bluuebunny/crossref_metadata_2025_split huggingface dataset:
2BALANCE: a cognitive-motor dual-task protocol for individuals with vestibular dysfunction
Authors: Danneels Maya , Van Hecke Ruth , Leyssens Laura , Degeest Sofie , Cambier Dirk , van de Berg Raymond , Van Rompaey Vincent , Maes Leen 
Published: April 2023

IntroductionAside from primary vestibular symptoms such as vertigo and dizziness, persons with vestibular dysfunction frequently express cognitive and motor problems. These symptoms have mainly been assessed in single-task setting, which might not represent activities of daily living accurately. Therefore, a dual-task protocol, consisting of the simultaneous performance of cognitive and motor tasks, was developed. This protocol assesses cognitive and motor performance in general, as well as cognitive-motor interference in specific.Methods and analysisThe motor component of the 2BALANCE protocol consists of a static and dynamic postural task. These motor tasks are combined with different cognitive tasks assessing visuospatial cognition, processing speed, working memory and response inhibition. First, test–retest reliability will be assessed with an interval of 2 weeks in a group of young adults. Second, the 2BALANCE protocol will be validated in persons with bilateral vestibulopathy. Finally, the protocol will be implemented in persons with unilateral vestibular loss.Discussion and conclusionsThe 2BALANCE project aims to elucidate the impact of vestibular dysfunction on cognitive and motor performance in dual-task setting. This protocol represents everyday situations better than single-task protocols, as dual-tasks such as reading street signs while walking are often encountered during daily activities. Ultimately, this project could enable individualised and holistic clinical care in these patients, taking into account single as well as dual-task performance.Ethics and disseminationThe current study was approved by the ethics committee of Ghent University Hospital on 5 July 2019 with registration number B670201940465. All research findings will be disseminated in peer-reviewed journals and presented at vestibular as well as multidisciplinary international conferences and meetings.Trials registration numberNCT04126798.
Value of Schwartz Rounds in promoting the emotional well-being of healthcare workers: a qualitative study
Authors: Ng Lillian , Schache Kiralee , Young Marie , Sinclair Joanna 
Published: April 2023

ObjectivesSchwartz Rounds are forums that enable healthcare staff to reflect on emotional and social dimensions of their work. In this study, we aimed to explore the experiences of Schwartz Rounds on emotional aspects of care and practice within a clinical environment.DesignUsing qualitative methods, we interviewed participants individually and in focus groups. Interviews were recorded, transcribed and analysed by thematic analysis.SettingThe study was based at a public health service Te Whatu Ora Counties Manukau in Auckland, New Zealand’s largest, most ethnically diverse population.ParticipantsParticipants were panellists who took part in successive Schwartz Rounds over a 10-month period. There were 17 participants with a range of experience (1–30 years) and occupations including clinical, allied, technical and administrative staff from medical specialties of plastic surgery, pain services, emergency medicine, intensive care, organ donation services, COVID-19 response and palliative care services.ResultsThree themes were identified: the need for emotional processing, valuing guided reflection and realising our humanity. The third theme ‘realising our humanity’ comprised altruism, connection and compassion. Schwartz Rounds provided staff with clear benefits: emotionally resonant experiences within an environment of psychological safety and connection to the wider organisation. The daunting nature of emotional disclosure was mitigated by a supportive audience.ConclusionThere is an organisational imperative to ensure that staff have opportunities to process intense emotions associated with healthcare work. Schwartz Rounds are one means to attend to the emotional welfare of healthcare staff, enabling them to gain different perspectives in the care of their patients and colleagues within system constraints.
Economic evaluation of an integrated virtual care programme for people with chronic illness who are frequent users of health services in Australia
Authors: Carter Hannah E , Wallis Shannon , McGowan Kelly , Graves Nicholas , Pitt Rachelle , Coffey Sue , Phillips Rachel , Parcell Melinda 
Published: April 2023

ObjectiveThe MeCare programme is a tailored virtual care initiative targeted at frequent users of health services who have at least one chronic condition including cardiovascular disease, chronic respiratory disease, diabetes or chronic kidney disease. The programme aims to prevent unnecessary hospitalisations by helping patients to self-manage, improve their health literacy and engage in positive health behaviours. This study investigates the impact of the MeCare programme on healthcare resource use, costs and patient-reported outcomes.Methods and analysisA retrospective pre–post study design was adopted. Data on emergency department presentations, hospital admissions, outpatient appointments and their associated costs were obtained from administrative databases. Probabilistic sensitivity analysis using Monte Carlo simulation was used to model changes in resource use and costs prior to, and following, participant enrolment on the MeCare programme. Generalised linear models were used to investigate the observed changes in patient-reported outcomes.ResultsThe MeCare programme cost $A624 per participant month to deliver. Median monthly rates of ED presentations, hospital admissions and average length of stay post-MeCare reduced by 76%, 50% and 12%, respectively. This translated to a median net cost saving of $A982 per participant month (IQR: −1936; −152). A significant, positive trend in patient experience based on responses to the Patient Assessment of Care for Chronic Conditions Questionnaire was observed over the duration of programme enrolment.DiscussionThe MeCare programme is likely to result in substantial cost savings to the health system, while maintaining or improving patient-reported outcomes. Further research in multisite randomised studies is needed to confirm the generalisability of these results.
Comparing biparametric to multiparametric MRI in the diagnosis of clinically significant prostate cancer in biopsy-naive men (PRIME): a prospective, international, multicentre, non-inferiority within-patient, diagnostic yield trial protocol
Authors: Asif Aqua , Nathan Arjun , Ng Alexander , Khetrapal Pramit , Chan Vinson Wai-Shun , Giganti Francesco , Allen Clare , Freeman Alex , Punwani Shonit , Lorgelly Paula , Clarke Caroline S , Brew-Graves Chris , Muirhead Nicola , Emberton Mark , Agarwal Ridhi , Takwoingi Yemisi , Deeks Jonathan J , Moore Caroline M , Kasivisvanathan Veeru 
Published: April 2023

IntroductionProstate MRI is a well-established tool for the diagnostic work-up for men with suspected prostate cancer (PCa). Current recommendations advocate the use of multiparametric MRI (mpMRI), which is composed of three sequences: T2-weighted sequence (T2W), diffusion-weighted sequence (DWI) and dynamic contrast-enhanced sequence (DCE). Prior studies suggest that a biparametric MRI (bpMRI) approach, omitting the DCE sequences, may not compromise clinically significant cancer detection, though there are limitations to these studies, and it is not known how this may affect treatment eligibility. A bpMRI approach will reduce scanning time, may be more cost-effective and, at a population level, will allow more men to gain access to an MRI than an mpMRI approach.MethodsProstate Imaging Using MRI±Contrast Enhancement (PRIME) is a prospective, international, multicentre, within-patient diagnostic yield trial assessing whether bpMRI is non-inferior to mpMRI in the diagnosis of clinically significant PCa. Patients will undergo the full mpMRI scan. Radiologists will be blinded to the DCE and will initially report the MRI using only the bpMRI (T2W and DWI) sequences. They will then be unblinded to the DCE sequence and will then re-report the MRI using the mpMRI sequences (T2W, DWI and DCE). Men with suspicious lesions on either bpMRI or mpMRI will undergo prostate biopsy. The main inclusion criteria are men with suspected PCa, with a serum PSA of ≤20 ng/mL and without prior prostate biopsy. The primary outcome is the proportion of men with clinically significant PCa detected (Gleason score ≥3+4 or Gleason grade group ≥2). A sample size of at least 500 patients is required. Key secondary outcomes include the proportion of clinically insignificant PCa detected and treatment decision.Ethics and disseminationEthical approval was obtained from the National Research Ethics Committee West Midlands, Nottingham (21/WM/0091). Results of this trial will be disseminated through peer-reviewed publications. Participants and relevant patient support groups will be informed about the results of the trial.Trial registration numberNCT04571840.
Stoichiometry-controlled chirality inversion in the amide-linked zinc bisporphyrinates induced by amino acid esters
Authors: Zhu Jiaxing , Fu Fangfang , Zhang Zhihao , Hu Chuanjiang , Wang Yong 
Published: April 2023

We investigated chirality transfer processes with two amide-linked zinc bisporphyrinates as hosts and chiral amino acid esters as guests. The linkers in these hosts contain a coordination site (pyridyl nitrogen or amino nitrogen). CD spectra were measured after titration of these zinc bisporphyrinates with amino acid esters. The CD spectra show that the signals were inverted during the titration. This result suggests that there is a two-step chirality induction process, which is most likely dominated by the corresponding 1:1 and 1:2 host-guest complexes. In the 1:1 complexes, the pyridyl nitrogen or amino nitrogen in the linkers is coordinated with zinc. NMR spectra confirmed such coordination interactions. Theoretical calculations also confirmed the corresponding chirality induction and inversion. This work provides a useful strategy to tune chirality transfer processes by introducing an extra coordination site in the linker.
Pd(II)dipyrrinato complexes: Synthesis, crystal structure and their antibacterial applications
Authors: Manav Neha , Chavda Jaydeepsinh , Kidwai Saqib , Singh Ramandeep , Mori Shigeki , Gupta Iti 
Published: April 2023

The synthesis and biological studies of a series of Pd(II)dipyrrinato complexes are reported. The thiogalactosyl and/or oligoethyleneglycol moieties were linked with themeso-aryl rings of the Pd(II)dipyrrinato complexes. The Pd(II)dipyrrinato complexes were characterized by MASS, IR, UV-Vis, and NMR spectroscopic techniques. Single crystal X-ray structure of the homoleptic Pd(II)dipyrrinato complex (Pd1) revealed typical square planar geometry around the metal center. The anti-bacterial studies of Pd(II) dipyrrinato complexes were performed on theM. Tuberculosis H37Rv and M. Bovis BCG strains and complex Pd4 showed excellent anti-TB activity with MIC values of 25 [Formula: see text]M and 12.5 [Formula: see text]M, respectively. The ease of synthesis and good MIC values of Pd(II)dipyrrinato complexes make them promising candidates for anti-TB activity.
Early Jurassic orthopteran insects from the southern Junggar Basin, NW China, with discussion of biodiversity changes of Orthoptera across the Triassic–Jurassic boundary
Authors: Xu Chunpeng , Fang Yanan , Fang Yan , Wang He , Zhou Qian , Jiang Xueying , Zhang Haichun 
Published: April 2023

Abstract

Orthoptera constitutes an important ecological component of the global fauna, but the order's Early Jurassic record is limited in China and its evolution is poorly understood after the end-Triassic mass extinction. Several orthopterans are described herein from the Lower Jurassic Badaowan and Sangonghe formations of the southern Junggar Basin, Xinjiang, NW China. From the Badaowan Formation, a new species,
Parahagla cheni
sp. nov., is established and assigned to Chifengiinae (Hagloidea: Prophalangopsidae), which represents the oldest record of this subfamily. From the Sangonghe Formation, a forewing fragment is attributed to
Sinagryllus xinjiangensis

Wang
et al.
, 2019

(Grylloidea: Baissogryllidae); another forewing fragment and a metathoracic leg without attribution are also described. The discovery of these fossils increases the biodiversity of Orthoptera in the Early Jurassic, and further indicates that orthopterans probably flourished in the Junggar area during the Early Jurassic. An analysis of orthopteran biodiversity at generic and species levels reveals an extinction in Orthoptera in the Late Triassic, especially for the superfamilies Hagloidea and Oedischioidea, which suffered a substantial extinction. This extinction occurred in the Late Triassic, earlier than the mass extinction of marine animals at the end of the Triassic.
An AADL Contract Language Supporting Integrated Model- and Code-Level Verification
Authors: Hatcliff John , Stewart Danielle , Belt Jason , . Robby , Schwerdfeger August 
Published: April 2023

Model-based systems engineering approaches support the early adoption of a model - a collection of abstractions - of the system under development. The system model can be augmented with key properties of the system including formal specifications of system behavior that codify portions of system and unit-level requirements. There are obvious gaps between the model with formally specified behavior and the deployed system. Previous work on component contract languages has shown how behavior can be specified in models defined using the Architecture Analysis and Design Language (AADL) - a SAE International standard (AS5506C). That work demonstrated the effectiveness of model-level formal methods specification and verification but did not provide a strong and direct connection to system implementations developed using conventional programming languages. In particular, there was no refinement of model-level contracts to programming language-level contracts nor a framework for formally verifying that program code conforms to model-level behavioral specifications.
To address these gaps and to enable the practical application of model-contract languages for verification of deployed high-integrity systems, this paper describes the design of the GUMBO AADL contract language that integrates and extends key concepts from earlier contract languages. The GUMBO contract language (GCL) is closely aligned to a formal semantics of the AADL run-time framework, which provides a platform- and language- independent specification of AADL semantics. We have enhanced the HAMR AADL code generation framework to translate model-level contracts to programming language-level contracts in the Slang high-integrity language. We demonstrate how the Logika verification tool can automatically verify that Slang-based AADL component implementations conform to contracts, both at the code-level and model-level. Slang-based implementations of AADL systems can be executed directly or compiled to C for deployments on Linux or the seL4 verified microkernel.
BET Inhibition Sensitizes Immunologically Cold Rb-Deficient Prostate Cancer to Immune Checkpoint Blockade
Authors: Olson Brian M. , Chaudagar Kiranj , Bao Riyue , Saha Sweta Sharma , Hong Christina , Li Marguerite , Rameshbabu Srikrishnan , Chen Raymond , Thomas Alison , Patnaik Akash 
Published: April 2023

Abstract
Non–T-cell–inflamed immunologically “cold” tumor microenvironments (TME) are associated with poor responsiveness to immune checkpoint blockade (ICB) and can be sculpted by tumor cell genomics. Here, we evaluated how retinoblastoma (Rb) tumor-suppressor loss-of-function (LOF), one of the most frequent alterations in human cancer and associated with lineage plasticity, poor prognosis, and therapeutic outcomes, alters the TME, and whether therapeutic strategies targeting the molecular consequences of Rb loss enhance ICB efficacy. We performed bioinformatics analysis to elucidate the impact of endogenous Rb LOF on the immune TME in human primary and metastatic tumors. Next, we used isogenic murine models of Rb-deficient prostate cancer for in vitro and in vivo mechanistic studies to examine how Rb loss and bromodomain and extraterminal (BET) domain inhibition (BETi) reprograms the immune landscape, and evaluated in vivo therapeutic efficacy of BETi, singly and in combination with ICB and androgen deprivation therapy. Rb loss was enriched in non–T-cell–inflamed tumors, and Rb-deficient murine tumors demonstrated decreased immune infiltration in vivo. The BETi JQ1 increased immune infiltration into the TME through enhanced tumor cell STING/NF-κB activation and type I IFN signaling within tumor cells, resulting in differential macrophage and T-cell–mediated tumor growth inhibition and sensitization of Rb-deficient prostate cancer to ICB. BETi can reprogram the immunologically cold Rb-deficient TME via STING/NF-κB/IFN signaling to sensitize Rb-deficient prostate cancer to ICB. These data provide the mechanistic rationale to test combinations of BETi and ICB in clinical trials of Rb-deficient prostate cancer.
Abstract 4066: Lipid nanoparticle library towards development next generation genomic medicines
Authors: Thomas Anitha , Jain Nikita , Nazaripour Sedigheh , Higgins Rehan , Chen Zhengyu , Abraham Suraj , Yee Leanna , Abbina Srinivas , Namala Gayatri Mehar , Son Helena , Sadat Sams , Chemmannur Sijo , Anantha Malathi , Sharma Ruchi , Tickner Kobe , Boyer Eve , Tsai Shannon , Thambatti Seetalakshmi , Mayya Vinay , Soon Emily , Paquette Jay 
Published: April 2023

Abstract
Ionizable amino lipids are a major constituent of the lipid nanoparticles for delivering nucleic acid therapeutics (e.g., DLin-MC3-DMA in ONPATTRO®, ALC-0315 in Comirnaty®, SM-102 in Spikevax®). Scarcity of lipids that are suitable for cell therapy, vaccination, and gene therapies continue to be a problem in advancing many potential diagnostic/therapeutic/vaccine candidates to the clinic.
Herein, we describe the development of novel ionizable lipids to be used as functional excipients for designing vehicles for nucleic acid therapeutics/vaccines in vivo or ex vivo use in cell therapy applications. We first studied the transfection efficiency (TE) of LNP-based mRNA formulations of these ionizable lipid candidates in primary human T cells and established a workflow for engineering of primary immune T cells. We then adapted this workflow towards bioengineering of CAR constructs to T cells towards non-viral CAR T therapy. Lipids were also tested in rodents for vaccine applications using self-amplifying RNA (saRNA) encoding various antigens. We have then evaluated various ionizable lipid candidates and their biodistribution along with the mRNA/DNA translation exploration using various LNP compositions. Further, using ionizable lipids from the library, we have shown gene editing of various targets in rodents.
We believe that these studies will pave the path to the advancement in nucleic acid based therapeutics and vaccines, or cell & gene therapy agents for early diagnosis and detection of cancer, and for targeted genomic medicines towards cancer treatment and diagnosis.
Citation Format: Anitha Thomas, Nikita Jain, Sedigheh Nazaripour, Rehan Higgins, Zhengyu Chen, Suraj Abraham, Leanna Yee, Srinivas Abbina, Gayatri Mehar Namala, Helena Son, Sams Sadat, Sijo Chemmannur, Malathi Anantha, Ruchi Sharma, Kobe Tickner, Eve Boyer, Shannon Tsai, Seetalakshmi Thambatti, Vinay Mayya, Emily Soon, Jay Paquette. Lipid nanoparticle library towards development next generation genomic medicines. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4066.
Abstract 4086: Mitigating the CD5 CAR-CD5 interaction enhances the functionality of CD5 CAR-T cells by alleviating the T-cell fratricide
Authors: Ho Lee Young , Yu Seung Rok , Jeong Jeong Hoon , Lee Hyeong Ji , Cho Hyeon Jeong , Kim Hyung Cheol 
Published: April 2023

Abstract
Chimeric antigen receptor (CAR) T-cell therapy has been used with unprecedented clinical responses in relapsed/refractory B-ALL or B-NHL, MM patients. However, CAR-T therapy has not yet been proven effective in other hematological malignancies, such as T cell lymphoma and leukemia (T-NHL/T-ALL) and acute myeloid leukemia (AML). Developing CAR-T cells for patients with T-cell malignancies remains challenging as most CARs targeting T-lineage antigens, such as CD5, CD7, and CD3, target themselves, potentially resulting in fratricide of CAR-T cells. Thus, there is a need for technical approaches to alleviate the fratricide of CAR-T to treat T-cell malignancies successfully. As part of the approach, we studied whether the affinity of CAR and cognate antigen expression of CAR-T cells influence the intensity of CAR-T`s fratricide and hypothesized that if a single chain Fragment variable (scFv) with a low intensity of fratricide is applied to T-lineage antigen-downregulated CAR-T cells, the effector function of CAR-T cell targeting T cell antigen can be maximized. For this, we screened full human scFvs targeting CD5, a pan T-cell marker, tested the affinity of scFvs for CD5 antigen, and generated anti-CD5 CAR-T cells (CAR5). We evaluated the intensity of in vitro fratricide in CAR5 based on cell expansion and cytokine secretion in vitro and tested their anti-tumor activity in a CD5+ T-ALL xenograft model (Jurkat). In addition, to minimize CAR recognition to a cognate antigen expressed in CAR-T cells, we also generated CD5-downregulated CAR5s (CD5-KD CAR5) using a short hairpin RNA cassette integrated into an anti-CD5 CAR vector to test if the downregulation of CD5 in CAR5s can reduce the fratricide. We found that a CAR5 clone (C7CAR5) with the lowest level of fratricide in vitro, showed superior anti-tumor activity compared to other CAR5s in vivo and that CD5-downregulated C7 CAR5 (CD5-KD C7CAR5) further reduced the fratricide, maximizing the anti-tumor activity. In conclusion, we demonstrate that high-affinity CAR may not always show superior functionality in T cell malignancy CAR-T therapy, explaining one or more strategies to alleviate the fratricide are required. These studies provide the foundation for developing CD5 CART products to treat relapsed T-cell malignancies.
Citation Format: Lee Young Ho, Seung Rok Yu, Jeong Hoon Jeong, Hyeong Ji Lee, Hyeon Jeong Cho, Hyung Cheol Kim. Mitigating the CD5 CAR-CD5 interaction enhances the functionality of CD5 CAR-T cells by alleviating the T-cell fratricide. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4086.