bluuebunny/crossref_metadata_2025_split huggingface dataset:
OUTREACH: phase 2 study of lisocabtagene maraleucel as outpatient or inpatient treatment at community sites for R/R LBCL
Authors: Linhares Yuliya , Freytes Cesar O. , Cherry Mohamad , Bachier Carlos , Maris Michael , Hoda Daanish , Varela Juan C. , Bellomo Courtney , Cross Scott , Essell James , Fanning Suzanne , Terebelo Howard , Yimer Habte , Courtright Jay , Sharman Jeff P. , Kostic Ana , Vedal Min , Ogasawara Ken , Avilion Ariel , Espinola Ricardo , Yuan Brenda , Mattar Bassam 
Published: September 2024

Abstract
Lisocabtagene maraleucel (liso-cel) is an autologous, CD19-directed, 4-1BB chimeric antigen receptor (CAR) T-cell product approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). We present the OUTREACH primary analysis, evaluating the safety and efficacy of outpatient monitoring after liso-cel treatment at community sites in the United States. Adults with R/R LBCL after ≥2 prior lines of therapy received liso-cel. Outpatient vs inpatient monitoring was per investigator discretion. The primary end points were incidences of grade ≥3 cytokine release syndrome (CRS), neurological events (NEs), prolonged cytopenia, and infections. Efficacy was a secondary end point. Eighty-two patients received liso-cel (outpatient monitored, 70%; inpatient monitored, 30%). The median follow-up was 10.6 months (range, 1.0-24.5). In outpatients and inpatients, grade ≥3 CRS occurred in 0% and 0%, NEs in 12% and 4%, infections in 12% and 8%, and prolonged cytopenia in 33% and 32%, respectively. Among outpatients, 25% were never hospitalized after infusion, and 32% were hospitalized ≤72 hours after the day of infusion; the median time to hospitalization was 5.0 days (range, 2-310). The median initial hospitalization duration after liso-cel was 6.0 days (range, 1-28) for outpatients and 15.0 days (range, 3-31) for inpatients. Objective response rate was 80%, complete response rate was 54%, and the median duration of response was 14.75 months (95% confidence interval, 5.0 to not reached). OUTREACH is, to our knowledge, the first and largest study to prospectively assess CAR T-cell therapy with outpatient monitoring in community-based medical centers. Liso-cel demonstrated meaningful efficacy with favorable safety in patients with R/R LBCL. Data support the feasibility of liso-cel administration at community sites with outpatient monitoring. This trial was registered at www.ClinicalTrials.gov as #NCT03744676.
Efficacy and safety of TPO receptor agonists in treatment of ITP associated with predominantly antibody deficiencies
Authors: Soulard Margaux , Galicier Lionel , Mahlaoui Nizar , Fieschi Claire , Deshayes Samuel , Gobert Delphine , Gourguechon Clément , Henique Hélène , Humbert Sebastien , Lacout Carole , Le Calloch Ronan , Michel Marc , Piel-julian Marie-lea , Viallard Jean François , Lescoat Alain , Godeau Bertrand , Perlat Antoinette 
Published: September 2024

Abstract
Predominantly antibody deficiencies have an estimated prevalence of &gt;1 in 25 000. Their classical phenotype entails the association of autoimmune manifestations with increased susceptibility to infections. Up to 8% of these patients ultimately develop immune thrombocytopenic purpura (ITP). Reducing the risk for infections and considering nonimmunosuppressive treatments, such as thrombopoietin receptor agonists (TPO-RAs), are important considerations for these patients. This nationwide retrospective case series assessed the outcomes and safety of TPO-RAs as treatment for ITP in adults diagnosed with predominantly antibody deficiencies. Response and complete response to treatment were defined as platelet count reaching 30 × 109/L and 100 × 109/L, respectively. We analyzed data from 28 patients. The median follow-up time after introduction of the first TPO-RAs was 33 months (range, 2 weeks to 10.6 years). After 6 weeks of follow-up, response was achieved in 24 of the 28 patients (85.7%), and among those, 21 patients (75%) displayed a complete response. At the last available follow-up visit, only 7 patients (25%) needed second-line therapies for ITP, and among those, only 5 patients (17.9%) received immunosuppressants. Only 3 patients (10.7%) reported laboratory-confirmed hepatobiliary adverse events of light or mild severity and 3 patients (10.7%) reported thrombotic events. In conclusion, TPO-RAs seemed to be an effective and safe option of treatment in these case series. Our results suggest that eltrombopag or romiplostim should be considered as second-line therapy for ITP related to predominantly antibody deficiencies.
Cycle route uptake and scenario estimation (CRUSE): an approach for developing strategic cycle network planning tools
Authors: Lovelace Robin , Talbot Joey , Vidal-Tortosa Eugeni , Mahfouz Hussein , Brick Elaine , Wright Peter , O’Toole Gary , Brennan Dan , Meade Suzanne 
Published: September 2024

AbstractThis paper describes an approach for developing strategic cycle network planning tools. Based on our experience developing and deploying the Cycle Route Uptake and Scenario Estimation (CRUSE) Tool for Ireland, we outline the underlying methods, including disaggregation of origin–destination data with the open source ‘odjitter’ software, incorporation of additional trip purposes, routing, scenario generation, and development of an intuitive user interface that is tested and used by practitioners. Commissioned by the national infrastructure agency Transport Infrastructure Ireland, CRUSE provides estimates of current and potential future cycling levels under ‘snapshot’ scenarios to inform investment decisions. The publicly available results at https://cruse.bike/ enable planners, engineers, and other stakeholders to make more evidence-based decisions. CRUSE goes beyond previous work by: modeling networks at high spatial resolution; simulating multiple trip purposes (social, shopping, personal utility, recreational, and cycle touring), supplementing official origin–destination datasets on travel for work and education; and providing estimates of ‘quietness’ (a proxy for cyclist comfort and route preference) at the route segment level. Three network types—‘Fastest’, ‘Balanced’, and ‘Quietest’—help plan both arterial and residential cycle networks. Workshops with stakeholders were used to inform the development of the tool. Feedback shows that the tool has a wide range of uses and is already being used in practice to inform urban, inter-urban, and rural cycle network designs. The approach is flexible and open source, allowing the underlying ideas and code to be adapted, supporting more evidence-based and effective cycling policies and interventions internationally.
QTL analysis to identify genes involved in the trade-off between silk protein synthesis and larva-pupa transition in silkworms
Authors: Gao Rui , Li Chunlin , Zhou Ang , Wang Xiachao , Lu Kupeng , Zuo Weidong , Hu Hai , Han Minjin , Tong Xiaoling , Dai Fangyin 
Published: September 2024

Abstract
Background
Insect-based food and feed are increasingly attracting attention. As a domesticated insect, the silkworm (Bombyx mori) has a highly nutritious pupa that can be easily raised in large quantities through large-scale farming, making it a highly promising source of food. The ratio of pupa to cocoon (RPC) refers to the proportion of the weight of the cocoon that is attributed to pupae, and is of significant value for edible utilization, as a higher RPC means a higher ratio of conversion of mulberry leaves to pupa. In silkworm production, there is a trade-off between RPC and cocoon shell ratiao(CSR), which refers the ratio of silk protein to the entire cocoon, during metamorphosis process. Understanding the genetic basis of this balance is crucial for breeding edible strains with a high RPC and further advancing its use as feed.

Results
Using QTL-seq, we identified a quantitative trait locus (QTL) for the balance between RPC and CSR that is located on chromosome 11 and covers a 9,773,115-bp region. This locus is an artificial selection hot spot that contains ten non-overlapping genomic regions under selection that were involved in the domestication and genetic breeding processes. These regions include 17 genes, nine of which are highly expressed in the silk gland, which is a vital component in the trade-off between RPC and CSR. These genes are annotate with function related with epigenetic modifications and the regulation of DNA replication et al. We identified one and two single nucleotide polymorphisms (SNPs) in the exons of teh KWMTBOMO06541 and KWMTBOMO06485 genes that result in amino acid changes in the protein domains. These SNPs have been strongly selected for during the domestication process. The KWMTBOMO06485 gene encodes the Bombyx mori (Bm) tRNA methyltransferase (BmDnmt2) and its knockout results in a significant change in the trade-off between CSR and RPC in both sexes.

Conclusions
Taken together, our results contribute to a better understanding of the genetic basis of RPC and CSR. The identified QTL and genes that affect RPC can be used for marker-assisted and genomic selection of silkworm strains with a high RPC. This will further enhance the production efficiency of silkworms and of closely-related insects for edible and feed purposes.
Transcriptomic insights into the epigenetic modulation of turnip mosaic virus evolution in Arabidopsis thaliana
Authors: Olmo-Uceda María J. , Ambrós Silvia , Corrêa Régis L. , Elena Santiago F. 
Published: September 2024

Abstract
Background
Plant-virus interaction models propose that a virus’s ability to infect a host genotype depends on the compatibility between virulence and resistance genes. Recently, we conducted an evolution experiment in which lineages of turnip mosaic virus (TuMV) were passaged in Arabidopsis thaliana genotypes carrying mutations in components of the DNA methylation and the histone demethylation epigenetic pathways. All evolved lineages increased infectivity, virulence and viral load in a host genotype-dependent manner.

Results
To better understand the underlying reasons for these evolved relationships, we delved into the transcriptomic responses of mutant and WT plant genotypes in mock conditions and infected with either the ancestral or evolved viruses. Such a comparison allowed us to classify every gene into nine basic expression profiles. Regarding the targets of viral adaptation, our analyses allowed the identification of common viral targets as well as host genotype-specific genes and categories of biological processes. As expected, immune response-related genes were found to be altered upon infection. However, we also noticed the pervasive over-representation of other functional groups, suggesting that viral adaptation was not solely driven by the level of expression of plant resistance genes. In addition, a significant association between the presence of transposable elements within or upstream the differentially expressed genes was observed. Finally, integration of transcriptomic data into a virus-host protein-protein interaction network highlighted the most impactful interactions.

Conclusions
These findings shed extra light on the complex dynamics between plants and viruses, indicating that viral infectivity depends on various factors beyond just the plant’s resistance genes.
Streptokinase reduces Streptococcus dysgalactiae subsp. equisimilis biofilm formation
Authors: Tölken Lea A. , Neufend Janine V. , Oppegaard Oddvar , Methling Karen , Moll Kirsten , Redanz Sylvio , Katsburg Miriam M.D. , Ali Murtadha Q. , Shumba Patience , Kreikemeyer Bernd , Skrede Steinar , Fulde Marcus , Norrby-Teglund Anna , Lalk Michael , Kittang Bård R. , Siemens Nikolai 
Published: September 2024

Abstract
Background
Streptococcus dysgalactiae subspecies equisimilis (SDSE) is increasingly recognized as an emerging cause of invasive diseases including necrotizing soft tissue infections (NSTIs). In contrast to the closely related Streptococcus pyogenes, SDSE infections mainly affect older and comorbid patients. Biofilm formation has been demonstrated in soft tissue biopsies of S. pyogenes NSTI cases.

Results
Here, we show that bacterial aggregations indicative of biofilms are also present in SDSE NSTI. Although streptokinase (Ska) activity and biofilm formation did not correlate in a diverse set of clinical SDSE isolates, addition of exogenous Ska at an early time point prevented biofilm formation for selected strains. Deletion of ska in SDSE S118 strain resulted in increased biofilm forming capacity. Ska-deficient mutant strain was characterized by a higher metabolic activity and consequent metabolome profiling of biofilms identified higher deposition of a wide range of metabolites as compared to the wild-type.

Conclusions
Our results argue that Ska suppresses biofilm formation in SDSE independent of its original plasminogen converting activity. However, the impact of biofilms and its consequences for patient outcomes in streptococcal NSTIs remain to be elucidated.
Discovery of a conserved translationally repressive upstream open reading frame within the iron-deficiency response regulator IDEF2
Authors: Carey-Fung Oscar , Beasley Jesse T. , Broad Ronan C. , Hellens Roger P. , Johnson Alexander A. T. 
Published: September 2024

Abstract
Background
Iron (Fe) deficiency affects 30–50% of the world’s population. Genetic biofortification of staple crops is a promising strategy for improving human nutrition, but the number of effective precision breeding targets for Fe biofortification is small. Upstream open reading frames (uORFs) are cis-regulatory elements within the 5’ leader sequence (LS) of genes that generally repress translation of the main open reading frame (mORF).

Results
We aligned publicly available rice (Oryza sativa L.) ribo-seq datasets and transcriptomes to identify putative uORFs within important Fe homeostasis genes. A dual luciferase assay (DLA) was used to determine whether these uORFs cause repression of mORF translation and pinpoint LS regions that can be mutated for mORF derepression. A translationally repressive uORF region was identified in two positive regulators of the Fe-deficiency response: IDEF1 and IDEF2. The IDEF2-uORF peptide was highly conserved among monocots and a mutation series in the 5’ LS of the wheat (Triticum aestivum L.) TaIDEF2-A1 gene demonstrated variable mORF derepression.

Conclusions
Together these results reveal a possible regulatory mechanism by which IDEF2 transcription factors modulate the Fe deficiency response in monocots, and highlight novel precision breeding targets to improve crop nutrition and abiotic stress tolerance.
Reframing conceptualizations of primary care involvement in opioid use disorder treatment
Authors: Chiu Kellia , Sud Abhimanyu 
Published: September 2024

Abstract
Background
Opioid-related harms and opioid use disorder (OUD) are health priorities requiring urgent policy responses. There have been many calls for improved OUD care in primary care, as well as increasing involvement of primary care providers in countries like Canada and Australia, which have been experiencing high rates of opioid-related harms.

Methods
Using Starfield’s 4Cs conceptualization of primary care functions, we examined how and why primary care systems may be suited towards, or pose challenges to providing OUD care, and identified health system opportunities to address these challenges. We conducted 14 semi-structured interviews with 16 key informants with experience in opioid use policy in Canada and Australia.

Results
Primary care was identified to be an ideal setting for OUD care delivery due to its potential as the first point of contact in the health system; the opportunity to offer other health services to people with OUD; and the ability to coordinate care with other health providers (e.g. specialists, social workers) and thus also provide care continuity. However, challenges include a lack of resources and support for chronic disease management more broadly in primary care, and the prevailing model of OUD treatment, where addictions care is not seen as part of comprehensive primary care. Additionally, the highly regulated OUD policy landscape is also a barrier, manifesting as a ‘regulatory cascade’ in which restrictive oversight of OUD treatment passes from regulators to health providers to patients, normalizing the overly restrictive nature and inaccessibility of OUD care.

Conclusions
While primary care is an essential arena for providing OUD care, existing sociocultural, political, health professional, and health system factors have led to the current model of care that limits primary care involvement. Addressing this may involve structurally embedding OUD care into primary care and strengthening primary care in general.
Mutational signatures in 175 Chinese gastric cancer patients
Authors: Liu Fatao , Hu Nan , Jiang Kewei , Liu Huaitian , Wang Mingyi , Hu Ying , Zhang Tongwu , Wu Ho-Hsiang , Yang Howard , Weng Hao , Dong Ping , Giffen Carol , Zhu Bin , Lee Maxwell P. , Abnet Christian C. , Taylor Philip R. , Liu Yun , Liu Yingbin , Goldstein Alisa M. 
Published: September 2024

Abstract
Background
Gastric cancer (GC), a molecularly heterogeneous disease, is the third leading cause of cancer death worldwide. The majority of GC cases worldwide occur in East Asia, predominantly China. Mutational Signature Framework offers an elegant approach to identify mutational processes present in tumors.

Methods
To identify mutational signature patterns, we conducted whole exome sequencing (WES) analysis in Chinese patients with GC. Mutect2 and MutsigCV were used to identify significantly mutated genes in 175 Chinese GC cases using paired tumor-normal tissues. We investigated mutational signatures using Catalogue of Somatic Mutations in Cancer (COSMIC) Version 2 (V2) and Version 3 (V3).

Results
We identified 104 mutated genes with P < 0.01. Seven genes (OR6B1, B2M, ELF3, RHOA, RPL22, TP53, ARIDIA) had q < 0.0001, including six previously associated with GC. Mutational signatures (COSMIC-V3) observed include 14 single base substitutions (SBS), one doublet base substitution (DBS) Signature A, and one InDel (ID2). The most frequent SBS signatures (SBS05, SBS01, SBS15, SBS20, SBS40) were also observed in 254 White GC cases from The Cancer Genome Atlas (TCGA) Project. However, SBS01 and SBS20 showed significant differences between Whites vs. All Asians (19.3% vs. 11.3% for SBS 1 (P = 0.012) and 11.4% vs. 5.9% for SBS20 (P = 0.025), respectively). Using COSMIC V2, signatures 6, 15, and 1 were the most frequent in Chinese GC cases. Further, most Chinese GC cases carried multiple signatures.

Conclusions
This effort represents the most detailed mutational signatures analysis of GC cases from China to date. Results hold promise for new insights in understanding risk and prognosis factors in GC.
Midwifery students’ satisfaction with simulation-based education and associated factors among governmental universities in Amhara region, Ethiopia 2022
Authors: Gebrekidan Fiker Chane , Aweke Amlaku Mulat , Gella Getahun Belay , Bekele Yibeltal Alemu 
Published: September 2024

Abstract
Background
Simulation is a method of learning in which the learner experiences a simulated situation instead of being physically present in the clinical area. Exposing students to simulation-based education improves learners’ clinical competence and ability to make decisions, which are crucial for today’s health workforce. When given the proper circumstances, such as receiving feedback on their performance, having the chance for repeated practice, and having simulation as a core component of the curriculum, simulated instruction greatly aids in learning. Although previous studies have been conducted in this area, there are gaps in determining the factors related to their learning environment and design characteristics.

Method
An institution-based cross-sectional study was conducted on 413 midwifery students in Amhara region universities from August 1–30, 2022. Study participants were selected via a simple random sampling technique. Data were collected from third and fourth-year undergraduate midwifery students through a self-administered questionnaire. Epi Data version 4.6 and Statistical Package for Social Sciences version 26 were used for data entry and analysis, respectively. Bivariable and multivariable logistic regression analyses were employed; a P-value of less than 0.05 was considered statistically significant in the study.

Result
This study revealed that 84.7% (95% CI: 81.1–88.3) of midwifery students in Amhara region universities were satisfied with simulation-based education. Year of study [AOR: 2.936; 95% CI (1.531–5.631)], adequate support [AOR: 2.903; 95% CI (1.217–6.922)], availability of instructors [AOR = 2.861, 95% CI (1.078–7.591)], and provision of checklists [AOR: 2.326; 95% CI (1.143–4.734)] were found to be statistically significant variables.

Conclusion
This study revealed undergraduate midwifery students were more satisfied with simulation-based education compared with previous studies conducted in Ethiopia. Predictor variables such as year of study, support, instructor availability, and provision of checklists were significantly associated with student satisfaction. Hence, midwifery departments should strengthen the support given by staff, encourage their instructors to be available during simulations, improve the utilization and provision of checklists to students as much as possible.
Longitudinal study of association between quality of life and grit in internal medicine residents in Ramathibodi Hospital
Authors: Kitthavorn Pattarapol , Srisuma Sahaphume , Hongsanguansri Sirichai , Morasert Thotsaporn 
Published: September 2024

Abstract
Background
Grit refers to a combination of perseverance and passion, which is essential for long-term success. Grit is associated with higher education attainment and a lower likelihood of burnout. Understanding how grit evolves during internal medicine residency training is important for providing better support to residents. The primary objective of the current study was to evaluate potential changes in the level of grit throughout the training program and investigate the association between grit and stress levels, quality of life (QoL), and satisfaction of learning scores.

Methods
We conducted a prospective study involving internal medicine residents enrolled in training programs from July 2022 to July 2023, except for the second-third-year residents of dermatology and neurology programs and the third-year residents of haematology and oncology programs, which are not part of the same training regimen. Data collection was conducted using questionnaires at the beginning of the training year and every three months until the end. Collected data included age, gender, habitat, working experience, financial burden, marital status, rotations, grit scores, QoL, stress score, and satisfaction of learning score during each trimester. Changes in grit over the year were examined using repeated measures analysis of variance adjusted by training program, financial status, working experience, habitat, marital status, and age. We performed multivariable linear regression models to explore associations between grit and the following domains: QoL, ST-5, and SoLs.

Results
Of 122 internal medicine residents in all three years of training, one resident dropped out during training, and another declined to participate. A total of 120 residents were included. Grit did not significantly change over time. Subgroup analysis of the first-year resident group revealed that grit significantly decreased (P = 0.049). Multivariable analysis revealed that grit was positively associated with QoL (β = 0.01, P < 0.001) and satisfaction of learning score (β = 0.07, P < 0.001) but inversely associated with stress score (β = − 0.04, P < 0.001).

Conclusions
Of all residents, grit did not change over a year. However, only the first-year residents reported a decrease in grit during a training year. Throughout first-year residents’ internal medicine residency training, grit was positively associated with QoL and satisfaction of learning score but negatively associated with stress level. These findings suggest the need for targeted interventions to support first-year residents and enhance their resilience throughout training.