bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-CCR9 chimeric antigen receptor T cells for T-cell acute lymphoblastic leukemia
Authors: Maciocia Paul M. , Wawrzyniecka Patrycja A. , Maciocia Nicola C. , Burley Amy , Karpanasamy Thaneswari , Devereaux Sam , Hoekx Malika , O’Connor David , Leon Theresa , Rapoz-D’Silva Tanya , Pocock Rachael , Rahman Sunniyat , Gritti Giuseppe , Yánez Diana C. , Ross Susan , Crompton Tessa , Williams Owen , Lee Lydia , Pule Martin A. , Mansour Marc R. 
Published: May 2022

Abstract
T cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy of immature T lymphocytes, associated with higher rates of induction failure compared with those in B cell acute lymphoblastic leukemia. The potent immunotherapeutic approaches applied in B cell acute lymphoblastic leukemia, which have revolutionized the treatment paradigm, have proven more challenging in T-ALL, largely due to a lack of target antigens expressed on malignant but not healthy T cells. Unlike B cell depletion, T-cell aplasia is highly toxic. Here, we show that the chemokine receptor CCR9 is expressed in &gt;70% of cases of T-ALL, including &gt;85% of relapsed/refractory disease, and only on a small fraction (&lt;5%) of normal T cells. Using cell line models and patient-derived xenografts, we found that chimeric antigen receptor (CAR) T-cells targeting CCR9 are resistant to fratricide and have potent antileukemic activity both in vitro and in vivo, even at low target antigen density. We propose that anti-CCR9 CAR-T cells could be a highly effective treatment strategy for T-ALL, avoiding T cell aplasia and the need for genome engineering that complicate other approaches.
Real-world effectiveness of CPX-351 vs venetoclax and azacitidine in acute myeloid leukemia
Authors: Matthews Andrew H. , Perl Alexander E. , Luger Selina M. , Loren Alison W. , Gill Saar I. , Porter David L. , Babushok Daria V. , Maillard Ivan P. , Carroll Martin P. , Frey Noelle V. , Hexner Elizabeth O. , Martin Mary Ellen , McCurdy Shannon R. , Stadtmauer Edward A. , Paralkar Vikram R. , Bruno Ximena Jordan , Hwang Wei-Ting , Margolis David , Pratz  Keith W. 
Published: May 2022

Abstract
CPX-351 and venetoclax and azacitidine (ven/aza) are both indicated as initial therapy for acute myeloid leukemia (AML) in older adults. In the absence of prospective randomized comparisons of these regimens, we used retrospective observational data to evaluate various outcomes for patients with newly diagnosed AML receiving either CPX-351 (n = 217) or ven/aza (n = 439). This study used both a nationwide electronic health record (EHR)-derived de-identified database and the University of Pennsylvania EHR. Our study includes 217 patients who received CPX-351 and 439 who received ven/aza. Paitents receiving ven/aza were older, more likely to be treated in the community, and more likely to have a diagnosis of de novo acute myeloid leukemia. Other baseline covariates were not statistically significantly different between the groups. Median overall survival (OS) for all patients was 12 months and did not differ based on therapy (13 months for CPX-351 vs 11 months for ven/aza; hazard ratio, 0.88; 95% confidence interval, 0.71-1.08; P = .22). OS was similar across multiple sensitivity analyses. Regarding safety outcomes, early mortality was similar (10% vs 13% at 60 days). However, documented infections were higher with CPX-351 as were rates of febrile neutropenia. Hospital length of stay, including any admission before the next cycle of therapy, was more than twice as long for CPX-351. In this large multicenter real-world dataset, there was no statistically significant difference in OS. Prospective randomized studies with careful attention to side effects, quality of life, and impact on transplant outcomes are needed in these populations.
JNK1 and JNK3: divergent functions in hippocampal metabolic-cognitive function
Authors: Busquets Oriol , Espinosa-Jiménez Triana , Ettcheto Miren , Olloquequi Jordi , Bulló Mònica , Carro Eva , Cantero José Luis , Casadesús Gemma , Folch Jaume , Verdaguer Ester , Auladell Carme , Camins Antoni 
Published: May 2022

Abstract
Background and aim
The appearance of alterations in normal metabolic activity has been increasingly considered a risk factor for the development of sporadic and late-onset neurodegenerative diseases. In this report, we induced chronic metabolic stress by feeding of a high-fat diet (HFD) in order to study its consequences in cognition. We also studied the effects of a loss of function of isoforms 1 and 3 of the c-Jun N-terminal Kinases (JNK), stress and cell death response elements.

Methods
Animals were fed either with conventional chow or with HFD, from their weaning until their sacrifice at 9 months. Before sacrifice, body weight, intraperitoneal glucose and insulin tolerance test (IP-GTT and IP‑ITT) were performed to evaluate peripheral biometrics. Additionally, cognitive behavioral tests and analysis of spine density were performed to assess cognitive function. Molecular studies were carried out to confirm the effects of metabolic stressors in the hippocampus relative to cognitive loss.

Results
Our studies demonstrated that HFD in Jnk3−/− lead to synergetic responses. Loss of function of JNK3 led to increased body weight, especially when exposed to an HFD and they had significantly decreased response to insulin. These mice also showed increased stress in the endoplasmic reticulum and diminished cognitive capacity. However, loss of function of JNK1 promoted normal or heightened energetic metabolism and preserved cognitive function even when chronically metabolically stressed.

Conclusions
Downregulation of JNK3 does not seem to be a suitable target for the modulation of energetic-cognitive dysregulations while loss of function of JNK1 seems to promote a good metabolic-cognitive profile, just like resistance to the negative effects of chronic feeding with HFD.
EGF signaling promotes the lineage conversion of astrocytes into oligodendrocytes
Authors: Liu Xinyu , Li Conghui , Li Jiao , Xie Lesi , Hong Zeng , Zheng Kang , Zhao Xiaofeng , Yang Aifen , Xu Xiaofeng , Tao Huaping , Qiu Mengsheng , Yang Junlin 
Published: May 2022

Abstract
Background
The conversion of astrocytes activated by nerve injuries to oligodendrocytes is not only beneficial to axonal remyelination, but also helpful for reversal of glial scar. Recent studies have shown that pathological niche promoted the Sox10-mediated astrocytic transdifferentiation to oligodendrocytes. The extracellular factors underlying the cell fate switching are not known.

Methods
Astrocytes were obtained from mouse spinal cord dissociation culture and purified by differential adherent properties. The lineage conversion of astrocytes into oligodendrocyte lineage cells was carried out by Sox10-expressing virus infection both in vitro and in vivo, meanwhile, epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR) inhibitor Gefitinib were adopted to investigate the function of EGF signaling in this fate transition process. Pharmacological inhibition analyses were performed to examine the pathway connecting the EGF with the expression of oligodendrogenic genes and cell fate transdifferentiation.

Results
EGF treatment facilitated the Sox10-induced transformation of astrocytes to O4+ induced oligodendrocyte precursor cells (iOPCs) in vitro. The transdifferentiation of astrocytes to iOPCs went through two distinct but interconnected processes: (1) dedifferentiation of astrocytes to astrocyte precursor cells (APCs); (2) transformation of APCs to iOPCs, EGF signaling was involved in both processes. And EGF triggered astrocytes to express oligodendrogenic genes Olig1 and Olig2 by activating extracellular signal-regulated kinase 1 and 2 (Erk1/2) pathway. In addition, we discovered that EGF can enhance astrocyte transdifferentiation in injured spinal cord tissues.

Conclusions
These findings provide strong evidence that EGF facilitates the transdifferentiation of astrocytes to oligodendrocytes, and suggest that targeting the EGF-EGFR-Erk1/2 signaling axis may represent a novel therapeutic strategy for myelin repair in injured central nervous system (CNS) tissues.
A Type-2 Fuzzy Approach to Driver-Automation Shared Driving Lane Keeping Control of Semi-Autonomous Vehicles Under Imprecise Premise Variable
Authors: Liu Yue , Xu Qing , Guo Hongyan , Zhang Hui 
Published: May 2022

AbstractThe driver-automation shared driving is a transition to fully-autonomous driving, in which human driver and vehicular controller cooperatively share the control authority. This paper investigates the shared steering control of semi-autonomous vehicles with uncertainty from imprecise parameter. By considering driver’s lane-keeping behavior on the vehicle system, a driver-automation shared driving model is introduced for control purpose. Based on the interval type-2 (IT2) fuzzy theory, moreover, the driver-automation shared driving model with uncertainty from imprecise parameter is described using an IT2 fuzzy model. After that, the corresponding IT2 fuzzy controller is designed and a direct Lyapunov method is applied to analyze the system stability. In this work, sufficient design conditions in terms of linear matrix inequalities are derived, to guarantee the closed-loop stability of the driver-automation shared control system. In addition, an $$H_{\infty }$$

H
∞

performance is studied to ensure the robustness of control system. Finally, simulation-based results are provided to demonstrate the performance of proposed control method. Furthermore, an existing type-1 fuzzy controller is introduced as comparison to verify the superiority of the proposed IT2 fuzzy controller.
CRISPR/Cas9 application in cancer therapy: a pioneering genome editing tool
Authors: Shojaei Baghini Sadegh , Gardanova Zhanna R. , Abadi Saeme Azizi Hassan , Zaman Burhan Abdullah , İlhan Ahmet , Shomali Navid , Adili Ali , Moghaddar Roozbeh , Yaseri Amirhossein Fakhre 
Published: May 2022

AbstractThe progress of genetic engineering in the 1970s brought about a paradigm shift in genome editing technology. The clustered regularly interspaced short palindromic repeats/CRISPR associated protein 9 (CRISPR/Cas9) system is a flexible means to target and modify particular DNA sequences in the genome. Several applications of CRISPR/Cas9 are presently being studied in cancer biology and oncology to provide vigorous site-specific gene editing to enhance its biological and clinical uses. CRISPR's flexibility and ease of use have enabled the prompt achievement of almost any preferred alteration with greater efficiency and lower cost than preceding modalities. Also, CRISPR/Cas9 technology has recently been applied to improve the safety and efficacy of chimeric antigen receptor (CAR)-T cell therapies and defeat tumor cell resistance to conventional treatments such as chemotherapy and radiotherapy. The current review summarizes the application of CRISPR/Cas9 in cancer therapy. We also discuss the present obstacles and contemplate future possibilities in this context.
Gaur genome reveals expansion of sperm odorant receptors in domesticated cattle
Authors: Low Wai Yee , Rosen Benjamin D. , Ren Yan , Bickhart Derek M. , To Thu-Hien , Martin Fergal J. , Billis Konstantinos , Sonstegard Tad S. , Sullivan Shawn T. , Hiendleder Stefan , Williams John L. , Heaton Michael P. , Smith Timothy P. L. 
Published: May 2022

AbstractBackgroundThe gaur (Bos gaurus) is the largest extant wild bovine species, native to South and Southeast Asia, with unique traits, and is listed as vulnerable by the International Union for Conservation of Nature (IUCN).ResultsWe report the first gaur reference genome and identify three biological pathways including lysozyme activity, proton transmembrane transporter activity, and oxygen transport with significant changes in gene copy number in gaur compared to other mammals. These may reflect adaptation to challenges related to climate and nutrition. Comparative analyses with domesticated indicine (Bos indicus) and taurine (Bos taurus) cattle revealed genomic signatures of artificial selection, including the expansion of sperm odorant receptor genes in domesticated cattle, which may have important implications for understanding selection for male fertility.ConclusionsApart from aiding dissection of economically important traits, the gaur genome will also provide the foundation to conserve the species.
Anthocyanin regulatory networks in Solanum tuberosum L. leaves elucidated via integrated metabolomics, transcriptomics, and StAN1 overexpression
Authors: Bao Yanru , Nie Tengkun , Wang Dongdong , Chen Qin 
Published: May 2022

Abstract
Background
Anthocyanins, which account for color variation and remove reactive oxygen species, are widely synthesized in plant tissues and organs. Using targeted metabolomics and nanopore full-length transcriptomics, including differential gene expression analysis, we aimed to reveal potato leaf anthocyanin biosynthetic pathways in different colored potato varieties.

Results
Metabolomics analysis revealed 17 anthocyanins. Their levels varied significantly between the different colored varieties, explaining the leaf color differences. The leaves of the Purple Rose2 (PurpleR2) variety contained more petunidin 3-O-glucoside and malvidin 3-O-glucoside than the leaves of other varieties, whereas leaves of Red Rose3 (RedR3) contained more pelargonidin 3-O-glucoside than the leaves of other varieties. In total, 114 genes with significantly different expression were identified in the leaves of the three potato varieties. These included structural anthocyanin synthesis–regulating genes such as F3H, CHS, CHI, DFR, and anthocyanidin synthase and transcription factors belonging to multiple families such as C3H, MYB, ERF, NAC, bHLH, and WRKY. We selected an MYB family transcription factor to construct overexpression tobacco plants; overexpression of this factor promoted anthocyanin accumulation, turning the leaves purple and increasing their malvidin 3-o-glucoside and petunidin 3-o-glucoside content.

Conclusions
This study elucidates the effects of anthocyanin-related metabolites on potato leaves and identifies anthocyanin metabolic network candidate genes.
Improving clinical trials using Bayesian adaptive designs: a breast cancer example
Authors: Hong Wei , McLachlan Sue-Anne , Moore Melissa , Mahar Robert K. 
Published: May 2022

Abstract
Background
To perform virtual re-executions of a breast cancer clinical trial with a time-to-event outcome to demonstrate what would have happened if the trial had used various Bayesian adaptive designs instead.

Methods
We aimed to retrospectively “re-execute” a randomised controlled trial that compared two chemotherapy regimens for women with metastatic breast cancer (ANZ 9311) using Bayesian adaptive designs. We used computer simulations to estimate the power and sample sizes of a large number of different candidate designs and shortlisted designs with the either highest power or the lowest average sample size. Using the real-world data, we explored what would have happened had ANZ 9311 been conducted using these shortlisted designs.

Results
We shortlisted ten adaptive designs that had higher power, lower average sample size, and a lower false positive rate, compared to the original trial design. Adaptive designs that prioritised small sample size reduced the average sample size by up to 37% when there was no clinical effect and by up to 17% at the target clinical effect. Adaptive designs that prioritised high power increased power by up to 5.9 percentage points without a corresponding increase in type I error. The performance of the adaptive designs when applied to the real-world ANZ 9311 data was consistent with the simulations.

Conclusion
The shortlisted Bayesian adaptive designs improved power or lowered the average sample size substantially. When designing new oncology trials, researchers should consider whether a Bayesian adaptive design may be beneficial.
Mucosal healing of small intestinal stricture is associated with improved prognosis post-dilation in Crohn’s disease
Authors: Hibiya Shuji , Ohtsuka Kazuo , Takenaka Kento , Kawamoto Ami , Matsuyama Yusuke , Udagawa Yumi , Motobayashi Maiko , Shimizu Hiromichi , Fujii Toshimitsu , Saito Eiko , Nagahori Masakazu , Okamoto Ryuichi , Watanabe Mamoru 
Published: May 2022

Abstract
Background
Small intestinal stricture is a major cause for surgery in Crohn’s disease (CD). Endoscopic balloon dilation (EBD) is performed for small intestinal strictures to avoid surgery, often repeatedly. However, factors that are associated with prognosis after EBD of small intestinal strictures remain poorly investigated. Mucosal healing is the therapeutic target in CD. We aimed to investigate the impact of mucosal healing defined by the presence of ulcers at the small intestinal stricture site on the prognosis of EBD in CD patients.

Methods
We retrospectively included patients with CD who underwent initial EBD for endoscopically impassable small intestinal strictures from January 2012 to March 2020 at a single center. The association between presence of ulcer at the stricture site and surgery after EBD was examined by Cox proportional hazards model.

Results
Of the 98 patients included, 63 (64.3%) had ulcer at the stricture site. 20 (31.7%) of these patients underwent surgery for the stricture in due course, whereas 4 (11.4%) of the patients without ulcer of the stricture underwent surgery. In multivariate analysis, patients with ulcer of the stricture had a significantly higher risk for surgery than those without ulcer (hazard ratio 4.84; 95% confidence interval 1.58–14.79).

Conclusion
Mucosal healing at the stricture site indicated a favorable prognosis after EBD for small intestinal strictures in CD.
Assessing socioeconomic inequalities in cognitive impairment among older adults: a study based on a cross-sectional survey in India
Authors: Muhammad T. , Srivastava Shobhit , Sekher T. V. 
Published: May 2022

Abstract
Background
The rapidly aging population is a major concern for countries, especially where cognitive health in older age is poor. The study examined the socioeconomic and health-related factors associated with cognitive impairment among older adults and the contribution of those factors to the concentration of low cognitive functioning among older adults from economically poor households.

Methods
Data this study were derived from the “Building Knowledge Base on Population Ageing in India” (BKPAI) survey, which was carried out in seven major states of India. The effective sample size for the analysis was 9176 older adults aged 60 years and above. Results from descriptive and bivariate analysis were reported in the initial stage. Multivariable logistic regression analysis was conducted to explore the associations. Additionally, the concentration index and concentration curve were used to measure socioeconomic inequality in cognitive impairment among older adults. Wagstaff decomposition was employed to explore the key contributors in the concentration index.

Results
Nearly 60% of older adults suffered from cognitive impairment in the study. The likelihood of cognitive impairment were higher among older adults with a low level of self-perceived income sufficiency [coefficient: 0.29; confidence interval (CI): 0.07- 0.52] compared to older adults with higher levels of perceived income status. Older adults with more than 10 years of schooling were less likely to be cognitively impaired [coefficient: -1.27; CI: − 1.50- -1.04] in comparison to those with no education. Cognitive impairment was concentrated among older adults from households with the lowest wealth quintile (concentration index (CCI): − 0.10: p < 0.05). Educational status explained 44.6% of socioeconomic inequality, followed by 31.8% by wealth status and 11.5% by psychological health. Apart from these factors, difficulty in instrumental activities of daily living (3.7%), caste (3.7%), and perceived income sufficiency to fulfil basic needs (3.0%) explained socioeconomic inequality in cognitive impairment among older adults.

Conclusions
Findings suggest that older adults with lower perceived income, lower levels of education, poor physical and mental health, and poor physical and social resources were more likely to be cognitively impaired. Education, wealth and psychological health are major contributors in socioeconomic inequality in late-life cognitive impairment, which may be target areas in future policy formulation to reduce the inequality in cognitive impairment in older Indian adults.
Indirect comparison of 48-week efficacy and safety of long-acting cabotegravir and rilpivirine maintenance every 8 weeks with daily oral standard of care antiretroviral therapy in participants with virologically suppressed HIV-1-infection
Authors: Chounta Vasiliki , Snedecor Sonya J. , Wu Sterling , Van de Velde Nicolas 
Published: May 2022

Abstract
Background
Efficacy and safety of long-acting cabotegravir (CAB) + rilpivirine (RPV) every 8 weeks (Q8W) versus daily oral standard of care (SoC) maintenance in treatment-experienced individuals with virologically suppressed human immunodeficiency virus type 1 (HIV-1) has not been directly compared in randomized clinical trials. This analysis aimed to indirectly compare these regimens.

Methods
An adjusted indirect treatment comparison of CAB + RPV Q8W with daily oral SoC was performed, using Phase 3 data from studies of CAB + RPV every 4 weeks (Q4W) vs SoC (ATLAS/FLAIR, n = 591 per group) and a Phase 3b trial of CAB + RPV Q8W vs Q4W (ATLAS-2M [excluding participants with prior CAB + RPV exposure]; n = 327 per group). Eligible participants were virologically suppressed (viral load < 50 HIV-1 ribonucleic acid (RNA) copies/mL), treatment-experienced individuals with HIV-1-infection. Treatment efficacy and safety assessments at Week 48 included virologic suppression and lack of virologic suppression (proportion of participants with plasma HIV-1 RNA < 50 copies/mL or ≥ 50 copies/mL, respectively; both as per FDA snapshot algorithm), CD4-cell count change from baseline, no virologic data, discontinuations due to adverse events (AEs), and overall AEs, serious AEs and Grade 3–5 AEs excluding injection-site reactions. A subgroup analysis stratified by baseline third active drug class was performed.

Results
Baseline characteristics between the Q4W arms of ATLAS/FLAIR and ATLAS-2M showed no significant differences or differences were not judged to be clinically relevant, apart from participants switching from a baseline third active drug class; more participants switched from integrase strand inhibitors in ATLAS/FLAIR, and from non-nucleoside reverse transcriptase inhibitors in ATLAS-2M. Injections of CAB + RPV Q8W showed no significant differences across efficacy and safety outcomes versus daily oral SoC. Univariate subgroup analysis found there were no significant differences on virologic suppression or lack of virologic suppression for any baseline third active drug class subgroup. These results suggest that CAB + RPV Q8W is non-inferior to daily oral SoC.

Conclusions
This analysis supports the therapeutic potential of CAB + RPV Q8W for virologically suppressed people living with HIV-1 infection seeking an alternative maintenance treatment option to daily oral SoC.
Trial registration: NCT02938520, NCT02951052, NCT03299049.