bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunohistochemical Phenotype of T Cells Invading Muscle in Inclusion Body Myositis
Authors: Matsubara Shiro , Suzuki Shigeaki , Komori Takashi 
Published: August 2022

Abstract
Inclusion body myositis (IBM) is an inflammatory myopathy of aged people with poor response to therapy. To characterize muscle-invading inflammatory cells, we performed immunohistochemical and ultrastructural studies on muscle biopsies from 10 patients with IBM with durations of illness from 3 to 84 months. At the surface of muscle fibers, 79% and 48% of CD8+ cells were positive for killer cell lectin-like receptor subfamily G, member 1 (KLRG1) and CD57, respectively. CD8+KLRG1+ cells are highly differentiated cytotoxic cells. On an average, 27% of CD8−CD57+KLRG1+ cells at the surface were CD4+. Proportions of CD28+ cells among KLRG1+ cells showed a negative correlation with duration of illness (r = −0.68). These changes indicated progressive differentiation of CD8+ T cells. Moreover, PD-1 expression on CD57+ and CD8+ cells increased early, then fluctuated, and reincreased in later stages. PD ligand-1 (PD-L1) and PD-L2 were expressed on adjacent cells including muscle fibers. T cell large granular lymphocytes (LGLs) are potent effector cells and cells with ultrastructure indistinguishable from LGLs were seen in the sarcoplasm along with lymphocytes undergoing degeneration. Together, along the course of IBM, some inflammatory cells retained the potential for cytotoxicity whereas others indicated suppression by exhaustion, senescence, or through the PD-1 pathway.
Social Stratification and Career Choice Anxieties in Nineteenth-Century Central Europe
Authors: Beilinson Orel 
Published: August 2022

Abstract
Central Europe around 1900 was marred with anxiety around the choice of career. This article weaves histories of education, labor, bureaucracy, and the social sciences to show how families reacted to changes in the labor market, including the opening of careers to talent and the mechanization of handicrafts. Parents found themselves unable to guide their children to a safe profession. Whereas previously, career choices were limited, changes in education and the labor market offered adolescents more options. Simultaneously, however, some occupations became endangered and others overcrowded. The erosion of labor stratification gave families the hope of social mobility but also upended their ontological security, as traditional roads to adulthood became impossible to follow. This article uses the discourse on career choice to write a history of this crisis. The discourse was born in early modern Europe to stop parents from forcing their children into a profession against the children’s wishes. In nineteenth-century Europe, however, parents and schools weaponized this discourse against each other to widen or narrow access to advanced education. Social scientists concerned with the industrial labor force joined the conversation by turning career choice into a matter of scientific expertise. Finally, the article shows how voluntary associations pioneered the provision of vocational guidance before state intervention after World War I. Thus, the article traces a significant transformation in the transition to adulthood and offers a prehistory of vocational guidance.
Enhanced proteostasis, lipid remodeling, and nitrogen remobilization define barley flag leaf senescence
Authors: Cohen Maja , Hertweck Kendra , Itkin Maxim , Malitsky Sergey , Dassa Bareket , Fischer Andreas M , Fluhr Robert 
Published: August 2022

Abstract
Leaf senescence is a developmental process allowing nutrient remobilization to sink organs. We characterized flag leaf senescence at 7, 14, and 21 d past anthesis in two near-isogenic barley lines varying in the allelic state of the HvNAM1 transcription factor gene, which influences senescence timing. Metabolomics and microscopy indicated that, as senescence progressed, thylakoid lipids were transiently converted to neutral lipids accumulating in lipid droplets. Senescing leaves also exhibited an accumulation of sugars including glucose, while nitrogen compounds (nucleobases, nucleotides, and amino acids) decreased. RNA-Seq analysis suggested lipid catabolism via β-oxidation and the glyoxylate cycle, producing carbon skeletons and feeding respiration as a replacement of the diminished carbon supply from photosynthesis. Comparison of the two barley lines highlighted a more prominent up-regulation of heat stress transcription factor- and chaperone-encoding genes in the late-senescing line, suggesting a role for these genes in the control of leaf longevity. While numerous genes with putative roles in nitrogen remobilization were up-regulated in both lines, several peptidases, nucleases, and nitrogen transporters were more highly induced in the early-senescing line; this finding identifies processes and specific candidates which may affect nitrogen remobilization from senescing barley leaves, downstream of the HvNAM1 transcription factor.
Two periods instead of one in a single 6.7 GHz methanol maser feature in G9.62+0.20E
Authors: MacLeod G C , Yonekura Y , Tanabe Y , Baan W A , Brogan C L , Burns R A , Chibueze J O , Houde M , Hunter T R , Kurtz S E , Rajabi F , Smits D P , Stecklum B , Sugiyama K 
Published: August 2022

ABSTRACT
The source G9.62+0.20E surprises yet again! Analysis of the associated methanol maser feature at vlsr = +8.8 km s−1 revealed a second period of P = 52.1 ± 0.3 d, along with the previously reported period P = 243 d for this source. Various explanations, harmonic flaring, Dicke’s superradiance, a secondary pulsation, or two different periodically varying radio sources in the field of view with associated methanol masers are presented. The latter two hypotheses appear more plausible but it is not clear which, if any, best describe these observations.
Phylogenomic Evidence for the Origin of Obligate Anaerobic Anammox Bacteria Around the Great Oxidation Event
Authors: Liao Tianhua , Wang Sishuo , Stüeken Eva E , Luo Haiwei 
Published: August 2022

Abstract
The anaerobic ammonium oxidation (anammox) bacteria can transform ammonium and nitrite to dinitrogen gas, and this obligate anaerobic process accounts for up to half of the global nitrogen loss in surface environments. Yet its origin and evolution, which may give important insights into the biogeochemistry of early Earth, remain enigmatic. Here, we performed a comprehensive phylogenomic and molecular clock analysis of anammox bacteria within the phylum Planctomycetes. After accommodating the uncertainties and factors influencing time estimates, which include implementing both a traditional cyanobacteria-based and a recently developed mitochondria-based molecular dating approach, we estimated a consistent origin of anammox bacteria at early Proterozoic and most likely around the so-called Great Oxidation Event (GOE; 2.32–2.5 Ga) which fundamentally changed global biogeochemical cycles. We further showed that during the origin of anammox bacteria, genes involved in oxidative stress adaptation, bioenergetics, and anammox granules formation were recruited, which might have contributed to their survival on an increasingly oxic Earth. Our findings suggest the rising levels of atmospheric oxygen, which made nitrite increasingly available, was a potential driving force for the emergence of anammox bacteria. This is one of the first studies that link the GOE to the evolution of obligate anaerobic bacteria.
Lower bone mineral density can be a risk for an enlarging bone marrow lesion: A longitudinal cohort study of Japanese women without radiographic knee osteoarthritis
Authors: Chiba Daisuke , Sasaki Eiji , Ota Seiya , Oyama Tetsushi , Ishibashi Hikaru , Kimura Yuka , Nakaji Shigeyuki , Ishibashi Yasuyuki 
Published: August 2022

ABSTRACT

Objectives
The aim is to elucidate the relationship between bone mineral density (BMD) at baseline and the change of bone marrow lesion (BML) during a 2-year follow-up (2YFU) period.

Methods
Seventy-eight female participants (mean age: 54.9 ± 9.6 years) without radiographic knee osteoarthritis were eligible. Based on right-knee magnetic resonance imaging, maximum BML area (BMLa) was calculated by tracing the BML border. The change in BMLa was defined using the following formula: [2YFU] – [Baseline] = ΔBMLa. Positive ΔBMLa was defined as enlarged; negative ΔBMLa was defined as regressed. Dual-energy X-ray absorptiometry was performed to measure the BMD of distal radius. Young adult mean [YAM (%)] of the BMD was used for statistical analysis. Linear regression analysis was conducted with ΔBMLa as the dependent variable and YAM as the independent variable. Receiver operating characteristic curve and logistic regression analyses were conducted for YAM to predict the prevalence of BML enlargement or regression.

Results
Twenty-six (33.3%) patients had enlarged BMLa, 12 (15.4%) participants showed regressing BMLa, and 40 (51.3%) patients remained stable. YAM was negatively associated with ΔBMLa (β: − 0.375, P = 0.046). The best predictor of BML enlargement risk was 85% (odds ratio: 8.383, P = 0.025).

Conclusions
Lower BMD could predict BML enlargement during a 2YFU period.
Trends in risks of malignancies in Japanese patients with rheumatoid arthritis: Analyses from a 14-year observation of the IORRA cohort
Authors: Sugimoto Naoki , Tanaka Eiichi , Inoue Eisuke , Abe Mai , Sugano Eri , Sugitani Naohiro , Saka Kumiko , Ochiai Moeko , Higuchi Yoko , Yamaguchi Rei , Ikari Katsunori , Nakajima Ayako , Yamanaka Hisashi , Harigai Masayoshi 
Published: August 2022

ABSTRACT

Objectives
The aim is to investigate the trends in risks of overall and site-specific malignancies in patients with rheumatoid arthritis (RA).

Methods
Among Japanese patients with RA enrolled in the Institute of Rheumatology, Rheumatoid Arthritis cohort, all malignancies that occurred from 2000 to 2013 were extracted. The standardized incidence ratios and 95% confidence intervals for overall and site-specific malignancies were calculated during three periods: pre-biologics, 2000–04; early biologics, 2005–09; and recent biologics, 2010–13. Risk factors for overall and specific malignancies were analysed using time-dependent Cox regression models.

Results
Among 11,299 patients with RA (68,483 person-years), 507 malignancies were confirmed. Similar risks were observed versus the general Japanese population for overall malignancies throughout the three periods, with standardized incidence ratios (95% confidence intervals) of 0.96 (0.80–1.14) in the pre-biologics period, 0.95 (0.82–1.09) in the early biologics period, and 0.87 (0.75–1.01) in the recent biologics period. A significantly increased risk for malignant lymphoma was observed throughout the observation period (standardized incidence ratio 4.61, 95% confidence interval 3.58–5.85). The disease activity was a significant risk factor for overall malignancies and lung cancer.

Conclusions
Despite the expanding use of methotrexate and biologics, there were no increases in malignancy risk in Japanese patients with RA.
Drug-survival profiling of second-line biologic therapy in rheumatoid arthritis: Choice of another tumour necrosis factor inhibitor or a biologic of different mode of action?
Authors: Shipa Muhammad R A , Di Cicco Maria , Balogh Emese , Nitu Naila A , Mainuddin M D , Bhadauria Naveen , Mukerjee Dev , Roussou Euthalia 
Published: August 2022

ABSTRACT

Objectives
To assess the best choice of second-line therapy between tumour necrosis factor-inhibitor (TNFi) and biologics of different-mode-of-action (BDMA-rituximab/tocilizumab/abatacept) in rheumatoid arthritis (RA) by evaluating drug-survival following discontinuation of the first-line TNFi.

Methods
This retrospective drug-survival study was performed across two different hospitals by conventional-statistics and machine-learning approach.

Results
From a total of 435 patients, 213 (48.9%; TNFi = 122, BDMA = 91) discontinued their second-line biologic {median drug-survival: TNFi, 27 months [95% confidence interval (95%CI) 22–32] vs BDMA, 37 months (95%CI 32–52)}. As a second-line biologic, BDMA was likely to reduce the risk of treatment-discontinuation [hazard-ratio (HR) 0.63, 95%CI 0.48–0.83] compared to TNFi, but only in seropositive-patients (HR 0.52, 95%CI 0.38–0.73), not in seronegative-RA. Drug-survival benefit of BDMA over TNFi was not observed if the seropositive-patients were previously exposed to monoclonal-TNFi (HR 0.77, 95%CI 0.49–1.22) versus soluble-TNFi (etanercept/biosimilars) or if the first-line TNFi was terminated within 23.9 months of initiation (HR 0.97, 95%CI 0.56–1.68).

Conclusions
BDMA, as a second-line biologic, is more likely to be sustained in seropositive-patients, particularly without prior exposure to monoclonal-TNFi. The drug-survival benefit of BDMA was not observed in seronegative-patients or if the first-line TNFi was stopped within 2 years.
FOXL2 and FOXA1 cooperatively assemble on the TP53 promoter in alternative dimer configurations
Authors: Choi Yuri , Luo Yongyang , Lee Seunghwa , Jin Hanyong , Yoon Hye-Jin , Hahn Yoonsoo , Bae Jeehyeon , Lee Hyung Ho 
Published: August 2022

Abstract
Although both the p53 and forkhead box (FOX) family proteins are key transcription factors associated with cancer progression, their direct relationship is unknown. Here, we found that FOX family proteins bind to the non-canonical homotypic cluster of the p53 promoter region (TP53). Analysis of crystal structures of FOX proteins (FOXL2 and FOXA1) bound to the p53 homotypic cluster indicated that they interact with a 2:1 stoichiometry accommodated by FOX-induced DNA allostery. In particular, FOX proteins exhibited distinct dimerization patterns in recognition of the same p53-DNA; dimer formation of FOXA1 involved protein–protein interaction, but FOXL2 did not. Biochemical and biological functional analyses confirmed the cooperative binding of FOX proteins to the TP53 promoter for the transcriptional activation of TP53. In addition, up-regulation of TP53 was necessary for FOX proteins to exhibit anti-proliferative activity in cancer cells. These analyses reveal the presence of a discrete characteristic within FOX family proteins in which FOX proteins regulate the transcription activity of the p53 tumor suppressor via cooperative binding to the TP53 promoter in alternative dimer configurations.
Artificial intelligence (AI)-based decision support improves reproducibility of tumor response assessment in neuro-oncology: An international multi-reader study
Authors: Vollmuth Philipp , Foltyn Martha , Huang Raymond Y , Galldiks Norbert , Petersen Jens , Isensee Fabian , van den Bent Martin J , Barkhof Frederik , Park Ji Eun , Park Yae Won , Ahn Sung Soo , Brugnara Gianluca , Meredig Hagen , Jain Rajan , Smits Marion , Pope Whitney B , Maier-Hein Klaus , Weller Michael , Wen Patrick Y , Wick Wolfgang , Bendszus Martin 
Published: August 2022

AbstractBackgroundTo assess whether artificial intelligence (AI)-based decision support allows more reproducible and standardized assessment of treatment response on MRI in neuro-oncology as compared to manual 2-dimensional measurements of tumor burden using the Response Assessment in Neuro-Oncology (RANO) criteria.MethodsA series of 30 patients (15 lower-grade gliomas, 15 glioblastoma) with availability of consecutive MRI scans was selected. The time to progression (TTP) on MRI was separately evaluated for each patient by 15 investigators over two rounds. In the first round the TTP was evaluated based on the RANO criteria, whereas in the second round the TTP was evaluated by incorporating additional information from AI-enhanced MRI sequences depicting the longitudinal changes in tumor volumes. The agreement of the TTP measurements between investigators was evaluated using concordance correlation coefficients (CCC) with confidence intervals (CI) and P-values obtained using bootstrap resampling.ResultsThe CCC of TTP-measurements between investigators was 0.77 (95% CI = 0.69,0.88) with RANO alone and increased to 0.91 (95% CI = 0.82,0.95) with AI-based decision support (P = .005). This effect was significantly greater (P = .008) for patients with lower-grade gliomas (CCC = 0.70 [95% CI = 0.56,0.85] without vs. 0.90 [95% CI = 0.76,0.95] with AI-based decision support) as compared to glioblastoma (CCC = 0.83 [95% CI = 0.75,0.92] without vs. 0.86 [95% CI = 0.78,0.93] with AI-based decision support). Investigators with less years of experience judged the AI-based decision as more helpful (P = .02).ConclusionsAI-based decision support has the potential to yield more reproducible and standardized assessment of treatment response in neuro-oncology as compared to manual 2-dimensional measurements of tumor burden, particularly in patients with lower-grade gliomas. A fully-functional version of this AI-based processing pipeline is provided as open-source (https://github.com/NeuroAI-HD/HD-GLIO-XNAT).
Five-Year Prospective Observational Study of African-American Men on Active Surveillance for Prostate Cancer Demonstrates Race Is Not Predictive of Oncologic Outcomes
Authors: Pincus Joshua , Greenberg Jacob W , Natale Caleb , Koller Christopher R , Miller Stephanie , Silberstein Jonathan L , Krane L Spencer 
Published: August 2022

Abstract

Introduction
This study aimed to evaluate if race impacted outcomes or risk of disease progression in men on active surveillance (AS) for prostate cancer. We present the results from our majority African-American cohort of men in an equal access setting over a 5-year follow-up period.

Patients and Methods
All patients who elected AS for prostate cancer at the Southeast Louisiana Veterans Health Care System are entered into a prospectively managed observational database. Patients were divided into groups based on self-reported race. Grade group progression was defined as pathologic upgrading above International Society of Urological Pathology Grade Group 1 disease on subsequent biopsies following diagnostic biopsy. All tests were 2 sided using a significance of .05.

Results
A total of 228 men met inclusion criteria in the study, including 154 non-Hispanic African American and 74 non-Hispanic Caucasian American men, with a median follow-up of 5 years from the initiation of AS. Race was not predictive of Gleason grade progression, AS discontinuation, or biochemical recurrence on Cox multivariate analysis (HR = 1.01, 0.94, 0.85, P = .96, .79, .81, respectively). On Kaplan-Meier analysis at 5 years, African-American progression-free, AS discontinuation free, and overall survival probability was comparable to their Caucasian American counterparts (P &gt; .05 for all).

Conclusions
Active surveillance is a safe treatment option for low and very low risk prostate cancer, regardless of race. African-American and Caucasian-American men did not have any significant difference in Gleason grade group progression in our cohort with 5-year follow-up.
POPEYE intercellular localization mediates cell-specific iron deficiency responses
Authors: Muhammad DurreShahwar , Clark Natalie M , Haque Samiul , Williams Cranos M , Sozzani Rosangela , Long Terri A 
Published: August 2022

Abstract
Plants must tightly regulate iron (Fe) sensing, acquisition, transport, mobilization, and storage to ensure sufficient levels of this essential micronutrient. POPEYE (PYE) is an iron responsive transcription factor that positively regulates the iron deficiency response, while also repressing genes essential for maintaining iron homeostasis. However, little is known about how PYE plays such contradictory roles. Under iron-deficient conditions, pPYE:GFP accumulates in the root pericycle while pPYE:PYE–GFP is localized to the nucleus in all Arabidopsis (Arabidopsis thaliana) root cells, suggesting that PYE may have cell-specific dynamics and functions. Using scanning fluorescence correlation spectroscopy and cell-specific promoters, we found that PYE–GFP moves between different cells and that the tendency for movement corresponds with transcript abundance. While localization to the cortex, endodermis, and vasculature is required to manage changes in iron availability, vasculature and endodermis localization of PYE–GFP protein exacerbated pye-1 defects and elicited a host of transcriptional changes that are detrimental to iron mobilization. Our findings indicate that PYE acts as a positive regulator of iron deficiency response by regulating iron bioavailability differentially across cells, which may trigger iron uptake from the surrounding rhizosphere and impact root energy metabolism.
JAK inhibitors in difficult-to-treat adult-onset Still’s disease and systemic-onset juvenile idiopathic arthritis
Authors: Gillard Louise , Pouchot Jacques , Cohen-Aubart Fleur , Koné-Paut Isabelle , Mouterde Gaël , Michaud Martin , Reumaux Héloïse , Savey Léa , Belot Alexandre , Fautrel Bruno , Mitrovic Stéphane 
Published: August 2022

AbstractObjectivesExcessive and inappropriate production of pro-inflammatory cytokines plays a key role in Still’s disease. Janus kinase inhibitor (JAKi) agents mainly block pro-inflammatory cytokine pathways, notably IL-6 and IFN. The objective was to assess the efficacy and safety of JAKi agents in difficult-to-treat systemic JIA or adult-onset Still’s disease (AOSD).MethodsThis retrospective study was based on a national survey conducted in the departments of rheumatology, paediatric rheumatology and internal medicine of French hospitals regarding systemic JIA and AOSD patients who received JAKi agents. The data were collected with a standardized questionnaire and analysed at different times (treatment initiation, months 1, 3 and 6 and the end of follow-up).ResultsNine patients (seven adults) were included. All patients showed inadequate response to CS or conventional synthetic or biologic DMARDs. Baricitinib was used in five patients, ruxolitinib in two, tofacitinib in two and upadacitinib in one. A JAKi was used combined with CS in all but two patients. A JAKi was associated with anakinra and CS in one patient, and with MTX, anakinra and CS in another. The median (range) follow-up was 16 (1–33) months. Two cases out of nine showed complete remission, 3/9 partial response and 4/9 treatment failure. At the last visit, CS could be decreased but not stopped. Tolerance of the JAKi was acceptable (no severe adverse events).ConclusionJAKi agents may be a therapeutic option for some patients with difficult-to-treat Still’s disease, especially those with partial response to medium- or high-dose CS or biologics.