bluuebunny/crossref_metadata_2025 huggingface dataset:
Gravity Wave Interaction With a Composite Pile–Rock Breakwater
Authors: Keerthi Raaj S. , Vijay K. G. , Neelamani S. , Saha Nilanjan , Sundaravadivelu R.
Published: November 2023

Surface gravity wave interaction with a novel composite pile–rock breakwater having a stack of porous plates fixed on its top is investigated in the present study. A numerical code based on the dual boundary element method (DBEM) is developed to understand the wave scattering and force coefficients within the framework of linearized potential flow theory. Out of the four different proposed configurations (pile–rock alone, vertical, horizontal, and H-shaped porous plate assembly with pile–rock), it is found that novel H-shaped porous plates with submerged pile–rock are effective in attenuating the wave energy. The parametric study for the H-shaped configuration with several key aspects like permeable plate porosity, horizontal plate's submergence depth, pile–rock relative height, and width of the pile–rock barriers are investigated. It is appropriate to use plate porosity in the range of 10–20% to secure wave transmission of less than 0.5 for a wide range of incident wave periods. By changing the relative submergence of the horizontal porous plate from (h2/h = 0.375–0.125), it is possible to reduce the wave transmission by about 10% but at the expense of increasing the vertical wave force by almost 50–75%. Increasing the pile–rock height (h1/h from 0.75 to 0.25) helps to reduce the wave transmission but significantly increases the horizontal wave force and moment on the perforated H-shaped barrier. The results of the parametric study can be used for optimizing the dimensions of the pile–rock cum porous plate wave barrier for a wide range of field conditions.
Numerical Study on the Automatic Ballast Control of a Floating Dock
Authors: Wen Xueliang , Zhang Jianan , García Conde Alejandro , Ong Muk Chen
Published: November 2023

The ballast control of a floating dock mainly relies on manual operations, which can be time-consuming and requires skilled workers. This study proposes an automatic ballast control system for floating docks, which improves operational efficiency and safety during the vessel docking process. A numerical model is developed to simulate the dynamic process of the floating dock's operations, which includes a six degrees-of-freedom (6DOF) model, a hydrostatic force model, a hydrodynamic force model, and a hydraulic model. The hydrostatic force model is developed using the Archimedes law and a strip theory along the longitudinal direction. The hydrodynamic model is made based on the effects of added mass and dynamic damping. The hydraulic model is proposed to deal with the hydraulic calculation of the ballast water system. The present automatic ballast control is designed based on a modified proportional controller (P-controller) to control the valve opening angles when the pitch or roll angles are larger than the corresponding threshold values. Without using controllers, the roll angles of the dock can reach 8.9 deg and 13 deg during the ballasting and de-ballasting operations, respectively. The present modified P-controller with optimized control parameters can stabilize the dock during the de-ballasting operation and keep the maximum pitch and roll angles no larger than 0.016 deg and 0.0783 deg, respectively. During the ballasting operation with the same control parameters, the roll and pitch are below 0.0604 deg and 0.0145 deg, respectively. The present automatic control will be further implemented in the vessel docking cases and can significantly improve the stability of the dock.
Experimentally Induced Pain Results in Reduced Activity of the Rotator Cuff Muscles in Healthy Subjects
Authors: Cooper Jennifer L. , Karduna Andrew R.
Published: November 2023

Shoulder pain is a complex, prevalent problem that is multifactorial in nature. While there are many potential causes, one common suspect is the rotator cuff musculature. The purpose of the present study was to induce pain in the supraspinatus muscle of healthy subjects and observe the resulting changes in muscle activity. Eight muscles on 23 subjects were assessed using electromyography: anterior, middle, and posterior deltoid; pectoralis major; upper trapezius; latissimus dorsi; serratus anterior; supraspinatus; and infraspinatus. It was hypothesized that the rotator cuff muscles would display reduced activity during pain, and that reductions in activity would remain after the pain had dissipated. Both of the rotator cuff muscles measured did indeed display reduced activity in a majority of the dynamic, isometric, and maximal contractions. Many of those reductions remained after the pain had subsided.
Grain-size variability in debris flows of different runout lengths, Wenchuan, China
Authors: Harvey Erin L. , Hales Tristram C. , Liu Jie , Hobley Daniel E.J. , Yang Fan , Xia Bing , Fan Xuanmei
Published: November 2023

Debris-flow grain-size distributions (GSDs) control runout length and mobility. Wide, bimodal GSDs and those containing a higher proportion of silt and clay have been shown experimentally to increase runout length. However, the relationship between grain size and mobility has not been well established in field conditions. Here, we compared the grain-size characteristics of two debris flows with considerably different runout lengths (1.5 km vs. 8 km) to understand the role of grain size in governing runout. The two debris flows were triggered in the same rainfall event from coseismic landslide debris generated in the 2008 Wenchuan earthquake in catchments with similar lithology and topography. We compared the deposited GSDs and their spatial patterns using our rare, three-dimensional GSD datasets. Surprisingly, the proportions of each size fraction deposited by the two flows were statistically indistinguishable. The spatial pattern of grain size differed between the two flows, with evidence of inverse grading only preserved in the smaller deposit. From these observations, we can infer that the GSDs of both flows were determined by the coseismic landslide source material, and that there was little difference in the GSDs of material entrained as the flows bulked. The contrasting spatial distributions of grains indicated that different internal processes were dominant within the two flows. These findings demonstrate that where GSDs are dominated by coarse grains and are governed by similar source conditions, grain size plays a lesser role relative to sediment supply and hydrology in controlling the runout length of large catastrophic post-earthquake debris flows.
Enhanced recovery support for people with eating disorders during the COVID-19 pandemic: quality improvement using a web-based, stepped-care programme in Canada
Authors: Wood Michael D , Smith Jeannine L , Healey Hannah , Görges Matthias , Lokker Cynthia
Published: November 2023

Background

Throughout the COVID-19 pandemic, the number of individuals struggling with eating disorders (EDs) increased substantially. Body Brave (a not-for-profit) created and implemented a web-based stepped-care Recovery Support Programme (RSP) to improve access to community-based ED services. This quality improvement study describes the RSP and assesses its ability to deliver timely access to treatment and platform engagement.

Methods

We conducted a retrospective cohort study comparing access to, and use of Body Brave services 6 months before and 12 months after implementation of the RSP platform (using 6-month increments for two postimplementation periods). Primary programme quality measures included registration requests, number of participants onboarded and time to access services; secondary measures included use of RSP action plans, attendance for recovery sessions and workshops, number of participants accessing treatment and text-based patient experience data.

Results

A substantial increase in registration requests was observed during the first postimplementation period compared with the preimplementation period (176.5 vs 85.5; p=0.028). When compared with the preimplementation period, the second postimplementation observed a significantly larger percentage of successfully onboarded participants (76.6 vs 37.9; p<0.01) and a reduction in the number of days to access services (2 days vs 31 days; p<0.01). Although participant feedback rates were low, many users found the RSP helpful, easy to access, user-friendly and were satisfied overall. Users provided suggestions for improvement (eg, a platform instructional video, offer multiple times of day for live sessions and drop-in hours).

Conclusions

Although clinical benefit needs to be assessed, our findings demonstrate that the RSP enabled participants to quickly onboard and access initial services and have informed subsequent improvements. Understanding initial programme effects and usage will help assess the feasibility of adapting and expanding the RSP across Canada to address the urgent need for low-barrier, patient-centred ED care.
Loss of ADAR1 in macrophages in combination with interferon gamma suppresses tumor growth by remodeling the tumor microenvironment
Authors: Lin Weiwei , Luo Yikai , Wu Jie , Zhang Haowan , Jin Ge , Guo Chahua , Zhou Hang , Liang Han , Xu Xiaoyan
Published: November 2023

Background

ADAR1, the major enzyme for RNA editing, has emerged as a tumor-intrinsic key determinant for cancer immunotherapy efficacy through modulating interferon-mediated innate immunity. However, the role of ADAR1 in innate immune cells such as macrophages remains unknown.

Methods

We first analyzed publicly accessible patient-derived single-cell RNA-sequencing and perturbed RNA sequencing data to elucidate the ADAR1 expression and function in macrophages. Subsequently, we evaluated the combined effects of ADAR1 conditional knockout in macrophages and interferon (IFN)-γ treatment on tumor growth in three distinct disease mouse models: LLC for lung cancer, B16-F10 for melanoma, and MC38 for colon cancer. To gain the mechanistic insights, we performed human cytokine arrays to identify differentially secreted cytokines in response to ADAR1 perturbations in THP-1 cells. Furthermore, we examined the effects of ADAR1 loss and IFN-γ treatment on vessel formation through immunohistochemical staining of mouse tumor sections and tube-forming experiments using HUVEC and SVEC4-10 cells. We also assessed the effects on CD8+T cells using immunofluorescent and immunohistochemical staining and flow cytometry. To explore the translational potential, we examined the consequences of injecting ADAR1-deficient macrophages alongside IFN-γ treatment on tumor growth in LLC-tumor-bearing mice.

Results

Our analysis on public data suggests that ADAR1 loss in macrophages promotes antitumor immunity as in cancer cells. Indeed, ADAR1 loss in macrophages combined with IFN-γ treatment results in tumor regression in diverse disease mouse models. Mechanistically, the loss of ADAR1 in macrophages leads to the differential secretion of key cytokines: it inhibits the translation of CCL20, GDF15, IL-18BP, and TIM-3 by activating PKR/EIF2α signaling but increases the secretion of IFN-γ through transcriptional upregulation and interleukin (IL)-18 due to the 5'UTR uORF. Consequently, decreased CCL20 and GDF15 and increased IFN-γ suppress angiogenesis, while decreased IL-18BP and TIM-3 and increased IL-18 induce antitumor immunity by enhancing cytotoxicity of CD8+T cells. We further demonstrate that combination therapy of injecting ADAR1-deficient macrophages and IFN-γ effectively suppresses tumors in vivo.

Conclusion

This study provides a comprehensive elucidation of how ADAR1 loss within macrophages contributes to the establishment of an antitumor microenvironment, suggesting the therapeutic potential of targeting ADAR1 beyond the scope of cancer cells.
Cytoplasmic-delivery of polyinosine-polycytidylic acid inhibits pancreatic cancer progression increasing survival by activating Stat1-CCL2-mediated immunity
Authors: Bhoopathi Praveen , Kumar Amit , Pradhan Anjan K , Maji Santanu , Mannangatti Padmanabhan , Windle Jolene J , Subler Mark A , Zhang Dongyu , Vudatha Vignesh , Trevino Jose G , Madan Esha , Atfi Azeddine , Sarkar Devanand , Gogna Rajan , Das Swadesh K , Emdad Luni , Fisher Paul B
Published: November 2023

Background

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer without effective therapies and with poor prognosis, causing 7% of all cancer-related fatalities in the USA. Considering the lack of effective therapies for this aggressive cancer, there is an urgent need to define newer and more effective therapeutic strategies. Polyinosine–polycytidylic acid (pIC) is a synthetic double-stranded RNA (dsRNA) which directly activates dendritic cells and natural killer cells inhibiting tumor growth. When pIC is delivered into the cytoplasm using polyethyleneimine (PEI), pIC-PEI, programmed-cell death is induced in PDAC. Transfection of [pIC]PEIinto PDAC cells inhibits growth, promotes toxic autophagy and also induces apoptosis in vitro and in vivo in animal models.

Methods

The KPC transgenic mouse model that recapitulates PDAC development in patients was used to interrogate the role of an intact immune system in vivo in PDAC in response to [pIC]PEI. Antitumor efficacy and survival were monitored endpoints. Comprehensive analysis of the tumor microenvironment (TME) and immune cells, cytokines and chemokines in the spleen, and macrophage polarization were analyzed.

Results

Cytosolic delivery of [pIC]PEIinduces apoptosis and provokes strong antitumor immunityin vivoin immune competent mice with PDAC. The mechanism underlying the immune stimulatory properties of [pIC]PEIinvolves Stat1 activation resulting in CCL2 and MMP13 stimulation thereby provoking macrophage polarization. [pIC]PEIinduces apoptosis via the AKT-XIAP pathway, as well as macrophage differentiation and T-cell activation via the IFNγ-Stat1-CCL2 signaling pathways in PDAC. In transgenic tumor mouse models, [pIC]PEIpromotes robust and profound antitumor activity implying that stimulating the immune system contributes to biological activity. The [pIC]PEIanti-PDAC effects are enhanced when used in combination with a standard of care (SOC) treatment, that is, gemcitabine.

Conclusions

In summary, [pIC]PEItreatment is non-toxic toward normal pancreatic cells while displaying strong cytotoxic and potent immune activating activities in PDAC, making it an attractive therapeutic when used alone or in conjunction with SOC therapeutic agents, potentially providing a safe and effective treatment protocol with translational potential for the effective therapy of PDAC.
Titin copy number variations associated with dominant inherited phenotypes
Authors: Perrin Aurélien , Métay Corinne , Savarese Marco , Ben Yaou Rabah , Demidov German , Nelson Isabelle , Solé Guilhem , Péréon Yann , Bertini Enrico Silvio , Fattori Fabiana , D'Amico Adele , Ricci Federica , Ginsberg Mira , Seferian Andreea , Boespflug-Tanguy Odile , Servais Laurent , Chapon Françoise , Lagrange Emmeline , Gaudon Karen , Bloch Adrien , Ghanem Robin , Guyant-Maréchal Lucie , Johari Mridul , Van Goethem Charles , Fardeau Michel , Morales Raul Juntas , Genetti Casie A , Marttila Minttu , Koenig Michel , Beggs Alan H , Udd Bjarne , Bonne Gisèle , Cossée Mireille
Published: November 2023

Background

Titinopathies are caused by mutations in the titin gene (TTN). Titin is the largest known human protein; its gene has the longest coding phase with 364 exons. Titinopathies are very complex neuromuscular pathologies due to the variable age of onset of symptoms, the great diversity of pathological and muscular impairment patterns (cardiac, skeletal muscle or mixed) and both autosomal dominant and recessive modes of transmission. Until now, only few CNVs inTTNhave been reported without clear genotype–phenotype associations.

Methods

Our study includes eight families with dominant titinopathies. We performed next-generation sequencing or comparative genomic hybridisation array analyses and found CNVs in theTTNgene. We characterised these CNVs by RNA sequencing (RNAseq) analyses in six patients’ muscles and performed genotype–phenotype inheritance association study by combining the clinical and biological data of these eight families.

Results

Seven deletion-type CNVs in theTTNgene were identified among these families. Genotype and RNAseq results showed that five deletions do not alter the reading frame and one is out-of-reading frame. The main phenotype identified was distal myopathy associated with contractures. The analysis of morphological, clinical and genetic data and imaging let us draw new genotype–phenotype associations of titinopathies.

Conclusion

IdentifyingTTNCNVs will further increase diagnostic sensitivity in these complex neuromuscular pathologies. Our cohort of patients enabled us to identify new deletion-type CNVs in theTTNgene, with unexpected autosomal dominant transmission. This is valuable in establishing new genotype–phenotype associations of titinopathies, mainly distal myopathy in most of the patients.
Vall d’Hebron Risk Score II for myocardial infarction and cardiac death
Authors: Romero-Farina Guillermo , Aguadé-Bruix Santiago , Ferreira González Ignacio
Published: November 2023

Objectives

The aim of this study was to create a new Vall d’Hebron Risk Score-II (VH-RS-II) for non-fatal myocardial infarction (MI) and/or cardiac death (CD), excluding patients with coronary revascularisation (CR) during the follow-up.

Methods

We analysed 5215 consecutive patients underwent gated single photon emission CT (SPECT); 2960 patients (age 64.2±11, male 58.1%) had no previous MI and/or CR, and 2255 patients (age 63.3±11, male 81.9%) had previous MI and/or CR. During a follow-up of 4.3±2.6 years, the cardiac event (MI and CD) was evaluated. This study was reviewed and approved by the ethics committee of our institution (number form trial register, PR(AG)168.2012). To obtain the predictor model, multivariate Cox regression analysis and multivariate logistic regression analysis were used. RS-VH-II was validated with 679 patients.

Results

In patients without previous MI and/or CR, age (HR: 1.01; p<0.001), diabetes (HR: 2.1, p=0.001), metabolic equivalent (METs) (HR: 0.89, p=0.038), ST segment depression (HR: 1.4, p=0.011), ejection fraction (EF) (HR: 0.97, p<0.001) and summed stress score (HR: 1.2, p<0.001) were the independent predictors of CE (C-statistic: 0.8). In patients with previous MI and/or CR, age (HR: 1.06, p<0.001), male (HR: 1.9, p=0.047), smoker (HR: 1.5, p=0.047), METs (HR: 0.8, p<0.001), ST segment depression (HR: 1.4, p=0.002), EF (HR: 0.96; p<0.001) and summed difference score (HR: 1.03, p=0.06) were the independent predictors of CE (C-statistic:0.8).

Conclusion

The VH-RS-II obtained from different clinical exercise and gated SPECT variables allow the risk stratification for MI and CD in patients with or without previous MI and/or CR in due form.
E-commerce licensing loopholes: a case study of online shopping for tobacco products following a statewide sales restriction on flavoured tobacco in California
Authors: Leas Eric C , Mejorado Tomas , Harati Raquel , Ellis Shannon , Satybaldiyeva Nora , Morales Nicolas , Poliak Adam
Published: November 2023

Introduction

Retailer licensing programmes can be an effective method of enforcing tobacco control laws, but most programmes do not require e-commerce retailers to obtain licenses. California’s implementation of a statewide flavour restriction (Senate Bill 793 (SB-793)) in December 2022 enforced through its tobacco retailer licensing programme presented an opportunity to assess whether the exclusion of e-commerce in the definition of ‘tobacco retailer’ might have resulted in a shift in consumer behaviour towards e-commerce.

Methods

To examine the association between SB-793 implementation and online shopping for tobacco, we collected weekly Google search rates related to online shopping for cigarettes and vaping products in California from January 2018 to May 2023. We compared observed rates of shopping queries after SB-793 implementation to counterfactual expected rates and prediction intervals (PI) calculated from autoregressive iterative moving average models fit to historical trends. Content analysis was performed on the search results to identify websites marketing flavoured vaping products and menthol cigarettes.

Results

The week SB-793 was implemented, shopping queries were 194.4% (95% PI 100.8% to 451.5%) and 161.7% (95% PI 81.7% to 367.5%) higher than expected for cigarettes and vapes, respectively. Cigarette shopping queries remained elevated significantly for 11 weeks and vape shopping queries for 6 weeks. All search results contained links to websites that offered flavoured vaping products or menthol cigarettes to Californian consumers.

Discussion

These findings raise concerns about potential loopholes in policy enforcement created by the absence of explicit regulations on e-commerce sales in retailer licensing programmes. Strengthening regulations to include e-commerce and monitoring e-commerce compliance are recommended to enhance the impact of laws enforced through retailer licensing programmes.
Prioritizing rapid COVID-19 testing in emergency general surgery patients decreases burden of inpatient hospital admission
Authors: Thomas Madeline B , Carmichael Heather , Harrison Madison , Abbitt Danielle , Moore Allison , Myers Quintin W O , Velopulos Catherine G
Published: November 2023

Objectives

The COVID-19 pandemic has changed delivery of emergency general surgery (EGS) and contributed to widespread bed shortages. At our institution, rapid testing is not routinely approved for EGS patients. We examined common EGS conditions (appendicitis and acute cholecystitis), hypothesizing that necessity of testing for COVID-19 significantly delayed operative intervention.

Methods

We performed a prepost study to examine a 2-month timeframe, or historical control, prior to COVID-19 testing (January 1, 2020–March 1, 2020) as well as a 2-month timeframe during the COVID-19 era (January 1, 2021–March 1, 2021). We chose conditions that are frequently treated surgically as outpatient or observation status. We examined time for COVID-19 test to result, and associated time to operative intervention (operating room (OR)) and need for admission.

Results

Median time to COVID-19 test results was 7.4 hours (IQR 5.8–13.1). For appendectomy, time to surgical consultation or case request did not differ between cohorts. Time to OR after case request was significantly longer (12.5 vs 1.9 hours, p<0.001) and patients more frequently required admission prior to operative intervention if receiving treatment in the COVID-19 timeframe. Similarly, for cholecystectomy there were no differences in time to surgical consultation or case request, but time to OR after case request was longer in the COVID-19 era (21.1 vs 9.0 hours, p<0.001).

Conclusion

While COVID-19 positivity rates have declined, the purpose of this study was to reflect on one element of our hospital system’s response to the COVID-19 pandemic. Based on our institutional experience, waiting for COVID-19 test results directly impacts time to surgery, as well as the need for admission for a historically outpatient procedure. In the future, if the healthcare system is asked to respond to another pandemic or similar situation, expediting time to OR to eliminate unnecessary time in the hospital and non-critical admissions should be paramount.

Level of evidence

Level III, prognostic/epidemiological.
Extraction of the strong coupling with HERA and EIC inclusive data
Authors: Cerci Salim , Demiroglu Zuhal Seyma , Deshpande Abhay , Newman Paul R. , Schmookler Barak , Sunar Cerci Deniz , Wichmann Katarzyna
Published: November 2023

Sensitivity to the strong coupling $$\alpha _S(M^2_Z)$$

α
S

(

M
Z
2

)

is investigated using existing Deep Inelastic Scattering data from HERA in combination with projected future measurements from the Electron Ion Collider (EIC) in a next-to-next-to-leading order QCD analysis. A potentially world-leading level of precision is achievable when combining simulated inclusive neutral current EIC data with inclusive charged and neutral current measurements from HERA, with or without the addition of HERA inclusive jet and dijet data. The result can be obtained with substantially less than one year of projected EIC data at the lower end of the EIC centre-of-mass energy range. Some questions remain over the magnitude of uncertainties due to missing higher orders in the theoretical framework.
A new low gain avalanche diode concept: the double-LGAD
Authors: Carnesecchi F. , Strazzi S. , Alici A. , Arcidiacono R. , Cartiglia N. , Cavazza D. , Durando S. , Ferrero M. , Margotti A. , Menzio L. , Nania R. , Sabiu B. , Scioli G. , Siviero F. , Sola V. , Vignola G.
Published: November 2023

This paper describes the new concept of the double LGAD (low-gain avalanche diodes). The goal was to increase the charge at the input of the electronics, keeping a time resolution equal to or better than a standard (single) LGAD; this has been realized by adding the charges of two coupled LGADs while still using a single front-end electronics. The study here reported has been done starting from single LGAD with a thickness of 25 µm, 35 µm and 50 µm.
Thermodynamics of Markovian Open Quantum Systems with Application to Lasers
Authors: Alicki R.
Published: November 2023

Göran Lindblad was one of the pioneers of what is now called quantum thermodynamics. From this vast and rapidly developing field, we have selected a sample of results concerning quantum open systems described by Markovian master equations of the Lindblad (Gorini–Kossakowski–Sudarshan) type, which are applied to models of lasers. One can study their thermodynamics using the properties of quantum relative entropy, also introduced by Lindblad.
Speaker-Aware Interactive Graph Attention Network for Emotion Recognition in Conversation
Authors: Jia Zhaohong , Shi Yunwei , Liu Weifeng , Huang Zhenhua , Sun Xiao
Published: November 2023

Recently,
E
motion
R
ecognition in
C
onversation (ERC) has attracted much attention and has become a hot topic in the field of natural language processing. Conversation is conducted in chronological order; current utterance is more likely influenced by nearby utterances. At the same time, speaker dependency also plays a core role in the conversation dynamic. The combined effect of the sequence-aware information and the speaker-aware information makes the emotion’s dynamic change. However, past works used simple information fusion methods to model the two kinds of information but ignored their interactive influence. Thus, we propose a novel method entitled SIGAT (
S
peaker-aware
I
nteractive
G
raph
A
ttention Ne
t
work) to solve the problem. The core module is a mutual interactive module in which a dual-connection (self-connection and interact-connection) graph attention network is constructed. The advantage of SIGAT is modeling the speaker-aware and sequence-aware information in a unified graph and updating them simultaneously. In this way, we model the interactive influence of them and obtain the final representations, which have richer contextual clues. Experimental results on the four public datasets demonstrate that SIGAT outperforms the state-of-the-art models.
QuCloud+: A Holistic Qubit Mapping Scheme for Single/Multi-programming on 2D/3D NISQ Quantum Computers
Authors: Liu Lei , Dou Xinglei
Published: November 2023

Qubit mapping for NISQ superconducting quantum computers is essential to fidelity and resource utilization. The existing qubit mapping schemes meet challenges, e.g., crosstalk, SWAP overheads, diverse device topologies, etc., leading to qubit resource underutilization and low fidelity in computing results. This article introduces QuCloud+, a new qubit mapping scheme that tackles these challenges. QuCloud+ has several new designs. (1) QuCloud+ supports single/multi-programming quantum computing on quantum chips with 2D/3D topology. (2) QuCloud+ partitions physical qubits for concurrent quantum programs with the crosstalk-aware community detection technique and further allocates qubits according to qubit degree, improving fidelity, and resource utilization. (3) QuCloud+ includes an X-SWAP mechanism that avoids SWAPs with high crosstalk errors and enables inter-program SWAPs to reduce the SWAP overheads. (4) QuCloud+ schedules concurrent quantum programs to be mapped and executed based on estimated fidelity for the best practice. Experimental results show that, compared with the existing typical multi-programming study [
12
], QuCloud+ achieves up to 9.03% higher fidelity and saves on the required SWAPs during mapping, reducing the number of CNOT gates inserted by 40.92%. Compared with a recent study [
30
] that enables post-mapping gate optimizations to further reduce gates, QuCloud+ reduces the post-mapping circuit depth by 21.91% while using a similar number of gates.
Automated Mapping of Adaptive App GUIs from Phones to TVs
Authors: Hu Han , Dong Ruiqi , Grundy John , Nguyen Thai Minh , Liu Huaxiao , Chen Chunyang
Published: November 2023

With the increasing interconnection of smart devices, users often desire to adopt the same app on quite different devices for identical tasks, such as watching the same movies on both their smartphones and TVs. However, the significant differences in screen size, aspect ratio, and interaction styles make it challenging to adapt Graphical User Interfaces (GUIs) across these devices. Although there are millions of apps available on Google Play, only a few thousand are designed to support smart TV displays. Existing techniques to map a mobile app GUI to a TV either adopt a responsive design, which struggles to bridge the substantial gap between phone and TV, or use mirror apps for improved video display, which requires hardware support and extra engineering efforts. Instead of developing another app for supporting TVs, we propose a semi-automated approach to generate corresponding adaptive TV GUIs, given the phone GUIs as the input. Based on our empirical study of GUI pairs for TVs and phones in existing apps, we synthesize a list of rules for grouping and classifying phone GUIs, converting them to TV GUIs, and generating dynamic TV layouts and source code for the TV display. Our tool is not only beneficial to developers but also to GUI designers, who can further customize the generated GUIs for their TV app development. An evaluation and user study demonstrate the accuracy of our generated GUIs and the usefulness of our tool.
From the chair
Authors: Harvey Christine
Published: November 2023

This special year-end issue is Part 1 of a two-part follow-up to our flagship conference, SC22. This part announces the professional society and conference award winners. The next issue will include perspectives from our student members and conference participants and other editorial content.
Genetic deficiency of the transcription factor NFAT1 confers protection against fibrogenic responses independent of immune influx
Authors: Vittal Ragini , Walker Natalie M. , McLinden A. Patrick , Braeuer Russell R. , Ke Fang , Fattahi Fatemeh , Combs Michael P. , Misumi Keizo , Aoki Yoshiro , Wheeler David S. , Wilke Carol A. , Huang Steven K. , Moore Bethany B. , Cao Pengxiu , Lama Vibha N.
Published: November 2023

Idiopathic pulmonary fibrosis (IPF) is a fatal disease with hallmarks of fibroblastic foci and exuberant matrix deposition, unknown etiology, and ineffective therapies. Several profibrotic/proinflammatory pathways are implicated in accelerating tissue remodeling toward a honeycombed end-stage disease. NFAT1 is a transcriptional factor activated in IPF tissues. Nfat1-deficient mice subjected to chronic injury are protected against fibrosis independent of immune influxes, with suppression of profibrotic mesenchymal phenotypes including proliferation, differentiation, resistance to apoptosis, and autotaxin-related migration.
Determination of Multicomponents in Rubi Fructus by Near-Infrared Spectroscopy Technique
Authors: Du Wenjun , Wu Chunyan , Yu Hesong , Kong Qingran , Xu Yunjian , Zhang Weidong
Published: November 2023

Objective. Rubi Fructus (RF) is a dry aggregate fruit of Rubus (Rosaceae). It has shown significant pharmacological effects such as anti-oxidation, hypoglycemic, and anti-inflammatory. A combination of near-infrared (NIR) spectroscopy and partial least squares regression (PLSR) under seven different spectral data preprocessing techniques was used to determine the performance of quantitative analysis correction models which employed moisure, ellagic acid, and total flavonoids as indicators of RF. Methods. Ninety-seven different RF batches were collected for NIR spectra. By using primary analysis techniques such as drying method, high-performance liquid chromatography (HPLC), and ultraviolet visible spectrophotometry (UV-Vis), the contents of moisure, ellagic acid, and total flavonoids were determined. The NIR spectral data and the primary analysis method data were correlated through PLSR. Seven methods were used for pretreating the spectral data, including no spectral pretreatment, first derivative, standard normalized variate, multiple scattering corrections, elimination of constant offset, and minimum maximum normalization. The quantitative analysis correction models adopted PLSR chemometrics for moisture, ellagic acid and total flavonoids were developed, and their effectiveness was evaluated using the correlation coefficient (R), ratio of prediction to deviation (RPD), and root mean square error (RMSE). Results. The first derivative was combined with variable standardization, elimination of constant offset, and multiple scattering corrections, respectively, to pretreat the PLSR models for moisture, ellagic acid, and total flavonoids. The R-values of the PLSR models for moisture, ellagic acid, and total flavonoids were, respectively, 0.9788, 0.9468, and 0.9748, all of which were higher than 0.90, and the RPD values were 4.9, 3.1, and 4.5, respectively, which were all larger than 3.0. The RMSE ratios of the calibration set and the test set were 0.98, 0.94, and 1.0, respectively. Conclusion. The R-values of the NIR-PLSR models for moisture, ellagic acid, and total flavonoids are all greater than 0.90 after suitable pretreatments, indicating that the models are reliable. The RPD values are more than 3.0, which indicate that the models are good and useable for quality control. The RMSE ratios are closed to 1, indicating that the calibration set and test set had same distribution and the models were not overfitting indicating good predictability.
Protocol for Electrical Conductivity Signal Collection and Processing in Scoliosis Surgery
Authors: Saghbiny Elie , Da Silva Jimmy , Chaimi Celia , Chandanson Thibault , Vialle Raphael
Published: November 2023

Introduction. Pedicle screw placement is a common procedure in spinal surgery. The misplacement rate with lateral and medial cortical perforation is 5–11%. Several techniques are used to decrease this rate. Many studies proved that electrical conductivity increases accuracy during pedicle screw placement but no study has interpreted conductivity values. Methods. The data are collected from patients operated for scoliosis in a single university hospital. After the posterior surgical approach is made, each pedicle is prepared classically. Instead of the classic curved pedicle probe, the surgeon uses a probe with the same shape that measures the conductivity at its tip. Conductivity values are recorded through a Bluetooth application. Each pedicle trajectory is then qualified after manual palpation with a feeler. A trajectory is qualified as optimal when palpation shows a bone tunnel without any breach, breached when there was a breach, and a modification of the probe direction was needed. A trajectory that does not meet the abovementioned definitions is excluded from the statistical analysis. Results. 21 patients with 457 pedicles are recorded. The average age of the population is 14.71 ± 1.86 years. 17 patients (81%) have idiopathic adolescent scoliosis. One patient has Rett syndrome, one has hypotonia, one has cerebral palsy, and one has congenital malformation. The depth of the instrument is measured semiautomatically. This technique is validated when compared with the manual technique using the Bland–Altman agreement method (mean differences = −0.279 mm, upper limit = 2.2 mm, and lower limit = −2.7 mm) and Deming regression (slope = 1.06 ± 0.004). Conclusion. This study establishes a protocol to collect electrical conductivity signals in spine surgery with synchronization to the depth of the instrument. Real-time conductivity signal feedback alerts the surgeon of a probable breach in the spinal canal, so he can change the direction of the pedicle aim.
Disruption of SUV39H1-Mediated H3K9 Methylation Sustains CAR T-cell Function
Authors: Jain Nayan , Zhao Zeguo , Koche Richard P. , Antelope Chenling , Gozlan Yosi , Montalbano Antonino , Brocks David , Lopez Michael , Dobrin Anton , Shi Yuzhe , Gunset Gertrude , Giavridis Theodoros , Sadelain Michel
Published: November 2023

Suboptimal functional persistence limits the efficacy of adoptive T-cell therapies. CD28-based chimeric antigen receptors (CAR) impart potent effector function to T cells but with a limited lifespan. We show here that the genetic disruption of SUV39H1, which encodes a histone-3, lysine-9 methyl-transferase, enhances the early expansion, long-term persistence, and overall antitumor efficacy of human CAR T cells in leukemia and prostate cancer models. Persisting SUV39H1-edited CAR T cells demonstrate improved expansion and tumor rejection upon multiple rechallenges. Transcriptional and genome accessibility profiling of repeatedly challenged CAR T cells shows improved expression and accessibility of memory transcription factors in SUV39H1-edited CAR T cells. SUV39H1 editing also reduces expression of inhibitory receptors and limits exhaustion in CAR T cells that have undergone multiple rechallenges. Our findings thus demonstrate the potential of epigenetic programming of CAR T cells to balance their function and persistence for improved adoptive cell therapies.

Significance:

T cells engineered with CD28-based CARs possess robust effector function and antigen sensitivity but are hampered by limited persistence, which may result in tumor relapse. We report an epigenetic strategy involving disruption of the SUV39H1-mediated histone-silencing program that promotes the functional persistence of CD28-based CAR T cells.

See related article by López-Cobo et al., p. 120.

This article is featured in Selected Articles from This Issue, p. 5
A Metabolic Gene Survey Pinpoints Fucosylation as a Key Pathway Underlying the Suppressive Function of Regulatory T Cells in Cancer
Authors: Pinioti Sotiria , Sharma Himal , Flerin Nina C. , Yu Qian , Tzoumpa Amalia , Trusso Cafarello Sarah , De Bousser Elien , Callewaert Nico , Oldenhove Guillaume , Schlenner Susan , Thienpont Bernard , Garg Abhishek D. , Di Matteo Mario , Mazzone Massimiliano
Published: November 2023

Forkhead box P3 (Foxp3)–expressing regulatory T cells (Treg) are the guardians of controlled immune reactions and prevent the development of autoimmune diseases. However, in the tumor context, their increased number suppresses antitumor immune responses, indicating the importance of understanding the mechanisms behind their function and stability. Metabolic reprogramming can affect Foxp3 regulation and, therefore, Treg suppressive function and fitness. Here, we performed a metabolic CRISPR/Cas9 screen and pinpointed novel candidate positive and negative metabolic regulators of Foxp3. Among the positive regulators, we revealed that targeting the GDP-fucose transporter Slc35c1, and more broadly fucosylation (Fuco), in Tregs compromises their proliferation and suppressive function both in vitro and in vivo, leading to alteration of the tumor microenvironment and impaired tumor progression and protumoral immune responses. Pharmacologic inhibition of Fuco dampened tumor immunosuppression mostly by targeting Tregs, thus resulting in reduced tumor growth. In order to substantiate these findings in humans, tumoral Tregs from patients with colorectal cancer were clustered on the basis of the expression of Fuco-related genes. FucoLOW Tregs were found to exhibit a more immunogenic profile compared with FucoHIGH Tregs. Furthermore, an enrichment of a FucoLOW signature, mainly derived from Tregs, correlated with better prognosis and response to immune checkpoint blockade in melanoma patients. In conclusion, Slc35c1-dependent Fuco is able to regulate the suppressive function of Tregs, and measuring its expression in Tregs might pave the way towards a useful biomarker model for patients with cancer.

See related Spotlight by Silveria and DuPage, p. 1570
A Case of Dellen Formation following 27-Gauge Vitrectomy with Rapid Improvement by Scleral and Conjunctival Sutures
Authors: Yamaguchi Saori , Yoshikawa Yuji , Chino Minami , Shinoda Kei
Published: November 2023

Introduction: Dellen is a corneal disease characterized by shallow, saucer-like excavations at the corneal margin. Herein, we presented a case of dellen formation that developed following a 27-gauge pars plana vitrectomy (PPV) and was rapidly resolved using scleral and conjunctival sutures. Case Presentation: A 73-year-old woman underwent a 27-gauge PPV for the epiretinal membrane of the right eye. Intraoperatively, owing to coexisting diabetic retinopathy, the peripheral vitreous was shaved, and retinal photocoagulation was performed on the peripheral retina. The intraocular pressure (IOP) was 15 mm Hg on 1 day after the PPV and on postoperative day 4; however, on day 14, the IOP decreased to 10 mm Hg, and conjunctival bleb formation was observed. By day 18, the bleb height remained unchanged, and dellen formation was noted at the corneal periphery. Because of marked corneal thinning, conjunctival and scleral sutures were placed 20 days following the PPV. Intraoperative findings revealed leakage from the scleral wound at the trocar puncture site. The IOP increased to 20 mm Hg at 19 h following the suture, resulting in the disappearance of the bleb and dellen. Since then, the bleb or dellen did not recur. Conclusion: We encountered a case of late-onset scleral wound cleavage 2 weeks following microincision vitreous surgery, resulting in bleb and dellen formation, which was immediately managed by the scleral and conjunctiva suturing.
Stratifying Future Stroke Risk with Incidentally- Discovered White Matter Disease Severity and Covert Brain Infarct Site
Authors: Wang Andy Y. , Leung Lester Y. , Puttock Eric J. , Luetmer Patrick H. , Kallmes David F. , Nelson Jason , Fu Sunyang , Zheng Chengyi , Liu Hongfang , Chen Wansu , Kent David M.
Published: November 2023

Background: Covert cerebrovascular disease (CCD) includes white matter disease (WMD) and covert brain infarction (CBI). Incidentally discovered CCD is associated with an increased risk of subsequent symptomatic stroke. However, it is unknown whether the severity of WMD or the location of CBI predicts risk. Objectives: The objective of this study was to examine the association of incidentally discovered WMD severity and CBI location with a risk of subsequent symptomatic stroke. Method: This retrospective cohort study includes patients ≥50 years old from the Kaiser Permanente Southern California health system who received neuroimaging for a nonstroke indication between 2009 and 2019. Incidental CBI and WMD were identified via natural language processing of the neuroimage report, and WMD severity was classified into grades. Results: 261,960 patients received neuroimaging, 78,555 (30.0%) were identified to have incidental WMD, and 12,857 were identified (4.9%) to have incidental CBI. Increasing WMD severity is associated with the increased incidence rate of future stroke. However, the stroke incidence rate in CT-identified WMD is higher at each level of severity compared to rates in MRI-identified WMD. Patients with mild WMD via CT have a stroke incidence rate of 24.9 per 1,000 person-years, similar to that of patients with severe WMD via MRI. Among incidentally discovered CBI patients with a determined CBI location, 97.9% have subcortical infarcts rather than cortical infarcts. CBI confers a similar risk of future stroke, whether cortical or subcortical, or whether MRI detected or CT detected. Conclusions: Increasing severity of incidental WMD is associated with an increased risk of future symptomatic stroke, dependent on the imaging modality. Subcortical and cortical CBI conferred similar risks.
Applying Computer-Based Language Test to Young Children
Authors: Hu Yunyi , Lee Kathy Yuet-Sheung , Lau Tammy Hui Mei , Yu Wilson Shing , Tong Michael C.F. , Ng Iris H.-Y. , Law Thomas
Published: November 2023

Introduction: This study aimed at exploring the feasibility of applying a computer-based language test to young children aged 2–4 years. Methods: Thirty-two Cantonese-speaking children, aged 2–4 years, were recruited from local kindergartens. All participants underwent an assessment using both the computer-based and paper-pencil versions of the Macau Cantonese Language Screening Scale for Preschool Children, following a crossover study design. A short break of 15–30 min was provided between the two assessments. The data were analysed at three levels: the overall test, subcategory, and individual item levels. At the overall test and subcategory levels, data were analysed using the paired samples t-test and ICC. At the item level, the percentage of agreement and Cohen’s kappa value were selected to assess the agreement of the two test formats. Results: Excellent agreement was found for the overall test level, and good agreement was observed for four of the five subcategories. At the individual item level, 28 of the 35 items showed more than 80% agreement, and 16 items showed substantial to almost perfect agreement. Conclusion: These results suggest that the two test formats give similar total scores and subcategory scores for children aged 2–4. For children older than 2 years and 6 months, the agreement for matching items is as high as 83.68% (1,318/1,575). The computer-based test is thus highly recommended for this group of children. For children younger than 2 years and 6 months, a modified computer-based test is suggested to accommodate their needs.
Measuring university size: A comparison of academic personnel versus scientific talent pool data
Authors: Lepori Benedetto , Bornmann Lutz , de Moya Anegón Félix
Published: November 2023

This paper compares two measures of the organizational size of higher education institutions (HEIs) widely used in the literature: the number of academic personnel (AP) measured according to definitions from international education statistics, and the scientific talent pool (STP) (i.e., the number of unique authors affiliated with the HEI as derived from the Scopus database). Based on their definitions and operationalizations, we derive expectations on the factors generating differences between these two measures, as related to the HEI’s research orientation and subject mix, as well as to the presence of a university hospital. We test these expectations on a sample of more than 1,500 HEIs in Europe by combining data from the European Tertiary Education Register and from the SCImago Institutions Ranking. Our results provide support for the expected relationships and also highlight cases where the institutional perimeter of HEIs is systematically different between the two sources. We conclude that these two indicators provide complementary measures of institutional size, one more focused on the organizational perimeter as defined by employment relationships, the other on the persons who contribute to the HEI’s scientific visibility. Comparing the two indicators is therefore likely to provide a more in-depth understanding of the HEI resources available.