bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-Cell RNA Analysis Reveals Cell-Intrinsic Functions of CAR T Cells Correlating with Response in a Phase II Study of Lymphoma Patients
Authors: Sarén Tina , Ramachandran Mohanraj , Gammelgård Gustav , Lövgren Tanja , Mirabello Claudio , Björklund Åsa K. , Wikström Kristina , Hashemi Jamileh , Freyhult Eva , Ahlström Håkan , Amini Rose-Marie , Hagberg Hans , Loskog Angelica , Enblad Gunilla , Essand Magnus 
Published: August 2023

Abstract

Purpose:
Although CD19 chimeric antigen receptor T cells (CAR-T) therapy has shown remarkable success in B-cell malignancies, a substantial fraction of patients do not obtain a long-term clinical response. This could be influenced by the quality of the individual CAR-T infusion product. To shed some light on this, clinical outcome was correlated to characteristics of CAR-T infusion products.

Patients and Methods:
In this phase II study, patients with B-cell lymphoma (n = 23) or leukemia (n = 1) received one or two infusions of third-generation CD19-directed CAR-Ts (2 × 108/m2). The clinical trial was registered at clinicaltrials.gov: NCT03068416. We investigated the transcriptional profile of individual CD19 CAR-T infusion products using targeted single-cell RNA sequencing and multicolor flow cytometry.

Results:
Two CAR-T infusions were not better than one in the settings used in this study. As for the CAR-T infusion products, we found that effector-like CD8+CAR-Ts with a high polyfunctionality, high cytotoxic and cytokine production profile, and low dysfunctional signature were associated with clinical response. An extended ex vivo expansion time during CAR-T manufacturing negatively influenced the proportion of effector CD8+CAR-Ts in the infusion product.

Conclusions:
We identified cell-intrinsic characteristics of effector CD8+CAR-Ts correlating with response that could be used as an indicator for clinical outcome. The results in the study also serve as a guide to CAR-T manufacturing practices.
Depth of Radiographic Response and Time to Tumor Regrowth Predicts Overall Survival Following Anti-VEGF Therapy in Recurrent Glioblastoma
Authors: Ellingson Benjamin M. , Hagiwara Akifumi , Morris Connor J. , Cho Nicholas S. , Oshima Sonoko , Sanvito Francesco , Oughourlian Talia C. , Telesca Donatello , Raymond Catalina , Abrey Lauren E. , Garcia Josep , Aftab Dana T. , Hessel Colin , Rachmilewitz Minei Tamar , Harats Dror , Nathanson David A. , Wen Patrick Y. , Cloughesy Timothy F. 
Published: August 2023

Abstract

Purpose:
Antiangiogenic therapies are known to cause high radiographic response rates due to reduction in vascular permeability resulting in a lower degree of contrast extravasation. In this study, we investigate the prognostic ability for model-derived parameters describing enhancing tumor volumetric dynamics to predict survival in recurrent glioblastoma treated with antiangiogenic therapy.

Experimental Design:
N = 276 patients in two phase II trials were used as training data, including bevacizumab ± irinotecan (NCT00345163) and cabozantinib (NCT00704288), and N = 74 patients in the bevacizumab arm of a phase III trial (NCT02511405) were used for validation. Enhancing volumes were estimated using T1 subtraction maps, and a biexponential model was used to estimate regrowth (g) and regression (d) rates, time to tumor regrowth (TTG), and the depth of response (DpR). Response characteristics were compared to diffusion MR phenotypes previously shown to predict survival.

Results:
Optimized thresholds occurred at g = 0.07 months−1 (phase II: HR = 0.2579, P = 5 × 10−20; phase III: HR = 0.2197, P = 5 × 10−5); d = 0.11 months−1 (HR = 0.3365, P &lt; 0.0001; HR = 0.3675, P = 0.0113); TTG = 3.8 months (HR = 0.2702, P = 6 × 10−17; HR = 0.2061, P = 2 × 10−5); and DpR = 11.3% (HR = 0.6326, P = 0.0028; HR = 0.4785, P = 0.0206). Multivariable Cox regression controlling for age and baseline tumor volume confirmed these factors as significant predictors of survival. Patients with a favorable pretreatment diffusion MRI phenotype had a significantly longer TTG and slower regrowth.

Conclusions:
Recurrent glioblastoma patients with a large, durable radiographic response to antiangiogenic agents have significantly longer survival. This information is useful for interpreting activity of antiangiogenic agents in recurrent glioblastoma.
Glioblastoma Vascular Plasticity Limits Effector T-cell Infiltration and Is Blocked by cAMP Activation
Authors: Qin Zixi , Huang Youwei , Li Zeying , Pan Guopeng , Zheng Liangying , Xiao Xiao , Wang Fang , Chen Jiahong , Chen Xueqin , Lin Xi , Li Kai , Yan Guangmei , Zhang Haipeng , Xing Fan 
Published: August 2023

Abstract
Glioblastoma (GBM) is the deadliest form of brain cancer. It is a highly angiogenic and immunosuppressive malignancy. Although immune checkpoint blockade therapies have revolutionized treatment for many types of cancer, their therapeutic efficacy in GBM has been far less than expected or even ineffective. In this study, we found that the genomic signature of glioma-derived endothelial cells (GdEC) correlates with an immunosuppressive state and poor prognosis of patients with glioma. We established an in vitro model of GdEC differentiation for drug screening and used this to determine that cyclic adenosine monophosphate (cAMP) activators could effectively block GdEC formation by inducing oxidative stress. Furthermore, cAMP activators impaired GdEC differentiation in vivo, normalized the tumor vessels, and altered the tumor immune profile, especially increasing the influx and function of CD8+ effector T cells. Dual blockade of GdECs and PD-1 induced tumor regression and established antitumor immune memory. Thus, our study reveals that endothelial transdifferentiation of GBM shapes an endothelial immune cell barrier and supports the clinical development of combining GdEC blockade and immunotherapy for GBM.
See related Spotlight by Lee et al., p. 1300
Arabe 330b
Authors: Ince Barış 
Published: August 2023

Abstract
This article is an examination of the vocalised quranic manuscript MS Paris, BnF Arabe 330b, currently found at the Bibliothèque nationale de France. The vocalisation system in the manuscript clearly reflects two canonical readings, namely those of Ḥamzah and Warsh, and has tremendous consistency with how medieval Islamic scholarship described these readings. This was established through a juxtaposition of the manuscript’s vocalisation, rasm and verse dividers with the classical Islamic qirāʾāt literature.
Mamlūk Qurʾān Manuscripts
Authors: Witkam Jan Just , van Putten Marijn 
Published: August 2023

Abstract
The present article focuses on additional texts or appendices by scribes to three Qurʾānic manuscripts of the Mamlūk era. These appendices were accidentally found in the collections of Dār al-Kutub al-Miṣriyyah in Cairo: in Maṣāḥif 81 dating from 734/1334; Maṣāḥif 94 from 830/1427; and Maṣāḥif 143 also from 879/1474–1475. The three manuscripts are one-volume luxury copies of the Qurʾān. The subjects of these scribal appendices are mostly matters of qirāʾāt, taǧwīd, and waqf. They make explicit some of the rules that all scribes have internalized for themselves, as is often the case with crafts, but which are rarely recorded. Two of the three texts examined here are short, no more than one or two pages, but an exception to this is the longer text at the end of Maṣāḥif 81, the oldest example of the scribal additions that are presented herewith. The appendices are presented in chronological order. First, every manuscript is described generally, then each appendix is presented in transcription and annotated translation. At the end, a glossary of the technical terminology in use is added. All appendices are shown in facsimile.
Scattered Leaves
Authors: Sahragard Mahdi 
Published: August 2023

Abstract
A number of folios of a grand Qurʾan, known as the Qurʾan of Bāysunghur, are preserved in collections across the world. No thorough research has been carried out on this manuscript due to the fact that the folios of this Qurʾan—the largest of the Islamic era—are scattered. Consequently, many points about the early details, the scribe and the history of the manuscript remain vague. Endowed between the late 12th/18th and the early 14th/20th century to the Āstān-i Quds-i Raḍavī Library and Museum in Mashhad, around sixty-five opisthographic folios of the Qurʾan are now kept in the collection. A close investigation of the folios not only rejects and proves earlier hypotheses but also presents new ones. After examining the codicological features of the work by comparing the information contained in the historical sources and the features of the manuscript, the present article speculates that the Qurʾan was commissioned by Ulugh Beg in Samarqand, to the scribes of the court scriptorium. Some folios were scattered in the course of the 10th/16th century and the rest during the occupation of Samarqand in the course of the 12th/18th century. Around sixty pages, however, were transferred to Imāmzāda Ibrāhīm of Qūchān and five pages were endowed to the Holy Shrine of Imām Riḍā during the 12th/18th century. Finally, in 1923, the remaining folios of the Imāmzāda were transferred to the Library of the Holy Shrine to be mended, where they have been kept ever since.
The Qurʾānic Codices and Fragments Ascribed to Imām ʿAlī and Other Shīʿa Imāms
Authors: Karimi-Nia Morteza 
Published: August 2023

Abstract
For nearly a thousand years, certain copies of the Qurʾān have been ascribed to such prominent Islamic figures as Imām ʿAlī and other Shīʿa Imāms. Although no evidence of ascription is found from the first three centuries, nearly two hundred copies of such manuscripts and fragments are found today around the world, especially in Shiite areas. After a historical overview of the phenomenon and classification of the various types of ascribed codices, this article provides evidence for the rejection of these ascriptions and that establishes the colophons as forgeries. The last part of the article includes a table of about two hundred Qurʾānic manuscripts ascribed to Shīʿa Imāms preserved in libraries and museums all over the world.
The Response of Extratropical Cyclone Propagation in the Northern Hemisphere to Global Warming
Authors: Crawford Alex D. , McCrystall Michelle R. , Lukovich Jennifer V. , Stroeve Julienne C. 
Published: August 2023

Abstract
Extratropical cyclones (ETCs) are a common source of natural hazards, from heavy rain to high winds, and the direction and speed of ETC propagation influence where impacts occur and for how long. Eighteen models from phase 6 of the Coupled Model Intercomparison Project (CMIP6) are used to examine the response of Northern Hemisphere ETC propagation to global warming. In winter, simulations show that ETCs become slower over North America and the Arctic but faster over the Pacific Ocean and part of Europe. In summer, storm propagation becomes slightly slower throughout much of the midlatitudes (30°–60°N). Trends in both seasons relate closely to the impact of global warming on upper-level (250 hPa) winds and the 850–250-hPa thickness gradient. Wherever local thickness gradients weaken in the future, ETCs travel more slowly; conversely, wherever they strengthen, ETCs travel more quickly. In contrast to past work, we find that winter storm propagation becomes more zonal over the Pacific and Atlantic Oceans, which may link to decreased atmospheric blocking and less-sinuous flow at 500 hPa. The importance of model projections of the 850–250-hPa thickness gradient for meridionality of ETC propagation remains uncertain for these regions. However, for North America, models that project stronger thickness gradients also project less-sinuous flow and more-zonal ETC propagation. Overall, this work highlights strong regional variation in how the speed and direction of ETC propagation, and the upper-level circulation patterns that govern them, respond to continued warming.

Significance Statement
Extratropical storms are common sources of natural hazards like heavy rain and high winds. In our analysis of projections from 18 climate models, we find that winter storms tend to move more slowly over midlatitude North America and the Arctic as the world warms but move faster over the North Pacific Ocean and part of Europe. Slight slowing of summer storms is projected throughout much of the midlatitudes. When storms move slower, their attendant hazards (like heavy precipitation) last longer for the areas they impact. Further, Atlantic winter storms travel more west to east instead of southwest to northeast, so they impact Iceland less often and the British Isles more often. Changes become more dramatic with each additional degree of global warming.
A Systematic Review of Cognitive Function, Anxiety, and Depression in Patients With Newly Diagnosed Primary Central Nervous System Lymphoma
Authors: Liu Ziyu , Zhuang Jingming , Wei Li , Lu Aiwen , Hou Jiangang , Yang Xiaoli 
Published: August 2023

Objective To retrospectively analyze the effects of different treatments on cognitive functioning, anxiety, and depression in patients with primary central nervous system lymphoma (PCNSL). Methods A comprehensive literature search was conducted in multiple databases including the Cochrane Library, CINAHL, PubMed, Web of Science, EMBASE, Sino Med, Wei Pu, Wan Fang, CNKI, and Google Scholar. The search included studies published through June 20, 2023, focusing on cognitive function, anxiety, and depression in adult patients newly diagnosed with PCNSL. Various measurement tools and scales were used to assess the primary outcomes. Descriptive systematic reviews were conducted to integrate the literature and summarize the effects of different treatment modalities on cognitive functioning, anxiety, and depression in PCNSL patients. This review was registered with PROSPERO (CRD42022370250). Results A total of 43 studies were included. Induction chemotherapy was associated with improved cognitive function and reduced anxiety and depression in the majority of patients. Whole-brain radiotherapy (WBRT) was found to lead to cognitive impairment, particularly in executive, attention, memory, and motor function. Low-dose WBRT, autologous stem cell transplantation (ASCT), and blood-brain barrier disruption (BBBD) treatments did not result in significant cognitive impairment. Anxiety and depression were observed to decrease over the long term. Conclusions Overall, the cognitive functioning, anxiety, and depression of patients with PCNSL can be improved with appropriate treatments. However, patients treated with WBRT are at a higher risk of cognitive decline compared to those receiving other treatment modalities. Therefore, special attention should be given to patients undergoing WBRT, and a comprehensive analysis should be conducted to reduce neurotoxicity and address early cognitive problems in these patients.
The behaviour change behind a successful pilot of hypoglycaemia reduction with HYPO-CHEAT
Authors: Worth Chris , Nutter Paul W , Salomon-Estebanez Maria , Auckburally Sameera , Dunne Mark J , Banerjee Indraneel , Harper Simon 
Published: August 2023

Background Children with hypoglycaemia disorders, such as congenital hyperinsulinism (CHI), are at constant risk of hypoglycaemia (low blood sugars) with the attendant risk of brain injury. Current approaches to hypoglycaemia detection and prevention vary from fingerprick glucose testing to the provision of continuous glucose monitoring (CGM) to machine learning (ML) driven glucose forecasting. Recent trends for ML have had limited success in preventing free-living hypoglycaemia, due to a focus on increasingly accurate glucose forecasts and a failure to acknowledge the human in the loop and the essential step of changing behaviour. The wealth of evidence from the fields of behaviour change and persuasive technology (PT) allows for the creation of a theory-informed and technologically considered approach. Objectives We aimed to create a PT that would overcome the identified barriers to hypoglycaemia prevention for those with CHI to focus on proactive prevention rather than commonly used reactive approaches. Methods We used the behaviour change technique taxonomy and persuasive systems design models to create HYPO-CHEAT (HYpoglycaemia-Prevention-thrOugh-Cgm-HEatmap-Assisted-Technology): a novel approach that presents aggregated CGM data in simple visualisations. The resultant ease of data interpretation is intended to facilitate behaviour change and subsequently reduce hypoglycaemia. Results HYPO-CHEAT was piloted in 10 patients with CHI over 12 weeks and successfully identified weekly patterns of hypoglycaemia. These patterns consistently correlated with identifiable behaviours and were translated into both a change in proximal fingerprick behaviour and ultimately, a significant reduction in aggregated hypoglycaemia from 7.1% to 5.4% with four out of five patients showing clinically meaningful reductions in hypoglycaemia. Conclusions We have provided pilot data of a new approach to hypoglycaemia prevention that focuses on proactive prevention and behaviour change. This approach is personalised for individual patients with CHI and is a first step in changing our approach to hypoglycaemia prevention in this group.
Comparison of effectiveness of different training tools on the level of knowledge about emergency management of avulsed teeth in non-dentists
Authors: Gümüşboğa Zekiye Şeyma , Duruk Gülsüm 
Published: August 2023

Objective Tooth avulsion is a type of trauma requiring an emergency response, and the level of knowledge of non-dentists on the emergency management of avulsed teeth is important for the prognosis of affected teeth. This study aimed to compare the effectiveness of training given using different tools on the level of knowledge about the emergency management of avulsed teeth in non-dentists. Methods A total of 125 individuals (female, 32.8%; male, 67.2%; mean age, 38.5 ± 7.32 years) participated in the study. The participants were randomly assigned to three groups, and the training was offered to these groups using different training tools (group 1, storybook; group 2, poster; group 3, ToothSOS App). A survey was conducted on all participants to measure their knowledge levels before training (T0), immediately after (T1), and 1 month later (T2). The Mann–Whitney U, Kruskal–Wallis, Wilcoxon, and Friedman tests were used for statistical analysis. Results The participants’ mean correct answer scores on a scale from 0 to 21 were 7.76 ± 4.00, 5.47 ± 4.71, and 7.38 ± 2.96 at T0 in groups 1, 2, and 3, respectively, and their mean scores increased to 14.68 ± 4.10, 13.74 ± 3.28, and 13.86 ± 3.01 at T1 and 13.41 ± 3.34, 12.34 ± 3.77, and 13.66 ± 3.56 at T2. The correct answer scores increased significantly at both T1 and T2 in all groups ( p < 0.001). Conclusion None of the training tools used in the study was superior in increasing the level of knowledge. More comprehensive and long-term studies on this subject are needed.
Attachment Behaviour, Attachment Representations, and Symptoms of Reactive Attachment Disorder and Disinhibited Social Engagement Disorder in Foster Children With Different Preplacement Experiences
Authors: Jorjadze Nino , Bovenschen Ina , Spangler Gottfried 
Published: August 2023

Foster care offers children a safe family environment and is effective in buffering the negative effects of early adversity. Specifically, foster care has been found to facilitate secure attachment to foster parents. However, there are limited data on attachment development in children entering foster care after the first year of life. In this study, we examined attachment behaviour and representations as well as symptoms of reactive attachment disorder (RAD) and disinhibited social engagement disorder (DSED) in 3–6 year-old foster children. We studied two subgroups of foster children with different preplacement experiences (Group 1: children entering foster care after living in institutions; Group 2: children entering foster care after living with their biological families) and compared them with a community sample. The results revealed that children in both foster care groups showed significantly lower attachment security at the behavioural level, higher hyperactivation and disorganization at the representational level, and significantly more symptoms of RAD and DSED than the children in the control group. Analyses did not indicate significant differences between the foster care groups. Moreover, no significant associations were found between attachment-related variables and preplacement experiences. This may be an indication that in long-term foster care, the quality of foster care becomes the major factor affecting a child’s attachment development. Thus, foster parents need supportive services and interventions with a focus on attachment development.
Therapist and supervisor perspectives about two train-the-trainer implementation strategies in schools: A qualitative study
Authors: Lawson Gwendolyn M. , Comly Rachel , Beidas Rinad S. , Khanna Muniya S. , Goldstein Jessica , Brizzolara-Dove Shelby , Wilson Tara , Rabenau-McDonnell Quinn , Eiraldi Ricardo 
Published: August 2023

Background Train-the-trainer (TT) implementation strategies (in which designated clinicians are trained to then train others in an intervention) are promising approaches to support mental health clinician use of evidence-based interventions in school contexts. However, there is little evidence to date examining clinicians’ perceptions of the acceptability and feasibility of TT strategies, or comparing clinicians’ perceptions of different types of TT strategies. Methods The current study was conducted as part of a larger hybrid effectiveness-implementation trial, in which school-based therapists and supervisors received one of two different types of implementation support to implement cognitive behavioral therapy (CBT) groups for anxiety: TT (i.e., initial training for therapists and supervisors) or enhanced TT (TT+; i.e., initial training for therapists and supervisors, and ongoing external consultation for supervisors). We used applied thematic analysis to compare qualitative interview transcripts from 28 therapist interviews and 33 supervisor interviews from therapists and supervisors who received TT or TT+ support and report themes that were similar and different across the two groups. Results Most themes were similar across the TT and TT+ conditions: therapists and supervisors in both conditions perceived the group anxiety intervention as acceptable and viewed supervision as acceptable, helpful, and feasible. Therapists and supervisors in both conditions had mixed impressions of the contextual appropriateness of the group anxiety intervention, and some reported logistical challenges with weekly supervision. Some unique themes were identified among the TT+ condition, including supervisors experiencing professional growth, and therapists and supervisors perceiving supervision as critically important and enjoyable. Conclusions These results suggest that TT implementation support, using a model in which an internal supervisor receives initial training and then provides ongoing supervision, is acceptable and feasible to support a group CBT intervention in schools. The results also highlight additional benefits that therapists and supervisors perceived when supervisors received ongoing consultation. Clinical Trial Registration Information The clinical trial from which these data were derived was registered at ClinicalTrials.gov ( https://clinicaltrials.gov/ ) prior to the time of first patient enrollment. The registration number is: NCT02651402.