bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of VISTA regulated via IFN-γ governs endogenous T-cell function and exhibits correlation with the efficacy of CD19 CAR-T cell treated B-malignant mice
Authors: Tang Donghai , Zhao Li , Yan Fen , Ren Chunxiao , Xu Kailin , Zhao Kai 
Published: June 2024

BackgroundDespite continuous improvements in the new target and construction of chimeric antigen receptor (CAR)-T, relapse remains a significant challenge following CAR-T therapy. Tumor microenvironment (TME) strongly correlates with the efficacy of CAR-T therapy. V-domain Ig suppressor of T-cell activation (VISTA), which exerts a multifaceted and controversial role in regulating the TME, acts not only as a ligand on antigen-presenting cells but also functions as a receptor on T cells. However, the characteristics and underlying mechanisms governing endogenous T-cell activation by VISTA, which are pivotal for reshaping the TME, remain incompletely elucidated.MethodsThe immunocompetent B acute lymphoblastic leukemia (B-ALL), lymphoma, and melanoma murine models were employed to investigate the characteristics of endogenous T cells within the TME following CD19 and hCAIX CAR-T cell therapy, respectively. Furthermore, we examined the role of VISTA controlled by interferon (IFN)-γ signaling in regulating endogenous T-cell activation and functionality in B-ALL mice.ResultsWe demonstrated that the administration of CD19 CAR-T or hCAIX CAR-T cell therapy elicited augmented immune responses of endogenous T cells within the TME of B-ALL, lymphoma, and melanoma mice, thereby substantiating the efficacy of CAR-T cell efficacy. However, in the TME lacking IFN-γ signaling, VISTA levels remained elevated, resulting in attenuated cytotoxicity of endogenous T cells and reduced B-ALL recipient survival. Mice treated with CD19 CAR-T cells exhibited increased proportions of endogenous memory T cells during prolonged remission, which possessed the tumor-responsive capabilities to protect against B-ALL re-challenge. Compared with wild-type (WT) CAR-T treated mice, the administration of IFN-γ−/−CAR-T to both WT and IFN-γ−/−recipients resulted in a reduction in the numbers of endogenous CD4+and CD8+effectors, while exhibiting increased populations of naïve-like CD4+T and memory CD8+T cells. VISTA expression consistently remained elevated in resting or memory CD4+T cells, with distinct localization from programmed cell death protein-1 (PD-1) expressing T subsets. Blocking the VISTA signal enhanced dendritic cell-induced proliferation and cytokine production by syngeneic T cells.ConclusionOur findings confirm that endogenous T-cell activation and functionality are regulated by VISTA, which is associated with the therapeutic efficiency of CAR-T and provides a promising therapeutic strategy for relapse cases in CAR-T therapy.
Fc–Fc interactions and immune inhibitory effects of IgG4: implications for anti-PD-1 immunotherapies
Authors: Zhang Weifeng , Chen Xueling , Chen Xingxing , Li Jirui , Wang Hui , Yan Xiaomiao , Zha Han , Ma Xiaonan , Zhao Chanyuan , Su Meng , Hong Liangli , Li Penghao , Ling Yanyu , Zhao Wenhui , Xia Yu , Li Baiyong , Zheng Tianjing , Gu Jiang 
Published: June 2024

BackgroundThe majority of anti-programmed cell-death 1 (PD-1) monoclonal antibodies (mAbs) use S228P mutation IgG4 as the structural basis to avoid the activation of immune cells or complement. However, little attention has been paid to the Fc–Fc interactions between IgG4 and other IgG Fc fragments that could result in adverse effects. Fc-null IgG1 framework is a potential safer alternative to avoid the undesirable Fc–Fc interactions and Fc receptor binding derived effects observed with IgG4. This study provides a comprehensive evaluation of anti-PD-1 mAbs of these two frameworks.MethodsTrastuzumab and rituximab (both IgG1), wildtype IgG1 and IgG4 were immobilized on nitrocellulose membranes, coated to microplates and biosensor chips, and bound to tumor cells as targets for Fc–Fc interactions. Wildtype IgG1 and IgG4, anti-PD-1 mAb nivolumab (IgG4 S228P), penpulimab (Fc-null IgG1), and tislelizumab (Fc-null IgG4 S228P-R409K) were assessed for their binding reactions to the immobilized IgG proteins and quantitative kinetic data were obtained. To evaluate the effects of the two anti-PD-1 mAbs on immune responses mediated by trastuzumab and rituximab in the context of combination therapy, we employed classic immune models for antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, and complement dependent cytotoxicity. Tumor-bearing mouse models, both wildtype and humanized, were used for in vivo investigation. Furthermore, we also examined the effects of IgG1 and IgG4 on diverse immune cell populationsResultsExperiments demonstrated that wildtype IgG4 and nivolumab bound to immobilized IgG through Fc–Fc interactions, diminishing antibody-dependent cell-mediated cytotoxicity and phagocytosis reactions. Quantitative analysis of kinetic parameters suggests that nivolumab and wildtype IgG4 exhibit comparable binding affinities to immobilized IgG1 in both non-denatured and denatured states. IgG4 exerted inhibitory effects on various immune cell types. Wildtype IgG4 and nivolumab both promoted tumor growth in wildtype mouse models. Conversely, wildtype IgG1, penpulimab, and tislelizumab did not show similar adverse effects.ConclusionsFc-null IgG1 represents a safer choice for anti-PD-1 immunotherapies by avoiding both the adverse Fc–Fc interactions and Fc-related immune inhibitory effects of IgG4. Fc-null IgG4 S228P-R409K and Fc-null IgG1 displayed similar structural properties and benefits. This study contributes to the understanding of immunotherapy resistance and the advancement of safer immune therapies for cancer.
Electromyography and range-of-motion measurements in German soldiers wearing different types of body armour while marching
Authors: Lang Patricia , Amann M , Riesner H-J , Friemert B , Siebers H , Betsch M , Palm H-G 
Published: June 2024

IntroductionIn this study, we used surface electromyography (EMG) electrodes in order to measure and compare activity in the neck, back and thigh muscles of soldiers wearing two different types of body armour. A secondary objective was to analyse shoulder and hip ranges of motion using inertial motion sensors.MethodsFourteen male soldiers were instructed to march 6 km on a treadmill while wearing different types of body armour. All participants wore shorts and a T-shirt and the same size vest regardless of their body size. We measured back and thigh muscle activity as well as shoulder and hip ranges of motion at regular intervals during the march.ResultsOver the course of a 6 km march, muscle activity was already increased to 1.3 to 2.0 times after putting on the vest and increased by up to 13 times during the march with equipment. The new vest with hip belt required higher levels of muscle activity.ConclusionsBody armour with hip belt placed higher levels of stress on back and neck muscles during a 6 km march than without. There was no major difference between the two types of body armour in terms of thigh muscle activity.Trial registration numberDRKS00016005.
Use of regional anesthesia within a pediatric interventional radiology suite reduced periprocedural opioid use without delaying the overall workflow: a retrospective study
Authors: Gaelen Jordan I , Wu Chunyi , Yang Amy , Rajeswaran Shankar , Lazar Alina , Cheon Eric C , Vargas Angelica A 
Published: June 2024

BackgroundNerve block utility has been extensively described in the operating room, however, there is a paucity of evidence regarding blocks in the interventional radiology (IR) suite, with no studies examining its safety and efficacy in children.MethodsA retrospective study was conducted at a single tertiary-care children’s hospital to evaluate the analgesic utility of nerve blocks during IR-performed sclerotherapy for bone cysts, venous malformations, and lymphatic malformations. Lymphatic and venous malformations were combined for final analysis. Patients between January 2016 and September 2022 had their medical records reviewed for procedural data, postprocedural pain scores, and analgesic administration data.Results309 patients were included in the final analysis. Opioids were required significantly less frequently intraprocedurally and postprocedurally across subgroups. The proportion of patients who received opioids during their hospital course was significant between block and non-block patients, respectively: bone cyst: 62.7% vs 100% (p<0.001); venous and lymphatic malformation: 65.7% vs 97.4% (p<0.001). Average maximum postanesthesia care unit (PACU) pain scores were significantly lower in bone cyst patients with no significant difference seen in pain scores among venous and lymphatic malformation patients. There were no reported nerve block-related complications.DiscussionNerve blocks demonstrated an opioid-sparing effect intraprocedurally and postprocedurally for all subgroups. Their use among bone cyst patients was associated with significant reductions in average maximum PACU pain scores. Nerve blocks may constitute an effective opioid-sparing component of multimodal analgesia in pediatric patients undergoing IR sclerosis procedures. Prospective data are needed to establish the optimal utility of nerve blocks in the IR setting.
Bring on the heat: thermal ecology of Tropidurus semitaeniatus in the Northeast of Brazil
Authors: Bruinjé Andre C. , Paiva Tales M.A. , Coelho Felipe E.A. , Costa Gabriel C. 
Published: June 2024

Body temperature is a key physiological trait for individual fitness. Its effects on behavior and metabolism determine organismal activity. Optimal body temperature can vary among individuals, and consequent activity asynchrony can thus enable the co-occurrence of otherwise competing social strategies. Here, we combine ex-situ experiments with environmental data to test whether variability in thermal traits can explain the maintenance of the alternative reproductive strategies of Tropidurus semitaeniatus (Spix, 1825) male morphs. We predict that morphs and sexes differ in thermal traits. Thus, we tested for differences in their behaviorally determined thermal traits: preferred ( Tp), body ( Tb), and habitat temperatures; basking cover preference (Coverpref); and physiological limits (critical thermal minimum CTmin; and maximum, CTmax). We also calculated T. semitaeniatus’ thermal tolerance traits and compiled a list of Tp for Tropidurids. We found that T. semitaeniatus maintains its Tb below Tp. In addition, and contrary to theoretical predictions for tropical lizards, we found that T. semitaeniatus has a high warming tolerance (8.3 °C) and thermal safety margin (2.4 °C). We found no thermal differences between morphs indicating that thermal ecology does not play a role in the co-existence of color morphs.
Targeting the TRIM14/USP14 Axis Enhances Immunotherapy Efficacy by Inducing Autophagic Degradation of PD-L1
Authors: Liu Di , Li Mengqiu , Zhao Zhiyao , Zhou Liang , Zhi Feng , Guo Zhiyong , Cui Jun 
Published: June 2024

Abstract
Immunotherapy has greatly improved cancer treatment in recent years by harnessing the immune system to target cancer cells. The first immunotherapeutic agent approved by the FDA was IFNα. Treatment with IFNα can lead to effective immune activation and attenuate tumor immune evasion, but persistent treatment has been shown to elicit immunosuppressive effects. Here, we identified an autophagy-dependent mechanism by which IFNα triggers tumor immune evasion by upregulating PD-L1 to suppress the antitumor activity of CD8+ T cells. Mechanistically, IFNα increased the transcription of TRIM14, which recruited the deubiquitinase USP14 to inhibit the autophagic degradation of PD-L1. USP14 removed K63-linked ubiquitin chains from PD-L1, impairing its recognition by the cargo receptor p62 (also known as SQSTM1) for subsequent autophagic degradation. Combining the USP14 inhibitor IU1 with IFNα and anti-CTLA4 treatment effectively suppressed tumor growth without significant toxicity. This work suggests a strategy for targeting selective autophagy to abolish PD-L1-mediated cancer immune evasion.
Significance: IFNα-induced TRIM14 transcription suppresses antitumor immunity by recruiting USP14 to inhibit autophagic degradation of PD-L1, indicating that targeting this axis could be an effective immunotherapeutic approach for treating cancer.
The Discovery of a Potent PARP1 Inhibitor Senaparib
Authors: Cai Sui X. , Ma Ning , Wang Xiaozhu , Guo Mingchuan , Jiang Yangzhen , Tian Ye E. 
Published: June 2024

Abstract
PARP1 is a critical enzyme involved in DNA damage repair. It belongs to a superfamily of proteins and catalyzes poly(ADP-ribosyl)ation (PARylation). PARP1 inhibitors are effective to treat tumors that have homologous recombination deficiency such as those with BRCA1/2 mutations. The PARP1 inhibitors that have been approved by FDA inhibit both PARP1 and PARP2. PARP2 has also been suggested to play a similar function in DNA repair as PARP1. In addition to inhibiting PARP1 enzymatic activities, PARP1 inhibitors cause the PARP1 enzyme to be “trapped” on DNA, stalling the DNA replication fork and eventually causing double-strand DNA breaks and cell death. Here, we report a PARP1 inhibitor, Senaparib, which has a novel chemical structure and high potency inhibiting PARP1/2 enzymes. Senaparib was highly potent in cell viability tests against tumor cells with BRCA1/2 mutations. It was efficacious in cell line-derived and patient-derived xenograft models in tumors harboring BRCA1/2 mutations. In combination studies, Senaparib used with temozolomide had shown strong synergistic cytotoxicity in both in vitro and in vivo experiments. Senaparib represents a novel class of PARP1 inhibitors that can be used for the treatment of cancer. A phase III clinical study of Senaparib for maintenance treatment following first-line chemotherapy in patients with advanced ovarian cancer has met its primary endpoint, and a new drug application of Senaparib has been accepted by the National Medical Products Administration of China for review.
Hypoxia-Induced Long Noncoding RNA HIF1A-
AS2 Regulates Stability of MHC Class I Protein in Head and Neck Cancer
Authors: Liao Tsai-Tsen , Chen Yu-Hsien , Li Zih-Yu , Hsiao An-Ching , Huang Ya-Li , Hao Ruo-Xin , Tai Shyh-Kuan , Chu Pen-Yuan , Shih Jing-Wen , Kung Hsing-Jien , Yang Muh-Hwa 
Published: June 2024

Abstract
Intratumoral hypoxia not only promotes angiogenesis and invasiveness of cancer cells but also creates an immunosuppressive microenvironment that facilitates tumor progression. However, the mechanisms by which hypoxic tumor cells disseminate immunosuppressive signals remain unclear. In this study, we demonstrate that a hypoxia-induced long noncoding RNA HIF1A Antisense RNA 2 (HIF1A-AS2) is upregulated in hypoxic tumor cells and hypoxic tumor-derived exosomes in head and neck squamous cell carcinoma (HNSCC). Hypoxia-inducible factor 1 alpha (HIF1α) was found to directly bind to the regulatory region of HIF1A-AS2 to enhance its expression. HIF1A-AS2 reduced the protein stability of major histocompatibility complex class I (MHC-I) by promoting the interaction between the autophagy cargo receptor neighbor of BRCA1 gene 1 (NBR1) protein and MHC-I, thereby increasing the autophagic degradation of MHC-I. In HNSCC samples, the expression of HIF1A-AS2 was found to correlate with hypoxic signatures and advanced clinical stages. Patients with high HIF1α and low HLA-ABC expression showed reduced infiltration of CD8+ T cells. These findings define a mechanism of hypoxia-mediated immune evasion in HNSCC through downregulation of antigen-presenting machinery via intracellular or externalized hypoxia-induced long noncoding RNA.
A Closer Look at Classification Evaluation Metrics and a Critical
Reflection of Common Evaluation Practice
Authors: Opitz Juri 
Published: June 2024

Abstract
Classification systems are evaluated in a countless number of papers. However, we find that evaluation practice is often nebulous. Frequently, metrics are selected without arguments, and blurry terminology invites misconceptions. For instance, many works use so-called ‘macro’ metrics to rank systems (e.g., ‘macro F1’) but do not clearly specify what they would expect from such a ‘macro’ metric. This is problematic, since picking a metric can affect research findings and thus any clarity in the process should be maximized. Starting from the intuitive concepts of bias and prevalence, we perform an analysis of common evaluation metrics. The analysis helps us understand the metrics’ underlying properties, and how they align with expectations as found expressed in papers. Then we reflect on the practical situation in the field, and survey evaluation practice in recent shared tasks. We find that metric selection is often not supported with convincing arguments, an issue that can make a system ranking seem arbitrary. Our work aims at providing overview and guidance for more informed and transparent metric selection, fostering meaningful evaluation.
Extensor Tendon Reconstruction in Vaughan–Jackson Syndrome: Surgical Technique and a Case Illustration
Authors: Jerome J. Terrence Jose , Karunanithi Dharani 
Published: June 2024

Background and Aims: Vaughan–Jackson syndrome, a complication of rheumatoid arthritis, presents with extensor tendon rupture, dorsal tenosynovitis, distal radioulnar synovitis, dorsal subluxation of the distal ulna, and wrist arthritis. This article aimed to present a surgical approach for Vaughan–Jackson syndrome, focusing on dorsal tenosynovectomy, distal ulnar resection and extensor tendon reconstruction. Case Description: A detailed case study is presented, highlighting the surgical technique employed for managing Vaughan–Jackson syndrome. Technical nuances and considerations are discussed. Results: The surgical technique described resulted in successful management of the patient’s Vaughan–Jackson syndrome, with restoration of hand and wrist function. Conclusion: Surgical intervention involving dorsal tenosynovectomy, distal ulnar resection, and extensor tendon reconstruction is a viable option for managing Vaughan–Jackson syndrome. This article provides insights into the surgical management of this complex condition, offering guidance for clinicians encountering similar cases.
Radiographic evaluation of robot-assisted versus manual total hip arthroplasty: a multicenter randomized controlled trial
Authors: Zhang Xianzuo , Shen Xianyue , Zhang Rongwei , Chen Mo , Ma Ruixiang , Zhang Zian , Zhang Haining , Yang Bo , Zhu Chen 
Published: June 2024

Abstract
Background
The effectiveness of robot-assisted surgery remains contentious due to the lack of high-quality randomized controlled trials (RCTs) to elevate the level of evidence. We aimed to evaluate the postoperative radiographic outcomes of robot-assisted (RAS-THA) versus manual (M-THA) total hip arthroplasty.

Methods
This multicenter RCT was performed from March 1, 2021 to December 1, 2021. Patients were randomly assigned to routine M-THA or to RAS-THA that used the TRex-RS orthopedic joint surgical navigation system. The primary outcome was to compare the acetabular component orientation, femoral stem alignment, femoral canal fill ratio, and leg length discrepancy between RAS-THA and M-THA using postoperative radiography. Subgroup analyses of the two groups stratified by surgical approach, gender, and BMI were also conducted.

Results
Seventy-three participants were randomly allocated to the RAS-THA group, while seventy-two participants were assigned to the M-THA group. Compared to the M-THA group, the RAS-THA group exhibited less variability in the preoperative planning of the vertical center of rotation (VCOR; P < 0.001), demonstrated a significant advantage in femoral stem alignment (P = 0.004), and showed pronounced decreases in inequality and in the variability in leg length discrepancy (P < 0.001). There was no significant difference in the Lewinnek safe-zone ratio (P = 0.081) and the femoral canal fill ratio (P > 0.05) between the two groups. Further subgroup analysis also showed that the RAS-THA group had fewer horizontal center of rotation (HCOR) and leg length differences when stratified by surgical approach, gender, and overweight status.

Conclusion
This RCT found that, regardless of the surgical approach, gender, or body mass index, RAS-THA can effectively improve the postoperative VCOR and significantly reduce the variability of leg length difference. RAS-THA should be considered an effective method to enhance surgical precision by achieving less variability in challenging patients with leg length discrepancies.
Trial registration: ChiCTR2100044124.
Effect of different lumbar–iliac fixation and sacral slope for Tile C1.3 pelvic fractures: a biomechanical study
Authors: Fan Shicai , Luo Hongjie , Chen Sheqiang , Xiang Haibo , Mai Qiguang , Zhu Zhenhua , Chen Yuhui , Hou Zhiyong , Chen Wei , Zhu Qingan , Zhang Yingze 
Published: June 2024

Abstract
Background
Lumbar–iliac fixation (LIF) is a common treatment for Tile C1.3 pelvic fractures, but different techniques, including L4–L5/L5 unilateral LIF (L4–L5/L5 ULIF), bilateral LIF (BLIF), and L4–L5/L5 triangular osteosynthesis (L4–L5/L5 TOS), still lack biomechanical evaluation. The sacral slope (SS) is key to the vertical shear of the sacrum but has not been investigated for its biomechanical role in lumbar–iliac fixation. The aim of this study is to evaluate the biomechanical effects of different LIF and SS on Tile C1.3 pelvic fracture under two-legged standing load in human cadavers.

Methods
Eight male fresh-frozen human lumbar–pelvic specimens were used in this study. Compressive force of 500 N was applied to the L4 vertebrae in the two-legged standing position of the pelvis. The Tile C1.3 pelvic fracture was prepared, and the posterior pelvic ring was fixed with L5 ULIF, L4–L5 ULIF, L5 TOS, L4–L5 TOS, and L4–L5 BLIF, respectively. Displacement and rotation of the anterior S1 foramen at 30° and 40° sacral slope (SS) were analyzed.

Results
The displacement of L4–L5/L5 TOS in the left–right and vertical direction, total displacement, and rotation in lateral bending decreased significantly, which is more pronounced at 40° SS. The difference in stability between L4–L5 and L5 ULIF was not significant. BLIF significantly limited left–right displacement. The ULIF vertical displacement at 40° SS was significantly higher than that at 30° SS.

Conclusions
This study developed an in vitro two-legged standing pelvic model and demonstrated that TOS enhanced pelvic stability in the coronal plane and cephalad–caudal direction, and BLIF enhanced stability in the left–right direction. L4–L5 ULIF did not further improve the immediate stability, whereas TOS is required to increase the vertical stability at greater SS.