bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of high-risk cytogenetics on outcomes for children and young adults receiving CD19-directed CAR T-cell therapy
Authors: Leahy Allison Barz , Devine Kaitlin J. , Li Yimei , Liu Hongyan , Myers Regina , DiNofia Amanda , Wray Lisa , Rheingold Susan R. , Callahan Colleen , Baniewicz Diane , Patino Maria , Newman Haley , Hunger Stephen P. , Grupp Stephan A. , Barrett David M. , Maude Shannon L. 
Published: December 2021

Abstract
Chimeric antigen receptor (CAR) T-cell therapy can induce durable remissions of relapsed/refractory B-acute lymphoblastic leukemia (ALL). However, case reports suggested differential outcomes mediated by leukemia cytogenetics. We identified children and young adults with relapsed/refractory CD19+ ALL/lymphoblastic lymphoma treated on 5 CD19-directed CAR T-cell (CTL019 or humanized CART19) clinical trials or with commercial tisagenlecleucel from April 2012 to April 2019. Patients were hierarchically categorized according to leukemia cytogenetics: High-risk lesions were defined as KMT2A (MLL) rearrangements, Philadelphia chromosome (Ph+), Ph-like, hypodiploidy, or TCF3/HLF; favorable as hyperdiploidy or ETV6/RUNX1; and intermediate as iAMP21, IKZF1 deletion, or TCF3/PBX1. Of 231 patients aged 1 to 29, 74 (32%) were categorized as high risk, 28 (12%) as intermediate, 43 (19%) as favorable, and 86 (37%) as uninformative. Overall complete remission rate was 94%, with no difference between strata. There was no difference in relapse-free survival (RFS; P = .8112), with 2-year RFS for the high-risk group of 63% (95% confidence interval [CI], 52-77). There was similarly no difference seen in overall survival (OS) (P = .5488), with 2-year OS for the high-risk group of 70% (95% CI, 60-82). For patients with KMT2A-rearranged infant ALL (n = 13), 2-year RFS was 67% (95% CI, 45-99), and OS was 62% (95% CI, 40-95), with multivariable analysis demonstrating no increased risk of relapse (hazard ratio, 0.70; 95% CI, 0.21-2.90; P = .7040) but a higher proportion of relapses associated with myeloid lineage switch and a 3.6-fold increased risk of all-cause death (95% CI, 1.04-12.75; P = .0434). CTL019/huCART19/tisagenlecleucel are effective at achieving durable remissions across cytogenetic categories. Relapsed/refractory patients with high-risk cytogenetics, including KMT2A-rearranged infant ALL, demonstrated high RFS and OS probabilities at 2 years.
Intestinal IL-33 promotes platelet activity for neutrophil recruitment during acute inflammation
Authors: Chen Zuojia , Luo Jialie , Li Jian , Kim Girak , Stewart Andy , Huang Yuefeng , Wu Chuan 
Published: December 2021

Abstract
Peripheral serotonin (5-HT) is mainly generated from the gastrointestinal tract and taken up and stored by platelets in the circulation. Although the gut is recognized as a major immune organ, how intestinal local immune responses control whole-body physiology via 5-HT remains unclear. Here, we show that intestinal inflammation enhances systemic platelet activation and blood coagulation. Intestinal epithelium damage induces elevated levels of the alarm cytokine interleukin-33 (IL-33), leading to platelet activation via promotion of gut-derived 5-HT release. More importantly, we found that loss of intestinal epithelial-derived IL-33 lowers peripheral 5-HT levels, resulting in compromised platelet activation and hemostasis. Functionally, intestinal IL-33 contributes to the recruitment of neutrophils to sites of acute inflammation by enhancing platelet activities. Genetic deletion of intestinal IL-33 or neutralization of peripheral IL-33 protects animals from lipopolysaccharide endotoxic shock through attenuated neutrophil extravasation. Therefore, our data establish a distinct role of intestinal IL-33 in activating platelets by promoting 5-HT release for systemic physiology and inflammation.
Factors associated with prolonged duration of viral clearance in non-severe SARS-CoV-2 patients in Osaka, Japan
Authors: Hoffman Emma Nakagawa , Kawachi Haruna , Hirayama Atsushi , Zhang Jingwen , Murayama Ayumi , Masui Jun , Fujita Satomi , Mori Yasushi , Hirayama Takanori , Ohara Toshitake , Asada Rumiko , Iso Hiroyasu 
Published: December 2021

Abstract
Background
We investigated factors associated with prolonged viral clearance of SARS-CoV-2 among non-severe adult patients in Osaka, Japan. A total of 706 laboratory-confirmed COVID-19 patients were enrolled in this longitudinal observational study between 29 January 2020 and 31 May 2020, across 62 hospitals and three non-hospital recuperation facilities.

Methods
Logistic regression analysis was performed to investigate the factors associated with prolonged (29 days: upper 25% in duration) viral clearance of SARS-CoV-2. Linear regression analysis was conducted to assess these factors 14 days after symptom onset.

Results
The median duration of viral clearance was 22 days from symptom onset. After adjustment for sex, age, symptoms, comorbidity, and location of recuperation, comorbidities were associated with prolonged duration: (OR, 1.77 [95% CI, 1.11–2.82]) for one, (OR, 2.47 [95% CI, 1.32–4.61]) for two or more comorbidities. Viral clearance 14 days after symptom onset was 3 days longer for one comorbidity and 4 days longer for two or more comorbidities compared to clearance when there was no comorbidity.

Conclusion
The presence of comorbidity was a robust factor associated with a longer duration of viral clearance, extending by 3 to 4 days compared to patients with no comorbidity.
Hospitalizations related to meningococcal infection in Spain from 1997 to 2018
Authors: Walter Stefan , Gil-Prieto Ruth , Gil-Conesa Mario , Rodriguez-Caravaca Gil , San Román Jesús , Gil de Miguel Angel 
Published: December 2021

Abstract
Background
Baseline hospitalization, mortality, and in-hospital fatality rates for meningococcal infection are required to evaluate preventive interventions, such as the inclusion of the conjugated quadrivalent meningococcal vaccine and serogroup B based protein vaccines.

Methods
All meningococcal infection–related hospitalizations in any diagnostic position in Spain from 1st January 1997 through 31st December 2018 were analysed. The annual hospitalization rate, mortality rate and case-fatality rate were calculated.

Results
The average hospitalization rate for meningococcal infection was 1.64 (95% CI 1.61 to 1.66) hospitalizations per 100,000 inhabitants during the study period and significantly decreased from 1997 to 2018. Hospitalizations for meningococcal infection decreased significantly with age and were concentrated in children under 5 years of age (46%). The hospitalization rates reached 29 per 100,000 and 24 per 100,000 children under 1 and 2 years of age, respectively. The in-hospital case-fatality rate was 7.45% (95% CI 7.03 to 7.86). Thirty percent of the deaths occurred in children under 5 years of age, and more than half occurred in adults. The case fatality rate increased significantly with age (p < 0.001).

Conclusion
It is necessary to maintain epidemiological surveillance of meningococcal infection to determine the main circulating serogroups involved, track their evolution, and evaluate preventive measures whose effectiveness must be assessed in all age groups.
Effectiveness and safety of pegylated liposomal doxorubicin versus epirubicin as neoadjuvant or adjuvant chemotherapy for breast cancer: a real-world study
Authors: Zhang Jin , Jiang Hongchuan , Zhang Jian , Bao Guoqiang , Zhang Guoqiang , Wang Haibo , Wang Xi 
Published: December 2021

Abstract
Background
Pegylated liposomal doxorubicin (PLD) is an improved formulation of doxorubicin with comparable effectiveness but significantly lower cardiotoxicity than conventional anthracycline. This study aimed to evaluate the real-world effectiveness and safety of PLD versus epirubicin as neoadjuvant or adjuvant treatment for breast cancer.

Methods
Clinical data of invasive breast cancer patients who received neoadjuvant or adjuvant chemotherapy with PLD or epirubicin were retrospectively collected. Propensity score matching (PSM) was performed to reduce the risk of selection bias. The molecular typing of these patients included Luminal A, Luminal B, HER2-positive, and basal-like/triple-negative. The primary outcome was pathological complete response (pCR) rate for neoadjuvant chemotherapy and 3-year disease-free survival (DFS) rate for adjuvant chemotherapy. Noninferiority was suggested if the lower limit of the 95% CI for the 3-year DFS rate difference was greater than − 10%. The secondary outcome was adverse reactions.

Results
A total of 1213 patients were included (neoadjuvant, n = 274; adjuvant, n = 939). pCR (ypT0/Tis ypN0) rates of patients who received neoadjuvant chemotherapy were 11.6% for the PLD group and 7.0% for the epirubicin group, but the difference was not statistically significant (P = 0.4578). The 3-year DFS rate of patients who received adjuvant chemotherapy was 94.9% [95%CI, 91.1–98.6%] for the PLD group and 95.4% [95%CI, 93.0–97.9%] for the epirubicin group (P = 0.5684). Rate difference between the two groups and its 95% CI was - 0.55 [− 5.02, 3.92]. The lower limit of the 95% CI was − 5.0% > − 10.0%, suggesting that PLD is not be inferior to epirubicin in adjuvant chemotherapy for breast cancer. The incidences of myelosuppression, decreased appetite, alopecia, gastrointestinal reactions, and cardiotoxicity were lower in the PLD group than in the epirubicin group, while the incidence of nausea was higher in the PLD group.

Conclusions
In the neoadjuvant and adjuvant treatment of breast cancer, effectiveness is similar but toxicities are different between the PLD-containing regimen and epirubicin-containing regimen. Therefore, further study is warranted to explore PLD-based neoadjuvant and adjuvant chemotherapy for breast cancer.
Characteristics of inhomogeneous lower extremity growth and development in early childhood: a cross-sectional study
Authors: Apibantaweesakul Sudarat , Omura Shiho , Qi Weihuang , Shiotani Hiroto , Evangelidis Pavlos E. , Sado Natsuki , Tanaka Fumiko , Kawakami Yasuo 
Published: December 2021

AbstractBackgroundEarly childhood is a transferring stage between the two accelerated growth periods (infant and adolescent). Body dimensions are related to physical growth and development. The purpose of this study was to investigate physical growth in terms of anthropometry, muscle growth of the lower extremity, and functional development over early childhood.MethodsA cross-sectional study was carried out on 29 preschool children (PS: 3–5 years), 21 school children (SC: 6–8 years), and 22 adults (AD: 20–35 years). Lower extremity characteristics (segmental dimensions, muscle and adipose tissue thicknesses of the thigh and lower leg), and voluntary joint torque (knee and ankle) were measured. Correlations between parameters and group comparisons were performed.ResultsAll the parameters except for body mass index (BMI) and subcutaneous adipose tissue thickness were correlated with age for PS and SC combined (r = 0.479–0.920,p < 0.01). Relative thigh and shank lengths to body height were greatest in AD and smallest in PS (p < 0.05) but the relative foot dimensions were significantly larger in PS and SC than in AD (p < 0.05). Relative subcutaneous adipose tissue thickness was largest in PS and lowest in AD. Muscle thickness and the muscle volume measure (estimated from muscle thickness and limb length) were significantly larger in older age groups (p < 0.05). All groups showed comparable muscle thickness when normalized to limb length. Joint torque normalized to estimated muscle volume was greatest for AD, followed by SC and PS (p < 0.05).ConclusionsRelative lower extremity lengths increase with age, except for the foot dimensions. Muscle size increases with age in proportion to the limb length, while relative adiposity decreases. Torque-producing capacity is highly variable in children and rapidly develops toward adulthood. This cross-sectional study suggests that children are not a small scale version of adults, neither morphologically nor functionally.
Demographic, clinical, and socioeconomic factors associated with delayed diagnosis and management of pediatric testicular torsion in West China: a retrospective study of 301 cases in a single tertiary children’s hospital
Authors: Yu Chengjun , Zhao Jie , Lu Jiandong , Wei Yi , Jiang Li , Zhao Tianxin , Lin Tao , He Dawei , Wen Sheng , Wu Shengde , Wei Guanghui 
Published: December 2021

Abstract
Background
To investigate the association between geographic, clinical, socioeconomic factors and delayed management of pediatric testicular torsion (TT) in West China.

Methods
A retrospective study was conducted on TT at Children’s Hospital of Chongqing Medical University in West China from November 2004 to December 2020. Univariate analysis and logistic regression analysis were conducted to determine the association between these factors and delayed management of TT.

Results
A total of 301 cases were included in this study. The misdiagnosis rate of TT in primary, secondary healthcare units and tertiary hospitals was 93.8, 71.1, and 8.9%, respectively. Approximately 26.9% of TT boys received timely surgical management (within 12 h from symptoms inset to surgery). Logistic regression analyses suggested the following factors were associated with delayed repair of TT:
age less than 6 years (P = 0.001), with a history of symptoms progress (P = 0.001) or former treatment (P <0.001), absence of other diagnosis (P = 0.011) and those boys living far away from the main city zones (P <0.001).

Conclusions
Delayed surgical management for TT was more likely for boys with age less than 6 years, the absence of other diagnosis, with a history of former treatment or symptoms progress, and those living far away from the main city zone. To maximize the possibility of timely surgical management for TT, it is vital to strengthen the public awareness of TT and conduct continuously re-education and update physicians working at primary and secondary healthcare units.
Patients’ views of shared decision making in inflammatory bowel disease: a survey in China
Authors: Xu Dingting , Zhang Hanyun , Chen Yan 
Published: December 2021

AbstractBackgroundRecently, decision-making process has become increasingly complex. But there is limited information on Chinese patients’ views of shared decision making (SDM) in inflammatory bowel disease (IBD). This questionnaire investigation aimed to understand Chinese patients’ perspectives and expectations of SDM in IBD and analyze the possible factors that influence their views.MethodsAn online survey was conducted from July 19th to 24th, 2020. A total of 1118 patients completed the survey.ResultsOne-third of patients were dissatisfied with the current decision-making model, and the satisfaction of inpatients was lower than that of outpatients. 84% of patients preferred to participate in SDM, who were young and had a high education level, high income, commercial insurance, strong learning ability and knowledge of SDM. Most of those who did not want to participate (72%) were worried about the cost. The kind of medicine (948, 84.8%), surgical indications (505, 45.2%) and operation methods (482, 43.1%) were the topics that patients thought most require SDM. Side effects of medicine (837, 74.9%), costs of therapy (675, 60.4%), and surgical risks (563, 50.4%) were considered to be the most influential factors for SDM. 52.7% of all patients hoped experts in different disciplines would participate in SDM. The most desirable amount of time for discussion was 30 to 60 min (562/1118, 50.3%), that were associated with the cost of SDM.ConclusionWe can meet the needs of patients by reducing costs and strengthening online patient education and exploring a model suitable for Chinese IBD patients.
Self-referral to inpatient treatment program in a community mental health Centre in Central Norway: investigating the implementation, professionals’ experiences and costs
Authors: Moljord Inger Elise Opheim , Stensvåg Kine Gabrielsen , Halsteinli Vidar , Rise Marit By 
Published: December 2021

Abstract
Background
Self-referral to inpatient treatment (SRIT) is built on user participation and patient autonomy. SRIT was conducted for patients with severe mental disorders in a Norwegian Community Mental Health Centre. The aims of the present study were to describe the implementation of SRIT, explore the professionals’ experiences of SRIT and assess the costs entailed.

Methods
Qualitative document analysis, interviews with professionals and quantitative analysis of register data from a randomized controlled trial were used.

Results
SRIT seemed to be implemented as intended. According to the professionals, SRIT allowed the patients to cope, be empowered, more active and responsible. Some professionals experienced increased responsibility for patients’ medication and for assessing health and suicide risks. SRIT did not reduce hospital costs. The professionals were satisfied with nurse-led SRIT treatment.

Conclusions
SRIT appears to be a high-quality mental health service that empowers and activates patients. Nurse-led treatment may entail more efficient use of professional resources.
In future implementations of SRIT, the efficient use of service resources and the administration of beds should be investigated. More flexible availability should be considered in line with the intentions behind SRIT, as well as ensuring adequate professional training in assessing health and suicide risk.
Nocturnal dexmedetomidine alleviates post–intensive care syndrome following cardiac surgery: a prospective randomized controlled clinical trial
Authors: Dong Chun-hui , Gao Chao-nan , An Xiao-hua , Li Na , Yang Le , Li De-cai , Tan Qi 
Published: December 2021

Abstract
Background
Dexmedetomidine is a sedative agent that may have the potential to reduce the risk of post-intensive care syndrome (PICS). This study aimed to establish whether prophylactic nocturnal dexmedetomidine safely reduces postoperative PICS incidence and to develop an easy-to-use model for predicting the risk of PICS following cardiac surgery.

Methods
This was a single-center, double-blind, randomized, prospective, placebo-controlled trial. Patients undergoing cardiac surgery were randomly assigned (1:1) to dexmedetomidine or placebo (normal saline) groups between January 2019 and July 2020. Dexmedetomidine or a similar volume of saline was administered, with an infusion rate up to 1.2 μg/kg/h until the RASS remained between − 1 and 0. The primary study endpoint was PICS incidence at 6 months follow-up, as defined by cognitive, physical, or psychological impairments.

Results
We assessed 703 individuals for eligibility, of whom 508 were enrolled. Of these, there were 251 in the dexmedetomidine group and 257 in the placebo group that received the trial agent, forming a modified intention-to-treat population. PICS incidence at 6-month follow-up was significantly decreased in the dexmedetomidine group (54/251, 21.5%) relative to the placebo group (80/257, 31.1%) (odds ratio [OR] 0.793, 95% CI 0.665–0.945; p = 0.014). Psychological impairment was significantly reduced in the dexmedetomidine group relative to the placebo group (18.7% vs. 26.8%, OR 0.806, CI 0.672–0.967, p = 0.029). However, dexmedetomidine treatment was associated with a higher rate of hypotension. A nomogram revealed that age, education, a medical history of diabetes and smoking, dexmedetomidine treatment, postoperative atrial fibrillation, and sequential organ failure assessment scores at 8 h post-surgery were independent predictors of PICS.

Conclusions
Prophylactic nocturnal dexmedetomidine administration significantly reduced PICS incidence by a marked reduction in psychological impairment within a 6-month follow-up period.

Trial registration
ChiCTR, ChiCTR1800014314. Registered 5 January 2018, http://www.chictr.org.cn/index.aspx
Length of metacarpal and metatarsal bones in five Iranian sheep breeds and their associations with ungula measurements
Authors: Azarpajouh Samaneh , Munita María Pia , Calderón Díaz Julia Adriana 
Published: December 2021

Abstract
Background
This study aimed to measure the length of metacarpal and metatarsal bones in five Iranian sheep breeds and to correlate the length of the bones with ungula measurements. Thoracic and pelvic limbs of 2-year-old, previously untrimmed, pastured Afshari, Moghani, Kurdi, Makoui, and Lori–Bakhtiari ewes, (n = 20 ewes per breed) were collected after slaughter. The following lengths were recorded in the metacarpal and metatarsal bones: from the margo proximalis lateralis to the lateral (L1) and medial (D1) cartilago physialis; from the margo proximalis lateralis to the margo abaxialis of the lateral (L2) and medial (D2) caput; from the cartilago physialis lateralis to the margo abaxialis of the lateral caput (X1); from the cartilago physialis medialis to the margo distalis of the caput ridge (X2) and from the margo axialis of cartilago physialis to the margo axialis of the lateral caput (X3). Additionally, measurements of the ungula including pars dorsalis length, pars mobilis lateralis and medialis height, pars dorsalis height to the ground and to the solea cornea, thickness of the solea in the pars dorsalis, pars mobilis lateralis and medialis, solea cornea length and angulus dorsalis were recorded in the medial and lateral digits of the thoracic and pelvic limbs. Data on length of the metatarsal and metacarpal bones were analysed using mixed model equations while Pearson correlations were calculated between metacarpal and metatarsal bones and ungula measurements.

Results
Lori- Bakhtiari and Moghani ewes had greater L1, L2, and D1 and D2 while X1, X2 and X3 was greater in Kurdi ewes (P < 0.05). Measurements such as L1, L2, D1 and D2 were greater in the metatarsal than in metacarpal bones (P < 0.05) and the opposite was observed for X1, X2 and X3 (P < 0.05). No asymmetry was observed between the lateral and medial measurements (P > 0.05). Low to moderate correlations were observed between bone and ungula measurements (P < 0.05).

Conclusion
Under the conditions of this study, differences in metacarpal and metatarsal bone measurements were observed between breeds but no asymmetry was observed between lateral and medial bones. Results indicate an association between metacarpal and metatarsal bones ungula measurements. This could provide baseline information for the development and/or improvement of current ungula health protocols in the studied sheep breeds.