bluuebunny/crossref_metadata_2025_split huggingface dataset:
A CD3 humanized mouse model unmasked unique features of T-cell responses to bispecific antibody treatment
Authors: Wang Lingling , Leach Vincent , Muthusamy Natarajan , Byrd John , Long Meixiao 
Published: October 2023

Abstract
T-cell bispecific antibodies (T-BsAbs) such as blinatumomab hold great promise for cancer immunotherapy. A better understanding of the in vivo immune response induced by T-BsAbs is crucial to improving their efficacy and safety profile. However, such efforts are hindered by the limitations of current preclinical models. To address this, we developed a syngeneic murine model with humanized CD3 and target antigen (CD20). This model enables the development of disseminated leukemia with a high tumor burden, which mirrors clinical findings in human patients with relapsed/refractory acute lymphoblastic leukemia. Treatment of this model with T-BsAbs results in cytokine release syndrome, with cytokine profiles and levels reflecting observations made in human patients. This model also faithfully recapitulates the dynamics of T-cell activation seen in human patients, including the temporary disappearance of T cells from the bloodstream. During this phase, T cells are sequestered in secondary lymphoid organs and undergo activation. Clinical correlative studies that rely primarily on peripheral blood samples are likely to overlook this critical activation stage, leading to a substantial underestimation of the extent of T-cell activation. Furthermore, we demonstrate that surface expression of the T-BsAb target antigen by leukemia cells triggers a swift immune response, promoting their own rejection. Humanizing the target antigen in the recipient mice is crucial to facilitate tolerance induction and successful establishment of high tumor burden. Our findings underscore the importance of meticulously optimized syngeneic murine models for investigating T-BsAb–induced immune responses and for translational research aimed at improving efficacy and safety.
Blinatumomab consolidation post–autologous stem cell transplantation in patients with diffuse large B-cell lymphoma
Authors: Ghobadi Armin , Foley Nicole C. , Cohen Jared , Rettig Michael P. , Cashen Amanda F. , Gehrs Leah , Christ Stephanie , Street Emily , Wallace Nicholas , Ritchey Julie , Mehta-Shah Neha , Westervelt Peter , Fehniger Todd A. , Kahl Brad , Bartlett Nancy L. , DiPersio John F. 
Published: October 2023

Abstract
Outcomes in patients with relapsed diffuse large B-cell lymphoma (DLBCL) who undergo autologous stem cell transplant (auto-SCT) are poor. Blinatumomab is a CD3/CD19 bispecific T-cell engager that directs cytotoxic T cells to CD19+ cells. Here, we performed a pilot study of blinatumomab consolidation after auto-SCT for 14 patients with DLBCL or transformed follicular lymphoma. All patients underwent standard-of-care auto-SCT with carmustine, etoposide, cytarabine, and melphalan (BEAM) conditioning followed by 1 cycle (4 weeks continuous infusion) of blinatumomab consolidation starting at day 42 after auto-SCT. All 14 patients treated on study completed BEAM auto-SCT and 1 cycle of posttransplant blinatumomab. Five patients developed grade 1 cytokine release syndrome (CRS), with no grade 2 or higher CRS. Immune effector cell–associated neurotoxicity syndrome was not observed. Patients were followed up for 3 years after auto-SCT, with median follow-up of 37 (range, 12-65) months. One-hundred days after auto-SCT (1 month after blinatumomab consolidation), 12 patients (86%) had achieved complete remission. At 1 year after auto-SCT, 7 patients (50%) remained in CR, and 1 patient had died of progressive disease. Patients who relapsed had a lower CD8:CD4 T-cell ratio before starting blinatumomab than patients who remained in remission. This pilot study demonstrates blinatumomab consolidation after auto-SCT is safe and well tolerated. Strategies to increase the CD8:CD4 ratio and use additional cycles of consolidation in a larger randomized trial are needed to confirm the efficacy of consolidation with blinatumomab after auto-SCT. This trial was registered at www.clinicaltrials.gov as #NCT03072771.
High PDL1/PDL2 gene expression correlates with worse outcome in primary mediastinal large B-cell lymphoma
Authors: Camus Vincent , Viailly Pierre-Julien , Drieux Fanny , Veresezan Elena-Liana , Sesques Pierre , Haioun Corinne , Durot Eric , Patey Martine , Rossi Cédric , Martin Laurent , Rainville Vinciane , Bohers Elodie , Ruminy Philippe , Penther Dominique , Kaltenbach Sophie , Bruneau Julie , Paillassa Jérome , Tournilhac Olivier , Willaume Alexandre , Antier Chloé , Lazarovici Julien , Lévêque Emilie , Decazes Pierre , Becker Stéphanie , Tonnelet David , Berriolo-Riedinger Alina , Gaulard Philippe , Tilly Hervé , Molina Thierry Jo , Traverse-Glehen Alexandra , Jardin Fabrice 
Published: October 2023

Abstract
Primary mediastinal B-cell lymphoma (PMBL) is an uncommon entity of aggressive B-cell lymphoma with an unusually good prognosis, except for 10-15% of chemotherapy-refractory cases. To identify earlier these higher risk patients, we performed molecular characterization of a retrospective multicenter cohort of patients treated with firstline immunochemotherapy. The traits of the patients with gene-expression profiling data (n = 120) were as follows: median age of 34 years (range, 18-67 years); female sex, 58.3%; elevated lactate dehydrogenase, 82.5%; Eastern Cooperative Oncology Group performance status score of 0 to 1, 85.7%; Ann Arbor stage I/II, 55%; International Prognostic Index score of 1 to 2, 64.4%; and median metabolic tumor volume, 290.4 cm3 (range, 15.7-1147.5 cm3). Among all 137 markers tested for correlation with survival data, only programmed death-ligand (PDL) 1 and PDL2 expression showed a prognostic impact. Overall, both PDL1 and PDL2 genes were highly expressed in 37 patients (30.8%; PDL1high/PDL2high). The baseline clinical characteristics of patients with PDL1high/PDL2high were similar to those of other patients. In univariate analysis, PDL1high/PDL2high status was associated with poor progression-free survival (PFS) (hazard ratio [HR], 4.292) and overall survival (OS; HR, 8.24). In multivariate analysis, PDL1high/PDL2high status was an independent prognostic factor of adverse outcomes (PFS: HR, 5.22; OS: HR, 10.368). We validated these results in an independent cohort of 40 patients and confirmed the significant association between PDL1high/PDL2high status and inferior PFS (HR, 6.11). High PDL1/PDL2 gene expression defines a population with strong immune privilege and poorer outcomes from standard chemotherapy who might benefit from firstline checkpoint inhibitor therapy.
Vision Sensing-Based Online Correction System for Robotic Weld Grinding
Authors: Ge Jimin , Deng Zhaohui , Wang Shuixian , Li Zhongyang , Liu Wei , Nie Jiaxu 
Published: October 2023

AbstractThe service cycle and dynamic performance of structural parts are affected by the weld grinding accuracy and surface consistency. Because of reasons such as assembly errors and thermal deformation, the actual track of the robot does not coincide with the theoretical track when the weld is ground offline, resulting in poor workpiece surface quality. Considering these problems, in this study, a vision sensing-based online correction system for robotic weld grinding was developed. The system mainly included three subsystems: weld feature extraction, grinding, and robot real-time control. The grinding equipment was first set as a substation for the robot using the WorkVisual software. The input/output (I/O) ports for communication between the robot and the grinding equipment were configured via the I/O mapping function to enable the robot to control the grinding equipment (start, stop, and speed control). Subsequently, the Ethernet KRL software package was used to write the data interaction structure to realize real-time communication between the robot and the laser vision system. To correct the measurement error caused by the bending deformation of the workpiece, we established a surface profile model of the base material in the weld area using a polynomial fitting algorithm to compensate for the measurement data. The corrected extracted weld width and height errors were reduced by 2.01% and 9.3%, respectively. Online weld seam extraction and correction experiments verified the effectiveness of the system’s correction function, and the system could control the grinding trajectory error within 0.2 mm. The reliability of the system was verified through actual weld grinding experiments. The roughness, Ra, could reach 0.504 µm and the average residual height was within 0.21 mm. In this study, we developed a vision sensing-based online correction system for robotic weld grinding with a good correction effect and high robustness.
CRISPR/Cas9-based depletion of 16S ribosomal RNA improves library complexity of single-cell RNA-sequencing in planarians
Authors: Wang Kuang-Tse , Adler Carolyn E. 
Published: October 2023

Abstract
Background
Single-cell RNA-sequencing (scRNA-seq) relies on PCR amplification to retrieve information from vanishingly small amounts of starting material. To selectively enrich mRNA from abundant non-polyadenylated transcripts, poly(A) selection is a key step during library preparation. However, some transcripts, such as mitochondrial genes, can escape this elimination and overwhelm libraries. Often, these transcripts are removed in silico, but whether physical depletion improves detection of rare transcripts in single cells is unclear.

Results
We find that a single 16S ribosomal RNA is widely enriched in planarian scRNA-seq datasets, independent of the library preparation method. To deplete this transcript from scRNA-seq libraries, we design 30 single-guide RNAs spanning its length. To evaluate the effects of depletion, we perform a side-by-side comparison of the effects of eliminating the 16S transcript and find a substantial increase in the number of genes detected per cell, coupled with virtually complete loss of the 16S RNA. Moreover, we systematically determine that library complexity increases with a limited number of PCR cycles following CRISPR treatment. When compared to in silico depletion of 16S, physically removing it reduces dropout rates, retrieves more clusters, and reveals more differentially expressed genes.

Conclusions
Our results show that abundant transcripts reduce the retrieval of informative transcripts in scRNA-seq and distort the analysis. Physical removal of these contaminants enables the detection of rare transcripts at lower sequencing depth, and also outperforms in silico depletion. Importantly, this method can be easily customized to deplete any abundant transcript from scRNA-seq libraries.
Genome-wide allele frequency studies in Pacific oyster families identify candidate genes for tolerance to ostreid herpesvirus 1 (OsHV-1)
Authors: Divilov Konstantin , Merz Noah , Schoolfield Blaine , Green Timothy J. , Langdon Chris 
Published: October 2023

AbstractBackgroundHost genetics influences the development of infectious diseases in many agricultural animal species. Identifying genes associated with disease development has the potential to make selective breeding for disease tolerance more likely to succeed through the selection of different genes in diverse signaling pathways. In this study, four families of Pacific oysters (Crassostrea gigas) were identified to be segregating for a quantitative trait locus (QTL) on chromosome 8. This QTL was previously found to be associated with basal antiviral gene expression and survival to ostreid herpesvirus 1 (OsHV-1) mortality events in Tomales Bay, California. Individuals from these four families were phenotyped and genotyped in an attempt to find candidate genes associated with the QTL on chromosome 8.ResultsGenome-wide allele frequencies of oysters from each family prior to being planting in Tomales Bay were compared with the allele frequencies of oysters from respective families that survived an OsHV-1 mortality event. Six significant unique QTL were identified in two families in these genome-wide allele frequency studies, all of which were located on chromosome 8. Three QTL were assigned to candidate genes (ABCA1,PIK3R1, andWBP2) that have been previously associated with antiviral innate immunity in vertebrates.ConclusionThe identification of vertebrate antiviral innate immunity genes as candidate genes involved in molluscan antiviral innate immunity reinforces the similarities between the innate immune systems of these two groups. Causal variant identification in these candidate genes will enable future functional studies of these genes in an effort to better understand their antiviral modes of action.
Establishing the core elements of a frailty at the front door model of care using a modified real-time Delphi technique
Authors: O’Shaughnessy Íde , Fitzgerald Christine , Whiston Aoife , Harnett Patrick , Whitty Helen , Mulligan Des , Mullaney Marian , Devaney Catherine , Lang Deirdre , Hardimann Jennifer , Condon Brian , Hayes Christina , Holmes Alison , Barry Louise , McCormack Claire , Bounds Megan , Robinson Katie , O’Connor Margaret , Ryan Damien , Shchetkovsky Denys , Steed Fiona , Carey Leonora , Ahern Emer , Galvin Rose 
Published: October 2023

AbstractBackgroundInnovations in models of care for older adults living with frailty presenting to the emergency department (ED) have become a key priority for clinicians, researchers and policymakers due to the deleterious outcomes older adults experience due to prolonged exposure to such an environment. This study aimed to develop a set of expert consensus-based statements underpinning operational design, outcome measurement and evaluation of a Frailty at the Front Door (FFD) model of care for older adults within an Irish context.MethodsA modified real-time Delphi method was used. Facilitation of World Café focus groups with an expert panel of 86 members and seperate advisory groups with a Public and Patient Involvement panel of older adults and members of the Irish Association of Emergency Medicine generated a series of statements on the core elements of the FFD model of care. Statements were analysed thematically and incorporated into a real-time Delphi survey, which was emailed to members of the expert panel. Members were asked to rank 70 statements across nine domains using a 9-point Likert scale. Consensus criteria were defined a priori and guided by previous research using 9-point rating scales.ResultsFifty members responded to the survey representing an overall response rate of 58%. Following analyses of the survey responses, the research team reviewed statements for content overlap and refined a final list of statements across the following domains: aims and objectives of the FFD model of care; target population; screening and assessment; interventions; technology; integration of care; evaluation and metrics; and research.ConclusionDevelopment of a consensus derived FFD model of care represents an important step in generating national standards, implementation of a service model as intended and enhances opportunities for scientific impact. Future research should focus on the development of a core outcome set for studies involving older adults in the ED.
Severe anemia, severe leukopenia, and severe thrombocytopenia of amphotericin B deoxycholate-based induction therapy in patients with HIV-associated talaromycosis: a subgroup analysis of a prospective multicenter cohort study
Authors: Zhou Yihong , Lu Tao , Li Yan , Qin Yuanyuan , Lu Yanqiu , Tian Qun , Lan Ke , Zhou Guoqiang , Qin Yingmei , Harypursat Vijay , Li Shunmei , Lin Shide , Chen Yaokai 
Published: October 2023

Abstract
Background
This study’s objective was to investigate the predictors for severe anemia, severe leukopenia, and severe thrombocytopenia when amphotericin B deoxycholate-based induction therapy is used in HIV-infected patients with talaromycosis.

Methods
A total of 170 HIV-infected patients with talaromycosis were enrolled from January 1st, 2019, to September 30th, 2020.

Results
Approximately 42.9%, 20.6%, and 10.6% of the enrolled patients developed severe anemia, severe leukopenia, and severe thrombocytopenia, respectively. Baseline hemoglobin level < 100 g/L (OR = 5.846, 95% CI: 2.765 ~ 12.363), serum creatinine level > 73.4 µmol/L (OR = 2.573, 95% CI: 1.157 ~ 5.723), AST/ALT ratio > 1.6 (OR = 2.479, 95% CI: 1.167 ~ 5.266), sodium level ≤ 136 mmol/liter (OR = 4.342, 95% CI: 1.747 ~ 10.789), and a dose of amphotericin B deoxycholate > 0.58 mg/kg/d (OR = 2.504, 95% CI:1.066 ~ 5.882) were observed to be independent risk factors associated with the development of severe anemia. Co-infection with tuberculosis (OR = 3.307, 95% CI: 1.050 ~ 10.420), and platelet level (per 10 × 109 /L) (OR = 0.952, 95% CI: 0.911 ~ 0.996) were shown to be independent risk factors associated with the development of severe leukopenia. Platelet level < 100 × 109 /L (OR = 2.935, 95% CI: 1.075 ~ 8.016) was identified as the independent risk factor associated with the development of severe thrombocytopenia. There was no difference in progression to severe anemia, severe leukopenia, and severe thrombocytopenia between the patients with or without fungal clearance at 2 weeks. 10 mg on the first day of amphotericin B deoxycholate was calculated to be independent risk factors associated with the development of severe anemia (OR = 2.621, 95% CI: 1.107 ~ 6.206). The group receiving a starting amphotericin B dose (10 mg, 20 mg, daily) exhibited the highest fungal clearance rate at 96.3%, which was significantly better than the group receiving a starting amphotericin B dose (5 mg, 10 mg, 20 mg, daily) (60.9%) and the group receiving a starting amphotericin B dose (5 mg, 15 mg, and 25 mg, daily) (62.9%).

Conclusion
The preceding findings reveal risk factors for severe anemia, severe leukopenia, and severe thrombocytopenia. After treatment with Amphotericin B, these severe adverse events are likely unrelated to fungal clearance at 2 weeks. Starting amphotericin B deoxycholate at a dose of 10 mg on the first day may increase the risk of severe anemia but can lead to earlier fungal clearance.

Trial registration
ChiCTR1900021195. Registered 1 February 2019.
Awareness of and willingness to use oral pre-exposure prophylaxis (PrEP) for HIV prevention among sexually active adults in Malawi: results from the 2020 Malawi population-based HIV impact assessment
Authors: Kabaghe Alinune Nathanael , Singano Victor , Payne Danielle , Maida Alice , Nyirenda Rose , Mirkovic Kelsey , Jahn Andreas , Patel Pragna , Brown Kristin , Farahani Mansoor , Kayigamba Felix , Tenthani Lyson , Ogollah Francis , Auld Andrew , Zulu Fatima , Msungama Wezi , Wadonda-Kabondo Nellie 
Published: October 2023

Abstract
Background
The World Health Organization recommends Pre-Exposure Prophylaxis (PrEP) for all populations at substantial risk of HIV infection. Understanding PrEP awareness and interest is crucial for designing PrEP programs; however, data are lacking in sub-Saharan Africa. In Malawi, oral PrEP was introduced in 2018. We analyzed data from the 2020 Malawi Population-based HIV Impact Assessment (MPHIA) to assess PrEP awareness and factors associated with PrEP interest in Malawi.

Methods
MPHIA 2020 was a national cross-sectional household-based survey targeting adults aged 15 + years. Oral PrEP was first described to the survey participants as taking a daily pill to reduce the chance of getting HIV. To assess awareness, participants were asked if they had ever heard of PrEP and to assess interest, were asked if they would take PrEP to prevent HIV, regardless of previous PrEP knowledge. Only sexually active HIV-negative participants are included in this analysis. We used multivariable logistic regression to assess sociodemographic factors and behaviors associated with PrEP interest. All results were weighted.

Results
We included 13,995 HIV-negative sexually active participants; median age was 29 years old. Overall, 15.0%, 95% confidence interval (CI): 14.2–15.9% of participants were aware of PrEP. More males (adjusted odds ratio (aOR): 1.3, 95% CI: 1.2–1.5), those with secondary (aOR: 1.5, 95% CI: 1.2-2.0) or post-secondary (aOR: 3.4, 95% CI: 2.4–4.9) education and the wealthiest (aOR: 1.6, 95% CI: 1.2-2.0) were aware of PrEP than female, those without education and least wealthy participants, respectively. Overall, 73.0% (95% CI: 71.8–74.1%) of participants were willing to use PrEP. Being male (aOR: 1.2; 95% CI: 1.1–1.3) and having more than one sexual partner (aOR: 1.7 95% CI: 1.4–1.9), were associated higher willingness to use PrEP.

Conclusions
In this survey, prior PrEP knowledge and use were low while PrEP interest was high. High risk sexual behavior was associated with willingness to use PrEP. Strategies to increase PrEP awareness and universal access, may reduce HIV transmission.
Ceftazidime/avibactam combined with colistin: a novel attempt to treat carbapenem-resistant Gram-negative bacilli infection
Authors: Zheng Zihao , Shao Ziqiang , Lu Lihai , Tang Siyu , Shi Kai , Gong Fangxiao , Liu Jingquan 
Published: October 2023

Abstract
Background
The rapid global emergence and spread of carbapenem-resistant Gram-negative bacilli (CR-GNB) is recognized as a major public health concern, and there are currently few effective treatments for CR-GNB infection. The aim of this study was to investigate the clinical characteristics and outcomes of patients with CR-GNB infections treated with ceftazidime/avibactam (CAZ/AVI) combined with colistin from October 2019 to February 2023 in China.

Methods
A total of 31 patients with CR-GNB infections were retrospectively identified using the electronic medical record system of Zhejiang Provincial People's Hospital.

Results
Thirty-one patients were treated with CAZ/AVI combined with colistin. Respiratory tract infections (87%) were most common. The common drug-resistant bacteria encompass Klebsiella pneumonia (54.8%), Acinetobacter baumannii (29.0%), and Pseudomonas aeruginosa (16.1%). The 30-day mortality rate was 29.0%, and the 7-day microbial clearance rate was 64.5%. The inflammatory marker CRP changes, but not PCT and WBC, were statistically significant on days 7 and 14 after combination therapy. There were seven patients developing acute renal injury (AKI) after combination therapy and treating with continuous renal replacement therapy (CRRT). Two patients developed diarrhea.

Conclusion
The combination of CAZ/AVI and colistin has potential efficacy in patients with CR-GNB infection, but more studies are needed to determine whether it can reduce 30-day mortality rates and increase 7-day microbial clearance. At the same time, the adverse reactions of combination therapy should not be ignored.