bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endothelial biomarkers and platelet reactivity on ticagrelor versus clopidogrel in patients after acute coronary syndrome with and without concomitant type 2 diabetes: a preliminary observational study
Authors: Chyrchel Bernadeta , Kruszelnicka Olga , Surdacki Andrzej 
Published: November 2022

Abstract
Background
Pleiotropic effects have been implicated in clinical benefits of ticagrelor compared to thienopyridine P2Y12 antagonists. There are conflicting data regarding effects of ticagrelor vs. thienopyridine P2Y12 blockers on endothelial function. Our aim was to compare endothelial biomarkers and their relations with platelet reactivity in real-world patients after acute coronary syndrome (ACS) on maintenance dual antiplatelet therapy (DAPT) with ticagrelor or clopidogrel stratified by diabetes status.

Methods
Biochemical indices of endothelial dysfunction/activation and platelet reactivity by multiple electrode aggregometry were compared in 126 stable post-ACS subjects (mean age: 65 ± 10 years, 92 men and 34 women), including patients with (n = 61) or without (n = 65) coexistent type 2 diabetes (T2DM) on uneventful maintenance DAPT with either ticagrelor (90 mg b.d.) or clopidogrel (75 mg o.d.) in addition to low-dose aspirin. Exclusion criteria included a complicated in-hospital course, symptomatic heart failure, left ventricular ejection fraction < 40% and relevant coexistent diseases except for well-controlled diabetes, mild renal insufficiency or hypertension.

Results
Clinical characteristics were similar in patients on ticagrelor (n = 62) and clopidogrel (n = 64). The adenosine diphosphate-induced platelet aggregation and circulating soluble P-selectin (sP-selectin) were decreased in ticagrelor users irrespective of T2DM status (p < 0.001 and p < 0.01 for platelet reactivity and sP-selectin, respectively). Plasma levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) were lower in T2DM subjects on ticagrelor vs. clopidogrel (758 ± 162 vs. 913 ± 217 µg/L, p < 0.01). In contrast, plasma sVCAM-1 was similar in non-diabetic patients on ticagrelor and clopidogrel (872 ± 203 vs. 821 ± 210 µg/L, p > 0.7). The concentrations of sE-selectin, monocyte chemoattractant protein-1 and asymmetric dimethylarginine did not differ according to the type of P2Y12 antagonist regardless of T2DM status. Platelet reactivity was unrelated to any endothelial biomarker in subjects with or without T2DM.

Conclusions
Our preliminary findings may suggest an association of ticagrelor-based maintenance DAPT with favorable endothelial effects compared to clopidogrel users in stable post-ACS patients with T2DM. If proven, this could contribute to more pronounced clinical benefits of ticagrelor in diabetic subjects.
Skipping breakfast during pregnancy and hypertensive disorders of pregnancy in Japanese women: the Tohoku medical megabank project birth and three-generation cohort study
Authors: Aizawa Misato , Murakami Keiko , Takahashi Ippei , Onuma Tomomi , Noda Aoi , Ueno Fumihiko , Matsuzaki Fumiko , Ishikuro Mami , Obara Taku , Hamada Hirotaka , Iwama Noriyuki , Saito Masatoshi , Sugawara Junichi , Yaegashi Nobuo , Kuriyama Shinichi 
Published: November 2022

Abstract
Background
Hypertensive disorders of pregnancy (HDP) adversely affect the prognosis of mother and child, and the prognosis depends on the subtype of HDP. Skipping breakfast may be associated with increased blood pressure due to disruption of the circadian clock, but the association with the development of HDP has not been studied. The purpose of this study was to examine the association between skipping breakfast and the development of HDP and HDP subtypes in Japanese pregnant women.

Methods
Of the pregnant women who participated in the Tohoku Medical Megabank Project Three-Generation Cohort Study, 18,839 who answered the required questions were included in the analysis. This study had a cross-sectional design. The breakfast intake frequency from pre-pregnancy to early pregnancy was classified into four groups: daily, 5–6 times per week, 3–4 times per week, and 0–2 times per week. HDP was classified into gestational hypertension (GH), chronic hypertension (CH), preeclampsia (PE), and severe preeclampsia (SuPE). Multiple logistic regression analysis and multinomial logistic analysis were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for breakfast intake frequency and development of HDP or HDP subtypes. We performed a stratified analysis based on energy intake.

Results
Of the participants, 74.3% consumed breakfast daily, and 11.1% developed HDP. Women who consumed breakfast 0–2 times per week had a higher risk of HDP (OR: 1.33, 95% CI: 1.14–1.56), CH (OR: 1.63, 95% CI: 1.21–2.19), and PE (OR: 1.68, 95% CI: 1.27–2.21) than those who consumed breakfast daily. No association was found between skipping breakfast and the risk of developing GH (OR: 1.26, 95% CI: 0.99–1.61) and SuPE (OR: 0.91, 95% CI: 0.55–1.49). Stratified analysis showed that the risk of developing HDP due to skipping breakfast was highest in the group with the highest daily energy intake.

Conclusions
Skipping breakfast during pre-to early pregnancy is associated with the development of HDP. Further longitudinal studies are required to clarify the causal association between skipping breakfast and HDP.
The long-term survival of the doublet regimen of concurrent chemoradiation therapy for locoregionally advanced nasopharyngeal carcinoma: a retrospective study
Authors: Wang Zhi-Qiang , Feng Xu-Dong , Ge Chun-Lei , Yang Yi , Liang Na , Ye Qing , Fu Yang , Wei Jian , Zhang Yong , Li Rong-Qing 
Published: November 2022

AbstractObjectiveThis study introduces innovative strategies, the doublet regimen of concurrent chemoradiotherapy, to ensure longer survival for locoregionally advanced nasopharyngeal carcinoma.MethodsWe retrospectively reviewed 104 locoregionally advanced nasopharyngeal carcinoma patients who underwent taxane combined platinum-based concurrent chemoradiotherapy in our center between January 2013 and December 2018. All statistical analyses were performed using the Kaplan–Meier method (SPSS 23.0). Different groups were compared with the Wilcoxon rank-sum test.ResultsUltimately, 104 patients were selected for this study, including 18 and 86 who received either concurrent chemoradiation therapy alone or concurrent chemoradiation therapy plus adjuvant chemotherapy, respectively. The median follow-up time for progression free survival was 53.0 months (IQR 48.5–57.5). The 3-years progression-free survival (PFS), overall survival (OS), local–regional recurrence-free survival (LRRFS) and distant metastasis-free survival (DMFS) rates of the doublet regimen of concurrent chemotherapy for locoregionally advanced nasopharyngeal carcinoma were 85.9%, 96.0%, 96.0% and 90.8%, respectively. Additionally, we analyzed the subgroups and found that the 3-years PFS, OS, LRRFS and DMFS rates for stage III versus stage IVa were 97.8% versus 75.5% (P = 0.000), 100% versus 92.5% (P = 0.004), 100% versus 92.4% (P = 0.015) and 97.8% versus 82.8% (P = 0.002), respectively. During concurrent chemotherapy, acute chemotherapy adverse events of grade 3 or 4 was only 18.3%. Leukopenia was the most common acute chemotherapy adverse event (in 10 patients [9.6%]), followed by neutropenia (in 8 patients [7.6%]).ConclusionThe doublet regimen of taxane plus platinum concurrent chemoradiotherapy resulted in improved long-term survival of locoregionally advanced nasopharyngeal carcinoma patients, especially for local control rate and warrants further prospective evaluation.
Early and late recurrence after hepatectomy in patients with low-level HBV-DNA hepatocellular carcinoma under antiviral therapy
Authors: Li Ziqiang , Tan Chengpeng , Liu Xiaohong , Feng Zhe , Li Kun 
Published: November 2022

Abstract
Background
Antiviral therapy has been shown to benefit long-term survival after curative hepatectomy in patients with hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) with high levels of HBV-DNA, but the impact of antiviral therapy on patient recurrence in patients with low levels of HBV-DNA remains less clear.

Methods
This was a retrospective cohort study analyzing 296 patients with HBV-associated HCC with HBV-DNA levels < 2000 IU/mL who underwent hepatectomy at Zhongnan Hospital of Wuhan University between March 2013 and December 2017, of whom 157 patients received antiviral therapy (antiviral group) and 139 patients did not receive antiviral therapy (non-antiviral group), propensity score matching was used for survival analysis of patients in both groups, and subgroup analysis of major risk factors was performed.

Results
The baseline characteristics of the two groups were comparable. At a median follow-up of 54 months, the 1-, 3-, and 5-year overall survival rates after propensity score matching (PSM) were 94.9%, 80.8%, 66.5%, and 90.9%, 64.6%, 49.4% for the antiviral and non-antiviral groups, respectively, p = 0.009, and the corresponding 1-, 3-, and 5-year RFS for the two groups were 81.8%, 76.8%, 76.8%, and 67.7%, 55.6%, 55.6%, respectively. p = 0.001, and the overall survival and recurrence-free survival were significantly better in the antiviral group than in the non-antiviral group. Multi-factor COX regression analysis showed that prothrombin time ≥ 13 s, methemoglobin level ≥ 20 ng/ml, platelet count ≥ 100 × 109/L, tumor size > 5 cm, tumor multiplicity was associated with early recurrence, and antiviral treatment was an independent protective factor for early recurrence of HCC (HR, 0.431; 95% CI 0.274–0.679; p < 0.001), but not associated with a low risk of late relapse (HR, 0.822; 95% CI 0.526–1.284; p = 0.389), and the main risk factors for late relapse included AST levels > 40 IU/ml, ALP levels > 130 IU/L, and the presence of satellite nodules, and subgroup analysis showed that compared to HBeAg-positive patients, antiviral therapy could significantly prolonged the recurrence-free survival of HBeAg-negative patients.

Conclusion
Antiviral therapy reduces early tumor recurrence after hepatectomy in patients with low levels of HBV-DNA.
Prognostic factors for continence after surgical correction of ectopic ureters of 51 dogs with long-term follow-up
Authors: Visser Judith , Fieten Hille , van Velzen Hannah Wikje , Zaal Marjanne Duke , Kummeling Anne 
Published: November 2022

AbstractBackgroundAn ectopic ureter is a congenital malformation characterized by caudal displacement of one or both ureteral orifices and is the most common cause of urinary incontinence in young dogs. Complete resolution of incontinence after surgery has been reported in 25–82% of dogs. The aim of this study was to identify preoperative prognostic factors for continence after surgical treatment of dogs with an ectopic ureter. Dogs were included if surgical correction of an ectopic ureter was performed and at least 1 year follow-up was available.ResultsFifty-one dogs met the inclusion criteria. The ectopic ureters were either intramural (91%) or extramural (9%). The ectopic ureters were bilateral in 49% of cases. Overall median follow-up time after surgery was 6.5 years (range 1–13 years). Surgical correction alone resolved urinary incontinence in 47% of cases. Low grade pre-operative incontinence, male sex and pre-operative presence of ureteral or renal pyelum dilation were significantly associated with urinary continence after surgery.ConclusionsDogs with severe preoperative incontinence were less likely to become completely continent after surgery, whereas male sex and preoperative dilation of the ureter or renal pyelum were positive prognostic indicators for continence. These results may assist in predicting outcome after surgical correction of ectopic ureters and suggest assessment of pre-operative urethral pressure profiling in future studies.
Dopamine-induced astrocytic Ca2+ signaling in mPFC is mediated by MAO-B in young mice, but by dopamine receptors in adult mice
Authors: Kim Sunpil , Kwon Jea , Park Mingu Gordon , Lee C. Justin 
Published: November 2022

AbstractDopamine (DA) plays a vital role in brain physiology and pathology such as learning and memory, motor control, neurological diseases, and psychiatric diseases. In neurons, it has been well established that DA increases or decreases intracellular cyclic AMP (cAMP) through D1-like or D2-like dopamine receptors, respectively. In contrast, it has been elusive how astrocytes respond to DA via Ca2+ signaling and regulate synaptic transmission and reward systems. Previous studies suggest various molecular targets such as MAO-B, D1R, or D1R–D2R heteromer to modulate astrocytic Ca2+ signaling. However, which molecular target is utilized under what physiological condition remains unclear. Here, we show that DA-induced astrocytic Ca2+ signaling pathway switches during development: MAO-B is the major player at a young age (5–6 weeks), whereas DA receptors (DARs) are responsible for the adult period (8–12 weeks). DA-mediated Ca2+ response in the adult period was decreased by either D1R or D2R blockers, which are primarily known for cyclic AMP signaling (Gs and Gi pathway, respectively), suggesting that this Ca2+ response might be mediated through Gq pathway by D1R–D2R heterodimer. Moreover, DAR-mediated Ca2+ response was not blocked by TTX, implying that this response is not a secondary response caused by neuronal activation. Our study proposes an age-specific molecular target of DA-induced astrocytic Ca2+ signaling: MAO-B in young mice and DAR in adult mice.
Pediatric out-of-hospital cardiac arrest in Denmark
Authors: Holgersen Mathias Geldermann , Jensen Theo W. , Breindahl Niklas , Kjerulff Julie L. B. , Breindahl Sara H. , Blomberg Stig Nikolaj Fasmer , Wolthers Signe Amalie , Andersen Lars Bredevang , Torp-Pedersen Christian , Mikkelsen Søren , Lippert Freddy , Christensen Helle Collatz ,   Danish Cardiac Arrest Registry Group
Published: November 2022

Abstract
Background
Pediatric out-of-hospital cardiac arrest (POHCA) has received limited attention. All causes of POHCA and outcomes were examined during a 4-year period in a Danish nationwide register and prehospital medical records. The aim was to describe the incidence, reversible causes, and survival rates for POHCA in Denmark.

Methods
This is a registry-based follow-up cohort study. All POHCA for a 4-year period (2016–2019) in Denmark were included. All prehospital medical records for the included subjects were reviewed manually by five independent raters establishing whether a presumed reversible cause could be assigned.

Results
We identified 173 cases within the study period. The median incidence of POHCA in the population below 17 years of age was 4.2 per 100,000 persons at risk. We found a presumed reversible cause in 48.6% of cases, with hypoxia being the predominant cause of POHCA (42.2%). The thirty-day survival was 40%. Variations were seen across age groups, with the lowest survival rate in cases below 1 year of age. Defibrillators were used more frequently among survivors, with 16% of survivors defibrillated bystanders as opposed to 1.9% in non-survivors and 24% by EMS personnel as opposed to 7.8% in non-survivors. The differences in initial rhythm being shockable was 34% for survivors and 16% for non-survivors.

Conclusion
We found pediatric out-of-hospital cardiac arrests was a rare event, with higher incidence and mortality in infants compared to other age groups of children. Use of defibrillators was disproportionally higher among survivors. Hypoxia was the most common presumed cause among all age groups.
Characteristics and therapeutic profile of TBI patients who underwent bilateral decompressive craniectomy: experience with 151 cases
Authors: Zhao Jian-Lan , Song Jie , Yuan Qiang , Bao Yi-Feng , Sun Yi-Rui , Li Zhi-Qi , Xi Cai-Hua , Yao Hai-Jun , Wang Mei-Hua , Wu Gang , Du Zhuo-Ying , Hu Jin , Yu Jian 
Published: November 2022

Abstract
Background
Decompressive craniectomy (DC) and intracranial pressure (ICP) monitoring are common approaches to reduce the death rate of Traumatic brain injury (TBI) patients, but the outcomes of these patients are unfavorable, particularly those who receive bilateral DC. The authors discuss their experience using ICP and other potential methods to improve the outcomes of TBI patients who receive bilateral DC.

Methods
Data from TBI patients receiving bilateral DC from Jan. 2008 to Jan. 2022 were collected via a retrospective chart review. Included patients who received unplanned contralateral DC after initial surgery were identified as unplanned secondary surgery (USS) patients. Patients’ demographics and baseline medical status; pre-, intra-, and postoperative events; and follow-up visit outcome data were analyzed.

Results
A total of 151 TBI patients were included. Patients who underwent USS experienced more severe outcomes as assessed using the 3-month modified Rankin Scale score (P = 0.024). In bilateral DC TBI patients, USS were associated with worsen outcomes, moreover, ICP monitoring was able to lower their death rate and was associated with a lower USS incidence. In USS patients, ICP monitoring was not associated with improved outcomes but was able to lower their mortality rate (2/19, 10.5%, vs. 10/25, 40.0%; P = 0.042).

Conclusion
The avoidance of USS may be associated with improved outcomes of TBI patients who underwent bilateral DC. ICP monitoring was a potential approach to lower USS rate in TBI patients, but its specific benefits were uncertain.
How do trial teams plan for retention during the design stage of the trial? A scoping review protocol
Authors: Murphy Ellen , Gillies Katie , Shiely Frances 
Published: November 2022

Abstract
Background
Retention remains a major challenge for many clinical trials. The SPIRIT guidelines state the following information on retention should be included in the trial protocol “Plans to promote participant retention and complete follow-up, including list of any outcome data to be collected for participants who discontinue or deviate from intervention protocols”. This guidance shows the importance of planning retention methods and handling missing data as this can impact how the results of the trial are interpreted. The most recent Cochrane review of strategies to improve retention in clinical trials highlighted that some trials implemented multiple retention strategies and we questioned whether the use of multiple strategies was planned at the design stage and included in the protocol or are strategies implemented when retention becomes an issue within the trial. The purpose of our scoping review is to establish if and how trial teams prepare for retention at the design phase of clinical trials.

Methods and analysis
We will follow the methodological framework and guidelines for scoping reviews outlined by the Joanna Briggs Institute. We will search MEDLINE/PubMed, Scopus, EMBASE, CINAHL (EBSCO), and Web of Science. A comprehensive search strategy for PubMed was developed in collaboration with an experienced research librarian. We will include protocols for phase 2, 3, and 4 RCTs as well as pilot and feasibility studies. The screening process will involve two reviewers. EM will independently screen all titles and abstracts. FS will screen 10% of the overall search output, and where necessary full protocol texts will be screened to determine eligibility. We will randomly sample eligible protocols to ensure the protocols represent a variety of trial and intervention types. Data will be extracted from each protocol and the results will be synthesised. The analysis will be qualitative using a narrative summary and descriptive statistics where appropriate.

Discussion
The scoping review will help trial methodologists better understand if retention strategies are planned for during the design stage of the trial contributing to the PRioRiTy II unanswered question “How should people who run trials plan for retention during their funding application and creation of the trial (protocol development)?”.
Precursor prioritization for p-cymene production through synergistic integration of biology and chemistry
Authors: Lin Hsi-Hsin , Mendez‐Perez Daniel , Park Jimin , Wang Xi , Cheng Yan , Huo Jiajie , Mukhopadhyay Aindrila , Lee Taek Soon , Shanks Brent H. 
Published: November 2022

AbstractThe strategy of synergistic application of biological and chemical catalysis is an important approach for efficiently converting renewable biomass into chemicals and fuels. In particular, the method of determining the appropriate intermediate between the two catalytic methods is critical. In this work, we demonstrate p-cymene production through the integration of biosynthesis and heterogenous catalysis and show how a preferred biologically derived precursor could be determined. On the biological side, we performed the limonene and 1,8-cineole production through the mevalonate pathway. Titers of 0.605 g/L and a 1.052 g/L were achieved, respectively. This difference is in agreement with the toxicity of these compounds toward the producing microorganisms, which has implications for subsequent development of the microbial platform. On the heterogeneous catalysis side, we performed the reaction with both biological precursors to allow for direct comparison. Using hydrogenation/dehydrogenation metals on supports with acid sites, both limonene and 1,8-cineole were converted to p-cymene with similar yields under equivalent reaction conditions. Thus, we could determine that the most promising strategy would be to target 1,8-cineole, the higher titer and lower toxicity bio-derived precursor with subsequent catalytic conversion to p-cymene. We further optimized the biological production of 1,8-cineole via fed-batch fermentation and reached the titer of 4.37 g/L which is the highest known 1,8-cineole titer from microbial production. This work provides a valuable paradigm for early stage considerations to determine the best route for the high-efficiency production of a target biobased molecule using an integration of biology and chemistry.
Multi-platform proteomic analysis of Alzheimer’s disease cerebrospinal fluid and plasma reveals network biomarkers associated with proteostasis and the matrisome
Authors: Dammer Eric B. , Ping Lingyan , Duong Duc M. , Modeste Erica S. , Seyfried Nicholas T. , Lah James J. , Levey Allan I. , Johnson Erik C. B. 
Published: November 2022

AbstractRobust and accessible biomarkers that can capture the heterogeneity of Alzheimer’s disease and its diverse pathological processes are urgently needed. Here, we undertook an investigation of Alzheimer’s disease cerebrospinal fluid (CSF) and plasma from the same subjects (n=18 control, n=18 AD) using three different proteomic platforms—SomaLogic SomaScan, Olink proximity extension assay, and tandem mass tag-based mass spectrometry—to assess which protein markers in these two biofluids may serve as reliable biomarkers of AD pathophysiology observed from unbiased brain proteomics studies. Median correlation of overlapping protein measurements across platforms in CSF (r~0.7) and plasma (r~0.6) was good, with more variability in plasma. The SomaScan technology provided the most measurements in plasma. Surprisingly, many proteins altered in AD CSF were found to be altered in the opposite direction in plasma, including important members of AD brain co-expression modules. An exception was SMOC1, a key member of the brain matrisome module associated with amyloid-β deposition in AD, which was found to be elevated in both CSF and plasma. Protein co-expression analysis on greater than 7000 protein measurements in CSF and 9500 protein measurements in plasma across all proteomic platforms revealed strong changes in modules related to autophagy, ubiquitination, and sugar metabolism in CSF, and endocytosis and the matrisome in plasma. Cross-platform and cross-biofluid proteomics represents a promising approach for AD biomarker development.