bluuebunny/crossref_metadata_2025_split huggingface dataset:
Seafloor Observation Scenario Exploration Tool: enabling representative exploration of the global deep seafloor
Authors: Johannes Kristen N. , Kennedy Brian R. C. , Bell Katherine L. C. 
Published: October 2023

Visual observation of the seafloor is invaluable in understanding deep-sea biogeography, uncovering and expanding key global geological, oceanographic, and climate processes. And yet, due to the expense, inefficiency, and inequitable distribution of deep-sea tools, we have barely explored a small, biased fraction of it. Systematic and efficient exploration of the entire deep sea will require a concerted global effort. The current study uses global-coverage geospatial data to develop an interactive online tool for deep seafloor observation planning (i.e., depths below 200 m). The Seafloor Observation Scenario Exploration Tool integrates stakeholder goals and constraints into a dynamic modeling process that combines information about seafloor depth, seafloor geomorphology features, sites of past seafloor observation, Exclusive Economic Zones, and vessel traffic density. With the tool, users can identify maximally suitable areas for seafloor observation, which we envision supporting seafloor expedition planning and marine conservation action.
Dissemination and characteristics of carbapenem-resistant Klebsiella pneumoniae in nine district hospitals in southwestern China
Authors: Wang Yonghong , Ouyang Yan , Xu Xiuyu , Sun Shan , Tian Xiaolang , Liu Hang , Xia Yun 
Published: October 2023

BackgroundCarbapenem-resistant Klebsiella pneumoniae (CRKP) is epidemically transmitted globally, but few studies focused on the prevalence in district-level hospitals. In this study, we investigated CRKP strains collected from nine district hospitals from September 2019 to September 2020, aiming to determine the resistance mechanisms, virulence profiles, and molecular epidemiological characteristics of CRKP in district hospitals in Southwest China.MethodsA total of 51 CRKP strains were collected from 9 district-level hospitals. Matrix-assisted laser desorption/ionization-time of flight mass spectrometer was used for strain identification review, and the micro-broth dilution method was used for antibiotic sensitivity detection. Molecular epidemiological investigation of strains was performed by multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) methods. PCR and efflux pump inhibition tests were used to detect CRKP resistance mechanisms. PCR and serum killing tests were used to detect capsular serotype, virulence-related genes, and virulence validation.ResultsThe CRKP strains in district hospitals presented high levels of MIC50 and MIC90 in carbapenem antibiotics especially ertapenem and meropenem. A total of 90.2% (46/51) CRKP strains were detected as carbapenemase producers, and the proportion of strains co-expressing carbapenemases was 11.8% (6/51). All CRKP strains were grouped into eight MLST types, and ST11 was the most prevalent genotype. A total of 11.8% (6/51) CRKP isolates were positive for the string test, and three strains of hypervirulent and carbapenem-resistant K. pneumoniae (HV-CRKP) were positive in serum killing test. The molecular typing of all the CRKP isolates was grouped into 29 different PFGE patterns, and 40 ST11 isolates belonged to 20 different PFGE clusters.ConclusionCRKP strains showed high-level antibiotic resistance and virulence phenotype in district hospitals in Southwest China, which suggested that we should immediately pay attention to the rapid dissemination of the CRKP in regional hospitals. Our study will provide new insights into the epidemiology of CRKP in regional hospitals, which will help regional hospitals develop nosocomial infection prevention and control policies tailored to local conditions.
Clinical effect of a modified superficial temporal artery-middle cerebral artery bypass surgery in Moyamoya disease treatment
Authors: Lu Liang , Huang Yimin , Han Yang , Li Yu , Wan Xueyan , Chen Juan , Zhang Xincheng , Shu Kai , Lei Ting , Wang Sheng , Gan Chao , Zhang Huaqiu 
Published: October 2023

BackgroundCerebral extracranial-intracranial (EC-IC) revascularization technique (superficial temporal artery-middle cerebral artery (STA-MCA) bypass grafting) has become the preferred surgical method for the treatment of Moyamoya disease (MMD). We attempted to completely free the two branches of the superficial temporal artery without disconnection. Extracranial and intracranial blood flow reconstruction were then modified by selectively performing a direct bypass technique on one branch and a patch fusion technique on the other of the STA based on the blood flow and the vascular diameter of the intracranial surface blood vessels.MethodsA series of modified STA-MCA bypass surgeries performed consecutively between March 2022 and March 2023 were reviewed and compared to conventional combined bypass surgeries performed during the same period. The following information was collected from all enrolled patients: demographic characteristics, clinical symptoms, and preoperative and postoperative imaging, including Suzuki stage and Matsushima grade. The modified Rankin scale (mRS) was used to assess the changes in neurological status before and after surgery.ResultsA total of 41 patients with Moyamoya disease (MMD) who underwent cerebral revascularization were included in this study, of which 30 were conventional revascularization and 11 were modified revascularization. The mean age was 49.91 years, and 18 (43.9%) of the patients were women. The modified group had a lower incidence of cerebral hyperperfusion syndrome (18.2%) than the conventional group (23.3%). After at least 3 months of follow-up, the bypass patency rate remained 100% in the modified group and 93.3% in the conventional group. All patients in the modified group achieved a better Matsushima grade (A + B), with six (54.5%) having an A and five (45.5%) having a B. In contrast, four patients (13.3%) in the conventional group had a Matsushima grade of C. In all, 72.8% of the modified group had postoperative mRS scores of 0 and 1, which was higher than that of the traditional group (63.3%).ConclusionThe improved STA-MCA bypass could provide blood flow to multiple cerebral ischemic areas, reduce excessive blood perfusion, and ensure blood supply to the scalp, with lower complications and better clinical benefits than the traditional combined bypass.
Whole exome sequencing of patients with varicella-zoster virus and herpes simplex virus induced acute retinal necrosis reveals rare disease-associated genetic variants
Authors: Heinz Johanna L. , Swagemakers Sigrid M. A. , von Hofsten Joanna , Helleberg Marie , Thomsen Michelle M. , De Keukeleere Kerstin , de Boer Joke H. , Ilginis Tomas , Verjans Georges M. G. M. , van Hagen Peter M. , van der Spek Peter J. , Mogensen Trine H. 
Published: October 2023

PurposeHerpes simplex virus (HSV) and varicella-zoster virus (VZV) are neurotropic human alphaherpesviruses endemic worldwide. Upon primary infection, both viruses establish lifelong latency in neurons and reactivate intermittently to cause a variety of mild to severe diseases. Acute retinal necrosis (ARN) is a rare, sight-threatening eye disease induced by ocular VZV or HSV infection. The virus and host factors involved in ARN pathogenesis remain incompletely described. We hypothesize an underlying genetic defect in at least part of ARN cases.MethodsWe collected blood from 17 patients with HSV-or VZV-induced ARN, isolated DNA and performed Whole Exome Sequencing by Illumina followed by analysis in Varseq with criteria of CADD score &gt; 15 and frequency in GnomAD &lt; 0.1% combined with biological filters. Gene modifications relative to healthy control genomes were filtered according to high quality and read-depth, low frequency, high deleteriousness predictions and biological relevance.ResultsWe identified a total of 50 potentially disease-causing genetic variants, including missense, frameshift and splice site variants and on in-frame deletion in 16 of the 17 patients. The vast majority of these genes are involved in innate immunity, followed by adaptive immunity, autophagy, and apoptosis; in several instances variants within a given gene or pathway was identified in several patients.DiscussionWe propose that the identified variants may contribute to insufficient viral control and increased necrosis ocular disease presentation in the patients and serve as a knowledge base and starting point for the development of improved diagnostic, prophylactic, and therapeutic applications.
Multimodal imaging features of retroperitoneal anastomosing hemangioma: a case report and literature review
Authors: Zhang Liqing , Wu Jian 
Published: October 2023

BackgroundAnastomotic hemangioma is a rare subtype of capillary hemangioma primarily found in the genitourinary tract. We present a case of a patient with an anastomotic hemangioma located in the retroperitoneal space; then, we explore and summarize the imaging features from previously reported cases for accurate diagnosis.Case presentationA 57-year-old woman complained of left lower back pain. Contrast-enhanced ultrasound revealed a hypoechoic mass with “slow-in and slow-out” enhancement. Abdominal CT scan displayed a well-defined, round soft tissue mass in the right retroperitoneal region with obvious enhancement. MRI indicated low signal on T1-weighted imaging, high signal on T2-weighted imaging and diffusion-weighted imaging, and progressive enhancement after enhancement. Surgical removal of the tumor was performed. Histopathological examination exhibited a distinct tumor border with interconnected blood vessels and a cavity lined by a single layer of cubic endothelial cells. Immunohistochemistry confirmed the presence of CD31[+] and CD34[+]. The final pathological diagnosis was anastomotic hemangioma. No recurrence was observed during a 40-month follow-up.ConclusionRetroperitoneal anastomotic hemangioma is a rare and benign neoplasm that may be misdiagnosed as ectopic pheochromocytoma or angiosarcoma. This case report presents and analyzes the imaging characteristics of a series of retroperitoneal anastomotic hemangiomas, which can be valuable for future diagnoses and help prevent unnecessary surgeries.
Plasma EBV DNA as a prognostic factor in EBV associated gastric cancer: a multicenter, prospective study (EBV PRESAGE study)
Authors: Alberti Andrea , Stocker Gertraud , Lordick Florian , Hacker Ulrich T. , Kobitzsch Benjamin , Haffner Ivonne , Baiocchi Gian Luca , Zamparini Manuel , Tiberio Guido A. M. , Baronchelli Carla , Caruso Arnaldo , Bossi Paolo , Berruti Alfredo 
Published: October 2023

PurposeThe Cancer Genome Atlas Research Network identified Epstein-Barr-Virus (EBV)-positive gastric cancer as a distinct molecular subtype. The prevalence is 8-9% and the histological examination shows pronounced lymphocytic infiltration, elevated levels of IFN-γ and consequently overexpression of PD-L1. The role of plasma EBV DNA load as a prognostic factor in patients with this cancer subtype is still to be defined.Methods and analysisThe present multicenter prospective observational study “EBV PRESAGE”, involving German and Italian cancer centers, aims to evaluate the prognostic role of plasma EBV DNA in EBV-related gastric cancer (GC). The objective is to study the association between plasma EBV DNA load at different consecutive time points and the patient’s prognosis. Every patient with a new diagnosis of gastric cancer (including gastroesophageal junction adenocarcinoma) will be screened for Epstein-Barr encoded small Region (EBER) on tissue biopsies using in situ hybridization (ISH). If EBER ISH is positive, blood analysis for plasma EBV DNA will be conducted. The plasma EBV quantitative analysis will be centralized, and extraction, detection, and quantification of EBV DNA in plasma samples will be performed using real-time PCR.DiscussionWe hypothesized that plasma EBV DNA represents a non-invasive tool for monitoring EBV-related GC and might be valuable as a prognostic marker.
Retrospective study of efficacy and adverse events of immune checkpoint inhibitors in 22 xeroderma pigmentosum patients with metastatic or unresectable cancers
Authors: Fernandez Elvelyn R. , Tamura Deborah , Khan Sikandar G. , Momen Sophie , Fassihi Hiva , Sarkany Robert , DiGiovanna John J. , Kraemer Kenneth H. 
Published: October 2023

BackgroundXeroderma pigmentosum (XP), a rare disease with defects in DNA repair genes, has &gt;1,000-fold increased risk of ultraviolet-induced skin cancers. Immune checkpoint inhibitors (ICIs) are used for treating cancers with large numbers of mutations but may also promote adverse events (AEs). Deficient DNA repair in XP patients may lead to increased numbers of mutations, leading to enhanced efficacy of cancer response or, alternatively, to increased AE in response to ICI. We sought to compare the efficacy and AE of ICI in XP patients with metastatic or unresectable cancers to that of ICI-treated patients in the general population.MethodsIn this retrospective study, we reviewed medical records of XP patients treated in the United States and in London (UK). We also reviewed published reports of ICI-treated XP patients and patients in the general population.ResultsMetastatic or unresectable cancers in all 22 (100%) XP patients showed regression or remission in response to ICI. The types and frequencies of AE in XP patients were similar to those reported among ICI-treated patients in the general population. However, two XP patients had concurrent additional cancers that did not respond to ICI, two XP patients had cancer recurrence or progression after initial response, and eight XP patients developed new skin cancers during or after ICI treatment.ConclusionIn this retrospective study with small sample size, XP patients demonstrated positive responses to ICI and the treatment was well tolerated but some patients developed new skin cancers while being treated. ICIs can be considered in treating metastatic or unresectable cancers in XP patients.
Similar adverse outcome rates with high or low oxygen saturation targets in an area with low background mortality
Authors: Willgerodt Nina , Bührer Christoph , Rossi Rainer , Kühn Thomas , Rüdiger Mario , Avenarius Stefan , Böttger Ralf , Olbertz Dirk M. , Proquitte Hans , Bittrich Hans-Jörg , Haase Roland , Fröhlich Matthias , Höhne Sybille , Thome Ulrich H. 
Published: October 2023

BackgroundRandomized controlled trials have indicated reduced mortality rates in very preterm infants assigned to high compared to low oxygen saturation (SpO2) target levels, accompanied by higher rates of retinopathy of prematurity and bronchopulmonary dysplasia. However, the benefit-to-harm ratio may depend on the local background mortality risk. We therefore aimed to quantify the risk–benefit ratios of different SpO2 target ranges in 10 tertiary newborn intensive care units (NICUs) in East Germany.MethodsIn a retrospective multicenter study, 1,399 infants born between 2008 and 2012 at a gestational age between 24 0/7 and 27 6/7 weeks and with a birthweight below 1,250 g were grouped according to the hospital's target SpO2 range [high oxygen saturation group (HOSG) above 90%], low oxygen saturation group (LOSG) below 90%] and the compliance of units with their target SpO2 range. The association between neonatal morbidities, neurodevelopmental outcomes, selected treatment strategies, and target SpO2 ranges was calculated using chi-squared and Mann Whitney U tests.ResultsNine of the ten participating NICUs met their SpO2 target ranges. Five units were considered as HOSG, and five units were considered as LOSG. Necrotizing enterocolitis and intraventricular hemorrhage grade ≥ 2 occurred significantly more frequently in the HOSG than in the LOSG (8.4% vs. 5.1%, p = 0.02; and 26.6% vs. 17.7%, p &lt; 0.001). No significant differences in the mortality rate and the rate of retinopathy of prematurity were found.ConclusionIn our patient population, a lower SpO2 target range was not associated with increased safety risks in extremely preterm infants. We cannot be sure that our outcome differences are associated with differences in oxygen saturations due to the retrospective study design and the differences in site practices.
Apelin receptor inhibition in ischemia-reperfused mouse hearts protected by endogenous n-3 polyunsaturated fatty acids
Authors: Zheng Shuang , Tan Weijiang , Li Xiang , Wang Lijing , Zhu Caiyi , Pyle W. Glen , Chen Jianxin , Wu Jian , Ren Xuecong , Chen Honghua , Zou Yunzeng , Backx Peter H. , Yang Feng Hua 
Published: October 2023

Background: While the protective effects of n-3 polyunsaturated fatty acids (PUFAs) on cardiac ischemia-reperfusion (IR) injury have been previously reported, limited data are available regarding how these fatty acids affect membrane receptors and their downstream signaling following IR injury. We aimed to identify potential receptors activated by n-3 PUFAs in IR hearts to understand the regulatory mechanisms of these receptors.Methods: We used fat-1 mice, which naturally have elevated levels of n-3 PUFAs, and C57BL/6J mice as a control group to create a myocardial IR injury model through Langendorff perfusion. We assessed the impact of endogenous n-3 PUFAs on left ventricular function, myocardial infarct size, myocardial apoptosis, and ATP production. RNA sequencing (RNA-seq) and bioinformatics analysis were conducted to identify molecular targets affected by n-3 PUFAs. Based on these analyses we then treated IR hearts of WT and fat-1 mice with an antagonist (ML221) or an agonist (apelin-13) for the predicted receptor to assess cardiac contractile function and intracellular signaling pathways. An in vitro hypoxia-reoxygenation (HR) model was also used to confirm the effects of n-3 PUFAs on the examined intracellular signaling pathways.Results: Endogenous n-3 PUFAs protected cardiac structure and function in post-IR hearts, and modulated phosphorylation patterns in the PI3K-AKT-mTOR signaling pathways. RNA-seq analysis revealed that n-3 PUFAs affected multiple biological processes as well as levels of the apelin receptor (APLNR). Consistent with a role for the PLNNR, ML221 synchronized the activation of the PI3K-AKT-mTOR signaling axis, suppressed the expression of PKCδ and phosphorylated p38α, upregulated PKCε expression, upregulated or restored the phosphorylation of myofilaments, and prevented myocardial injury and contractile dysfunction in WT IR hearts. By contrast, apelin-13 disrupted the PI3K-AKT-mTOR signaling axis in post-IR fat-1 hearts. The phosphorylation signaling targeted by APLNR inhibition in post-IR fat-1 hearts was also observed after treating HR cells with eicosatetraenoic acid (EPA).Conclusion: Endogenous n-3 PUFAs protect against post-IR injury and preserve cardiac contractile function possibly through APLNR inhibition. This inhibition synchronizes the PI3K-AKT-mTOR axis, suppresses detrimental phosphorylation signaling, and restores or increases myofilament phosphorylation in post-IR hearts. The beneficial effects observed in fat-1 transgenic mouse hearts can be attributed, at least in part, to elevated EPA levels. This study is the first to demonstrate that n-3 PUFAs protect hearts against IR injury through APLNR inhibition.
Effectiveness of dapagliflozin as an insulin adjunct in type 1 diabetes: a semi-mechanistic exposure-response model
Authors: Sokolov Victor , Yakovleva Tatiana , Penland Robert C. , Boulton David W. , Tang Weifeng 
Published: October 2023

Introduction: Dapagliflozin-induced improvement of glycemic control in patients with inadequately controlled type 1 diabetes (T1D) is complicated by the delicate balance between blood glucose and exogenous insulin. In this work, we developed a semi-mechanistic population exposure-response model using pooled patient-level data to characterize the joint effect of dapagliflozin and insulin on average daily glucose concentrations and glycated hemoglobin (HbA1c) levels in patients with T1D.Methods: A non-linear mixed-effects model was developed in Monolix (Lixoft, France) and R software (R Project, www.r-project.org) using pooled patient-level data from phase 2 and phase 3 trials (NCT01498185, NCT02460978, NCT02268214).Results: Because of the apparent lack of association between bolus insulin dose and glucose concentrations measured by continuous glucose monitoring the model was able to capture the quantitative link between basal, but not bolus, insulin dose and plasma glucose. Even so, this association remained flat, with a 50% decrease in the basal insulin dose from pretreatment level, resulting in ∼5% increase in glucose exposure. Therefore, dapagliflozin efficacy was not significantly affected by the insulin dose adjustment, with 24-week HbA1c reduction on 10-mg dapagliflozin treatment changing from −0.5 [95% CI: −0.55, −0.45] to −0.42 [95%CI: −0.48, −0.36] after adjustment. At the same time, the analysis revealed ∼2-fold steeper slope of glucose-HbA1c relationship in dapagliflozin-treated patients vs. control group, suggesting the presence of additional dapagliflozin treatment–related benefits, not explained by the dapagliflozin-mediated ∼4% increase in plasma hemoglobin levels. Finally, the efficacy of 5 and 10-mg doses, represented by the mean HbA1c reduction at week 24 of dapagliflozin treatment, was shown to be notably greater than the 1- and 2.5-mg doses.Discussion: This research is an attempt to deconvolute and reconstruct dapagliflozin-HbA1c dose-response relationship in T1D by accounting for the drug’s action on both daily insulin dose and plasma glucose on a subject-level. While the model is able to adequately capture the observed data, it also revealed that the variability in CGM is poorly approximated by the variability in insulin dose alone. Furthermore, the slope of CGM/HbA1c relationship may differ depending on the population and treatment scenarios. As such, a deeper dive into the physiological mechanisms is required to better quantify the intricate network of glycemic response under dapagliflozin treatment.