bluuebunny/crossref_metadata_2025_split huggingface dataset:
The escape of CRISPR-mediated gene editing inZymomonas mobilis
Authors: Chen Mao , Huang Yuhuan , Zheng Yudi , Wu Bo , He Mingxiong 
Published: January 2023

AbstractClustered Regularly Interspaced Short Palindromic Repeats (CRISPR) systems have been widely applied for gene or genome editing. Adequate checking is important to screen mutants after CRISPR-mediated editing events. Here, we report gene escape cases after the knockout by Type I-F native CRISPR system in Zymomonas mobilis. Through amplifying both the gene of interest and its flanking homologous arms, followed by curing the editing plasmid, we found different destinies for gene-editing events. Some genes were readily knocked out and followed by the easy plasmid curing. In some other cases, however, the editing plasmid was difficult to remove from the cell, or the deleted genes were transferred into the editing plasmid. For example, the targeted region of fur can be integrated into the editing plasmid after the knockout, resulting in a spurious editing event. We supposed that the transfer of the gene may be attributed to bacterial insertion sequences. Searching for literatures on the gene knockout using CRISPR in bacteria reveals that the escape event is likely underestimated due to inadequate validation in other microbes. Hence, several strategies are proposed to enhance gene knockout and plasmid curing.
The Decision Trees Method to Support the Choice of Economic Evaluation Procedure: The Case of Protection Forests
Authors: Bruzzese Stefano , Blanc Simone , Brun Filippo 
Published: January 2023

Abstract
The adoption of nature-based solutions, such as forests, is playing an increasingly important role in risk analysis and related decision-making. However, decision-makers struggle to put a value on the services provided by these solutions, as there is no reference market, and are thus faced with several challenges, which relate to the choice of the best forest management program or the interventions needed to make a forest resistant and resilient to the expected negative impacts of ongoing climate change. In this article, we started with an exploratory analysis to identify the key factors in the choice of an economic method to build predictive models to support the choice in an evaluation of the forest protection service against natural hazards. The exploratory analysis showed that non-demand-based methods have a good degree of replicability and reliability and are cheaper, whereas stated preference methods can estimate the intangible component. Concerning predictive models, almost all methods showed a high level of correct classification (95%), apart from the avoided damages method (90%) and, more generally, there is no method that is valid for all operational contexts but rather the choice changes depend on the demands made by the stakeholders and their availability in economic, human, and technological terms. In conclusion, it should be remembered that the methodological framework chosen should not be seen as a substitute for the human ability to analyze complex situations but rather as an aid to this process.
Study Implications: The adoption of decision support systems and methodological frameworks and guidelines can help decision-makers to make the most effective and efficient choices, in terms of time needed, resources used, and intervention costs. The combination of this decision support system with other tools, such as frameworks and guidelines, provides a flexible support system aimed at improving the design and implementation of future ecosystem service assessments and management as well as related decision-making.
Risk Variants in or NearZBTB40ANDNFATC1Increase the Risk of Both IBD and Adverse Bone Health Outcomes Highlighting Common Genetic Underpinnings Across Both Diseases
Authors: Cushing Kelly C , Chen Yanhua , Du Xiaomeng , Chen Vincent , Kuppa Annapurna , Higgins Peter , Speliotes Elizabeth K 
Published: January 2023

AbstractBackgroundInflammatory bowel disease (IBD) is associated with an increased risk of osteoporosis and bone fracture. The aims of this study were to (1) confirm the association between IBD and low bone density and (2) test for shared risk variants across diseases.MethodsThe study cohort included patients from the Michigan Genomics Initiative. Student’s t tests (continuous) and chi-square tests (categorical) were used for univariate analyses. Multivariable logistic regression was performed to test the effect of IBD on osteoporosis or osteopenia. Publicly available genome-wide association summary statistics were used to identify variants that alter the risk of IBD and bone density, and Mendelian randomization (MR) was used to identify causal effects of genetically predicted IBD on bone density.ResultsThere were 51 405 individuals in the Michigan Genomics Initiative cohort including 10 378 (20.2%) cases of osteoporosis or osteopenia and 1404 (2.7%) cases of IBD. Patients with osteoporosis or osteopenia were more likely to be older (64 years of age vs 56 years of age; P &lt; .001), female (67% vs 49%; P &lt; .001), and have a lower body mass index (29 kg/m2 vs 30 kg/m2; P &lt; .001). IBD patients with (odds ratio, 4.60; 95% confidence interval, 3.93-5.37) and without (odds ratio, 1.77; 95% confidence interval, 1.42-2.21) steroid use had a significantly higher risk of osteoporosis or osteopenia. Twenty-one IBD variants associated with reduced bone mineral density at P ≤ .05 and 3 IBD risk variants associated with reduced bone mineral density at P ≤ 5 × 10-8. Of the 3 genome-wide significant variants, 2 increased risk of IBD (rs12568930-T: MIR4418;ZBTB40; rs7236492-C: NFATC1). MR did not reveal a causal effect of genetically predicted IBD on bone density (MR Egger, P = .30; inverse variance weighted, P = .63).ConclusionsPatients with IBD are at increased risk for low bone density, independent of steroid use. Variants in or near ZBTB40 and NFATC1 are associated with an increased risk of IBD and low bone density.
Comparison of a Novel Thin-Walled 25-gauge Needle Push Button Blood Collection Set to a Standard 23-gauge Needle in a Cancer Patient Population
Authors: Kirchhoff Daniel , Baser Raymond , Kwong David , Ramanathan Lakshmi , McCash Samuel I 
Published: January 2023

Abstract

Background
Phlebotomy can be an uncomfortable and even painful experience that increases in likelihood in patients who require frequent blood draws, such as those with cancer. The 25-gauge BD Vacutainer® UltraTouch™ Push Button Blood Collection Set has a smaller outer bore needle size and unique bevel configuration, which in theory should reduce pain associated with phlebotomy. Smaller needles typically cause less pain, however, they have a higher incidence of compromising the specimen integrity. Innovative engineering allows this particular needle to maintain a larger inner bore size similar to a standard 23-gauge needle. This study compares pain and specimen integrity between this novel device and a standard 23-gauge needle.

Methods
Two cohorts of 190 patients each had phlebotomy performed with either needle. Pain experienced was assessed by patient surveys, rating pain from 0 (low) to 10 (high). Sample integrity was assessed by determining the hemolysis index (Abbott Architect c8000).

Results
No statistically significant difference in median pain scores was observed between the 2 cohorts, P-value: 0.068. The 23-gauge cohort more frequently reported 3+ pain than the 25-gauge cohort, 14/190 vs 5/190. Pain scoring 1 and 2 was more frequent in the 25-gauge cohort, 84/190 vs 54/190. Pain scores of 0 were more frequent in the 23-gauge cohort, 122/190 vs 101/190. This stratification is statistically significant, P-value: 0.003. The 25-gauge needle showed no increase in hemolysis rates, P-value: 0.5.

Conclusions
Sample integrity was identical between both needles. The 25-gauge needle resulted in less 3+ pain, while pain scoring 1 and 2 was more frequent in the 25-gauge cohort.
Women’s Fertility and Labor Market Responses to a Health Innovation
Authors: Bhalotra Sonia , Venkataramani Atheendar , Walther Selma 
Published: January 2023

AbstractWe investigate women’s fertility, labor, and marriage market responses to a health innovation that led to reductions in mortality from treatable causes, and especially large declines in child mortality. We find delayed childbearing, with lower intensive and extensive margin fertility, a decline in the chances of ever having married, increased labor force participation, and an improvement in occupational status. Our results provide the first evidence that improvements in child survival allow women to start fertility later and invest more in the labor market. We present a new theory of fertility that incorporates dynamic choices and reconciles our findings with existing models of behavior.
The Canadian Society for Immunology's 34th annual meeting 2022: symposia minireview
Authors: Carter Emily B , Pugh-Toole Morgan , Kabil Ahmed , Boudreau Jeanette E , Nersesian Sarah 
Published: January 2023

Abstract
The Canadian Society for Immunology 2022 Annual Meeting (June 17–20, 2022) brought together immunologists from across the country to discuss current topics and cutting-edge research in immunology. Here we highlight the published work presented during three thematic symposia (1) Immune Development and Layered Immunity; (2) Primary Immune Deficiencies from Thymic Developmental Defects to Dysregulation and Inflammation; and (3) Opposing Inflammatory and Suppressive Regulation of Anti-Tumor Immunity.
Observer error in grassland vegetation surveys: effects on species diversity metrics and species–abundance relationships
Authors: Morrison Lloyd W , Leis Sherry A , DeBacker Michael D 
Published: January 2023

AbstractWe investigated the effect of observer error on four commonly used species diversity measures: species richness, Shannon–Weiner diversity, Shannon–Weiner evenness and Simpson’s index of diversity. We also evaluated how observer error affects inferences derived from multivariate analyses of species–abundance relationships as determined by non-metric multidimensional scaling (NMS) ordination. Grassland vegetation was sampled by three different botanists at two national park units in Missouri and Kansas, USA. The same plots were sampled by two of the botanists, who compiled lists of species composition and estimated foliar cover. Differences in the data records were then compared. Pseudoturnover (i.e. apparent turnover due to observer error) ranged from 17.1% to 22.1%, and differences in cover class estimation ranged from 21.5% to 30.5%. The percentage difference in species diversity measures between pairs of observers depended on how data were summarized, but were always &lt;20%, and often &lt;10%. Based on these results, species diversity metrics are affected to a relatively smaller extent by observer error than turnover indices. Turnover indices, however, contain more information because they track individual species, whereas species are interchangeable in most species diversity indices. Thus, less of the error is identified because of how species diversity indices are calculated. NMS ordinations revealed that while the characterizations of some plots by different observers were similar, differences between observers’ records for other plots resulted in greater separation in ordination space. Points representing one observer’s records were often shifted in ordination space in the same direction compared with the other observer.
Sophorolipids produced by Yarrowia lipolytica grown on Moringa oleifera oil cake protect against acetic acid-induced colitis in rats: impact on TLR-4/p-JNK/NFκB-p65 pathway
Authors: Nooman Mohamed U , Al-kashef Amr S , Rashad Mona M , Khattab Abd El-Nasser A , Ahmed Kawkab A , Abbas Samah S 
Published: January 2023

Abstract

Objectives
Toll-like receptor-4 (TLR-4) activation plays a major role in triggering oxidative stress (OS) and inflammation implicated in the pathogenesis of ulcerative colitis (UC). Due to sophorolipids (SLs) antioxidant and anti-inflammatory properties, they are interestingly becoming more valued for their potential effectiveness in treating a variety of diseases. This study was designed to explore the effect of SLs produced by microbial conversion of Moringa oleifera oil cake using isolated yeast Yarrowia lipolytica against UC induced by acetic acid (AA) in rats.

Methods
The produced SLs were identified by FTIR, 1H NMR and LC-MS/MS spectra, and administered orally for 7 days (200 mg/kg/day) before AA (2 ml, 4% v/v) to induce UC intrarectally on day eight. Biochemically, the levels of TLR-4, c-Jun N-terminal kinase (JNK), nuclear factor kappa B-p65 (NFκB-p65), interleukin-1beta (IL-1β), malondialdehyd, glutathione, Bax/Bcl2 ratio and the immunohistochemical evaluation of inducible nitric oxide synthase and caspase-3 were assayed.

Key findings
SLs significantly reduced OS, inflammatory and apoptotic markers in AA-treated rats, almost like the reference sulfasalazine.

Conclusions
This study provided a novel impact for SLs produced by microbial conversion of M. oleifera oil cake against AA-induced UC in rats through hampering the TLR-4/p-JNK/NFκB-p65 signalling pathway.
Long-term evaluation of E6011, an anti-fractalkine monoclonal antibody, in patients with rheumatoid arthritis inadequately responding to biological disease-modifying antirheumatic drugs
Authors: Tanaka Yoshiya , Takeuchi Tsutomu , Yamanaka Hisashi , Nanki Toshihiro , Umehara Hisanori , Yasuda Nobuyuki , Tago Fumitoshi , Kitahara Yasumi , Kawakubo Makoto , Torii Kentaro , Hojo Seiichiro , Kawano Tetsu , Imai Toshio 
Published: January 2023

ABSTRACT

Objectives
The objective of the study is to evaluate the long-term safety and efficacy of E6011, a humanized anti-fractalkine monoclonal antibody, in patients with rheumatoid arthritis with an inadequate response to biological disease-modifying antirheumatic drugs.

Methods
In the double-blind treatment phase (24 weeks), placebo or E6011 400 mg was administered until Week 10. Thereafter, E6011 200 mg or 400 mg was administered to Week 22. Subjects who completed the evaluation at Week 24 of the treatment phase were rolled over into the extension phase. The extension phase lasted until Week 104, and all subjects received E6011 400 mg or 200 mg every 2 weeks in an open-label manner until Week 102.

Results
A total of 47 subjects completed the double-blind treatment phase and were rolled over into the extension phase. In total, 46 (97.9%) subjects experienced any adverse events, and the incidence of treatment-related adverse events was 57.4%. No clear efficacy trend in the American College of Rheumatology 20% response rates was observed.

Conclusions
E6011 was well tolerated in active rheumatoid arthritis patients who had shown an inadequate response to biologic disease-modifying antirheumatic drugs, but no clear benefit in the American College of Rheumatology 20% response rates was observed. Further studies are needed to clarify the clinical benefit of E6011.
Factors associated with osteoporosis and fractures in patients with systemic lupus erythematosus: Kyoto Lupus Cohort
Authors: Nakajima Tomoya , Doi Hiroshi , Watanabe Ryu , Murata Koichi , Takase Yudai , Inaba Ryuta , Itaya Takahiro , Iwasaki Takeshi , Shirakashi Mirei , Tsuji Hideaki , Kitagori Koji , Akizuki Shuji , Nakashima Ran , Onishi Akira , Yoshifuji Hajime , Tanaka Masao , Ito Hiromu , Hashimoto Motomu , Ohmura Koichiro , Morinobu Akio 
Published: January 2023

ABSTRACT

Objectives
Osteoporosis and compression fractures of the lumbar spine are some of the major adverse effects of glucocorticoid therapy in patients with systemic lupus erythematosus (SLE). This study examined the association between bone mineral density, bone turnover markers, presence of vertebral fractures, and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index in SLE patients.

Methods
This was a cross-sectional study of 246 outpatients with SLE at the Kyoto University Hospital. Lumbar and femoral bone mineral density was measured with dual-energy X-ray absorptiometry, and the presence of vertebral fractures was determined using X-ray, computed tomography, or magnetic resonance imaging.

Results
On multiple regression analysis, both high lumbar and femoral T-scores were associated with the concomitant use of hydroxychloroquine (P = .018 and P = .037, respectively), no use of bisphosphonate or denosumab (P = .004 and P = .038, respectively), high body mass index (P &lt; .001), and low bone-specific alkaline phosphatase level (P = .014 and P = .002, respectively). Vertebral fractures showed a significant association with Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index score (P &lt; .001) and femoral T-score (P &lt; .001).

Conclusion
Vertebral fracture was associated with SLE-associated organ damage, and serum bone-specific alkaline phosphatase level is a potentially useful marker for osteoporosis monitoring in SLE patients.
GBMdeconvoluteR accurately infers proportions of neoplastic and immune cell populations from bulk glioblastoma transcriptomics data
Authors: Ajaib Shoaib , Lodha Disha , Pollock Steven , Hemmings Gemma , Finetti Martina A , Gusnanto Arief , Chakrabarty Aruna , Ismail Azzam , Wilson Erica , Varn Frederick S , Hunter Bethany , Filby Andrew , Brockman Asa A , McDonald David , Verhaak Roel G W , Ihrie Rebecca A , Stead Lucy F 
Published: January 2023

Abstract

Background
Characterizing and quantifying cell types within glioblastoma (GBM) tumors at scale will facilitate a better understanding of the association between the cellular landscape and tumor phenotypes or clinical correlates. We aimed to develop a tool that deconvolutes immune and neoplastic cells within the GBM tumor microenvironment from bulk RNA sequencing data.

Methods
We developed an IDH wild-type (IDHwt) GBM-specific single immune cell reference consisting of B cells, T-cells, NK-cells, microglia, tumor associated macrophages, monocytes, mast and DC cells. We used this alongside an existing neoplastic single cell-type reference for astrocyte-like, oligodendrocyte- and neuronal progenitor-like and mesenchymal GBM cancer cells to create both marker and gene signature matrix-based deconvolution tools. We applied single-cell resolution imaging mass cytometry (IMC) to ten IDHwt GBM samples, five paired primary and recurrent tumors, to determine which deconvolution approach performed best.

Results
Marker-based deconvolution using GBM-tissue specific markers was most accurate for both immune cells and cancer cells, so we packaged this approach as GBMdeconvoluteR. We applied GBMdeconvoluteR to bulk GBM RNAseq data from The Cancer Genome Atlas and recapitulated recent findings from multi-omics single cell studies with regards associations between mesenchymal GBM cancer cells and both lymphoid and myeloid cells. Furthermore, we expanded upon this to show that these associations are stronger in patients with worse prognosis.

Conclusions
GBMdeconvoluteR accurately quantifies immune and neoplastic cell proportions in IDHwt GBM bulk RNA sequencing data and is accessible here: https://gbmdeconvoluter.leeds.ac.uk.
Phytochrome F mediates red light responsiveness additively with phytochromes B1 and B2 in tomato
Authors: Balderrama Daniel , Barnwell Samantha , Carlson Keisha D , Salido Elsa , Guevara Ruby , Nguyen Christina , Madlung Andreas 
Published: January 2023

AbstractPhytochromes are red light and far-red light sensitive, plant-specific light receptors that allow plants to orient themselves in space and time. Tomato (Solanum lycopersicum) contains a small family of five phytochrome genes, for which to date stable knockout mutants are only available for three of them. Using CRISPR technology, we created multiple alleles of SlPHYTOCHROME F (phyF) mutants to determine the function of this understudied phytochrome. We report that SlphyF acts as a red/far-red light reversible low fluence sensor, likely through the formation of heterodimers with SlphyB1 and SlphyB2. During photomorphogenesis, phyF functions additively with phyB1 and phyB2. Our data further suggest that phyB2 requires the presence of either phyB1 or phyF during seedling de-etiolation in red light, probably via heterodimerization, while phyB1 homodimers are required and sufficient to suppress hypocotyl elongation in red light. During the end-of-day far-red response, phyF works additively with phyB1 and phyB2. In addition, phyF plays a redundant role with phyB1 in photoperiod detection and acts additively with phyA in root patterning. Taken together, our results demonstrate various roles for SlphyF during seedling establishment, sometimes acting additively, other times acting redundantly with the other phytochromes in tomato.
A systematic review on suicide because of social isolation/and loneliness: does COVID-19 make a difference?
Authors: Blázquez-Fernández Carla , Lanza-León Paloma , Cantarero-Prieto David 
Published: January 2023

Abstract

Background
Suicide is a significant cause of death worldwide. Various purposes can explain why people choose to attempt or commit suicide such as mental-health disorders, income-related-factors, quality of life or issues related to social context. This study aims to identify an updated association between ‘isolation’ and suicides.

Methods
In this regard, we had made a systematic review of the most recent papers, published from January 2016 to March 2022, thought the most acknowledged databases. This review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for systematic reviews. To the best of our knowledge, this issue is very important due to the indirect relationship between COVID-19 and suicides.

Results
Our analysis demonstrates that suicide and -social isolation and loneliness- have a positive and direct relationship although these findings varied slightly by areas. Moreover, most of the attention is focused on the youth during the most recent period and this is a real problem because economies cannot afford losing (young) population.

Conclusions
In order to prevent suicides, public policies should prevent suicidal thoughts that it could induce to terminate the lives of individuals in their most productive years and harmful outcomes to their families and friends.
Primary Cutaneous Peripheral T-Cell Lymphoma With Follicular Helper T-Cell Phenotype: Report of 2 Epstein–Barr Virus–Positive Cases
Authors: Chiang Chien-Ta , Chuang Shih-Sung , Lin Hsuen-Fu , Li Wei-Hsuan , Chiang Ying-Yi , Chen Bo-Jung 
Published: January 2023

Abstract:
Primary cutaneous T-cell lymphoma is distinct from nodal T-cell lymphoma clinically and pathologically. Recently, primary cutaneous follicular helper T-cell lymphoma (PC-TFHL) has been described as a peripheral T-cell lymphoma with T-follicular helper (TFH) cell phenotype. PC-TFHL usually presents as multiple plaques and nodules of skin with an indolent clinical course, but without association with Epstein–Barr virus. In this article, we report 2 rare cases of PC-TFHL which are Epstein–Barr virus–positive and with an aggressive clinical course. We discuss the challenges in the differential diagnoses, particularly with primary cutaneous extranodal NK/T-cell lymphoma, and nodal T-cell lymphoma of TFH origin with secondary cutaneous involvement.