bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dapagliflozin reduces systemic inflammation in patients with type 2 diabetes without known heart failure
Authors: Wang Dennis D. , Naumova Anna V. , Isquith Daniel , Sapp Jamie , Huynh Kim A. , Tucker Isabella , Balu Niranjan , Voronyuk Anna , Chu Baocheng , Ordovas Karen , Maynard Charles , Tian Rong , Zhao Xue-Qiao , Kim Francis 
Published: June 2024

Abstract
Objective
Sodium glucose cotransporter 2 (SGLT2) inhibitors significantly improve cardiovascular outcomes in diabetic patients; however, the mechanism is unclear. We hypothesized that dapagliflozin improves cardiac outcomes via beneficial effects on systemic and cardiac inflammation and cardiac fibrosis.

Research and design methods
This randomized placebo-controlled clinical trial enrolled 62 adult patients (mean age 62, 17% female) with type 2 diabetes (T2D) without known heart failure. Subjects were randomized to 12 months of daily 10 mg dapagliflozin or placebo. For all patients, blood/plasma samples and cardiac magnetic resonance imaging (CMRI) were obtained at time of randomization and at the end of 12 months. Systemic inflammation was assessed by plasma IL-1B, TNFα, IL-6 and ketone levels and PBMC mitochondrial respiration, an emerging marker of sterile inflammation. Global myocardial strain was assessed by feature tracking; cardiac fibrosis was assessed by T1 mapping to calculate extracellular volume fraction (ECV); and cardiac tissue inflammation was assessed by T2 mapping.

Results
Between the baseline and 12-month time point, plasma IL-1B was reduced (− 1.8 pg/mL, P = 0.003) while ketones were increased (0.26 mM, P = 0.0001) in patients randomized to dapagliflozin. PBMC maximal oxygen consumption rate (OCR) decreased over the 12-month period in the placebo group but did not change in patients receiving dapagliflozin (− 158.9 pmole/min/106 cells, P = 0.0497 vs. − 5.2 pmole/min/106 cells, P = 0.41), a finding consistent with an anti-inflammatory effect of SGLT2i. Global myocardial strain, ECV and T2 relaxation time did not change in both study groups.

Clinical Trial.gov Registration
NCT03782259.
Capmatinib is an effective treatment for MET-fusion driven pediatric high-grade glioma and synergizes with radiotherapy
Authors: Zuckermann Marc , He Chen , Andrews Jared , Bagchi Aditi , Sloan-Henry Roketa , Bianski Brandon , Xie Jia , Wang Yingzhe , Twarog Nathaniel , Onar-Thomas Arzu , Ernst Kati J. , Yang Lei , Li Yong , Zhu Xiaoyan , Ocasio Jennifer K. , Budd Kaitlin M. , Dalton James , Li Xiaoyu , Chepyala Divyabharathi , Zhang Junyuan , Xu Ke , Hover Laura , Roach Jordan T. , Chan Kenneth Chun-Ho , Hofmann Nina , McKinnon Peter J. , Pfister Stefan M. , Shelat Anang A. , Rankovic Zoran , Freeman Burgess B. , Chiang Jason , Jones David T. W. , Tinkle Christopher L. , Baker Suzanne J. 
Published: June 2024

Abstract
Background
Pediatric-type diffuse high-grade glioma (pHGG) is the most frequent malignant brain tumor in children and can be subclassified into multiple entities. Fusion genes activating the MET receptor tyrosine kinase often occur in infant-type hemispheric glioma (IHG) but also in other pHGG and are associated with devastating morbidity and mortality.

Methods
To identify new treatment options, we established and characterized two novel orthotopic mouse models harboring distinct MET fusions. These included an immunocompetent, murine allograft model and patient-derived orthotopic xenografts (PDOX) from a MET-fusion IHG patient who failed conventional therapy and targeted therapy with cabozantinib. With these models, we analyzed the efficacy and pharmacokinetic properties of three MET inhibitors, capmatinib, crizotinib and cabozantinib, alone or combined with radiotherapy.

Results
Capmatinib showed superior brain pharmacokinetic properties and greater in vitro and in vivo efficacy than cabozantinib or crizotinib in both models. The PDOX models recapitulated the poor efficacy of cabozantinib experienced by the patient. In contrast, capmatinib extended survival and induced long-term progression-free survival when combined with radiotherapy in two complementary mouse models. Capmatinib treatment increased radiation-induced DNA double-strand breaks and delayed their repair.

Conclusions
We comprehensively investigated the combination of MET inhibition and radiotherapy as a novel treatment option for MET-driven pHGG. Our seminal preclinical data package includes pharmacokinetic characterization, recapitulation of clinical outcomes, coinciding results from multiple complementing in vivo studies, and insights into molecular mechanism underlying increased efficacy. Taken together, we demonstrate the groundbreaking efficacy of capmatinib and radiation as a highly promising concept for future clinical trials.
Effects of super-enhancers in cancer metastasis: mechanisms and therapeutic targets
Authors: Liu Shenglan , Dai Wei , Jin Bei , Jiang Feng , Huang Hao , Hou Wen , Lan Jinxia , Jin Yanli , Peng Weijie , Pan Jingxuan 
Published: June 2024

AbstractMetastasis remains the principal cause of cancer-related lethality despite advancements in cancer treatment. Dysfunctional epigenetic alterations are crucial in the metastatic cascade. Among these, super-enhancers (SEs), emerging as new epigenetic regulators, consist of large clusters of regulatory elements that drive the high-level expression of genes essential for the oncogenic process, upon which cancer cells develop a profound dependency. These SE-driven oncogenes play an important role in regulating various facets of metastasis, including the promotion of tumor proliferation in primary and distal metastatic organs, facilitating cellular migration and invasion into the vasculature, triggering epithelial-mesenchymal transition, enhancing cancer stem cell-like properties, circumventing immune detection, and adapting to the heterogeneity of metastatic niches. This heavy reliance on SE-mediated transcription delineates a vulnerable target for therapeutic intervention in cancer cells. In this article, we review current insights into the characteristics, identification methodologies, formation, and activation mechanisms of SEs. We also elaborate the oncogenic roles and regulatory functions of SEs in the context of cancer metastasis. Ultimately, we discuss the potential of SEs as novel therapeutic targets and their implications in clinical oncology, offering insights into future directions for innovative cancer treatment strategies.
Association between monocyte-to-high-density lipoprotein-cholesterol ratio and gallstones in U.S. adults: findings from the National Health and Nutrition Examination Survey 2017–2020
Authors: Liu Xingwu , Yan Guanyu , Xu Boyang , Sun Mingjun 
Published: June 2024

Abstract
Background
Studies have indicated that monocyte-to-high-density lipoprotein cholesterol ratio (MHR) can be a reliable indicator of various diseases. However, the association between MHR and gallstone prevalence remains unclear. Therefore, this study aimed to explore any potential association between MHR and gallstone prevalence.

Methods
This study used data from the National Health and Nutrition Examination Survey (NHANES) 2017–March 2020. MHR was calculated as the monocyte count ratio to high-density lipoprotein cholesterol levels. Multiple logistic regression models, Cochran-Armitage trend test, and subgroup analyses were used to examine the association between MHR and gallstones.

Results
This study included 5907 participants, of whom 636 (10.77%) were gallstone formers. The study participants had a mean age of 50.78 ± 17.33 years. After accounting for multiple covariables, the multiple logistic regression model showed a positive linear association between MHR and gallstone odds. The subgroup analyses and interaction testing results revealed that the association between MHR and gallstones was statistically different across strata, including sex, smoking, asthma, and hypertension.

Conclusions
Gallstone prevalence positively associated with elevated MHR, indicating that MHR can be employed as a clinical indicator to assess gallstone prevalence.
Association between maternal blood lipids and neonatal hypoglycaemia in pregnancy with gestational diabetes mellitus: a cohort study
Authors: Zhang Mo , Huang Xiaoqing , Lin Suiwen , Liu Bin 
Published: June 2024

Abstract
Background
Gestational diabetes mellitus (GDM) prevalence is on the rise globally. Offspring of diabetic mothers face increased risk of neonatal hypoglycaemia (NH), and women with GDM have abnormal lipid profiles. However, there is no consensus on the link between maternal blood lipids and NH in infants from mothers with GDM. This study aimed to explore how maternal blood lipids affect NH.

Methods
A retrospective cohort study was conducted at the First Affiliated Hospital of Sun Yat-sen University. Information on participants’ baseline characteristics and maternal metabolic profiles of glucose and lipids was collected. Significant variables from the univariate analysis were included in logistic regression, which was used to construct the predictive model for NH. A nomogram was constructed for visualizing the model and assessed using the area under the receiver operating characteristic (ROC) curve (AUC).

Results
Neonatal capillary blood glucose (CBG) decreased rapidly in the first hour after birth, increased gradually from the first to the second hour, and then remained stable. In the NH group, 86.11% (502/583) of hypoglycaemia cases occurred within the first two hours after birth. Multivariate logistic regression suggested that the lipid indices of maternal apoprotein B/apoprotein A1 (Apo-B/Apo-A1) (odds ratio (OR) = 1.36, 95% confidence intervals (CIs): 1.049–1.764, P = 0.02) and apoprotein E (Apo-E) (OR = 1.014, 95% CIs: 1.004–1.024, P = 0.004) were positively associated with NH in neonates from mothers with GDM. Triglycerides (TGs) (OR = 0.883, 95% CIs: 0.788–0.986, P = 0.028) were inversely associated with NH. Maternal glycated haemoglobin (HbA1c), age, twin pregnancy and caesarean delivery also had predictive value of NH. The AUC of the nomogram derived from these factors for the prediction model of NH was 0.657 (95% CIs: 0.630–0.684).

Conclusions
The present study revealed that the Apo-B/Apo-A1 and Apo-E levels were associated with an increased risk of NH. A nomogram was developed to forecast the risk of NH in babies born to mothers with GDM, incorporating maternal blood lipids, HbA1c, age, twin pregnancy, and caesarean section. The trajectory of glycaemia for neonates indicates the need for intensive CBG monitoring within 2 h of birth for neonates from mothers with GDM.
Longitudinal strain correlates with 6-minute walk distance whereas ejection fraction and diastolic parameters do not
Authors: Petersen John W. , Bracewell Natalie , Schneider Kevin M. , Latner Joshua , Yang Shuang , Guo Yi 
Published: June 2024

Abstract
Background
Impaired functional capacity is a common symptom in patients with heart failure. Standard measures of left ventricular (LV) function, such as ejection fraction (EF) and LV diastolic parameters, do not correlate with measures of functional capacity. The aim of this study is to determine if measures of global and regional LV strain better correlate with 6-minute walk distance than does EF or measures of LV diastolic function.

Methods
120 patients referred to a cardiology clinic for evaluation of known or suspected heart failure were approached for enrollment. Of those 120 patients, 58 had an echocardiogram within 3 months of enrollment with images adequate for regional and global strain assessment, had no contra-indication to exercise testing, and had no previously documented non-cardiac explanation for dyspnea on exertion. In those 58 patients, 6-minute walk distance was measured, LV EF was determined with Simpson’s biplane method, and global and regional longitudinal strain were measured with TomTec Image Arena 4.5.1 software.

Results
LV EF had no correlation with 6-minute walk distance (r = 0.22, p = 0.09) even when controlling for age, gender, and BMI (p = 0.07). No measures of LV diastolic function (including E velocity, Deceleration Time, e’ annular velocities, or E/e’) had a correlation with 6-minute walk distance. Multiple measures of global and regional LV longitudinal systolic function had a correlation with 6-minute walk distance. Longitudinal strain of the basal LV segments had the strongest correlation with 6-minute walk distance (r= -0.36, p = 0.005), and correlation persisted after controlling for age, gender, BMI, and systolic blood pressure (p = 0.004).

Conclusions
Longitudinal strain correlates with a measure of functional capacity, but LVEF and traditional measures of LV diastolic dysfunction do not. Measures of longitudinal strain, especially in basal LV segments, will likely be an important marker of clinically relevant LV function.

Graphical Abstract
Low-dose overlap initiation with split tablets of buprenorphine in intubated intensive care unit patients with opioid use disorder
Authors: Szczesniak Laura , Britton Sarah , RN Theresa Baxter , Sullivan Ross 
Published: June 2024

Abstract
Background
As the opioid public health crisis evolves to include fentanyl and other potent synthetic opioids, more patients are admitted to the hospital with serious complications of drug use and frequently require higher levels of care, including intensive care unit (ICU) admission, for acute and chronic conditions related to opioid use disorder (OUD). This patient population poses a unique challenge when managing sedation and ensuring adequate ventilation while intubated given their high opioid requirements. Starting a patient on medications such as buprenorphine may be difficult for inpatient providers unfamiliar with its use, which may lead to undertreatment of patients with OUD, prolonged mechanical ventilation and length of stay.

Methods
We developed a 7-day buprenorphine low dose overlap initiation (LDOI) schedule for patients with OUD admitted to the ICU (Table 1). Buprenorphine tablets were split by pharmacists and placed into pre-made blister packs as a kit to be loaded into the automated medication dispensing machine for nursing to administer daily. An internal quality review validated the appropriate dosing of split-dose tablets. To simplify order entry and increase prescriber comfort with this new protocol, we generated an order set within our electronic health record software with prebuilt buprenorphine titration orders. This protocol was implemented alongside patient and healthcare team education and counseling on the LDOI process, with follow-up offered to all patients upon discharge.

Results
Here we report a series of 6 ICU patients started on buprenorphine using the LDOI schedule with split buprenorphine tablets. None of the 6 patients experienced precipitated withdrawal upon buprenorphine initiation using the LDOI schedule, and 5/6 patients were successfully extubated during the buprenorphine initiation. Four of six patients had a decrease in daily morphine milligram equivalents, with 3 patients transitioning to buprenorphine alone.

Conclusion
Initiating buprenorphine via LDOI was found to be successful in the development of a protocol for critically ill patients with OUD. We examined LDOI of buprenorphine in intubated ICU patients and found no events of acute precipitated withdrawal. This protocol can be used as a guide for other institutions seeking to start critically ill patients on medication treatment for OUD during ICU admission.
“If it wasn’t for them, I don’t think I would be here”: experiences of the first year of a safer supply program during the dual public health emergencies of COVID-19 and the drug toxicity crisis
Authors: Kolla Gillian , Pauly Bernie , Cameron Fred , Hobbs Heather , Ranger Corey , McCall Jane , Majalahti Jerry , Toombs Kim , LeMaistre Jack , Selfridge Marion , Urbanoski Karen 
Published: June 2024

Abstract
Background
In response to the devastating drug toxicity crisis in Canada driven by an unregulated opioid supply predominantly composed of fentanyl and analogues, safer supply programs have been introduced. These programs provide people using street-acquired opioids with prescribed, pharmaceutical opioids. We use six core components of safer supply programs identified by people who use drugs to explore participant perspectives on the first year of operations of a safer supply program in Victoria, BC, during the dual public health emergencies of COVID-19 and the drug toxicity crisis to examine whether the program met drug-user defined elements of an effective safer supply model.

Methods
This study used a community-based participatory research approach to ensure that the research was reflective of community concerns and priorities, rather than being extractive. We interviewed 16 safer supply program participants between December 2020 and June 2021. Analysis was structured using the six core components of effective safer supply from the perspective of people who use drugs, generated through a prior study.

Results
Ensuring access to the ‘right dose and right drugs’ of medications was crucial, with many participants reporting success with the available pharmaceutical options. However, others highlighted issues with the strength of the available medications and the lack of options for smokeable medications. Accessing the safer supply program allowed participants to reduce their use of drugs from unregulated markets and manage withdrawal, pain and cravings. On components related to program operations, participants reported receiving compassionate care, and that accessing the safer supply program was a non-stigmatizing experience. They also reported receiving support to find housing, access food, obtain ID, and other needs. However, participants worried about long term program sustainability.

Conclusions
Participants in the safer supply program overwhelmingly appreciated it and felt it was lifesaving, and unlike other healthcare or treatment services they had previously accessed. Participants raised concerns that unless a wider variety of medications and ability to consume them by multiple routes of administration became available, safer supply programs would remain unable to completely replace substances from unregulated markets.
The impact of a reproductive health voucher in Uganda using a quasi-experimental matching design
Authors: Andersson Christian , Kawuki Tonny , Månsson Jonas , Nankaja Christine , Sund Krister , Wigren Emma , Zungu Mathias Mulumba 
Published: June 2024

AbstractThis study assesses the impact of a voucher project that targeted vulnerable and poor pregnant women in Uganda. Highly subsidised vouchers gave access to a package of safe delivery services consisting of four antenatal visits, safe delivery, one postnatal visit, the treatment and management of selected pregnancy-related medical conditions and complications, and emergency transport. Vouchers were sold during the project’s operational period from 2016 to 2019. This study covers 8 out of 25 project-benefiting districts in Uganda and a total of 1,881 pregnancies, including both beneficiary and non-beneficiary mothers. Using a matching design, the results show a positive effect on the survival of new-born babies. The difference in the survival rate between the control group and the treatment group is 5.4% points, indicating that the voucher project reduced infant mortality by more than 65 per cent.
Depression symptoms and suicidal ideation among HIV infected Rwandans: the mediating and moderating effects of complicated grief and substance abuse
Authors: Uwiringiyimana Anualitha , Niyonsenga Japhet , Lisette Kethina Gaju , Bugenimana Athanasie , Mutabaruka Jean , Nshimiyimana Augustin 
Published: June 2024

Abstract
Background
People with HIV/AIDS (PWHA) have 7–36 times greater risk for completed suicide associated with depression symptoms compared to general population. However, no study has sufficiently analyzed the mediating or moderating variables of the relationship between depression and suicidal ideation in Rwanda.

Objectives
This study aimed to examine how complicated grief mediates and substance abuse moderates the effects of depression symptoms on suicidal ideation.

Methods
Data were collected from a convenient sample of 140 participants (M-age = 38.79 years, SD = 10.218) receiving antiretroviral therapy (ART) at Remera Health Center in a cross-sectional study. Multiple linear regression and Sobel test were used to examine the relationships between depression symptoms, complicated grief, suicidal ideation, and substance abuse.

Results
The results indicated that 29% of the sample had clinically significant symptoms of depression and 18% had suicidal ideation. The interaction between substance abuse and depression symptoms (β = .468, t = 8.02, p = 0.000) was a significant predictor, explaining the 55.7% of variance in suicidal ideation. Furthermore, the Sobel test demonstrated that complicated grief mediated the effects of depression symptoms (t = 4.67, SE = 0.0101, p ≤ 0.001) on suicidal ideation.

Conclusion
The results suggest that depression symptoms are associated with an increased risk of suicidal ideation, and this risk significantly amplified in the presence of complicated grief and substance abuse. These findings highlight the importance of integrating mental health services, particularly those addressing depression, complicated grief, and substance abuse, into HIV care programs to mitigate the risk of suicidal ideation among PWHA.
Interrelations of managing position with person-environment fit of gender-role orientation, and burnout
Authors: Wacker Eva , Fischer Axel , Schorlemmer Julia 
Published: June 2024

Abstract
Background
In previous studies a moderator effect of management position could be found between Person-environment fit of masculinity, and burnout. Present study goals are to analyze previous fundings of the importance of the individual gender-role in relation to the work environment in more detail.

Methods
In this cross sectional explanative study, an online survey took place using Gender Role Orientation Scale (GTS +) by Altstötter-Gleich and DearEmployee-Survey by Wiedemann et al. The sample consists of 891 participants–516 female (58%), 373 male (42%), among those 277 executives (32%) and 594 participants without managerial responsibility (68%), age 17–70 years (M = 29.86; S = 7.67). Four groups were divided according to P-E fit in femininity and P-E fit in masculinity, this enabled a more precise distinction between the participants. The proportions of executives were determined, and compared in each group by a $${\chi }^{2}$$

χ

2

-Test Hierarchical linear regression models predicting burnout and proving moderator effects of managerial position were calculated for each group.

Results
The proportions of executives were the highest in the two groups with participants, who had a higher individual masculinity compared to their work environment. A moderator effect of managerial position between P-E fit in masculinity and burnout was found in group “Indifferent” (participants with lower feminity and masculinity compared with work environment). With a worse P-E fit in masculinity burnout values rise for individuals with no managerial position. On the other hand, among leaders burnout values decrease a worse P-E fit in masculinity.

Conclusions
People with a high individual masculinity compared to work environment tend more to be selected as managers, regardless of the individual characteristics of femininity, which may generally lead to a highly masculine and less feminine leadership and corporate culture. This culture could increase burnout risk for people with low individual masculinity and high feminity scores compared to work environment as well as for persons with low individual masculinity and feminity compared to work environment, especially if they are not in a managerial position.