bluuebunny/crossref_metadata_2025_split huggingface dataset:
How I treat transplant-eligible patients with myelofibrosis
Authors: Kröger Nicolaus , Wolschke Christine , Gagelmann Nico 
Published: August 2023

Abstract
Despite the approval of Janus kinase inhibitors and novel agents for patients with myelofibrosis (MF), disease-modifying responses remain limited, and hematopoietic stem cell transplantation (HSCT) remains the only potentially curative treatment option. The number of HSCTs for MF continues to increase worldwide, but its inherent therapy-related morbidity and mortality limit its use for many patients. Furthermore, patients with MF often present at an older age, with cytopenia, splenomegaly, and severe bone marrow fibrosis, posing challenges in managing them throughout the HSCT procedure. Although implementation of molecular analyses enabled improved understanding of disease mechanisms and subsequently sparked development of novel drugs with promising activity, prospective trials in the HSCT setting are often lacking, making an evidence-based decision process particularly difficult. To illustrate how we approach patients with MF with respect to HSCT, we present 3 different clinical scenarios to capture relevant aspects that influence our decision making regarding indication for, or against, HSCT. We describe how we perform HSCT according to different risk categories and, furthermore, discuss our up-to-date approach to reduce transplant-related complications. Last, we show how to harness graft-versus-MF effects, particularly in the posttransplant period to achieve the best possible outcomes for patients.
DHODH: a promising target in the treatment of T-cell acute lymphoblastic leukemia
Authors: Sexauer Amy N. , Alexe Gabriela , Gustafsson Karin , Zanetakos Elizabeth , Milosevic Jelena , Ayres Mary , Gandhi Varsha , Pikman Yana , Stegmaier Kimberly , Sykes David B. 
Published: August 2023

Abstract
Patients with relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL) have a poor prognosis with few therapeutic options. With the goal of identifying novel therapeutic targets, we used data from the Dependency Map project to identify dihydroorotate dehydrogenase (DHODH) as one of the top metabolic dependencies in T-ALL. DHODH catalyzes the fourth step of de novo pyrimidine nucleotide synthesis. Small molecule inhibition of DHODH rapidly leads to the depletion of intracellular pyrimidine pools and forces cells to rely on extracellular salvage. In the absence of sufficient salvage, this intracellular nucleotide starvation results in the inhibition of DNA and RNA synthesis, cell cycle arrest, and, ultimately, death. T lymphoblasts appear to be specifically and exquisitely sensitive to nucleotide starvation after DHODH inhibition. We have confirmed this sensitivity in vitro and in vivo in 3 murine models of T-ALL. We identified that certain subsets of T-ALL seem to have an increased reliance on oxidative phosphorylation when treated with DHODH inhibitors. Through a series of metabolic assays, we show that leukemia cells, in the setting of nucleotide starvation, undergo changes in their mitochondrial membrane potential and may be more highly dependent on alternative fuel sources. The effect on normal T-cell development in young mice was also examined to show that DHODH inhibition does not permanently damage the developing thymus. These changes suggest a new metabolic vulnerability that may distinguish these cells from normal T cells and other normal hematopoietic cells and offer an exploitable therapeutic opportunity. The availability of clinical-grade DHODH inhibitors currently in human clinical trials suggests a potential for rapidly advancing this work into the clinic.
Phase 1 study of vibecotamab identifies an optimized dose for treatment of relapsed/refractory acute myeloid leukemia
Authors: Ravandi Farhad , Bashey Asad , Foran James , Stock Wendy , Mawad Raya , Short Nicholas , Yilmaz Musa , Kantarjian Hagop , Odenike Olatoyosi , Patel Anand , Garcha Raman , Ainsworth William Barrett , Clynes Raphael , Kanodia Jitendra , Ding Ying , Li Huajiang , Kye Steve , Mims Alice 
Published: August 2023

Abstract
Acute myeloid leukemia (AML), an aggressive malignancy with unmet medical need, lacks immunotherapeutic options. CD123, the cellular receptor for interleukin-3, expressed in AML is an attractive target for tumor-specific therapy. Vibecotamab (XmAb14045), a humanized bispecific antibody, monovalently binds both CD3 and CD123 to recruit cytotoxic T cells to kill CD123+ tumor cells. This phase 1 study’s primary objectives were safety and tolerability and identification of a maximum tolerated dose/recommended dose for use as monotherapy in patients with relapsed/refractory AML. Identification of a recommended phase 2 vibecotamab dose comprised 3 step-up doses (Week 1), which were noted to reduce cytokine response syndrome (CRS), followed by weekly dosing (1.7 μg/kg, Cohort -1D). In 16 of 120 patients, at least 1 treatment-emergent adverse event was classified as a dose-limiting toxicity. CRS, the most common adverse event (59.2%), managed with premedication, were mostly ≤grade 2. A secondary objective was assessment of efficacy in patients with CD123-expressing leukemias. A total of 10 of 111 (9.0%) efficacy-evaluable patients with AML achieved an overall response of morphologic leukemia-free state or better with an overall objective response rate (ORR) of 9.0%. Response was only observed in patients receiving a target dose of 0.75 μg/kg or higher (n = 87) in which the efficacy-evaluable ORR was 11.5%. Response was associated with lower baseline blast counts in blood and bone marrow (&lt;25%) suggesting potential benefit. This trial was registered at www.clinicaltrials.gov as #NCT02730312.
Improving the lightfastness and thermal stability of black urushi (oriental lacquer) by kraft lignin oleate
Authors: Tsuchiya Takao , Narita Chieko , Yamada Kazushi , Moreno Adrian , Sipponen Mika H. , Tsuda Hitomi , Okahisa Yoko 
Published: August 2023

AbstractUrushi, an oriental lacquer, is sensitive to light and easily deteriorates upon light exposure, leading to the fading and loss of gloss of its coatings. In this study, we attempted to improve the lightfastness of black urushi by utilizing the UV-absorbing properties of kraft lignin. Oleic acid-esterified kraft lignin was prepared and added to the black urushi to improve the compatibility. No aggregation of oleic acid-esterified lignin occurred in the black urushi, and the physical properties of the films were maintained to a large extent. A possible chemical interaction between lignin and black urushi was suggested upon thermal analysis. It was also found that the addition of lignin improved the thermal dimensional stability of black urushi. Finally, the high gloss factor of the black urushi film was maintained by adding oleic acid-esterified lignin after 168 h of light irradiation. Oleic acid-esterified lignin therefore appears as a promising functional additive to improve photostability of urushi coatings.
Clinical characterization of patients with HLA-B27-associated uveitis and evaluation of the impact of systemic treatment on the recurrence rate: a cross-sectional study
Authors: Pineda-Sierra Juan Sebastián , Cifuentes-González Carlos , Rojas-Carabali William , Muñoz-Vargas Paula Tatiana , Henao-Posada Alejandro , de-la-Torre Alejandra 
Published: August 2023

Abstract
Introduction
Despite HLA-B27-associated uveitis is one of the most frequent etiologies of uveitis worldwide, there are scarce studies on the clinical spectrum of this disease and the implications of therapeutic strategies used in the Latin-American population, with none conducted in Colombia. Thus, this study aimed to describe the clinical characteristics of a cohort of patients with positive HLA-B27-associated uveitis in Colombia and evaluate the impact of systemic treatment on the recurrence rate.

Methods
We retrospectively reviewed 490 clinical charts of patients with uveitis, searching for those with positive HLA-B27-associated uveitis over eight years in a referral center in Bogotá, Colombia. We used descriptive statistics to summarize demographic and clinical characteristics and conducted a Chi-square test, Fisher Exact test, Spearman correlation, and Mann–Whitney test to assess associations between treatment strategies and the recurrences rate.

Results
We analyzed 39 patients (59% females) with positive HLA-B27-associated uveitis, with a median age at the first consultation of 44.5 years (Range: 2–80) and a mean follow-up time of 86.4 weeks (1.65 years). Most patients had unilateral uveitis (53.8%) and an anterior anatomical diagnosis (76.6%); two had anterior chamber fibrinous reaction, and only one had hypopyon. Most patients did not show associated systemic symptoms (66.7%). Topical corticosteroids, NSAIDs, methotrexate, mydriatics, and adalimumab were the most used treatments. The most common complications included cataracts, posterior synechiae, and macular edema. We identified that the rate of recurrences decreases over time (r = -0.6361, P = 0.002571), and this decrease seems to be associated with the initiation of disease-modifying antirheumatic drugs (DMARDs) in chronic and recurrent cases.

Conclusion
The clinical spectrum of HLA-B27-associated uveitis in Colombian patients is distinct from other latitudes. Notably, we found a female predominance, older age at presentation, higher frequency of bilateral and vitreous involvement, and lower frequency of concomitant systemic diseases. Additionally, our results suggest that DMARDs such as methotrexate and biologic agents are good therapeutic options to avoid recurrences in chronic and recurrent cases.
Complete-genome sequencing and comparative genomic characterization of blaNDM-5 carrying Citrobacter freundii isolates from a patient with multiple infections
Authors: Ye Jianzhong , Jin Lulu , Li Yaling , Xu Hao , Lin Yishuai , Zhou Tieli , Zheng Beiwen , Wang Maofeng , Wang Zhongyong 
Published: August 2023

Abstract
Background
The emergence and wide spread of carbapenemase-producing Enterobacteriaceae (CPE) poses a growing threat to global public health. However, clinically derived carbapenemase-producing Citrobacter causing multiple infections has rarely been investigated. Here we first report the isolation and comparative genomics of two blaNDM-5 carrying Citrobacter freundii (C. freundii) isolates from a patient with bloodstream and urinary tract infections.

Results
Antimicrobial susceptibility testing showed that both blaNDM-5 carrying C. freundii isolates were multidrug-resistant. Positive modified carbapenem inactivation method (mCIM) and EDTA-carbapenem inactivation method (eCIM) results suggested metallo-carbapenemase production. PCR and sequencing confirmed that both metallo-carbapenemase producers were blaNDM-5 positive. Genotyping and comparative genomics analyses revealed that both isolates exhibited a high level of genetic similarity. Plasmid analysis confirmed that the blaNDM-5 resistance gene is located on IncX3 plasmid with a length of 46,161 bp, and could successfully be transferred to the recipient Escherichia coli EC600 strain. A conserved structure sequence (ISAba125-IS5-blaNDM-5-trpF-IS26-umuD-ISKox3) was found in the upstream and downstream of the blaNDM-5 gene.

Conclusions
The data presented in this study showed that the conjugative blaNDM-5 plasmid possesses a certain ability to horizontal transfer. The dissemination of NDM-5-producing C. freundii isolates should be of close concern in future clinical surveillance. To our knowledge, this is the first study to characterize C. freundii strains carrying the blaNDM-5 gene from one single patient with multiple infections.
Opioid prescribing for acute postoperative pain: an overview of systematic reviews related to two consensus statements relevant at patient, prescriber, system and public health levels
Authors: McCorquodale C. L. , Greening R. , Tulloch R. , Forget P. 
Published: August 2023

Abstract
Background
National guidelines for rational opioid prescribing for acute postoperative pain are needed to optimise postoperative pain control and function whilst minimising opioid-related harm.

Objectives
This overview of systematic reviews aims to summarise and critically assess the quality of systematic reviews related to the 20 recommendations from two previously published consensus guideline papers (ten relevant at patient and prescriber levels and ten at a system / Public Health level). It also aims to identify gaps in research that require further efforts to fill these in order to augment the evidence behind creating national guidelines for rational opioid prescribing for acute postoperative pain.

Methods
A systematic database search using PubMed/MEDLINE and Cochrane was conducted in November 2022. Furthermore, reference lists were reviewed. All identified systematic reviews were assessed for eligibility. Data from each study was extracted using a pre-standardised data extraction form. The methodological quality of the included reviews was assessed by two independent reviewers using the AMSTAR 2 checklist. Descriptive synthesis of the results was performed.

Results
A total of 12 papers were eligible for analysis. Only eight out of the total 20 prioritised recommendations had systematic reviews that provided evidence related to them. These systematic reviews were most commonly of critically low quality.

Conclusion
The consensus papers provide guidance and recommendations based on the consensus of expert opinion that is based on the best available evidence. However, there is a lack of evidence supporting many of these consensus statements. Efforts to further analyse interventions that aim to reduce the rates of opioid prescribing and their adverse effects should therefore continue.
Primary care services in the English NHS: are they a thorn in the side of integrated care systems? A qualitative analysis
Authors: Mitchell Claire , Higgerson James , Tazzyman Abigail , Whittaker Will 
Published: August 2023

Abstract
Background
As integrated care systems are embedded across England there are regions where the integration process has been evaluated and continues to evolve. Evaluation of these integrated systems contributes to our understanding of the challenges and facilitators to this ongoing process. This can support integrated care systems nationwide as they continue to develop. We describe how two integrated care partnerships in different localities, at differing stages of integration with contrasting approaches experienced challenges specifically when integrating with primary care services. The aim of this analysis was to focus on primary care services and how their existing structures impacted on the development of integrated care systems.

Methods
We carried out an exploratory approach to re-analysing our previously conducted 51 interviews as part of our prior evaluations of integrated health and care services which included primary care services. The interview data were thematically analysed, focussing on the role and engagement of primary care services with the integrated care systems in these two localities.

Results
Four key themes from the data are discussed: (i) Workforce engagement (engagement with integration), (ii) Organisational communication (information sharing), (iii) Financial issues, (iv) Managerial information systems (data sharing, IT systems and quality improvement data). We report on the challenges of ensuring the workforce feel engaged and informed. Communication is a factor in workforce relationships and trust which impacts on the success of integrated working. Financial issues highlight the conflict between budget decisions made by the integrated care systems when primary care services are set up as individual businesses. The incompatibility of information technology systems hinders integration of care systems with primary care.

Conclusions
Integrated care systems are national policy. Their alignment with primary care services, long considered to be the cornerstone of the NHS, is more crucial than ever. The two localities we evaluated as integration developed both described different challenges and facilitators between primary care and integrated care systems. Differences between the two localities allow us to explore where progress has been made and why.
Gastrıc cancer surgery in elderly patients: promising results from a mid-western population
Authors: Yazici Hilmi , Esmer Ahmet Cem , Eren Kayaci Ayse , Yegen Sevket Cumhur 
Published: August 2023

Abstract
Backgrounds
Extended resection for gastric cancer in elderly patients is still challenging for surgeons. This study aimed to evaluate the prognosis and the postoperative outcomes of elderly patients underwent gastric cancer surgery in a high-volume center.

Methods
The medical records of patients with gastric cancer surgery at Marmara University Hospital’s General Surgery Department were examined retrospectively. Patients were divided into two groups: Age ≤ 70 and Age > 70. The clinicopathological data of the patients were compared. The prognostic factors regarding gastric cancer surgery were analyzed with Cox proportional regression models. Kaplan Meier analysis and log-rank test were used to compare Overall Survival (OS) and Cancer-Specific Survival (CSS) among the groups. Competing risk regression analysis was used to examine cause-specific hazards among elderly patients.

Results
The number of eligible patients was 250. Age > 70 group was 68 patients, and Age ≤ 70 group was 182 patients. There is no significant difference between the patient’s demographics or pathological outcomes. Neoadjuvant therapies performed less in elderly patients [40 (22%) vs. 7 (10%), p: 0.03, respectively]. There was no significant difference in severe complication (≥ Grade III) rates in both groups. Multivariate analysis showed that advanced T stage and adjacent organ invasion were the independent risk factors for OS. No significant difference was observed between the groups regarding OS (Log Rank (Mantel-Cox): 0.102). Younger patients have worse CSS than those who are older. Cause-specific hazard model demonstrated a not increased hazard ratio [HR: 1.04(0.78–1.38)] for elderly patients for OS and CSS.

Conclusion
Gastric resections can be safely performed for elderly patients diagnosed with gastric cancer. This study showed that growing age is no longer a factor that will affect the clinician’s decision in performing surgery in gastric cancer patients.
Association between all-cause mortality and trajectories across quality and duration of sleep and cognitive function: based on Group-Based Multivariate Trajectory modeling
Authors: Lin Jianlin , Xiao Jian , Li Qiao , Cao Li 
Published: August 2023

AbstractBackgroundSleep duration and quality are associated with cognition, but the interaction of the 3 indicators and their association with all-cause mortality is unclear.MethodsWe used data from the Chinese Longitudinal Healthy Longevity Survey from 2005–2018 to identify latent trajectories of sleep duration, sleep quality, and cognitive function. Secondly, the multinomial logistic model was adopted to determine predictors of trajectory groups. Finally, the Cox regression model was used to examine the association between these trajectory groups and all-cause mortality.ResultsA total of 5046 adults (49% women) with an average age of 76.34 were included in the study. The median follow-up period was 11.11 years, during which 1784 (35%) participants died. We identified 4 latent groups among older adults: ‘Good-performance’ (51%), ‘Decreasing’ (26%), ‘Oversleep & cognitive impairment’ (12%), and ‘Sleep-deprived’ (11%). Individuals in the ‘Decreasing’ had a 51% increased risk of all-cause mortality (HR = 1.51, 95% CI: 1.25 – 1.81,p < .001). Individuals in the ‘Oversleep & cognitive impairment’ had a 170% increased risk of all-cause mortality (HR = 2.7 95% CI: 2.13 – 3.43,p < .001). Women had a higher risk of all-cause mortality regardless of trajectory group (47–143% men VS. 74–365% women). Both urban and rural areas have a similarly increased risk of all-cause mortality (48–179%).ConclusionsOur study reveals the latent trajectories across sleep duration, sleep quality, and cognitive function in older Chinese and further explores their association with death. These findings provide a rational basis for cognitive interventions and reduce all-cause mortality.
Older adults, clinicians, and researchers’ preferences for measuring adherence to resistance and balance exercises
Authors: McArthur Caitlin , Duhaime Gabriella , Gonzalez David , Notthoff Nanna , Theou Olga , Kehler Scott , Quigley Adria 
Published: August 2023

Abstract
Background
Resistance and balance training are important exercise interventions for older populations living with chronic diseases. Accurately measuring if an individual is adhering to exercises as prescribed is important to determine if lack of improvement in health outcomes is because of issues with adherence. Measuring adherence to resistance and balance exercises is limited by current methods that depend heavily on self-report and are often better at and tailored towards capturing aerobic training parameters (e.g., step count, minutes of moderate to vigorous physical activity). Adherence measures must meet users’ needs to be useful.

Methods
Using a Dillman tailored study design, we surveyed researchers who conduct exercise trials, clinicians who prescribe exercise for older adults, and older adults to determine: (1) how they are currently measuring adherence; (2) barriers and facilitators they have experienced to measurement; and (3) the information they would like collected about adherence (e.g., repetitions, sets, intensity, duration, frequency, quality). Surveys were disseminated internationally through professional networks, professional organizations, and social media. Participants completed an online survey between August 2021 and April 2022.

Results
Eighty-eight older adults, 149 clinicians, and 41 researchers responded to the surveys. Most clinicians and researchers were between the ages of 30 and 39 years, and 70.0% were female. Most older adults were aged 70–79 years, and 46.6% were female. Diaries and calendars (either analog or digital) were the most common current methods of collecting adherence data. Users would like information about the intensity and quality of exercises completed that are presented in clear, easy to use formats that are meaningful for older adults where all data can be tracked in one place. Most older adults did not measure adherence because they did not want to, while clinicians most frequently reported not having measurement tools for adherence. Time, resources, motivation, and health were also identified as barriers to recording adherence.

Conclusions
Our work provides information about current methods of measuring exercise adherence and suggestions to inform the design of future adherence measures. Future measures should comprehensively track adherence data in one place, including the intensity and quality of exercises.