bluuebunny/crossref_metadata_2025_split huggingface dataset:
CAR T cells and time-limited ibrutinib as treatment for relapsed/refractory mantle cell lymphoma: the phase 2 TARMAC study
Authors: Minson Adrian , Hamad Nada , Cheah Chan Y. , Tam Constantine , Blombery Piers , Westerman David , Ritchie David , Morgan Huw , Holzwart Nicholas , Lade Stephen , Anderson Mary Ann , Khot Amit , Seymour John F. , Robertson Molly , Caldwell Imogen , Ryland Georgina , Saghebi Javad , Sabahi Zahra , Xie Jing , Koldej Rachel , Dickinson Michael 
Published: October 2023

Abstract
CD19-directed chimeric antigen receptor T cells (CAR-T) achieve high response rates in patients with relapsed/refractory mantle cell lymphoma (MCL). However, their use is associated with significant toxicity, relapse concern, and unclear broad tractability. Preclinical and clinical data support a beneficial synergistic effect of ibrutinib on apheresis product fitness, CAR-T expansion, and toxicity. We evaluated the combination of time-limited ibrutinib and CTL019 CAR-T in 20 patients with MCL in the phase 2 TARMAC study. Ibrutinib commenced before leukapheresis and continued through CAR-T manufacture for a minimum of 6 months after CAR-T administration. The median prior lines of therapy was 2; 50% of patients were previously exposed to a Bruton tyrosine kinase inhibitor (BTKi). The primary end point was 4-month postinfusion complete response (CR) rate, and secondary end points included safety and subgroup analysis based on TP53 aberrancy. The primary end point was met; 80% of patients demonstrated CR, with 70% and 40% demonstrating measurable residual disease negativity by flow cytometry and molecular methods, respectively. At 13-month median follow-up, the estimated 12-month progression-free survival was 75% and overall survival 100%. Fifteen patients (75%) developed cytokine release syndrome; 12 (55%) with grade 1 to 2 and 3 (20%) with grade 3. Reversible grade 1 to 2 neurotoxicity was observed in 2 patients (10%). Efficacy was preserved irrespective of prior BTKi exposure or TP53 mutation. Deep responses correlated with robust CAR-T expansion and a less exhausted baseline T-cell phenotype. Overall, the safety and efficacy of the combination of BTKi and T-cell redirecting immunotherapy appears promising and merits further exploration. This trial was registered at www.ClinicalTrials.gov as #NCT04234061.
Cerebral hemodynamic changes after haploidentical hematopoietic stem cell transplant in adults with sickle cell disease
Authors: Aumann Megan A. , Richerson Wesley , Song Alexander K. , Davis L. Taylor , Pruthi Sumit , Davis Samantha , Patel Niral J. , Custer Chelsea , Kassim Adetola A. , DeBaun Michael R. , Donahue Manus J. , Jordan Lori C. 
Published: October 2023

Abstract
Preliminary evidence from a series of 4 adults with sickle cell disease (SCD) suggests that hematopoietic stem cell transplant (HSCT) improves cerebral hemodynamics. HSCT largely normalizes cerebral hemodynamics in children with SCD. We tested the hypothesis in adults with SCD that cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO2) measured using magnetic resonance imaging, normalized to healthy values, comparing measurements from ∼1 month before to 12 to 24 months after HSCT (n = 11; age, 33.3 ± 8.9 years; 389 ± 150 days after HSCT) with age-, race- and sex-matched values from healthy adults without sickle trait (n = 28; age, 30.2 ± 5.6 years). Before transplant, 7 patients had neurological indications for transplant (eg, overt stroke) and 4 had nonneurological reasons for haploidentical bone marrow transplant (haplo-BMT). All received haplo-BMT from first-degree relatives (parent, sibling, or child donor) with reduced-intensity preparation and maintained engraftment. Before transplant, CBF was elevated (CBF, 69.11 ± 24.7 mL/100 g/min) compared with that of controls (P = .004). Mean CBF declined significantly after haplo-BMT (posttransplant CBF, 48.2 ± 13.9 mL/100 g/min; P = .003). OEF was not different from that of controls at baseline and did not change significantly after haplo-BMT (pretransplant, 43.1 ± 6.7%; posttransplant, 39.6 ± 7.0%; P = .34). After transplant, CBF and OEF were not significantly different from controls (CBF, 48.2 ± 13.4 mL/100 g/min; P = .78; and OEF, 39.6 ± 7.0%; P &gt; .99). CMRO2 did not change significantly after haplo-BMT (pretransplant, 3.18 ± 0.87 mL O2/100 g/min; posttransplant, 2.95 ± 0.83; P = .56). Major complications of haplo-BMT included 1 infection-related death and 1 severe chronic graft-versus-host disease. Haplo-BMT in adults with SCD reduces CBF to that of control values and maintains OEF and CMRO2 on average at levels observed in healthy adult controls. The trial was registered at www.clinicaltrials.gov as #NCT01850108.
Real-world characteristics of “super-responders” to mepolizumab and benralizumab in severe eosinophilic asthma and eosinophilic granulomatosis with polyangiitis
Authors: Portacci Andrea , Campisi Raffaele , Buonamico Enrico , Nolasco Santi , Pelaia Corrado , Crimi Nunzio , Benfante Alida , Triggiani Massimo , Spadaro Giuseppe , Caiaffa Maria Filomena , Scioscia Giulia , Detoraki Aikaterini , Valenti Giuseppe , Papia Francesco , Tomasello Alessandra , Scichilone Nicola , Pelaia Girolamo , Crimi Claudia , Carpagnano Giovanna Elisiana 
Published: October 2023

BackgroundThe current definition of severe eosinophilic asthma (SEA) super-responders to biologic treatment does not include patients with other eosinophil-based comorbidities. Although eosinophilic granulomatosis with polyangiitis (EGPA) is frequently associated with SEA, we lack data on a possible super-response to biologic treatments in patients suffering from these two diseases. We aim to assess super-responder features in real-life patients with SEA and EGPA treated with mepolizumab and benralizumab.MethodsWe enrolled 39 patients with SEA and EGPA eligible for treatment with mepolizumab or benralizumab. Super-responder assessment was performed considering oral corticosteroid (OCS) cessation, lack of exacerbations, forced expiratory volume in 1 s and Asthma Control Test (ACT) improvement.ResultsSuper-responders showed worse clinical baseline characteristics than non-super-responder patients, with a greater improvement in severe asthma exacerbations, OCS dose reduction and ACT score increase. Definition of super-responders was consistent only considering a 12-month course of monoclonal antibody, lacking sensitivity in earlier evaluations.ConclusionMepolizumab and benralizumab are safe and effective in patients with EGPA and SEA, since a consistent proportion of patients show a super-response after 12 months of treatment. Further studies will address specific criteria for super-responder assessment in these patients.
Integrative genome-scale analyses reveal post-transcriptional signatures of early human small intestinal development in a directed differentiation organoid model
Authors: Hung Yu-Han , Capeling Meghan , Villanueva Jonathan W. , Kanke Matt , Shanahan Michael T. , Huang Sha , Cubitt Rebecca , Rinaldi Vera D. , Schimenti John C. , Spence Jason R. , Sethupathy Praveen 
Published: October 2023

Abstract
Background
MicroRNAs (miRNAs) are important post-transcriptional gene regulators controlling cellular lineage specification and differentiation during embryonic development, including the gastrointestinal system. However, miRNA-mediated regulatory mechanisms involved in early embryonic development of human small intestine (SI) remains underexplored. To explore candidate roles for miRNAs in prenatal SI lineage specification in humans, we used a multi-omic analysis strategy in a directed differentiation model that programs human pluripotent stem cells toward the SI lineage.

Results
We leveraged small RNA-seq to define the changing miRNA landscape, and integrated chromatin run-on sequencing (ChRO-seq) and RNA-seq to define genes subject to significant post-transcriptional regulation across the different stages of differentiation. Small RNA-seq profiling revealed temporal dynamics of miRNA signatures across different developmental events of the model, including definitive endoderm formation, SI lineage specification and SI regional patterning. Our multi-omic, integrative analyses showed further that the elevation of miR-182 and reduction of miR-375 are key events during SI lineage specification. We demonstrated that loss of miR-182 leads to an increase in the foregut master marker SOX2. We also used single-cell analyses in murine adult intestinal crypts to support a life-long role for miR-375 in the regulation of Zfp36l2. Finally, we uncovered opposing roles of SMAD4 and WNT signaling in regulating miR-375 expression during SI lineage specification. Beyond the mechanisms highlighted in this study, we also present a web-based application for exploration of post-transcriptional regulation and miRNA-mediated control in the context of early human SI development.

Conclusion
The present study uncovers a novel facet of miRNAs in regulating prenatal SI development. We leveraged multi-omic, systems biology approaches to discover candidate miRNA regulators associated with early SI developmental events in a human organoid model. In this study, we highlighted miRNA-mediated post-transcriptional regulation relevant to the event of SI lineage specification. The candidate miRNA regulators that we identified for the other stages of SI development also warrant detailed characterization in the future.
Transcriptomic analysis reveals a tissue-specific loss of identity during ageing and cancer
Authors: dos Santos Gabriel Arantes , Chatsirisupachai Kasit , Avelar Roberto A. , de Magalhães João Pedro 
Published: October 2023

Abstract
Introduction
Understanding changes in cell identity in cancer and ageing is of great importance. In this work, we analyzed how gene expression changes in human tissues are associated with tissue specificity during cancer and ageing using transcriptome data from TCGA and GTEx.

Results
We found significant downregulation of tissue-specific genes during ageing in 40% of the tissues analyzed, which suggests loss of tissue identity with age. For most cancer types, we have noted a consistent pattern of downregulation in genes that are specific to the tissue from which the tumor originated. Moreover, we observed in cancer an activation of genes not usually expressed in the tissue of origin as well as an upregulation of genes specific to other tissues. These patterns in cancer were associated with patient survival. The age of the patient, however, did not influence these patterns.

Conclusion
We identified loss of cellular identity in 40% of the tissues analysed during human ageing, and a clear pattern in cancer, where during tumorigenesis cells express genes specific to other organs while suppressing the expression of genes from their original tissue. The loss of cellular identity observed in cancer is associated with prognosis and is not influenced by age, suggesting that it is a crucial stage in carcinogenesis.
Antimicrobial resistance profiles of salmonella spp. and escherichia coli isolated from fresh nile tilapia (oreochromis niloticus) fish marketed for human consumption
Authors: Mumbo Millicent T. , Nyaboga Evans N. , Kinyua Johnson K. , Muge Edward K. , Mathenge Scholastica G. K. , Rotich Henry , Muriira Geoffrey , Njiraini Bernard , Njiru Joshua M. 
Published: October 2023

AbstractBackgroundSalmonellaspp. and pathogenic strains ofEscherichia coliare among the major foodborne zoonotic pathogens. These bacterial pathogens cause human illnesses characterized by hemorrhagic colitis, vomiting, nausea, and other agent-related symptoms. The increasing occurrence of antimicrobial resistance in these pathogens is also a serious public health concern globally. Regular surveillance of phenotypes and genotypes ofSalmonellaspp. andEscherichia colifrom animal-derived foods is necessary for effective reduction and control of these foodborne pathogens. This study was conducted to assess the occurrence, antimicrobial resistance, virulence genes and genetic diversity ofSalmonellaspp. andE. coliisolates from fresh Nile tilapia obtained from retail markets in Nairobi, Kenya.MethodsA total of 68 fresh Nile tilapia fish samples were collected from retail markets and used for isolation ofSalmonellaspp. andE. coli. Antimicrobial susceptibilities of the isolates weretested by Kirby-Bauer agar disc diffusion method. According to the antimicrobial resistance profiles, the multi-drug resistant isolates were identified by 16 S rRNA sequencing and phylogenetic analysis using the Bayesian inference method. The MDRSalmonellaspp. andE. coliisolates were subjected to PCR-based screening for the detection virulence and antibiotic resistance genes.ResultsThe prevalence of contamination of the fish samples withSalmonellaspp. andE.coliwas 26.47% and 35.29% respectively. Overall phenotypic resistance among theSalmonellaspp. ranged from 5.5% for ceftazidime, chloramphenicol, meropenem, nitrofurantoin and streptomycin and 22.2% for penicillin-G. ForE. coliphenotypic resistance ranged from 4.2% for ceftazidime and chloramphenicol and 25% for rifampicin. Multi-drug resistance was observed in threeSalmonellaspp. and twoE. coliisolates. Results of 16 S rRNA sequences, sequence alignment and phylogenic trees confirmed the identified MDR isolates asS. typhymuriumWES-09,S. typhymuriumMAK-22,S. typhimuriumEMB-32 andE. coliMAK-26 andE. coliLAN-35. The presence of antibiotic-resistance genes belonging to β-lactamases, tetracycline, sulfonamide, trimethoprim and aminoglycosides-resistant genes were detected in all the identified MDR isolates.ConclusionsThe findings from this study indicate that Nile tilapia (Oreochromis niloticus) sold in retail markets can acts as reservoirs ofSalmonellaspp. andE.colipathogens linked to human disease, some of which were multidrug resistance to critically important antimicrobials. Both microorganisms are of zoonotic significance and represent a significant public health risk to the society.
Bacterial colony size growth estimation by deep learning
Authors: Nagy Sára Ágnes , Makrai László , Csabai István , Tőzsér Dóra , Szita Géza , Solymosi Norbert 
Published: October 2023

AbstractThe bacterial growth rate is important for pathogenicity and food safety. Therefore, the study of bacterial growth rate over time can provide important data from a medical and veterinary point of view. We trained convolutional neural networks (CNNs) on manually annotated solid medium cultures to detect bacterial colonies as accurately as possible. Predictions of bacterial colony size and growth rate were estimated from image sequences of independent Staphylococcus aureus cultures using trained CNNs. A simple linear model for control cultures with less than 150 colonies estimated that the mean growth rate was 60.3 $$\mu m/h$$

μ
m
/
h

for the first 24 h. Analyzing with a mixed effect model that also takes into account the effect of culture, smaller values of change in colony size were obtained (control: 51.0 $$\mu m/h$$

μ
m
/
h

, rifampicin pretreated: 36.5$$\mu m/h$$

μ
m
/
h

). An increase in the number of neighboring colonies clearly reduces the colony growth rate in the control group but less typically in the rifampicin-pretreated group. Based on our results, CNN-based bacterial colony detection and the subsequent analysis of bacterial colony growth dynamics might become an accurate and efficient tool for bacteriological work and research.
Prehospital factors associated with out-of-hospital cardiac arrest outcomes in a metropolitan city: a 4-year multicenter study
Authors: Ahn Jae Yun , Ryoo Hyun Wook , Moon Sungbae , Jung Haewon , Park Jungbae , Lee Won Kee , Kim Jong-yeon , Lee Dong Eun , Kim Jung Ho , Lee Sang-Hun 
Published: October 2023

Abstract
Background
Prehospital factors play a vital role in out-of-hospital cardiac arrest (OHCA) survivability, and they vary between countries and regions. We investigated the prehospital factors associated with OHCA outcomes in a single metropolitan city in the Republic of Korea.

Methods
This study included adult medical OHCA patients enrolled prospectively, using data from the citywide OHCA registry for patients registered between 2018 and 2021. The primary outcome was survival to hospital discharge. Multivariable logistic regression analysis was conducted to determine the factors associated with the study population’s clinical outcomes, adjusting for covariates. We performed a sensitivity analysis for clinical outcomes only for patients without prehospital return of spontaneous circulation prior to emergency medical service departure from the scene.

Results
In multivariable logistic regression analysis, older age (odds ratio [OR] 0.96; 95% confidence interval [CI] 0.95–0.97), endotracheal intubation (adjusted odds ratio [aOR] 0.29; 95% [CIs] 0.17–0.51), supraglottic airway (aOR 0.29; 95% CI 0.17–0.51), prehospital mechanical chest compression device use (OR 0.13; 95% CI 0.08–0.18), and longer scene time interval (OR 0.96; 95% CI 0.93–1.00) were negatively associated with survival. Shockable rhythm (OR 24.54; 95% CI 12.99–42.00), pulseless electrical activity (OR 3.11; 95% CI 1.74–5.67), and witnessed cardiac arrest (OR 1.59; 95% CI 1.07–2.38) were positively associated with survival. In the sensitivity analysis, endotracheal intubation, supraglottic airway, prehospital mechanical chest compression device use, and longer scene time intervals were associated with significantly lower survival to hospital discharge.

Conclusions
Regional resuscitation protocol should be revised based on the results of this study, and modifiable prehospital factors associated with lower survival of OHCA should be improved.
Imaging findings and clinical relevance of 68Ga-Pentixafor PET in atherosclerosis: a systematic review
Authors: Wang Min , Zhang Jiayu , Ma Jiao , Liu Liyi , Wang Jia , Zhang Chunyin 
Published: October 2023

Abstract
Objective
We aimed to perform a qualitative synthesis of evidence on the role of 68Ga-Pentixafor PET in atherosclerosis.

Methods
A systematic search of the PubMed and Embase databases for studies reporting the evaluation of atherosclerotic lesions by 68Ga-Pentixafor PET was performed with a search time frame from database creation to 2022-12-26. The diagnostic test evaluation tool QUADAS-2 was used to evaluate the quality of the included literature and to perform descriptive analyses of relevant outcome indicators.

Results
A total of 6 studies with 280 patients were included. One study reported only imaging outcome metrics, while the other five studies reported imaging outcome metrics and clinical correlation metrics. For imaging outcomes, three studies reported imaging results for 68Ga-Pentixafor PET only, and the other three studies reported imaging results for comparative analysis of 68Ga-Pentixafor PET with 18F-FDG PET. For clinical correlation, three studies reported the correlation between tracer uptake and cardiovascular risk factors, one study reported the correlation between tracer uptake and plaque calcification, and one study reported the correlation between all three: tracer uptake, cardiovascular risk factors, and plaque calcification.

Conclusion
68Ga-Pentixafor PET has a good imaging effect on atherosclerotic lesions, and it is a promising imaging modality that may replace 18F-FDG PET for atherosclerosis imaging in the future. In patients with atherosclerosis, there is a clear clinical correlation between cardiovascular risk factors, tracer uptake, and plaque calcification.
Non-contrast low-dose CT can be used for volumetry of ADPKD
Authors: Yoo Jaeyeong , Kim Jin up , Kim Jisu , Jeon Sohyun , Song Young-jin , Choi Kwang-ho , Kim Seok-hyung , Yoon Jong-woo , Kim Hyunsuk 
Published: October 2023

Abstract
Background
Kidney volume provides important information for the diagnosis and prognosis of autosomal dominant polycystic kidney disease (ADPKD), as well as for the evaluation of the effects of drugs such as tolvaptan. Non-contrast computed tomography (CT) is commonly used for volumetry, and this study examined the correspondence and correlation of kidney volume measured by standard-dose or low-dose CT.

Methods
Axial standard-dose and low-dose CT images with 1-mm slices were obtained from 24 ADPKD patients. The kidney was segmented in the Synapse 3D software and the kidney volume was calculated using stereology. The kidney volume was compared between the two sets of images using R2, Bland-Altman plots, coefficient of variation, and intra-class correlation coefficients (ICCs).

Results
The mean age of the 24 patients was 48.4 ± 10.9 years, and 45.8% were men (n = 11). The mean total kidney volume on standard-dose CT was 1501 ± 838.2 mL. The R2 of volume between standard-dose and low-dose CT was 0.995. In the Bland-Altman plot, except for one case with a large kidney volume, the two measurements were consistent, and the coefficient of variation and ICC were also good (0.02, 0.998). The CT radiation dose (dose-length product) was 229 ± 68 mGy·cm for standard-dose CT and 50 ± 19 mGy·cm for low-dose CT. A comparable volume was obtained with 20% of the radiation dose of standard-dose CT.

Conclusions
Standard-dose and low-dose CT showed comparable kidney volume in ADPKD. Therefore, low-dose CT can substitute for ADPKD volumetry while minimizing radiation exposure.
Qualitative assessment of the patient experience of primary hyperoxaluria type 1: an observational study
Authors: Danese David , Goss Diana , Romano Carla , Gupta Catherine 
Published: October 2023

AbstractBackgroundWithout effective intervention, primary hyperoxaluria type 1 (PH1) causes oxalate-induced kidney damage, leading to end-stage kidney disease and serious complications throughout the body. Although PH1 carries a heavy burden that impacts quality of life, literature on the experiences of those living with PH1 and caring for patients with PH1 is limited. This study aimed to describe the diagnostic journey in PH1 and characterize patients’ and caregivers’ self-reported experiences throughout the disease course.MethodsThis was an observational study involving in-depth, semi-structured telephone interviews. Dominant trends were assessed using constant comparative analysis to identify themes in interviewees’ descriptions of their experiences. Individuals aged ≥ 12 years and caregivers of children aged 6–17 years with genetically confirmed PH1 were eligible. Informed consent/assent and ability to read and speak English were required.ResultsInterviewees (16 patients, 12 caregivers) reported a prolonged diagnostic journey due to low disease awareness, among other factors. Upon diagnosis, PH1 was frequently symptomatic, typically involving kidney stone-related symptoms but also potentially symptoms arising beyond the kidneys. PH1 most commonly led to worry and social impairment in adolescents, impaired physical function in adults, and a range of impacts on caregivers. In late-stage disease, dialysis was the most burdensome aspect of living with PH1 (due to time requirements, limitations from living with a catheter, etc.), and this burden was exacerbated by the COVID-19 pandemic. Benefits desired from PH1 management included reductions in laboratory measures of oxalate burden, kidney stone and urination frequency, and oxalate-related skin ulcers.ConclusionsPH1 greatly impacts patients’ and caregivers’ lives, primarily due to burdensome disease manifestations and associated emotional, physical, and practical impacts, as well as disease management challenges – particularly those related to dialysis in late-stage disease.