bluuebunny/crossref_metadata_2025_split huggingface dataset:
CAR T cells targeting CD99 as an approach to eradicate T-cell acute lymphoblastic leukemia without normal blood cells toxicity
Authors: Shi Jiangzhou , Zhang Zijian , Cen Hong , Wu Han , Zhang Shangkun , Liu Jiaxing , Leng Yingqi , Ren Anqi , Liu Xiyu , Zhang Zhijie , Tong Xiqin , Liang Jinjue , Li Zhe , Zhou Fuling , Huang Liang , Qin You , Yang Kunyu , Zhang Tongcun , Zhu Haichuan 
Published: October 2021

AbstractCAR T cell therapy has shown dramatic clinical success in relapsed or refractory B-ALL and other hematological malignancies. However, the loss of specific antigens, cell fratricide, T cell aplasia, and normal T cell separation are challenges in treating T cell leukemia/lymphoma with CAR T therapy. CD99 is a promising antigen to target T-ALL and AML as it is strongly expressed on the majority of T-ALL and AML. Here, we isolated a low-affinity CD99 (12E7) antibody, which specifically recognizes leukemia cells over normal blood cells. Moreover, T cells transduced with an anti-CD99-specific CAR that contained the 12E7 scFv expanded with minor fratricide and without normal blood cells toxicity. We observed that our anti-CD99 CAR T cells showed robust cytotoxicity specifically against CD99+ T-ALL cell lines and primary tumor cells in vitro and significantly prolonged cell line-derived xenografts (CDXs) or patient-derived xenografts (PDXs) models survival in vivo. Together, our results demonstrate that anti-CD99 CAR T cells could specifically recognize and efficiently eliminate CD99+ leukemia cells.
Alloantigen-activated (AAA) CD4+ T cells reinvigorate host endogenous T cell immunity to eliminate pre-established tumors in mice
Authors: Mochizuki Kazuhiro , Kobayashi Shogo , Takahashi Nobuhisa , Sugimoto Kotaro , Sano Hideki , Ohara Yoshihiro , Mineishi Shin , Zhang Yi , Kikuta Atsushi 
Published: October 2021

Abstract
Background
Cancer vaccines that induce endogenous antitumor immunity represent an ideal strategy to overcome intractable cancers. However, doing this against a pre-established cancer using autologous immune cells has proven to be challenging. “Allogeneic effects” refers to the induction of an endogenous immune response upon adoptive transfer of allogeneic lymphocytes without utilizing hematopoietic stem cell transplantation. While allogeneic lymphocytes have a potent ability to activate host immunity as a cell adjuvant, novel strategies that can activate endogenous antitumor activity in cancer patients remain an unmet need. In this study, we established a new method to destroy pre-developed tumors and confer potent antitumor immunity in mice using alloantigen-activated CD4+ (named AAA-CD4+) T cells.

Methods
AAA-CD4+ T cells were generated from CD4+ T cells isolated from BALB/c mice in cultures with dendritic cells (DCs) induced from C57BL/6 (B6) mice. In this culture, allogeneic CD4+ T cells that recognize and react to B6 mouse-derived alloantigens are preferentially activated. These AAA-CD4+ T cells were directly injected into the pre-established melanoma in B6 mice to assess their ability to elicit antitumor immunity in vivo.

Results
Upon intratumoral injection, these AAA-CD4+ T cells underwent a dramatic expansion in the tumor and secreted high levels of IFN-γ and IL-2. This was accompanied by markedly increased infiltration of host-derived CD8+ T cells, CD4+ T cells, natural killer (NK) cells, DCs, and type-1 like macrophages. Selective depletion of host CD8+ T cells, rather than NK cells, abrogated this therapeutic effect. Thus, intratumoral administration of AAA-CD4+ T cells results in a robust endogenous CD8+ T cell response that destroys pre-established melanoma. This locally induced antitumor immunity elicited systemic protection to eliminate tumors at distal sites, persisted over 6 months in vivo, and protected the animals from tumor re-challenge. Notably, the injected AAA-CD4+ T cells disappeared within 7 days and caused no adverse reactions.

Conclusions
Our findings indicate that AAA-CD4+ T cells reinvigorate endogenous cytotoxic T cells to eradicate pre-established melanoma and induce long-term protective antitumor immunity. This approach can be immediately applied to patients with advanced melanoma and may have broad implications in the treatment of other types of solid tumors.
Mechanistic and therapeutic insight into the effects of cinnamon in polycystic ovary syndrome: a systematic review
Authors: Maleki Vahid , Faghfouri Amir Hossein , Tabrizi Fatemeh Pourteymour Fard , Moludi Jalal , Saleh-Ghadimi Sevda , Jafari-Vayghan Hamed , Qaisar Shaimaa A. 
Published: October 2021

AbstractPolycystic
ovary syndrome (PCOS) is one of the most common endocrine diseases in the women at their reproductive age. Nowadays, the use of herbal compounds for lesser side effects, as compared to drug treatments, has become popular for the prevention and reduction of the complications of this disease. Evidence suggests that cinnamon, given its antioxidant and anti-inflammatory properties, can be associated with reduced metabolic complications from chronic non-communicable diseases. This systematic review aimed to determine the potential effect of cinnamon on the metabolic status in the PCOS. PICO framework for current systematic review was Population (P): subjects with PCOS; Intervention (I): oral cinnamon supplement; Comparison (C): the group as control or administered placebo; and Outcome (O): changed inflammatory, oxidative stress, lipid profile, glycemic, hormonal and anthropometric parameters and ovarian function. PubMed, Scopus, EMBASE, ProQuest and Google Scholar were searched from their very inception until January, 2020, considering specific keywords to explore the related studies. Out of 266 studies retrieved by the search strategy, only nine were eligible for evaluation. All clinical trials, animal studies, and published English-language journal studies were eligible for this review. The results showed that increased high-density lipoprotein and insulin sensitivity were increased by the cinnamon supplementation while low-density lipoprotein, triglyceride, and blood glucose were decreased in patients with PCOS. However, the results related to the potential effects of cinnamon on body weight and body mass index were inconsistent, thus calling for further studies. Also, despite improved results regarding the effect of cinnamon on oxidative stress and ovarian function, further studies are required to explore the precise mechanisms. Overall, the effects of cinnamon on the improvement of metabolic status in PCOS were promising. However, to observe clinical changes following cinnamon supplementation in PCOS, more clinical trials with higher doses of cinnamon and a longer duration of intervention are needed.
Evolving outcomes of extracorporeal membrane oxygenation support for severe COVID-19 ARDS in Sorbonne hospitals, Paris
Authors: Schmidt Matthieu , Langouet Elise , Hajage David , James Sarah Aissi , Chommeloux Juliette , Bréchot Nicolas , Barhoum Petra , Lefèvre Lucie , Troger Antoine , de Chambrun Marc Pineton , Hékimian Guillaume , Luyt Charles-Edouard , Dres Martin , Constantin Jean-Michel , Fartoukh Muriel , Leprince Pascal , Lebreton Guillaume , Combes Alain ,   for the GRC RESPIRE Sorbonne Université
Published: October 2021

Abstract
Background
Extracorporeal membrane oxygenation (ECMO) was frequently used to treat patients with severe coronavirus disease-2019 (COVID-19)-associated acute respiratory distress (ARDS) during the initial outbreak. Care of COVID-19 patients evolved markedly during the second part of 2020. Our objective was to compare the characteristics and outcomes of patients who received ECMO for severe COVID-19 ARDS before or after July 1, 2020.

Methods
We included consecutive adults diagnosed with COVID-19 in Paris–Sorbonne University Hospital Network ICUs, who received ECMO for severe ARDS until January 28, 2021. Characteristics and survival probabilities over time were estimated during the first and second waves. Pre-ECMO risk factors predicting 90-day mortality were assessed using multivariate Cox regression.

Results
Characteristics of the 88 and 71 patients admitted, respectively, before and after July 1, 2020, were comparable except for older age, more frequent use of dexamethasone (18% vs. 82%), high-flow nasal oxygenation (19% vs. 82%) and/or non-invasive ventilation (7% vs. 37%) after July 1. Respective estimated probabilities (95% confidence intervals) of 90-day mortality were 36% (27–47%) and 48% (37–60%) during the first and the second periods. After adjusting for confounders, probability of 90-day mortality was significantly higher for patients treated after July 1 (HR 2.27, 95% CI 1.02–5.07). ECMO-related complications did not differ between study periods.

Conclusions
90-day mortality of ECMO-supported COVID-19–ARDS patients increased significantly after July 1, 2020, and was no longer comparable to that of non-COVID ECMO-treated patients. Failure of prolonged non-invasive oxygenation strategies before intubation and increased lung damage may partly explain this outcome.
Artificial image objects for classification of breast cancer biomarkers with transcriptome sequencing data and convolutional neural network algorithms
Authors: Chen Xiangning , Chen Daniel G. , Zhao Zhongming , Balko Justin M. , Chen Jingchun 
Published: October 2021

AbstractBackgroundTranscriptome sequencing has been broadly available in clinical studies. However, it remains a challenge to utilize these data effectively for clinical applications due to the high dimension of the data and the highly correlated expression between individual genes.MethodsWe proposed a method to transform RNA sequencing data into artificial image objects (AIOs) and applied convolutional neural network (CNN) algorithms to classify these AIOs. With the AIO technique, we considered each gene as a pixel in an image and its expression level as pixel intensity. Using the GSE96058 (n = 2976), GSE81538 (n = 405), and GSE163882 (n = 222) datasets, we created AIOs for the subjects and designed CNN models to classify biomarker Ki67 and Nottingham histologic grade (NHG).ResultsWith fivefold cross-validation, we accomplished a classification accuracy and AUC of 0.821 ± 0.023 and 0.891 ± 0.021 for Ki67 status. For NHG, the weighted average of categorical accuracy was 0.820 ± 0.012, and the weighted average of AUC was 0.931 ± 0.006. With GSE96058 as training data and GSE81538 as testing data, the accuracy and AUC for Ki67 were 0.826 ± 0.037 and 0.883 ± 0.016, and that for NHG were 0.764 ± 0.052 and 0.882 ± 0.012, respectively. These results were 10% better than the results reported in the original studies. For Ki67, the calls generated from our models had a better power for prediction of survival as compared to the calls from trained pathologists in survival analyses.ConclusionsWe demonstrated that RNA sequencing data could be transformed into AIOs and be used to classify Ki67 status and NHG with CNN algorithms. The AIO method could handle high-dimensional data with highly correlated variables, and there was no need for variable selection. With the AIO technique, a data-driven, consistent, and automation-ready model could be developed to classify biomarkers with RNA sequencing data and provide more efficient care for cancer patients.
Supine vs upright exercise in patients with hepatopulmonary syndrome and orthodeoxia: study protocol for a randomized controlled crossover trial
Authors: Parikh Harsh , Lui Eric , Faughnan Marie E. , Al-Hesayen Abdul , Segovia Stephanie , Gupta Samir 
Published: October 2021

AbstractBackgroundThe hepatopulmonary syndrome (HPS) is a pulmonary complication of liver disease found in 10 to 32% of patients with cirrhosis and is characterized by intrapulmonary vascular dilatations and abnormal oxygenation. Liver transplantation is the only effective therapy for this disease. Patients with HPS have significant exercise limitations, impacting their quality of life and associated with poor liver transplant outcomes. Many patients with HPS exhibit orthodeoxia—an improvement in oxygenation in the supine compared to the upright position. We hypothesize that exercise capacity will be superior in the supine compared to the upright position in such patients.MethodsWe propose a randomized controlled crossover trial in patients with moderate HPS (PaO2< 80 mmHg) and orthodeoxia (supine to upright PaO2decrease > 4 mmHg) comparing the effect of supine vs upright position on exercise. Patients with pulmonary hypertension, FEV1/FVC ratio < 0.65, significant coronary artery disease, disorders preventing or contraindicating use of a cycle ergometer, and/or moderate or severe ascites will be excluded. Participants will be randomized to cycle ergometry in either the supine or upright position. After a short washout period (a minimum of 1 day to a maximum of 4 weeks), participants will crossover and perform an exercise in the alternate position. Exercise will be performed at a constant work rate of 70–85% of the predicted peak work rate until the “stopping time” is reached, defined by exhaustion, profound desaturation, or safety concerns (drop in systolic blood pressure or life-threatening arrhythmia). The primary outcome will be the difference in the stopping time between exercise positions, compared with a repeated measures analysis of variance method with a mixed effects model approach. The model will be adjusted for period effects.P< 0.05 will be considered statistically significant.DiscussionHPS patients have hypoxemia leading to significant exercise limitations. If our study is positive, a supine exercise regimen could become a routine prescription for patients with HPS and orthodeoxia, enabling them to exercise more effectively. Future studies could explore the corresponding effects of a supine exercise training regimen on physiologic variables such as long-term exercise capacity, quality of life, dyspnea, and liver transplantation outcomes.Trial registrationClinicalTrials.govProtocol Registration and Results System (PRS)NCT04004104. Registered on 1 July 2019
Complementary feeding methods in the first year of life: a study protocol for a randomized clinical trial
Authors: Nunes Leandro Meirelles , Führ Jordana , Belin Christy Hannah Sanini , Moreira Paula Ruffoni , Neves Renata Oliveira , de Brito Mariana Lopes , Morando Lorenzo Andreazza , Mariath Adriela Azevedo Souza , Gomes Erissandra , Bernardi Juliana Rombaldi 
Published: October 2021

Abstract
Background
The traditional spoon-feeding approach to introduction of solid foods during the complementary feeding period is supported by consensus in the scientific literature. However, a method called Baby-Led Introduction to SolidS (BLISS) has been proposed as an alternative, allowing infants to self-feed with no adult interference. To date, there have been no trials in the Brazilian population to evaluate the effectiveness of BLISS in comparison to the traditional approach.

Methods/design
To evaluate and compare three different complementary feeding methods. Data on 144 mother-child pairs will be randomized into intervention groups by methods: (A) strict Parent-Led Weaning; (B) strict Baby-Led Introduction to SolidS; and (C) a mixed method. Prospective participants from Porto Alegre, Brazil, and nearby cities will be recruited through the Internet. The interventions will be performed by nutritionists and speech therapists, at 5.5 months of age of the child, at a private nutrition office equipped with a test kitchen where meals will be prepared according to the randomized method. The pairs will be followed up at 7, 9, and 12 months of age. Data will be collected through questionnaires designed especially for this study, which will include a 24h child food recall, questionnaires on the child’s and parents’ eating behavior, oral habits, eating difficulties, and choking prevalence. At 12 months of age, children will undergo blood collection to measure hemoglobin, ferritin, and C-reactive protein, saliva collection for analysis of genetic polymorphisms, and oral examination. Anthropometric parameters (child and maternal) will be measured at the baseline intervention, at a 9 month home visit, and at the end-of-study visit at the hospital. The primary outcome will be child growth and nutritional status z-scores at 12 months; secondary outcomes will include iron status, feeding behavior, acceptability of the methods, dietary variety, choking, eating behaviors, food preferences, acceptance of bitter and sweet flavors, suction, oral habits, oral hygiene behavior, dental caries, gingival health status, and functional constipation.

Discussion
The trial intends to ascertain whether there are potential advantages to the BLISS complementary feeding method in this specific population, generating data to support families and healthcare providers.

Trial registration
Brazilian Clinical Trials Registry (ReBEC): RBR- 229scm number U1111-1226-9516. Registered on September 24, 2019.
Clinical effectiveness and safety of baricitinib for the treatment of juvenile idiopathic arthritis-associated uveitis or chronic anterior antinuclear antibody-positive uveitis: study protocol for an open-label, adalimumab active-controlled phase 3 clinical trial (JUVE-BRIGHT)
Authors: Ramanan Athimalaipet V. , Guly Catherine M. , Keller Stuart Y. , Schlichting Douglas E. , de Bono Stephanie , Liao Ran , Quartier Pierre 
Published: October 2021

Abstract
Background
Juvenile idiopathic arthritis (JIA) is the most common pediatric rheumatic disease and the most common systemic disorder associated with uveitis in childhood. Uveitis is more common in JIA patients who are antinuclear antibody (ANA)-positive, have an early-onset disease, and have oligoarticular arthritis. JIA-associated uveitis (JIA-uveitis) is typically anterior, chronic, bilateral, nongranulomatous, and asymptomatic. Visual outcomes in JIA-uveitis have improved with current screening and treatment options; however, many patients fail to respond or do not achieve long-lasting remission. Baricitinib, an oral selective Janus kinase (JAK)1 and 2 inhibitor, may impact key cytokines implicated in the pathogenesis of JIA-uveitis or ANA-positive uveitis, representing a potential novel treatment option for disease management.

Methods
The multicenter, phase 3 trial will be conducted using an open-label Bayesian design. The study will enroll at least 20 and up to 40 patients aged 2 to <18 years with active JIA-uveitis or chronic ANA-positive uveitis without systemic features. At least 20 patients who have had an inadequate response or intolerance to methotrexate (MTX-IR), but not biologic disease-modifying antirheumatic drugs (bDMARDs), will be randomized (1:1) to open-label baricitinib or adalimumab. Approximately 20 additional patients who are MTX-IR or bDMARD inadequate responders will receive baricitinib treatment. Patients will be treated with once daily oral baricitinib at a fixed dose by age group (4 mg for patients aged ≥6 to <18 years and 2 mg for patients <6 years) or adalimumab (20 mg for patients weighing <30 kg and 40 mg for patients ≥30 kg) as a subcutaneous injection every 2 weeks. Treatment with stable background conventional synthetic DMARDs, low-dose corticosteroids, and/or nonsteroidal anti-inflammatory drugs is allowed. The primary endpoint is the proportion of patients with response at week 24. Patients may continue treatment for up to 5 years.

Discussion
This is the first pediatric clinical trial to assess the clinical effectiveness and safety of a JAK inhibitor in JIA-uveitis or chronic ANA-positive uveitis. A novel Bayesian design is used to assess the efficacy of baricitinib, including an adalimumab reference arm, in this small patient population with unmet medical need.

Trial registration
EudraCT 2019-000119-10. Registered on January 4, 2019; NCT04088409. Registered on September 12, 2019
Effect of domperidone (leisguard®) on antibody titers, inflammatory markers and creatinine in dogs with leishmaniosis and chronic kidney disease
Authors: Cavalera Maria Alfonsa , Gernone Floriana , Uva Annamaria , D’Ippolito Paola , Roura Xavier , Paltrinieri Saverio , Zatelli Andrea 
Published: October 2021

Abstract
Background
Immunotherapeutic drugs, such as domperidone, have been shown to be promising treatments against canine leishmaniosis (CanL), but limited data are available. The aim of this pilot study (therapeutic, prospective and non-controlled) was to evaluate the effect of domperidone on serum antibody titers of Leishmania infantum, globulins, gamma globulins, acute-phase proteins (e.g. C-reactive protein [CRP]), big endothelin-1 (big ET-1), serum creatinine (SC) and proteinuria in dogs with leishmaniosis affected by chronic kidney disease (CKD).

Methods
Dogs were recruited if “exposed” to or “infected” with L. infantum and affected by CKD (IRIS stage 1 [proteinuric] or IRIS stage 2–3a [SC < 3.5 mg/dl; proteinuric or non-proteinuric]). After inclusion, an oral suspension of domperidone was administered, and the dogs were followed up for 180 days, with checks at 30, 60, 90 and 180 days after initial treatment.

Results
Of the 14 recruited dogs, nine showed a statistically significant reduction in SC (χ2 = 9.1, df = 3, P = 0.028), but not in the urine protein/creatinine ratio (χ2 = 6.43, df = 3, P = 0.092). All dogs showed a significant reduction in antibody titers for L. infantum (χ2 = 9.56, df = 2, P = 0.008), globulins (χ2 = 11.08, df = 3, P = 0.011) and gamma globulins (χ2 = 12.38, df = 3, P = 0.006) during the study period. There was also a statistically significant reduction in CRP (χ2 = 16.7,
df = 3, P = 0.001), but not in big ET-1 (χ2 = 2.04, df = 3, P = 0.563).

Conclusions
This study provides preliminary results on the ability of domperidone to improve SC and reduce anti-L. infantum antibody titers, globulins, gamma globulins and CRP in dogs with leishmaniosis and CKD.

Graphical abstract