bluuebunny/crossref_metadata_2025_split huggingface dataset:
Momelotinib long-term safety and survival in myelofibrosis: integrated analysis of phase 3 randomized controlled trials
Authors: Verstovsek Srdan , Mesa Ruben , Gupta Vikas , Lavie David , Dubruille Viviane , Cambier Nathalie , Platzbecker Uwe , Hus Marek , Xicoy Blanca , Oh Stephen T. , Kiladjian Jean-Jacques , Vannucchi Alessandro M. , Gerds Aaron , Egyed Miklos , Mayer Jiří , Sacha Tomasz , Kawashima Jun , Morris Marc , Huang Mei , Harrison Claire 
Published: July 2023

Abstract
Momelotinib is the first inhibitor of Janus kinase 1 (JAK1) and JAK2 shown to also inhibit activin A receptor type 1 (ACVR1), a key regulator of iron homeostasis, and has demonstrated improvements in splenomegaly, constitutional symptoms, and anemia in myelofibrosis (MF). This long-term analysis pooled data from 3 randomized phase 3 studies of momelotinib (MOMENTUM, SIMPLIFY-1, and SIMPLIFY-2), representing MF disease from early (JAK inhibitor–naive) to late (JAK inhibitor–experienced) stages. Patients in the control arms (danazol in MOMENTUM, ruxolitinib in SIMPLIFY-1, and best available therapy in SIMPLIFY-2) could cross over to receive momelotinib at the end of the 24-week randomized period, and all patients could continue momelotinib treatment after the completion of these studies via an extended access protocol (XAP). Across these studies, 725 patients with MF received momelotinib; 12% remained on therapy for ≥5 years, with a median treatment exposure of 11.3 months (range, 0.1-90.4 months). The most common nonhematologic treatment-emergent adverse event (AE) occurring in ≥20% of patients was diarrhea (any grade, 27% and grade ≥3, 3%). Any-grade thrombocytopenia, anemia, and neutropenia occurred in 25%, 23%, and 7% of patients, respectively. The most common reason for momelotinib discontinuation was thrombocytopenia (4% discontinuation rate). The incidence of AEs of clinical importance (eg, infections, malignant transformation, peripheral neuropathy, and hemorrhage) did not increase over time. This analysis of one of the largest randomized trial databases for a JAK inhibitor to date in MF demonstrated a consistent safety profile of momelotinib without long-term or cumulative toxicity. These trials were registered at www.clinicaltrials.gov as: MOMENTUM (#NCT04173494), SIMPLIFY-1 (#NCT01969838), SIMPLIFY-2 (#NCT02101268), and XAP (#NCT03441113).
Tissue factor activates the coagulation cascade in mouse models of acute promyelocytic leukemia
Authors: Hisada Yohei , Kawano Tomohiro , Archibald Sierra J. , Welch John S. , Reeves Brandi N. , Mackman Nigel 
Published: July 2023

Abstract
Acute promyelocytic leukemia (APL) is associated with a high risk of bleeding and thrombosis. APL patients have an activated coagulation system, hyperfibrinolysis, and thrombocytopenia. APL cells express tissue factor (TF), a receptor and cofactor for factor VII/VIIa. This study had 2 goals. Firstly, we measured biomarkers of coagulation and fibrinolysis activation as well as platelet counts and bleeding in both mouse xenograft and allograft models of APL. Secondly, we determined the effect of inhibiting TF on the activation of coagulation in these models. We observed increased levels of plasma thrombin-antithrombin complexes (TAT), D-dimer, and plasmin-antiplasmin complexes, reduced platelet counts, and increased tail bleeding in both mouse models of APL. Fibrinogen levels decreased in the xenograft model but not in the allograft model. In contrast, the red blood cell count decreased in the allograft model but not in the xenograft model. Inhibition of APL-derived human TF with an anti-human TF monoclonal antibody reduced the level of TAT, increased platelet count, and normalized tail bleeding in a xenograft model. Inhibition of all sources of TF (APL cells and host cells) in the allograft model with a rat anti-mouse TF monoclonal antibody decreased the levels of TAT but did not affect the platelet count. Our study demonstrates that TF plays a central role in the activation of coagulation in both the xenograft and allograft mouse models of APL. These APL mouse models can be used to investigate the mechanisms of coagulopathy and thrombocytopenia in APL.
Heterologous production and secretion of active-form plant peroxidase in Brevibacillus choshinensis and their monolignol polymerization abilities analysis
Authors: Ishikura Hinako , Konishi Yuka , Miura Jun , Dohi Moeka , Kawai Shinya 
Published: July 2023

AbstractPlant peroxidases are important for several processes, such as defense against pathogens, and auxin metabolism. In this study, we report the active production and secretion of plant peroxidase and mutated enzymes in the bacterium Brevibacillus choshinensis for the first time in the world. We introduced mutations into prxA3a, an anionic peroxidase gene of hybrid aspen, Populus × kitakamiensis, to substitute the amino acid residues at the surface of the protein and analyzed their modified substrate specificities. We have also reported heterologous expression of PrxA3a and mutated enzymes in yeast. Enzymes secreted in the culture medium by B. chosinensis were purified by Ni affinity chromatography, anion-exchange chromatography, and size-exclusion chromatography. The ability of the mutated enzymes to polymerize sinapyl alcohol, a monolignol, was higher than that of the wild-type enzyme. In particular, the FYAW-mutated enzyme produced by the bacterium showed higher polymerization activity, similar to that of the FYAW-mutated enzyme produced by yeast.
Physician-staffed prehospital units: a retrospective follow-up from an urban area in Scandinavia
Authors: Strandqvist Erik , Olheden Staffan , Bäckman Anders , Jörnvall Henrik , Bäckström Denise 
Published: July 2023

Abstract
Background
The aim of this study was to determine when and how rapid response vehicles (RRVs) make a difference in prehospital care by investigating the number and kinds of RRV assignment dispatches and the prehospital characteristics and interventions involved.

Methods
This retrospective cohort study was based on data from a quality assurance system where all assignments are registered. RRV staff register every assignment directly at the site, using a smartphone, tablet, or computer. There is no mandatory information requirement or time limit for registration. The study includes data for all RRVs operating in Region Stockholm, three during daytime hours and one at night – from January 1, 2021 to December 31, 2021.

Results
In 2021, RRVs in Stockholm were dispatched on 11,283 occasions, of which 3,571 (31.6%) resulted in stand-downs. In general, stand-downs were less common for older patients. The most common dispatch category was blunt trauma (1,584 or 14.0%), which accounted for the highest frequency of stand-downs (676 or 6.0%). The second most common category was cardiac arrest (1,086 or 9.6%), followed by shortness of breath (691 or 6.1%), medical not specified (N/S) (596 or 5.3%), and seizures (572 or 5.1%).

Conclusion
The study findings confirm that RRVs provide valuable assistance to the ambulance service in Stockholm, especially for cardiac arrest and trauma patients. In particular, RRV personnel have more advanced medical knowledge and can administer medications and perform interventions that the regular ambulance service cannot provide.
A novel nomogram and risk stratification system predicting the cancer-specific survival of patients with gastric neuroendocrine carcinoma: a study based on SEER database and external validation
Authors: Song Xue , Xie Yangyang , Lou Yafang 
Published: July 2023

Abstract
Background
Gastric neuroendocrine carcinoma (GNEC) is a rare histology of gastric cancer. The retrospective study was designed to construct and validate a nomogram for predicting the cancer-specific survival (CSS) of postoperative GNEC patients.

Methods
Data for 28 patients from the Hangzhou TCM Hospital were identified as the external validation cohort. A total of 1493 patients were included in the SEER database and randomly assigned to the training group (1045 patients) and internal validation group (448 patients). The nomogram was constructed using the findings of univariate and multivariate Cox regression studies. The model was evaluated by consistency index (C-index), calibration plots, and clinical net benefit. Finally, the effect between the nomogram and AJCC staging system was compared by net reclassification index (NRI) and integrated discrimination improvement (IDI).

Results
Age, gender, grade, T stage, N stage, metastasis, primary site, tumor size, RNE, and chemotherapy were incorporated in the nomogram. The C-indexes were 0.792 and 0.782 in the training and internal verification sets. The 1-, 3-, and 5-year CSS predicted by the nomogram and actual measurements had good agreement in calibration plots. The 1-, 3-, and 5-year NRI were 0.21, 0.29, and 0.37, respectively. The 1-, 3-, and 5-year IDI values were 0.10, 0.12, and 0.13 (P < 0.001), respectively. In 1-, 3-, and 5-year CSS prediction using DCA curves, the nomogram outperformed the AJCC staging system. The nomogram performed well in both the internal and external validation cohorts.

Conclusion
We developed and validated a nomogram to predict 1-, 3-, and 5-year CSS for GNEC patients after surgical resection. This well-performing model could help doctors enhance the treatment plan.
A population-based cohort study on changes in breast, lung and colorectal cancer incidence and mortality among non-Western immigrant women
Authors: Lamminmäki Maarit , Leivonen Aku , Heinävaara Sirpa , Nygård Mari , Ursin Giske , Campbell Suzanne , Stefansdóttir Hrefna , Hirvonen Elli , Toikkanen Salla , Vejborg Ilse Merete Munk , Njor Sisse Helle , Sarkeala Tytti 
Published: July 2023

Abstract
Background
Cancer risk varies geographically, and migrants are influenced by different risk factors before, during and after migration. Increased migration from non-Western countries to the Nordic countries calls for a better understanding of the migrants’ cancer risk and the change in risk patterns over time. The aim of this study was to compare the incidence and mortality of breast, colorectal and lung cancer between non-Western immigrant and the native female population in Denmark, Finland, Iceland, and Norway.

Material and methods
Data from national registries were processed and pre-analysed in each country. Multivariate Poisson regression models were used to model the relative differences in incidence and mortality as rate ratios (RR). The country-specific estimates and summary statistics were pooled together using a random effects model.

Results
Non-Western immigrant women had significantly lower breast (RR 0.71, 0.65–0.78), colorectal (RR 0.72, 0.57–0.92) and lung (RR 0.55, 0.42–0.72) cancer incidence rates than native women, and the risk of these cancers among immigrant women increased with duration of residence. Differences were parallel in breast, colorectal and lung cancer mortality (RR 0.64, 0.55–0.74; RR 0.66, 0.48–0.92; RR 0.51, 0.34–0.79). Among immigrant women, higher education increased the risk for breast cancer and decreased it for lung cancer.

Conclusion
The results significantly complement and add to the previous findings of cancer burden and cancer burden transition among migrants and provide evidence of a prolonged cancer risk advantage among non-Western immigrant women. However, the findings show an increasing risk of lifestyle-related cancers with increasing duration of residence in the host country. Further studies are needed to discover underlying reasons for this phenomenon.
Severe macular complications in glaucoma: high-resolution multimodal imaging characteristics and review of the literature
Authors: Lama Hugo , Pâques Michel , Brasnu Emmanuelle , Vu Jade , Chaumette Céline , Dupas Bénédicte , Fardeau Christine , Chehaibou Ismaël , Rouland Jean-François , Besombes Guillaume , Labetoulle Marc , Labbé Antoine , Rousseau Antoine 
Published: July 2023

Abstract
Purpose
To describe imaging characteristics of severe macular complications occurring in glaucoma and discuss available treatments.

Methods
Retrospective case series of glaucomatous patients with macular retinoschisis (MR) and/or serous retinal detachment (SRD). Patients underwent a complete ophthalmological examination and multimodal imaging including retinography, SD-OCT, fluorescein and indocyanine green angiography (FA & ICGA) and adaptive optics (AO).

Results
Ten eyes (8 patients) were included. Initial BCVA was 1.04 ± 1.12 logMAR and IOP was 24.0 ± 9.3mmHg. All eyes presented with MR while SRD was present in 5 eyes (5 patients), with a central macular thickness of 573 ± 152 μm. FA and ICGA allowed to exclude leakage in all cases. A focal lamina cribrosa defect (LCD) was found in four eyes (4 patients) using OCT, with AO providing en-face visualization of the defect in one eye. Outer retinal hole was present in 3 eyes (3 patients). No visual improvement or resolution of the macular retinoschisis was observed in eyes with medical or surgical IOP control (N = 9). Vitrectomy with internal membrane limiting peeling and gas tamponade was performed in one eye with good visual results.

Conclusions
Multimodal high-resolution imaging is essential to diagnose severe macular complications associated with advanced glaucoma.
The efficacy and safety of varenicline nasal spray for the management of dry eye signs: a systematic review and meta-analysis
Authors: Bashrahil Bader , Taher Nada , Alzahrani Ziyad , Alnabihi Ahmed , Aldahlawi Abdulaziz , Alkhathlan Mohammed , Alghamdi Saeed 
Published: July 2023

AbstractBackgroundDry eye disease (DED) is caused by a persistently unstable tear film leading to ocular discomfort and is treated mainly with tear supplementation. There is emerging evidence that nicotinic acetylcholine receptor (nAChR) agonists (e.g., varenicline and simpinicline) nasal sprays are effective for DED. Our systematic review and meta-analysis assessed the efficacy and safety of varenicline nasal spray (VNS) for DED treatment.MethodsThe Medline, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched. Only randomized controlled trials (RCTs) that evaluated the efficacy of VNS versus placebo were included. The efficacy endpoint was the mean change in the anesthetized Schirmer test score (STS), a measure of basal tear production, from baseline. The safety endpoints were serious adverse events (SAEs) and adverse events (AEs). The standardized mean difference (SMD) was used for continuous outcomes, while the risk ratio (RR) was used to demonstrate dichotomous variables. The certainty of the evidence was rated utilizing the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The risk of bias assessment was conducted using the Revised Cochrane risk of bias tool for randomized trials.ResultsThree RCTs (n = 1063) met the eligibility criteria. All RCTs had a low risk of bias. The meta-analysis found a statistically significant increase in the mean STS change from baseline on day 28. The pooled analysis found no significant difference between VNS and placebo in the frequency of SAEs and ocular AEs. However, VNS had a significant effect on developing nasal cavity-related AEs.ConclusionVNS caused a highly significant improvement regarding the efficacy endpoint but caused an increased frequency of some nasal cavity-related AEs (i.e., cough and throat irritation). However, it caused neither SAEs nor ocular AEs. Included studies had a low risk of bias.
The impact of neighborhood mental health on the mental health of older adults
Authors: Gong Rengui , Xia Dongping , Hu Zan , Hu Yangming 
Published: July 2023

Abstract
Background
In this article, we use cross-sectional data obtained from the 2018 China Health and Aging Tracking Survey (CHARLS) to examine the impact of neighborhood mental health at the community level on the mental health of older adults aged 60 years and older.

Methods
NMH is the average mental health of older adults in the same community, excluding the older adults themselves. The explained variable mental health in this paper was measured using the simple CES-D depression scale. The mediating variables were social connectedness, social participation and social inclusion, and the instrumental variables were physical exercise and amusement. regression analysis was conducted using OLS regression models, two-stage least squares (IV-2SLS) instrumental variables to address the two-way causality of NMH and MH, and KHB decomposition was used to investigate the effect mechanism.

Results
Baseline regressions showed that the neighborhood mental health effect positively influenced the mental health of older adults (Coef. = 0.356, 95% CI 0.315,0.397). The neighborhood mental health effect estimated by IV-2SLS (Coef. = 0.251, 95% CI 0.096,0.405) was higher than the OLS regression, indicating endogeneity. The mediated effects of KHB showed total (Coef. = 0.356, 95% CI 0.314,0.398), direct (Coef. = 0.281, 95% CI 0.232,0.330), and indirect effects (Coef. = 0.075, 95% CI 0.049,0.101). While the total effect was 1.266 times higher than the direct effect, 21.03% of the total effect came from mediating variables.

Conclusions
First, the neighborhood mental health effect has a positive impact on the mental health of older adults, but there are heterogeneous differences based on gender, age, and place of residence. Second, the results of the IV-2SLS estimation showed that the effect of the neighborhood mental health effect was underestimated if endogenous problems were not controlled for. Third, the effect of neighborhood mental health on older adults' mental health was tested to be stable. Moreover, social connectedness, social participation, and social interaction are important mediating mechanisms for the effect of neighborhood mental health on older adults' mental health. This study provides new perspectives and ideas for an in-depth understanding of the mental health of older adults in the context of social transformation in China.
Effectiveness of health promotion intervention on the knowledge and selected practices related with oral cancer among a group of vulnerable youth in Sri Lanka
Authors: Dhanapriyanka Manori , RDFC Kanthi , Jayasekara Prasanna 
Published: July 2023

AbstractBackgroundThere has been a noticeable trend of younger people being diagnosed with oral cancer, particularly among those from low socio-economic backgrounds. Poor knowledge on risk factors toward oral cancer and the growing fashion of using tobacco also identified among younger generation. Present study aimed to assess the effectiveness of a health promotion intervention to improve the knowledge and encourage positive practices associated with oral cancer among a group of vulnerable youth in Sri Lanka.MethodsThe study was a community based quasi experimental study, conducted in urban slums in the district of Colombo, Sri Lanka. Sample size for one group was 120 youth participants aged between 15 and 24 years. Health promotion intervention was implemented to the intervention group and follow up period was 6 months. The control group did not receive the intervention. Awareness of oral cancer and oral potentially malignant disorders, tobacco chewing practice (betel quid chewing and commercially prepared tobacco and areca nut packet (CPTAP) chewing) and self-mouth examination practice were assessed at the beginning and after 6 months in both groups using an interviewer administered questionnaire. Changes in the knowledge, self-mouth examination practice, quit rate and fresh up take rate were computed to determine the effectiveness.ResultsThere was no loss to follow up. No significant difference was observed between the groups in pre intervention assessment regarding the knowledge, tobacco chewing and self-mouth examination practices. Knowledge score was significantly differed between the groups P = 0.000 in the post intervention assessment as well as among females P = 0.001. Quit rate of the tobacco chewing practice, betel chewing practice and CPTAP chewing practice among intervention group was 33%, 70%, and 13% respectively while control group did not have any quitters, P = 0.001. Fresh up take rate of tobacco chewing in the intervention group was 6.7% compared to the 37.5% in the control group, P = 0.001. Practicing self-mouth examination was significantly higher in intervention group in post intervention assessment, P = 0.000.ConclusionMulticomponent health promotion intervention (Advocacy, Interactive discussions, IEC materials and Community mobilization) was significantly effective in enhancing the knowledge, increasing self-mouth examination practice, and reducing tobacco chewing practice among a vulnerable group of youth in Sri Lanka.
Abnormal adenosine metabolism of neutrophils inhibits airway inflammation and remodeling in asthma model induced by Aspergillus fumigatus
Authors: Liu Ting-ting , Wang Yue-li , Zhang Zhi , Jia Li-xin , Zhang Jing , Zheng Shuai , Chen Zhi-hua , Shen Hua-hao , Piao Chun-mei , Du Jie 
Published: July 2023

Abstract
Background
Neutrophils consume a large amount of energy when performing their functions. Compared with other white blood cells, neutrophils contain few mitochondria and mainly rely on glycolysis and gluconeogenesis to produce ATP. The inflammatory site is hypoxic and nutrient poor. Our aim is to study the role of abnormal adenosine metabolism of neutrophils in the asthmatic airway inflammation microenvironment.

Method
In this study, an asthma model was established by intratracheal instillation of Aspergillus fumigatus extract in Ecto-5'-Nucleotidase (CD73) gene–knockout and wild-type mice. Multiple analyses from bronchoalveolar lavage fluid (BALF) were used to determine the levels of cytokines and chemokines. Immunohistochemistry was used to detect subcutaneous fibrosis and inflammatory cell infiltration. Finally, adenosine 5’-(α, β-methylene) diphosphate (APCP), a CD73 inhibitor, was pumped subcutaneously before Aspergillus attack to observe the infiltration of inflammatory cells and subcutaneous fibrosis to clarify its therapeutic effect.

Result
PAS staining showed that CD73 knockout inhibited pulmonary epithelial cell proliferation and bronchial fibrosis induced by Aspergillus extract. The genetic knockdownof CD73 significantly reduced the production of Th2 cytokines, interleukin (IL)-4, IL-6, IL-13, chemokine (C–C motif) ligand 5 (CCL5), eosinophil chemokine, neutrophil IL-17, and granulocyte colony-stimulating factor (G-CSF). In addition, exogenous adenosine supplementation increased airway inflammation. Finally, the CD73 inhibitor APCP was administered to reduce inflammation and subcutaneous fibrosis.

Conclusion
Elevated adenosine metabolism plays an inflammatory role in asthma, and CD73 could be a potential therapeutic target for asthma.