bluuebunny/crossref_metadata_2025_split huggingface dataset:
Addressing Inequity in Continuous Glucose Monitoring Access: Leveraging the Hospital in the Continuum of Care
Authors: Rickards Gabriella M. , Harrod Julia C. , Del Valle Kayla , Caballero A. Enrique , Palermo Nadine E. , McDonnell Marie E. 
Published: November 2024

Background: While continuous glucose monitoring (CGM) has transformed the care of people with diabetes (PWD) in the ambulatory setting, there continue to be significant barriers to access. With CGM on the horizon in the acute care setting, it is important to consider the potential for this shift to improve ambulatory CGM access to those at the highest risk of morbidity and mortality. Methods: In this commentary, we review the existing literature on the specific barriers to CGM access for individuals with diabetes in the United States including racial disparities, provider bias, cost and shortage of specialty diabetes care. Key areas explored include the importance of CGM in diabetes management, the consequences of disparities in access to CGM, and leveraging the inpatient setting to promote equitable care and better outcomes for PWD. Results: We present a vision for a new care model, which leverages the transition of care from the hospital to successfully incorporate CGM into the discharge plan. Conclusions: Given that CGM utilization is associated with improved outcomes and reduced rates of hospitalization and emergency department visits, a care model that facilitates CGM access upon transition from inpatient to ambulatory care can enhance health equity and quality of life for people with diabetes.
Providing personalised care for people with tuberculosis: an evaluation of enhanced case management in a UK TB Network 2013 to 2021
Authors: Crocker-Buque Tim , Hayden Harry , White Jacqui , Dekoningh Jennifer , Belton Moerida , Boparai Narinder , Brown James , Brown Mike , Hawley Danielle , Lozewicz Stefan , Miller Rob , Moores Rachel , Moshal Karyn , Potter Jessica , Lipman Marc ,   on behalf of the North Central London Tuberculosis Service
Published: November 2024

Objectives Evaluating the outcomes of enhanced case management (ECM) for patients with tuberculosis (TB) in the North Central London TB Service (NCLTBS). Design Retrospective cohort study. Setting The NCLTBS provides care for persons diagnosed with TB across north and central London. Management involves both medical and psychosocial support, leading to the implementation ECM to provide additional non-clinical assistance to patients at risk of treatment non-completion. However, there has been limited evaluation of its outcomes. Participants All adults with TB notified to NCLTBS between January 2013 and June 2021. Main outcome measures Descriptive socio-economic and clinical characteristics grouped by binary ECM status (yes/no) and level (0–3). Clinical outcomes at 12 months (completed treatment, death, lost-to-follow-up, continuing on treatment) were compared using multivariable logistic regression. Results Totally, 2437 patients were included (57.2% male, 79.1% born outside the UK). Overall, 82.3% completed treatment and 4.1% died. Factors associated with mortality included older age (over 70 years odds ratio (OR) 3.3), inpatient diagnosis (OR 4.4), and mental health issues (OR 2.2). 52.8% received ECM, with the proportion increasing over time, and 76% of this group successfully competed treatment. Conclusions This comprehensive evaluation of ECM in a diverse London population indicates high treatment completion rates even among those with multiple social risk factors. However, ECM needs of patients has increased over time, with a particular rise in patients requiring the highest support level. Given the small difference between standard care and ECM categories 1 and 2, there may be scope to simplify the system.
Management of Tricuspid Atresia With Normally Related Great Arteries and Left-Sided Obstruction
Authors: Palacio Andres M. , Williams William G. , Barron David J. , Argo Madison B. , Jegatheeswaran Anusha , Jacobs Marshall L. , Bondarenko Igor , Welke Karl F. , Kirklin James K. , Karamlou Tara , Alsoufi Bahaaldin , McCrindle Brian W. ,   for the Congenital Heart Surgeons Society
Published: November 2024

Background Tricuspid atresia (TA) is the second most common form of functionally univentricular heart. For patients with TA and normally related great arteries (Type I), left ventricular outflow tract obstruction (LVOTO) is rare. Methods From the Congenital Heart Surgeons’ Society multi-institutional cohort of 445 patients with Type I TA enrolled from 1999 to 2024 from 42 sites, 14 infants (3%) had interventions for associated LVOTO, either at presentation or after their first TA-related intervention. Results Of seven infants initially undergoing Norwood/Damus-Kaye-Stansel (DKS), six survived to Stage II, of whom five survived with one developing pulmonary hypertension and four achieving Fontan. An additional seven infants who were first managed with pulmonary artery band placement subsequently had bidirectional superior cavopulmonary anastomosis (BCPA) and a DKS procedure; there were six survivors, all achieving Fontan. All ten survivors who underwent the Fontan procedure had normal left ventricular and mitral valve function at the latest follow-up. The overall Kaplan-Meier survival estimate at 20 years for these 14 patients was 79% (70% CI, 66%-88%), and the median follow-up was 8.3 years (0.24-21.5). Conclusions While infants with TA and transposition of the great arteries are more likely to have LVOTO, this can also occur in the setting of normally related great arteries. Infants with Type I TA and LVOTO can be managed in the neonatal period with the Norwood procedure ensuring complete arch relief with acceptable outcomes. If LVOTO becomes evident after initial pulmonary artery band placement, a subsequent DKS procedure facilitates satisfactory success to Fontan.
Bivalent CD47 immunotoxin for targeted therapy of T-cell acute lymphoblastic leukemia
Authors: Ma Jihong , Wang Zhaohui , Mintzlaff Danielle , Zhang Huiping , Ramakrishna Rashmi , Davila Eduardo , Witkowski Matthew T. , Lucia M. Scott , Schwartz Marc S. , Pomfret Elizabeth A. , Mathes David W. , Wang Zhirui 
Published: November 2024

Abstract
CD47 is overexpressed on the surface of many types of cancer cells, including T-cell acute lymphoblastic leukemia (T-ALL) cells. In this study, we have developed a diphtheria toxin (DT)–based bivalent anti-human CD47 immunotoxin (bi-CD47-IT) for the targeted therapy of CD47+ cancers using a unique DT-resistant yeast Pichia pastoris expression system. Bi-CD47-IT demonstrated compelling in vivo efficacy in multiple T-ALL cell line–derived xenograft (CDX) and patient-derived xenograft (PDX) mouse models. Bi-CD47-IT significantly prolonged the median survival of the tumor-bearing mice and highly effectively depleted the T-ALL blast cells in the peripheral blood, spleen, liver, bone marrow, brain, and spinal cord in the T-ALL CDX and PDX mouse models. Bi-CD47-IT cured 60% of tumor-bearing mice in a T-ALL Molt-4 CDX mouse model. Because CD47 is also expressed on normal tissues, including red blood cells and lymphocytes, specificity is a concern. We thus analyzed the in vitro binding avidity and hemagglutination of bi-CD47-IT in human red blood cells, finding no binding or hemagglutination. We further performed a toxicity study of bi-CD47-IT in humanized mice, which showed that bi-CD47-IT transiently depleted the human lymphocytes for ∼4 weeks after the 10-day treatment. No clinical adverse events were observed. As a result, bi-CD47-IT appears to possess the “optimal” binding avidity, with effective binding to human CD47+ T-ALL tumor cells, no binding to human red blood cells, and weak binding to human lymphocytes. We believe that bi-CD47-IT is a promising and safe therapeutic drug candidate for the targeted therapy of CD47+ cancers.
Preclinical efficacy of CDK7 inhibitor–based combinations against myeloproliferative neoplasms transformed to AML
Authors: Fiskus Warren , Mill Christopher P. , Bose Prithviraj , Masarova Lucia , Pemmaraju Naveen , Dunbar Andrew , Birdwell Christine E. , Davis John A. , Das Kaberi , Hou Hanxi , Manshouri Taghi , Jain Antrix , Malovannaya Anna , Philip Kevin , Alhamadani Noor , Matthews Alicia , Lin Katie , Flores Lauren B. , Loghavi Sanam , DiNardo Courtney , Su Xiaoping , Rampal Raajit K. , Bhalla Kapil N. 
Published: November 2024

Abstract
Rising blast percentage or secondary acute myeloid leukemia (sAML) transformation in myeloproliferative neoplasms (MPNs) leads to JAK1/2 inhibitor (JAKi) therapy resistance and poor survival. Here, we demonstrate that treatment with the CDK7 inhibitor (CDK7i) SY-5609 depletes phenotypically characterized post-MPN sAML stem/progenitor cells. In cultured post-MPN sAML SET2, HEL and patient-derived (PD) post-MPN sAML cells, SY-5609 treatment inhibited growth and induced lethality while sparing normal cells. RNA-sequencing analysis after SY-5609 treatment reduced mRNA expression of MYC, MYB, CDK4/6, PIM1, and CCND1 but increased expression of CDKN1A and BCL2L1. Mass spectrometry of SY-5609–treated MPN-sAML cells also reduced c-Myc, c-Myb, PIM1, and CDK4/6 but increased p21, caspase-9, and BAD protein levels. CRISPR-mediated CDK7 depletion also reduced cell viability of HEL cells. Cytometry by time of flight (CyTOF) analysis of SY-5609–treated PD post-MPN sAML stem/progenitor cells showed reduced c-Myc, CDK6, and PU.1 but increased protein levels of CD11b, p21, and cleaved caspase-3. Cotreatment with SY-5609 and ruxolitinib was synergistically lethal in HEL, SET2, and PD post-MPN sAML cells. A CRISPR screen in sAML cells revealed BRD4, CBP, and p300 as codependencies with CDK7i. Accordingly, cotreatment with SY-5609 and the bromodomain and extra-terminal protein inhibitor (BETi) OTX015 or pelabresib or the CBP/p300 inhibitor GNE-049 was synergistically lethal in MPN-sAML cells (including those exhibiting TP53 loss). Finally, in the HEL-Luc/GFP xenograft model, compared with each agent alone, cotreatment with SY-5609 and OTX015 reduced sAML burden and improved survival without host toxicity. These findings demonstrate promising preclinical activity of CDK7i-based combinations with BETi or CBP/p300 inhibitor against advanced MPNs, including post-MPN sAML.
Formoterol dynamically alters endocannabinoid tone in the periaqueductal gray inducing headache
Authors: Peterson Ingrid L. , Liktor-Busa Erika , Karlage Kelly L. , Young Sally J. , Scholpa Natalie E. , Schnellmann Rick G. , Largent-Milnes Tally M. 
Published: November 2024

Abstract
Background
Headache is a pain disorder present in populations world-wide with a higher incidence in females. Specifically, the incidences of medication overuse headache (MOH) have increased worldwide. Comorbidities of MOH include photosensitivity, anxiety, “brain fog”, and decreased physical activity. The FDA-approved long-lasting selective β2-adrenergic receptor agonist, formoterol, is currently approved for use in severe asthma and chronic obstructive pulmonary disease. Recently, interest in repurposing formoterol for use in other disorders including Alzheimer’s disease, and neuropathic pain after spinal cord injury and traumatic brain injury has gained traction. Thus, revisiting known side-effects of formoterol, like headache and anxiety, could inform treatment paradigms. The endocannabinoid (eCB) system is implicated in the etiology of preclinical headache, with observed decreases in the circulating levels of endogenous cannabinoids, referred to as Clinical Endocannabinoid Deficiency. As cross-talk between the eCB system and adrenergic receptors has been reported, this study investigated the role of the eCB system and ability of formoterol to induce headache-like periorbital allodynic behavior.

Methods
Female 8-week-old C57Bl/6J mice were treated daily with formoterol (0.3 mg/kg, i.p.) for up to 42-days, during which they were assessed for periorbital allodynia, open field/novel object recognition, and photosensitivity. At the end of the study, the periaqueductal grey (PAG), a brain region known to contribute to both headache induction and maintenance, was collected and subjected to LC-MS to quantify endocannabinoid levels.

Results
Mice exhibited periorbital allodynia at nearly all time points tested and photosensitivity from 28-days onward. Levels of endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), along with cannabinoid receptor 1 (CB1R) expression were altered by both age and upon treatment with formoterol. Administration of FAAH/MAGL inhibitors, to target the eCB system, and a non-selective cannabinoid receptor agonist, WIN 55,212 reversed the formoterol-induced periorbital allodynia.

Conclusions
These results suggest that formoterol is dysregulates eCB tone to drive headache-like periorbital allodynic behaviors. These results could help inform preventative treatment options for individuals receiving formoterol, as well as provide information on the interaction between the eCB and adrenergic system.

Graphical Abstract
Development of a core outcome set for psychological therapy trials on acute psychiatric inpatient wards
Authors: Jacobsen Pamela , Berry Katherine , Clarkson Lucy , Hiscocks Rebecca , Hopkins India , Morgan Ceri , Tandon Dhaarna , Teale Ashley-Louise , Tyler Natasha , Wood Lisa 
Published: November 2024

Abstract
Background
Consensus on what outcomes should be included in trials of psychological therapies on acute psychiatric inpatient wards is currently lacking. Inclusion of different viewpoints, including service user perspectives, is crucial in ensuring that future trials measure outcomes which are meaningful and important. Development of a Core Outcome Set (COS), a minimum standardised set of outcomes to be measured and reported, would help improve synthesis and interpretation of clinical trial data in this area.

Methods
Stage 1 of the COS development involved compiling a comprehensive long-list of outcomes from key sources including i) a systematic review of outcomes from published trials, ii) online survey of key stakeholders (service users, carers, healthcare professionals, researchers, and end users of research), iii) qualitative interviews with service users and carers. Stage 2 involved stakeholder groups short-listing the outcomes using consensus methods (e-Delphi survey). The final outcome set was derived from the short-list at a consensus meeting of stakeholders, facilitated by an Independent Chair.

Results
A long-list of 68 outcomes was compiled from the systematic review (n = 30 trials), online stakeholder survey (n = 100 participants) and qualitative interviews (n = 15 participants). Fifty stakeholders took part in the e-Delphi study, where the long-list was cut down to a short-list of 12 outcomes over 2 rounds. Nine stakeholders took part in the final consensus meeting, and after some outcomes were removed and/or amalgamated, a final set of 6 outcomes was recommended for inclusion in the COS. These were Ability to Cope, Hopefulness, Quality of Life, Psychosis Symptoms, Mood, and Self-Harm Behaviours.

Conclusions
Widespread future adoption of the COS will reduce research waste by ensuring that outcomes are more easily comparable across trials, and that the full range of stakeholder priorities are represented in trial outcomes. This makes it more likely that effective therapies will be identified in a timely fashion and successfully implemented in routine clinical practice. The final 6-outcome COS should be feasible to implement given the need keep participant burden to a minimum in inpatient trials. Further work is needed to make recommendations for the best outcome measurement instruments to use, including the use of patient-reported outcomes alongside clinician-rated measures.

Trial registration
Not applicable.
Lipoxin A4 improves cardiac remodeling and function in diabetes-associated cardiac dysfunction
Authors: Fu Ting , Mohan Muthukumar , Bose Madhura , Brennan Eoin P. , Kiriazis Helen , Deo Minh , Nowell Cameron J. , Godson Catherine , Cooper Mark E. , Zhao Peishen , Kemp-Harper Barbara K. , Woodman Owen L. , Ritchie Rebecca H. , Kantharidis Phillip , Qin Cheng Xue 
Published: November 2024

Abstract
Background
Diabetic heart disease may eventually lead to heart failure, a leading cause of mortality in diabetic individuals. The lack of effective treatments for diabetes-induced heart failure may result from a failure to address the underlying pathological processes, including chronic, low-grade inflammation. Previous studies have reported that lipoxin A4 (LXA4), known to promote resolution of inflammation, attenuates diabetes-induced atherosclerosis, but its impact on diabetic hearts has not been sought. Thus, we aimed to determine whether LXA4 therapeutic treatment attenuates diabetes-induced cardiac pathology.

Methods
Six-week-old male apolipoprotein E-deficient (ApoE−/−) mice were followed for 16 weeks after injection of streptozotocin (STZ, 55 mg/kg/day, i.p. for 5 days) to induce type-1 diabetes (T1DM). Treatment with LXA4 (5 μg/kg, i.p.) or vehicle (0.02% ethanol, i.p.) was administered twice weekly for the final 6 weeks. One week before endpoint, echocardiography was performed within a subset of mice from each group. At the end of the study, mice were euthanized with sodium pentobarbital (100 mg/kg i.p.) and hearts were collected for ex vivo analysis, including histological assessment, gene expression profiling by real-time PCR and protein level measurement by western blot.

Results
As expected diabetic mice showed a significant elevation in plasma glycated hemoglobin (HbA1c) and glucose levels, along with reduced body weight. Vehicle-treated diabetic mice exhibited increased cardiac inflammation, macrophage content, and an elevated ratio of M1-like to M2-like macrophage markers. In addition, myocardial fibrosis, cardiomyocytes apoptosis and hypertrophy (at the genetic level) were evident, with echocardiography revealing early signs of left ventricular (LV) diastolic dysfunction. Treatment with LXA4 ameliorated diabetes-induced cardiac inflammation, pro-inflammatory macrophage polarization and cardiac remodeling (especially myocardial fibrosis and cardiomyocytes apoptosis), with ultimate improvement in cardiac function. Of note, this improvement was independent of glucose control.

Conclusions
These findings demonstrated that LXA4 treatment attenuated the extent of cardiac inflammation in diabetic hearts, resulting in limited cardiac remodeling and improved LV diastolic function. This supports further exploration of LXA4-based therapy for the management of diabetic heart disease. The recent development of stable LXA4 mimetics holds potential as a novel strategy to treat cardiac dysfunction in diabetes, paving the way for innovative and more effective therapeutic strategies.

Graphical Abstract
Co-expression gene module analysis in response to attenuated cercaria vaccine reveals a critical role for NK cells in protection against Schistosoma mansoni
Authors: Neto Almiro Pires da Silva , Vitoriano-Souza Juliana , Khouri Mariana Ivo , Favaro Regiane Degan , Wilson Robert Alan , Leite Luciana Cezar de Cerqueira , Ramos Pablo Ivan Pereira , Farias Leonardo Paiva 
Published: November 2024

Abstract
Background
Despite decades of research, an effective schistosomiasis vaccine remains elusive. The radiation-attenuated (RA) cercarial vaccine remains the best model for eliciting high levels of protection. We have recently explored this model in mice to identify potentially protective pathways by examining gene expression patterns in peripheral blood mononuclear cells (PBMC).

Methods
Herein, we reanalyzed the transcriptomic data from PBMC obtained from vaccinated and infected C57BL/6 mice in three timepoints (Days 7 and 17 after infection or vaccination and Day 7 post-challenge). In addition, we generated new data on PBMC collected 35 days after infection. Deconvolution analysis was performed to estimate immune cell composition by CIBERSORTx. Gene co-expression networks and over-representation analysis (ORA) were performed using the CEMiTool package. Protein-protein interaction networks were constructed using STRING, and the hub proteins for each module were identified using Cytoscape.

Results
Co-expression network analysis identified a module (M2) associated with the infection process, grouping genes related to a Th2 immune response, and a second module (M6) associated with the vaccination process, displaying pathways related to a Th1 response, CD8 + T cells and NK cells. Within each module, five hub proteins were identified based on protein-protein interaction networks. The M2 infection module revealed Chil3, Il4, Cx3cr1, Emr1 and Ccl2 as hubs, while module M6, associated with vaccination, disclosed Prf1, Klrc1, IFN-γ, Ncr1 and Tbx21 as hub proteins.

Conclusions
Our data point to the potentiald role of NK cells that may contribute to the RA vaccine response through the production of IFN-γ orchestrated by the T-bet transcription factor (Tbx21).

Graphical Abstract
Efficacy of probiotics as adjuvant therapy in bronchial asthma: a systematic review and meta-analysis
Authors: Balan Divya , Baral Tejaswini , Manu Mohan K. , Mohapatra Aswini Kumar , Miraj Sonal Sekhar 
Published: November 2024

Abstract
Background
Asthma is a chronic, heterogeneous disease characterized by airway inflammation. Asthma exacerbations significantly increase the disease burden, necessitating new therapeutic approaches. Emerging evidence suggests probiotics, through the gut-lung axis, may benefit asthma management by modulating immune responses and reducing inflammation.

Methods
This systematic review and meta-analysis adhered to PRISMA guidelines and was registered with PROSPERO (CRD42023480098). A comprehensive search of PubMed, Scopus, Web of Science, and Embase was conducted up to March 2024. Inclusion criteria encompassed randomized controlled trials (RCTs) evaluating probiotic interventions in asthma patients. Statistical analysis was done using RevMan 5.3, with odds ratios (OR) and 95% confidence intervals (CI) calculated, and heterogeneity assessed using I2 statistics.

Results
Twelve RCTs, comprising 1401 participants, met the inclusion criteria. The probiotic strains investigated included various Lactobacillus and Bifidobacterium species. Meta-analysis revealed significant improvements in asthma control test scores (OR 1.18, 95% CI: 1.18–3.64, p = 0.0001) following probiotic supplementation. Probiotics also improved fractional exhaled nitric oxide (FeNO) in one study, but pooled FeNO and eosinophil data were not statistically significant (p = 0.46 and p = 0.29, respectively). One study observed fewer asthma exacerbations in the probiotic group (24/212) compared to placebo (67/210), with no difference in exacerbation duration.

Conclusion
Probiotic supplementation may be beneficial in improving asthma symptom control with no significant impact on lung function indices or eosinophil levels. Probiotics can be a potential adjunctive therapy in asthma management, particularly for asthma symptom control.