bluuebunny/crossref_metadata_2025_split huggingface dataset:
Feasibility, accessibility and acceptability a pharmacist-led ear health intervention at rural community pharmacies (LISTEN UP): a mixed-methods study in Queensland, Australia
Authors: Taylor Selina , Cairns Alice , Glass Beverley Dawn 
Published: April 2022

ObjectiveEar disease in rural and remote communities is occurring at high rates, with limited access to health services and health providers contributing to the problem. Community pharmacists are well-placed to provide expanded services to improve ear health in rural communities. We aimed to evaluate the feasibility, accessibility and acceptability of a pharmacist-led intervention for ear disease in consumers presenting to community pharmacy.DesignProspective preintervention and postintervention mixed-methods study. An ethnographic lens of rural culture was applied to the descriptive qualitative component of the study.SettingTwo rural community pharmacies in Queensland, Australia.ParticipantsPeople aged 6 months or older, who present with an ear complaint to a participating community pharmacy.InterventionLISTEN UP (Locally Integrated Screening and Testing Ear aNd aUral Programme) is a community pharmacy-based intervention to improve the management of ear health. Trained pharmacists conducted ear examinations using otoscopy and tympanometry on consumers following a LISTEN UP protocol. They made recommendations including no treatment, pharmacy only products or general practitioner (GP) referral. Consumers were contacted 7 days later for follow-up.Results55 rural consumers participated in the study. The most commonly reported complaints were ‘blocked ear’ and ‘ear pain’. Pharmacists recommended over-the-counter products to two-thirds of the participants and referred one quarter to a GP. 90% (50/55) of the consumers were highly satisfied with the service and would recommend the service. All consumers described the service positively with particular reference to convenience, improved confidence and appreciation of the knowledge gained about their ear complaint. Pharmacists were motivated to upskill and manage workflow to incorporate the service and expected both consumers and GPs to be more accepting of future expanded services as a result of LISTEN UP. However, without funding to provide the service, during the study other remunerated pharmacy tasks took priority over providing LISTEN UP.ConclusionRural community pharmacists can provide an acceptable and accessible ear health service; however, it is not feasible without a clear funding structure to provide resources including additional pharmacists, equipment and training.Trial registration numberACTRN12620001297910.
How midwives implemented teleconsultations during the COVID-19 health crisis: a mixed-methods study
Authors: Rousseau Anne , Gaucher Laurent , Gautier Sylvain , Mahrez Ines , Baumann Sophie 
Published: April 2022

ObjectivesOur primary and secondary objectives were to measure and understand the determinants of independent midwives' implementation of teleconsultations and their intention to continue these in the future.DesignA two-phase mixed-methods approach: (1) quantitative data to measure factors determining the initiation and continuation of teleconsultation, collected by an online survey from 29 April to 15 May 2020, at the end of the first COVID-19 lockdown, followed by (2) qualitative data to understand these determinants, by interviewing some participants in May–July 2020 to explore the quantitative findings in more detail.SettingMainland FranceParticipantsThe target population comprised independent midwives currently practising in France.Primary and secondary outcome measuresThe primary and secondary outcomes were binary variables: implementation of teleconsultations, and intention to continue them. The qualitative results provided the themes explaining these decisions.ResultsWe obtained 1491 complete responses from independent midwives, that is, 28.3% of French independent midwives, and interviewed 22 volunteers among them. Among the 1491, 88.5% implemented teleconsultations and 65.8% intended to continue them. Both individual and organisational factors favoured implementation of teleconsultations: older age (adjusted OR (aOR): 0.40, 95% CI: 0.28 to 0.58), female gender (aOR: 6.88, 95% CI: 2.71 to 17.48), married or living with a partner (aOR: 1.67, 95% CI: 1.10 to 2.52) and working in a group practice (midwives only—aOR: 2.34, 95% CI: 1.47 to 3.72; multiprofessional group—aOR: 1.75, 95% CI: 1.16 to 2.64). The qualitative analysis did not identify any new factors but helped us to understand the satisfaction better: midwives adopted telemedicine for their patients' access to and continuity of care, to maintain their professional activity and income, and to limit the risks of infection.ConclusionPersonal and organisational factors motivated the implementation of teleconsultation during the pandemic, but maintaining it raises technical, regulatory, and ethical issues.
Comparison of the Near Eye Tool for Refractive Assessment (NETRA) and non-cycloplegic subjective refraction
Authors: Hasrod Nabeela , Rubin Alan 
Published: April 2022

ObjectiveThe NETRA (Near Eye Tool for Refractive Assessment) is a smartphone-based refractive tool that allows for self-evaluation of refractive error. This study investigates the validity of the NETRA with and without cycloplegia to non-cycloplegic subjective refractions (SR).Methods and analysisParticipants underwent NETRA measurements without cycloplegia, and again after the administration of cycloplegia (cyclopentolate hydrochloride 1%). Non-cycloplegic SR were also performed. Variation of refractive measurements in symmetric dioptric power space were investigated using stereo-pair comets, hypothesis tests for variances and means. Bland-Altman plots were applied to better understand validity of the NETRA against non-cycloplegic SR. Coefficients of repeatability and intraclass correlation coefficients were also determined.ResultsThe sample included 22 women (64.7%) and 12 men (35.3%); most were indigenous Africans (52.9%) with mean age and SD of 20.24±1.95 years. Variation of refractive measurements were mainly stigmatic (spherical), and variation of NETRA measurements decreased after cycloplegia. The pre-cycloplegia NETRA measurements (and their means) for the right and left eyes were more negative (myopic) in power than the post-cycloplegia NETRA measurements and means. On average, eyes were approximately 1.25 D more myopic with the NETRA without cycloplegia. With cycloplegia, NETRA results were in closer agreement with non-cycloplegic SR for the same eyes.ConclusionNETRA validity to SR, even in the absence of cycloplegia, suggests the instrument may be useful in geographical regions where self-refractions might be potentially helpful in addressing limitations in eye and vision care.
Linear optics of the eye and optical systems: a review of methods and applications
Authors: Evans Tanya , Rubin Alan 
Published: April 2022

The purpose of this paper is to review the basic principles of linear optics. A paraxial optical system is represented by a symplectic matrix called the transference, with entries that represent the fundamental properties of a paraxial optical system. Such an optical system may have elements that are astigmatic and decentred or tilted. Nearly all the familiar optical properties of an optical system can be derived from the transference. The transference is readily obtainable, as shown, for Gaussian and astigmatic optical systems, including systems with elements that are decentred or tilted. Four special systems are described and used to obtain the commonly used optical properties including power, refractive compensation, vertex powers, neutralising powers, the generalised Prentice equation and change in vergence across an optical system. The use of linear optics in quantitative analysis and the consequences of symplecticity are discussed.A systematic review produced 84 relevant papers for inclusion in this review on optical properties of linear systems. Topics reviewed include various magnifications (transverse, angular, spectacle, instrument, aniseikonia, retinal blur), cardinal points and axes of the eye, chromatic aberrations, positioning and design of intraocular lenses, flipped, reversed and catadioptric systems and gradient indices. The optical properties are discussed briefly, with emphasis placed on results and their implications. Many of these optical properties have applications for vision science and eye surgery and some examples of using linear optics for quantitative analyses are mentioned.
B-flavor tagging at Belle II
Authors: Abudinén F. , Akopov N. , Aloisio A. , Babu V. , Banerjee Sw. , Bauer M. , Bennett J. V. , Bernlochner F. U. , Bessner M. , Bettarini S. , Bilka T. , Bilokin S. , Biswas D. , Bodrov D. , Borah J. , Bračko M. , Branchini P. , Budano A. , Campajola M. , Casarosa G. , Cecchi C. , Cheaib R. , Chekelian V. , Chen C. , Chen Y. Q. , Cho H. -E. , Cunliffe S. , De Nardo G. , De Pietro G. , de Sangro R. , Dey S. , Canto A. Di , Capua F. Di , Dong T. V. , Dujany G. , Ecker P. , Eliachevitch M. , Ferber T. , Forti F. , Ganiev E. , Gaz A. , Gelb M. , Gemmler J. , Godang R. , Goldenzweig P. , Graziani E. , Hara K. , Hershenhorn A. , Higuchi T. , Hill E. C. , Hohmann M. , Humair T. , Inguglia G. , Junkerkalefeld H. , Karl R. , Kato Y. , Keck T. , Kiesling C. , Kim C. -H. , Kohani S. , Komarov I. , Kraetzschmar T. M. G. , Križan P. , Krohn J. F. , Kuhr T. , Kumar J. , Kumara K. , Kurz S. , Lacaprara S. , La Licata C. , Laurenza M. , Lautenbach K. , Lee S. C. , Lieret K. , Gioi L. Li , Liu Q. Y. , Longo S. , Maggiora M. , Manoni E. , Marinas C. , Martini A. , Meier F. , Merola M. , Metzner F. , Milesi M. , Miyabayashi K. , Mohanty G. B. , Mueller F. , Murphy C. , Oxford E. R. , Park S. -H. , Passeri A. , Pham F. , Piilonen L. E. , Pokharel S. , Prim M. T. , Pulvermacher C. , Rados P. , Ritter M. , Rostomyan A. , Sandilya S. , Santelj L. , Sato Y. , Schwartz A. J. , Sevior M. E. , Soffer A. , Spataro S. , Stroili R. , Sutcliffe W. , Tagnani D. , Takizawa M. , Tamponi U. , Tenchini F. , Torassa E. , Urquijo P. , Vitale L. , Yusa Y. , Zani L. , Zhou Q. D. , Žlebčík R. , Zupanc A. 
Published: April 2022

AbstractWe report on new flavor tagging algorithms developed to determine the quark-flavor content of bottom (
"Image missing") mesons at Belle II. The algorithms provide essential inputs for measurements of quark-flavor mixing and charge-parity violation. We validate and evaluate the performance of the algorithms using hadronic
"Image missing" decays with flavor-specific final states reconstructed in a data set corresponding to an integrated luminosity of 62.8 fb$$^{-1}$$

-
1

, collected at the "Equation missing" resonance with the Belle II detector at the SuperKEKB collider. We measure the total effective tagging efficiency to be $$\begin{aligned} \varepsilon _\mathrm{eff} = \big (30.0 \pm 1.2(\text {stat}) \pm 0.4(\text {syst})\big )\% \end{aligned}$$

ε
eff

=

(

30.0
±
1.2

(
stat
)

±
0.4

(
syst
)

)

%

for a category-based algorithm and $$\begin{aligned} \varepsilon _\mathrm{eff} = \big (28.8 \pm 1.2(\text {stat}) \pm 0.4(\text {syst})\big )\% \end{aligned}$$

ε
eff

=

(

28.8
±
1.2

(
stat
)

±
0.4

(
syst
)

)

%

for a deep-learning-based algorithm.
Cardiopulmonary Rehabilitation in Elderly Patients with Heart Failure: A Prospective Cohort Study
Authors: Zhou Haitao , Dong Aishu , Xu Xiaoqing , Zhu Jianing , Shi Bowen 
Published: April 2022

Objective. To determine the impact of cardiopulmonary rehabilitation administered through WeChat on exercising resilience and life quality in aged people with heart failure (HF). Methods. We conducted prospective cohort study that included 80 heart failure patients who were admitted to the Second Affiliated Hospital of Wenzhou Medical University from June 2018 to September 2020, 80 patients with heart failure. Patients were grouped according to their use of WeChat for rehabilitation. WeChat cohort provides remote supervision of rehabilitation and nursing guidance through WeChat. Specifically, the findings below were predetermined and compared across treatment groups utilizing analysis of variance corrected for baseline levels of the end measure and location: changes in the length of cardiopulmonary exercise tests, peak VO2, the proportion of predicted maximum VO2, and variation in the distance covered during the 6-minute walk distance (6MWD) assessment. Comparison of negative emotions between two groups, a Self-rating Depression Scale (SDS) and Self-rating Anxiety Scale (SAS), and Survey Short Form-36 (SF36) at baseline and at month 2. Results. In contrast with the control cohort, the WeChat cohort did not show any significant differences in general data (

P

> 0.05). After the rehabilitation, the WeChat group has a notably higher level in 6MWD than in the control group. Prior to the rehabilitation, there were no statistical gaps between the two cohorts in terms of SAS and SDS scores (

P

> 0.05). Even though the two cohorts saw a decline in SAS and SDS scores following nursing, the observation cohort indicated a much relatively low level in contrast with the control cohort (

P

< 0.05). The comparison of the SF-36 scores between the two cohorts revealed no significant differences (

P

> 0.05). Following nursing, the scores of the two cohorts declined significantly, with the control cohort scoring far lower than the other (

P

< 0.05). Conclusions. In summary, cardiopulmonary rehabilitation via WeChat is very beneficial for HF patients who are at a stable phase of the disease. It may substantially improve patients’ exercise stamina, reduce adverse emotions, boost patients’ quality of life, and have significant clinical relevance.
Rapid Screening Using Pathomorphologic Interpretation to Detect BRAFV600E Mutation and Microsatellite Instability in Colorectal Cancer
Authors: Fujii Satoshi , Kotani Daisuke , Hattori Masahiro , Nishihara Masato , Shikanai Toshihide , Hashimoto Junji , Hama Yuki , Nishino Takuya , Suzuki Mizuto , Yoshidumi Ayatoshi , Ueno Makoto , Komatsu Yoshito , Masuishi Toshiki , Hara Hiroki , Esaki Taito , Nakamura Yoshiaki , Bando Hideaki , Yamada Tomoyuki , Yoshino Takayuki 
Published: April 2022

Abstract

Purpose:
Rapid decision-making is essential in precision medicine for initiating molecular targeted therapy for patients with cancer. This study aimed to extract pathomorphologic features that enable the accurate prediction of genetic abnormalities in cancer from hematoxylin and eosin images using deep learning (DL).

Experimental Design:
A total of 1,657 images (one representative image per patient) of thin formalin-fixed, paraffin-embedded tissue sections from either primary or metastatic tumors with next-generation sequencing–confirmed genetic abnormalities—including BRAFV600E and KRAS mutations, and microsatellite instability high (MSI-H)—that are directly relevant to therapeutic strategies for advanced colorectal cancer were obtained from the nationwide SCRUM-Japan GI-SCREEN project. The images were divided into three groups of 986, 248, and 423 images to create one training and two validation cohorts, respectively. Pathomorphologic feature-prediction DL models were first developed on the basis of pathomorphologic features. Subsequently, gene-prediction DL models were constructed for all possible combinations of pathomorphologic features that enabled the prediction of gene abnormalities based on images filtered by the combination of pathomorphologic feature-prediction models.

Results:
High accuracies were achieved, with AUCs &gt; 0.90 and 0.80 for 12 and 27, respectively, of 33 analyzed pathomorphologic features, with high AUCs being yielded for both BRAFV600E (0.851 and 0.859) and MSI-H (0.923 and 0.862).

Conclusions:
These findings show that novel next-generation pathology methods can predict genetic abnormalities without the need for standard-of-care gene tests, and this novel next-generation pathology method can be applied for colorectal cancer treatment planning in the near future.
Hallmarks of Resistance to Immune-Checkpoint Inhibitors
Authors: Karasarides Maria , Cogdill Alexandria P. , Robbins Paul B. , Bowden Michaela , Burton Elizabeth M. , Butterfield Lisa H. , Cesano Alessandra , Hammer Christian , Haymaker Cara L. , Horak Christine E. , McGee Heather M. , Monette Anne , Rudqvist Nils-Petter , Spencer Christine N. , Sweis Randy F. , Vincent Benjamin G. , Wennerberg Erik , Yuan Jianda , Zappasodi Roberta , Lucey Vanessa M. Hubbard , Wells Daniel K. , LaVallee Theresa 
Published: April 2022

Abstract

Immune-checkpoint inhibitors (ICI), although revolutionary in improving long-term survival outcomes, are mostly effective in patients with immune-responsive tumors. Most patients with cancer either do not respond to ICIs at all or experience disease progression after an initial period of response. Treatment resistance to ICIs remains a major challenge and defines the biggest unmet medical need in oncology worldwide. In a collaborative workshop, thought leaders from academic, biopharma, and nonprofit sectors convened to outline a resistance framework to support and guide future immune-resistance research. Here, we explore the initial part of our effort by collating seminal discoveries through the lens of known biological processes. We highlight eight biological processes and refer to them as immune resistance nodes. We examine the seminal discoveries that define each immune resistance node and pose critical questions, which, if answered, would greatly expand our notion of immune resistance. Ultimately, the expansion and application of this work calls for the integration of multiomic high-dimensional analyses from patient-level data to produce a map of resistance phenotypes that can be utilized to guide effective drug development and improved patient outcomes.
A Costimulatory CAR Improves TCR-based Cancer Immunotherapy
Authors: Omer Bilal , Cardenas Mara G. , Pfeiffer Thomas , Daum Rachel , Huynh Mai , Sharma Sandhya , Nouraee Nazila , Xie Cicilyn , Tat Candise , Perconti Silvana , Van Pelt Stacey , Scherer Lauren , DeRenzo Chris , Shum Thomas , Gottschalk Stephen , Arber Caroline , Rooney Cliona M. 
Published: April 2022

Abstract

T-cell receptors (TCR) recognize intracellular and extracellular cancer antigens, allowing T cells to target many tumor antigens. To sustain proliferation and persistence, T cells require not only signaling through the TCR (signal 1), but also costimulatory (signal 2) and cytokine (signal 3) signaling. Because most cancer cells lack costimulatory molecules, TCR engagement at the tumor site results in incomplete T-cell activation and transient antitumor effects. To overcome this lack of signal 2, we genetically modified tumor-specific T cells with a costimulatory chimeric antigen receptor (CoCAR). Like classical CARs, CoCARs combine the antigen-binding domain of an antibody with costimulatory endodomains to trigger T-cell proliferation, but CoCARs lack the cytotoxic CD3ζ chain to avoid toxicity to normal tissues. We first tested a CD19-targeting CoCAR in combination with an HLA-A*02:01-restricted, survivin-specific transgenic TCR (sTCR) in serial cocultures with leukemia cells coexpressing the cognate peptide–HLA complex (signal 1) and CD19 (signal 2). The CoCAR enabled sTCR+ T cells to kill tumors over a median of four additional tumor challenges. CoCAR activity depended on CD19 but was maintained in tumors with heterogeneous CD19 expression. In a murine tumor model, sTCR+CoCAR+ T cells improved tumor control and prolonged survival compared with sTCR+ T cells. We further evaluated the CoCAR in Epstein–Barr virus–specific T cells (EBVST). CoCAR-expressing EBVSTs expanded more rapidly than nontransduced EBVSTs and delayed tumor progression in an EBV+ murine lymphoma model. Overall, we demonstrated that the CoCAR can increase the activity of T cells expressing both native and transgenic TCRs and enhance antitumor responses.
Molecular Signature of Tumor-Associated High Endothelial Venules That Can Predict Breast Cancer Survival
Authors: Sawada Junko , Hiraoka Nobuyoshi , Qi Rongsu , Jiang Lu , Fournier-Goss Ashley E. , Yoshida Masayuki , Kawashima Hiroto , Komatsu Masanobu 
Published: April 2022

Abstract

High endothelial venules (HEV) are specialized post-capillary venules that recruit naïve lymphocytes to lymph nodes. HEVs are essential for the development of adaptive immunity. HEVs can also develop in tumors where they are thought to be important for recruiting naïve T cells and B cells into the tumors and locally enhancing antitumor immunity by supporting the formation of tertiary lymphoid structures. Herein, we used comparative transcriptome analysis of human breast cancer to investigate genes differentially expressed between tumor-associated HEVs and the rest of the tumor vasculature. Tumor vessels highly expressing HEV-upregulated genes, such as the homeobox gene MEOX2 and the tetraspanin gene TSPAN7, were associated with extensive infiltration of T and B cells and the occurrence of tertiary lymphoid structures, which is known to predict therapeutic responses to immune-checkpoint inhibitors. Moreover, high transcript counts of these genes in clinical tumor specimens were associated with a significant survival benefit in advanced breast cancer. The molecular signature of HEVs identified herein may be useful for guiding immunotherapies and provides a new direction for investigating tumor-associated HEVs and their clinical significance.
See related Spotlight by Gallimore, p. 371.
Loss of LRRC33-Dependent TGFβ1 Activation Enhances Antitumor Immunity and Checkpoint Blockade Therapy
Authors: Jiang Aiping , Qin Yan , Springer Timothy A. 
Published: April 2022

Abstract

TGFβ has multiple roles and gene products (TGFβ1, -β2, and -β3), which make global targeting of TGFβ undesirable. Expression of TGFβ requires association with milieu molecules, which localize TGFβ to the surface of specific cells or extracellular matrices. Here, we found that LRRC33 was specifically associated with TGFβ1, not TGFβ2 and TGFβ3, and was required for surface display and activation of TGFβ1 on tumor-infiltrating myeloid cells. Loss of LRRC33-dependent TGFβ1 activation slowed tumor growth and metastasis by enhancing innate and adaptive antitumor immunity in multiple mouse syngeneic tumor models. LRRC33 loss resulted in a more immunogenic microenvironment, with decreased myeloid-derived suppressor cells, more active CD8+ T and NK cells, and more skewing toward tumor-suppressive M1 macrophages. LRRC33 loss and PD-1 blockade synergized in controlling B16.F10 tumor growth. Our results demonstrate the importance of LRRC33 in tumor biology and highlight the therapeutic potential of dual blockade of the LRRC33/TGFβ1 axis and PD-1/PD-L1 in cancer immunotherapy.