bluuebunny/crossref_metadata_2025_split huggingface dataset:
Towards High Dynamic Operations With Parallel-Serial Hybrid Robots
Authors: Sagar Keerthi , Ramadoss Vishal , Zoppi Matteo 
Published: November 2023

Abstract
Hybrid manipulators are a combination of parallel and serial linkage connection robots which can exhibit high articulation and achieve modularity in design. This paper presents the results on the kinematic modeling and motion generation of a parallel-serial hybrid robot architecture. Parallel mechanisms are increasingly being employed as a reconfigurable subsystem alongside serial kinematic chains for high speed machining and manufacturing operations. These kinematic structures have known to have superior stiffness and dynamic properties at the expense of increased complexity in modeling and control. For a specific application of placing fixture heads along sheet metal, a hybrid parallel-serial manipulator is developed. It consists of a spherical revolute (SR) 4-degree-of-freedom (DOF) serial arm mounted on a (3-DOF) parallel manipulator with two UPR (4-DOF) legs constrained to move in a common rotating plane, and an SPR (5-DOF) leg. The kinematic architecture utilizes parallel linkage as a positioning manipulator, whereas the serial arm provides the necessary dexterity and increased workspace required for the task. An approach to model such complex kinematic structures with the evaluation of workspace and motion generation is discussed. The presented approach is finally validated both in simulation and with experiments performed on the real platform.
Chat Generative Pretrained Transformer: Extinction of the Designer or Rise of an Augmented Designer
Authors: Gill Amaninder Singh 
Published: November 2023

Abstract
Systematic design process is used in engineering systems design to develop solutions to problems of varying complexity. There have been efforts within the community to develop tools to perform automated generative design at varying stages of the systematic design process. However, a Large Language Model (LLM) has never been used. To this end, this paper presents an initial investigation into the use of OpenAI’s ChatGPT to automatically generate solutions to an engineering problem. It is demonstrated that for the most part ChatGPT is quite capable of generating conceptual design for an engineering problem. In light of this technology, this paper floats questions on the future direction of research and education for the engineering systems design community.
Multi-Task Multi-Fidelity Machine Learning for Reliability-Based Design With Partially Observed Information
Authors: Xu Yanwen , Wu Hao , Liu Zheng , Wang Pingfeng 
Published: November 2023

Abstract
In complex engineering systems, assessing system performance and underlying failure mechanisms with respect to uncertain variables requires repeated testing, which is often limited by test capacity and computational budget and fails to accurately capture the complex system’s high-dimensional nature. A method that can efficiently use information that is partially available from various sources is thus urgently needed for complex system design. This paper presents a multi-fidelity surrogate modeling strategy that efficiently utilizes partially observed information (POI) from various sources, including data with different fidelity and dimensionality. Additionally, in reliability analysis and design optimization tasks, multiple constraints must be evaluated concurrently for each design point. However, as the complexity of systems increases, the number of constraints grows, resulting in a rapid increase in computational effort. Therefore, a multi-fidelity multi-task surrogate modeling framework with POI was proposed to aid in the development of surrogate models, which increases the effectiveness of reliability analysis. The proposed multi-fidelity multi-task machine learning (MFMT-ML) model utilizes a Bayesian framework, which significantly improves the predictive model’s performance and provides uncertainty quantification of the prediction. It also offers premium features such as using multi-fidelity sources of data points and POI, allowing simultaneous evaluation of multiple constraints through a single test, and offering a highly accurate and efficient reliability-based design optimization framework through knowledge sharing. By incorporating partially observed information from various sources, our approach offers a promising avenue for improving system performance prediction accuracy and efficiency while reducing the cost and complexity of complex system design.
Unraveling shared risk factors for diabetic foot ulcer: a comprehensive Mendelian randomization analysis
Authors: Yin Kangli , Qiao Tianci , Zhang Yongkang , Liu Jiarui , Wang Yuzhen , Qi Fei , Deng Junlin , Zhao Cheng , Xu Yongcheng , Cao Yemin 
Published: November 2023

IntroductionDiabetic foot ulcer (DFU) stands as a severe diabetic lower extremity complication, characterized by high amputation rates, mortality, and economic burden. We propose using Mendelian randomization studies to explore shared and distinct risk factors for diabetic lower extremity complications.Research design and methodsWe selected uncorrelated genetic variants associated with 85 phenotypes in five categories at the genome-wide significance level as instrumental variables. Genetic associations with DFU, diabetic polyneuropathy (DPN), and diabetic peripheral artery disease (DPAD) were obtained from the FinnGen and UK Biobank studies.ResultsBody mass index (BMI) emerged as the only significant risk factor for DPAD, DPN, and DFU, independent of type 2 diabetes, fasting glucose, fasting insulin, and HbA1c. Educational attainment stood out as the sole significant protective factor against DPAD, DPN, and DFU. Glycemic traits below the type 2 diabetes diagnosis threshold showed associations with DPAD and DPN. While smoking history exhibited suggestive associations with DFU, indicators of poor nutrition, particularly total protein, mean corpuscular hemoglobin, and mean corpuscular volume, may also signal potential DFU occurrence.ConclusionsEnhanced glycemic control and foot care are essential for the diabetic population with high BMI, limited education, smoking history, and indicators of poor nutrition. By focusing on these specific risk factors, healthcare interventions can be better tailored to prevent and manage DFU effectively.
Utility of surveillance data for planning for dengue elimination in Yogyakarta, Indonesia: a scenario-tree modelling approach
Authors: Bannister-Tyrrell Melanie , Hillman Alison , Indriani Citra , Ahmad Riris Andono , Utarini Adi , Simmons Cameron P , Anders Katherine L , Sergeant Evan 
Published: November 2023

IntroductionField trials and modelling studies suggest that elimination of dengue transmission may be possible through widespread release ofAedes aegyptimosquitoes infected with the insect bacteriumWolbachia pipientis(wMel strain), in conjunction with routine dengue control activities. This study aimed to develop a modelling framework to guide planning for the potential elimination of locally acquired dengue in Yogyakarta, a city of almost 400 000 people in Java, Indonesia.MethodsA scenario-tree modelling approach was used to estimate the sensitivity of the dengue surveillance system (including routine hospital-based reporting and primary-care-based enhanced surveillance), and time required to demonstrate elimination of locally acquired dengue in Yogyakarta city, assuming the detected incidence of dengue decreases to zero in the future. Age and gender were included as risk factors for dengue, and detection nodes included the probability of seeking care, probability of sample collection and testing, diagnostic test sensitivity and probability of case notification. Parameter distributions were derived from health system data or estimated by expert opinion. Alternative simulations were defined based on changes to key parameter values, separately and in combination.ResultsFor the default simulation, median surveillance system sensitivity was 0.131 (95% PI 0.111 to 0.152) per month. Median confidence in dengue elimination reached 80% after a minimum of 13 months of zero detected dengue cases and 90% confidence after 25 months, across different scenarios. The alternative simulations investigated produced relatively small changes in median system sensitivity and time to elimination.ConclusionThis study suggests that with a combination of hospital-based surveillance and enhanced clinic-based surveillance for dengue, an acceptable level of confidence (80% probability) in the elimination of locally acquired dengue can be reached within 2 years. Increasing the surveillance system sensitivity could shorten the time to first ascertainment of elimination of dengue and increase the level of confidence in elimination.
CD8+chimeric antigen receptor T cells manufactured in absence of CD4+cells exhibit hypofunctional phenotype
Authors: Lee Sang Yun , Lee Dong Hoon , Sun Wei , Cervantes-Contreras Francisco , Basom Ryan S , Wu Feinan , Liu Si , Rai Richa , Mirzaei Hamid R , O’Steen Shyril , Green Damian J , Shadman Mazyar , Till Brian G 
Published: November 2023

BackgroundCell culture conditions during manufacturing can impact the clinical efficacy of chimeric antigen receptor (CAR) T cell products. Production methods have not been standardized because the optimal approach remains unknown. Separate CD4+and CD8+cultures offer a potential advantage but complicate manufacturing and may affect cell expansion and function. In a phase 1/2 clinical trial, we observed poor expansion of separate CD8+cell cultures and hypothesized that coculture of CD4+cells and CD8+cells at a defined ratio at culture initiation would enhance CD8+cell expansion and simplify manufacturing.MethodsWe generated CAR T cells either as separate CD4+and CD8+cells, or as combined cultures mixed in defined CD4:CD8 ratios at culture initiation. We assessed CAR T cell expansion, phenotype, function, gene expression, and in vivo activity of CAR T cells and compared these between separately expanded or mixed CAR T cell cultures.ResultsWe found that the coculture of CD8+CAR T cells with CD4+cells markedly improves CD8+cell expansion, and further discovered that CD8+cells cultured in isolation exhibit a hypofunctional phenotype and transcriptional signature compared with those in mixed cultures with CD4+cells. Cocultured CAR T cells also confer superior antitumor activity in vivo compared with separately expanded cells. The positive impact of CD4+cells on CD8+cells was mediated through both cytokines and direct cell contact, including CD40L-CD40 and CD70-CD27 interactions.ConclusionsOur data indicate that CD4+cell help during cell culture maintains robust CD8+CAR T cell function, with implications for clinical cell manufacturing.
Non-invasive CT imaging biomarker to predict immunotherapy response in gastric cancer: a multicenter study
Authors: Huang Weicai , Xiong Wenjun , Tang Lei , Chen Chuanli , Yuan Qingyu , Zhang Cheng , Zhou Kangneng , Sun Zepang , Zhang Taojun , Han Zhen , Feng Hao , Liang Xiaokun , Zhong Yonghong , Deng Haijun , Yu Lequan , Xu Yikai , Wang Wei , Shen Lin , Li Guoxin , Jiang Yuming 
Published: November 2023

BackgroundDespite remarkable benefits have been provided by immune checkpoint inhibitors in gastric cancer (GC), predictions of treatment response and prognosis remain unsatisfactory, making identifying biomarkers desirable. The aim of this study was to develop and validate a CT imaging biomarker to predict the immunotherapy response in patients with GC and investigate the associated immune infiltration patterns.MethodsThis retrospective study included 294 GC patients who received anti-PD-1/PD-L1 immunotherapy from three independent medical centers between January 2017 and April 2022. A radiomics score (RS) was developed from the intratumoral and peritumoral features on pretreatment CT images to predict immunotherapy-related progression-free survival (irPFS). The performance of the RS was evaluated by the area under the time-dependent receiver operating characteristic curve (AUC). Multivariable Cox regression analysis was performed to construct predictive nomogram of irPFS. The C-index was used to determine the performance of the nomogram. Bulk RNA sequencing of tumors from 42 patients in The Cancer Genome Atlas was used to investigate the RS-associated immune infiltration patterns.ResultsOverall, 89 of 294 patients (median age, 57 years (IQR 48–66 years); 171 males) had an objective response to immunotherapy. The RS included 13 CT features that yielded AUCs of 12-month irPFS of 0.787, 0.810 and 0.785 in the training, internal validation, and external validation 1 cohorts, respectively, and an AUC of 24-month irPFS of 0.805 in the external validation 2 cohort. Patients with low RS had longer irPFS in each cohort (p<0.05). Multivariable Cox regression analyses showed RS is an independent prognostic factor of irPFS. The nomogram that integrated the RS and clinical characteristics showed improved performance in predicting irPFS, with C-index of 0.687–0.778 in the training and validation cohorts. The CT imaging biomarker was associated with M1 macrophage infiltration.ConclusionThe findings of this prognostic study suggest that the non-invasive CT imaging biomarker can effectively predict immunotherapy outcomes in patients with GC and is associated with innate immune signaling, which can serve as a potential tool for individual treatment decisions.
Vessel wall MRI characteristics associated with intraprocedural stent thrombosis during angioplasty for intracranial atherosclerotic stenosis
Authors: Ma Xiaotong , Yan Peng , Ju Jiachen , Yang Zhengyu , Wang Wenjuan , Wang Qiuting , Liu Xiaohui , Xia Zhangyong , Sun Qinjian 
Published: November 2023

Background
Few studies have so far explored plaque characteristics on high-resolution magnetic resonance vessel wall imaging (HR-VWI) associated with intraprocedural stent thrombosis (IPST) during angioplasty for intracranial atherosclerotic stenosis (ICAS). We aimed to investigate the plaque features on HR-VWI associated with IPST during stenting for ICAS.

Methods
This study recruited 77 patients with ICAS who underwent intracranial stenting using the Gateway-Wingspan system, and were performed with enhanced pre- and post-contrast T1-weighted HR-VWI on a 3.0T MRI scanner before angioplasty. During stenting for ICAS, eight patients (male: 100%, age mean ± standard deviation (SD): 58.7±2.47) developed IPST within 30 minutes after stenting. To ensure comparability, 16 patients who had undergone intracranial stenting but did not develop IPST were matched as controls for this study. Univariable and binary logistic models were used to explore the plaque characteristics on HR-VWI associated with IPST.

Results
Patients who developed IPST had less plaque diffusion (37.50% vs 81.25%, p=0.036), a more severe degree of area stenosis (median 96.30% vs 81.65%, p<0.01), and a higher plaque enhancement index (median 37.99 vs 13.12, p<0.01) compared with those who did not. After multivariate adjustment, IPST was independently associated with a more severe degree of area stenosis (adjusted odds ratio (OR) 1.20, 95% confidence interval (CI) 1.01–1.43, p=0.044) and a higher plaque enhancement index (adjusted OR 1.17, 95% CI 1.01 to 1.36, p=0.036).

Conclusion
Intraprocedural stent thrombosis during intracranial angioplasty for patients with ICAS may be independently associated with a higher plaque enhancement index and a more severe degree of area stenosis on HR-VWI.
Topoisomerase 1 Inhibition in MYC-Driven Cancer Promotes Aberrant R-Loop Accumulation to Induce Synthetic Lethality
Authors: Lin Peter , Lourenco Corey , Cruickshank Jennifer , Palomero Luis , van Leeuwen Jenna E. , Tong Amy H. Y. , Chan Katherine , El Ghamrasni Samah , Pujana Miquel Angel , Cescon David W. , Moffat Jason , Penn Linda Z. 
Published: November 2023

Abstract

MYC is a central regulator of gene transcription and is frequently dysregulated in human cancers. As targeting MYC directly is challenging, an alternative strategy is to identify specific proteins or processes required for MYC to function as a potent cancer driver that can be targeted to result in synthetic lethality. To identify potential targets in MYC-driven cancers, we performed a genome-wide CRISPR knockout screen using an isogenic pair of breast cancer cell lines in which MYC dysregulation is the switch from benign to transformed tumor growth. Proteins that regulate R-loops were identified as a potential class of synthetic lethal targets. Dysregulated MYC elevated global transcription and coincident R-loop accumulation. Topoisomerase 1 (TOP1), a regulator of R-loops by DNA topology, was validated to be a vulnerability in cells with high MYC activity. Genetic knockdown of TOP1 in MYC-transformed cells resulted in reduced colony formation compared with control cells, demonstrating synthetic lethality. Overexpression of RNaseH1, a riboendonuclease that specifically degrades R-loops, rescued the reduction in clonogenicity induced by TOP1 deficiency, demonstrating that this vulnerability is driven by aberrant R-loop accumulation. Genetic and pharmacologic TOP1 inhibition selectively reduced the fitness of MYC-transformed tumors in vivo. Finally, drug response to TOP1 inhibitors (i.e., topotecan) significantly correlated with MYC levels and activity across panels of breast cancer cell lines and patient-derived organoids. Together, these results highlight TOP1 as a promising target for MYC-driven cancers.

Significance:
CRISPR screening reveals topoisomerase 1 as an immediately actionable vulnerability in cancers harboring MYC as a driver oncoprotein that can be targeted with clinically approved inhibitors.
American Gun Violence & Mental Illness: Reducing Risk,
Restoring Health, Respecting Rights & Reviving
Communities
Authors: Swanson Jeffrey W. , Rosenberg Mark L. 
Published: November 2023

Abstract
Intentional injuries claimed nearly two hundred lives every day in the United States in 2020, about two-thirds of them suicides, each a story of irretrievable human loss. This essay addresses the complex intersection of injurious behavior with mental illness and access to firearms. It explores what more can be done to stop gun violence while respecting the rights of lawful gun owners, preserving the dignity of persons with mental illnesses, and promoting racial equity. Strategies to prevent firearm injury in the United States are uniquely conditioned by a constitutional right to bear arms, the cultural entrenchment and prevalence of private gun ownership, and strident political disagreement on regulatory solutions to stem gun violence. Broad implementation of a range of complementary policies is needed, including community-based programs to address the social and developmental determinants of violence, improved access to a continuum of mental health services, firearm restrictions based on behavioral indicators of risk (not mental illness, per se), licensing for firearm purchase or ownership, comprehensive background checks for firearm purchase, and supply-side approaches to interrupt illegal firearm markets.
Rethinking Psychiatry: Solutions for a Sociogenic
Crisis
Authors: Hansen Helena , Gutierrez Kevin J. , Garcia Saudi 
Published: November 2023

Abstract
This essay draws on Frantz Fanon's insights about the sociogenesis of psychiatric disorders, and on the insights of feminist standpoint theory, to sketch a map toward sociogenic mental health. We argue that psychiatry should move away from iatrogenesis (the harms of our current individual-level and pathologizing approach) toward sociogenesis of mental health through robust collaboration with social movements of oppressed people, and their collective healing approaches, ranging from harm reduction centers to community gardens. The essay ends with the outlines of a reinvented, community collaborative psychiatry that supports sociogenesis.
Disorders of Mood: The Experience of Those Who Have
Them
Authors: Jamison Kay Redfield 
Published: November 2023

Abstract
Mood disorders are common, painful, and closely tied to suicide and alcohol and substance use. They are also treatable. Mania and depression, a part of the human record for as long as it has been kept, were well-recognized and described by physicians of antiquity. Our knowledge of mood disorders has broadened and deepened in the many centuries since those early times, and crosses many scientific and clinical fields, including genetics, neuropharmacology, neuroimaging, psychopathology, and neuropsychology. We have as well a rich history of personal narratives of depression and bipolar disorder that gives a different but essential perspective; I present several of these accounts here.
Good Mental Health Care: What It Is, What It Is Not & What It
Could Be
Authors: Kleinman Arthur , Gardner Caleb 
Published: November 2023

Abstract
What makes for good mental health care? What are the barriers to good care and, when they can be overcome, what accounts for successful treatment? What does successful treatment and care, in fact, mean? Can they mean different things to different people? If so, how can we think about them in a practical way that is useful to patients, families, and clinicians? On the one hand, from work infields as various as neuroscience, clinical psychology, and anthropology, we are learning (and rediscovering) more and more about how the human mind works and the many ways that psychological suffering can be preempted and treated. On the other hand, in many ways, the mental health care system is either dysfunctional or working against what we know to be best for psychological and social flourishing-the disappearance, for example, of true “care” from medical and mental health care systems. In this essay, set against the background of diverse perspectives provided by the foregoing essays in this volume, we attempt to frame and address some of these basic questions, giving priority to practical, down-to-earth, lay, and professional considerations.
Epistolary Strategies of Negotiation: Reading a Fraternal Dispute at the Mughal Court, 1593–1594
Authors: Ghosh Shounak 
Published: November 2023

Abstract
This article examines a dispute between the Mughal emperor Akbar and his foster brother Mirzā ʿ⁠Azīz Koka in the late sixteenth century through a study of two epistolary compositions (inshāʾ) – a royal mandate (farmān) issued by Akbar and a petition (ʿ⁠arẓ-dāsht) from the mirzā in response. By focusing on the language of negotiation in these letters, I argue that epistolary practices were critical for reconfiguring kinship bonds, imperial service, and courtly disposition that were central to the rupture in fraternal and courtly relations. Letters served as the discursive site to reiterate norms of courtly comportment, register complaints against controversial actions, express emotions, and record reactions to exigent situations. Finally, the correspondence reveals the ways in which the complex dynamics of a court society were deeply intertwined with global power contestations and could have far-reaching implications on the imperial competition between early modern Islamic empires.
Regulating Carbon Assets Insider Trading: A US-EU Comparison to Protect Carbon Market Integrity
Authors: Oh Seokjin 
Published: November 2023

Abstract
Given that policy information significantly affects the supply and demand of carbon assets, that the major factor impacting carbon asset market price is the size of supply and demand of the assets, and that, unlike commodities, outsiders are not allowed to access policy information, carbon asset insider trading can be implemented majorly as a form of corruption between authorities and entities. In this context, this paper discusses the regulatory vacuum of the US legal system relevant to carbon asset trading. The basis of the argument is in the comparison of legal system between the EU and the US.