bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preferential expansion of CD8+ CD19-CAR T cells postinfusion and the role of disease burden on outcome in pediatric B-ALL
Authors: Talleur Aimee C. , Qudeimat Amr , Métais Jean-Yves , Langfitt Deanna , Mamcarz Ewelina , Crawford Jeremy Chase , Huang Sujuan , Cheng Cheng , Hurley Caitlin , Madden Renee , Sharma Akshay , Suliman Ali , Srinivasan Ashok , Velasquez M. Paulina , Obeng Esther A. , Willis Catherine , Akel Salem , Karol Seth E. , Inaba Hiroto , Bragg Allison , Zheng Wenting , Zhou Sheng M. , Schell Sarah , Tuggle-Brown MaCal , Cullins David , Patil Sagar L , Li Ying , Thomas Paul G. , Zebley Caitlin , Youngblood Benjamin , Pui Ching-Hon , Lockey Timothy , Geiger Terrence L. , Meagher Michael M. , Triplett Brandon M. , Gottschalk Stephen 
Published: April 2022

Abstract
T cells expressing CD19-specific chimeric antigen receptors (CD19-CARs) have potent antileukemia activity in pediatric and adult patients with relapsed and/or refractory B-cell acute lymphoblastic leukemia (B-ALL). However, not all patients achieve a complete response (CR), and a significant percentage relapse after CD19-CAR T-cell therapy due to T-cell intrinsic and/or extrinsic mechanisms. Thus, there is a need to evaluate new CD19-CAR T-cell products in patients to improve efficacy. We developed a phase 1/2 clinical study to evaluate an institutional autologous CD19-CAR T-cell product in pediatric patients with relapsed/refractory B-ALL. Here we report the outcome of the phase 1 study participants (n = 12). Treatment was well tolerated, with a low incidence of both cytokine release syndrome (any grade, n = 6) and neurotoxicity (any grade, n = 3). Nine out of 12 patients (75%) achieved a minimal residual disease-negative CR in the bone marrow (BM). High disease burden (≥40% morphologic blasts) before CAR T-cell infusion correlated with increased side effects and lower response rate, but not with CD19-CAR T-cell expansion. After infusion, CD8+ CAR T cells had a proliferative advantage over CD4+ CAR T cells and at peak expansion, had an effector memory phenotype with evidence of antigen-driven differentiation. Patients that proceeded to allogeneic hematopoietic cell transplantation (AlloHCT) had sustained, durable responses. In summary, the initial evaluation of our institutional CD19-CAR T-cell product demonstrates safety and efficacy while highlighting the impact of pre-infusion disease burden on outcomes. This trial was registered at www.clinicaltrials.gov as #NCT03573700.
Desmopressin response depends on the presence and type of genetic variants in patients with type 1 and type 2 von Willebrand disease
Authors: Atiq Ferdows , Heijdra Jessica , Snijders Fleur , Boender Johan , Kempers Eva , van Heerde Waander L. , Maas Dominique P. M. S. M. , Krouwel Sandy , Schoormans Selene C. , de Meris Joke , Schols Saskia E. M. , van Galen Karin P. M. , van der Bom Johanna G. , Cnossen Marjon H. , Meijer Karina , Fijnvandraat Karin , Eikenboom Jeroen , Leebeek Frank W. G. 
Published: April 2022

Abstract
Patients with type 1 and type 2 von Willebrand disease (VWD) can be treated with desmopressin. Although a previous study has shown that the location of the causative VWF gene variant is associated with desmopressin response in type 1 VWD, the association between variants in the VWF gene and desmopressin response is not yet fully understood. Our primary aim was to compare desmopressin response in type 1 VWD patients with and without a VWF gene variant. Secondly, we investigated whether desmopressin response depends on specific VWF gene variants in type 1 and type 2 VWD. We included 250 patients from the Willebrand in the Netherlands study: 72 type 1 without a VWF gene variant, 108 type 1 with a variant, 45 type 2A, 16 type 2M, and 9 type 2N patients. VWF gene was analyzed with ion semiconductor sequencing and Multiplex Ligation-dependent Probe Amplification. Complete response to desmopressin was observed in all type 1 VWD patients without a variant, 64.3% of type 1 patients with a variant, and 31.3% of type 2 patients (P &lt; .001). Despite a large interindividual variability in desmopressin response, patients with the same variant had comparable desmopressin responses. For instance, in 6 type 1 patients with exon 4 to 5 deletion, mean VWF activity at 1 hour after desmopressin was 0.81 IU/mL, with a coefficient of variation of 22.9%. In conclusion, all type 1 VWD patients without a VWF gene variant respond to desmopressin. In type 1 and type 2 VWD patients with a VWF variant, desmopressin response highly depends on the VWF gene variants.
Prevalence and burden of chronic cough in China: a national cross-sectional study
Authors: Huang Kewu , Gu Xiaoying , Yang Ting , Xu Jianying , Yang Lan , Zhao Jianping , Zhang Xiangyan , Bai Chunxue , Kang Jian , Ran Pixin , Shen Huahao , Wen Fuqiang , Chen Yahong , Sun Tieying , Shan Guangliang , Lin Yingxiang , Wu Sinan , Wang Ruiying , Shi Zhihong , Xu Yongjian , Ye Xianwei , Song Yuanlin , Wang Qiuyue , Zhou Yumin , Li Wen , Ding Liren , Wan Chun , Yao Wanzhen , Guo Yanfei , Xiao Fei , Lu Yong , Peng Xiaoxia , Xiao Dan , Bu Xiaoning , Zhang Hong , Zhang Xiaolei , An Li , Zhang Shu , Cao Zhixin , Zhan Qingyuan , Yang Yuanhua , Liang Lirong , Dai Huaping , Cao Bin , He Jiang , Chung Kian Fan , Wang Chen 
Published: April 2022

BackgroundChronic cough is a common complaint, but there are no population-based data on its burden in China. We determined the prevalence of chronic cough and its impact on health status in adults stratified by sex, age and the diagnosis of COPD or the presence of small airway dysfunction (SAD).MethodsA representative sample of 57 779 Chinese adults aged 20 years or older was recruited and pulmonary function test was measured. Chronic cough was defined as cough lasting for >3 months in each year. Quality of life was assessed by the 12-item Short Form Health Survey (SF-12), and self-reported history of hospital visits was recorded.ResultsChronic cough was found in 3.6% (95% CI 3.1–4.1) of Chinese adults, 2.4% (95% CI 1.9–3.1) of those aged 20–49 years and 6.0% (95% CI 5.3–6.8) of those aged 50 years or older. Individuals with chronic cough had an impaired physical component summary (PCS) score of the SF-12 (p<0.0001) and more emergency visits (p=0.0042) and hospital admissions (p=0.0002). Furthermore, the impact of chronic cough on PCS score was more significant in those aged 50 years or older, or with COPD (p=0.0018 or 0.0002, respectively), with the impact on hospital admission being more significant in those with COPD or with SAD (p=0.0026 or 0.0065, respectively).ConclusionsChronic cough is prevalent in China and is associated with a poorer health status, especially in individuals aged 50 years or older and those with the diagnosis of COPD or SAD.
Multiplex bacterial PCR in the bronchoalveolar lavage fluid of non-intubated patients with suspected pulmonary infection: a quasi-experimental study
Authors: Salina Anna , Schumann Desiree M. , Franchetti Léo , Jahn Kathleen , Purkabiri Kurosch , Müller Raphael , Strobel Werner , Khanna Nina , Tamm Michael , Stolz Daiana 
Published: April 2022

BackgroundEarly pathogen identification in pulmonary infection is crucial to guide antibacterial therapy and decrease length of hospital stay. We hypothesise that compared to conventional diagnostic methods, a multiplex bacterial polymerase chain reaction assay has a higher diagnostic yield in bronchoalveolar lavage (BAL) fluid and improved clinical outcomes in patients with suspicion of pulmonary infection.MethodsA prospective, monocentric, quasi-experimental, observational study was carried out. Unselected patients with suspected pulmonary infection who underwent bronchoscopy with BAL were included in the study over a period of 1 year. In addition to conventional diagnostic methods, a multiplex PCR bacterial assay was performed in BAL on a 2 week on: 1 week off pre-determined schedule. No therapeutic recommendations were provided to the treating physician.Results605 cases were included, 54% of whom were immunosuppressed. Conventional diagnostic methods detected 56% of the bacteria evidenced by PCR. PCR failed to detect bacteria in 4% of the cases with a positive conventional diagnostic result. After bronchoscopy, 42% of the patients received antibacterial therapy for pulmonary infection for a median of 12 antibiotic days. There was no statistically significant difference in length of hospital stay (median 8versus8; p=0.839), antibiotic exposure (median 11versus14; p=0.362) or number of antibiotics prescribed (median 2versus2; p=0.595) between the two groups.ConclusionsA multiplex bacterial PCR detected more bacteria in BAL fluid than conventional diagnostic methods. However, without a specific antibiotic stewardship approach and a clear understanding of the clinical implications of a positive or negative PCR result, the PCR results did not influence clinical outcomes.
Nonpharmaceutical interventions to prevent viral respiratory infection in community settings: an umbrella review
Authors: Zhao Hedi , Jatana Sukhdeep , Bartoszko Jessica , Loeb Mark 
Published: April 2022

BackgroundRespiratory viruses pose an important public health threat to most communities. Nonpharmaceutical interventions (NPIs) such as masks, hand hygiene or physical distancing, among others, are believed to play an important role in reducing transmission of respiratory viruses. In this umbrella review, we summarise the evidence of the effectiveness of NPIs for the prevention of respiratory virus transmission in the community setting.ObservationsA systematic search of PubMed, Embase, Medline and Cochrane reviews resulted in a total of 24 studies consisting of 11 systematic reviews and meta-analyses, 12 systematic reviews without meta-analyses and one standalone meta-analysis. The current evidence from these data suggests that hand hygiene is protective against respiratory viral infection. The use of hand hygiene and facemasks, facemasks alone and physical distancing were interventions with inconsistent evidence. Interventions such as school closures, oral hygiene or nasal saline rinses were shown to be effective in reducing the risk of influenza; however, the evidence is sparse and mostly of low and critically low quality.ConclusionsStudies on the effectiveness of NPIs for the prevention of respiratory viral transmission in the community vary in study design, quality and reported effectiveness. Evidence for the use of hand hygiene or facemasks is the strongest; therefore, the most reasonable suggestion is to use hand hygiene and facemasks in the community setting.
Three important short-chain fatty acids (SCFAs) attenuate the inflammatory response induced by 5-FU and maintain the integrity of intestinal mucosal tight junction
Authors: Yue Xi , Wen Sun , Long-kun Ding , Man Yan , Chang Sun , Min Zhang , Shuang-yu Li , Xin Qian , Jie Ma , Liang Wu 
Published: April 2022

Abstract
Background
5-Fluorouracil (5-FU) is a used chemotherapy drug for cancer, and its main side effect is intestinal mucositis which causes chemotherapy to fail. It was known that short-chain fatty acids (SCFAs) can inhibit immune cell release of various proinflammatory factors and inhibit excessive intestinal inflammation. However, the inhibitory effect of SCFAs on 5-FU-induced intestinal mucositis is still unclear.

Results
To simulate the effects of SCFAs on immune and intestinal epithelial cells, the cells (THP-1 cells and Caco-2 cells) were pretreated with sodium acetate (NaAc), sodium propionate (NaPc) and sodium butyrate (NaB), then inflammation was induced by 5-FU. The expressions of reactive oxygen species (ROS), Beclin-1, LC3-II, NF-κB p65, NLRP3 inflammasome, proinflammatory/anti-inflammatory cytokines and mucosal tight junction proteins were determined. In our results, the three SCFAs could inhibit ROS expressions, NLRP3, Caspase-1, IL-1β, IL-6, IL-18, Beclin-1 and LC3-II, when induced by 5-FU. In a 5-FU-induced chemoentermuctis mouse model, Lactobacillus rhamnoides can increase the concentrations of three SCFAs in faeces and increase the concentrations of IL-1β, IL-6 and IgA in serum, and decrease the expressions of NLRP3 and IL-17 in spleen cells. The expressions of ZO-1 and Occludin in intestinal mucosa were significantly increased.

Conclusions
These results indicated that the three SCFAs can effectively suppress the inflammation of THP-1 cells and Caco-2 cells and maintain tight junction integrity in intestinal mucosal epithelial cells.
Comparison of carotid atherosclerotic plaque characteristics between symptomatic patients with transient ischemic attack and stroke using high-resolution magnetic resonance imaging
Authors: Lu Mingming , Zhang Lichen , Yuan Fei , Peng Peng , Zhang Hongtao , Liu Shitong , He Yao , Cai Jianming , Zhao Xihai 
Published: April 2022

Abstract
Background
This study aimed to compare the characteristics of carotid plaques between patients with transient ischemic attack (TIA) and ischemic stroke using magnetic resonance (MR) imaging.

Methods
Patients with a recent ischemic stroke or TIA who exhibited atherosclerotic plaques of carotid arteries in the symptomatic sides determined by MR vessel wall imaging were recruited. The plaque morphology and compositions including intraplaque hemorrhage (IPH), lipid-rich necrotic-core (LRNC) and calcification were compared between TIA and stroke patients. Logistic regression was performed to relate the plaque characteristics to the types of ischemic events.

Results
A total of 270 patients with TIA or ischemic stroke were recruited. Stroke patients had a significantly higher prevalence of diabetes (42.2% vs. 28.2%, p = 0.021), greater mean wall area (35.1 ± 10.1 mm2 vs. 32.0 ± 7.7 mm2, p = 0.004), mean wall thickness (1.3 ± 0.2 mm vs. 1.2 ± 0.2 mm, p = 0.001), maximum normalized wall index (NWI)(63.9% ± 6.0% vs. 62.2% ± 5.9%, p = 0.023) and %volume of LRNC (9.7% ± 8.2% vs. 7.4% ± 7.9%, p = 0.025) in the carotid arteries compared to those with TIA. After adjustment for clinical factors, above characteristics of carotid arteries were significantly associated with the type of ischemic events. After further adjustment for maximum NWI, this association remained statistically significant (OR, 1.41; CI, 1.01–1.96; p = 0.041).

Conclusions
Ischemic stroke patients had larger plaque burden and greater proportion of LRNC in carotid plaques compared to those with TIA. This study suggests that ischemic stroke patients had more vulnerable plaques compared to those with TIA.
Airway management procedures in Swedish emergency department patients - a national retrospective study
Authors: Wilhelms Susanne B. , Wilhelms Daniel B. 
Published: April 2022

Abstract
Background
With the on-going debate about which specialty should be responsible for intubations in the emergency department in mind, the aim of this study was to describe the prevalence of endotracheal intubation and other airway management procedures in emergency department patients in Sweden.

Methods
All patients registered in the Swedish Intensive Care Registry with admission date from January 1 2013 until June 7 2018 and reported admission type “from the emergency department” or “emergency department” reported in the SAPS3 scoring were included. All patients missing codes for procedures were excluded.

Results
A total of 110,072 admissions from an emergency department to an ICU were registered during the study period. Of these, 41,619 admissions (37.8%) were excluded due to lack of codes for medical procedures. The remaining 68,453 admissions (62.2%) were included, and 31,888 emergency airway procedures (within 3 h from admission time to the intensive care unit) were registered. Invasive emergency airway procedures were the most common type of airway procedure (n = 23,446), followed by non-invasive airway procedures (n = 8377) and high-flow nasal cannula (n = 880). In 2017 a total of 4720 invasive emergency airway management procedures were registered.

Conclusions
The frequency of invasive airway management procedures in Swedish EDs is low. With approximately 1.9 million adult ED visits per year, this gives an estimated incidence of 2.4 invasive airway management procedures per thousand ED visits in 2017.

Trial registration
Not applicable.
Bayesian adaptive design for pediatric clinical trials incorporating a community of prior beliefs
Authors: Wang Yu , Travis James , Gajewski Byron 
Published: April 2022

Abstract
Background
Pediatric population presents several barriers for clinical trial design and analysis, including ethical constraints on the sample size and slow accrual rate. Bayesian adaptive design methods could be considered to address these challenges in pediatric clinical trials.

Methods
We developed an innovative Bayesian adaptive design method and demonstrated the approach as a re-design of a published phase III pediatric trial. The innovative design used early success criteria based on skeptical prior and early futility criteria based on enthusiastic prior extrapolated from a historical adult trial, and the early and late stopping boundaries were calibrated to ensure a one-sided type I error of 2.5%. We also constructed several alternative designs which incorporated only one type of prior belief and the same stopping boundaries. To identify a preferred design, we compared operating characteristics including power, expected trial size and trial duration for all the candidate adaptive designs via simulation when performing an increasing number of equally spaced interim analyses.

Results
When performing an increasing number of equally spaced interim analyses, the innovative Bayesian adaptive trial design incorporating both skeptical and enthusiastic priors at both interim and final analyses outperforms alternative designs which only consider one type of prior belief, because it allows more reduction in sample size and trial duration while still offering good trial design properties including controlled type I error rate and sufficient power.

Conclusions
Designing a Bayesian adaptive pediatric trial with both skeptical and enthusiastic priors can be an efficient and robust approach for early trial stopping, thus potentially saving time and money for trial conduction.
Development and validation of a prognostic nomogram for gallbladder cancer patients after surgery
Authors: Xu Xinsen , He Min , Wang Hui , Zhan Ming , Yang Linhua 
Published: April 2022

Abstract
Background
Gallbladder cancer is associated with late diagnosis and poor prognosis. Current study aims to develop a prognostic nomogram for predicting survival of gallbladder cancer patients after surgery.

Methods
Two large cohorts were included in this analysis. One consisted of 1753 gallbladder cancer patients from the Surveillance, Epidemiology, and End Results (SEER) database, and the other consisted of 239 patients from Shanghai Renji hospital. Significant prognostic factors were identified and integrated to develop the nomogram. Then the model was subjected to bootstrap internal validation and external validation.

Results
Univariate and multivariate analysis indicated that age, tumor histology, T-stage, N-stage and M-stage were significant prognostic factors, which were all included to build the nomogram. The model showed good discrimination, with a concordance index (C-index) of 0.724 (95% CI, 0.708–0.740), and good calibration. Application of the nomogram in the validation cohort still presented good discrimination (C-index, 0.715 [95% CI 0.672–0.758]) and good calibration. In the primary cohort, the C-index of the nomogram was 0.724, which was significantly higher than the Nevin staging system (C-index = 0.671; P < 0.001) and the 8th TNM staging system (C-index = 0.682; P < 0.001). In the validation cohort, the C-index of the nomogram was 0.715, which was also higher than the Nevin staging system (C-index = 0.692; P < 0.05) and the 8th TNM staging system (C-index = 0.688; P = 0.06).

Conclusions
The proposed nomogram resulted in more-accurate prognostic prediction for patients with gallbladder cancer after surgery.
Anti-LGI1 encephalitis recurring 3 years after the first episode: a case report
Authors: Fujita Hiroaki , Shioda Mukuto , Suzuki Keisuke 
Published: April 2022

Abstract
Background
Patients with antibodies against leucine-rich glioma-inactivated 1 (LGI1) present with limbic encephalitis, which is clinically characterized by a subacute disturbance of memory and behavior, often experience seizures. Most patients have a monophasic course, often with hyponatremia.

Case presentation
Herein, we report a 67-year-old Japanese male presenting with involuntary neck movement, abnormal behavior and apraxia. He was disoriented to time and place and occasionally unable to follow directions. Laboratory tests revealed the patient had hyponatremia (131 mEq/L). Cerebrospinal fluid (CSF) analysis showed that the cell count (1/μL) and protein content (33 mg/dL) were in the normal ranges. Electroencephalography showed transient theta bursts in the right frontal lobe. Magnetic resonance imaging (MRI) of the brain demonstrated hyperintensities in the medial temporal lobe and basal forebrain on fluid-attenuated inversion recovery (FLAIR) without gadolinium enhancement. Anti-voltage-gated potassium channel (Anti-VGKC) complex antibodies were below the reference level for limbic encephalitis. Although the diagnosis was unknown, intravenous methylprednisolone therapy was effective. Three years later, the patient began to speak incoherently and became disoriented to time. FLAIR MRI of the brain revealed recurrence in the left medial temporal lobe. The patient’s serum sodium level was 131 mEq/L. After intravenous methylprednisolone therapy, he regained alertness. A CSF sample stored at the time of the first attack was assayed and the patient was found to be LGI1-positive and CASPR-2-negative, and the diagnosis of anti-LGI1 encephalitis was made.

Conclusions
Monitoring serum sodium levels and the preserved samples from the first episode were useful for diagnosis.