bluuebunny/crossref_metadata_2025_split huggingface dataset:
Framework humanization optimizes potency of anti-CD72 nanobody CAR-T cells for B-cell malignancies
Authors: Temple William C , Nix Matthew A , Naik Akul , Izgutdina Adila , Huang Benjamin J , Wicaksono Gianina , Phojanakong Paul , Serrano Juan Antonio Camara , Young Elizabeth P , Ramos Emilio , Salangsang Fernando , Steri Veronica , Xirenayi Simayijiang , Hermiston Michelle , Logan Aaron C , Stieglitz Elliot , Wiita Arun P 
Published: November 2023

BackgroundApproximately 50% of patients who receive anti-CD19 CAR-T cells relapse, and new immunotherapeutic targets are urgently needed. We recently described CD72 as a promising target in B-cell malignancies and developed nanobody-based CAR-T cells (nanoCARs) against it. This cellular therapy design is understudied compared with scFv-based CAR-T cells, but has recently become of significant interest given the first regulatory approval of a nanoCAR in multiple myeloma.MethodsWe humanized our previous nanobody framework regions, derived from llama, to generate a series of humanized anti-CD72 nanobodies. These nanobody binders were inserted into second-generation CD72 CAR-T cells and were evaluated against preclinical models of B cell acute lymphoblastic leukemia and B cell non-Hodgkin’s lymphoma in vitro and in vivo. Humanized CD72 nanoCARs were compared with parental (“NbD4”) CD72 nanoCARs and the clinically approved CD19-directed CAR-T construct tisangenlecleucel. RNA-sequencing, flow cytometry, and cytokine secretion profiling were used to determine differences between the different CAR constructs. We then used affinity maturation on the parental NbD4 construct to generate high affinity binders against CD72 to test if higher affinity to CD72 improved antitumor potency.ResultsToward clinical translation, here we humanize our previous nanobody framework regions, derived from llama, and surprisingly discover a clone (“H24”) with enhanced potency against B-cell tumors, including patient-derived samples after CD19 CAR-T relapse. Potentially underpinning improved potency, H24 has moderately higher binding affinity to CD72 compared with a fully llama framework. However, further affinity maturation (KD<1 nM) did not lead to improvement in cytotoxicity. After treatment with H24 nanoCARs, in vivo relapse was accompanied by CD72 antigen downregulation which was partially reversible. The H24 nanobody clone was found to have no off-target binding and is therefore designated as a true clinical candidate.ConclusionThis work supports translation of H24 CD72 nanoCARs for refractory B-cell malignancies, reveals potential mechanisms of resistance, and unexpectedly demonstrates that nanoCAR potency can be improved by framework alterations alone. These findings may have implications for future engineering of nanobody-based cellular therapies.
Single-cell RNA-sequencing atlas reveals an FABP1-dependent immunosuppressive environment in hepatocellular carcinoma
Authors: Tang Weiwei , Sun Guangshun , Ji Gu-Wei , Feng Tingting , Zhang Qian , Cao Hengsong , Wu Wenhao , Zhang Xiaoyi , Liu Chuan , Liu Hanyuan , Huang Tian , Liu Li , Xia Yongxiang , Wang Xuehao 
Published: November 2023

BackgroundSingle-cell RNA sequencing, also known as scRNA-seq, is a method profiling cell populations on an individual cell basis. It is particularly useful for more deeply understanding cell behavior in a complicated tumor microenvironment. Although several previous studies have examined scRNA-seq for hepatocellular carcinoma (HCC) tissues, no one has tested and analyzed HCC with different stages.MethodsIn this investigation, immune cells isolated from surrounding normal tissues and cancer tissues from 3 II-stage and 4 III-stage HCC cases were subjected to deep scRNA-seq. The analysis included 15 samples. We distinguished developmentally relevant trajectories, unique immune cell subtypes, and enriched pathways regarding differential genes. Western blot and co-immunoprecipitation were performed to demonstrate the interaction between fatty acid binding protein 1 (FABP1) and peroxisome proliferator-activated receptor gamma(PPARG). In vivo experiments were performed in a C57BL/6 mouse model of HCC established via subcutaneous injection.ResultsFABP1 was discovered to be overexpressed in tumor-associated macrophages (TAMs) with III-stage HCC tissues compared with II-stage HCC tissues. This finding was fully supported by immunofluorescence detection in significant amounts of HCC human samples. FABP1 deficiency in TAMs inhibited HCC progression in vitro. Mechanistically, FABP1 interacted with PPARG/CD36 in TAMs to increase fatty acid oxidation in HCC. When compared with C57BL/6 mice of the wild type, tumors in FABP1–/– mice consistently showed attenuation. The FABP1–/– group’s relative proportion of regulatory T cells and natural killer cells showed a downward trend, while dendritic cells, M1 macrophages, and B cells showed an upward trend, according to the results of mass cytometry. In further clinical translation, we found that orlistat significantly inhibited FABP1 activity, while the combination of anti-programmed cell death 1(PD-1) could synergistically treat HCC progression. Liposomes loaded with orlistat and connected with IR780 probe could further enhance the therapeutic effect of orlistat and visualize drug metabolism in vivo.ConclusionsScRNA-seq atlas revealed an FABP1-dependent immunosuppressive environment in HCC. Orlistat significantly inhibited FABP1 activity, while the combination of anti-PD-1 could synergistically treat HCC progression. This study identified new treatment targets and strategies for HCC progression, contributing to patients with advanced HCC from new perspectives.
Chimeric antigen receptor T cells to target CD79b in B-cell lymphomas
Authors: Chu Fuliang , Cao Jingjing , Liu Jingwei , Yang Haopeng , Davis Timothy J , Kuang Shao-qing , Cheng Xiaoyun , Zhang Zheng , Karri Swathi , Vien Long T , Bover Laura , Sun Ryan , Vega Francisco , Green Michael , Davis Richard Eric , Neelapu Sattva S 
Published: November 2023

BackgroundChimeric antigen receptor (CAR) T cells targeting CD19 mediate potent and durable effects in B-cell malignancies. However, antigen loss or downregulation is a frequent cause of resistance. Here, we report development of a novel CAR T-cell therapy product to target CD79b, a pan B-cell antigen, widely expressed in most B-cell lymphomas.MethodsWe generated a novel anti-CD79b monoclonal antibody by hybridoma method. The specificity of the antibody was determined by testing against isogenic cell lines with human CD79b knock-in or knock-out. A single-chain variable fragment derived from the monoclonal antibody was used to make a panel of CD79b-targeting CAR molecules containing various hinge, transmembrane, and co-stimulatory domains. These were lentivirally transduced into primary T cells and tested for antitumor activity in in vitro and in vivo B-cell lymphoma models.ResultsWe found that the novel anti-CD79b monoclonal antibody was highly specific and bound only to human CD79b and no other cell surface protein. In testing the various CD79b-targeting CAR molecules, superior antitumor efficacy in vitro and in vivo was found for a CAR consisting CD8α hinge and transmembrane domains, an OX40 co-stimulatory domain, and a CD3ζ signaling domain. This CD79b CAR specifically recognized human CD79b-expressing lymphoma cell lines but not CD79b knock-out cell lines. CD79b CAR T cells, generated from T cells from either healthy donors or patients with lymphoma, proliferated, produced cytokines, degranulated, and exhibited robust cytotoxic activity in vitro against CD19+and CD19–lymphoma cell lines and patient-derived lymphoma tumors relapsing after prior CD19 CAR T-cell therapy. Furthermore, CD79b CAR T cells were highly efficient at eradicating pre-established lymphoma tumors in vivo in three aggressive lymphoma xenograft models, including two cell line-derived xenografts and one patient-derived xenograft. Notably, these CAR T cells did not demonstrate any significant tonic signaling activity or markers of exhaustion.ConclusionOur results indicated that this novel CD79b CAR T-cell therapy product has robust antitumor activity against B-cell lymphomas. These results supported initiation of a phase 1 clinical trial to evaluate this product in patients with relapsed or refractory B-cell lymphomas.
Predictors requiring special attention to prevent clavicle fracture nonunion: a systematic review of literature
Authors: Irfan Shayan Ali , Ali Abid Anwar , Ashkar Anusha , Akram Usama , Fatima Sameen , Baig Mirza M Ali , Khan Muhammad Waqas 
Published: November 2023

BackgroundClavicle fracture (CF) is the tenth most prevalent fracture, accounting for an annual incidence of 37/10,000. This systematic review highlights the factors contributing to the nonunion union of the clavicular fracture.MethodA systematic search was conducted using three web-based databases up to August 12, 2022, for conducting qualitative analysis. Articles were screened for relevance, and only studies that met inclusion criteria based on PECOS; P (patients): participants diagnosed with clavicular fracture; E (exposure): nonunion, C (control): not applicable; O (outcomes): factors contributing to nonunion or delayed union; S (studies): trials and observational studies. The Newcastle-Ottawa Scale was used to assess the quality of the cohort studies. The Cochrane risk of bias tool was used to assess the bias in randomized control trials.ResultsTen studies were selected after the final literature search. Two thousand seven hundred and sixty-six adult participants who were radiologically and clinically diagnosed with nonunion clavicular fracture were included to pool the qualitative results. Fall was the most dominant cause of clavicular fracture, followed by road traffic collisions. Open reduction was widely used to treat nonunion correction. The qualitative results suggested a prominent correlation of nonunion with advancing age, female gender, high energy trauma, high Disabilities of the Arm, Shoulder, and Hand Score, smoking, fracture displacement, clavicular shortening, the callus on radiography, and fracture movement. The mid-shaft fracture was the most dominant type of fracture in the included studies; highly associated with nonunion in comparison to medial or lateral CF. The previous history of operation was an independent factor contributing to nonunion.ConclusionThe results of this systematic review suggested the predictors contributing to nonunion in the CF. Demographic factors such as advancing age with female gender are at higher risk of developing clavicular nonunion. Smoking was the most dominantly highlighted environmental factor contributing to nonunion. Diaphyseal or midshaft fracture was the most common site for nonunion. Therefore, we suggested that patients with the predictors mentioned above require special attention to prevent nonunion of the CFs. More studies should be conducted on this subject to assess the factors that pose a risk associated with the nonunion of the bone for better clinical management and outcomes of the fracture.
Acetabular fractures in elderly patients are associated with high rates of complications during the initial admission
Authors: Simske Natasha , Furdock Ryan , Heimke Isabella , Vallier Heather A 
Published: November 2023

BackgroundAcetabular fractures among the elderly are common. Identification of risk factors predisposing elderly patients to in-hospital complications is critical to mitigating morbidity and mortality.MethodsA retrospective cohort study was performed including 195 patients ≥60 years old who sustained acetabulum fractures treated at a single level 1 trauma center. Operative (n=110, 56.4%) or non-operative management was undertaken, and complications during the index hospitalization were defined.ResultsSeventy-three patients (37%) developed a complication during their hospitalization. Most common complications were acute respiratory failure: 13.3%, pneumonia: 10.3%, urinary tract infection: 10.3%, cardiac dysrhythmia: 9.7%, and acute kidney injury: 6.2%. On multivariable analysis, factors associated with in-hospital complications were increased age (adjusted OR (AOR): 1.06, 95% CI: 1.01 to 1.11, p=0.013), more comorbidities (AOR: 1.69, 95% CI: 1.07 to 2.65, p=0.024), operative management (AOR: 0.3, 95% CI: 0.12 to 0.76, p=0.011), and increased length of stay (AOR: 1.34, 95% CI: 1.2 to 1.51, p<0.001).ConclusionsAcetabular fractures in the elderly are associated with high rates of in-hospital complications. Advanced age, more medical comorbidities and longer lengths of stay predicted higher risk of developing complications. Whereas operative management was associated with lower risk of developing complications during the initial admission, it is important to note the selection bias in which healthier patients with improved baseline functionality may be more likely to undergo operative management.Level of evidenceLevel III therapeutic.
Probing gluon saturation via diffractive jets in ultra-peripheral nucleus-nucleus collisions
Authors: Iancu E. , Mueller A. H. , Triantafyllopoulos D. N. , Wei S. Y. 
Published: November 2023

AbstractWe argue that semi-inclusive photo-production of a pair of hard jets via coherent diffraction in nucleus-nucleus ultra-peripheral collisions at high energy is a golden channel to study gluon saturation. The dominant contribution is the diffractive production of three jets in an asymmetric configuration. Two of the jets are hard and propagate at nearly central pseudo-rapidities. The third jet is semi-hard, with transverse momentum comparable to the nuclear saturation momentum, and is well separated in pseudo-rapidity from the hard dijets. The emission of the semi-hard jet allows for strong scattering, thus avoiding the “higher-twist” suppression of the exclusive dijet production due to colour transparency. We compute the trijet cross-section using the diffractive TMD factorisation which emerges from the CGC effective theory at high energy. The cross-section is controlled by gluon saturation, which leaves its imprints on the structure of the final state, notably on the rapidity distribution.
The $$\mathcal{O}(\alpha _t+\alpha _\lambda +\alpha _\kappa )^2$$ correction to the $$\rho $$ parameter and its effect on the W boson mass calculation in the complex NMSSM
Authors: Dao Thi Nhung , Gabelmann Martin , Mühlleitner Margarete 
Published: November 2023

AbstractWe present the prediction of the electroweak $$\rho $$
ρ
parameter and the W boson mass in the CP-violating Next-to-Minimal Supersymmetric extension of the Standard Model (NMSSM) at the two-loop order. The $$\rho $$
ρ
parameter is calculated at the full one-loop and leading and sub-leading two-loop order $${\mathcal {O}}(\alpha + \alpha _t\alpha _s + \left( \alpha _t+\alpha _\lambda +\alpha _\kappa \right) ^2)$$

O
(
α
+

α
t

α
s

+

α
t

+

α
λ

+

α
κ

2

)

. The new $$\Delta \rho $$

Δ
ρ

prediction is incorporated into a prediction of $$M_W$$

M
W

via a full supersymmetric (SUSY) one-loop calculation of $$\Delta r$$

Δ
r

. Furthermore, we include all known state-of-the-art SM higher-order corrections to $$\Delta r$$

Δ
r

. By comparing results for $$\Delta \rho $$

Δ
ρ

obtained using on-shell (OS) and $$\overline{\text {DR}}$$

DR
¯

renormalization conditions in the top/stop sector, we find that the scheme uncertainty is reduced at one-loop order by 55%, at two-loop $${\mathcal {O}}(\alpha _s\alpha _t)$$

O
(

α
s

α
t

)

by 22%, and at two-loop $${\mathcal {O}}(\alpha _t+\alpha _\kappa +\alpha _\lambda )^2$$

O

(

α
t

+

α
κ

+

α
λ

)

2

by 16%, respectively. The influence of the two-loop results on the $$M_W$$

M
W

mass prediction is found to be sub-leading. The new calculation is made public in the computer program . We perform an extensive comparison in the W-mass, Higgs boson mass and the muon anomalous magnetic moment prediction between our calculation and three other publicly available tools and find very good agreement provided that the input parameters and renormalization scales are treated in the same way. Finally, we study the impact of the CP-violating phases on the W-mass prediction which is found to be smaller than the overall size of the SUSY corrections.
When Life is Endangered
Authors: Verde Danilo 
Published: November 2023

Abstract
This paper aims to shed new light on the understudied classical Hebrew formulaic expression יום/עת צרה, “day/time of distress,” by investigating the Hebrew Bible, the Hebrew texts of Ben Sira, and the Dead Sea Scrolls. After describing the formulaic dimension of this phrase and its fixed linguistic and conceptual patterns, it will be argued that the concept of narrowness usually attributed to צרה does not stand out when this lexeme is in collocation with יום/עת. The formulaic expression יום/עת צרה indicates the inner turmoil caused by threats to life. The notion of narrowness may belong to the etymology and meaning potential of צרה, but is insufficient to describe the patchwork of emotional states that assaults on life cause in those who go through the יום/עת צרה. It will also be shown that sometimes the idiomatic expression יום/עת צרה is replaced by cognate phrases that, although semantically similar, are usually used to convey ideas that are not intrinsic to the widely used phrase יום/עת צרה.
Ashes still smoking: the influence of fire and land cover on Pantanal ecoregion amphibians
Authors: Moreira Leonardo F.B. , Smaniotto Natália P. , Ceron Karoline , Santana Diego J. , Ferreira Vanda L. , Strüssmann Christine , Galatti Ulisses 
Published: November 2023

Abstract
Fire and land cover are two elements intertwined with the natural history of organisms from seasonally dry environments. Here, we investigated the influence of fire attributes (burned area and frequently-burned area) and land cover on the relative abundance of three amphibians from the Pantanal ecoregion that belong to distinct ecomorphological groups: Chiasmocleis albopunctata, Pseudis platensis, and Scinax acuminatus. We systematically reviewed amphibian ecology studies in the Pantanal and analysed quantitative data between 2000 and 2021, comprising 34 sites from 12 amphibian surveys. Amphibian abundance, land cover, and fire data were assessed within buffers of a 1000 m radius. Species abundance was correlated with burned area and wetland cover. While the abundance of C. albopunctata and P. platensis decreased with burned area in the last three years, the abundance of S. acuminatus increased with wetland cover. Despite the claimed resilience of species inhabiting grasslands and savannas, there was substantial evidence for the influence of burned areas, even under modest human land use. Our findings illustrate that a broad array of land cover and fire attributes may influence amphibian persistence in the Pantanal ecoregion, with the magnitude depending on species traits often overlooked in modelling approaches.
Constructing a Sensory Alternative to the Ongwen Judgment
Authors: Viswanath Raghavi , Li Fangyi 
Published: November 2023

Abstract
Much ink has been spilt criticising the icc’s Ongwen trial judgment for its failure to grasp the cultural context in which the accused Ongwen and the Acholi community were embedded. Some scholars blame this on the poor quality of translation services, others attribute it to the ‘binarism’ of judgments. We offer another explanation for the Ongwen judgment’s deficiencies: its purely textual format. The judgment shows that the continued preference for textual judgments in international criminal law sterilises victims’ experiences, decontextualises evidence, and muffles objectivity. This ties into the historical preference for text over senses, a colonially engineered decision aimed at suppressing non-Western epistemologies. In this paper, we call for the international criminal law judgment to embrace ‘the opportunities of the wider sensory field’. Drawing on the pervasive sensory dimensions of international criminal law, we argue that a sensory reimagination of judgments would better serve international criminal law’s affective potential by empowering survivors and achieving a more reparative and reconstructive justice.
“Dificultades engañosas”: Observations and Suppositions on the Artistic Style of Cretan Icons by Domenikos Theotokopoulos before El Greco
Authors: Bekiaris Antonis , Kastrinakis Nikos , Konstantios Nikolas 
Published: November 2023

Abstract
The works that can be attributed to the Cretan period of Domenikos Theotokopoulos (El Greco) – which is to say the Evangelist Luke Painting the Virgin and Child, the Adoration of the Magi, and the Dormition of the Virgin – are informed by a single stylistic concept and, at the same time, differ significantly in style from most contemporary Cretan paintings. This is demonstrated through an analysis of their respective style and their comparison with the Adoration of the Magi by Michael Damaskinos and the Dormition of the Virgin by Georgios Klontzas. Theotokopoulos integrates the figures into a homogeneous pictorial space in which the relations among them, and between them and the light, are less descriptive than organic and “natural.” This introduces a materialistic dimension into his style that had not formerly been present in Cretan painting. This style was perhaps a response to the need to redefine the Byzantine painting tradition in a more radical way.
The Faunal Remains from the Cistercian Nunnery of St Theodore in Nicosia, Cyprus
Authors: Hadjikoumis Angelos 
Published: November 2023

Abstract
The study of the faunal assemblage from St Theodore Abbey provides an opportunity to explore human–animal interactions in the context of a Cistercian nunnery in Cyprus functioning from ca. 1230 to ca. 1550. Within the limitations of a modest sample size, the analyses provide valuable insights into animal-related economic activities, diet, and status at the nunnery. The main components of the animal economy were pig and goat husbandry, while donkeys, horses, and possibly cattle were used in transportation and agricultural work. Besides pork and goat meat, the diet was complemented with chicken rearing and the secondary products of goat and sheep, as well as the occasional wild hare, fish, and birds. With the data at hand, it is difficult to elucidate the diet of different groups of people at the nunnery. Nevertheless, there are indications of high economic and social status in the form of tender meat (kids/lambs, piglets, young chicken, and possibly imported fish).
A small-scale study exploring the efficacy of scale modelling as an open intervention for military veterans with mental health conditions
Authors: Lawrence Ceri , Ellison Diane 
Published: November 2023

Introduction: Medical discharges due to mental health conditions have steadily increased within the British Armed Forces since 2007, with post-traumatic stress disorder (PTSD) cited for 41% of these. Mental health conditions can adversely impact engagement in activities of daily living. Research has shown that meaningful activity has benefits for mental well-being and engagement in this population. Aims: This small-scale study aimed to determine whether scale modelling had a measurable impact on veteran well-being and to describe how the results of this study may inform future occupational therapy research with veterans. Method: This was a retrospective quantitative design using the Short Warwick and Edinburgh Mental Wellbeing Scale to gather pre- and post-engagement data from veterans attending scale-modelling groups. Results: N = 12. There was a positive difference between pre- and post-engagement in scale modelling, p < 0.05, and effect size 0.61 within a limited participant pool. The Model-of-Human-Occupation and the Occupational Perspective of Health framework demonstrated that participants who found meaning and value in an activity were most likely to benefit from it. Conclusion: This study suggests that scale modelling enables health, well-being and independence for veterans if found meaningful by them. This is a limited-size study contributing to an under-researched area, opening pathways for further research with this participant group.