bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new perspective on NO pathway in sepsis and ADMA lowering as a potential therapeutic approach
Authors: Singh Jaipal , Lee Young , Kellum John A. 
Published: August 2022

AbstractThe nitric oxide pathway plays a critical role in vascular homeostasis. Increased levels of systemic nitric oxide (NO) are observed in preclinical models of sepsis and endotoxemia. This has led to the postulation that vasodilation by inducible nitric oxide synthase (iNOS) generated NO may be a mechanism of hypotension in sepsis. However, contrary to the expected pharmacological action of a nitric oxide synthase (NOS) inhibitor, clinical studies with L-NAME produced adverse cardiac and pulmonary events, and higher mortality in sepsis patients. Thus, the potential adverse effects of NO in human sepsis and shock have not been fully established. In recent years, the emerging new understanding of the NO pathway has shown that an endogenously produced inhibitor of NOS, asymmetric dimethylarginine (ADMA), a host response to infection, may play an important role in the pathophysiology of sepsis as well as organ damage during ischemia–reperfusion. ADMA induces microvascular dysfunction, proinflammatory and prothrombotic state in endothelium, release of inflammatory cytokines, oxidative stress and mitochondrial dysfunction. High levels of ADMA exist in sepsis patients, which may produce adverse effects like those observed with L-NAME. Several studies have demonstrated the association of plasma ADMA levels with mortality in sepsis patients. Preclinical studies in sepsis and ischemia–reperfusion animal models have shown that lowering of ADMA reduced organ damage and improved survival. The clinical finding with L-NAME and the preclinical research on ADMA “bed to bench” suggest that ADMA lowering could be a potential therapeutic approach to attenuate progressive organ damage and mortality in sepsis. Testing of this approach is now feasible by using the pharmacological molecules that specifically lower ADMA.
Molecular profiling of human non-small cell lung cancer by single-cell RNA-seq
Authors: Li Qingqing , Wang Rui , Yang Zhenlin , Li Wen , Yang Jingwei , Wang Zhijie , Bai Hua , Cui Yueli , Tian Yanhua , Wu Zixin , Guo Yuqing , Xu Jiachen , Wen Lu , He Jie , Tang Fuchou , Wang Jie 
Published: August 2022

AbstractBackgroundLung cancer, one of the most common malignant tumors, exhibits high inter- and intra-tumor heterogeneity which contributes significantly to treatment resistance and failure. Single-cell RNA sequencing (scRNA-seq) has been widely used to dissect the cellular composition and characterize the molecular properties of cancer cells and their tumor microenvironment in lung cancer. However, the transcriptomic heterogeneity among various cancer cells in non-small cell lung cancer (NSCLC) warrants further illustration.MethodsTo comprehensively analyze the molecular heterogeneity of NSCLC, we performed high-precision single-cell RNA-seq analyses on 7364 individual cells from tumor tissues and matched normal tissues from 19 primary lung cancer patients and 1 pulmonary chondroid hamartoma patient.ResultsIn 6 of 16 patients sequenced, we identified a significant proportion of cancer cells simultaneously expressing classical marker genes for two or even three histologic subtypes of NSCLC—adenocarcinoma (ADC), squamous cell carcinoma (SCC), and neuroendocrine tumor (NET) in the same individual cell, which we defined as mixed-lineage tumor cells; this was verified by both co-immunostaining and RNA in situ hybridization. These data suggest that mixed-lineage tumor cells are highly plastic with mixed features of different types of NSCLC. Both copy number variation (CNV) patterns and mitochondrial mutations clearly showed that the mixed-lineage and single-lineage tumor cells from the same patient had common tumor ancestors rather than different origins. Moreover, we revealed that patients with high mixed-lineage features of different cancer subtypes had worse survival than patients with low mixed-lineage features, indicating that mixed-lineage tumor features were associated with poorer prognosis. In addition, gene signatures specific to mixed-lineage tumor cells were identified, includingAKR1B1. Gene knockdown and small molecule inhibition ofAKR1B1can significantly decrease cell proliferation and promote cell apoptosis, suggesting thatAKR1B1plays an important role in tumorigenesis and can serve as a candidate target for tumor therapy of NSCLC patients with mixed-lineage tumor features.ConclusionsIn summary, our work provides novel insights into the tumor heterogeneity of NSCLC in terms of the identification of prevalent mixed-lineage subpopulations of cancer cells with combined signatures of SCC, ADC, and NET and offers clues for potential treatment strategies in these patients.
Early persistence on therapy impacts drug-free remission: a case-control study in a cohort of Hispanic patients with recent-onset rheumatoid arthritis
Authors: Contreras-Yáñez Irazú , Guaracha-Basáñez Guillermo Arturo , Cuevas-Montoya Maximiliano , de Jesús Hernández-Bautista José , Pascual-Ramos Virginia 
Published: August 2022

AbstractBackgroundMedication adherence is suboptimal in rheumatoid arthritis (RA) patients and impacts outcomes. DMARD-free remission (DFR) is a sustainable and achievable outcome in a minority of RA patients. Different factors have been associated with DFR, although persistence in therapy (PT), a component of the adherence construct, has never been examined. The study’s primary aim was to investigate the impact of PT’s characteristics on DFR in a cohort of Hispanic patients with recent-onset RA.MethodsA single data abstractor reviewed the charts from 209 early (symptoms duration ≤ 1 year) RA patients. All the patients had prospective assessments of disease activity and PT and at least 1 year of follow-up, which was required for the DFR definition. DFR was defined when patients achieved ≥ 1 year of continuous Disease Activity Score-28 joints evaluated ≤ 2.6, without DMARDs and corticosteroids. PT was defined based on pre-specified criteria and recorded through an interview from 2004 to 2008 and thereafter through a questionnaire. Cases (patients who achieved ≥ 1 DFR status) were paired with controls (patients who never achieved DFR during their entire follow-up) according to ten relevant variables (1:2). Cox regression analysis estimated hazard ratios (HRs) for DFR according to two characteristics of PT: the % of the patient follow-up PT and early PT (first 2 years of patients’ follow-up).ResultsIn March 2022, the population had 112 (55–181) patient/years follow-up. There were 23 patients (11%) with DFR after 74 months (44–122) of follow-up, and the DFR status was maintained during 48 months (18–82). Early PT was associated with DFR, while the % of the patient follow-up PT was not: HR = 3.84 [1.13–13.07] when the model was adjusted for cumulativeNof DMARDs/patient and 3.16 [1.14–8.77] when also adjusted for baseline SF-36 physical component score. A lowerNof cumulative DMARDs/patient was also retained in the models. Receiving operating curve to define the best cutoff of patient follow-up being PT to predict DFR was 21 months: sensitivity of 0.739, specificity of 0.717, and area under the curve of 0.682 (0.544–0.821).ConclusionsDFR status might be added to the benefits of adhering to prescribed treatment.
Exploring women’s experiences participating in yoga after a cancer diagnosis: a protocol for a meta-synthesis
Authors: Price Jenson , Brunet Jennifer 
Published: August 2022

AbstractBackgroundThe benefits of yoga for clinical and non-clinical populations have been summarized in published systematic reviews. The vast majority of systematic reviews on the topic are syntheses of quantitative research that evaluated the effects of yoga. As qualitative research related to women’s experiences participating in yoga after a cancer diagnosis is growing in quantity, systematic synthesis and integration of qualitative research are necessary to facilitate the transfer of knowledge. This paper describes the protocol for a meta-synthesis of qualitative research exploring women’s experiences participating in yoga after a cancer diagnosis.MethodsUsing a meta-study methodology, six electronic databases were searched to identify relevant articles. Additionally, the reference lists of relevant articles retrieved during the electronic database search were scanned to identify other relevant articles. Two reviewers independently screened the titles and abstracts, retaining those that appeared to relate to the review objectives. Next, they reviewed the retained full-text articles to assess eligibility according to four inclusion criteria. They will extract data from eligible studies and assess the quality of included studies. Data analysis will involve three main analytical steps: meta-data analysis, meta-method analysis, and meta-theory analysis. Findings from the three analytical steps will be interpreted collectively to generate additional insights beyond the findings of the primary studies to facilitate a more comprehensive understanding of women’s experiences participating in yoga after a cancer diagnosis.DiscussionBy systematically collecting, analysing, and interpreting findings across multiple primary qualitative studies, we will develop an overarching narrative and interpretation of the role and value of yoga for women diagnosed with cancer. A synthesis of qualitative research is vital as it embraces the heterogeneity of the research so as to provide important context for understanding the experiences of various women participating in yoga.Systematic review registrationPROSPEROCRD42021229253
Prone position reduces the risk of patients with mild or moderate COVID-19 progressing to severe or even critical cases: a retrospective study
Authors: Xu Chuan-cai , Xu Jia-li , Wang Xiao-fei , Meng Shen , Ye Sheng , Tang Xiao-miao , Lei Wei 
Published: August 2022

Abstract
Background
To investigate whether prone position can reduce the risk of patients with mild or moderate COVID-19 who progress to severe or critical illness.

Methods
The prone position group was treated in prone position on the day of admission in addition to conventional treatment. Indicators such as saturation of pulse oximetry (SpO2), heart rate, blood pressure, respiratory rate, and prone position-related adverse events were recorded before prone ventilation, 5 min after prone position and 30 min after prone position. Meanwhile, the cases of severe and critical patients, the percentage of transformation and the final clinical outcome of this group were analyzed. Conversion rates and mortality were calculated for patients with mild or moderate COVID-19 retrieved from the database who received only conventional care without combined prone positioning as control group.

Results
(1) A total of 34 patients were included in prone position group. There were significant differences in SpO2 between the first 4 days after admission and the day of discharge (F = 3.17, P < 0.001). (2) The main complications were back and neck muscle soreness (55.9%), followed by abdominal distension (8.9%). (3) In control group, a total of 4873 cases of mild and moderate patients were included from 19 literatures, with an average deterioration rate of 22.7% and mortality rate of 1.7%. (4) In prone position group, there were no severe or critical transformation cases and also no death cases. The prone position group had a significantly lower deterioration rate when compared with the control group (χ2 = 9.962, P < 0.01).

Conclusion
Prone position improves SpO2 in patients with mild or moderate COVID-19. It can also reduce the percentage of mild or moderate patients progressing to severe or critical patients. The application of prone position is a simple, feasible, safe and effective treatment method in such patients.
Full automation of total metabolic tumor volume from FDG-PET/CT in DLBCL for baseline risk assessments
Authors: Jemaa S. , Paulson J. N. , Hutchings M. , Kostakoglu L. , Trotman J. , Tracy S. , de Crespigny A. , Carano R. A. D. , El-Galaly T. C. , Nielsen T. G. , Bengtsson T. 
Published: August 2022

AbstractBackgroundCurrent radiological assessments of18fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging data in diffuse large B-cell lymphoma (DLBCL) can be time consuming, do not yield real-time information regarding disease burden and organ involvement, and hinder the use of FDG-PET to potentially limit the reliance on invasive procedures (e.g. bone marrow biopsy) for risk assessment.MethodsOur aim is to enable real-time assessment of imaging-based risk factors at a large scale and we propose a fully automatic artificial intelligence (AI)-based tool to rapidly extract FDG-PET imaging metrics in DLBCL. On availability of a scan, in combination with clinical data, our approach generates clinically informative risk scores with minimal resource requirements. Overall, 1268 patients with previously untreated DLBCL from the phase III GOYA trial (NCT01287741) were included in the analysis (training:n = 846; hold-out:n = 422).ResultsOur AI-based model comprising imaging and clinical variables yielded a tangible prognostic improvement compared to clinical models without imaging metrics. We observed a risk increase for progression-free survival (PFS) with hazard ratios [HR] of 1.87 (95% CI: 1.31–2.67) vs 1.38 (95% CI: 0.98–1.96) (C-index: 0.59 vs 0.55), and a risk increase for overall survival (OS) (HR: 2.16 (95% CI: 1.37–3.40) vs 1.40 (95% CI: 0.90–2.17); C-index: 0.59 vs 0.55). The combined model defined a high-risk population with 35% and 42% increased odds of a 4-year PFS and OS event, respectively, versus the International Prognostic Index components alone. The method also identified a subpopulation with a 2-year Central Nervous System (CNS)-relapse probability of 17.1%.ConclusionOur tool enables an enhanced risk stratification compared with IPI, and the results indicate that imaging can be used to improve the prediction of central nervous system relapse in DLBCL. These findings support integration of clinically informative AI-generated imaging metrics into clinical workflows to improve identification of high-risk DLBCL patients.Trial RegistrationRegistered clinicaltrials.gov number: NCT01287741.Graphical Abstract
Transformation and gene-disruption in the apple-pathogen, Neonectria ditissima
Authors: Vélëz Heriberto , af Sätra Jonas Skytte , Odilbekov Firuz , Bourras Salim , Garkava-Gustavsson Larisa , Dalman Kerstin 
Published: August 2022

Abstract
Background
Apple production in Sweden and elsewhere is being threatened by the fungus, Neonectria ditissima, which causes a disease known as European canker. The disease can cause extensive damage and the removal of diseased wood and heavily infected trees can be laborious and expensive. Currently, there is no way to eradicate the fungus from infected trees and our knowledge of the infection process is limited. Thus, to target and modify genes efficiently, the genetic transformation technique developed for N. ditissima back in 2003 was modified.

Results
The original protocol from 2003 was upgraded to use enzymes currently available in the market for making protoplasts. The protoplasts were viable, able to uptake foreign DNA, and able to regenerate back into a mycelial colony, either as targeted gene-disruption mutants or as ectopic mutants expressing the green fluorescent protein (GFP).

Conclusions
A new genetic transformation protocol has been established and the inclusion of hydroxyurea in the buffer during the protoplast-generation step greatly increased the creation of knockout mutants via homologous recombination. Pathogenicity assays using the GFP-mutants showed that the mutants were able to infect the host and cause disease.
Evaluating surface coatings to reduce bone cement adhesion to point of care 3D printed molds in the intraoperative setting
Authors: Beitler Brian , Roytman Gregory R. , Parmer Grace , Tommasini Steven M. , Wiznia Daniel H. 
Published: August 2022

Abstract
Background
Polymethyl methacrylate, or “bone cement,” can be used intraoperatively to replace damaged or diseased bone and to deliver local antibiotics. 3D printed molds allow surgeons to form personalized and custom shapes with bone cement. One factor hindering the clinical utility of anatomically accurate 3D printed molds is that cured bone cement can be difficult to remove due to the strong adhesion between the mold and the bone cement. One way to reduce the adhesion between the 3D printed mold and the cured bone cement is with the use of a surface coating, such as a lubricant. This study sought to determine the optimal surface coating to prevent bone cement adhesion to 3D printed molds that could be utilized within a sterile operating room environment.

Methods
Hemispheric molds were 3D printed using a stereolithography printer. The molds were coated with four sterile surface coatings available in most operating theatres (light mineral oil, bacitracin ointment, lubricating jelly, and ultrasound transmission gel). Polymethyl methacrylate with tobramycin antibiotic was mixed and poured into the molds. The amount of force needed to “push out” the cured bone cement from the molds was measured to determine the efficacy of each surface coating. Tukey’s multiple comparison test was performed to compare the results of the pushout test.

Results
The average pushout force for the surface coatings, in increasing order, were as follows (mean ± standard deviation) --- bacitracin ointment: 9.10 ± 6.68 N, mineral oil: 104.93 ± 69.92 N, lubricating jelly: 147.76 ± 63.77 N, control group: 339.31 ± 305.20 N, ultrasound transmission gel 474.11 ± 94.77 N. Only the bacitracin ointment required significantly less pushout force than the control (p = 0.0123).

Conclusions
The bacitracin ointment was the most effective surface coating, allowing the bone cement to be pushed out of the mold using the least amount of force. In addition, the low standard deviation speaks to the reliability of the bacitracin ointment to reduce mold adhesion compared to the other surface coatings. Given its efficacy as well as its ubiquitous presence in the hospital operating room setting, bacitracin ointment is an excellent choice to prevent adhesion between bone cement and 3D printed molds intraoperatively.
Calcium carbide–induced derangement of hematopoiesis and organ toxicity ameliorated by cyanocobalamin in a mouse model
Authors: Ouma Pherah A. , Mwaeni Victoria K. , Amwayi Peris W. , Isaac Alfred Orina , Nyariki James Nyabuga 
Published: August 2022

Abstract
Background
Calcium carbide (CaC2) is a chemical primarily used in the production of acetylene gas. The misuse of CaC2 to induce fruit ripening is a global challenge with a potential adverse effects to human health. Additionally, CaC2 is known to contain some reasonable amount of arsenic and phosphorous compounds that are toxic and pose a danger to human health when ingested. The current study sought to characterize CaC2 toxicity and elucidate any protective effects by cyanocobalamin (vitamin B12), a well-established antioxidant and anti-inflammatory bio-molecule. Female Swiss white mice were randomly assigned into three groups; the first group was the control, while the second group was administered with CaC2. The third group received CaC2 followed by administration of vitamin B12. The mice were sacrificed at 60 days post treatment, hematological, biochemical, glutathione assay, cytokine ELISA and standard histopathology was performed.

Results
CaC2 administration did not significantly alter the mice body weight. CaC2 administration resulted in a significant decrease in packed cell volume (PCV), hemoglobin (Hb), red blood cells (RBCs) and RBC indices; indicative of CaC2-driven normochromic microcytic anaemia. Further analysis showed CaC2-driven leukopenia. Evidently, vitamin B12 blocked CaC2-driven suppression of PCV, Hb, RBCs and WBCs. Monocytes and neutrophils were significantly up-regulated by CaC2. CaC2-induced elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and bilirubin signaled significant liver damage. Notably, vitamin B12 stabilized AST, ALT and bilirubin in the presence of CaC2, an indication of a protective effect. Histopathological analysis depicted that vitamin B12 ameliorated CaC2-driven liver and kidney injury. CaC2 resulted in the depletion of glutathione (GSH) levels in the liver; while in the brain, kidney and lungs, the GSH levels were elevated. CaC2 administration resulted in elevation of pro-inflammatory cytokines TNF-α and IFN-γ. Vitamin B12 assuaged the CaC2-induced elevation of these pro-inflammatory cytokines.

Conclusions
These findings demonstrate for the first time that oral supplementation with vitamin B12 can protect mice against CaC2-mediated toxicity, inflammation and oxidative stress. The findings provide vital tools for forensic and diagnostic indicators for harmful CaC2 exposure; while providing useful insights into how vitamin B12 can be explored further as an adjunct therapy for CaC2 toxicity.
Elotuzumab Plus Pomalidomide and Dexamethasone for Relapsed/Refractory Multiple Myeloma: Final Overall Survival Analysis From the Randomized Phase II ELOQUENT-3 Trial
Authors: Dimopoulos Meletios A. , Dytfeld Dominik , Grosicki Sebastian , Moreau Philippe , Takezako Naoki , Hori Mitsuo , Leleu Xavier , LeBlanc Richard , Suzuki Kenshi , Raab Marc S. , Richardson Paul G. , Popa McKiver Mihaela , Jou Ying-Ming , Yao David , Das Prianka , San-Miguel Jesús 
Published: August 2022

PURPOSE In the phase II ELOQUENT-3 trial (ClinicalTrials.gov identifier: NCT02654132 ), elotuzumab combined with pomalidomide/dexamethasone (EPd) significantly improved progression-free survival (PFS) versus pomalidomide/dexamethasone (Pd) in patients with relapsed/refractory multiple myeloma (RRMM) previously treated with lenalidomide and a proteasome inhibitor (PI). Here, we present the final overall survival (OS) results. METHODS Patients with RRMM who had received ≥ 2 prior lines of therapy, with disease refractory to last therapy and either refractory or relapsed and refractory to lenalidomide and a PI were randomly assigned (1:1) to receive EPd or Pd. The primary end point was PFS per investigator assessment. ORR and OS were secondary end points planned to be tested hierarchically. RESULTS A total of 117 patients were randomly assigned to EPd (n = 60) and Pd (n = 57). Among treated patients (EPd 60, Pd 55), there were 37 (61.7%) deaths in the EPd group and 41 (74.5%) in the Pd group, most commonly because of disease progression (EPd 41.7%, Pd 49.1%). Median (95% CI) OS was significantly improved with EPd (29.8 [22.9 to 45.7] months) versus Pd (17.4 [13.8 to 27.7] months), with a hazard ratio of 0.59 (95% CI, 0.37 to 0.93; P = .0217). OS benefit with EPd was observed in most patient subgroups. The safety profile of EPd was consistent with prior reports with no new safety signals detected. CONCLUSION EPd demonstrated a statistically significant improvement in OS versus Pd in patients with RRMM previously treated with lenalidomide and a PI who had disease refractory to last therapy. In this setting, ELOQUENT-3 is the first randomized study of a triplet regimen incorporating a monoclonal antibody and Pd to improve both PFS and OS significantly.