bluuebunny/crossref_metadata_2025_split huggingface dataset:
Group cognitive stimulation therapy versus usual care for people with intellectual disabilities and dementia (CST-IDD) in the UK: protocol for a mixed-methods feasibility randomised controlled trial
Authors: Ali Afia , Aguirre Elisa , Carter Joanna , Hoare Sarah , Brackley Kate , Goulden Nia , Hoare Zoe , Clarke Caroline S , Charlesworth Georgina , Acton Danny , Spector Aimee 
Published: April 2023

IntroductionThe prevalence of dementia is almost five times higher in people with intellectual disabilities compared with the general population. However, evidence-based treatments for this population are lacking, as most randomised controlled trials for dementia interventions have not included people with intellectual disabilities. Cognitive stimulation therapy (CST) has a robust evidence base in the general dementia population, consistently showing benefits to cognition, quality of life and being cost-effective. We are conducting a mixed-methods feasibility trial of group CST for people with intellectual disabilities and dementia, to determine if a future definitive randomised controlled trial is feasible.Methods and analysisFifty individuals with intellectual disabilities and dementia will be randomised to either the intervention arm (14 sessions of group CST plus treatment as usual) or the control arm (treatment as usual). Randomisation will occur after informed consent has been obtained and baseline assessments completed. Each arm will have 25 participants, with the intervention arm divided into five or more CST groups with three to five participants in each. The outcomes will be feasibility of recruitment, acceptability and adherence of the intervention, suitability of study outcome measures and feasibility of collecting resource use data. Quantitative and qualitative approaches, including semistructured interviews with group participants, carers and group facilitators, will be employed to assess these outcomes.Ethics and disseminationThis study has been approved by Essex REC (Ref: 21/EE/027) and the HRA ethical approval process through the Integrated Research Application System (IRAS ID: 306 756). We plan to publish the results in peer-reviewed journals and conferences as well as provide feedback to funders, sponsors and study participants.Trial registration numberISRCTN88614460.
Survey of exercise testing and training in cystic fibrosis clinics in the UK: a decade of progress
Authors: Tomlinson Owen William , Saynor Zoe L , Stevens Daniel , Antoun Joe , Urquhart Don S , Williams Craig Anthony 
Published: April 2023

ObjectivesRegular exercise testing is recommended for people with cystic fibrosis (pwCF), as is the provision and regular review of exercise training programmes. A previous survey on exercise testing and training for pwCF in the UK was conducted over a decade ago. With the landscape of CF changing considerably during this time, this survey aimed to evaluate UK-based exercise testing and training practices for pwCF a decade on.DesignCross-sectional, online survey.ParticipantsA survey was distributed electronically to UK CF clinics and completed by the individual primarily responsible for exercise services. Descriptive statistics and qualitative analyses were undertaken.ResultsIn total, 31 CF centres participated, representing ~50% of UK specialist clinics. Of these, 94% reported using exercise testing, 48% of which primarily use cardiopulmonary exercise testing. Exercise testing mostly occurs at annual review (93%) and is most often conducted by physiotherapists (62%). A wide variation in protocols, exercise modalities, normative reference values and cut-offs for exercise-induced desaturation are currently used. All centres reportedly discuss exercise training with pwCF; 94% at every clinic appointment. However, only 52% of centres reportedly use exercise testing to inform individualised exercise training. Physiotherapists typically lead discussions around exercise training (74%).ConclusionsThese data demonstrate that the majority of respondent centres in the UK now offer some exercise testing and training advice for pwCF, representing a marked improvement over the past decade. However, continued efforts are now needed to standardise exercise practices, particularly regarding field testing practices and the translation of test results into personalised training programmes for pwCF.
Morpho-mechanistic screening criteria for the echocardiographic detection of rheumatic heart disease
Authors: Hunter Luke David , Doubell Anton Frans , Pecoraro Alfonso Jan Kemp , Monaghan Mark , Lloyd Guy , Lombard Carl , Herbst Philipus George 
Published: April 2023

IntroductionScreening echocardiography, guided by the current World Heart Federation (WHF) criteria, has important limitations that impede the establishment of large-scale rheumatic heart disease (RHD) control programmes in endemic regions. The criteria misclassify a significant number of normal cases as borderline RHD. Prior attempts to simplify them are limited by incorporation bias due to the lack of an externally validated, accurate diagnostic test for RHD. We set out to assess novel screening criteria designed to avoid incorporation bias and to compare this against the performance of the current WHF criteria.MethodsThe performance of the WHF and the morpho-mechanistic (MM) RHD screening criteria (a novel set of screening criteria that evaluate leaflet morphology, motion and mechanism of regurgitation) as well as a simplified RHD MM ‘rule-out’ test (based on identifying a predefined sign of anterior mitral valve leaflet restriction for the mitral valve and any aortic regurgitation for the aortic valve) were assessed in two contrasting cohorts: first, a low-risk RHD cohort consisting of children with a very low-risk RHD profile. and second, a composite reference standard (CRS) RHD-positive cohort that was created using a composite of two criteria to ensure a cohort with the highest possible likelihood of RHD. Subjects included in this group required (1) proven, prior acute rheumatic fever and (2) current evidence of predefined valvular regurgitation on echocardiography.ResultsIn the low-risk RHD cohort (n=364), the screening specificities for detecting RHD of the MM and WHF criteria were 99.7% and 95.9%, respectively (p=0.0002). The MM rule-out test excluded 359/364 cases (98.6%). In the CRS RHD-positive cohort (n=65), the screening sensitivities for the detection of definite RHD by MM and WHF criteria were 92.4% and 89.2%, respectively (p=0.2231). The MM RHD rule-out test did not exclude any cases from the CRS RHD-positive cohort.ConclusionOur proposed MM approach showed an equal sensitivity to the WHF criteria but with significantly improved specificity. The MM RHD rule-out test excluded RHD-negative cases while identifying all cases within the CRS RHD-positive cohort. This holds promise for the development of a two-step RHD screening algorithm to enable task shifting in RHD endemic regions.
Vector Aided Microenvironment programming (VAMP): reprogramming the TME with MVA virus expressing IL-12 for effective antitumor activity
Authors: Seclì Laura , Infante Luigia , Nocchi Linda , De Lucia Maria , Cotugno Gabriella , Leoni Guido , Micarelli Elisa , Garzia Irene , Avalle Lidia , Sdruscia Giulia , Troise Fulvia , Allocca Simona , Romano Giuseppina , Scarselli Elisa , D'Alise Anna Morena 
Published: April 2023

BackgroundTumor microenvironment (TME) represents a critical hurdle in cancer immunotherapy, given its ability to suppress antitumor immunity. Several efforts are made to overcome this hostile TME with the development of new therapeutic strategies modifying TME to boost antitumor immunity. Among these, cytokine-based approaches have been pursued for their known immunomodulatory effects on different cell populations within the TME. IL-12 is a potent pro-inflammatory cytokine that demonstrates striking immune activation and tumor control but causes severe adverse effects when systemically administered. Thus, local administration is considered a potential strategy to achieve high cytokine concentrations at the tumor site while sparing systemic adverse effects.MethodsModified Vaccinia Ankara (MVA) vector is a potent inducer of pro-inflammatory response. Here, we cloned IL-12 into the genome of MVA for intratumoral immunotherapy, combining the immunomodulatory properties of both the vector and the cargo. The antitumor activity of MVA-IL-12 and its effect on TME reprogramming were investigated in preclinical tumor models. RNA sequencing (RNA-Seq) analysis was performed to assess changes in the TME in treated and distal tumors and the effect on the intratumoral T-cell receptor repertoire.ResultsIntratumoral injection of MVA-IL-12 resulted in strong antitumor activity with the complete remission of established tumors in multiple murine models, including those resistant to checkpoint inhibitors. The therapeutic activity of MVA-IL-12 was associated with very low levels of circulating cytokine. Effective TME reprogramming was demonstrated on treatment, with the reduction of immunosuppressive M2 macrophages while increasing pro-inflammatory M1, and recruitment of dendritic cells. TME switch from immunosuppressive into immunostimulatory environment allowed for CD8 T cells priming and expansion leading to tumor attack.ConclusionsIntratumoral administration of MVA-IL-12 turns immunologically ‘cold’ tumors ‘hot’ and overcomes resistance to programmed cell death protein-1 blockade.
What is the best target in a treat-to-target strategy in rheumatoid arthritis? Results from a systematic review and meta-regression analysis
Authors: Messelink Marianne A , den Broeder Alfons A , Marinelli Florine E , Michgels Edwin , Verschueren P , Aletaha Daniel , Tekstra Janneke , Welsing Paco M J 
Published: April 2023

ObjectivesA treat-to-target (T2T) strategy has been shown to be superior to usual care in rheumatoid arthritis (RA), but the optimal target remains unknown. Targets are based on a disease activity measure (eg, Disease Activity Score-28 (DAS28), Simplified Disease Activity Indices/Clinical Disease Activity Indices (SDAI/CDAI), and a cut-off such as remission or low disease activity (LDA). Our aim was to compare the effect of different targets on clinical and radiographic outcomes.MethodsCochrane, Embase and (pre)MEDLINE databases were searched (1 June 2022) for randomised controlled trials and cohort studies after 2003 that applied T2T in RA patients for ≥12 months. Data were extracted from individual T2T study arms; risk of bias was assessed with the Cochrane Collaboration tool. Using meta-regression, we evaluated the effect of the target used on clinical and radiographic outcomes, correcting for heterogeneity between and within studies.Results115 treatment arms were used in the meta-regression analyses. Aiming for SDAI/CDAI-LDA was statistically superior to targeting DAS-LDA regarding DAS-remission and SDAI/CDAI/Boolean-remission outcomes over 1–3 years. Aiming for SDAI/CDAI-LDA was also significantly superior to DAS-remission regarding both SDAI/CDAI/Boolean-remission (over 1–3 years) and mean SDAI/CDAI (over 1 year). Targeting DAS-remission rather than DAS-LDA only improved the percentage of patients in DAS-remission, and only statistically significantly after 2–3 years of T2T. No differences were observed in Health Assessment Questionnaire and radiographic progression.ConclusionsTargeting SDAI/CDAI-LDA, and to a lesser extent DAS-remission, may be superior to targeting DAS-LDA regarding several clinical outcomes. However, due to the risk of residual confounding and the lack of data on (over)treatment and safety, future studies should aim to directly and comprehensively compare targets.PROSPERO registration numberCRD42021249015.
Hypernuclei production with a modified coalescence model in BUU transport calculations
Authors: Balassa Gábor , Wolf György 
Published: April 2023

AbstractIn this paper, the usual momentum- and coordinate-space distance criteria for creating nuclear clusters in transport simulations are readdressed by using a dynamical, covariant description in an off-shell Boltzmann-Uehling-Uhlenbeck transport approach. The free parameter of this clustering scheme is the cluster formation time, which is fitted through the FOPI data of low energy charged cluster multiplicities in Au+Au collisions at 150 A MeV, and 400 A MeV incident energies. The coalescence model is used to estimate the yields of the $$^3$$

3

H$$_\Lambda $$

Λ

, $$^5$$

5

H$$_{\Lambda \Lambda }$$

Λ
Λ

, $$^6$$

6

He$$_{\Lambda \Lambda }$$

Λ
Λ

single and double strange hypernuclei in central Au+Au collisions between 2, and 20 A GeV incident energies, giving comparable results to estimations from other methods.
Analysis of localized CP asymmetry in $${\bar{B}}_{s}^{0} \rightarrow \pi ^+\pi ^-\pi ^{0}(K^{0})$$
Authors: Shi De-Sen , Lü Gang , Zhao Yan-Lin , Na-Wang  , Guo Xin-Heng 
Published: April 2023

AbstractAn investigation about localized CP asymmetries for the processes of $${\bar{B}}_{s}^{0} \rightarrow \pi ^{+}\pi ^{-}\pi ^{0} (K^{0})$$

B

¯

s

0

→

π
+

π
-

π
0

(

K
0

)

is presented in this paper. The innovation of this paper is that there is a consideration of three-particle $$\rho ^0(770)$$

ρ
0

(
770
)

, $$\omega (782)$$

ω
(
782
)

and $$\phi (1020)$$

ϕ
(
1020
)

interferences effect. Generally, $$\omega (782)$$

ω
(
782
)

and $$\phi (1020)$$

ϕ
(
1020
)

both can decay into $$\pi ^+\pi ^-$$

π
+

π
-

pair where can cause extremely small contribution from isospin symmetry breaking. Nevertheless, our analysis shows that $${\bar{B}}_{s}^{0} \rightarrow \pi ^+\pi ^-\pi ^{0}(K^{0})$$

B

¯

s

0

→

π
+

π
-

π
0

(

K
0

)

decay process can bring differential CP asymmetry about $$65\%$$

65
%

($$36\%$$

36
%

) because of isospin symmetry breaking. To be better compared with the data from experimental in the future, we integrate CP asymmetry over the invariant mass and obtain localized CP asymmetry value for the decay $${\bar{B}}_{s}^{0} \rightarrow \pi ^+\pi ^-\pi ^{0} (K^{0})$$

B

¯

s

0

→

π
+

π
-

π
0

(

K
0

)

. We find that there is an evident signal about CP asymmetry at invariant mass value $$m(\pi ^{+}\pi ^{-})$$

m
(

π
+

π
-

)

below the mass of $$\rho ^{0}(770)$$

ρ
0

(
770
)

with the decay $${\bar{B}}_{s}^{0} \rightarrow \pi ^+\pi ^{-}\pi ^{0}$$

B

¯

s

0

→

π
+

π
-

π
0

.
Replica wormhole as a vacuum-to-vacuum transition
Authors: An Yang , Cheng Peng 
Published: April 2023

AbstractThe recent developments related to the black hole information paradox have brought us a confusing object: the replica wormhole. We are trying to better understand the object from the viewpoint of the thermo-mixed double and spontaneous symmetry breaking. In this paper, we show that the replica wormhole can be regarded as a transition between different degenerate vacua, and the corresponding gravitational partition function should be controlled by the manifold of the degenerate vacua. We also check the wormhole partition function in two-dimensional Jackiw–Teitelboim gravity and show that the wormhole saddle is indeed controlled by the dimension of the degenerate vacua. Moreover, it is suggested that the replica wormhole geometries connecting different vacua can be related to the measurement process of soft hair that compares different vacuum configurations.
HMT: A Hardware-centric Hybrid Bonsai Merkle Tree Algorithm for High-performance Authentication
Authors: Shadab Rakin Muhammad , Zou Yu , Gandham Sanjay , Awad Amro , Lin Mingjie 
Published: April 2023

The Bonsai Merkle tree (BMT) is a widely used tree structure for authentication of metadata such as encryption counters in a secure computing system. Common BMT algorithms were designed for traditional Von Neumann architectures with a software-centric implementation in mind and as such, they are predominantly recursive and sequential in nature. However, the modern heterogeneous computing platforms employing Field-Programmable Gate Array (FPGA) devices require concurrency-focused algorithms to fully utilize the versatility and parallel nature of such systems. The recursive nature of traditional BMT algorithms makes them challenging to implement in such hardware-based setups.
Our goal for this work is to introduce HMT, a hardware-friendly BMT algorithm that enables the verification and update processes to function independently and provides the benefits of relaxed update while being comparable to the eager update in terms of update complexity. The methodology of HMT contributes both novel algorithmic revisions and innovative hardware techniques to implementing BMT. We mathematically demonstrate the challenges of potentially unbounded recursions in relaxed BMT updates. To solve this problem, we use a partitioned BMT caching scheme that allocates a separate write-back cache for each BMT level—thus allowing for low and fixed upper bounds for dirty evictions compared to the traditional BMT caches. Then we introduce the aforementioned hybrid BMT algorithm that is hardware-targeted, parallel, and relaxes the update depending on BMT cache hit but makes the update conditions more flexible compared to lazy update to save additional write-backs.
Deploying this new algorithm, we have designed a new BMT controller with a dataflow architecture including speculative buffers and parallel write-back engines to facilitate performance-enhancing mechanisms (like multiple concurrent authentication and independent updates) that were not possible with the conventional lazy algorithm. Our empirical performance measurements on a Xilinx U200 accelerator FPGA have demonstrated that HMT can achieve up to 7× improvement in bandwidth and 4.5× reduction in latency over lazy-update BMT baseline and up to 14% faster execution in standard benchmarks compared to a state-of-the-art, eager-update BMT solution.
Tumor-Derived Small Extracellular Vesicles Inhibit the Efficacy of CAR T Cells against Solid Tumors
Authors: Zhong Wenqun , Xiao Zebin , Qin Zhiyuan , Yang Jingbo , Wen Yi , Yu Ziyan , Li Yumei , Sheppard Neil C. , Fuchs Serge Y. , Xu Xiaowei , Herlyn Meenhard , June Carl H. , Puré Ellen , Guo Wei 
Published: April 2023

Abstract

Chimeric antigen receptor (CAR) T-cell therapy has shown remarkable success in the treatment of hematologic malignancies. Unfortunately, it has limited efficacy against solid tumors, even when the targeted antigens are well expressed. A better understanding of the underlying mechanisms of CAR T-cell therapy resistance in solid tumors is necessary to develop strategies to improve efficacy. Here we report that solid tumors release small extracellular vesicles (sEV) that carry both targeted tumor antigens and the immune checkpoint protein PD-L1. These sEVs acted as cell-free functional units to preferentially interact with cognate CAR T cells and efficiently inhibited their proliferation, migration, and function. In syngeneic mouse tumor models, blocking tumor sEV secretion not only boosted the infiltration and antitumor activity of CAR T cells but also improved endogenous antitumor immunity. These results suggest that solid tumors use sEVs as an active defense mechanism to resist CAR T cells and implicate tumor sEVs as a potential therapeutic target to optimize CAR T-cell therapy against solid tumors.

Significance:
Small extracellular vesicles secreted by solid tumors inhibit CAR T cells, which provide a molecular explanation for CAR T-cell resistance and suggests that strategies targeting exosome secretion may enhance CAR T-cell efficacy.
See related commentary by Ortiz-Espinosa and Srivastava, p. 2637
Identifying Radiographic and Clinical Indicators to Reduce the Occurrence of Nontherapeutic Laparotomy for Blunt Bowel and Mesenteric Injury
Authors: Blackley Shem K. , Smith William C. , Lee Yann-Leei , Kinnard Christopher , Williams Ashley Y. , Butts Charles C. , Mbaka Maryann I. , Haiflich Andrew , Bright Andrew , Simmons Jon D. , Polite Nathan M. 
Published: April 2023

Background Roughly 5% of patients with blunt abdominal trauma (BAT) have a blunt bowel and/or mesenteric injury (BBMI). Determining the need for operative management in these patients can be challenging when hemodynamically stable. Single center studies have proposed scoring systems based on CT findings to guide management. Our study aimed to determine the predictability of abdominopelvic CT scan (CT A/P) findings in conjunction with clinical exam to determine the necessity of operative intervention for BBMI. Methods Patients presenting from 2017 to 2022 to the University of South Alabama Level 1 Trauma Center after motor vehicle collision were retrospectively reviewed. Patients with CT findings suggestive of BBMI were further analyzed, noting CT findings, Glasgow coma scale (GCS), shock index, abdominal exam, operative or nonoperative management, and intraoperative intervention. Results 1098 patients with BAT underwent CT A/P. 139 patients had ≥1 finding suggestive of BBMI. 38 patients underwent surgical exploration and 30 had surgically confirmed BBMI. 27 patients required intervention for BBMI. Univariate analysis indicated that pneumoperitoneum ( p < 0.0001), active extravasation of contrast ( p = 0.0001), hemoperitoneum without solid organ injury (SOI) ( p < 0.0001), peritonitis ( p < 0.0001), and mesenteric stranding( p < 0.05) were significantly associated with intervention. Conclusion In total, 30 patients had surgically confirmed BBMI. Active extravasation, pneumoperitoneum, hemoperitoneum without SOI, mesenteric stranding, and peritonitis were significant indicators of BBMI requiring intervention. CT and clinical findings cannot reliably predict the need for surgical intervention without ≥1 of these findings. Initial nonoperative management with serial clinical exams should be strongly considered to reduce incidence of nontherapeutic laparotomies.
It’s Not Only What You Say, But Also How You Say It: Machine Learning Approach to Estimate Trust from Conversation
Authors: Li Mengyao , Erickson Isabel M , Cross Ernest V , Lee John D 
Published: April 2023

Objective The objective of this study was to estimate trust from conversations using both lexical and acoustic data. Background As NASA moves to long-duration space exploration operations, the increasing need for cooperation between humans and virtual agents requires real-time trust estimation by virtual agents. Measuring trust through conversation is a novel and unintrusive approach. Method A 2 (reliability) × 2 (cycles) × 3 (events) within-subject study with habitat system maintenance was designed to elicit various levels of trust in a conversational agent. Participants had trust-related conversations with the conversational agent at the end of each decision-making task. To estimate trust, subjective trust ratings were predicted using machine learning models trained on three types of conversational features (i.e., lexical, acoustic, and combined). After training, model explanation was performed using variable importance and partial dependence plots. Results Results showed that a random forest algorithm, trained using the combined lexical and acoustic features, predicted trust in the conversational agent most accurately [Formula: see text]. The most important predictors were a combination of lexical and acoustic cues: average sentiment considering valence shifters, the mean of formants, and Mel-frequency cepstral coefficients (MFCC). These conversational features were identified as partial mediators predicting people’s trust. Conclusion Precise trust estimation from conversation requires lexical cues and acoustic cues. Application These results showed the possibility of using conversational data to measure trust, and potentially other dynamic mental states, unobtrusively and dynamically.