bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase 3 randomized trial of mavorixafor, a CXCR4 antagonist, for WHIM syndrome
Authors: Badolato Raffaele , Alsina Laia , Azar Antoine , Bertrand Yves , Bolyard Audrey A. , Dale David , Deyà-Martínez Àngela , Dickerson Kathryn E. , Ezra Navid , Hasle Henrik , Kang Hyoung Jin , Kiani-Alikhan Sorena , Kuijpers Taco W. , Kulagin Alexander , Langguth Daman , Levin Carina , Neth Olaf , Olbrich Peter , Peake Jane , Rodina Yulia , Rutten Caroline E. , Shcherbina Anna , Tarrant Teresa K. , Vossen Matthias G. , Wysocki Christian A. , Belschner Andrea , Bridger Gary J. , Chen Kelly , Dubuc Susan , Hu Yanping , Jiang Honghua , Li Sunny , MacLeod Rick , Stewart Murray , Taveras Arthur G. , Yan Tina , Donadieu Jean 
Published: April 2024

Abstract
We investigated efficacy and safety of mavorixafor, an oral CXCR4 antagonist, in participants with warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome, a rare immunodeficiency caused by CXCR4 gain-of-function variants. This randomized (1:1), double-blind, placebo-controlled, phase 3 trial enrolled participants aged ≥12 years with WHIM syndrome and absolute neutrophil count (ANC) ≤0.4 × 103/μL. Participants received once-daily mavorixafor or placebo for 52 weeks. The primary end point was time (hours) above ANC threshold ≥0.5 × 103/μL (TATANC; over 24 hours). Secondary end points included TAT absolute lymphocyte count ≥1.0 × 103/μL (TATALC; over 24 hours); absolute changes in white blood cell (WBC), ANC, and absolute lymphocyte count (ALC) from baseline; annualized infection rate; infection duration; and total infection score (combined infection number/severity). In 31 participants (mavorixafor, n = 14; placebo, n = 17), mavorixafor least squares (LS) mean TATANC was 15.0 hours and 2.8 hours for placebo (P &lt; .001). Mavorixafor LS mean TATALC was 15.8 hours and 4.6 hours for placebo (P &lt; .001). Annualized infection rates were 60% lower with mavorixafor vs placebo (LS mean 1.7 vs 4.2; nominal P = .007), and total infection scores were 40% lower (7.4 [95% confidence interval [CI], 1.6-13.2] vs 12.3 [95% CI, 7.2-17.3]). Treatment with mavorixafor reduced infection frequency, severity, duration, and antibiotic use. No discontinuations occurred due to treatment-emergent adverse events (TEAEs); no related serious TEAEs were observed. Overall, mavorixafor treatment demonstrated significant increases in LS mean TATANC and TATALC, reduced infection frequency, severity/duration, and was well tolerated. The trial was registered at www.clinicaltrials.gov as #NCT03995108.
Ibrutinib as part of risk-stratified treatment for posttransplant lymphoproliferative disorder: the phase 2 TIDaL trial
Authors: Chaganti Sridhar , Maycock Shanna , McIlroy Graham , Jackson Aimee , Bishop Rebecca , Johnson Sarah , Kanfer Edward , Kassam Shireen , Cwynarski Kate , Wrench David , Arumainathan Arvind , Fox Christopher P. , Johnson Rod , McKay Pam , Paneesha Shankara , Rowntree Clare , Balotis Constantine , Collins Graham P. , Davies Andrew , Wright Josh , Burns Sarah , Laurence Arian , Wheatley Keith , Menne Tobias 
Published: April 2024

Abstract
Posttransplant lymphoproliferative disorder (PTLD) is a rare complication of solid organ transplantation, and cytotoxic chemotherapy is associated with treatment-related morbidity and mortality. Current treatment takes a sequential, risk-stratified approach, and patients with low-risk disease after initial immunotherapy can avoid escalation to immunochemotherapy. TIDaL is a prospective, single-arm phase 2 trial investigating the activity and tolerability of ibrutinib combined with risk-stratified therapy for first-line treatment of PTLD. Eligible patients were adults with newly diagnosed CD20+ B-cell PTLD after solid organ transplant and performance status 0 to 2. Initial treatment comprised 49 days of ibrutinib 560 mg once daily, with 4 doses of weekly rituximab. Treatment response on interim scan and baseline International Prognostic Index were used to allocate patients to either a low-risk arm (who continued ibrutinib, alongside 4 further doses of 3-weekly rituximab) or high-risk (escalation to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone [R-CHOP] immunochemotherapy, with ibrutinib continuing in patients aged &lt;65 years). The primary outcome was complete response on interim scan, achieved by 11 of 38 patients (29%; 95% confidence interval [CI], 15-46). This did not reach the prespecified threshold for clinically significant activity. Secondary outcomes included allocation to the low-risk arm (41% of patients), 2-year progression-free survival (58%; 95% CI, 44-76), and 2-year overall survival (76%; 95% CI, 63-91). Adverse events were mostly hematological, gastrointestinal, and infective. Although TIDaL does not support adding ibrutinib into first-line treatment of PTLD, increasing the proportion of patients who can be treated without cytotoxic chemotherapy remains an important aim of future research. This trial was registered at www.clinicaltrials.gov as #ISRCTN32667607.
Alternative donor transplantation for severe aplastic anemia: a comparative study of the SAAWP EBMT
Authors: Montoro Juan , Eikema Dirk-Jan , Tuffnell Joe , Potter Victoria , Kalwak Krzysztof , Halkes Constantijn J. M. , Kulagin Alexander , Collin Matthew , Wynn Robert F. , Robinson Stephen , Nicholson Emma , Sengeloev Henrik , Clay Jennifer , Halahleh Khalid , Skorobogatova Elena , Sanz Jaime , Passweg Jakob , Mielke Stephan , Ryhänen Samppa , Carpenter Ben , Gedde-Dahl Tobias , Tholouli Eleni , Fanin Renato , Lewalle Philippe , Kulasekararaj Austin , Risitano Antonio , Peffault de Latour Régis 
Published: April 2024

Abstract
Selecting the most suitable alternative donor becomes challenging in severe aplastic anemia (SAA) when a matched sibling donor (MSD) is unavailable. We compared outcomes in patients with SAA undergoing stem cell transplantation (SCT) from matched unrelated donors (MUD) (n = 1106), mismatched unrelated donors (MMUD) (n = 340), and haploidentical donors (Haplo) (n = 206) registered in the European Society for Blood and Marrow Transplantation database (2012-2021). For Haplo SCT, only those receiving posttransplant cyclophosphamide for graft-versus-host disease (GVHD) prophylaxis were included. Median age was 20 years, and the median time from diagnosis to transplantation 8.7 months. Compared with MUD, MMUD (hazard ratio [HR], 2.93; 95% confidence interval [CI], 1.52-5.6) and Haplo (HR, 5.15; 95% CI, 2.5-10.58) showed significantly higher risks of primary graft failure. MUD had lower rates of acute GVHD compared with MMUD and Haplo (grade 2-4: 13%, 22%, and 19%, respectively; P &lt; .001; grade 3-4: 5%, 9%, and 7%, respectively; P = .028). The 3-year nonrelapse mortality rate was 14% for MUD, 19% for MMUD, and 27% for Haplo (P &lt; .001), whereas overall survival and GVHD and relapse-free survival (GRFS) rates were 81% and 73% for MUD, 74% and 65% for MMUD, and 63% and 54% for Haplo, respectively (P &lt; .001). In addition to donor type, multivariable analysis identified other factors associated with GRFS such as patient age, performance status, and interval between diagnosis and transplantation. For patients with SAA lacking an MSD, our findings support MUDs as the preferable alternative donor option. However, selecting between an MMUD and Haplo donor remains uncertain and requires further exploration.
miR-29b-3p regulates cardiomyocytes pyroptosis in CVB3-induced myocarditis through targeting DNMT3A
Authors: Wang Ya , Zhang Zhengyang , Li Hui , Wang Min , Qiu Yuting , Lu Lili 
Published: April 2024

Abstract
Background
Viral myocarditis (VMC) is a disease resulting from viral infection, which manifests as inflammation of myocardial cells. Until now, the treatment of VMC is still a great challenge for clinicians. Increasing studies indicate the participation of miR-29b-3p in various diseases. According to the transcriptome sequencing analysis, miR-29b-3p was markedly upregulated in the viral myocarditis model. The purpose of this study was to investigate the role of miR-29b-3p in the progression of VMC.

Methods
We used CVB3 to induce primary cardiomyocytes and mice to establish a model of viral myocarditis. The purity of primary cardiomyocytes was identified by immunofluorescence. The cardiac function of mice was detected by Vevo770 imaging system. The area of inflammatory infiltration in heart tissue was shown by hematoxylin and eosin (H&E) staining. The expression of miR-29b-3p and DNMT3A was detected by quantitative real time polymerase chain reaction (qRT–PCR). The expression of a series of pyroptosis-related proteins was detected by western blot. The role of miR-29b-3p/DNMT3A in CVB3-induced pyroptosis of cardiomyocytes was studied in this research.

Results
Our data showed that the expression of miR-29b-3p was upregulated in CVB3-induced cardiomyocytes and heart tissues in mice. To explore the function of miR-29b-3p in CVB3-induced VMC, we conducted in vivo experiments by knocking down the expression of miR-29b-3p using antagomir. We then assessed the effects on mice body weight, histopathology changes, myocardial function, and cell pyroptosis in heart tissues. Additionally, we performed gain/loss-of-function experiments in vitro to measure the levels of pyroptosis in primary cardiomyocytes. Through bioinformatic analysis, we identified DNA methyltransferases 3A (DNMT3A) as a potential target gene of miR-29b-3p. Furthermore, we found that the expression of DNMT3A can be modulated by miR-29b-3p during CVB3 infection.

Conclusions
Our results demonstrate a correlation between the expression of DNMT3A and CVB3-induced pyroptosis in cardiomyocytes. These findings unveil a previously unidentified mechanism by which CVB3 induces cardiac injury through the regulation of miR-29b-3p/DNMT3A-mediated pyroptosis.
Improving soil organic carbon mapping in farmlands using machine learning models and complex cropping system information
Authors: Ou Jianxiong , Wu Zihao , Yan Qingwu , Feng Xiangyang , Zhao Zilong 
Published: April 2024

AbstractObtaining accurate spatial maps of soil organic carbon (SOC) in farmlands is crucial for assessing soil quality and achieving precision agriculture. The cropping system is an important factor that affects the soil carbon cycle in farmlands, and different agricultural managements under different cropping systems lead to spatial heterogeneity of SOC. However, current research often ignores differences in the main controlling factors of SOC under different cropping systems, especially when the cropping pattern is complex, which is not conducive to farmland zoning management. This study aims to (i) obtain the spatial distribution map of six cropping systems by using multi-phase HJ-CCD satellite images; (ii) explore the stratified heterogeneous relationship between SOC and environmental variables under different cropping systems by using the Cubist model; and (iii) predict the spatial map of SOC. The Xiantao, Tianmen, and Qianjiang cities, which are the core agricultural areas of the Jianghan Plain, were selected as the study area. Results showed that the SOC content in rice–wheat rotation was the highest among the six cropping systems. The Cubist model outperformed random forest, ordinary kriging, and multiple linear regression in SOC mapping. The results of the Cubist model showed that cropping system, climate, soil attributes, and vegetation index were important influencing factors of SOC in farmlands. The main controlling factors of SOC under different cropping systems were different. Specifically, summer crop types had a greater influence on spatial variations in SOC than winter crops. Paddy–upland rotation was more affected by river distance and NDVI, while upland–upland rotation was more affected by irrigation-related factors. This work highlights the differentiated main controlling factors of SOC under different cropping systems and provides data support for farmland zoning management. The Cubist model can improve the prediction accuracy of SOC under complex cropping systems.
The distinct cell physiology of Bradyrhizobium at the population and cellular level
Authors: Medici Ian F. , Bartrolí Leila , Guaimas Francisco F. , Fulgenzi Fabiana R. , Molina Charo Luciana , Sánchez Ignacio Enrique , Comerci Diego J. , Mongiardini Elías , Soler-Bistué Alfonso 
Published: April 2024

AbstractThe α-Proteobacteria belonging to Bradyrhizobium genus are microorganisms of extreme slow growth. Despite their extended use as inoculants in soybean production, their physiology remains poorly characterized. In this work, we produced quantitative data on four different isolates: B. diazoefficens USDA110, B. diazoefficiens USDA122, B. japonicum E109 and B. japonicum USDA6 which are representative of specific genomic profiles. Notably, we found conserved physiological traits conserved in all the studied isolates: (i) the lag and initial exponential growth phases display cell aggregation; (ii) the increase in specific nutrient concentration such as yeast extract and gluconate hinders growth; (iii) cell size does not correlate with culture age; and (iv) cell cycle presents polar growth. Meanwhile, fitness, cell size and in vitro growth widely vary across isolates correlating to ribosomal RNA operon number. In summary, this study provides novel empirical data that enriches the comprehension of the Bradyrhizobium (slow) growth dynamics and cell cycle.
The gut microbiota facilitate their host tolerance to extreme temperatures
Authors: Wang Ziguang , Wu Yujie , Li Xinxin , Ji Xiaowen , Liu Wei 
Published: April 2024

Abstract
Background
Exposure to extreme cold or heat temperature is one leading cause of weather-associated mortality and morbidity in animals. Emerging studies demonstrate that the microbiota residing in guts act as an integral factor required to modulate host tolerance to cold or heat exposure, but common and unique patterns of animal-temperature associations between cold and heat have not been simultaneously examined. Therefore, we attempted to investigate the roles of gut microbiota in modulating tolerance to cold or heat exposure in mice.

Results
The results showed that both cold and heat acutely change the body temperature of mice, but mice efficiently maintain their body temperature at conditions of chronic extreme temperatures. Mice adapt to extreme temperatures by adjusting body weight gain, food intake and energy harvest. Fascinatingly, 16 S rRNA sequencing shows that extreme temperatures result in a differential shift in the gut microbiota. Moreover, transplantation of the extreme-temperature microbiota is sufficient to enhance host tolerance to cold and heat, respectively. Metagenomic sequencing shows that the microbiota assists their hosts in resisting extreme temperatures through regulating the host insulin pathway.

Conclusions
Our findings highlight that the microbiota is a key factor orchestrating the overall energy homeostasis under extreme temperatures, providing an insight into the interaction and coevolution of hosts and gut microbiota.
Developing an interprofessional decision support tool for diabetic foot ulcers management in primary care within the family medicine group model: a Delphi study in Canada
Authors: Brousseau-Foley Magali , Blanchette Virginie , Houle Julie , Trudeau François 
Published: April 2024

Abstract
Background
Primary care professionals encounter difficulties coordinating the continuum of care between primary care providers and second-line specialists and adhere to practice guidelines pertaining to diabetic foot ulcers management. Family medicine groups are providing primary care services aimed to improve access, interdisciplinary care, coordination and quality of health services, and reduce emergency department visits. Most professionals working in family medicine groups are primary care physicians and registered nurses. The aim of this study was to develop and validate an interprofessional decision support tool to guide the management of diabetic foot ulcers for primary care professionals working within the family medicine group model.

Methods
A one-page decision tool developed by the research team was validated by an expert panel using a three-round Delphi protocol held between December 2019 and August 2021. The tool includes 43 individual actions and a care pathway from initial presentation to secondary prevention. Data collection was realized with both paper and electronic questionnaires, and answers were compiled in an electronic spreadsheet. Data was analyzed with use of descriptive statistics, and consensus for each item was defined as ≥ 80% agreement.

Results
Experts from 12 pre-identified professions of the diabetic foot ulcer interdisciplinary care team were included, 39 participants out of the 59 invited to first round (66.1%), 34 out of 39 for second (87.2%) and 22 out of 34 for third (64.7%) rounds. All items included in the final version of the decision support tool reached consensus and were deemed clear, relevant and feasible. One or more professionals were identified to be responsible for every action to be taken.

Conclusions
This study provided a comprehensive decision support tool to guide primary care professionals in the management of diabetic foot ulcers. Implementation and evaluation in the clinical setting will need to be undertaken in the future.
Integrated clinical and genomic models using machine-learning methods to predict the efficacy of paclitaxel-based chemotherapy in patients with advanced gastric cancer
Authors: Choi Yonghwa , Lee Jangwoo , Shin Keewon , Lee Ji Won , Kim Ju Won , Lee Soohyeon , Choi Yoon Ji , Park Kyong Hwa , Kim Jwa Hoon 
Published: April 2024

Abstract
Background
Paclitaxel is commonly used as a second-line therapy for advanced gastric cancer (AGC). The decision to proceed with second-line chemotherapy and select an appropriate regimen is critical for vulnerable patients with AGC progressing after first-line chemotherapy. However, no predictive biomarkers exist to identify patients with AGC who would benefit from paclitaxel-based chemotherapy.

Methods
This study included 288 patients with AGC receiving second-line paclitaxel-based chemotherapy between 2017 and 2022 as part of the K-MASTER project, a nationwide government-funded precision medicine initiative. The data included clinical (age [young-onset vs. others], sex, histology [intestinal vs. diffuse type], prior trastuzumab use, duration of first-line chemotherapy), and genomic factors (pathogenic or likely pathogenic variants). Data were randomly divided into training and validation sets (0.8:0.2). Four machine learning (ML) methods, namely random forest (RF), logistic regression (LR), artificial neural network (ANN), and ANN with genetic embedding (ANN with GE), were used to develop the prediction model and validated in the validation sets.

Results
The median patient age was 64 years (range 25–91), and 65.6% of those were male. A total of 288 patients were divided into the training (n = 230) and validation (n = 58) sets. No significant differences existed in baseline characteristics between the training and validation sets. In the training set, the areas under the ROC curves (AUROC) for predicting better progression-free survival (PFS) with paclitaxel-based chemotherapy were 0.499, 0.679, 0.618, and 0.732 in the RF, LR, ANN, and ANN with GE models, respectively. The ANN with the GE model that achieved the highest AUROC recorded accuracy, sensitivity, specificity, and F1-score performance of 0.458, 0.912, 0.724, and 0.579, respectively. In the validation set, the ANN with GE model predicted that paclitaxel-sensitive patients had significantly longer PFS (median PFS 7.59 vs. 2.07 months, P = 0.020) and overall survival (OS) (median OS 14.70 vs. 7.50 months, P = 0.008). The LR model predicted that paclitaxel-sensitive patients showed a trend for longer PFS (median PFS 6.48 vs. 2.33 months, P = 0.078) and OS (median OS 12.20 vs. 8.61 months, P = 0.099).

Conclusions
These ML models, integrated with clinical and genomic factors, offer the possibility to help identify patients with AGC who may benefit from paclitaxel chemotherapy.
Comparative characteristics of early-onset vs. late-onset advanced colorectal cancer: a nationwide study in China
Authors: Liu Hongwei , Xu Huifang , Liu Yin , Zhao Yuqian , Zhang Xi , Yu Yanqin , Du Lingbin , Liu Yunyong , Wang Wenjun , Cao Helu , Ma Li , Huang Juanxiu , Cao Ji , Li Li , Fan Yanping , Gu Xiaofen , Feng Changyan , Zhu Qian , Wang Xiaohui , Du Jingchang , Zhang Shaokai , Qiao Youlin 
Published: April 2024

Abstract
Background
The incidence of early-onset colorectal cancer (EOCRC, diagnosed in patients under the age of 50 years) has been increasing around the world. Here, we aimed to systematically identify distinctive features of EOCRC.

Methods
From 2020 to 2021, we conducted a nationwide survey in 19 hospitals, collecting data on advanced CRC patients’ demographics, clinical features, disease knowledge, medical experiences, expenditures, and health-related quality of life (HRQOL). We compared these features between EOCRC and late-onset colorectal cancer (LOCRC, ≥ 50 years old) groups and analyzed the association between EOCRC and HRQOL using multivariate linear regression.

Findings
In total, 991 patients with EOCRC and 3581 patients with LOCRC were included. Compared to the LOCRC group, the EOCRC group had higher levels of education, were more informed about the risk factors for CRC, were more likely to have widespread metastases throughout the body, were more inclined to undergo gene testing, and were more likely to opt for targeted therapy, radiotherapy, and chemotherapy. However, HRQOL in the EOCRC group was similar to that of the LOCRC group, and no significant association was observed between EOCRC and HRQOL (beta: -0.753, P value: 0.307).

Interpretation
In Chinese patients, EOCRC patients had more aggressive features. Despite undergoing more intensified treatments and gene testing, they had similar HRQOL compared with LOCRC. These findings advocate for a more tailored approach to treatment, especially for young CRC patients with advanced TNM stages and metastasis.