bluuebunny/crossref_metadata_2025_split huggingface dataset:
Follow-up from the A041202 study shows continued efficacy of ibrutinib regimens for older adults with CLL
Authors: Woyach Jennifer A. , Perez Burbano Gabriela , Ruppert Amy S. , Miller Cecelia , Heerema Nyla A. , Zhao Weiqiang , Wall Anna , Ding Wei , Bartlett Nancy L. , Brander Danielle M. , Barr Paul M. , Rogers Kerry A. , Parikh Sameer A. , Stephens Deborah M. , Brown Jennifer R. , Lozanski Gerard , Blachly James , Nattam Sreenivasa , Larson Richard A. , Erba Harry , Litzow Mark , Luger Selina , Owen Carolyn , Kuzma Charles , Abramson Jeremy S. , Little Richard F. , Dinner Shira , Stone Richard M. , Uy Geoffrey , Stock Wendy , Mandrekar Sumithra J. , Byrd John C. 
Published: January 2024

Abstract
A041202 (NCT01886872) is a phase 3 study comparing bendamustine plus rituximab (BR) with ibrutinib and the combination of ibrutinib plus rituximab (IR) in previously untreated older patients with chronic lymphocytic leukemia (CLL). The initial results showed that ibrutinib-containing regimens had superior progression-free survival (PFS) and rituximab did not add additional benefits. Here we present an updated analysis. With a median follow-up of 55 months, the median PFS was 44 months (95% confidence interval [CI], 38-54) for BR and not yet reached in either ibrutinib-containing arm. The 48-month PFS estimates were 47%, 76%, and 76% for BR, ibrutinib, and IR, respectively. The benefit of ibrutinib regimens over chemoimmunotherapy was consistent across subgroups of patients defined by TP53 abnormalities, del(11q), complex karyotype, and immunoglobulin heavy chain variable region (IGHV). No significant interaction effects were observed between the treatment arm and del(11q), the complex karyotype, or IGHV. However, a greater difference in PFS was observed among the patients with TP53 abnormalities. There was no difference in the overall survival. Notable adverse events with ibrutinib included atrial fibrillation (afib) and hypertension. Afib was observed in 11 patients (pts) on BR (3%) and 67 pts on ibrutinib (18%). All-grade hypertension was observed in 95 pts on BR (27%) and 263 pts on ibrutinib (55%). These data show that ibrutinib regimens prolong PFS compared with BR for older patients with treatment-naïve CLL. These benefits were observed across subgroups, including high-risk groups. Strikingly, within the ibrutinib arms, there was no inferior PFS for patients with abnormalities in TP53, the highest risk feature observed in CLL. These data continue to demonstrate the efficacy of ibrutinib in treatment-naïve CLL.
OsUGE2 Regulates Plant Growth through Affecting ROS Homeostasis and Iron Level in Rice
Authors: Yang Shuaiqi , Chen Nana , Qi Jiaxuan , Salam Abdul , Khan Ali Raza , Azhar Wardah , Yang Chunyan , Xu Nuo , Wu Junyu , Liu Yihua , Liu Bohan , Gan Yinbo 
Published: January 2024

Abstract
Background
The growth and development of rice (Oryza sativa L.) are affected by multiple factors, such as ROS homeostasis and utilization of iron. Here, we demonstrate that OsUGE2, a gene encoding a UDP-glucose 4-epimerase, controls growth and development by regulating reactive oxygen species (ROS) and iron (Fe) level in rice. Knockout of this gene resulted in impaired growth, such as dwarf phenotype, weakened root growth and pale yellow leaves. Biochemical analysis showed that loss of function of OsUGE2 significantly altered the proportion and content of UDP-Glucose (UDP-Glc) and UDP-Galactose (UDP-Gal). Cellular observation indicates that the impaired growth may result from decreased cell length. More importantly, RNA-sequencing analysis showed that knockout of OsUGE2 significantly influenced the expression of genes related to oxidoreductase process and iron ion homeostasis. Consistently, the content of ROS and Fe are significantly decreased in OsUGE2 knockout mutant. Furthermore, knockout mutants of OsUGE2 are insensitive to both Fe deficiency and hydrogen peroxide (H2O2) treatment, which further confirmed that OsUGE2 control rice growth possibly through Fe and H2O2 signal. Collectively, these results reveal a new pathway that OsUGE2 could affect growth and development via influencing ROS homeostasis and Fe level in rice.
Urban (UMaaS) and rural (RMaaS) mobility as a service (MaaS): practical insights from international practitioners and experts
Authors: Milne Jenny , Beecroft Mark , Nelson John D. , Greening Philip , Cottrill Caitlin , Wright Steve 
Published: January 2024

AbstractThe concept and potential of Mobility as a Service (MaaS) has been the subject of significant debate in academia and industry for nearly a decade. There are several city-based Mobility as a Service (MaaS) pilots globally. There remains a significant lack of practitioner evidence of MaaS with the focus on city-based solutions rather than in rural and suburban areas. To that end, this paper asks four research questions to contribute to the gap in Rural MaaS (RMaaS) and Urban MaaS (UMaaS); firstly, is MaaS a mobility option for rural areas given the identified evidence in scientific literature? Secondly, how do practitioner experiences with MaaS (in all areas) differ considering factors like phraseology, geography, available modes, transportation, the origin and implementation stages? Thirdly, what practical learnings can be drawn from practitioners in the field? Fourthly, what is the future of MaaS for rural and urban areas. The research and findings are based upon grey literature and twenty semi-structured interviews with representatives from research or government organisations, public bodies, MaaS technology suppliers, transport operators and experts. Each participant discussed and contributed to the practicalities around real-world applications of MaaS in urban, regional, or rural areas. The analysis produced 2 applied tools which will be useful to practitioners interested in MaaS; a Thematic Map visualising the common matters emerging from the interviews revolving around ‘People, Policy, Practice and Pilots (4Ps); a Practical Framework for Implementing MaaS tool, which can be used by any practitioner at any stage of a MaaS project.
DNI-MDCAP: improvement of causal MiRNA-disease association prediction based on deep network imputation
Authors: Han Yu , Zhou Qiong , Liu Leibo , Li Jianwei , Zhou Yuan 
Published: January 2024

Abstract
Background
MiRNAs are involved in the occurrence and development of many diseases. Extensive literature studies have demonstrated that miRNA-disease associations are stratified and encompass ~ 20% causal associations. Computational models that predict causal miRNA-disease associations provide effective guidance in identifying novel interpretations of disease mechanisms and potential therapeutic targets. Although several predictive models for miRNA-disease associations exist, it is still challenging to discriminate causal miRNA-disease associations from non-causal ones. Hence, there is a pressing need to develop an efficient prediction model for causal miRNA-disease association prediction.

Results
We developed DNI-MDCAP, an improved computational model that incorporated additional miRNA similarity metrics, deep graph embedding learning-based network imputation and semi-supervised learning framework. Through extensive predictive performance evaluation, including tenfold cross-validation and independent test, DNI-MDCAP showed excellent performance in identifying causal miRNA-disease associations, achieving an area under the receiver operating characteristic curve (AUROC) of 0.896 and 0.889, respectively. Regarding the challenge of discriminating causal miRNA-disease associations from non-causal ones, DNI-MDCAP exhibited superior predictive performance compared to existing models MDCAP and LE-MDCAP, reaching an AUROC of 0.870. Wilcoxon test also indicated significantly higher prediction scores for causal associations than for non-causal ones. Finally, the potential causal miRNA-disease associations predicted by DNI-MDCAP, exemplified by diabetic nephropathies and hsa-miR-193a, have been validated by recently published literature, further supporting the reliability of the prediction model.

Conclusions
DNI-MDCAP is a dedicated tool to specifically distinguish causal miRNA-disease associations with substantially improved accuracy. DNI-MDCAP is freely accessible at http://www.rnanut.net/DNIMDCAP/.
COVID-19 vaccination uptake and receptivity among veterans enrolled in homelessness-tailored primary health care clinics: provider trust vs. misinformation
Authors: Gin June L. , Balut Michelle D. , Dobalian Aram 
Published: January 2024

Abstract
Background
Compared to the general population, individuals experiencing homelessness are at greater risk of excess morbidity and mortality from COVID-19 but have been vaccinated at lower rates. The U.S. Department of Veterans Affairs (VA)’s Homeless Patient Aligned Care Team (HPACT) program integrates health care and social services for Veterans experiencing homelessness to improve access to and utilization of care.

Methods
This study explores the vaccination uptake behavior and attitudes through a qualitative comparative case study of two HPACT clinics, one in California (CA) and one in North Dakota (ND). Semi-structured telephone interviews were conducted with Veterans enrolled in the two VA HPACT clinics from August to December 2021 with 20 Veterans (10 at each clinic).

Results
Four themes emerged from the interviews: (1) Vaccination uptake and timing— While half of the Veterans interviewed were vaccinated, ND Veterans were more likely to be vaccinated and got vaccinated earlier than CA Veterans; (2) Housing— Unsheltered or precariously housed Veterans were less likely to be vaccinated; (3) Health Care— Veterans reporting positive experiences with VA health care and those who trusted health providers were more likely to vaccinate than those with negative or nuanced satisfaction with health care; (4) Refusers’ Conspiracy Theories and Objectivity Claims— Veterans refusing the vaccine frequently mentioned belief in conspiracy theories while simultaneously asserting their search for objective information from unbiased sources.

Conclusions
These findings amplify the importance of improving access to population-tailored care for individuals experiencing homelessness by reducing patient loads, expanding housing program enrollment, and increasing the provider workforce to ensure personalized care. Health care providers, and housing providers, social workers, and peers, who offer information without discrediting or criticizing Veterans’ beliefs, are also key to effectively delivering vaccine messaging to this population.
Retrospective database analysis for clinical diagnoses commonly associated with pneumococcal diseases in the Malaysian healthcare system over a 3-year period (2013–2015)
Authors: Sundaramurthy Saravanan S. R. , Allen Kristen E. , Fletcher Mark A. , Liew Kok Fui , Borhanuddin Boekhtiar , Ali Mohammad , Morales Graciela , Gessner Bradford , Naidoo Jerusha , Southern Jo 
Published: January 2024

Abstract
Background
Pneumococcal disease caused by Streptococcus pneumoniae is an important cause of morbidity and mortality across all ages, particularly in younger children and older adults. Here, we describe pneumococcal disease hospitalizations at Ministry of Health (MoH) facilities in Malaysia between 2013 and 2015.

Methods
This was a retrospective databases analysis. Tabular data from the Malaysian Health Data Warehouse (MyHDW) were used to identify microbiologically confirmed, pneumococcal disease hospitalizations and deaths during hospitalization, using hospital-assigned ICD-10 codes (i.e., classified as meningitis, pneumonia, or non-meningitis non-pneumonia). Case counts, mortality counts, and case fatality rates were reported by patient age group and by Malaysian geographic region.

Results
A total of 683 pneumococcal disease hospitalizations were identified from the analysis: 53 pneumococcal meningitis hospitalizations (5 deaths and 48 discharges), 413 pneumococcal pneumonia hospitalizations (24 deaths and 389 discharges), and 205 non-meningitis non-pneumonia pneumococcal disease hospitalizations (58 deaths and 147 discharges). Most hospitalizations occurred in children aged < 2 years. Crude mortality was highest among children aged < 2 years (for all three disease categories), among adults aged ≥ 65 years (for pneumococcal pneumonia), or among adults aged 65–85 years (for non-meningitis non-pneumonia pneumococcal disease). The case fatality rate, all ages included, was 5.8% for pneumococcal pneumonia, 9.1% for pneumococcal meningitis, and 28.3% for non-meningitis non-pneumonia pneumococcal disease.

Conclusions
Our study is the first to document pneumococcal disease hospitalizations and deaths during hospitalization in Malaysia. Although this database analysis likely underestimated case counts, and the true disease burden could be even greater, the study demonstrates a substantial burden of pneumococcal disease. Public health measures, including vaccination, would significantly contribute to the prevention of hospitalizations and deaths associated with pneumococcal disease in Malaysia.
Multiple intracellular pathogen infections with ocular pathologies associated with adult-onset immunodeficiency due to anti-interferon-γ autoantibodies: a case report
Authors: Ning Yan , Yu Qingliang , Liang Hanlin , Wu Siyao , Liang Siqiao , Liang Xiaona , He Zhiyi 
Published: January 2024

Abstract
Background
Autoantibodies against interferon-γ (IFN-γ) can inhibit IFN-γ-dependent signal transducer and activator of transcription 1 phosphorylation and thus increase the risk of infection with intracellular pathogens, such as Talaromyces marneffei (TM), nontuberculous mycobacteria (NTMs), and Mycobacterium tuberculosis (TB). Here, we report a rare case of triple infection caused by TM, NTM, and TB in a human immunodeficiency virus–negative patient.

Case presentation
A middle-aged female was admitted to our hospital after experiencing recurrent rash, cough, and expectoration for 4 months. She was successively diagnosed with NTM, TM, and TB infections without conventional immunosuppression-associated factors. However, after effective anti-infective treatment, the patient was confirmed to have allergic conjunctivitis and was successfully treated with corticosteroids and immunosuppressants. The most conspicuous characteristics were recurrent infection and immune disorders.

Conclusions
High-titer anti-IFN-γ autoantibodies are strongly associated with severe and disseminated infections, such as NTM, TM, and TB. It is characterized by persistently high degree of inflammation and high immunoglobin levels.
RGD-p21Ras-scFv expressed prokaryotically on a pilot scale inhibits ras-driven colorectal cancer growth by blocking p21Ras-GTP
Authors: Lin Peng , Qian Jing , Huang Cheng-Cheng , Xu Wen-Mang , Wang Yuan-Yuan , Gao Zi-Ran , Zheng Shi-Qi , Wang Peng , Jia Da-Qi , Feng Qiang , Yang Ju-Lun 
Published: January 2024

Abstract
Background
Ras gene mutation and/or overexpression are drivers in the progression of cancers, including colorectal cancer. Blocking the Ras signaling has become a significant strategy for cancer therapy. Previously, we constructed a recombinant scFv, RGD-p21Ras-scFv by linking RGD membrane-penetrating peptide gene with the anti-p21Ras scFv gene. Here, we expressed prokaryotically RGD-p21Ras-scFv on a pilot scale, then investigated the anti-tumor effect and the mechanism of blocking Ras signaling.

Methods
The E. coli bacteria which could highly express RGD-p21Ras-scFv was screened and grown in 100 L fermentation tank to produce RGD-p21Ras-scFv on optimized induced expression conditions. The scFv was purified from E. coli bacteria using His Ni-NTA column. ELISA was adopted to test the immunoreactivity of RGD-p21Ras-scFv against p21Ras proteins, and the IC50 of RGD-p21Ras-scFv was analyzed by CCK-8. Immunofluorescence colocalization and pull-down assays were used to determine the localization and binding between RGD-p21Ras-scFv and p21Ras. The interaction forces between RGD-p21Ras-scFv and p21Ras after binding were analyzed by molecular docking, and the stability after binding was determined by molecular dynamics simulations. p21Ras-GTP interaction was detected by Ras pull-down. Changes in the MEK-ERK /PI3K-AKT signaling paths downstream of Ras were detected by WB assays. The anti-tumor activity of RGD-p21Ras-scFv was investigated by nude mouse xenograft models.

Results
The technique of RGD-p21Ras-scFv expression on a pilot scale was established. The wet weight of the harvested bacteria was 31.064 g/L, and 31.6 mg RGD-p21Ras-scFv was obtained from 1 L of bacterial medium. The purity of the recombinant antibody was above 85%, we found that the prepared on a pilot scale RGD-p21Ras-scFv could penetrate the cell membrane of colon cancer cells and bind to p21Ras, then led to reduce of p21Ras-GTP (active p21Ras). The phosphorylation of downstream effectors MEK-ERK /PI3K-AKT was downregulated. In vivo antitumor activity assays showed that the RGD-p21Ras-scFv inhibited the proliferation of colorectal cancer cell lines.

Conclusion
RGD-p21Ras-scFv prokaryotic expressed on pilot-scale could inhibited Ras-driven colorectal cancer growth by partially blocking p21Ras-GTP and might be able to be a hidden therapeutic antibody for treating RAS-driven tumors.
Low serum apolipoprotein A1 level predicts poor prognosis of patients with diffuse large B-cell lymphoma in the real world: a retrospective study
Authors: Huang Xiaoling , Wang Ying , Huang Zhenyu , Chen Xuzheng , Lin Qiuyan , Huang Haobo , Fan Liping 
Published: January 2024

Abstract
Background
Apolipoprotein A1 (ApoA1) is a member of the apolipoprotein family with diverse functions. It is associated with the pathogenesis and prognosis of several types of tumors. However, the role of serum apolipoprotein A1 (ApoA1) in the prognosis of patients with diffuse large B-cell lymphoma (DLBCL) remains unclear. This study aimed to elucidate its influence on clinical outcomes in patients with DLBCL.

Methods
We retrospectively analyzed a cohort of 1583 consecutive DLBCL patients admitted to the Fujian Medical University Union Hospital between January 2011 and December 2021. 949 newly diagnosed DLBCL patients who met the inclusion criteria were enrolled for statistical analysis. Receiver operating characteristic curve analysis was performed to determine the optimal cut-off value for serum ApoA1 levels for prognostic prediction among patients with DLBCL. The correlations between serum ApoA1 levels and clinical and laboratory parameters were analyzed. Prognostic significance was analyzed using univariate and multivariate Cox proportional hazards models.

Results
Newly diagnosed patients with DLBCL demonstrated low serum ApoA1 levels (< 0.925 g/L), had more B symptoms, higher levels of serum lactate dehydrogenase (LDH) (>upper limit of normal), poorer performance status (Eastern Cooperative Oncology Group score of 2–4), higher percentage of advanced stage and non-germinal center B-cell (non-GCB) subtype, more cases of > 1 extranodal site, higher International Prognostic Index (IPI) score (3–5), and higher incidence of relapse or refractory diseases compared with those with high serum ApoA1 levels (≥ 0.925 g/L). Low serum ApoA1 levels were an independent adverse prognostic factor for overall survival (OS) but not progression-free survival (PFS).

Conclusions
Low serum ApoA1 levels were associated with poor treatment response and inferior survival in newly diagnosed patients with DLBCL.
Impulsive and compulsive reading comprehension in the prison population
Authors: Muñoz-López Lucas , Serrano Francisca , López-Torrecillas María del Carmen , Sánchez-Barrera María Blasa , Martín Ignacio , López-Torrecillas Francisca 
Published: January 2024

Abstract
Background
Developmental dyslexia is characterized by reading and writing deficits that persist into adulthood. Dyslexia is strongly associated with academic underachievement, as well as impulsive, compulsive, and criminal behaviors.
The aims of this study were to investigate impulsive or compulsive reading comprehension, analyzing the differences in reading errors between two distinct groups —one with Antisocial Personality Disorder (ASPD) and another with Obsessive–Compulsive Personality Disorder (OCPD) and examine their correlation with criminal behavior within a prison population.

Methods
We gathered data from 194 participants: 81 with ASPD and 113 with OCPD from a prison center. Participants took part in interviews to gather data on demographic, criminal, and behavioral data. Additionally, the participants underwent various assessments, including the International Examination for Personality Disorders; Symptom Inventory, and Battery for the Assessment of Reading Processes in Secondary and High School – Revised.

Results
Our analysis revealed differences in reading skills between the ASPD and OCPD groups. Specifically, the OCPD group showed poorer performance on lexical selection, semantic categorization, grammar structures, grammatical judgements, and expository comprehension when compared with the ASPD group. Conversely, the OCPD group obtained higher scores on narrative comprehension relative to the ASPD group.

Conclusions
The OCPD group showed slow lexical-phonological coding and phonological activation.
Application of the Boruta algorithm to assess the multidimensional determinants of malnutrition among children under five years living in southern Punjab, Pakistan
Authors: Saleem Javeria , Zakar Rubeena , Butt Muhammad Salman , Aadil Rana Muhammad , Ali Zulfiqar , Bukhari Gul Mehar Javaid , Ishaq Muhammad , Fischer Florian 
Published: January 2024

Abstract
Background
Malnutrition causes nutrient deficiencies that have both physical and clinical consequences in severe acute malnutrition children. Globally, there were 47 million wasted children under the age of five in 2019. One in four were located in sub-Saharan Africa, with half being in South Asia. This study aims to apply the Boruta algorithm to identify the determinants of undernutrition among children under five living in Dera Ghazi Khan, one of the marginalized districts of densely populated Punjab Province in Pakistan.

Methods
A multicenter cross-sectional study design was used to collect data from 185 children with severe acute malnutrition aged under five years visiting the OTPs centers located in Dera Ghazi Khan, Punjab, Pakistan. A purposive sampling technique was used to collect data using a pretested structured questionnaire from parents/caregivers regarding family sociodemographic characteristics, child nutrition, and biological and healthcare characteristics. Anthropometric measurements, including height, weight, and mid-upper arm circumference, were collected. The Boruta models were used to incorporate the children’s anthropometric, nutritional, and household factors to determine the important predictive variables for undernutrition using the Boruta package in R studio.

Results
This study included 185 children, with a mean age of 15.36 ± 10.23 months and an MUAC of 10.19 ± 0.96 cm. The Boruta analysis identifies age, mid-upper arm circumference, weaning practices, and immunization status as important predictors of undernutrition. Income per month, exclusive breastfeeding, and immunization status were found to be key factors of undernutrition in children under the age of five.

Conclusion
This study highlights age, mid-upper arm circumference, weaning practices, and immunization status as key determinants of weight-for-height and weight-for-age in children under five years. It also suggests that economic context may influence undernutrition. The findings can guide targeted strategies for combating undernutrition.