bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplemental Material: Sulfur isotopes of lamprophyres and implications for the control of metasomatized lithospheric mantle on the giant Jiaodong gold deposits, East China
Authors: WANG XIANG , Wang Zaicong , et al.
Published: December 2023

The whole-rock elemental and isotopic composition of lamprophyres and mafic dikes in the Jiaodong Peninsula, Eastern China (Table) and details of modelling calculation (Text).
Ultrasound-guided serratus anterior plane block to prevent neurocognitive impairment in elderly patients after thoracoscopic lobectomy: protocol for a single-centre, double-blind, randomised controlled trial
Authors: Wang Dan-Yang , Feng Di , Liu Mei-Yun , Wu Wei , Xu Huan , Shi Hong
Published: December 2023

Introduction

Postoperative neurocognitive dysfunction (PND), including postoperative delirium (POD), is a common complication in elderly patients after major surgeries, often leading to poor postoperative recovery. Although the pathological mechanism underlying PND is still unclear, postoperative pain is strongly associated with the development of PND. The ultrasound-guided serratus anterior plane block (SAPB) has been reported to relieve postoperative pain in thoracic surgery. Therefore, this prospective trial hypothesises that SAPB may reduce the incidence of PND in the elderly undergoing thoracoscopic lobectomy.

Methods and analysis

This study is designed as a single-centre, double-blind, randomised controlled clinical trial. A total of 256 elderly patients scheduled to undergo thoracoscopic lobectomy at Shanghai Pulmonary Hospital will be randomly assigned to general anaesthesia group or SAPB group. The primary outcome is the incidence of PND 7 days postoperatively or before discharge from hospital. The secondary outcomes include the occurrence of POD, the postoperative pain scores, Quality of Recovery at 1–2 days postoperatively and incidence of PND at 3 months postoperatively. The levels of fasting blood glucose in peripheral blood will be examined before and 1–2 days postoperatively.

Ethics and dissemination

The trial has been approved by the Clinical Research Ethics Committee of Shanghai Pulmonary Hospital (identifier: K20-290). All participants will be required to provide written informed consent before any protocol-specific procedures. Findings will be disseminated in a peer-reviewed journal and in national and/or international meetings to guide future practice.

Trial registration number

ChiCTR2100052633.
Impact of health system governance on healthcare quality in low-income and middle-income countries: a scoping review
Authors: George Joby , Jack Susan , Gauld Robin , Colbourn Timothy , Stokes Tim
Published: December 2023

Introduction

Improving healthcare quality in low-/middle-income countries (LMICs) is a critical step in the pathway to Universal Health Coverage and health-related sustainable development goals. This study aimed to map the available evidence on the impacts of health system governance interventions on the quality of healthcare services in LMICs.

Methods

We conducted a scoping review of the literature. The search strategy used a combination of keywords and phrases relevant to health system governance, quality of healthcare and LMICs. Studies published in English until August 2023, with no start date limitation, were searched on PubMed, Cochrane Library, CINAHL, Web of Science, Scopus, Google Scholar and ProQuest. Additional publications were identified by snowballing. The effects reported by the studies on processes of care and quality impacts were reviewed.

Results

The findings from 201 primary studies were grouped under (1) leadership, (2) system design, (3) accountability and transparency, (4) financing, (5) private sector partnerships, (6) information and monitoring; (7) participation and engagement and (8) regulation.

Conclusions

We identified a stronger evidence base linking improved quality of care with health financing, private sector partnerships and community participation and engagement strategies. The evidence related to leadership, system design, information and monitoring, and accountability and transparency is limited.
mHealth application for improving treatment outcomes for patients with multidrug-resistant tuberculosis in Vietnam: an economic evaluation protocol for the V-SMART trial
Authors: Cheng Qinglu , Dang Tho , Nguyen Thu-Anh , Velen Kavindhran , Nguyen Viet Nhung , Nguyen Binh Hoa , Vu Dinh Hoa , Long Chuong Huynh , Do Thu Thuong , Vu Truong-Minh , Marks Guy B , Yapa Manisha , Fox Gregory J , Wiseman Virginia
Published: December 2023

Introduction

The Strengthen the Management of Multidrug-Resistant Tuberculosis in Vietnam (V-SMART) trial is a randomised controlled trial of using mobile health (mHealth) technologies to improve adherence to medications and management of adverse events (AEs) in people with multidrug-resistant tuberculosis (MDR-TB) undergoing treatment in Vietnam. This economic evaluation seeks to quantify the cost-effectiveness of this mHealth intervention from a healthcare provider and societal perspective.

Methods and analysis

The V-SMART trial will recruit 902 patients treated for MDR-TB across seven participating provinces in Vietnam. Participants in both intervention and control groups will receive standard community-based therapy for MDR-TB. Participants in the intervention group will also have a purpose-designed App installed on their smartphones to report AEs to health workers and to facilitate timely management of AEs. This economic evaluation will compare the costs and health outcomes between the intervention group (mHealth) and the control group (standard of care). Costs associated with delivering the intervention and health service utilisation will be recorded, as well as patient out-of-pocket costs. The health-related quality of life (HRQoL) of study participants will be captured using the 36-Item Short Form Survey (SF-36) questionnaire and used to calculate quality-adjusted life-years (QALYs). Incremental cost-effectiveness ratios (ICERs) will be based on the primary outcome (proportion of patients with treatment success after 24 months) and QALYs gained. Sensitivity analysis will be conducted to test the robustness of the ICERs. A budget impact analysis will be conducted from a payer perspective to provide an estimate of the total budget required to scale-up delivery of the intervention.

Ethics and dissemination

Ethical approval for the study was granted by the University of Sydney Human Research Ethics Committee (2019/676), the Scientific Committee of the Ministry of Science and Technology, Vietnam (08/QD-HDQL-NAFOSTED) and the Institutional Review Board of the National Lung Hospital, Vietnam (13/19/CT-HDDD). Study findings will be published in peer-reviewed journals and conference proceedings.

Trial registration number

ACTRN12620000681954.
Applications of implementation science frameworks, models and theories in disparities-focused cancer screening interventions: a scoping review protocol
Authors: Xiong Serena , Klesges Lisa , Doering Michelle , Pratt Rebekah J
Published: December 2023

Background

Implementation science (IS) frameworks, models and theories (FMTs) have gained popularity in guiding the implementation and evaluation of evidence-based interventions (EBIs) for cancer screening. However, there are significant research gaps in understanding their applications in cancer health disparities contexts. This paper outlines a scoping review protocol designed to explore the utilisation of IS FMTs in cancer screening EBIs to inform intervention designs and adaptations.

Methods and analysis

This scoping review protocol adheres to Arksey and O’Malley’s five-step methodological framework for conducting scoping studies. Search strategies were conducted in five bibliographic databases: Ovid MEDLINE, PubMed, Scopus, Web of Science and EMBASE. The search was run on 22 June 2023 with an English language filter and a date limit of 2001-current. Two reviewers will independently screen studies for inclusion and exclusion criteria. A third reviewer will be consulted, where appropriate at any of the review stages, to achieve consensus or resolve conflicts. Data will be collected, managed and analysed using Covidence. A narrative synthesis, based on Popayet al’s methodology, will guide reporting and summarisation of results. The review will adhere to the PRISMA Extension for Scoping Reviews guidelines.

Ethics and dissemination

This scoping review is a novel approach for examining a growing corpus of research literature on IS FMT applications used in cancer screening EBIs. As a secondary analysis, this scoping review does not require approval from an institutional review board. We anticipate the review will produce insightful information (eg, challenges, key areas for future directions) on the applications of IS TMFs in designing, deploying and testing EBIs for populations experiencing cancer screening disparities. We will disseminate the results through journals and conferences targeting IS and cancer prevention researchers and practitioners.
Protocol for a systematic review of reviews on training primary care providers in dermoscopy to detect skin cancers
Authors: McCaffrey Nikki , Bucholc Jessica , Ng Leo , Chai Kevin , Livingstone Ann , Murphy April , Gordon Louisa G
Published: December 2023

Introduction

Globally, incidence, prevalence and mortality rates of skin cancers are escalating. Earlier detection by well-trained primary care providers in techniques such as dermoscopy could reduce unnecessary referrals and improve longer term outcomes. A review of reviews is planned to compare and contrast the conduct, quality, findings and conclusions of multiple systematic and scoping reviews addressing the effectiveness of training primary care providers in dermoscopy, which will provide a critique and synthesis of the current body of review evidence.

Methods and analysis

Four databases (Cochrane, CINAHL, EMBASE and MEDLINE Complete) will be comprehensively searched from database inception to identify published, peer-reviewed English-language articles describing scoping and systematic reviews of the effectiveness of training primary care providers in the use of dermoscopy to detect skin cancers. Two researchers will independently conduct the searches and screen the results for potentially eligible studies using ‘Research Screener’ (a semi-automated machine learning tool). Backwards and forwards citation tracing will be conducted to supplement the search. A narrative summary of included reviews will be conducted. Study characteristics, for example, population; type of educational programme, including content, delivery method, duration and assessment; and outcomes for dermoscopy will be extracted into a standardised table. Data extraction will be checked by the second reviewer. Methodological quality will be evaluated by two reviewers independently using the Critical Appraisal Tool for Health Promotion and Prevention Reviews. Results of the assessments will be considered by the two reviewers and any discrepancies will be resolved by team consensus.

Ethics and dissemination

Ethics approval is not required to conduct the planned systematic review of peer-reviewed, published articles because the research does not involve human participants. Findings will be published in a peer-reviewed journal, presented at leading public health, cancer and primary care conferences, and disseminated via website postings and social media channels.

PROSPERO registration number

CRD42023396276.
How did New Zealand’s regional District Health Board groupings work to improve service integration and health outcomes: a realist evaluation
Authors: Penno Erin , Atmore Carol , Maclennan Brett , Richard Lauralie , Wyeth Emma , Richards Rosalina , Doolan-Noble Fiona , Gray Andrew R , Sullivan Trudy , Gauld Robin , Stokes Tim
Published: December 2023

Objectives

In Aotearoa New Zealand (NZ), integration across the healthcare continuum has been a key approach to strengthening the health system and improving health outcomes. A key example has been four regional District Health Board (DHB) groupings, which, from 2011 to 2022, required the country’s 20 DHBs to work together regionally. This research explores how this initiative functioned, examining how, for whom and in what circumstances regional DHB groupings worked to deliver improvements in system integration and health outcomes and equity.

Design

We used a realist-informed evaluation study design. We used documentary analysis to develop programme logic models to describe the context, structure, capabilities, implementation activities and impact of each of the four regional groupings and then conducted interviews with stakeholders. We developed a generalised context-mechanisms-outcomes model, identifying key commonalities explaining how regional work ‘worked’ across NZ while noting important regional differences.

Setting

NZ’s four regional DHB groupings.

Participants

Forty-nine stakeholders from across the four regional groupings. These included regional DHB governance groups and coordinating regional agencies, DHB senior leadership, Māori and Pasifika leadership and lead clinicians for regional work streams.

Results

Regional DHB working was layered on top of an already complex DHB environment. Organisational heterogeneity and tensions between local and regional priorities were key contextual factors. In response, regional DHB groupings leveraged a combination of ‘hard’ policy and planning processes, as well as ‘soft’, relationship-based mechanisms, aiming to improve system integration, population health outcomes and health equity.

Conclusion

The complexity of DHB regional working meant that success hinged on building relationships, leadership and trust, alongside robust planning and process mechanisms. As NZ reorients its health system towards a more centralised model underpinned by collaborations between local providers, our findings point to a need to align policy expectations and foster environments that support connection and collegiality across the health system.
Cross-sectional study assessing health outcome priorities of older adults with multimorbidity at a primary care setting in Singapore
Authors: Ng Xin Rong , Tey Yu Xuan Sheryl , Lew Kaiwei Jeremy , Lee Poay Sian Sabrina , Lee Eng Sing , Sim Sai Zhen
Published: December 2023

Objectives

Managing older adults with multimorbidity may be challenging due to the conflicting benefits and harms of multiple treatments. Thus, it is important to identify patients’ health outcome priorities to align treatment goals with their health preferences. This study aimed to use the Outcome Prioritisation Tool (OPT) to describe the health outcome priorities of older adults with multimorbidity and determine the factors associated with these priorities. Additionally, it aimed to assess the ease of completing the OPT in Singapore’s primary care population.

Design

Cross-sectional study conducted from January to March 2022.

Setting

A public primary care centre in Singapore.

Participants

65 years and older with multimorbidity.

Outcome measures

Primary outcome measure was the most important health outcome priorities on the OPT. Secondary outcome measures were factors affecting these priorities and ease of completing the OPT.

Results

We enrolled 180 participants (mean age: 73.2±6.1 years). Slightly more than half (54.4%) prioritised ‘staying alive’, while the remainder (45.6%) prioritised ‘maintaining independence’ (25.6%), ‘relieving pain’ (10.6%) and ‘relieving other symptoms’ (9.4%). Participants with six or more chronic conditions were three times (OR 3.03 (95% CI1.09 to 8.42)) more likely to prioritise ‘staying alive’ compared with participants with three conditions. Most participants (69.4%) agreed that the OPT was easy to complete, and the mean time taken to complete the OPT was 3.8±1.6 minutes.

Conclusion

‘Staying alive’ was the most important health outcome priority, especially for older adults with six or more chronic conditions. The OPT was easily completed among older adults with multimorbidity in primary care. Further qualitative studies can be conducted to understand the factors influencing patients’ priorities and explore the relevance of the OPT in guiding treatment decisions.
Feebly-interacting particles: FIPs 2022 Workshop Report
Authors: Antel C. , Battaglieri M. , Beacham J. , Boehm C. , Buchmüller O. , Calore F. , Carenza P. , Chauhan B. , Cladè P. , Coloma P. , Crivelli P. , Dandoy V. , Darmé L. , Dey B. , Deppisch F. F. , De Roeck A. , Drewes M. , Echenard B. , Flambaum V. V. , Foldenauer P. , Gatti C. , Giannotti M. , Golutvin A. , Gonzalez-Garcia M. C. , Gori S. , Goudzovski E. , Granelli A. , Grote H. , Guellati-Khelifa S. , Hajer J. , Harris P. , Hearty C. , Heuchel D. , Hostert M. , Junius S. , Kahlhoefer F. , Klaric J. , Kling F. , Klose P. , Knolle J. , Kopp J. , Kwon O. , Lantwin O. , Lanfranchi G. , Li L. , Lindner A. , Lopez-Pavon J. , Marocco J. , Martin J. W. , Middleton S. , Milstead S. , Oceano I. , O’Hare C. A. J. , Paoloni A. , Pascoli S. , Petcov S. T. , Pospelov M. , Pöttgen R. , Raggi M. , Ripellino G. , Samsonov I. B. , Sandner S. , Söldner-Rembold S. , Shelton J. , Song N. , Sun C. , Stadnik Y. V. , Tastet J.-L. , Toro N. , Tran N. , Trevisani N. , Ulmer S. , Urrea S. , Velghe B. , Wallisch B. , Wong Y. Y. Y. , Zorbilmez C. , Zurek K.
Published: December 2023

Particle physics today faces the challenge of explaining the mystery of dark matter, the origin of matter over anti-matter in the Universe, the origin of the neutrino masses, the apparent fine-tuning of the electro-weak scale, and many other aspects of fundamental physics. Perhaps the most striking frontier to emerge in the search for answers involves new physics at mass scales comparable to familiar matter, below the GeV-scale, or even radically below, down to sub-eV scales, and with very feeble interaction strength. New theoretical ideas to address dark matter and other fundamental questions predict such feebly interacting particles (FIPs) at these scales, and indeed, existing data provide numerous hints for such possibility. A vibrant experimental program to discover such physics is under way, guided by a systematic theoretical approach firmly grounded on the underlying principles of the Standard Model. This document represents the report of the FIPs 2022 workshop, held at CERN between the 17 and 21 October 2022 and aims to give an overview of these efforts, their motivations, and the decadal goals that animate the community involved in the search for FIPs.
A Smart Status Based Monitoring Algorithm for the Dynamic Analysis of Memory Safety
Authors: Chen Zhe , Yan Rui , Ma Yingzi , Sui Yulei , Xue Jingling
Published: December 2023

C is a dominant programming language for implementing system and low-level embedded software. Unfortunately, the unsafe nature of its low-level control of memory often leads to memory errors. Dynamic analysis has been widely used to detect memory errors at runtime. However, existing monitoring algorithms for dynamic analysis are not yet satisfactory, as they cannot deterministically and completely detect some types of errors, such as segment confusion errors, sub-object overflows, use-after-frees and memory leaks.

We propose a new monitoring algorithm, namely
Smatus
, short for
smart status
, that improves memory safety by performing comprehensive dynamic analysis. The key innovation is to maintain at runtime a small
status node
for each memory object. A status node records the
status value
and
reference count
of an object, where the status value denotes the liveness and segment type of this object, and the reference count tracks the number of pointer variables pointing to this object.
Smatus
maintains at runtime a pointer metadata for each pointer variable, to record not only the base and bound of a pointer’s referent but also the address of the referent’s status node. All the pointers pointing to the same referent share the same status node in their pointer metadata. A status node is
smart
in the sense that it is automatically deleted when it becomes useless (indicated by its reference count reaching zero). To the best of our knowledge,
Smatus
represents the most comprehensive approach of its kind.

We have evaluated
Smatus
by using a large set of programs including the NIST Software Assurance Reference Dataset, MSBench, MiBench, SPEC and stress testing benchmarks. In terms of effectiveness (detecting different types of memory errors),
Smatus
outperforms state-of-the-art tools, Google’s AddressSanitizer, SoftBoundCETS and Valgrind, as it is capable of detecting more errors. In terms of performance (the time and memory overheads),
Smatus
outperforms SoftBoundCETS and Valgrind in terms of both lower time and memory overheads incurred, and is on par with AddressSanitizer in terms of the time and memory overhead tradeoff made (with much lower memory overheads incurred).
Review—Advances in PVC-Based Blend Nanocomposites
Authors: Fariha Samiya , Islam Mohammed Saydul , Rockshat Md. , Umme Hani Sanjana , Islam Jahidul , Zabed Hossain M. , Khandaker Mayeen Uddin , Rahman Ismail M. M. , Chowdhury Faisal Islam
Published: December 2023

PVC (polyvinyl chloride) is a thermoplastic polymer used extensively in industrial applications. The potentiality of PVC lies in various parameters, such as high tensile strength, biodegradability, large surface area, chemical stability, low weight, durability, cost-effectiveness, and availability. However, the low thermal stability and brittleness of pure PVC limit its acceptance in widespread applications. Therefore, modifying PVC with metal oxides and carbon nanofillers could substantially improve thermal stability, mechanical strength, biocompatibility, surface area, conductivity, etc. Enhanced properties in modified PVC result from the chemical and physical interaction between polymer and functionalized nanofillers and the good dispersion capability of nanofillers on polymer matrix, which is attributed to the excellent performances of nanocomposites in diverse fields. This paper aims to present an overview of the characterization, preparation, and applications of blend nanocomposites of PVC, which would benefit future developments in this field.
Inducing Crystal Phase Transformation of Titanium Oxide by Pulse Laser Irradiation
Authors: Tsutsumi Masaki , Tanaka Hidekazu
Published: December 2023

To selectively pattern titanium oxide with desired properties, we report inducing crystal phase transformation from rutile TiO2 to γ/λ-Ti3O5 and corundum Ti2O3 by pulse laser irradiation. The crystal phase of the produced titanium oxide could be systematically controlled by laser fluence. This crystal phase transformation simultaneously increased the electrical conductivity with changing the electrical conduction mechanism from band conduction to variable-range hopping conduction. This report also proposes the mechanism of the crystal phase transformation. Comparing thermodynamic calculations and finite element simulations of the temperature rise due to laser irradiation showed that this phase transformation can be interpreted as a reduction reaction caused by laser heating. Our findings indicate that laser irradiation can spatially pattern various crystal phases of titanium oxides on a substrate, and this technique will enable the regioselective, fine, and highly productive fabrication process of titanium oxide-based electronic devices.
Direct Observation of the Stretching of the Photoinduced Current Relaxation in α-Ga2O3 Schottky Diodes
Authors: Schemerov Ivan V. , Polyakov Alexander Y. , Vasilev Anton A. , Nikolaev Vladimir I. , Pechnikov Alexey I. , Chernykh Alexey V. , Romanov Andrey A. , Pearton Stephen J.
Published: December 2023

Relaxation of photoinduced current in α-Ga2O3-based Schottky diodes was measured. Such Schottky diodes were fabricated using α-Ga2O3 films grown by Halide Vapor Phase Epitaxy (HVPE) on basal plane sapphire. Their photosensitivity in UV-C region was very high and several orders of magnitude higher than for visible light. The photoinduced current rise and decay times are found to be quite long, which is attributed to the hole capture by deep acceptors and to the effects of potential fluctuations. Due to these problems the photoinduced current relaxation process consists of several steps and takes more than hundreds of seconds. The characteristic relaxation times were calculated using the logarithmic differential analysis that demonstrated that the build-up and decay processes can be accurately described by stretched exponents with different broadening factors β. It was shown that additional illumination by long-wave light can help to observe the slowing of the relaxation speed. The temperature activation energies for photoinduced current decay and rise times are 0.37 ± 0.03 eV and 0.06 ± 0.005 eV respectively.
Formulas for the Number of Weak Homomorphisms from Paths to Ladder Graphs and Stacked Prism Graphs
Authors: Yingtaweesittikul Hatairat , Panma Sayan , Rochanakul Penying
Published: December 2023

Let

G

and

H

be graphs. A mapping

f

from

V

G

to

V

H

is called a weak homomorphism from

G

to

H

if

f

x

=
f

y

or

f

x

,
f

y

∈
E

H

whenever

x
,
y

∈
E

G

. A ladder graph is the Cartesian product of two paths, where one of the paths has only one edge. A stacked prism graph is the Cartesian product of a path and a cycle. In this paper, we provide a formula to determine the number of weak homomorphisms from paths to ladder graphs and a formula to determine the number of weak homomorphisms from paths to stacked prism graphs.
Vitamin D Deficiency and the Presentation of Primary Hyperparathyroidism: A Mini Review
Authors: Yedla Niharika , Kim Hyon , Sharma Anupa , Wang Xiangbing
Published: December 2023

The clinical presentation of primary hyperparathyroidism (PHPT) has evolved over the years from a symptomatic disorder to a predominantly asymptomatic condition. Altered vitamin D metabolism seems to play a role in the presentation of PHPT and may exacerbate the severity of disease. The epidemiology of PHPT differs in the developing versus the developed world, where more severe phenotypes occur in regions where vitamin D deficiency is common. Although it has been validated that patients with PHPT should be vitamin D sufficient, the threshold to supplement in relation to the severity of PHPT and the degree of vitamin D deficiency remains controversial. This review will highlight some of the controversy regarding vitamin D deficiency and the different phenotypes of PHPT.
Comprehensive Comparison of AAV Purification Methods: Iodixanol Gradient Centrifugation vs. Immuno-Affinity Chromatography
Authors: Lam Anh K. , Mulcrone Patrick L. , Frabutt Dylan , Zhang Junping , Chrzanowski Matthew , Arisa Sreevani , Munoz Maite , Li Xin , Biswas Moanaro , Markusic David , Herzog Roland W. , Xiao Weidong
Published: December 2023

Recombinant adeno-associated viruses (AAVs) have emerged as a widely used gene delivery platform for both basic research and human gene therapy. To ensure and improve the safety profile of AAV vectors, substantial efforts have been dedicated to the vector production process development using suspension HEK293 cells. Here, we studied and compared two downstream purification methods, iodixanol gradient ultracentrifugation versus immuno-affinity chromatography (POROS™ CaptureSelect™ AAVX column). We tested multiple vector batches that were separately produced (including AAV5, AAV8, and AAV9 serotypes). To account for batch-to-batch variability, each batch was halved for subsequent purification by either iodixanol gradient centrifugation or affinity chromatography. In parallel, purified vectors were characterized, and transduction was compared both in vitro and in vivo in mice (using multiple transgenes: Gaussia luciferase, eGFP, and human factor IX). Each purification method was found to have its own advantages and disadvantages regarding purity, viral genome (vg) recovery, and relative empty particle content. Differences in transduction efficiency were found to reflect batch-to-batch variability rather than disparities between the two purification methods, which were similarly capable of yielding potent AAV vectors.
Identification and Verification of the Blue Pigment in the Edible Jellyfish (Rhopilema esculentum)
Authors: Chen Bailing , Li Yulong , Gao Qidou , Li Yunfeng , Bao Xiangbo , Zheng Jie , Zhou Zunchun
Published: December 2023

Rhopilema esculentum is widely cultured in Chinese coastal regions and has thousand years of consumption history in China. Despite R. esculentum owns multiple colors (mainly ochre and blue) in aquaculture ponds, little is known about the pigments and color formation. This study identified and verified the blue pigment of R. esculentum. Results showed that the blue pigment of R. esculentum has 262 amino acids with 54.96% identity to the blue pigment protein precursor of Rhizostoma pulmo. The blue pigment of R. esculentum has Kringle and Frizzled domains, which is in accordance with rhizostomins characteristics. Compared to ochre R. esculentum, the expression level of blue pigment increased 3.49-fold in blue R. esculentum. In addition, overexpression of the blue pigment in Rhodosporidium toruloides made transformant cells blue under blue light excitation. Our findings provide knowledge for the blue color formation of R. esculentum and will benefit the color selection of R. esculentum with excellent traits.
Applying the Operational Design Domain Concept to Vehicles Equipped with Advanced Driver Assistance Systems for Enhanced Safety
Authors: Kang Heejin , Lee Yoseph , Jeong Harim , Park Giok , Yun Ilsoo
Published: December 2023

Advanced driver assistance systems (ADASs) assist drivers by alerting them of the occurrence of events based on the sensing capabilities of the vehicle, reducing the effort required by drivers. Most vehicles that are recently launched vehicles have been endowed with ADAS, thereby significantly reducing traffic accidents. However, the Insurance Institute for Highway Safety has reported that traffic accidents caused by driver negligence may increase as drivers have become accustomed to using ADAS. Therefore, drivers must be provided with sufficient information on the appropriate use of ADAS through user manuals. In this study, the regulations regarding the presentation of the operational design domain (ODD) in ADAS user manuals were analyzed. The results indicated that most user manuals do not sufficiently specify the ODD, which is claimed important by various organizations for ensuring safe driving. Additionally, the expression of the limitations and performance of ADAS is ambiguous because most countries are not regulated to explicitly present the ODD when writing ADAS user manuals. Therefore, in this study, the ODD guidelines for presenting ADAS specific to vehicle manufacturers and governments have been outlined in addition to guidelines for drivers on using ADAS. These guidelines can contribute to the development of clear ADAS user manuals, which in turn can ensure the safe driving of ADAS-equipped vehicles.
Feature Aggregation with Two‐Layer Ensemble Framework for Multilingual Speech Emotion Recognition
Authors: Ough Sangho , Pyo Sejong , Kim Taeyong
Published: December 2023

In this study, we present a framework for improving the accuracy of speech emotion recognition in a multilingual environment. In our prior experiments, where machine learning (ML) models were trained to predict emotions in Korean and then tested in English, as well as vice versa, we observed a dependency on language in emotion recognition, resulting in poor accuracy. We suspect that this may be related to the spectral differences in certain emotions between Korean and English and to the tendency for different formant values to have different acoustic frequencies. For this study, we investigated several different methods, including models with mixed databases, a single database, and bagging, boosting, and voting ML algorithms. Finally, we developed a framework consisting of two branches: one for the aggregation of high‐dimensional features from multilingual data and one for a two‐layered ensemble framework for emotion classification. In the ensemble framework for Korean and English (EF‐KEN), features are extracted and ensemble models are trained, boosted, and evaluated by applying them to different spoken languages (English and Korean). The final experimental result demonstrates a meaningful improvement in an environment with two different languages.
Immune Modulation of Innate and Adaptive Responses Restores Immune Surveillance and Establishes Antitumor Immunologic Memory
Authors: Alvero Ayesha B. , Fox Alexandra , Madina Bhaskara Reddy , Krady Marie M. , Gogoi Radhika , Chehade Hussein , Nakaar Valerian , Almassian Bijan , Yarovinsky Timur O. , Rutherford Thomas , Mor Gil
Published: December 2023

Current immunotherapies have proven effective in strengthening antitumor immune responses, but constant opposing signals from tumor cells and the surrounding microenvironment eventually lead to immune escape. We hypothesized that in situ release of antigens and regulation of both the innate and adaptive arms of the immune system would provide a robust and long-term antitumor effect by creating immunologic memory against tumors. To achieve this, we developed CARG-2020, a genetically modified virus-like vesicle (VLV) that is a self-amplifying RNA with oncolytic capacity and encodes immune regulatory genes. CARG-2020 carries three immune modulators: (i) the pleiotropic antitumor cytokine IL12, in which the subunits (p35 and p40) are tethered together; (ii) the extracellular domain (ECD) of the protumor IL17RA, which serves as a dominant-negative antagonist; and (iii) a shRNA targeting PD-L1. Using a mouse model of ovarian cancer, we demonstrated the oncolytic effect and immune-modulatory capacities of CARG-2020. By enhancing IL12 and blocking IL17 and PD-L1, CARG-2020 successfully reactivated immune surveillance by promoting M1, instead of M2, macrophage differentiation, inhibiting MDSC expansion and establishing a potent CD8+ T cell–mediated antitumoral response. Furthermore, we demonstrated that this therapeutic approach provided tumor-specific and long-term protection against the establishment of new tumors. Our results provide a rationale for the further development of this platform as a therapeutic modality for ovarian cancer patients to enhance antitumor responses and prevent a recurrence.
Sustained Disease Control in Immune Checkpoint Blockade Responders with Microsatellite Instability-high Colorectal Cancer after Treatment Termination
Authors: Simmons Kristen , Thomas Jane V. , Ludford Kaysia , Willis Jason A. , Higbie Victoria S. , Raghav Kanwal P.S. , Johnson Benny , Dasari Arvind , Kee Bryan K. , Parseghian Christine M. , Lee Michael S. , Le Phat H. , Morelli Maria P. , Shen John Paul , Bent Alisha , Vilar Eduardo , Wolff Robert A. , Kopetz Scott , Overman Michael J. , Morris Van Karlyle
Published: December 2023

Immune checkpoint inhibitors improve survival in patients with mismatch repair deficiency/microsatellite instability-high (MSI-H) colorectal cancer. The recurrence outcomes following discontinuation of immunotherapy after prolonged disease control have not been definitively reported in large series. Records from patients with advanced MSI-H colorectal cancer from The University of Texas – MD Anderson Cancer Center who received immunotherapy between 2014 and 2022 and stopped after prolonged clinical benefit were reviewed. Median progression-free and overall survival were estimated. Associations between the event of recurrence and coexisting mutations (KRAS/NRAS, BRAFV600E), metastatic organ involvement (lung, liver, lymph node, or peritoneum), metastatic timing (synchronous vs. metachronous), prior immunotherapy [anti-PD-(L)1 alone or in combination with anti-CTLA antibodies], etiology of MSI status (sporadic vs. hereditary non-polyposis colorectal cancer), and duration of immunotherapy were assessed. Sixty-four patients with MSI-H colorectal cancer without progression on immunotherapy were reviewed. Of these 48 and 16 received anti-PD(L)1 antibody alone or in combination with anti-CTLA-4 antibody, respectively. Median exposure to immunotherapy was 17.6 months (range, 1.3–51.9). After a median follow-up of 22.6 months (range, 0.3–71.7) after stopping immunotherapy, 56 of 64 patients (88%) remained without disease progression. Lung metastases were associated with recurrence/progression (OR, 6.1; P = 0.04), but coexisting mutation, primary tumor sidedness, and immunotherapy were not. These data provide a retrospective, single-institution analysis that showed that most patients with advanced MSI-H colorectal cancer do not recur after treatment cessation, regardless of the reason for stopping treatment or a variety of patient and disease features, supporting an optimistic prognosis of sustained disease control.

Significance:

Outcomes for patients with MSI-H colorectal cancer stopping immunotherapy after disease control remain unknown. Sixty-four patients with MSI-H colorectal cancer from our institution stopping treatment for sustained benefit or toxicity were retrospectively assessed. After median follow up of 22 months and median immunotherapy exposure of 18 months, 88% patients remained without progression. All patients who recurred or progressed and were rechallenged with immunotherapy have continued to experience disease control.
Secreted Frizzled-Related Protein 4 Induces Gastric Cancer Progression and Resistance to Cisplatin and Oxaliplatin via β-Catenin Dysregulation
Authors: Chen Chun-Han , Chen Chih-Jung , Huang Yi-Ching , Huang Po-Shuan , Chi Hsiang-Cheng , Chuang Huei-Chieh , Lin Meng-Hung , Huang Tzu-Hao , Hsu Jun-Te , Chen Cheng-Yi
Published: December 2023

Introduction: Gastric cancer is the fifth most common cancer and third leading cause of cancer-related death worldwide. There are three main ways to treat gastric cancer: surgical resection, radiation therapy, and drug therapy. Furthermore, combinations of two to three regimens can improve survival. However, the survival outcomes of chemotherapy in advanced gastric cancer patients are still unsatisfactory. Unfortunately, no widely useful biomarkers have been verified to predict the efficacy of chemotherapy for locally advanced gastric cancer. Methods: An MTT assay was used to determine the cell viability after cisplatin or oxaliplatin treatment. Western blotting and immunohistochemistry were utilized to examine the secreted frizzled-related protein 4 (sFRP4) level and associated signaling pathways. Immunofluorescence staining was utilized to analyze the location of β-catenin. Colony formation and Transwell assays were used to analyze the functions related with cisplatin, oxaliplatin, and sFRP4. Results: We have found that gastric cancer patients treated with combinations of 5-fluorouracil (5-FU) and cisplatin regimens have better survival rates than those treated with 5-FU-based chemotherapy alone. sFRP4 was selected as a potential target from stringent analysis and intersection of 5-FU and cisplatin resistance-related gene sets. sFRP4 was shown to be overexpressed in clinical gastric tumor tissues and positively correlated with a worse survival rate. In addition, sFRP4 and β-catenin were upregulated in cisplatin- and oxaliplatin-resistant gastric cancer cells compared to parental cells. Immunofluorescence staining and nuclear fractionation showed that β-catenin was translocated from the cytosol into the nucleus. Moreover, sFRP4 was detected in the conditioned medium of these resistant cells, which indicates that sFRP4 might have an extracellular role in chemotherapy resistance. Increased migration capacity and dysregulation of epithelial-mesenchymal transition-related markers, which might result from the dysregulation of sFRP4, were observed in cisplatin- and oxaliplatin-resistant gastric cancer cells. Discussion/Conclusion: In summary, sFRP4 might play a critical role in resistance to cisplatin and oxaliplatin, cell metastasis, and poor prognosis in gastric cancer via the Wnt-β-catenin pathway. Investigations of the molecular mechanism underlying sFRP4-modulated cancer progression and chemotherapeutic outcomes can provide additional therapeutic strategies for gastric cancer.
Inhibition of Heat Shock Protein 90 Lowered Intraocular Pressure without Affecting the Production of Aqueous Humor in Rabbits
Authors: Takahashi Yuji , Otsuka Tomohiro , Arakawa Reijiro , Naito Akira
Published: December 2023

Introduction: Heat shock protein (Hsp) 90 is one of the most abundant proteins in unstressed cells and regulates stability and functional maintenance of client proteins. In ocular tissue, Hsp90 is widely expressed in the cornea and retina and has multiple roles in these tissues. The expression of HSPs was induced in the retinas of glaucomatous patients and laser-induced glaucoma in monkey while their mechanisms remain to be elucidated. For this reason, we tried to elucidate the role of Hsp90 in intraocular pressure (IOP) regulation in rabbits. Methods: IOP was measured by a pneumatonometer before and after intracameral injection of Hsp90 inhibitors. The aqueous flow rate was measured by fluorophotometry. Trans-epithelial electrical resistance was measured in primary human trabecular meshwork cells. Results: 17-AAG, a specific Hsp90 inhibitor, significantly lowered IOP at concentrations of more than 30 μm in normotensive rabbits. Other Hsp90 inhibitors also significantly lowered IOP in normotensive rabbits at a dose of 100 μm. No reduction of aqueous humor production was observed by injection of 17-AAG in rabbits. Topical administration of pilocarpine tended to attenuate the IOP-lowering effects induced by the Hsp90 inhibitor. No reduction of trans-epithelial electrical resistance was observed by inhibition of Hsp90 in culture cells. Conclusions: These results indicated that intraocular Hsp90 regulates IOP, and the inhibition of Hsp90 by Hsp90 inhibitor decreases IOP without affecting aqueous humor production in rabbits. Further research in elucidating the mechanism of Hsp90 inhibitors will result in a better understanding of the role of Hsp90 in the regulation of IOP.
Recurrent Mutations in Refractory/Relapsed Diffuse Large B-Cell Lymphoma by Targeted Gene Sequencing
Authors: Sharma Aditi , Das Ashim , Bal Amanjit , Srinivasan Radhika , Malhotra Pankaj , Prakash Gaurav , Kumar Rajender
Published: December 2023

Introduction: Whole-genome sequencing of diffuse large B-cell lymphoma (DLBCL) has identified recurrent mutations involved in pathogenesis and potentially affecting response to therapy. In this pilot study, a targeted gene panel was created to identify mutations associated with relapse/refractoriness. Material and Methods: A 14-gene targeted panel was designed to sequence thirteen patients who were in remission and 8 cases that had relapsed/refractory to treatment. A paired diagnostic biopsy and a relapse biopsy were sequenced to find genes repeatedly altered in relapse. Results: A total of 751 nonsynonymous and truncating mutations were identified. Truncated mutations in NOTCH1, TNFAIP3, and CD58 were associated with poor treatment outcomes. In cases that did not respond to treatment, a high number of mutations were found in the EZH2 gene, followed by the DNA-binding domain of TP53 and MYD88. Termination mutations in the intracellular domain of NOTCH were found in 75% of non-responsive cases. Co-occurrence of loss of function mutations of TNFAIP3 and missense mutations in MYD88 was associated with a non-responsive cohort. Discussion: The study highlights mutations associated with chemotherapeutic response in DLBCL with implications for initial diagnostic biopsy response prediction.
Clarification of ambiguous genus records for Australian Cleridae (Coleoptera: Cleroidea)
Authors: BARTLETT JUSTIN S.
Published: December 2023

The status of the genera Balcus Sharp, Gastrocentrum Gorham, Korynetes Herbst, Solervicensia Barr, Monophylla Spinola and Thanasimus Latreille in Australia is assessed based on review of dubious or ambiguous published Australian records of the following species-group taxa: Balcus violaceus (Fabricius), a New Zealand species listed as Australian by Schenkling (1906); Gastrocentrum dux (Westwood), described from Australia by Westwood (1853); Korynetes abdominalis (Fabricius), an Indian species listed as Australian by Schenkling (1906); Korynetes coeruleus (De Geer), a Palearctic species with a synonym, Corynetes unicolor Chevrolat, 1876, described from Australia; Monophylla terminata (Say), a North American species with a synonym, Elasmocerus picticollis Blackburn, 1901, described from Australia; Solervicensia ovata (Spinola), a South American species with two synonyms (one newly proposed) described from Australia, viz. Labasiella duboulayi Pic, 1950, and Korynetes nigrosignatus Pic, 1941 new synonym; and Thanasimus dubius (Fabricius), a North American species introduced to Australia for the biological control of Ips grandicollis (Eichhoff) (Scolytinae). All six of the abovementioned genera are deemed absent from Australia due to the lack of evidence for the occurrence of representative species within the Australian political region.
Evaluating the Performance of the North Pacific Victoria Mode as an ENSO Predictor Based on Multimodel Ensemble Hindcasts
Authors: Ren Zhengyi , Ding Ruiqiang , Mao Jiangyu , Ji Kai , Li Zongrong
Published: December 2023

The Victoria mode (VM), similar to the Pacific meridional mode (PMM), is forced by North Pacific Oscillation atmospheric variability. Both the boreal spring VM and PMM can trigger the onset of El Niño–Southern Oscillation (ENSO) events in the following winter. Previous studies have examined the precursor relationship between the PMM and ENSO based on a subset of models drawn from the North American Multimodel Ensemble (NMME) system. They suggested that the PMM can act as a precursor to El Niño events, whereas it fails to predict La Niña events. Utilizing the hindcasts of these models from NMME, this study further investigates the role of the VM as an ENSO predictor to examine the real usefulness of the VM for ENSO prediction. When compared with the PMM, the VM can predict both El Niño and La Niña events with some skill, showing that the VM seems to be a more reliable predictor of ENSO. We found that the unique role of the VM in ENSO prediction originates from the symmetric impact of the VM on ENSO events. The VM, as a basin-scale sea surface temperature (SST) pattern, combines the role of the SST over the subtropical northeastern Pacific that is similar to the PMM in initializing El Niño events with that of the SST over the western North Pacific that is different from PMM in initializing La Niña events, resulting in the symmetric effect of the VM on ENSO prediction. Thus, it is useful to consider VM variability as a reference for ENSO prediction.

Significance Statement

We aim to investigate whether the robust relationship between the boreal spring Victoria mode (VM) and the following winter ENSO in observations and climate models has any real predictive use, thus bridging the gap between theory and practical application. Our analyses based mainly on model hindcast datasets examine the forecasting skill of the VM for El Niño and La Niña events. We also reveal the symmetric impact of VM on ENSO through the analysis of observations, which explains the VM’s skill in predicting both El Niño and La Niña events. This study deepens our understanding of the effect of North Pacific SST variability on ENSO.