bluuebunny/crossref_metadata_2025_split huggingface dataset:
PPARα Agonism Enhances Immune Response to Radiotherapy While Dietary Oleic Acid Results in Counteraction
Authors: Ross Richard Blake , Gadwa Jacob , Yu Justin , Darragh Laurel B. , Knitz Michael W. , Nguyen Diemmy , Olimpo Nicholas A. , Abdelazeem Khalid N.M. , Nguyen Alexander , Corbo Sophia , Van Court Benjamin , Beynor Jessica , Neupert Brooke , Saviola Anthony J. , D'Alessandro Angelo , Karam Sana D. 
Published: February 2024

Abstract

Purpose:
Head and neck cancer (HNC) improvements are stagnant, even with advances in immunotherapy. Our previous clinical trial data show that altered fatty acid (FA) metabolism correlates with outcome. We hypothesized that pharmacologic and dietary modulation of FA catabolism will affect therapeutic efficacy.

Experimental Design:
We performed in vivo and in vitro experiments using PPARα agonism with fenofibrate (FF) or high oleic acid diets (OAD) with radiotherapy, generating metabolomic, proteomic, stable isotope tracing, extracellular flux analysis, and flow-cytometric data to investigate these alterations.

Results:
FF improved antitumor efficacy of high dose per fraction radiotherapy in HNC murine models, whereas the OAD reversed this effect. FF-treated mice on the control diet had evidence of increased FA catabolism. Stable isotope tracing showed less glycolytic utilization by ex vivo CD8+ T cells. Improved efficacy correlated with intratumoral alterations in eicosanoid metabolism and downregulated mTOR and CD36.

Conclusions:
Metabolic intervention with increased FA catabolism improves the efficacy of HNC therapy and enhances antitumoral immune response.
Statins Prevent the Deleterious Consequences of Placental Chemerin Upregulation in Preeclampsia
Authors: Tan Lunbo , Kluivers Ans C.M. , Cruz-López Edwyn O. , Broekhuizen Michelle , Chen Zhongli , Neuman Rugina I. , Schoenmakers Sam , Ruijgrok Liesbeth , van de Velde Daan , de Winter Brenda C.M. , van den Bogaerdt Antoon J. , Lu Xifeng , Danser A.H. Jan , Verdonk Koen 
Published: February 2024

BACKGROUND:
Chemerin, an inflammatory adipokine, is upregulated in preeclampsia, and its placental overexpression results in preeclampsia-like symptoms in mice. Statins may lower chemerin.

METHODS:
Chemerin was determined in a prospective cohort study in women suspected of preeclampsia and evaluated as a predictor versus the sFlt-1 (soluble fms-like tyrosine kinase-1)/PlGF (placental growth factor) ratio. Chemerin release was studied in perfused placentas and placental explants with or without the statins pravastatin and fluvastatin. We also addressed statin placental passage and the effects of chemerin in chorionic plate arteries.

RESULTS:
Serum chemerin was elevated in women with preeclampsia, and its addition to a predictive model yielded significant effects on top of the sFlt-1/PlGF ratio to predict preeclampsia and its fetal complications. Perfused placentas and explants of preeclamptic women released more chemerin and sFlt-1 and less PlGF than those of healthy pregnant women. Statins reversed this. Both statins entered the fetal compartment, and the fetal/maternal concentration ratio of pravastatin was twice that of fluvastatin. Chemerin constricted plate arteries, and this was blocked by a chemerin receptor antagonist and pravastatin. Chemerin did not potentiate endothelin-1 in chorionic plate arteries. In explants, statins upregulated low-density lipoprotein receptor expression, which relies on the same transcription factor as chemerin, and NO release.

CONCLUSIONS:
Chemerin is a biomarker for preeclampsia, and statins both prevent its placental upregulation and effects, in an NO and low-density lipoprotein receptor–dependent manner. Combined with their capacity to improve the sFlt-1/PlGF ratio, this offers an attractive mechanism by which statins may prevent or treat preeclampsia.
Assessment of Price Variation in Coronary Artery Bypass Surgery at US Hospitals
Authors: Wei Chen , Paranjpe Ishan , Sharma Pranav , Milligan Michael , Lam Miranda , Heidenreich Paul A. , Kalwani Neil , Schulman Kevin , Sandhu Alexander 
Published: February 2024

Background
Little is known about hospital pricing for coronary artery bypass grafting (CABG). Using new price transparency data, we assessed variation in CABG prices across US hospitals and the association between higher prices and hospital characteristics, including quality of care.

Methods and Results
Prices for diagnosis related group code 236 were obtained from the Turquoise database and linked by Medicare Facility ID to publicly available hospital characteristics. Univariate and multivariable analyses were performed to assess factors predictive of higher prices. Across 544 hospitals, median commercial and self‐pay rates were 2.01 and 2.64 times the Medicare rate ($57 240 and $75 047, respectively, versus $28 398). Within hospitals, the 90th percentile insurer‐negotiated price was 1.83 times the 10th percentile price. Across hospitals, the 90th percentile commercial rate was 2.91 times the 10th percentile hospital rate. Regional median hospital prices ranged from $35 624 in the East South Central to $84 080 in the Pacific. In univariate analysis, higher inpatient revenue, greater annual discharges, and major teaching status were significantly associated with higher prices. In multivariable analysis, major teaching and investor‐owned status were associated with significantly higher prices (+$8653 and +$12 200, respectively). CABG prices were not related to death, readmissions, patient ratings, or overall Centers for Medicare and Medicaid Services hospital rating.

Conclusions
There is significant variation in CABG pricing, with certain characteristics associated with higher rates, including major teaching status and investor ownership. Notably, higher CABG prices were not associated with better‐quality care, suggesting a need for further investigation into drivers of pricing variation and the implications for health care spending and access.
Cortical Spreading Depolarization in Moyamoya Vasculopathy: A Case Series
Authors: Dömer Patrick , Helgers Simeon O.A. , Meinert Franziska , Sánchez-Porras Renán , Mathys Christian , Witt Karsten , Vajkoczy Peter , Hecht Nils , Woitzik Johannes 
Published: February 2024

BACKGROUND:
Spreading depolarization describes a near-complete electrical discharge with altered local cerebral blood flow. It is described in association with acute and chronic diseases like hemorrhagic stroke or migraine. Moyamoya vasculopathy is a chronic, progressive cerebrovascular disorder leading to cerebral hypoperfusion, hemodynamically insufficient basal collateralization, and increased cortical microvascularization.

METHODS:
In a prospective case series, we monitored for spontaneous spreading depolarization activity by using intraoperative laser speckle imaging for real-time visualization and measurement of cortical perfusion and cerebrovascular reserve capacity during cerebral revascularization in 4 consecutive patients with moyamoya.

RESULTS:
Spontaneous spreading depolarization occurrence was documented in a patient with moyamoya before bypass grafting. Interestingly, this patient also exhibited a marked preoperative increase in angiographic collateral vessel formation.

CONCLUSIONS:
The spontaneous occurrence of SDs in moyamoya vasculopathy could potentially provide an explanation for localized cortical infarction and increased cortical microvascular density in these patients.
Evaluation of Large Ischemic Cores to Predict Outcomes of Thrombectomy: A Proposal of a Novel Treatment Phase
Authors: Umemura Takeru , Tanaka Yuko , Kurokawa Toru , Miyaoka Ryo , Idei Masaru , Ohta Hirotsugu , Yamamoto Junkoh 
Published: February 2024

Background
Endovascular treatment of large ischemic cores is challenging. The severity of ischemic stress is assessed using the apparent diffusion coefficient (ADC). We aimed to evaluate the ADC in patients with a low Alberta Stroke Program Early CT [Computed Tomography] Score using diffusion‐weighted imaging and whether it correlates with clinical outcomes.

Methods
This study included consecutive patients with acute large ischemic stroke (Alberta Stroke Program Early CT Score‐diffusion‐weighted imaging ≤5) who underwent endovascular treatment with successful recanalization between April 2014 and March 2023. The most frequent ADC (peak ADC) and diffusion‐weighted imaging lesion volumes were assessed. The primary outcome was the 3‐month modified Rankin Scale (mRS) score. Good (mRS score, 0–3) and poor clinical outcomes (mRS score, 4–6) were compared to confirm whether ADC was associated with clinical outcomes.

Results

In total, 78 patients were enrolled in this study; 30 had an mRS score of 0 to 3 at 3 months. The peak ADC in these patients was significantly higher than that in patients with mRS scores of 4 to 6 (
P
= 0.0002). In multivariate analysis, peak ADC was strongly associated with good clinical outcomes (odds ratio, 1.231;
P
= 0.0135) rather than onset‐to‐recanalization time and ischemic core volume. The optimal peak ADC threshold for discriminating between the mRS groups was 520×10
−6
mm
2
/s with a sensitivity of 75% and a specificity of 73%. Good clinical outcomes were more frequently observed in patients with peak ADC ≥520×10
−6
mm
2
/s (
P
<0.0001).

Conclusion

In large ischemic cores, diffusion‐weighted imaging lesions with peak ADCs ≥520×10
−6
mm
2
/s are associated with favorable outcomes. Evaluation of the ischemic core is necessary to confirm endovascular treatment.
The comparative effectiveness of combined hydrodilatation/corticosteroid procedure with two different quantities for adhesive capsulitis
Authors: Lin Chien-Lin , Chuang Tien-Yow , Lin Pei-Hsin , Wang Kevin A , Chuang Eric , Wang Jia-Chi 
Published: February 2024

Objective To assess the efficacy of injecting various amounts of fluid into the shoulder joints for capsule distension in patients with adhesive capsulitis. Design A randomized controlled trial. Setting Outpatient clinic of a tertiary care centre. Participants Eighty-four patients with adhesive capsulitis underwent a baseline (time0), 6 weeks (time1), and 12 weeks (time2) follow-up after hydrodilitation. Intervention Group 1 (n  =  42) received 20 ml of lidocaine, steroid, and saline hydrodilatation via posterior glenohumeral recess, while Group 2 (n  =  42) received 10 ml of lidocaine, steroid, and saline hydrodilitation. Main measures The primary outcome was the visual analogue scale for pain. The secondary outcomes were shoulder pain and disability index (SPADI) and ROM of the shoulder. Results There was a significant reduce in VAS scores for pain, SPADI scores, and increased shoulder ROM in both groups over time; however, the group-by-time interactions for any of the outcomes between groups were not significant except VAS pain in motion. Post-hoc pairwise analysis of the marginal effect of time and group showed that the significant difference of VAS in motion is due to time effect: time1 vs time0 (95% CI −4.09 to −2.68), time2 vs time0 (−4.21 to −2.77), and time2 vs time1 (−0.83 to 0.63), without between-group difference: group 1 vs group 2 (−0.38 to 0.59). Conclusion Our study suggests hydrodilatation achieved an optimal effect at time1 for patients with adhesive capsulitis in both groups, and adding more saline offers additional benefits in flexion and external roatation until time2.
Pregnancy- and parenting-related barriers to receiving medication for opioid use disorder: A multi-paneled qualitative study of women in treatment, women who terminated treatment, and the professionals who serve them
Authors: Apsley Hannah B , Brant Kristina , Brothers Sarah , Harrison Eric , Skogseth Emma , Schwartz Robert P , Jones Abenaa A 
Published: February 2024

Background: Women face unique barriers when seeking treatment for substance use disorders, often related to pregnancy and parenting. Objectives: This study adds to the extant literature by elucidating the pregnancy- and parenting-related barriers women face when initiating or continuing medication for opioid use disorder, specifically. Design: This study is based on qualitative semi-structured interviews. Methods: Three subgroups participated in semi-structured interviews regarding their experiences (N = 42): women with current or past opioid use disorders who have used or were presently using medication for opioid use disorder, professionals working in substance use disorder treatment programs, and criminal justice professionals. Results: Three parenting-related subthemes were identified: (1) insufficient access to childcare to navigate appointments and meetings, (2) fear of losing custody of, or access to, one’s children, and (3) prioritizing one’s children’s needs before one’s own. Three subthemes were identified with regard to pregnancy as a barrier: (1) hesitancy among physicians to prescribe medication for opioid use disorder for pregnant patients, (2) limited access to resources in rural areas, and (3) difficulty navigating a complex, decentralized health system. Conclusion: Systemic changes are needed to reduce pregnant and parenting women’s barriers to seeking medication for opioid use disorder. These include improved childcare support at both in-patient and outpatient treatment programs, which would assuage women’s barriers related to childcare, as well as their fears of losing access to their children if they spend time away from their children for treatment. An additional systemic improvement that may reduce barriers for these women is access to comprehensive, integrated care for their prenatal care, postpartum care, pediatric appointments, and appropriate substance use disorder treatment.
Cerebral pulsatility in relation with various imaging markers of cerebral small vessel disease: a longitudinal community-based study
Authors: Zhong Weiyi , Xia Yiwei , Ying Yunqing , Wang Yi , Yang Lumeng , Liang Xiaoniu , Zhao Qianhua , Wu Jianjun , Liang Zonghui , Wang Xiaoxiao , Cheng Xin , Ding Ding , Dong Qiang 
Published: February 2024

Background: Cerebral pulsatility is thought to reflect arterial stiffness and downstream microvascular resistance. Although previous studies indicated cerebral pulsatility might closely relate to development of cerebral small vessel disease (SVD), yet evidence remain controversial and longitudinal data are rare. Objective: We aimed to explore relationships of cerebral pulsatility with severity and progression of various SVD imaging markers among the community-dwelling elderly. Design: A longitudinal cohort study. Methods: As part of the prospective community-based Shanghai Aging Study cohort, dementia- and stroke-free elderly were recruited for baseline assessment of cerebral pulsatility and SVD severity during 2010–2011 and traced for SVD progression during 2016–2017. Cerebral pulsatility was quantified for both anterior and posterior circulation with transcranial Doppler ultrasound. SVD imaging markers were measured with brain magnetic resonance imaging (MRI) including white matter hyperintensities (WMHs), enlarged perivascular spaces (ePVS), lacunes, and microbleeds. The cross-sectional and longitudinal relationships between cerebral pulsatility and SVD were analyzed by univariable and multivariable regression models. Results: Totally, 188 eligible subjects were included at baseline and out of them, 100 (53.19%) returned for a 7-year follow-up. At baseline, increased pulsatility of posterior circulation was independently associated with more periventricular WMH (PWMH) and ePVS in basal ganglia (BG-ePVS) but not with other SVD markers. Longitudinally, higher posterior pulsatility predicted greater PWMH progression in participants with hypertension (β = 2.694, standard error [SE] = 1.112, p = 0.020), whereas pulsatility of anterior circulation was shown to prevent BG-ePVS progression among followed-up elderly (β = −6.737, SE = 2.685, p = 0.012). However, no significant relationship was found between cerebral pulsatility and burden of lacunes or cerebral microbleeds. Conclusion: Higher pulsatility of posterior circulation could worsen PWMH progression, especially for participants with hypertension. But for development of ePVS, increased cerebral pulsatility could play a compensatory role among several healthy elderly. The distinct relationships between cerebral pulsatility and various SVD markers emphasized the importance of individualized SVD management.
Eomesodermin-expressing CD4+ Th cells and association with pregnancy in multiple sclerosis
Authors: Faissner Simon , Bongert Marielena , Trendelenburg Paulina , Thiel Sandra , Yamamura Takashi , Hellwig Kerstin , Gold Ralf 
Published: February 2024

Background: Pregnancy in patients with multiple sclerosis (MS) is accompanied by a decline of relapse activity with increased risk of relapses 3 months post-partum, for unknown reasons. Eomesodermin+ T-helper cells (Eomes+ Th cells) are known to mediate neuroinflammation and disease progression in MS and are induced by prolactin-secreting cells. Objectives: Here, investigated immune cell alterations and the pathophysiological role of Eomes+ Th cells for disease activity during pregnancy and post-partum in MS. Methods: We enrolled n = 81 pregnant patients with relapsing-remitting MS (RRMS), n = 27 post-partum RRMS and n = 26 female RRMS control patients under the umbrella of the German Multiple Sclerosis and Pregnancy Registry. Clinical data were collected and immune cell alterations were analysed using flow cytometry. Results: While CD3+CD4+ Th cells were unaffected, CD3+CD8+ cytotoxic T-cells were elevated post-partum ( p = 0.02) with reduced B-cell frequencies ( p = 0.01) compared to non-pregnant RRMS patients. NK cells were elevated during first trimester ( p = 0.02) compared to the third trimester. Frequencies of Eomes+ Th and Eomes+ Tc cells did not differ. There was no correlation of prolactin release and expression of Eomes+ Th cells. However, Eomes+ Th cells correlated with lower frequencies of regulatory T-cells during second ( r = −0.42; p < 0.05) and third trimester ( r = −0.37; p < 0.05). Moreover, Eomes+ Th cells correlated with frequencies of B-cells during third trimester ( r = 0.54; p = 0.02). Frequencies of Eomes+ Th cells were not associated with the number of relapses before pregnancy, during pregnancy or post-partum. However, Eomes+ Th cells strongly correlated with disability post-partum as assessed using the EDSS ( r = 0.52; p = 0.009). Discussion: Pregnancy in MS is associated with robust immunological alterations. Eomes+ Th cells are capable of inducing immune cell alterations during the course of pregnancy, most evident during the second and third trimester as shown with a correlation of reduced Treg cells and a significant increase of B-cells. Importantly, Eomes+ Th cells correlate with disability post-partum. In summary, during late pregnancy in MS an inflammatory, cytotoxic and dysregulated immunological environment is primed gaining function post-delivery. This may be responsible for post-partum disability accumulation.
Investigation of the Effect of 70 Potential Interferents on Measurement Results of Two Blood Glucose Monitoring Systems
Authors: Baumstark Annette , Pleus Stefan , Mende Jochen , Jendrike Nina , Tesar Martina , Schauer Sebastian , Sugiyama Takayuki , Aoki Takashi , Sugiura Mako , Freckmann Guido , Haug Cornelia 
Published: February 2024

Background: Reliable blood glucose (BG) measurements are important for people with diabetes to manage their therapy as well as in point-of-care testing (POCT) performed by health care professionals to monitor BG of patients or even to diagnose diabetes. Among other factors, endogenous and exogenous substances present in blood samples can impact the measurement results. To ensure and prove that blood glucose monitoring systems (BGMSs) are robust in terms of potential interferents, manufacturers have to perform extensive evaluations. Method: An interference screening test was performed for three reagent system lots of a POCT system and of a BGMS for self-monitoring of BG. A paired-difference approach based on ISO 15197:2013 and CLSI guideline EP07 was used with venous whole blood samples at two different glucose concentrations. Seventy potential interferents expected to be common in people with diabetes were evaluated. Results: The interference effects were determined as normalized biases between test samples and corresponding control samples. For 69 of the 70 investigated potential interferents, both systems met the predefined acceptance criteria, with the normalized biases falling within ±10 mg/dL or ±10% at glucose concentrations ≤100 mg/dL or >100 mg/dL, respectively, for each of the three evaluated reagent system lots. Conclusions: The BGMS investigated in this study were found to be robust with respect to the 70 evaluated potential interferents. Interference effects were observed only for N-Acetyl-L-cysteine. Extensive evaluations of potential interfering factors can make an important contribution to ensure reliability of BGMS.
Association of Burnout With Primary Care Clinician Perception of Team-Based Scheduling Support
Authors: Funk Kylee A. , Stillman Martin , Wang Qi , Manser Sarah Turcotte , Rogers Elizabeth A. 
Published: February 2024

Introduction: Primary care clinician burnout is pervasive and detrimental. How components of teamwork and clinic culture might contribute to burnout remains unsettled. Objective: To examine associations between primary care clinician perceptions of specific components of teamwork and of organizational culture, and perceived stress and burnout. Methods: Cross-sectional survey study of primary care clinicians from 5 county health system clinics. Measures: Perceptions of teamwork related to coordination of care, and clinic provision of chronic disease self-management support; values alignment and workplace equity; and demographics. Data Analysis: Descriptive statistics and Spearman’s correlations to examine associations, controlling for clinic and examining response variability by clinic. Results: Of 72 clinicians, 64% were female and 32% non-white. About 56% had worked at least 4 years and half worked 5 to 6 half days/week or more in their clinic. Clinicians who reported having someone on the clinician’s care team routinely schedule follow-up appointments for patients with complex chronic illnesses reported lower stress and burnout. Those who perceived greater values alignment with their clinic and greater personal and employee equitable treatment had lower stress and burnout. Conclusions: Teamwork among clinicians and non-clinical staff, a component of teamwork that is not well-considered in current literature, could be an important piece of the puzzle to decrease the persistent and challenging issue of stress and burnout among primary care clinicians.