bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Sepsis on Death as Modified by Solid Organ Transplantation
Authors: Ackerman Kevin S , Hoffman Katherine L , Díaz Iván , Simmons Will , Ballman Karla V , Kodiyanplakkal Rosy P , Schenck Edward J 
Published: March 2023

AbstractBackgroundPatients who have undergone solid organ transplants (SOT) have an increased risk for sepsis compared with the general population. Paradoxically, studies suggest that SOT patients with sepsis may experience better outcomes compared with those without a SOT. However, these analyses used previous definitions of sepsis. It remains unknown whether the more recent definitions of sepsis and modern analytic approaches demonstrate a similar relationship.MethodsUsing the Weill Cornell-Critical Care Database for Advanced Research, we analyzed granular physiologic, microbiologic, comorbidity, and therapeutic data in patients with and without SOT admitted to intensive care units (ICUs). We used a survival analysis with a targeted minimum loss-based estimation, adjusting for within-group (SOT and non-SOT) potential confounders to ascertain whether the effect of sepsis, defined by sepsis-3, on 28-day mortality was modified by SOT status. We performed additional analyses on restricted populations.ResultsWe analyzed 28 431 patients: 439 with SOT and sepsis, 281 with SOT without sepsis, 6793 with sepsis and without SOT, and 20 918 with neither. The most common SOT types were kidney (475) and liver (163). Despite a higher severity of illness in both sepsis groups, the adjusted sepsis-attributable effect on 28-day mortality for non-SOT patients was 4.1% (95% confidence interval [CI], 3.8–4.5) and −14.4% (95% CI, −16.8 to −12) for SOT patients. The adjusted SOT effect modification was −18.5% (95% CI, −21.2 to −15.9). The adjusted sepsis-attributable effect for immunocompromised controls was −3.5% (95% CI, −4.5 to −2.6).ConclusionsAcross a large database of patients admitted to ICUs, the sepsis-associated 28-day mortality effect was significantly lower in SOT patients compared with controls.
Adherence to NCCN Genetic Testing Guidelines in Pancreatic Cancer and Impact on Treatment
Authors: Crowley Fionnuala , Gandhi Sonal , Rudshteyn Michelle , Sehmbhi Mantej , Cohen Deirdre J 
Published: March 2023

AbstractIntroductionNational Comprehensive Cancer Network (NCCN) 2019 Guidelines recommend universal germline (GL) testing for patients (pts) with pancreatic cancer (PC), given germline mutations (gMut) can occur at a similar rate irrespective of an individual’s family history of cancer. Molecular analysis of tumors in those with metastatic disease is also recommended. We aimed to determine rates of genetic testing at our institution, factors associated with testing, and outcomes of those tested.MethodsFrequency of GL and somatic testing was examined in pts diagnosed with non-endocrine PC, with &gt;2 visits between June 2019 and June 2021 at the Mount Sinai Health System. The clinicopathological variables and treatment outcomes were also recorded.ResultsA total of 149 pts met the inclusion criteria. Sixty-six pts (44%) underwent GL testing: 42 (28%) at time of diagnosis with the remainder later in treatment. The rate of GL testing increased every year: 33% (2019), 44% (2020), and 61% (2021). A family history of cancer was the only variable associated with the decision to perform GL testing. Eight pts (12% of pts tested) had pathological gMut: BRCA1 (1), BRCA2 (1), ATM (2), PALB2 (2), NTHL1 (1), both CHEK2 and APC (1). Neither gBRCA pt received a PARP inhibitor, all except one received first-line platinum. Ninety-eight pts (65.7%) had molecular tumor testing (66.7% of patients with metastases). Two pts with BRCA2 somatic mut did not have GL testing. Three pts received targeted therapies.ConclusionGenetic testing based on provider discretion results in low rates of GL testing. Early results of genetic testing can have an impact on treatment decisions and trajectory of disease. Initiatives to increase testing are needed but must be feasible in real-world clinic settings.
Feasibility of Point-of-Care Genomic Profiling in the Diagnosis and Treatment of Cancer of Unknown Primary
Authors: Wang Xin , Beharry Andrea , Sheffield Brandon S , Cheema Parneet K 
Published: March 2023

AbstractIntroductionCancer of unknown primary remains a challenging clinical entity. Despite receiving empiric chemotherapy, median overall survival is approximately 6-12 months. Site-specific therapy based on molecular characterization has been shown to improve outcomes; however, feasibility outside of clinical trials, especially in community centers, is lacking. This study explores the application of rapid next-generation sequencing in defining cancer of unknown primary and to identify therapeutic biomarkers.MethodsA retrospective chart review was performed by identifying pathological samples designated cancer of unknown primary. Next-generation sequencing testing was based on an automated workflow utilizing the Genexus integrated sequencer, validated for clinical use. Genomic profiling was further integrated within a routine immunohistochemistry service, with results reported directly by anatomic pathologists.ResultsBetween October 2020 and October 2021, 578 solid tumor samples underwent genomic profiling. Among this cohort, 40 were selected based on an initial diagnosis of cancer of unknown primary. The median (range) age at diagnosis was 70 (42-85) and 23 (57%) were female. Genomic data were used to support a site-specific diagnosis in 6 patients (15%). Median turnaround time was 3 business days (IQR: 1-5). Most common alterations identified were KRAS (35%), CDKN2A (15%), TP53 (15%), and ERBB2 (12%). Actionable molecular targeted therapies were identified in 23 (57%) patients, including alterations in BRAF, CDKN2A, ERBB2, FGFR2, IDH1, and KRAS. Immunotherapy-sensitizing mismatch repair deficiency was identified in 1 patient.ConclusionThis study supports the adoption of rapid next-generation sequencing among patients with cancer of unknown primary. We also demonstrate the feasibility of integration of genomic profiling with diagnostic histopathology and immunohistochemistry in a community practice setting. Diagnostic algorithms incorporating genomic profiling to better define cancer of unknown primary should be considered for future study.
PagUNE12 encodes a basic helix-loop-helix transcription factor that regulates the development of secondary vascular tissue in poplar
Authors: Song Chengwei , Guo Yayu , Shen Weiwei , Yao Xiaomin , Xu Huimin , Zhao Yuanyuan , Li Ruili , Lin Jinxing 
Published: March 2023

Abstract
Secondary growth in woody plants generates new cells and tissues via the activity of the vascular cambium and drives the radial expansion of stems and roots. It is regulated by a series of endogenous factors, especially transcription factors. Here, we cloned the basic helix–loop–helix (bHLH) transcription factor gene UNFERTILIZED EMBRYO SAC12 (UNE12) from poplar (Populus alba × Populus glandulosa Uyeki) and used biochemical, molecular, and cytological assays to investigate the biological functions and regulatory mechanism of PagUNE12. PagUNE12 mainly localized in the nucleus and possessed transcriptional activation activity. It was widely expressed in vascular tissues, including primary phloem and xylem and secondary phloem and xylem. Poplar plants overexpressing PagUNE12 showed significantly reduced plant height, shorter internodes, and curled leaves compared with wild-type plants. Optical microscopy and transmission electron microscopy revealed that overexpressing PagUNE12 promoted secondary xylem development, with thicker secondary cell walls than wild-type poplar. Fourier transform infrared spectroscopy, confocal Raman microscopy, and 2D Heteronuclear Single Quantum Correlation analysis indicated that these plants also had increased lignin contents, with a lower relative abundance of syringyl lignin units and a higher relative abundance of guaiacyl lignin units. Therefore, overexpressing PagUNE12 promoted secondary xylem development and increased the lignin contents of secondary xylem in poplar, suggesting that this gene could be used to improve wood quality in the future.
ABRE-BINDING FACTOR3-WRKY DNA-BINDING PROTEIN44 module promotes salinity-induced malate accumulation in pear
Authors: Alabd Ahmed , Cheng Haiyan , Ahmad Mudassar , Wu Xinyue , Peng Lin , Wang Lu , Yang Shulin , Bai Songling , Ni Junbei , Teng Yuanwen 
Published: March 2023

Abstract
Malate impacts fruit acidity and plays a vital role in stress tolerance. Malate accumulation is induced by salinity in various plants as a metabolite in coping with this stress. However, the exact molecular mechanism responsible for salinity-induced malate accumulation remains unclear. Here, we determined that salinity treatment induces malate accumulation in pear (Pyrus spp.) fruit, calli, and plantlets compared to the control. Genetic and biochemical analyses established the key roles of PpWRKY44 and ABRE-BINDING FACTOR3 (PpABF3) transcription factors in promoting malate accumulation in response to salinity. We found that PpWRKY44 is involved in salinity-induced malate accumulation by directly binding to a W-box on the promoter of the malate-associated gene aluminum-activated malate transporter 9 (PpALMT9) to activate its expression. A series of in-vivo and in-vitro assays revealed that the G-box cis-element in the promoter of PpWRKY44 was targeted by PpABF3, which further enhanced salinity-induced malate accumulation. Taken together, these findings suggest that PpWRKY44 and PpABF3 play positive roles in salinity-induced malate accumulation in pears. This research provides insights into the molecular mechanism by which salinity affects malate accumulation and fruit quality.
Neofunctionalization of tandem duplicate genes encoding putative β-L-arabinofuranosidases in Arabidopsis
Authors: Tao Feng , Sollapura Vishwanath , Robert Laurian S , Fan Chuanzhu 
Published: March 2023

Abstract
Tandem duplication, one of the major types of duplication, provides the raw material for the evolution of divergent functions. In this study, we identified 1 pair of tandem duplicate genes (AT5G12950 and AT5G12960) in Arabidopsis (Arabidopsis thaliana) that originated within the last 16 million years after the split of Arabidopsis from the Capsella-Boechera ancestor. We systematically used bioinformatic tools to redefine their putative biochemical function as β-L-arabinofuranosidases that release L-Arabinose from the β-L-Araf-containing molecules in Arabidopsis. Comprehensive transcriptomic and proteomic analyses using various datasets showed divergent expression patterns among tissues between the 2 duplicate genes. We further collected phenotypic data from 2 types of measurements to indicate that AT5G12950 and AT5G12960 have different roles resulting in divergent phenotypic effects. Overall, AT5G12950 and AT5G12960 represent putative β-L-arabinofuranosidase encoding genes in Arabidopsis. After duplication, 1 duplicate copy developed diverged biological functions and contributed to a different phenotypic evolution in Arabidopsis.
Transcription factors GmERF1 and GmWRKY6 synergistically regulate low phosphorus tolerance in soybean
Authors: Wang Ruiyang , Liu Xiaoqian , Zhu Hongqing , Yang Yuming , Cui Ruifan , Fan Yukun , Zhai Xuhao , Yang Yifei , Zhang Shanshan , Zhang Jinyu , Hu Dandan , Zhang Dan 
Published: March 2023

Abstract
Soybean (Glycine max) is a major grain and oil crop worldwide, but low phosphorus (LP) in soil severely limits the development of soybean production. Dissecting the regulatory mechanism of the phosphorus (P) response is crucial for improving the P use efficiency of soybean. Here, we identified a transcription factor, GmERF1 (ethylene response factor 1), that is mainly expressed in soybean root and localized in the nucleus. Its expression is induced by LP stress and differs substantially in extreme genotypes. The genomic sequences of 559 soybean accessions suggested that the allelic variation of GmERF1 has undergone artificial selection, and its haplotype is significantly related to LP tolerance. GmERF1 knockout or RNA interference resulted in significant increases in root and P uptake efficiency traits, while the overexpression of GmERF1 produced an LP-sensitive phenotype and affected the expression of 6 LP stress-related genes. In addition, GmERF1 directly interacted with GmWRKY6 to inhibit transcription of GmPT5 (phosphate transporter 5), GmPT7, and GmPT8, which affects plant P uptake and use efficiency under LP stress. Taken together, our results show that GmERF1 can affect root development by regulating hormone levels, thus promoting P absorption in soybean, and provide a better understanding of the role of GmERF1 in soybean P signal transduction. The favorable haplotypes from wild soybean will be conducive to the molecular breeding of high P use efficiency in soybean.
Acinetobacter baumannii adaptation to the host pH microenvironment is mediated by allelic variation in a single residue of BauA protein
Authors: Li Tao , Luo Deyan , Ning Nianzhi , Liu Xiong , Chen Fanghong , Zhang Liangyan , Bao Chunmei , Li Zhan , Li Deyu , Gu Hongjing , Qu Fen , Yang Xiaolan , Huang Yanyu , Li Boan , Wang Hui 
Published: March 2023

Abstract
Acinetobacter baumannii has been listed as one of the most critical pathogens in nosocomial infections; however, the key genes and mechanisms to adapt to the host microenvironment lack in-depth understanding. In this study, a total of 76 isolates (from 8 to 12 isolates per patient, spanning 128 to 188 days) were longitudinally collected from eight patients to investigate the within-host evolution of A. baumannii. A total of 70 within-host mutations were identified, 80% of which were nonsynonymous, indicating the important role of positive selection. Several evolutionary strategies of A. baumannii to increase its potential to adapt to the host microenvironment were identified, including hypermutation and recombination. Six genes were mutated in isolates from two or more patients, including two TonB-dependent receptor genes (bauA and BJAB07104_RS00665). In particular, the siderophore receptor gene bauA was mutated in multiple isolates from four patients with three MLST types, and all mutations were at amino acid 391 in ligand-binding sites. With 391T or 391A, BauA was more strongly bound to siderophores, which promoted the iron-absorption activity of A. baumannii at acidic or neutral pH, respectively. Through the A/T mutation at site 391 of BauA, A. baumannii displayed two reversible phases to adapt to distinct pH microenvironments. In conclusion, we demonstrated the comprehensive within-host evolutionary dynamics of A. baumannii, and discovered a key mutation of BauA site 391 as a genetic switch to adapt to different pH values, which may represent a model in the pathogen evolutionary adaption of the host microenvironment.
Generalized matter parities from finite modular symmetries
Authors: Kobayashi Tatsuo , Nishimura Satsuki , Otsuka Hajime , Tanimoto Morimitsu , Yamamoto Kei 
Published: March 2023

AbstractWe classify a supersymmetric extension of the Standard Model by discrete symmetries originating from finite modular symmetries ΓN. Since all the couplings in supersymmetric theories of finite modular symmetries ΓN are described by holomorphic modular forms with even modular weights, renormalizable and non-renormalizable operators such as baryon- and/or lepton-number violating operators are severely constrained. From the modular transformation of matter multiplets with modular weight 1/M, we find $\mathbb {Z}_{2M}$ symmetries, including the generalized baryon and lepton parities, R-parity, $\mathbb {Z}_3$ baryon triality and $\mathbb {Z}_6$ proton hexality. Such $\mathbb {Z}_{2M}$ symmetries are enlarged to $\mathbb {Z}_{2M} \rtimes \mathbb {Z}_2^{\text{CP}}$ symmetries together with the CP transformation.
Imperfect Risk Sharing and the Business Cycle
Authors: Berger David , Bocola Luigi , Dovis Alessandro 
Published: March 2023

Abstract
This article studies the macroeconomic implications of imperfect risk sharing implied by a class of New Keynesian models with heterogeneous agents. The models in this class can be equivalently represented as a representative-agent economy with wedges. These wedges are functions of households’ consumption shares and relative wages, and they identify the key cross-sectional moments that govern the impact of households’ heterogeneity on aggregate variables. We measure the wedges using U.S. household-level data and combine them with a representative-agent economy to perform counterfactuals. We find that deviations from perfect risk sharing implied by this class of models account for only 7% of output volatility on average but can have sizable output effects when nominal interest rates reach their lower bound.
N-glycan in the variable region of monoclonal ACPA (CCP-Ab1) promotes the exacerbation of experimental arthritis
Authors: Kawataka Masatoshi , Ouhara Kazuhisa , Kobayashi Eiji , Shinoda Koichiro , Tobe Kazuyuki , Fujimori Ryousuke , Mizuno Noriyoshi , Sugiyama Eiji , Ozawa Tatsuhiko , Kishi Hiroyuki 
Published: March 2023

Abstract

Objectives
The variable region of most ACPA IgG molecules in the serum of RA patients carries N-glycan (N-glycanV). To analyse the pathogenicity of N-glycanV of ACPAs, we analysed the pathogenicity of a monoclonal ACPA, CCP-Ab1, with or without N-glycanV, which had been isolated from a patient with RA.

Methods
CCP-Ab1 with no N-glycosylation site in the variable region (CCP-Ab1 N-rev) was generated, and antigen binding, the effect on in vitro differentiation of osteoclasts from bone marrow mononuclear cells of autoimmune arthritis–prone SKG mice (the cell size of TRAP+ cells and bone resorption capacity) and the in vivo effect on the onset or exacerbation of autoimmune arthritis in SKG mice were evaluated in comparison with glycosylated CCP-Ab1.

Results
Amino acid residues in citrullinated peptide (cfc1), which are essential for binding to CCP-Ab1 N-rev and original CCP-Ab1, were almost identical. The size of TRAP+ cells was significantly larger and osteoclast bone resorption capacity was enhanced in the presence of CCP-Ab1, but not with CCP-Ab1 N-rev. This enhancing activity required the sialic acid of the N-glycan and Fc region of CCP-Ab1. CCP-Ab1, but not CCP-Ab1 N-rev, induced the exacerbation of experimental arthritis in the SKG mouse model.

Conclusions
These data showed that N-glycanV was required for promoting osteoclast differentiation and bone resorption activity in both in vitro and in vivo assays. The present study demonstrated the important role of N-glycanV in the exacerbation of experimental arthritis by ACPAs.
Comparisons of SLE-DAS and SLEDAI-2K and classification of disease activity based on the SLE-DAS with reference to patient-reported outcomes
Authors: Onishi Akira , Tsuji Hideaki , Takase Yudai , Nakakubo Yuto , Iwasaki Takeshi , Kozuki Tomohiro , Yoshida Tsuneyasu , Shirakashi Mirei , Onizawa Hideo , Hiwa Ryosuke , Kitagori Koji , Akizuki Shuji , Nakashima Ran , Yoshifuji Hajime , Tanaka Masao , Morinobu Akio 
Published: March 2023

Abstract

Objectives
Although the SLE Disease Activity Score (SLE-DAS) and its definitions to classify disease activity have been recently developed to overcome the drawbacks of the SLE Disease Activity Index 2000 (SLEDAI-2K), the performance of the SLE-DAS for patient-reported outcomes (PROs) has not been fully examined. We aimed to compare SLE-DAS with SLEDAI-2K and validate the classifications of disease activity based on SLE-DAS in terms of PROs.

Methods
We assessed generic quality of life (QoL) using the Medical Outcome Survey 36-Item Short-Form Health Survey (SF-36), disease-specific QoL using the lupus patient-reported outcome tool (LupusPRO), burden of symptoms using the SLE Symptom Checklist (SSC), patient global assessment (PtGA) and physician global assessment (PhGA).

Results
Of the 335 patients with SLE, the magnitudes of the mean absolute error, root mean square error, Akaike information criterion, and Bayesian information criterion were comparable for most PROs between the SLE-DAS and SLEDAI-2K. In contrast, SLEDAI-2K had a higher predictive value for health-related QoL of LupusPRO and PtGA than SLE-DAS. Low disease activity, Boolean and index-based remission and categories of disease activity (remission, mild and moderate/severe activity) were significantly associated with health-related QoL in LupusPRO, SSC and PhGA, but not SF-36 or PtGA.

Conclusion
No clear differences were identified in the use of the SLE-DAS over the SLEDAI-2K in assessing PROs in patients with SLE. The classification of disease activity based on the SLE-DAS was validated against several PROs. SLE-DAS and its categories of disease activity effectively explain some of the PROs.
‘The Unseen Enemy Persists’: Delusion, Trauma and the South African War in Australian Asylum Case Notes
Authors: Karageorgos Effie 
Published: March 2023

Summary
Australian troops travelling to South Africa in 1899 to join Britain in fighting the Boers left behind communities consumed with the conflict. The colonies that would form the Australian nation in 1901 organised parades, concerts and eagerly awaited news from the battlefield. This article analyses these cultural responses to the South African War alongside the experiences of institutionalised delusional men. It traces ways the conflict penetrated the walls of Australian asylums, and the minds of the insane within them, as well as the sane existing in society. Delusions based on the conflict appeared not only in the words of men who had travelled to South Africa, but also those who were evidently deeply affected by Australian involvement in the war, following the fervour within the societies from which they came. The resulting analysis of the words and experiences of the insane expands the historiography of the conflict in new ways.
How can ultrasonography help in the management of CPPD? From diagnosis to clinical subset identification
Authors: Filippou Georgios , Sirotti Silvia 
Published: March 2023

Purpose of review
Clinical manifestations of calcium pyrophosphate deposition (CPPD) disease are quite heterogeneous, ranging from asymptomatic presentation to severe forms of arthritis. In recent years, imaging, particularly ultrasound (US) has gained a central role for the diagnosis of CPPD. However, many questions are still open. Aim of this review is to present how US could be a key tool in the diagnosis and assessment of CPPD and for the identification of subsets of the disease.

Recent findings
awareness and research interest around CPPD is increasing in the recent years, as several international taskforces are working on the validation of outcome measures and classification criteria for CPPD, but many pieces of the puzzle are still missing. Recent studies demonstrated that CPPD is an underdiagnosed disease, frequently misdiagnosed as rheumatoid arthritis or polymyalgia rheumatica. US has been increasingly used in the past decade for the diagnosis of CPPD and US definitions have been validated by the OMERACT US working group in the recent years, making of US a valuable tool for diagnosis.

Summary
The most challenging aspects of CPPD are the differential diagnosis with other form of arthritis of the elderly, and the classification of patients in clinical subsets. In this review, we will present the available data for the use of US in the diagnosis of CPPD and we will provide a mainly experienced-based approach to the potential role of the technique in differential diagnosis and phenotypization of patients.