bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elimination of CaMKIIδ Autophosphorylation by CRISPR-Cas9 Base Editing Improves Survival and Cardiac Function in Heart Failure in Mice
Authors: Lebek Simon , Caravia Xurde M. , Chemello Francesco , Tan Wei , McAnally John R. , Chen Kenian , Xu Lin , Liu Ning , Bassel-Duby Rhonda , Olson Eric N. 
Published: September 2023

BACKGROUND:

Cardiovascular diseases are the main cause of worldwide morbidity and mortality, highlighting the need for new therapeutic strategies. Autophosphorylation and subsequent overactivation of the cardiac stress-responsive enzyme CaMKIIδ (Ca
2+
/calmodulin-dependent protein kinase IIδ) serves as a central driver of multiple cardiac disorders.

METHODS:

To develop a comprehensive therapy for heart failure, we used CRISPR-Cas9 adenine base editing to ablate the autophosphorylation site of CaMKIIδ. We generated mice harboring a phospho-resistant CaMKIIδ mutation in the germline and subjected these mice to severe transverse aortic constriction, a model for heart failure. Cardiac function, transcriptional changes, apoptosis, and fibrosis were assessed by echocardiography, RNA sequencing, terminal deoxynucleotidyl transferase dUTP nick end labeling staining, and standard histology, respectively. Specificity toward
CaMKIIδ
gene editing was assessed using deep amplicon sequencing. Cellular Ca
2+
homeostasis was analyzed using epifluorescence microscopy in Fura-2–loaded cardiomyocytes.

RESULTS:

Within 2 weeks after severe transverse aortic constriction surgery, 65% of all wild-type mice died, and the surviving mice showed dramatically impaired cardiac function. In contrast to wild-type mice, CaMKIIδ phospho-resistant gene-edited mice showed a mortality rate of only 11% and exhibited substantially improved cardiac function after severe transverse aortic constriction. Moreover, CaMKIIδ phospho-resistant mice were protected from heart failure–related aberrant changes in cardiac gene expression, myocardial apoptosis, and subsequent fibrosis, which were observed in wild-type mice after severe transverse aortic constriction. On the basis of identical mouse and human genome sequences encoding the autophosphorylation site of
CaMKIIδ
, we deployed the same editing strategy to modify this pathogenic site in human induced pluripotent stem cells. It is notable that we detected a >2000-fold increased specificity for editing of
CaMKIIδ
compared with other
CaMKII
isoforms, which is an important safety feature. While wild-type cardiomyocytes showed impaired Ca
2+
transients and an increased frequency of arrhythmias after chronic β-adrenergic stress,
CaMKIIδ
-edited cardiomyocytes were protected from these adverse responses.

CONCLUSIONS:
Ablation of CaMKIIδ autophosphorylation by adenine base editing may offer a potential broad-based therapeutic concept for human cardiac disease.
Modeling the cell-type-specific mesoscale murine connectome with anterograde tracing experiments
Authors: Koelle Samson , Mastrovito Dana , Whitesell Jennifer D. , Hirokawa Karla E. , Zeng Hongkui , Meila Marina , Harris Julie A. , Mihalas Stefan 
Published: September 2023

Abstract
The Allen Mouse Brain Connectivity Atlas consists of anterograde tracing experiments targeting diverse structures and classes of projecting neurons. Beyond regional anterograde tracing done in C57BL/6 wild-type mice, a large fraction of experiments are performed using transgenic Cre-lines. This allows access to cell-class-specific whole-brain connectivity information, with class defined by the transgenic lines. However, even though the number of experiments is large, it does not come close to covering all existing cell classes in every area where they exist. Here, we study how much we can fill in these gaps and estimate the cell-class-specific connectivity function given the simplifying assumptions that nearby voxels have smoothly varying projections, but that these projection tensors can change sharply depending on the region and class of the projecting cells. This paper describes the conversion of Cre-line tracer experiments into class-specific connectivity matrices representing the connection strengths between source and target structures. We introduce and validate a novel statistical model for creation of connectivity matrices. We extend the Nadaraya-Watson kernel learning method that we previously used to fill in spatial gaps to also fill in gaps in cell-class connectivity information. To do this, we construct a “cell-class space” based on class-specific averaged regionalized projections and combine smoothing in 3D space as well as in this abstract space to share information between similar neuron classes. Using this method, we construct a set of connectivity matrices using multiple levels of resolution at which discontinuities in connectivity are assumed. We show that the connectivities obtained from this model display expected cell-type- and structure-specific connectivities. We also show that the wild-type connectivity matrix can be factored using a sparse set of factors, and analyze the informativeness of this latent variable model.
Assessing the effectiveness of a school educational video on cancer and radiotherapy
Authors: Minamitani Masanari , Katano Atsuto , Nakagawa Keiichi 
Published: September 2023

Background: Japan has recently begun introducing educational programmes on cancer as part of health and physical education (HPE) classes in schools. In support of this work, the Japanese Society for Radiation Oncology has developed an educational video to enhance children’s understanding of cancer and radiotherapy. Objectives: This study examined the perceived effectiveness of this video among teachers and clarified whether their specialisation played a role in their responses. Methods: An online survey was administered to junior and senior high school teachers without a history of cancer. Respondents’ demographic characteristics, healthy lifestyle habits, anxiety about cancer treatment and knowledge about cancer and radiotherapy were surveyed pre- and post-video. We compared the data from science teachers, HPE teachers and teachers of other specialties. Subsequently, we performed a multiple logistic regression analysis to estimate significant factors that predicted post-watch correct-answer rates. Results: Science teachers were less anxious about radiotherapy and surgery than the other-specialty teachers. They were also the most knowledgeable about cancer and radiotherapy. Post-viewing correct-answer rates improved, except for questions about the work of medical physicists and damage to normal cells. The multiple regression analysis identified age (β = .07), sex (β = .08), anxiety about radiotherapy (β = −.09) and pre-video correct-answer rates (β = .46) as significant factors predicting post-watch correct-answer rates. Conclusion: The video was beneficial in enhancing teachers’ understanding of cancer and radiotherapy. Compared with HPE and other-specialty teachers, science teachers were superior in terms of cancer and radiotherapy comprehension. There may be value in exploring possibilities for cross-disciplinary instruction involving not only HPE but also science teachers in cancer education, especially radiotherapy education.
White Parent and Caregiver Perceptions of, and Resistance to, Equity and Anti-Racism Work in an Independent School
Authors: Clonan-Roy Katherine “Katie” , Maton Rhiannon , Jacobs Charlotte E. , Matthews Casey , Kokozos Michael , Kitzmiller Erika 
Published: September 2023

Background: Between early 2020 and today, our society has experienced a distressing global pandemic, horrifying brutalities committed against BIPOC individuals and communities, uprisings for racial justice, and a violent attack on our nation’s capital. While these events and phenomena have been challenging and traumatic, they have also inspired calls for equity-focused action within and beyond schools. Purpose: Many schools have intensified their diversity, equity, inclusion, justice, and anti-racism (DEIJA) work by revising their curricula, providing equity-focused professional development for educators, offering extracurricular programs like affinity and accountability spaces for BIPOC and white students, and many other initiatives. However, this work has occurred against a contentious backdrop, including parent and caregiver resistance to DEIJA work and attacks on schools for allegedly teaching critical race theory. Research Design: Between the summer of 2020 and the spring of 2022, we conducted research with one independent school, called the Waterford School, in a metropolitan area as it engaged in intensified DEIJA work. During this time, we surveyed and ran focus groups with caregivers, students, faculty, staff, and administrators to capture their experiences with and perspectives on school DEIJA work. White caregivers were the most vocal and resistant constituent group, and in this article, we examine the perspectives that they brought to these conversations on Waterford’s DEIJA initiatives. Conclusions: This analysis shows how, in both their support of and dissent to the DEIJA work, white caregivers’ perspectives often reflected and reinforced characteristics associated with white supremacy culture (WSC). We also show how caregivers’ perspectives on the DEIJA work and pressure on Waterford often posed racial equity detours, which created an illusion of progress toward racial equity while obscuring ongoing racial inequity.
Effectiveness and safety of opioids on breathlessness and exercise endurance in patients with chronic obstructive pulmonary disease: A systematic review and meta-analysis of randomised controlled trials
Authors: Liu Meilu , Xiao Wei , Du Longyi , Yu Yan , Chen Xugui , Mao Bing , Fu Juanjuan 
Published: September 2023

Background: Opioids are recommended to treat advanced refractory dyspnoea despite optimal therapy by the American Thoracic Society clinical practice guidelines, while newly published randomised controlled trials of opioids in chronic obstructive pulmonary disease yield conflicting results. Aim: This study aimed to evaluate the effectiveness and safety of opioids for patients with chronic obstructive pulmonary disease. Design: Systematic review and meta-analysis (PROSPERO CRD42021272556). Data sources: Databases of PubMed, EMBASE and CENTRAL were searched from inception to 2022 for eligible randomised controlled trials. Results: Twenty-four studies including 975 patients, were included. In cross-over studies, opioids improved breathlessness (standardised mean difference, −0.43; 95% CI, −0.55 to −0.30; I2 = 18%) and exercise endurance (standardised mean difference, 0.22; 95% CI, 0.02–0.41; I2 = 70%). However, opioids failed to improve dyspnoea (standardised mean difference, −0.02; 95% CI, −0.22 to 0.19; I2 = 39%) and exercise endurance (standardised mean difference, 0.00; 95% CI, −0.27 to 0.27; I2 = 0%) in parallel control studies that administered sustained-release opioids for more than 1 week. The opioids used in most crossover studies were short-acting and rarely associated with serious adverse effects. Only minor side effects such as dizziness, nausea, constipation and vomiting were identified for short-acting opioids. Conclusions: Sustained-release opioids did not improve dyspnoea and exercise endurance. Short-acting opioids appeared to be safe, have potential to lessen dyspnoea and improve exercise endurance, supporting benefit in managing episodes of breathlessness and providing prophylactic treatment for exertional dyspnoea.
Associations Between Patient-Reported Experiences with Opioid Use Disorder Treatment and Unmet Treatment Needs and Discontinuation Among Virginia Medicaid Members
Authors: Marks Sarah J. , Pham Huyen , McCray Neil , Palazzolo Jennifer , Harrell Ashley , Lowe Jason , Bachireddy Chethan , Guerra Lauren , Cunningham Peter J. , Barnes Andrew J. 
Published: September 2023

Background: Many payers, including Medicaid, the largest payer of opioid use disorder (OUD) treatment, are pursuing treatment-related quality improvement initiatives. Yet, how patient-reported experiences with OUD treatment relate to patient-centered outcomes remains poorly understood. Aim: To examine associations between Medicaid members’ OUD treatment experiences, outpatient treatment settings, demographic and social factors, and members’ self-report of unmet needs during treatment and treatment discontinuation. Methods: A sample of Virginia Medicaid members aged 21 years or older with OUD diagnoses who received outpatient OUD treatment completed a mail survey between January 2020 and August 2021 (n = 1042, weighted n = 9244). A treatment experience index was constructed from responses to four items from the Consumer Assessment of Healthcare Providers and Systems (CAHPS) relating to feelings of involvement, safety, and respect and having treatment explained in an understandable way; two additional CAHPS items: “given options for treatment” and “able to refuse treatment” were also assessed. Weighted imputed logistic regressions tested adjusted associations between members’ treatment experiences, demographic and social factors, and two outcomes capturing unmet needs during treatment and treatment discontinuation. Results: More positive scores on the treatment experiences index were associated with lower adjusted odds of reporting unmet needs during treatment (aOR: 0.52, 95% CI: 0.41-0.66) and discontinuation (aOR: 0.63, 95% CI: 0.47-0.79). Respondents with serious psychological distress had higher odds of reporting unmet needs during treatment (aOR: 1.69 95% CI: 1.14-2.51) and discontinuation (aOR: 1.84, 95% CI: 1.21-2.82), as did individuals with housing insecurity (unmet needs: (aOR: 1.65, 95% CI: 1.11-2.44); treatment discontinuation: (aOR: 1.56, 95% CI: 1.04-2.36)). Conclusion: Using a first-of-its-kind survey of Medicaid members with OUD, we found that members who had more positive treatment experiences were less likely to report unmet treatment needs and discontinue treatment. Care approaches focused on improving patient experience are critical to delivering effective, high-quality OUD treatment.
Breastfeeding Behavior Within the Covid-19 Related Obstetric and Neonatal Outcome Study (CRONOS)
Authors: Zöllkau Janine , Heimann Yvonne , Hagenbeck Carsten , Pecks Ulrich , Abou-Dakn Michael , Schlösser Rolf , Schohe Anna , Dressler-Steinbach Iris , Manz Maike , Banz-Jansen Constanze , Reuschel Edith , Iannaccone Antonella , Bohlmann Michael K. , Kraft Katrina , Fill Malfertheiner Sara , Wimberger Pauline , Kolben Thomas , Bartmann Catharina , Longardt Ann-Carolin 
Published: September 2023

Background: The SARS-CoV-2 pandemic and its influence on peripartum processes worldwide led to issues in breastfeeding support. Research Aim: The aim of this study was to describe breastfeeding behavior and peripartum in-hospital management during the pandemic in Germany and Austria. Methods: This study was a descriptive study using a combination of secondary longitudinal data and a cross-sectional online survey. Registry data from the prospective multicenter COVID-19 Related Obstetric and Neonatal Outcome Study (CRONOS) cohort study (longitudinal, medical records of 1,815 parent-neonate pairs with confirmed SARS-CoV-2 infection during pregnancy) and a cross-sectional online survey of CRONOS hospitals’ physicians ( N = 67) were used for a descriptive comparison of feeding outcomes and postpartum management. Results: In 93.7% (n = 1700) of the cases in which information on the neonate's diet was provided, feeding was with the mother’s own milk. Among neonates not receiving their mother’s own milk, 24.3% ( n = 26) reported SARS-CoV-2 infection as the reason. Peripartum maternal SARS-CoV-2 infection, severe maternal COVID-19 including the need for intensive care unit (ICU) treatment or invasive ventilation, preterm birth, mandatory delivery due to COVID-19, and neonatal ICU admission were associated with lower rates of breastfeeding. Rooming-in positively influenced breastfeeding without affecting neonatal SARS-CoV-2 frequency (4.2% vs. 5.6%). CRONOS hospitals reported that feeding an infant their mother’s own milk continued to be supported during the pandemic. In cases of severe COVID-19, four of five hospitals encouraged breastfeeding. Conclusion: Maintaining rooming-in and breastfeeding support services in the CRONOS hospitals during the pandemic resulted in high breastfeeding rates.
Use of wound infusion catheters for postoperative local anaesthetic administration in cats
Authors: Kazmir-Lysak Kristina , Torres-Cantó Lucía , Ingraffia Sara , Romanelli Giorgio , Massari Federico , Rossanese Matteo , Compagnone Krizia , Pisani Guido , Cinti Filippo , Montinaro Vincenzo , Collivignarelli Francesco , Okushima Sayaka , Vallefuoco Rosario 
Published: September 2023

Objectives The present study aimed to document the use of the wound infusion catheter (WIC) following a variety of surgical procedures in cats, investigating complications and risk factors associated with catheter placement or local anaesthetic (LA) administration. Methods A retrospective, multicentric study was performed. Medical databases of eight veterinary referral hospitals from 2010 to 2021 were searched to identify records of cats where WICs were used. Information regarding signalment, type of surgery, size and type of WIC placed, and LA protocol used, as well as postoperative complications, were retrieved. Results One hundred and sixty-six cases fulfilled the inclusion criteria. Feline injection site sarcoma resection was the most common surgery. Overall complications were identified in 22/166 cats (13.2%). Thirteen cats (7.8%) experienced wound-related complications, whereas nine cats (5.4%) experienced drug-delivery complications. The only factor associated with an increased risk of complications was the amount of a single dose of LA delivered through the catheter ( P <0.001). An amount higher than 2.5 ml of LA delivered at each administration was associated with an increased risk of complications. All complications were minor and self-limiting. Conclusions and relevance WICs were used for a large variety of surgical procedures with different protocols of LA administration as part of a multimodal analgesic plan in cats. The risk of complications was relatively low and self-limiting, suggesting its safe use in cats. Further prospective studies are required to evaluate efficacy of postoperative analgesia and to determine the suitable protocol for WIC handling and maintenance.
Pegylated-l-asparaginase therapy for feline large cell lymphoma: 82 cases (2017–2020)
Authors: Bik Céline A , Ruijter Bart R , Van den Bossche Lindsay , Teske Erik , Niessen Stijn JM , Forcada Yaiza 
Published: September 2023

Objectives The present study aimed to investigate pegylated-l-asparaginase monotherapy for feline large cell lymphoma as a potential alternative to palliative corticosteroids treatment in animals whose owners declined cytotoxic chemotherapy. Methods A retrospective, descriptive case series of cats treated initially with pegylated-l-asparaginase as a sole therapy for feline large cell lymphoma is reported. The treatment protocol consisted of 12 intramuscular injections of pegylated-l-asparaginase with increasing intervals. If cats were unresponsive to pegylated-l-asparaginase monotherapy, a second-line treatment was initiated. Signalment, origin of lymphoma, staging, treatment, possible adverse events and follow-up data were extracted from the medical records. Responses and survival data were analysed. Results Eighty-two cats with lymphoma of five different anatomic types were included: alimentary, abdominal extra-alimentary, peripheral nodal, nasal/nasopharyngeal and other (mediastinal, renal [solitary] and miscellaneous combined in one group for analytical purposes). The response rate was 74.1% (95% confidence interval = 63.4–83.5) with 38.3% (95% confidence interval = 27.8–48.8) in complete remission. The median disease-free period and calculated overall survival time were 70 days (12–1702+) and 79 days (1–1715+), respectively. The response rate was significantly correlated with the origin of the lymphoma and the combined group had a significantly lower response rate ( P = 0.035). Twenty-four cats were also treated with corticosteroids. There was no significant difference in outcomes between the group treated with or without corticosteroids. Adverse events were present in a small number of cats (14/82). The majority of these adverse events were mild to moderate in 5/14 cats; however, the adverse events were severe enough to cause discontinuation of therapy. Conclusions and relevance Based on the response rate and median disease-free period, treatment with pegylated-l-asparaginase is inferior when compared with historical chemotherapy protocols. However, some cats demonstrated an exceptional long disease-free period. Therefore, pegylated-l-asparaginase could be offered as an alternative to corticosteroid therapy alone. Further studies are needed to evaluate the additional benefit over palliative corticosteroid monotherapy.
Understanding the Shared Meaning of Recovery From Substance Use Disorders: New Findings From the What is Recovery? Study
Authors: Zemore Sarah E , Ziemer Kelly L , Gilbert Paul A , Karno Mitchell P , Kaskutas Lee Ann 
Published: September 2023

Background: Substance use disorder (SUD) resolution typically involves a long-term, comprehensive process of change now widely referred to as “recovery.” Yet, definitions of recovery vary substantially, producing significant confusion. To support formal recovery definitions, we aimed to systematically identify recovery elements that are central to those in recovery and shared regardless of subgroup/pathway. Methods: Data were from the What is Recovery? Study, involving a diverse, national, online survey of people in recovery (N = 9341). Surveys included a 35-item recovery measure reflecting 4 domains; participants reported whether or not each element definitely belonged in their recovery definitions. Analyses examined item endorsements overall and among 30 subgroups defined a priori (by sociodemographics, substance use characteristics, and help-seeking history) to determine where items met study-specific centrality thresholds (ie, endorsement by ⩾80% and top-10 ranking, by endorsement level). We then classified items as “core” if meeting centrality thresholds both overall and for all 30 subgroups, and “prevalent” if meeting centrality thresholds overall and for 26 to 29 subgroups. Results: Four “core” recovery elements emerged, including a process of growth or development; being honest with oneself; taking responsibility for the things one can change; and reacting in a more balanced way. Four “prevalent” recovery elements also emerged, referencing the ability to enjoy life and handle negative feelings without substance use; abstinence and/or nonproblematic substance use; and living a life that contributes. Subgroups differing most in their endorsements included those reporting mild/moderate SUD severity; non-abstinent recovery; and no specialty treatment or mutual-help group attendance. Conclusions: Recovery elements identified here partially reflect some stakeholder definitions, but offer greater specificity and include novel elements (eg, personal integrity). Elements may point to areas of functioning that are damaged in the addiction process and can support an addiction-free life. Findings should inform institutional recovery definitions; SUD services and research; and communications about recovery.