bluuebunny/crossref_metadata_2025_split huggingface dataset:
BRCA1/2 Mutations and Cardiovascular Function in Breast Cancer Survivors
Authors: Demissei Biniyam G. , Lv WenJian , Wilcox Nicholas S. , Sheline Karyn , Smith Amanda M. , Sturgeon Kathleen M. , McDermott-Roe Chris , Musunuru Kiran , Lefebvre Bénédicte , Domchek Susan M. , Shah Payal , Ky Bonnie 
Published: February 2022

ObjectiveAnimal models suggest that BRCA1/2 mutations increase doxorubicin-induced cardiotoxicity risk but data in humans are limited. We aimed to determine whether germline BRCA1/2 mutations are associated with cardiac dysfunction in breast cancer survivors.MethodsIn a single-center cross-sectional study, stage I-III breast cancer survivors were enrolled according to three groups: (1) BRCA1/2 mutation carriers treated with doxorubicin; (2) BRCA1/2 mutation non-carriers treated with doxorubicin; and (3) BRCA1/2 mutation carriers treated with non-doxorubicin cancer therapy. In age-adjusted analysis, core-lab quantitated measures of echocardiography-derived cardiac function and cardiopulmonary exercise testing (CPET) were compared across the groups. A complementary in vitro study was performed to assess the impact of BRCA1 loss of function on human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) survival following doxorubicin exposure.ResultsSixty-seven women with mean (standard deviation) age of 50 (11) years were included. Age-adjusted left ventricular ejection fraction (LVEF) was lower in participants receiving doxorubicin regardless of BRCA1/2 mutation status (p = 0.03). In doxorubicin-treated BRCA1/2 mutation carriers and non-carriers, LVEF was lower by 5.4% (95% CI; −9.3, −1.5) and 4.8% (95% CI; −9.1, −0.5), respectively compared to carriers without doxorubicin exposure. No significant differences in VO2max were observed across the three groups (poverall = 0.07). Doxorubicin caused a dose-dependent reduction in viability of iPSC-CMs in vitro without differences between BRCA1 mutant and wild type controls (p &gt; 0.05).ConclusionsBRCA1/2 mutation status was not associated with differences in measures of cardiovascular function or fitness. Our findings do not support a role for increased cardiotoxicity risk with BRCA1/2 mutations in women with breast cancer.
Along-Strike Variation in Accretion, Non-accretion, and Subduction Erosion Recorded in Rocks of the Jurassic-Neogene Convergent Plate Margin of California
Authors: Wakabayashi John 
Published: February 2022

Post-subduction dextral faulting was restored to evaluate the spatial distribution of units of the Franciscan subduction complex of California that formed as a result of subduction accretion. The Franciscan and related rocks of western California exhibit significant along-strike variation in its recording of subduction-accretion processes. Most notably, two segments 830 km apart record subduction erosion associated with low-angle subduction events that took place at ca. 120 Ma and ca. 80–70 Ma in the north and south, respectively. This spatial relationship is not affected by restoration of post-subduction dextral slip because none of the slip passes between the two inboard tectonic windows. Between these segments the subduction complex records net accretion from ca.175 Ma to 12 Ma, but includes horizons recording non-accretion. None of the accreted units of the subduction complex are preserved over the entire length of the subduction complex. One unit, however, correlated on the basis of its structural level in the subduction complex and distinctive detrital zircon age spectra, accreted at about 80–83 Ma extends a strike length of 580 km, an amount increased to 850 km with restoration of post-subduction dextral faulting. The long-strike length of accretion of this unit demonstrates that detrital zircon age populations of subduction complex clastic rocks are poor indicators of strike-slip displacement. Some reaches of the subduction complex include schistose blueschist facies rocks (most Franciscan blueschist facies rocks are not schistose), whereas others do not, and some reaches lack blueschist facies rocks altogether. The significant along-strike variation in the Franciscan and related rock units reflects temporal and spatial differences in history of accretion, non-accretion, subduction erosion, and probably subduction dip. Similar time and space variation in processes and resultant geologic record should be expected for other subduction complexes of the world.
A High-Density Genetic Map and QTL Fine Mapping for Growth- and Sex-Related Traits in Red Swamp Crayfish (Procambarus clarkii)
Authors: Guo Xin-Fen , Zhou Yu-Lin , Liu Min , Li Zhi , Zhou Li , Wang Zhong-Wei , Gui Jian-Fang 
Published: February 2022

Red swamp crayfish (Procambarus clarkii) is a commercially important species in global aquaculture and most successfully invasive freshwater shrimp in China. In order to determine the genetic basis of growth- and sex-related traits, a high-density genetic linkage map was constructed using 2b-RAD sequencing technology in a full-sib family. The consensus map contains 4,878 SNP markers assigned to 94 linkage groups (LGs) and spanned 6,157.737 cM with an average marker interval of 1.26 cM and 96.93% genome coverage. The quantitative trait locus (QTL) mapping for growth and sex traits was performed for the first time. QTL mapping uncovers 28 QTLs for growth-related traits in nine LGs, explaining 7.9–14.4% of the phenotypic variation, and identifies some potential candidate growth-related genes such as mih, lamr, golgb1, nurf301, and tbcd1 within the QTL intervals. A single major locus for sex determination was revealed in LG20 that explains 59.3–63.7% of the phenotypic variations. Some candidate sex-related genes, such as vps4bl, ssrf, and acot1, were identified in the QTL intervals and found to be differentially expressed in the muscle tissues between the females and the males. Furthermore, the identified SNPs were revealed to be female heterozygotes, suggesting that red swamp crayfish might have the female heterogametic ZZ/ZW sex determination system. The present study provides a valuable resource for marker-assisted selection and genetic improvement and for further genetic and genomic research in red swamp crayfish.
​Circulating Cytokines in Myocardial Infarction Are Associated With Coronary Blood Flow
Authors: Kalinskaya Anna , Dukhin Oleg , Lebedeva Anna , Maryukhnich Elena , Rusakovich Georgy , Vorobyeva Daria , Shpektor Alexander , Margolis Leonid , Vasilieva Elena 
Published: February 2022

BackgroundThe level of systemic inflammation correlates with the severity of the clinical course of acute myocardial infarction (AMI). It has been shown that circulating cytokines and endothelial dysfunction play an important role in the process of clot formation. The aim of our study was to assess the concentration of various circulating cytokines, endothelial function and blood clotting in AMI patients depending on the blood flow through the infarction-related artery (IRA).MethodsWe included 75 patients with AMI. 58 presented with ST-elevation myocardial infarction (STEMI) and 17 had non-ST-elevation myocardial infarction (non-STEMI). A flow-mediated dilation test (FMD test), thrombodynamics and rotational thromboelastometry as well as assessment of 14 serum cytokines using xMAP technology were performed.FindingsNon-STEMI-patients were characterized by higher levels of MDC, MIP-1β, TNF-α. Moreover, we observed that patients with impaired blood flow through the IRA (TIMI flow 0-1) had higher average and initial clot growth rates, earlier onset of spontaneous clots, C-reactive protein (CRP) and IL-10 compared to patients with preserved blood flow through the IRA (TIMI flow 2-3). Patients with TIMI 2-3 blood flow had higher level of IP-10. IL-10 correlated with CRP and pro-inflammatory cytokines levels, initial clot growth rate and clot lysis time in TIMI 0-1 patients. All these differences were statistically significant.InterpretationWe demonstrated that concentrations of the inflammatory cytokines correlate not only with the form of myocardial infarction (STEMI or non-STEMI), but also with the blood flow through the infarct-related artery. Inflammatory response, functional state of endothelium, and clot formation are closely linked with each other. A combination of these parameters affects the patency of the infarct-related artery.
A Necroptosis-Related Prognostic Model of Uveal Melanoma Was Constructed by Single-Cell Sequencing Analysis and Weighted Co-Expression Network Analysis Based on Public Databases
Authors: Xie Jiaheng , Chen Liang , Tang Qikai , Wei Wei , Cao Yuan , Wu Chuyan , Hang Jing , Zhang Kai , Shi Jingping , Wang Ming 
Published: February 2022

BackgroundUveal melanoma(UVM) is the most common intraocular malignancy and has a poor prognosis. The clinical significance of necroptosis(NCPS) in UVM is unclear.MethodsWe first identified necroptosis genes in UVM by single-cell analysis of the GSE139829 dataset from the GEO database and weighted co-expression network analysis of TCGA data. COX regression and Lasso regression were used to construct the prognostic model. Then survival analysis, immune microenvironment analysis, and mutation analysis were carried out. Finally, cell experiments were performed to verify the role of ITPA in UVM.ResultBy necroptosis-related prognostic model, UVM patients in both TCGA and GEO cohorts could be classified as high-NCPS and low-NCPS groups, with significant differences in survival time between the two groups (P&lt;0.001). Besides, the high-NCPS group had higher levels of immune checkpoint-related gene expression, suggesting that they might be more likely to benefit from immunotherapy. The cell experiments confirmed the role of ITPA, the most significant gene in the model, in UVM. After ITPA was knocked down, the activity, proliferation, and invasion ability of the MuM-2B cell line were significantly reduced.ConclusionOur study can provide a reference for the diagnosis and treatment of patients with UVM.
Multisystemic Sarcoidosis Presenting With Leg Ulcers, Pancytopenia, and Polyserositis Was Successfully Treated With Glucocorticoids: A Case Report and Literature Review
Authors: Qiao Xin , He Shan , Altawil Abdullah , Wang Qiu-yue , Kang Jian , Li Wen-yang , Yin Yan 
Published: February 2022

IntroductionSarcoidosis is a chronic granulomatous disease of unknown etiology. A variety of studies have pointed out that almost every part of the body can be affected, but it most often affected the lungs and intrathoracic lymph nodes. However, cases of sarcoidosis involving multiple organs in one patient are rarely reported. We describe a unique case of sarcoidosis, which was characterized by multiorgan involvement, including leg ulcers, splenomegaly, pancytopenia, and polyserositis. Glucocorticoids were effective during the treatment of the above lesions. This case highlights the diversity of clinical manifestations of sarcoidosis and emphasizes the importance of its differential diagnosis and the periodical follow-up. These are crucial to physicians in the diagnosis and treatment of sarcoidosis.Main Symptoms and Important Clinical FindingsA 30-year-old male complained about intermittent fever 3 years ago. A computed tomographic scan of the chest showed lymphadenopathy in the mediastinum and hilar regions. Routine blood tests showed leukopenia and mild anemia. The pathologic result of mediastinal lymph node biopsy was granulomatous lesions; thus, the patient was diagnosed with type II sarcoidosis without glucocorticoid therapy. In the following 2 years, the patient suffered from intermittent fever accompanied by dyspnea, fatigue, occasional cough, less sputum, and apparent weight loss. Abnormal physical examinations included leg ulcers and splenomegaly. Laboratory and physical tests revealed pancytopenia, polyserositis, and enlargement of lymph nodes. The pathological findings of leg ulceration, pleura, and left supraclavicular lymph node all suggested granulomas.Diagnosis, Interventions, and OutcomesIt strongly suggested sarcoidosis since tuberculosis, lymphoma, and connective tissue disease were all excluded. Due to severe conditions and multiorgan involvement, we tried to provide methylprednisolone for this patient. After 9 months of oral glucocorticoids therapy, his subjective symptoms as well as hematological and radiological findings were all improved. His leg skin ulceration and scab were also completely disappeared.ConclusionSarcoidosis has diverse clinical presentations, and many patients present with atypical symptoms. It needs to be timely identified by the clinician and carefully differentiated from other diseases with similar findings so as to make an accurate diagnosis. In this case, the patient had a poor clinical response to glucocorticoids in the early stage of treatment due to the severe condition and multi-organ involvement. It is worth noting that the patient had improved significantly after 9 months of treatment of corticosteroids, which suggested that follow-up is critical.
Over-the-Scope Clip Applications as First-Line Therapy in the Treatment of Upper Non-variceal Gastrointestinal Bleeding, Perforations, and Fistulas
Authors: Qiu Jiayu , Xu Jun , Zhang Yanxia , Liao Foqiang , Zhu Zhenhua , Shu Xu , Chen Youxiang , Pan Xiaolin 
Published: February 2022

BackgroundThe over-the-scope clip (OTSC) is an innovative device and has been successfully used in endoscopic treatment, however, there is a lack of clinical data from China. The aim of this study is to investigate the OTSC applications in the treatment of upper non-variceal gastrointestinal bleeding (UNVGIB), perforations, and fistulas in China.MethodsIn total, 80 patients were treated with one OTSC respectively as first-line therapy in our endoscopy center between January 2016 and November 2020. Among them, 41 patients had UNVGIB, 34 patients had perforations, and five patients had fistulas. The technical and clinical success rates were used to assess the efficacy of OTSC on the above diseases. In addition, we compared the hemostatic efficacy of OTSC with the standard endoscopic therapy in ulcer bleeding and Dieulafoy's lesion by propensity score matching analysis.ResultsIn general, the OTSCs were applied successfully in all patients and achieved 100% (80/80) technical success. The clinical success of all patients was 91.3% (73/80). Among 41 patients with UNVGIB, the clinical success was 85.4% (35/41); 6 patients presented with recurrence. For patients of Dieulafoy's lesion and under antithrombotic therapy, we found that OTSC treatment had both efficient and reliable hemostasis effects. In addition, according to the characteristics of ulcers, site of bleeding lesion, and Blatchford score, all patients received similar and reliable clinical success rates. After propensity score matching, we found that OTSC treatment had low rebleeding rates when compared with standard endoscopic therapy in both Dieulafoy's lesion (15.0 vs 30.0%) and ulcer bleeding (17.6 vs 29.4%). Among 34 patients with perforations, the clinical success was 100% (34/34). Among five patients with fistulas, only one patient failed in maintaining the OTSC before esophageal fistula healing, and the clip achieved an overall clinical success of 80% (4/5).ConclusionThe OTSC represents a safe and effective endoscopic therapy for UNVGIB, perforations, and fistulas as first-line treatment, especially for Dieulafoy's lesion or patients under antithrombotic therapy for UNVGIB, etc. However, OTSC application in these specific lesions or patients lacks adequate evidence as first-line treatment. Therefore, further larger sample and multi-center clinical trials are required to improve its indications in clinical treatment.
The Improved Catheterization Is Associated With the Deeper Radial Arteries in Ultrasound-Guided Dynamic Needle Tip Positioning Technique
Authors: Tian Yuan , Bai Bing , Zhang Yuelun , Che Lu , Wang Jin , Wang Yi , Yu Chunhua , Huang Yuguang 
Published: February 2022

ObjectiveThis study aimed to determine the associations between the first-attempt success and arterial depth in ultrasound-guided radial artery catheterization (RAC) with dynamic needle tip positioning (DNTP) technique. This study also aimed to further explore the cut-off depth correlated to improved first-attempt success catheterization in less time.MethodsThe cases undertaken by RAC within the DNTP technique between March 2019 and July 2020 were extracted from our institutional cohort database. Relevant variables were collected, including patients' demographics and catheterized information. Univariable and multivariable logistic regression analyses were performed to determine the association. The receiver operating characteristic (ROC) curve and the Youden index were used to explore the cut-off values of the arterial depth. Categorized cases according to the cut-off values, the Kaplan-Meier analysis, and the log-rank test were used to determine the difference of first-attempt success with limited catheterized time between groups.ResultsIn this study, 119 patients were enrolled and 98 achieved first-attempt success. The first-attempt success catheterization was observed to be correlated to arterial depth (p &lt; 0.01, odds ratio 6.47). An optimal cut-off depth of 2.25 mm was found using the Youden index (0.53) by ROC curve (area under curve 0.77). Arterial depth of more than 2.25 mm was correlated to improved first-attempt success catheterization in less time (log-rank p &lt; 0.01).ConclusionTo achieve first-attempt success catheterization using the DNTP technique, an arterial depth of more than 2.25 mm was associated with less catheterized time.
New Remote Cerebral Microbleeds on T2*-Weighted Echo Planar MRI After Intravenous Thrombolysis for Acute Ischemic Stroke
Authors: Jabłoński Bartosz , Gójska-Grymajło Anna , Ossowska Daria , Szurowska Edyta , Wyszomirski Adam , Rojek Bartłomiej , Karaszewski Bartosz 
Published: February 2022

BackgroundThe main and well-defined complication of intravenous administration of recombinant tissue plasminogen activator (tPA) in patients with acute ischemic stroke (AIS) is symptomatic intracranial hemorrhage (sICH). However, rtPA might also be connected with the formation of cerebral microbleeds (CMBs), located remotely from the ischemic lesions, that may remain clinically silent. This association might be important because the load of CMBs has been associated with cognitive impairment. We investigated whether administration of rtPA in AIS results in the appearance of new CMBs and if the initial load of CMBs is associated with hemorrhagic transformation.MethodsA total of fifty-nine consecutive patients with AIS treated with rtPA underwent MRI including T2*-weighted Echo Planar Imaging (T2*-EPI) shortly before and 7–9 days after rtPA administration. We calculated the load of new CMBs located outside the MR diffusion restriction area in the follow-up imaging and assessed hemorrhagic transformation with ECASS-II scoring.ResultsA total of forty-nine patients were included for the final analysis. On initial T2*-EPI-GRE, 37 baseline microbleeds (CMBs) were observed in 14 patients (28.6%). On follow-up T2*-EPI-GRE amount of CMBs increased to a total number of 103. New CMBs were found in 5 (14.3%) of 35 patients without and in 9 (64.3%) of 14 with any baseline CMBs. Multiple logistic regression analysis indicated that presence of baseline CMBs (risk ratio [RR] 5.95, 95% CI 2.69–13.20, p &lt; 0.001) and lower platelets level (risk ratio [RR] 0.992, 95% CI 0.986–0.998, p = 0.007) were independently associated with new CMBs. The baseline load of CMBs was not associated with the risk of hemorrhagic transformation.ConclusionIn this study, new CMBs were found in nearly 30% of patients with AIS on the 7–9 days after rtPA treatment. Baseline CMBs correlated with a higher risk of new CMBs appearing after the rtPA treatment, independently of other factors. At the same time, in our sample, baseline CMBs did not correlate with an increased risk of hemorrhagic transformation. Since the associations between the CMBs load and cognitive impairment have already been proved, further studies are warranted to investigate possible associations between the thrombolytic treatment of patients with AIS, mainly those with baseline CMBs, and the risk of earlier cognitive decline.
Magnetic Resonance Neurography Reveals Smoking-Associated Decrease in Sciatic Nerve Structural Integrity in Type 2 Diabetes
Authors: Jende Johann M. E. , Mooshage Christoph , Kender Zoltan , Kopf Stefan , Groener Jan B. , Heiland Sabine , Juerchott Alexander , Nawroth Peter , Bendszus Martin , Kurz Felix T. 
Published: February 2022

ObjectiveIt is controversially discussed in how far smoking contributes to diabetic polyneuropathy (DPN) in type 2 diabetes (T2D). Diffusion-weighted magnetic resonance neurography (MRN) at 3 Tesla has been shown to provide objective values for structural nerve integrity in patients with T2D. The aim of this study was to investigate the contribution of cigarette smoking on structural nerve integrity in T2D.MethodsThis cross-sectional prospective cohort study investigated the structural integrity of the sciatic nerve in 10 smokers, 40 never-smokers, and 20 ex-smokers with T2D and 10 healthy control subjects, using diffusion tensor imaging MRN at 3 Tesla and semi-automated nerve fiber tracking. Results were correlated with clinical, electrophysiological, and serological data.ResultsThe sciatic nerve’s fractional anisotropy (FA), a parameter for structural nerve integrity, was significantly lower in smokers with T2D when compared to controls (p = 0.002) and never-smokers (p = 0.015), and lower in ex-smokers when compared to controls (p = 0.015). In addition, sciatic nerve radial diffusivity, a marker of myelin damage, was increased in smokers versus controls and never-smokers (p = 0.048, p = 0.049, respectively). Furthermore, FA in T2D patients was negatively correlated with clinical and electrophysiological markers of DPN. FA also showed negative correlations with the pulse wave velocity, a marker of arterial stiffness and associated microangiopathy, in controls (r = −0.70; p = 0.037), never-smokers (r = −0.45; p = 0.004), ex-smokers (r = −0.55; p = 0.009), and a similar trend in smokers (r = −0.63; p = 0.076). Negative correlations were found between FA and skin auto-fluorescence, a marker of tissue advanced glycation end product accumulation and therefore long-term glycemic stress in T2D, in never-smokers (r = −0.39; p = 0.020) and smokers (r = −0.84; p = 0.004), but not in ex-smokers (r = −0.07; p = 0.765).ConclusionThe findings indicate that smoking contributes to sciatic nerve damage in T2D, potentially worsening DPN due to glycemic stress and less microangiopathy-associated myelin damage in active smokers, while angiopathic effects predominate in ex-smokers. To stop smoking may therefore pose a promising preventive measure to slow the progression of DPN in T2D.