severity based on use of supplemental oxygen or baseline FVC % pred (≤70% or >70%). We estimated a meaningful change threshold of ≥ –2 units for K-BILD total score for defining patients who remain stable/improvedversusthose with progressive deterioration.ConclusionsOur results validate K-BILD as a tool for assessing HRQoL in patients with progressive fibrosing ILD and set a meaningful change threshold of ≥ –2 units for K-BILD total score.
Developmental series of gene expression clarifies maternal mRNA provisioning and maternal-to-zygotic transition in a reef-building coral
Authors: Chille Erin , Strand Emma , Neder Mayaan , Schmidt Valeria , Sherman Madeleine , Mass Tali , Putnam Hollie 
Published: November 2021

AbstractBackgroundMaternal mRNA provisioning of oocytes regulates early embryogenesis. Maternal transcripts are degraded as zygotic genome activation (ZGA) intensifies, a phenomenon known as the maternal-to-zygotic transition (MZT). Here, we examine gene expression over nine developmental stages in the Pacific rice coral,Montipora capitata, from eggs and embryos at 1, 4, 9, 14, 22, and 36 h-post-fertilization (hpf), as well as swimming larvae (9d), and adult colonies.ResultsWeighted Gene Coexpression Network Analysis revealed four expression peaks, identifying the maternal complement, two waves of the MZT, and adult expression. Gene ontology enrichment revealed maternal mRNAs are dominated by cell division, methylation, biosynthesis, metabolism, and protein/RNA processing and transport functions. The first MZT wave occurs from ~4-14 hpf and is enriched in terms related to biosynthesis, methylation, cell division, and transcription. In contrast, functional enrichment in the second MZT wave, or ZGA, from 22 hpf-9dpf, includes ion/peptide transport and cell signaling. Finally, adult expression is enriched for functions related to signaling, metabolism, and ion/peptide transport. Our proposed MZT timing is further supported by expression of enzymes involved in zygotic transcriptional repression (Kaiso) and activation (Sox2), which peak at 14 hpf and 22 hpf, respectively. Further, DNA methylation writing (DNMT3a) and removing (TET1) enzymes peak and remain stable past ~4 hpf, suggesting that methylome programming occurs before 4 hpf.ConclusionsOur high-resolution insight into the coral maternal mRNA and MZT provides essential baseline information to understand parental carryover effects and the sensitivity of developmental success under increasing environmental stress.
Multiomics study of a heterotardigrade, Echinisicus testudo, suggests the possibility of convergent evolution of abundant heat-soluble proteins in Tardigrada
Authors: Murai Yumi , Yagi-Utsumi Maho , Fujiwara Masayuki , Tanaka Sae , Tomita Masaru , Kato Koichi , Arakawa Kazuharu 
Published: November 2021

Abstract
Background
Many limno-terrestrial tardigrades can enter an ametabolic state, known as anhydrobiosis, upon desiccation, in which the animals can withstand extreme environments. Through genomics studies, molecular components of anhydrobiosis are beginning to be elucidated, such as the expansion of oxidative stress response genes, loss of stress signaling pathways, and gain of tardigrade-specific heat-soluble protein families designated CAHS and SAHS. However, to date, studies have predominantly investigated the class Eutardigrada, and molecular mechanisms in the remaining class, Heterotardigrada, still remains elusive. To address this gap in the research, we report a multiomics study of the heterotardigrade Echiniscus testudo, one of the most desiccation-tolerant species which is not yet culturable in laboratory conditions.

Results
In order to elucidate the molecular basis of anhydrobiosis in E. testudo, we employed a multi-omics strategy encompassing genome sequencing, differential transcriptomics, and proteomics. Using ultra-low input library sequencing protocol from a single specimen, we sequenced and assembled the 153.7 Mbp genome annotated using RNA-Seq data. None of the previously identified tardigrade-specific abundant heat-soluble genes was conserved, while the loss and expansion of existing pathways were partly shared. Furthermore, we identified two families novel abundant heat-soluble proteins, which we named E. testudo Abundant Heat Soluble (EtAHS), that are predicted to contain large stretches of disordered regions. Likewise the AHS families in eutardigrada, EtAHS shows structural changes from random coil to alphahelix as the water content was decreased in vitro. These characteristics of EtAHS proteins are analogous to those of CAHS in eutardigrades, while there is no conservation at the sequence level.

Conclusions
Our results suggest that Heterotardigrada have partly shared but distinct anhydrobiosis machinery compared with Eutardigrada, possibly due to convergent evolution within Tardigrada. (276/350).
Construction of a high-density genetic map and detection of a major QTL of resistance to powdery mildew (Erysiphe necator Sch.) in Caucasian grapes (Vitis vinifera L.)
Authors: Possamai Tyrone , Wiedemann-Merdinoglu Sabine , Merdinoglu Didier , Migliaro Daniele , De Mori Gloria , Cipriani Guido , Velasco Riccardo , Testolin Raffaele 
Published: November 2021

AbstractBackgroundVitis viniferaL. is the most cultivated grapevine species worldwide.Erysiphe necatorSch., the causal agent of grape powdery mildew, is one of the main pathogens affecting viticulture.V. viniferahas little or no genetic resistances againstE. necatorand the grape industry is highly dependent on agrochemicals. Some CaucasianV. viniferaaccessions have been reported to be resistant toE. necatorand to have no genetic relationships to known sources of resistance to powdery mildew. The main purpose of this work was the study and mapping of the resistance toE. necatorin the Caucasian grapes ‘Shavtsitska’ and ‘Tskhvedianis tetra’.ResultsThe Caucasian varieties ‘Shavtsitska’ and ‘Tskhvedianis tetra’ showed a strong partial resistance toE. necatorwhich segregated in two cross populations: the resistant genotypes delayed and limited the pathogen mycelium growth, sporulation intensity and number of conidia generated. A total of 184 seedlings of ‘Shavtsitska’ x ‘Glera’ population were genotyped through the Genotyping by Sequencing (GBS) technology and two high-density linkage maps were developed for the cross parents. The QTL analysis revealed a major resistance locus, explaining up to 80.15% of the phenotypic variance, on ‘Shavtsitska’ linkage group 13, which was associated with a reduced pathogen infection as well as an enhanced plant necrotic response. The genotyping of 105 Caucasian accessions with SSR markers flanking the QTL revealed that the resistant haplotype of ‘Shavtsitska’ was shared by ‘Tskhvedianis tetra’ and a total of 25 Caucasian grape varieties, suggesting a widespread presence of this resistance in the surveyed germplasm. The uncovered QTL was mapped in the region where theRen1locus of resistance toE. necator, identified in theV. vinifera‘Kishmish vatkana’ and related grapes of Central Asia, is located. The genetic analysis conducted revealed that the Caucasian grapes in this study exhibit a resistant haplotype different from that of Central Asian grape accessions.ConclusionsThe QTL isolated in ‘Shavtsitska’ and present in the CaucasianV. viniferavarieties could be a new candidate gene of resistance toE. necatorto use in breeding programmes. It co-localizes with theRen1locus but shows a different haplotype from that of grapevines of Central Asia. We therefore consider that the Caucasian resistance locus, namedRen1.2, contains a member of a cluster of R-genes, of which the region is rich, and to be linked with, or possibly allelic, toRen1.
Optimising an intervention to support home-living older adults at risk of malnutrition: a qualitative study
Authors: Payne Liz , Ghio Daniela , Grey Elisabeth , Slodkowska-Barabasz Joanna , Harris Philine , Sutcliffe Michelle , Green Sue , Roberts Helen C. , Childs Caroline , Robinson Sian , Gudgin Bernard , Holloway Pam , Kelly Jo , Wallis Kathy , Dean Oliver , Aveyard Paul , Gill Paramjit , Stroud Mike , Little Paul , Yardley Lucy , Morrison Leanne 
Published: November 2021

Abstract
Background
In the UK, about 14% of community-dwelling adults aged 65 and over are estimated to be at risk of malnutrition. Screening older adults in primary care and treating those at risk may help to reduce malnutrition risk, reduce the resulting need for healthcare use and improve quality of life. Interventions are needed to raise older adults’ risk awareness, offer relevant and meaningful strategies to address risk and support general practices to deliver treatment and support.

Methods
Using the Person-based Approach and input from Patient and Public Involvement representatives, we developed the ‘Eat well, feel well, stay well’ intervention. The intervention was optimised using qualitative data from think aloud and semi-structured process evaluation interviews with 23 and 18 older adults respectively. Positive and negative comments were extracted to inform rapid iterative modifications to support engagement with the intervention. Data were then analysed thematically and final adjustments made, to optimise the meaningfulness of the intervention for the target population.

Results
Participants’ comments were generally positive. This paper focuses predominantly on participants’ negative reactions, to illustrate the changes needed to ensure that intervention materials were optimally relevant and meaningful to older adults. Key factors that undermined engagement included: resistance to the recommended nutritional intake among those with reduced appetite or eating difficulties, particularly frequent eating and high energy options; reluctance to gain weight; and a perception that advice did not align with participants’ specific personal preferences and eating difficulties. We addressed these issues by adjusting the communication of eating goals to be more closely aligned with older adults’ beliefs about good nutrition, and acceptable and feasible eating patterns. We also adjusted the suggested tips and strategies to fit better with older adults’ everyday activities, values and beliefs.

Conclusions
Using iterative qualitative methods facilitated the identification of key behavioural and contextual elements that supported engagement, and issues that undermined older adults’ engagement with intervention content. This informed crucial revisions to the intervention content that enabled us to maximise the meaningfulness, relevance and feasibility of the key messages and suggested strategies to address malnutrition risk, and therefore optimise engagement with the intervention and the behavioural advice it provided.
Gonorrhoea: a systematic review of prevalence reporting globally
Authors: Whelan Jane , Abbing-Karahagopian Victoria , Serino Laura , Unemo Magnus 
Published: November 2021

Abstract
Background
The World Health Organization (WHO) recommends periodic gonorrhoea prevalence assessments in the general population or proxies thereof (including pregnant women, women attending family planning clinics, military recruits, and men undergoing employment physicals for example) and in population groups at increased risk, including men-who-have-sex-with-men (MSM) and sex workers.

Method
We evaluated reported prevalence data, including estimates from proxy general population samples to reflect the WHO recommendations. We describe the outcomes from the general population country-by-country and extend previous reviews to include MSM, sex workers, and extragenital infections.

Result and conclusion
In our systematic search, 2015 titles were reviewed (January 2010–April 2019) and 174 full-text publications were included. National, population-based prevalence data were identified in only four countries (the United States of America, the United Kingdom, Peru, New Caledonia) and local population-based estimates were reported in areas within five countries (China, South Africa, Brazil, Benin, and Malawi). The remaining studies identified only reported test positivity from non-probability, proxy general population samples. Due to the diversity of the reviewed studies, detailed comparison across studies was not possible. In MSM, data were identified from 64 studies in 25 countries. Rectal infection rates were generally higher than urogenital or pharyngeal infection rates, where extragenital testing was conducted. Data on sex workers were identified from 41 studies in 23 countries; rates in female sex workers were high. Current prevalence monitoring was shown to be highly suboptimal worldwide. Serial prevalence monitoring of critical epidemiological variables, and guidelines to optimize prevalence study conduct and reporting beyond antenatal settings are recommended.