bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from Chimeric Antigen Receptor T Cell with an Inducible Caspase-9 Suicide Gene Eradicates Uveal Melanoma Liver Metastases via B7-H3 Targeting
Authors: Ventin Marco , Cattaneo Giulia , Arya Shahrzad , Jia Jingyu , Gelmi Maria C. , Sun Yi , Maggs Luke , Ksander Bruce R. , Verdijk Robert M. , Boland Genevieve M. , Jenkins Russell W. , Haq Rizwan , Jager Martine J. , Wang Xinhui , Ryeom Sandra , Ferrone Cristina R.
Published: August 2024

AbstractPurpose:
Uveal melanoma (UM) is the most common intraocular malignant tumor. Despite successful treatment of the primary tumor, about 50% of patients will recur with systemic diseases for which there are no effective treatment strategies. Here we investigated the preclinical efficacy of a chimeric antigen receptor (CAR) T-cell–based immunotherapy targeting B7-H3.
Experimental Design:
B7-H3 expression on primary and metastatic human UM samples and cell lines was assessed by RNA sequencing, flow cytometry, and immunohistochemistry. Antitumor activity of CAR T cells targeting B7-H3 was tested in vitro with UM cell lines, patient-derived organotypic tumor spheroids from patients with metastatic UM, and in immunodeficient and humanized murine models.
Results:
B7-H3 is expressed at high levels in >95% UM tumor cells in vitro and in vivo. We generated a B7-H3 CAR with an inducible caspase-9 (iCas9) suicide gene controlled by the chemical inducer of dimerization AP1903, which effectively kills UM cells in vitro and eradicates UM liver metastases in murine models. Delivery of iCas9.B7-H3 CAR T cells in experimental models of UM liver metastases demonstrates a durable antitumor response, even upon tumor rechallenge or in the presence of a significant metastatic disease burden. We demonstrate effective iCas9.B7-H3 CAR T-cell elimination in vitro and in vivo in response to AP1903. Our studies demonstrate more effective tumor suppression with iCas9.B7-H3 CAR T cells as compared to a B7-H3-targeted humanized monoclonal antibody.
Conclusions:
These studies support a phase I clinical trial with iCas9.B7-H3 CAR T cells to treat patients with metastatic UM.
Dendritic Cell Plasticity, Radiation, and Newton's Third Law
Authors: Kalinski Pawel , Gandhi Shipra , Kokolus Kathleen M.
Published: August 2024

Regulatory T cells protect damaged tissues but can undermine the effects of cancer treatments, including radiotherapy (RTx). Intratumoral immunostimulatory dendritic cells (type 1 conventional dendritic cells) respond to RTx with the production of regulatory T cell–attracting MDC/CCL22, undermining RTx effects. That effect can be reversed by EGFR-targeted IFNα, highlighting cDC1 plasticity and relevance as therapeutic targets.

See related article by Bugno et al., p. 4450
Figure S2 from A Selective FGFR1/2 PROTAC Degrader with Antitumor Activity
Authors: Kong Ying , Zhao Xinyue , Wang Zhaofu , Yuan Siqi , Chen Sheng , Lou Shidi , Ma Shichao , Li Yunfeng , Wang Xinghao , Ge Yangfeng , Li Guobin , Yang Hongbing , Zhao Mengxi , Li Dandan , Zhang Hailong , Tan Wenfu , Wang Juan
Published: August 2024

Chemical structure. A-C, Structure of BGJ398 (A), BR-cpd7 (B) and BR-cpd7 NC (C).
Supplemental Table S2 from Enhancing Standard of Care Chemotherapy Efficacy Using DNA-Dependent Protein Kinase (DNA-PK) Inhibition in Preclinical Models of Ewing Sarcoma
Authors: Collins Victor J. , Ludwig Katelyn R. , Nelson Ariana E. , Sundara Rajan Soumya , Yeung Choh , Vulikh Ksenia , Isanogle Kristine A. , Mendoza Arnulfo , Difilippantonio Simone , Karim Baktiar O. , Caplen Natasha J. , Heske Christine M.
Published: August 2024

In vivo compound preparation and administration information
Supplementary Figure 1 from SMG5 Inhibition Restrains Hepatocellular Carcinoma Growth and Enhances Sorafenib Sensitivity
Authors: Fang Nan , Liu Bing , Pan Qiuzhong , Gong Tingting , Zhan Meixiao , Zhao Jingjing , Wang Qijing , Tang Yan , Li Yongqiang , He Jia , Xiang Tong , Sun Fengze , Lu Ligong , Xia Jianchuan
Published: August 2024

Supplementary Figure 1. Chemical structure of NMDl14
Figure S2 from Exploiting Metabolic Defects in Glioma with Nanoparticle-Encapsulated NAMPT Inhibitors
Authors: Murray Matthew A. , Noronha Katelyn J. , Wang Yazhe , Friedman Anna P. , Paradkar Sateja , Suh Hee-Won , Sundaram Ranjini K. , Brenner Charles , Saltzman W.M. , Bindra Ranjit S.
Published: August 2024

Efficacy of BNP GMX1778 in PPM1Dtrnc. isogenic model.
Supplementary Figure S4 from Targeting CD33+ Acute Myeloid Leukemia with GLK-33, a Lintuzumab–Auristatin Conjugate with a Wide Therapeutic Window
Authors: Satomaa Tero , Pynnönen Henna , Aitio Olli , Hiltunen Jukka O. , Pitkänen Virve , Lähteenmäki Tuula , Kotiranta Titta , Heiskanen Annamari , Hänninen Anna-Liisa , Niemelä Ritva , Helin Jari , Kuusanmäki Heikki , Vänttinen Ida , Rathod Ramji , Nieminen Anni I. , Yatkin Emrah , Heckman Caroline A. , Kontro Mika , Saarinen Juhani
Published: August 2024

Comparison of MTD and TI of GLK-33 with comparator ADCs.
Data from First-in-Human Stage III/IV Melanoma Clinical Trial of Immune Priming Agent IFx-Hu2.0
Authors: Markowitz Joseph , Shamblott Michael , Brohl Andrew S. , Sarnaik Amod A. , Eroglu Zeynep , Khushalani Nikhil I. , Dukes Christopher W. , Chamizo Alejandra , Bastawrous Marina , Garcia Edward T. , Dehlawi Ashraf , Chen Pei-Ling , De Aquino Deanryan B. , Sondak Vernon K. , Tarhini Ahmad A. , Kim Youngchul , Lawman Patricia , Pilon-Thomas Shari
Published: August 2024

Abstract
IFx-Hu2.0 was designed to encode part of the Emm55 protein contained within a plasmid in a formulation intended for transfection into mammalian cells. IFx-Hu2.0 promotes both adaptive and innate immune responses in animal studies. Furthermore, previous studies have demonstrated safety/efficacy in equine, canine, and murine species. We present the first-in-human study of IFx-Hu2.0, administered by intralesional injection into melanoma tumors of seven patients with stage III/IV unresectable melanoma. No dose-limiting toxicities attributable to IFx-Hu2.0 were observed. Grade 1/2 injection site reactions were observed in five of seven patients. IgG and IgM responses to Emm55 peptides and known melanoma antigens were seen in the peripheral blood, suggesting that IFx-Hu2.0 acts as an individualized “in situ vaccine.” Three of four patients previously refractory to anti-PD1 experienced clinical benefit upon subsequent anti-PD1–based treatment. Therefore, this approach is feasible, and clinical/correlative outcomes warrant further investigation for treating patients with metastatic melanoma with an immune priming agent.
Supplementary Figure S17 from Overexpression of an Engineered SERPINB9 Enhances Allogeneic T-cell Persistence and Efficacy
Authors: Teo Pei Y. , Jung Youngrock , Quach David H. , Koh Joanna , Ong Richard W. , Goh Angeline , Tan Alrina , Ng Chee H. , Seh Cheah C. , Tan Kar W. , Horak Ivan D. , Low Lionel
Published: August 2024

Supplementary Figure S17. CD30-positive B-cell acute lymphoblastic leukemia (B-ALL) burden of two in-vivo models that were being used to test SB9-mediated protection of ‘donor’ cells against allorejection (allorejection model) and AICD (AICD model), respectively. Bioluminescence signals from HLADKO NALM6-CD30.eGFP-ffLuc that were prepared from either FACS (allorejection model) or clonal selection (AICD model) were measured at baseline (day 0). Each point represents an individual mouse. The lines with error bars indicate mean + SD.
Retrospective, Real Life Study on the Effectiveness and Safety of a Depigmented-Polymerized Subcutaneous Vaccine Containing a Mixture of Grasses and Olea europaea
Authors: Pérez Montero Ana , Sanz-Rosa David , Carnés Jerónimo
Published: August 2024

Introduction: Allergen immunotherapy is the only modifying treatment of the natural course of respiratory allergic diseases; however, the lack of evidence leads to little inconclusive results. Real life studies are on the rise and are becoming a valuable tool to confirm and complement findings from clinical trials. The objective of this study was to evaluate the effectiveness and safety of a depigmented-polymerized undiluted subcutaneous extract of grass and olive pollen, under routine clinical practice conditions. Methods: This was an observational, retrospective, longitudinal, single-center study on the use of a 2-pollen (grass mix and Olea europaea) undiluted subcutaneous extract over at least 3 consecutive years. Data were collected from 76 patients (n = 44 female; median age: 12.5 years old) diagnosed with allergic rhinoconjunctivitis with/without allergic asthma due to sensitization to both grasses and O. europaea. Primary and secondary effectiveness endpoints were symptom severity, concomitant medication, and immunological profile before and after completing the immunotherapy. A 2-year follow-up of patients’ symptoms and medication history after completing the subcutaneous immunotherapy (SCIT) was performed. Results: There was a significant improvement of symptoms and medication consumption after 3 years of SCIT treatment, and a significant decrease in specific IgE levels for grasses and O. europaea was observed after finishing the treatment. Conclusion: Three years treatment of allergic patients using an undiluted mixture of two allergen extracts was shown to be safe and effective for rhinitis and asthma, with efficacy maintained for at least 2 years after finishing SCIT. These results reinforce the importance of real life clinical data in addition to those from clinical trials, helping to individualize allergic treatments.
Semaglutide Ameliorates Hepatocyte Steatosis in a Cell Co-Culture System by Downregulating the IRE1α-XBP1-C/EBPα Signaling Pathway in Macrophages
Authors: Hu Qin , Zhang Li , Tao YiTing , Xie ShuangLin , Wang AiYun , Luo Caiying , Yang RenHua , Shen Zhiqiang , He Bo , Fang Yu , Chen Peng
Published: August 2024

Introduction: Non-alcoholic fatty liver disease (NAFLD) is currently the most common type of chronic liver disease. Semaglutide is a glucose-lowering drug administered for the treatment of type 2 diabetes mellitus (T2DM) and is clinically effective in the treatment of NAFLD. X-box binding protein 1 (XBP1) is related to the pathogenesis of both NAFLD and T2DM. The aim of the present study was to demonstrate whether the underlying mechanism of semaglutide treatment for NAFLD is via downregulation of the inositol-requiring transmembrane kinase/endonuclease-1α (IRE1α)-XBP1-CCAAT/enhancer binding protein α (C/EBPα) signaling pathway in macrophages. Methods: In the present study, NAFLD cell modeling was induced by oleic acid (0.4 mm) and palmitic acid (0.2 mm). Hepatocytes (AML12) and macrophages (RAW264.7) were co-cultured in 6-well Transwell plates. Semaglutide (60 or 140 nm) was administrated for 24 h, while pioglitazone (2 μm) and toyocamycin (200 nm) were used as a positive control drug and a XBP1 inhibitor, respectively. Autophagy and apoptosis of AML12 cells were detected by transmission electron microscopy and Western blotting (WB). Hepatocyte steatosis was evaluated by adopting total intracellular triglyceride determination, analysis of the relative expression of proteins and genes associated with lipid metabolism and hepatocyte Oil red O staining. Detection of inflammation factors was conducted by ELISA and WB. To explore the underlying mechanism of NAFLD treatment with semaglutide, the relative expression of related proteins and genes were tested. Results: Our study demonstrated that semaglutide treatment improved autophagy and inhibited apoptosis of hepatocytes, while notably ameliorating steatosis of hepatocytes. In addition, inflammation was attenuated in the NAFLD cell co-culture model after semaglutide administration. Semaglutide also significantly reduced the protein and gene expression levels of the IRE1α-XBP1-C/EBPα signaling pathway in macrophages. Conclusion: Semaglutide partially ameliorated NAFLD by downregulating the IRE1α-XBP1-C/EBPα signaling pathway in macrophages. These findings may provide a potential theoretical basis for semaglutide therapy for NAFLD.
Thrombin Generation Is Associated With Extracellular Vesicle and Leukocyte Lipid Membranes in Atherosclerotic Cardiovascular Disease
Authors: Protty Majd B. , Tyrrell Victoria J. , Allen-Redpath Keith , Soyama Shin , Hajeyah Ali A. , Costa Daniela , Choudhury Anirban , Mitra Rito , Sharman Amal , Yaqoob Parveen , Jenkins P. Vince , Yousef Zaheer , Collins Peter W. , O’Donnell Valerie B.
Published: August 2024

BACKGROUND:

Clotting, leading to thrombosis, requires interactions of coagulation factors with the membrane aminophospholipids (aPLs) phosphatidylserine and phosphatidylethanolamine. Atherosclerotic cardiovascular disease (ASCVD) is associated with elevated thrombotic risk, which is not fully preventable using current therapies. Currently, the contribution of aPL to thrombotic risk in ASCVD is not known. Here, the aPL composition of circulating membranes in ASCVD of varying severity will be characterized along with the contribution of external facing aPL to plasma thrombin generation in patient samples.

METHODS:

Thrombin generation was measured using a purified factor assay on platelet, leukocyte, and extracellular vesicles (EVs) from patients with acute coronary syndrome (n=24), stable coronary artery disease (n=18), and positive risk factor (n=23) and compared with healthy controls (n=24). aPL composition of resting/activated platelet and leukocytes and EV membranes was determined using lipidomics.

RESULTS:

External facing aPLs were detected on EVs, platelets, and leukocytes, elevating significantly following cell activation. Thrombin generation was higher on the surface of EVs from patients with acute coronary syndrome than healthy controls, along with increased circulating EV counts. Thrombin generation correlated significantly with externalized EV phosphatidylserine, plasma EV counts, and total EV membrane surface area. In contrast, aPL levels and thrombin generation from leukocytes and platelets were not impacted by disease, although circulating leukocyte counts were higher in patients.

CONCLUSIONS:

The aPL membrane of EV supports an elevated level of thrombin generation in patient plasma in ASCVD. Leukocytes may also play a role although the platelet membrane did not seem to contribute. Targeting EV formation/clearance and developing strategies to prevent the aPL surface of EV interacting with coagulation factors represents a novel antithrombotic target in ASCVD.
Leisure Sedentary Behavior, Physical Activities, and Cardiovascular Disease Among Individuals With Metabolic Dysfunction–Associated Fatty Liver Disease
Authors: Wu Hanzhang , Wei Jiahe , Chen Wenjuan , Chen Liangkai , Zhang Jihui , Wang Ningjian , Wang Shuai , Tan Xiao
Published: August 2024

BACKGROUND:

Metabolic dysfunction–associated fatty liver disease is a significant risk factor for cardiovascular disease (CVD). This study assesses the association between leisure-time physical activity, sedentary behavior, and CVD risk among patients with metabolic dysfunction–associated fatty liver disease, considering genetic predisposition to CVD.

METHODS:

This cohort study included 157 794 participants with metabolic dysfunction–associated fatty liver disease from the UK Biobank who were free of CVD at baseline. The study measured leisure-time sedentary behaviors (watching TV, using a computer, and driving) and physical activities (walking for pleasure, light and heavy do-it-yourself activities, strenuous sports, and other exercises) in terms of frequency and duration over the 4 weeks before assessment. Both a Cox proportional hazard model and an isotemporal substitution model were utilized in the study to assess the association between leisure sedentary behavior, physical activities, and CVD risk.

RESULTS:

During a median 12.5 years of follow-up, 26 355 CVD cases were reported, including 19 746 coronary heart disease, 4836 stroke, and 7398 heart failure cases. High physical activity levels were linked to a significantly lower risk of CVD (21%), coronary heart disease (20%), stroke (15%), and heart failure (31%). In contrast, individuals with >6.5 h/d of sedentary behavior faced a 16% to 21% higher risk of these conditions compared with those with ≤3.5 h/d. Notably, replacing 30 minutes of inactivity with physical activity reduced CVD risks by 3% to 16%, particularly with strenuous sports. A significant interaction was observed between physical activity, sedentary behavior, and genetic predisposition in relation to stroke risk.

CONCLUSIONS:

Among patients with metabolic dysfunction–associated fatty liver disease, higher leisure-time physical activity levels correlate with reduced CVD risks, while increased sedentary behavior is linked to higher CVD risks. Replacing sedentary time with physical activity consistently shows benefits in reducing CVD outcomes, irrespective of genetic predisposition.
Quality of Life and Exercise Capacity in Early Stage and Subclinical Hypertrophic Cardiomyopathy: A Secondary Analysis of the VANISH Trial
Authors: Ireland Catherine G. , Burstein Danielle S. , Day Sharlene M. , Axelsson Raja Anna , Russell Mark W. , Zahka Kenneth G. , Pereira Alexandre , Canter Charles E. , Bach Richard G. , Wheeler Matthew T. , Rossano Joseph W. , Owens Anjali T. , Bundgaard Henning , Mestroni Luisa , Taylor Matthew R.G. , Patel Amit R. , Wilmot Ivan , Soslow Jonathan H. , Becker Jason R. , Giverts Ilya , Orav E. John , Claggett Brian , Lin Kimberly Y. , Ho Carolyn Y.
Published: August 2024

BACKGROUND:

The health-related quality of life (HRQOL) and cardiopulmonary exercise testing (CPET) performance of individuals with subclinical and early stage hypertrophic cardiomyopathy (HCM) have not been systematically studied. Improved understanding will inform the natural history of HCM and factors influencing well-being.

METHODS:

VANISH trial (Valsartan for Attenuating Disease Evolution in Early Sarcomeric HCM) participants with early stage sarcomeric HCM (primary analysis cohort) and subclinical HCM (sarcomere variant without left ventricular hypertrophy comprising the exploratory cohort) who completed baseline and year 2 HRQOL assessment via the pediatric quality of life inventory and CPET were studied. Metrics correlating with baseline HRQOL and CPET performance were identified. The impact of valsartan treatment on these measures was analyzed in the early stage cohort.

RESULTS:

Two hundred participants were included: 166 with early stage HCM (mean age, 23±10 years; 40% female; 97% White; and 92% New York Heart Association class I) and 34 subclinical sarcomere variant carriers (mean age, 16±5 years; 50% female; and 100% White). Baseline HRQOL was good in both cohorts, although slightly better in subclinical HCM (composite pediatric quality of life score 84.6±10.6 versus 90.2±9.8;
P
=0.005). Both cohorts demonstrated mildly reduced functional status (mean percent predicted peak oxygen uptake 73±16 versus 78±12 mL/kg per minute;
P
=0.18). Percent predicted peak oxygen uptake and peak oxygen pulse correlated with HRQOL. Valsartan improved physical HRQOL in early stage HCM (adjusted mean change in pediatric quality of life score +4.1 versus placebo;
P
=0.01) but did not significantly impact CPET performance.

CONCLUSIONS:

Functional capacity can be impaired in young, healthy people with early stage HCM, despite New York Heart Association class I status and good HRQOL. Peak oxygen uptake was similarly decreased in subclinical HCM despite normal left ventricular wall thickness and excellent HRQOL. Valsartan improved physical pediatric quality of life scores but did not significantly impact CPET performance. Further studies are needed for validation and to understand how to improve patient experience.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01912534.
What It Takes To Be a Platelet: Evolving Concepts in Platelet Production
Authors: Carminita Estelle , Becker Isabelle C. , Italiano Joseph E.
Published: August 2024

Platelets are among the most abundant cells within the circulation. Given that the platelet lifespan is 7 to 10 days in humans, a constant production of around 100 billion platelets per day is required. Platelet production from precursor cells called megakaryocytes is one of the most enigmatic processes in human biology. Although it has been studied for over a century, there is still controversy about the exact mechanisms leading to platelet release into circulation. The formation of proplatelet extensions from megakaryocytes into bone marrow sinusoids is the best-described mechanism explaining the origin of blood platelets. However, using powerful imaging techniques, several emerging studies have recently raised challenging questions in the field, suggesting that small platelet-sized structures called buds might also contribute to the circulating platelet pool. How and whether these structures differ from microvesicles or membrane blebs, which have previously been described to be released from megakaryocytes, is still a matter of discussion. In this review, we will summarize what the past and present have revealed about platelet production and whether mature blood platelets might emerge via different mechanisms.
Epigenetic Clock at Birth and Childhood Blood Pressure Trajectory: A Prospective Birth Cohort Study
Authors: Hu Jie , Yaskolka Meir Anat , Hong Xiumei , Wang Guoying , Hu Frank B. , Wang Xiaobin , Liang Liming
Published: August 2024

BACKGROUND:

The impact of methylation gestational age (GAmAge; a biomarker of fetal maturity) at birth on childhood blood pressure (BP) trajectories is unknown.

METHODS:

This cohort study included 500 boys and 440 girls with data on cord blood DNA methylation and BP at 3 to 15 years of age. Systolic BP (SBP) and diastolic BP percentiles were calculated based on clinical guidelines. Time-series K-means clustering identified 4 distinct SBP and diastolic BP percentile trajectories: high-steady, high-decrease, normal-increase, and normal-steady. GAmAge was estimated using an existing pediatric epigenetic clock. Extrinsic age acceleration was calculated as residuals of associations between GAmAge and chronological gestational age. Intrinsic age acceleration was calculated using the same method adjusting for cord blood cell compositions.

RESULTS:

Extrinsic age acceleration and intrinsic age acceleration were inversely associated with repeated measures of BP percentiles. Significant inverse associations were observed between extrinsic age acceleration and SBP percentiles in boys (β=−2.02;
P
=0.02) but not in girls (β=−0.49;
P
=0.58). Both extrinsic age acceleration and intrinsic age acceleration were inversely associated with SBP percentiles in girls born preterm (<37 weeks; β
EAA
=−2.95; β
IAA
=−3.00;
P
<0.05). Compared with the normal-steady SBP trajectory, significant inverse associations were observed between intrinsic age acceleration and high-steady, high-decrease, and normal-increase SBP trajectories in boys (odds ratio, 0.73–0.81;
P
<0.03), and significant positive associations were observed for high-decrease and normal-increase SBP trajectories in girls (odds ratio, 1.26–1.38;
P
<0.01). Significant sex differences were observed (
P
sex-interaction
<2×10
−16
).

CONCLUSIONS:

GAmAge acceleration at birth was inversely associated with child BP, and such association was more pronounced in boys than in girls. Our findings may shed new light on the developmental origins of high BP and sex differences in cardiovascular risk.
Childhood adversity predicts striatal functional connectivity gradient changes after acute stress
Authors: Liu Xiang-Shen , Haak Koen V. , Figa Karolina , Vrijsen Janna N. , Oldehinkel Marianne , Mulders Peter C.R. , Collard Rose M. , van Eijndhoven Philip F.P. , Beckmann Christian F. , Fernández Guillén , Tendolkar Indira , Kohn Nils
Published: August 2024

As a primary risk factor for psychiatric vulnerability, childhood adversity (CA) leads to several maladaptive behavioral and brain functional changes, including domains of emotion, motivation, and stress regulation. Previous studies on acute stress identified the potential role of a striatum-centered network in revealing the psychopathology outcomes related to CA. To elucidate the interplay between CA, acute stress, and striatal functions in psychiatric disorders, more evidence from large-scale brain connectivity studies in diverse psychiatric populations is necessary. In a sample combining 150 psychiatric patients and 26 controls, we utilized “connectopic gradients” to capture the functional topographic organizations of striatal connectivity during resting-state scans conducted before and after stress induction. Connectivity gradients in rest and under stress were linked to different CA types and their frequency by Spearman correlation. Linear mixed models and moderation models were built to clarify the role of symptom strengths in these correlations. We found one type of CA—emotional neglect negatively predicted the post-stress-induction gradient shape, and stress reactive changes in the anterior-posterior orientation of the first-order striatal gradient. Moderation models revealed the observed correlations were selectively present in individuals with elevated comorbidity. Our results may provide new psychopathology-related biomarkers by tracking stress-induced changes in the general motivation systems. This demonstrates new perspectives in characterizing the striatal network and understanding its alterations in response to adverse childhood experiences.
Confucius Repeats Himself: On the Nature and Sources of the Lunyu 論語 (Selected Teachings)
Authors: Crone Thomas
Published: August 2024

This article explores the much-debated origins of the Confucian classic Lunyu 論語. The author examines two well-known types of repetitions in the text: doublets and formulaic phrases. The results of the analysis confirm previous research suggesting that the Lunyu is the accumulative result of various independent collections of concise anecdotes and sayings, but also indicate that these small literary items derived from more comprehensive and complex written and/or memorized compositions. As a result, this article joins recent studies on the textual history of the Lunyu that demand a new hermeneutic approach to the text and a rewriting of the literary history of pre-Qin Masters literature (zhuzi shu 諸子書). Confucian didactic dialogues and speeches such as those found in traditionally transmitted Zhou period texts and recently discovered bamboo manuscripts are to be seen as Masters literature’s primordial ancestors, while the Lunyu ought to be treated as a conglomeration of derived second-generation products.
Textual Evidence for Sino-Tibetan Buddhism in Xixia
Authors: Solonin Kirill
Published: August 2024

The article introduces four case studies to argue for the existence of Sino-Tibetan Buddhism in the Xixia Kingdom (1038–1227). The first case is based on the Yuan period (1271–1368) ritual compilations by the Tangut monk Yixing Huijue 一行慧覺 (d. 1319?); the three others are based on material dating from the Xixia period. The study examines textual examples of Sino-Tibetan intercourse and concludes that the major framework for exchange was Avataṃsaka Buddhism, which adopted elements of Tibetan Buddhism in a discourse generally limited to the Sinitic agenda. One example demonstrates a divergent perspective: Sinitic commentarial devices are used to pursue a generally Tibetan agenda. The four case studies confirm the existence of Sino-Tibetan predispositions in Tangut Buddhism, but do not provide sufficient information to determine its broader scope.
Gramsci, Polanyi and the Labor Politics of Social Protection
Authors: Arnold Dennis
Published: August 2024

The works of Polanyi and Gramsci, taken together, help us to disentangle the multiple understands of and politics around social protection. Despite Gramsci’s convincing analysis of hegemony as the organization of class struggle within limits of capitalism, he does not have a theory of counterhegemony. Polanyi, meanwhile, does not focus attention on the power of capitalist hegemony, yet his displacement of experience from production to exchange creates the grounds for a potential counterhegemony. The article analyzes how, despite apparent efforts to de-commodify labor and social protections, precarity has become more deeply engrained among the laboring poor. While precarity is not necessarily new to populations across the South, the way in which commodification has become hegemonic is, and the objective of the article is to better understand the role of social protection in shaping workers’ experiences, and consider potential strategic directions to advance universal social protection.
Chitons of the genus Cryptoplax (Mollusca: Polyplacophora) from the Spratly Islands, South China Sea
Authors: SIRENKO BORIS I. , SAITO HIROSHI , NGUYEN TAI-TU
Published: August 2024

Four species of the polyplacophoran genus Cryptoplax were identified among chiton samples collected from the Spratly Islands (Truong Sa), South China Sea. Among them, one is described as new species C. acerocostata n. sp.. The other three species, namely, C. larvaeformis (Burrow, 1815), C. brunoi Saito, 2023, and C. burrowi (E. A. Smith, 1884), are reported for the first time from the Spratly Islands. Color and SEM photographs of their features are given for all four species.
Impact of fiber orientation on cutting forces and surface quality in flax/epoxy composite machining
Authors: Slamani Mohamed , Chafai Hamza , Chatelain Jean-François
Published: August 2024

Flax/epoxy composites are recognized as an eco-friendly alternative to synthetic fibers in engineering. Understanding how fiber orientation affects cutting forces and surface characteristics is essential for machining these materials. This study investigates the relationship between fiber orientation and cutting forces (feed, normal, passive) as well as surface roughness in flax/epoxy composites. Results show that fiber orientation significantly impacts cutting forces. Cutting parallel to fibers (0° and 90° orientations) generally requires less force, with 0° needing higher normal force. At 0° orientation, feed force is 46.47  N, normal force is 58.86  N, and passive force is 54.44  N. At 90° orientation, feed force is 56.66  N, normal force is 44.68  N, and passive force is 50.95  N. Oblique orientations (45° and −45°) require higher forces, especially 45°, with the highest normal force of 77.95  N. Surface roughness analysis shows 90° orientation results in the lowest average roughness (Ra) of 10.97 µm but the highest surface roughness (Sa) of 34.25 µm. Conversely, 45° orientation has the highest Ra of 14.2 µm but lower Sa of 22.6 µm. Ra and Sa values for 0° orientation are 13.72 µm and 24.6 µm, and for −45° orientation, they are 12.3 µm and 21.8 µm. Correlation analysis reveals significant relationships between cutting parameters and surface quality, with higher feed rates correlating with smoother surfaces (lower Sa and Ra values). Fiber orientation also significantly influences fluffing defects, with 0° orientation minimizing these defects, while 45° and −45° orientations result in varied patterns.
E-mmortal: Death Anxiety is Related to Selfie Behaviors
Authors: Etgar Shir , Shutzman Bar , Shani-Sherman Tal , Amichai-Hamburger Yair
Published: August 2024

Given the widespread phenomenon of selfies, numerous studies are examining the motivations behind taking and sharing selfies. The current paper suggests an additional possible motivation, namely, decreasing death anxiety. People are motivated to decrease their death anxiety by preserving a fake feeling of immortality. One known way to achieve this goal is by using photography. Therefore, we suggest that selfie behaviors are a way to fulfill the need to remain immortal. A hundred undergraduate students ( Mage = 22.33) answered self-reported questionnaires regarding selfie motivations, selfie-taking frequency, selfie-sharing frequency, and death anxiety. All of those selfie measurements were indeed positively related to death anxiety. Moreover, many previous studies suggested that narcissism motivates selfie behaviors. In an exploratory approach, we examined whether death anxiety mediates this relationship. Indeed, death anxiety fully mediated the relationships between narcissism and selfie motivations and between narcissism and selfie-taking frequency, suggesting that the well-documented association between selfie behaviors and narcissism might be driven by death anxiety. Those preliminary results indicate that death anxiety is associated with selfie behaviors, opening new avenues for understanding the motivations underlying selfie behaviors.
Cognitive Dysfunction in Unipolar Depression
Authors: Rakesh C  , Sharma Rachit , Singh Charanpreet
Published: August 2024

Background:

Cognitive dysfunctions play a critical role in the psychopathology of depression. They regulate various psychosocial and functional outcomes and affect workplace functionality, productivity, and relapses. An objective evaluation of affected cognitive domains is germane in understanding the relapses and functional recovery in depression. Thus, to know cognitive dysfunctions beyond affective biases, this study was conducted to compare the cognitive functions of drug-naïve patients with unipolar depression with healthy matched controls.

Methods:

Fifty patients diagnosed with unipolar depression as per the International Classification of Diseases, tenth revision: Diagnostic Criteria for Research (Depressive Episode and Recurrent Depressive Disorder) and 50 healthy controls were enrolled on an outpatient basis from January 2022 to June 2023. Cases were regrouped as mild, moderate, and severe based on Beck’s Depression Inventory (BDI-II). A battery of tests assessed the cognitive functions: Wisconsin Card Sorting Test, Trail Making Test, Visual Retention subtests of PGI Battery of Brain Dysfunction, Digit Span, and Verbal Memory. The Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire was used for a subjective assessment of cognitive functioning.

Results:

The sociodemographic characteristics of cases and controls did not differ significantly. However, within-group and between-group analyses revealed significantly lower performance of cases compared to controls. Cognitive impairment was positively correlated with BDI-II scores.

Conclusion:

Depression is associated with dysfunction in the domains of planning, attention, sustained attention, and visual and verbal memory. This dysfunction is independent of cognitive and affective bias and may exist even after clinical remission.
Dual immunoadsorption for ABO-incompatible heart transplantation in a 35 kg child
Authors: Crook Richard , Cohen Marc , Mimic Branko , Fenton Matthew , Issitt Richard
Published: August 2024

Intraoperative anti-A/B immunoadsorption (ABO-IA) was recently introduced for ABO-incompatible (ABOi) heart transplantation. Here we report the first case of a patient transplanted with ABO-IA, that was of an age and weight that required two ABO-IA columns run in parallel, to enable the reduction in antibody titres to a sufficiently low level in the time available during implantation of the donor organ.
Effects of Low-intensity Ultrasound on Root Resorptions Induced by a System of Associated Forces
Authors: Boutiah Toufik , Laraba Safia , Menjel Radouane , Slimani Lotfi , Boutefnouchet Abdelatif , Tahar Ali , Khadir Mohamed Tarek
Published: August 2024

Introduction

The bio-stimulatory effects of low-intensity ultrasound on dental tissues which were clinically introduced in 2004 demonstrated a reduction in root resorption in maxillary premolars subjected to a force level of 50 g. Similar results by applying a torque of 50 g to the maxillary premolars were obtained in 2016; however, the effects of low-intensity pulsed ultrasound (LIPUS) on the presence of high-intensity forces are not yet known.

Aim

The purpose of this study was to examine the effects of LIPUS on a sample of 40 patients.

Methods

The analysis was conducted by applying two forces to teeth no. 14 and 24, each with an intensity greater than 50 g, and applied at two different points on the coronal surface. Subsequently, LIPUS was applied daily for 20 minutes to tooth no. 14, while tooth no. 24 served as a control. The study lasted for 28 days.

Results

Overall, the group treated with LIPUS demonstrated an improvement in the average total volume and percentage of root resorption compared to the control group. The same results emerged for the diameter, depth, and surface of the gaps of resorption.

Conclusion

This study showed that it was possible to reduce root resorption in the presence of forces with intensities greater than 50 g. Nevertheless, a longer period of study will make it possible to obtain more rational results as to the effectiveness of low-intensity ultrasound on root resorption induced by orthodontic treatment.
Coastal flooding in Kołobrzeg (Kolberg) area, southern Baltic Sea, in the light of historical and geological data
Authors: Piotrowski Andrzej , Brose Fritz , Sydor Paweł
Published: August 2024

The Baltic Sea is not a typical tsunami area, but there are reports of coastal flooding, with its traces preserved in deposits from Germany, Finland and Sweden, and more recently from Poland. In this study an attempt was made to verify historical and legendary accounts of the ‘Sea Bear’ (‘der Seebär’) phenomenon. In the descriptions of folk accounts, the phenomenon has the features such as suddenness, speed, short duration, independence from the atmospheric conditions on land and sea. The search for coastal flooding deposits was conducted around the town of Kołobrzeg (Kolberg), located on the southern coast of the Baltic Sea. For the study area in chronicle record exist information about two events (17 September 1497 and 1 March 1779). For both events no record has been found in geological profiles, probably due to strong anthropogenic transformation of the subsurface layers. However there is quite precise information from chronicle records on the extent of the event from 17 September 1497 and on the thickness of the sandy layer left by the flooding. Based on this information in the Kołobrzeg area the range of the sand layer was 1400 m from the seashore, and its thickness locally reached approximately 10 cm. The flood height estimated according to the above-presented assumptions was 4.9 m a.s.l. In the Baltic Sea area, coastal flooding is possibly due to atmospheric forcing which can be responsible for an external waves event and devastating long waves, which have the same spatial and temporal scale as typical tsunami waves.
Book review: Thomas Cottier and Zaker Ahmad (Eds.), The Prospects of Common Concern of Humankind in International Law
Authors: Athar ud din
Published: August 2024

Thomas Cottier and Zaker Ahmad (Eds.), The Prospects of Common Concern of Humankind in International Law (Cambridge University Press, 2021), xxii + 468 pp. $35.99, ISBN: 978-1-1088-7873-9 (Paperback).
An RFE-aided Transformer-SVM framework for multi-bolt connection loosening identification using wavelet entropy of vibro-acoustic modulation signals
Authors: Li Xiao-Xue , Li Dan , Ren Wei-Xin , Sun Xiang-Tao
Published: August 2024

To ensure structural safety and integrity, a novel framework is developed for detecting the loosening of multi-bolt connections using wavelet entropy of vibro-acoustic modulation (VAM) signals. Wavelet entropy is employed as the dynamic index to capture the intricate time-frequency characteristics that are indicative of the connection status. Taking the wavelet entropy vectors as input, the proposed framework distinguishes itself by integrating a Transformer model for high-dimensional feature extraction with the recursive feature elimination (RFE) for essential feature selection, followed by a support vector machine (SVM) model for classification. Specifically, the Transformer model with innovative positional encoding capability helps to extract the time-dependent transient features that are sensitive to the bolt loosening. The RFE process reduces the data dimensionality while discerning the diagnostic information for more accurate classification. Through the experiment on a four-bolt joint, the identification results with cross-validation showed high accuracy and robustness of the proposed framework across various loosening cases. It outperformed the traditional SVM, long short-term memory network (LSTM), convolutional neural network (CNN)-SVM models without and with RFE, as well as the Transformer-SVM model without RFE, achieving an accuracy increase of 15.72%, 11.74%, 9.47%, 5.49%, and 5.06%, respectively. The proposed framework was demonstrated to be able to learn the damage-sensitive features more effectively from wavelet entropy data, marking a significant advancement in the health monitoring of engineering structures with high-strength bolt connections.
Introduction: hyper-visuality: images in the era of social platforms, digital archives and computational economies
Authors: D’Armenio Enzo , Dondero Maria Giulia
Published: August 2024

Images are today at the centre of multiple social and technological tensions as a consequence of the adoption of digital coding, of the massive diffusion of social networks and of the algorithmic processing to which they are subject, resulting in new opportunities for developing analytical inquiries and meaning-producing social actions. In this introduction, the authors intend to reconstruct the broad context that makes images one of the most important resources of the digital era and to focus on some of the research tracks that characterize it. In the first part, they begin by focusing on the relationship between images and the digital, which they retrace in accordance with the selection of three key moments: the transition from ontology to the epistemology of digital media; the opening, by social networks and portable devices, of a field for the computational study of contemporary cultures; and, finally, the analytical potential arising from the encounter between digital archives and computer algorithms. In the second part, they present the three axes around which this issue is structured: archives, identity and algorithms. They first of all discuss the concept of the archive, by presenting four different understandings it has come to bear in conjunction with digital encoding – the archive as heritage, resource, effect and as database. They go on to address the relation between images and identities, arguing that social platforms and visual apps are a new domain for identity experimentation and social aggregation. Finally, they discuss the issue of algorithms and more generally of the new computational economy that associates large amounts of data with their mobilization as operational images.
Inherit or innovate?–evidence from China’s auto industry’s new car series naming
Authors: Wei Jiuchang , Zhou Hairao , Zhao Yang
Published: August 2024

The automotive industry introduces a sizable number of new automobile products annually. The naming of new products may have significant impact on their market performance. Diverging from prior research on the impact of product names, companies’ innovative consciousness endows them with a certain level of proactive positioning, thereby implementing independent naming strategies after considering product factors and consumer preferences passively. This paper analyzes the drivers of the market performance of sequential products on the naming of new products in Chinese automotive industry. We collected market share data and names of various car series from January 2007 to September 2022. Then, we calculated semantic distances between names and performed empirical tests. Our findings show that firms demonstrate a risk preference pattern contrary to traditional prospect theory when using the previous car series’ market share as a reference point. In the interplay between market orientation and risk preferences, the relationship between the market share of the last car series and the similarity in names between old and new car series follows an inverted U-shaped pattern. This study extends the discussion on risk preferences within the behavioral theory of the firm (BTOF) and proposes a decision mechanism for product naming that considers market and firm factors during the response phase of market orientation.
Preventing Verbal Memory Decline: Anatomic Clues to Predict Risk of Laser Ablation Versus Resection?
Authors: Munger Clary Heidi M.
Published: August 2024

[Box: see text]
Coagulation factor VIII: biological basis of emerging hemophilia A therapies
Authors: Samelson-Jones Benjamin J. , Doshi Bhavya S. , George Lindsey A.
Published: August 2024

Coagulation factor VIII (FVIII) is essential for hemostasis. After activation, it combines with activated FIX (FIXa) on anionic membranes to form the intrinsic Xase enzyme complex, responsible for activating FX in the rate-limiting step of sustained coagulation. Hemophilia A (HA) and hemophilia B are due to inherited deficiencies in the activity of FVIII and FIX, respectively. Treatment of HA over the last decade has benefited from an improved understanding of FVIII biology, including its secretion pathway, its interaction with von Willebrand factor in circulation, the biochemical nature of its FIXa cofactor activity, the regulation of activated FVIII by inactivation pathways, and its surprising immunogenicity. This has facilitated biotechnology innovations with first-in-class examples of several new therapeutic modalities recently receiving regulatory approval for HA, including FVIII-mimetic bispecific antibodies and recombinant adeno-associated viral (rAAV) vector–based gene therapy. Biological insights into FVIII also guide the development and use of gain-of-function FVIII variants aimed at addressing the limitations of first-generation rAAV vectors for HA. Several gain-of-function FVIII variants designed to have improved secretion are currently incorporated in second-generation rAAV vectors and have recently entered clinical trials. Continued mutually reinforcing advancements in the understanding of FVIII biology and treatments for HA are necessary to achieve the ultimate goal of hemophilia therapy: normalizing hemostasis and optimizing well-being with minimal treatment burden for all patients worldwide.
Activity behaviours and quality of life in patients with malignant pleural effusion
Authors: Iacopetta Bianca M. , Lam David C.L. , Ngai Jenny C.L. , Chan Johnny W.M. , Chiang Fifian K.Y. , Lui Macy M.S. , Law W.L. , Chan Ken K.P. , McVeigh Joanne , Peddle-McIntyre Carolyn J. , Lee Y.C. Gary
Published: August 2024

Background and objective

Accelerometery is used to measure activity behaviours in patients with malignant pleural effusion (MPE). This study aimed to evaluate physical activity and sedentary behaviour profiles of patients with MPE in Hong Kong, and to explore relationships between activity behaviours and quality of life (QoL). We also compared clinician-recorded performance status measures with objective measures of activity levels.

Methods

Participants wore an Actigraph GT3X+ accelerometer continuously for 7 consecutive days. The EuroQoL 5 Dimensions 5 Levels (EQ-5D-5L) was used to assess five dimensions of QoL and correlate with activity behaviours. The Eastern Cooperative Oncology Group (ECOG) performance status was documented by clinicians at baseline.

Results

Fifty-one patients with MPE received accelerometers; 94% had ≥1 valid day of data. Participants spent 76% (sd2.32) of waking hours sedentary, 23% (sd1.40) of waking hours in light activity and 0.3% (median, interquartile range 0.0–1.5) in moderate-to-vigorous physical activity (MVPA). Higher light activity and MVPA behaviours were associated with increased participation in self-care tasks (rs=−0.43, p=0.003; rs=−0.45, p=0.001, respectively) and usual activities (rs=−0.42, p=0.003; rs=−0.45, p=0.001, respectively). Patients with an ECOG status of 0 or 1 spent an average of 75% of waking hours sedentary.

Conclusion

This is the first report of physical activity behaviours in patients with MPE in Hong Kong, demonstrating high sedentary behaviours and low physical activity which correlated to dimensions of QoL. Clinician-rated performance status was not reflected in accelerometery data, suggesting a discrepancy between performance status measures and objective measures of activity in patients with MPE.