bluuebunny/crossref_metadata_2025_split huggingface dataset:
Construction of refined staging classification systems integrating FIGO/T‐categories and corpus uterine invasion for non‐metastatic cervical cancer
Authors: Huang Xiao‐Dan , Chen Kai , Shi Liu , Luo Ying‐Shan , Ou‐Yang Yi , Li Jun‐Yun , Huo Lan‐Qing , Huang Lin , Chen Fo‐Ping , Cao Xin‐Ping 
Published: June 2023

AbstractBackgroundTo investigate the prognostic value of corpus uterine invasion (CUI) in cervical cancer (CC), and determine the necessity to incorporate it for staging.MethodsA total of 809 cases of biopsy‐proven, non‐metastatic CC were identified from an academic cancer center. Recursive partitioning analysis (RPA) method was used to develop the refined staging systems with respect to overall survival (OS). Internal validation was performed by using calibration curve with 1000 bootstrap resampling. Performances of the RPA‐refined stages were compared against the conventional FIGO 2018 and 9th edition TNM‐stage classifications by the receiver operating characteristic curve (ROC) and decision curve analysis (DCA).ResultsWe identified that CUI was independently prognostic for death and relapse in our cohort. RPA modeling using a two‐tiered stratification by CUI (positive and negative) and FIGO/T‐categories divided CC into three risk groupings (FIGO I′‐III'/T1′‐3′), with 5‐year OS of 90.8%, 82.1%, and 68.5% for proposed FIGO stage I′–III', respectively (p ≤ 0.003 for all pairwise comparisons), and 89.7%, 78.8%, and 68.0% for proposed T1′‐3′, respectively (p < 0.001 for all pairwise comparisons). The RPA‐refined staging systems were well validated with RPA‐predicted OS rates showed optimal agreement with actual observed survivals. Additionally, the RPA‐refined stages outperformed the conventional FIGO/TNM‐stage with significantly higher accuracy of survival prediction (AUC: RPA‐FIGO vs. FIGO, 0.663 [95% CI 0.629–0.695] vs. 0.638 [0.604–0.671], p = 0.047; RPA‐T vs. T, 0.661 [0.627–0.694] vs. 0.627 [0.592–0.660], p = 0.036).ConclusionCUI affects the survival outcomes in patients with CC. Disease extended to corpus uterine should be classified as stage III/T3.
Treatment outcome comparisons of first‐line targeted therapy in patients with KRAS wild‐type metastatic colorectal cancer: A nationwide database study
Authors: Liang Yi‐Hsin , Chen Kuo‐Hsing , Shao Yu‐Yun 
Published: June 2023

AbstractBackgroundThe first‐line systemic therapy for metastatic colorectal cancer (mCRC) is a combination of one targeted therapy agent and a chemotherapy doublet. Whether bevacizumab or anti‐epidermal growth factor receptor (anti‐EGFR) monoclonal antibody (mAb) is the more effective addition to a chemotherapy doublet as the first‐line treatment for inoperable KRAS wild‐type mCRC remains controversial in prior clinical trials. Moreover, the association between the sidedness of primary tumors and the efficacy of anti‐EGFR mAb needs to be addressed.MethodsWe established a cohort of patients with KRAS wild‐type mCRC who were treated with first‐line targeted therapy plus doublet chemotherapy between 2013 and 2018 using Taiwan's National Health Insurance Research Database. Secondary surgery was defined as either resection of primary tumors, liver metastases, lung metastases, or radiofrequency ablation.ResultsA total of 6482 patients were included; bevacizumab and anti‐EGFR mAb were the first‐line targeted therapies in 3334 (51.4%) and 3148 (48.6%) patients, respectively. Compared with those who received bevacizumab, patients who received anti‐EGFR mAb exhibited significantly longer overall survival (OS; median, 23.1 vs. 20.2 months, p = 0.012) and time to treatment failure (TTF; median, 11.3 vs. 10 months, p < 0.001). Among left‐sided primary tumors, the OS and TTF benefits of anti‐EGFR mAb remained. Among right‐sided primary tumors, the OS and TTF were similar regardless of the type of targeted therapy. In multivariate analyses, first‐line anti‐EGFR mAb therapy remained an independent predictor of longer OS and TTF for left‐sided primary tumors. Patients who received anti‐EGFR mAb were more likely to receive secondary surgery (29.6% vs. 22.6%, p < 0.0001) than patients who received bevacizumab.ConclusionFor patients who received first‐line doublet chemotherapy for KRAS wild‐type mCRC, adding anti‐EGFR mAb was associated with significantly longer OS and TTF, especially for left‐sided primary tumors.
Synthesis of S‐Adenosyl‐L‐Methionine Analogs with Extended Transferable Groups for Methyltransferase‐Directed Labeling of DNA and RNA
Authors: Malikėnas Martynas , Masevičius Viktoras , Klimašauskas Saulius 
Published: June 2023

AbstractS‐Adenosyl‐L‐methionine (AdoMet) is a ubiquitous methyl donor for a variety of biological methylation reactions catalyzed by methyltransferases (MTases). AdoMet analogs with extended propargylic chains replacing the sulfonium‐bound methyl group can serve as surrogate cofactors for many DNA and RNA MTases, enabling covalent derivatization and subsequent labeling of their cognate target sites in DNA or RNA. Although AdoMet analogs with saturated aliphatic chains are less popular than propargylic ones, they can be useful for dedicated studies that require certain chemical derivatization. Here we describe synthetic procedures for the preparation of two AdoMet analogs, one with a transferable 6‐azidohex‐2‐ynyl group (carrying an activating C≡C triple bond and a terminal azide functionality), and the other one with a transferable ethyl‐2,2,2‐d3 group (an isotope‐labeled aliphatic moiety). Our synthetic approach is based on direct chemoselective alkylation of S‐adenosyl‐L‐homocysteine at sulfur with a corresponding nosylate or triflate, respectively, under acidic conditions. We also describe synthetic routes to 6‐azidohex‐2‐yn‐1‐ol and conversion of the alcohols to corresponding nosylate and triflate alkylators. Using these protocols, the synthetic AdoMet analogs can be prepared within 1 to 2 weeks. © 2023 Wiley Periodicals LLC.Basic Protocol 1: Synthesis of 6‐azidohex‐2‐yn‐1‐olBasic Protocol 2: Synthesis of 4‐nitrobenzenesulfonateBasic Protocol 3: Synthesis of trifluoromethanesulfonatesBasic Protocol 4: S‐Alkylation of AdoHcy with sulfonatesBasic Protocol 5: Purification and characterization of AdoMet analogs
Comparative Study of the Crystal Structure and Simulated 3D Structure of the Hsp90N‐Inhibitor Complex
Authors: Qin Wei , Li Jie , Wang Ming‐Chan , Li Xin‐Yu , Li Peng‐Quan , Zhao Dong , Chu Hai‐Qing , Fu Jia , He Chun‐Xia , Li Hui‐Jin , Xing Lu , Zhou Xin , Zhang Ye , Sun Fang‐Yun , Cao Hui‐Ling 
Published: June 2023

AbstractThe crystal structure of a target‐ligand plays an indispensable role in rational drug design, structural optimization, and understanding the molecular interaction mechanism. For drug targets without crystal structures, the simulated 3D structure will provide an alternative important reference. However, the credibility of the simulated structure and its difference from the real crystal structure deserve deep consideration. The complex crystal structures of the target Hsp90N and its four small molecular inhibitors has previously been successfully determined. Herein, computer‐aided molecular docking technology is applied to predict complex 3D structures, and the comparison between the simulated 3D structures and crystal structures is analyzed. Compared with the complex crystal structures, the simulated 3D structures of the four groups have higher consistency with the main chains, whereas the branch chains, binding modes of inhibitors, and molecular interactions are different in detail. Thus, the simulated 3D complex structure can provide useful information to guide drug design and structural optimization of inhibitors when the crystal structure is missing, but it cannot replace the crystal structure and should be used with caution.
DNA methylation in small cell lung cancer
Authors: Zhu Xianmin , Gao Yuehua , Feng Yimiao , Zheng Jie , Dong Yixiao , Zhang Peng , Zhu Yuming , Fan Guoping 
Published: June 2023

AbstractSmall cell lung cancer (SCLC) originates from pulmonary neuroendocrine cells and accounts for approximately 15% of lung cancer incidents. Patients with SCLC have a very low survival rate due to fast progression and early metastasis. Despite the recent approval of immune checkpoint blockade for treatment of SCLC by US FDA, conventional platinum chemotherapy remains the first‐line treatment which always develops quick drug resistance. To define targets for diagnosis and treatment, SCLC has been categorized by different molecular markers. The most popular markers include genomic mutations in tumour suppressor genes such as TP53 and RB1 and expression of lineage‐specific transcription factors (TFs), that is ASCL1, NEUROD1, POU2F3 and YAP1. As DNA methylation is an important hallmark of cancer, efforts were made to investigate the mechanisms of DNA methylation involved in SCLC progression. Indeed, SCLC has distinct pattern of DNA methylation due to its different features compared to non‐SCLC and other tumours. In this review, we summarized the mechanisms of DNA methylation in SCLC which are associated with lineage‐specific TFs, cell proliferation, anti‐apoptosis, drug resistance, immune evasion and metastasis. We foresaw the challenges of applying DNA methylation in clinical diagnosis and treatment and discussed new approaches and technologies to overcome them. Combined with other gene regulatory information such as transcription and histone modification, DNA methylation/hydroxymethylation in SCLC will be resolved at single‐cell resolution to dissect the tumour microenvironment. The huge multiomics data will be processed and integrated with clinical data such as clinical images and pathological histochemistry by artificial intelligence and cloud computing. Circulating cell‐free DNA methylation will greatly enhance early diagnosis and prognosis prediction. New organoid and organ chip models will break through the obstacles of sampling limitation, faithfully simulate the physiology of human tissues and enable examining spatiotemporal DNA methylation during SCLC progression.
The utility of coded very high frequency telemetry for monitoring reintroduced mammal populations
Authors: Frick Chloe H. , Hole Donell , Sandow Derek , Olds Liberty G. M. , Ostendorf Bertram , Taggart David , Roshier David 
Published: June 2023

AbstractVery high frequency (VHF) radio tracking technology deployed on terrestrial vertebrates has been well utilized in ecology without much evolution since the 1960s. With the advent of multi‐species rewilding projects, and the new field of reintroduction biology, there has been an increase in requirements for telemetry systems to monitor survival and mortality for many animals simultaneously. Common, pulsed VHF can only monitor one individual on each radio frequency, and the number of individuals monitored is constrained by the amount of time spent on each frequency to facilitate a detection and the number of receivers. Coded VHF largely removes these constraints by using a digital code that can simultaneously monitor up to 512 individuals on a single frequency. Incorporated into an autonomous monitoring system, the coded VHF system also greatly reduces time in the field to confirm the status of individuals. Here we demonstrate the utility of coded VHF technologies applied to monitoring a reintroduced population of brush‐tailed bettong (Bettongia penicillata) on the Southern Yorke Peninsula in southern Australia. A system of autonomous monitoring towers was able to monitor 28 different individuals simultaneously without having to change frequency on any of the towers. During a single 24‐h period, one individual was recorded 24,078 times. Key benefits of the high detection rate and autonomous recording are, a timely response to mortalities or a predation event, the detection of nocturnal, cryptic, or burrowing species whenever they are active, and the reduced need for personnel to be in the field.
Species diversity, primary productivity, and photosynthetic pathway in grasslands of eastern Pennsylvania
Authors: Fetcher Ned , Stratford Jeffrey A. , Steele Michael A. , Klemow Kenneth M. 
Published: June 2023

AbstractWe examined the relationship between primary productivity and diversity for grassland, meadow, and savanna (GMS) vegetation in northeastern Pennsylvania, USA, where the landscape is primarily forests, agriculture, and urban or suburban development. We surveyed primary productivity, plant species diversity, invertebrate order diversity, and avian abundance and species diversity for 14 grasslands and open areas that were actively managed and three that apparently occurred naturally. Four grasslands were dominated by warm‐season grasses with the C4 photosynthetic pathway, nine were dominated by C3 grasses, forbs, and shrubs, and four had a mixture of both types. We found hump‐shaped relationships for plant species richness and bird species richness as a function of productivity but not for invertebrate order richness. Richness of invertebrates and birds increased linearly with the number sampled at each site. The number of plant species declined with increasing proportion of warm‐season grasses, as did the number of invertebrate orders collected in sweep samples, avian abundance, and avian species richness. Multiple regression showed that both landscape and vegetative characteristics influenced the bird community. Bird species richness increased with the area of the sites, the ratio of area to edge, and the distance to the nearest open area. There was no evidence for the influence of the relative abundance of native plant species on bird or invertebrate richness. GMS restoration of farmlands and mine lands with plantings of warm‐season grasses, while possibly beneficial for some forms of wildlife, seems to be less effective in maintaining the diversity of invertebrates and birds than a mixture of warm‐season grasses, cool‐season grasses, forbs, and shrubs.
Toward an extreme world: The hyper‐arid ecosystem as a natural model
Authors: Groner Elli , Babad Avshalom , Berda Swiderski Naomi , Shachak Moshe 
Published: June 2023

AbstractThe forecasted increased frequency and intensity of extreme climatic events may strongly affect ecosystem structure and function in the future. It is unclear how ecosystems will function in the long run over a large spatial scale under a new extreme water cycle. This open question calls for a conceptual framework as a fundamental basis for theoretical and experimental exploration of ecosystem function on a large scale driven by an extreme climate envelope. To assess the problem on a large scale, we investigated hyper‐arid ecosystems (HAEs) as natural tangible models that already function under an extreme climatic envelope. Our new assertion is that if extreme climate change drives arid lands to function under alternate extreme conditions, then arid land ecosystems will function like an HAE as an alternative state, rather than progress to desertification. To support our assertion, we developed a conceptual framework of HAEs that includes a geo‐hydrological “abiotic engine” that drives HAE function by soil moisture diversity and plant functional groups. Based on this conceptual framework, we suggest incorporating two new hypotheses in climate change studies to advance our understanding of responses of large‐scale, water‐limited ecosystems: (1) Hydro‐climatic extremes in water‐limited ecosystems will reduce the degree of resource conservation by slope ecosystems due to reduction in plant cover and soil. The decreased ecosystem function on the slope will be compensated for by increasing the effect of the abiotic engine on the ephemeral stream, thus enhancing meta‐ecosystem functioning in the ephemeral stream. (2) In water‐limited ecosystems, climate change toward hydro‐climatic extremes will rescale the dominant hydro‐ecological processes of pulse–reserve, source–sink, and connectivity along the semiarid, arid, and HA gradients in two ways: (i) shrinking of both spatial and temporal dimensions; and (ii) shrinking in the temporal dimension and expanding in the spatial dimensions. The first rescaling trajectory is related to biodiversity–ecosystem function and the second to the abiotic engine processes.
Diagnostic performance of the EU TI‐RADS and ACR TI‐RADS scoring systems in predicting thyroid malignancy
Authors: Chatti Hiba‐Allah , Oueslati Ibtissem , Azaiez Aymen , Marrakchi Jihen , Boukriba Seif , Mizouni Habiba , Haouet Slim , Besbes Ghazi , Yazidi Meriem , Chihaoui Melika 
Published: June 2023

AbstractIntroductionSeveral ultrasound scoring systems have been developed to stratify the risk of malignancy of thyroid nodules, including ACR (American College of Radiology) and EU (European) TI‐RADS. This study aimed to assess the diagnostic performance of these two classifications using histology as a reference standard.MethodsIt was a single‐centre, retrospective study including 156 patients who underwent thyroidectomy. Ultrasound data of 198 nodules (99 malignant nodules and 99 benign nodules) were analysed. Both classifications were applied for all nodules.ResultsUltrasound criteria associated with malignancy were solid composition (OR=7.81; p < 10−3), hypoechoic character (OR=16.42; p < 10−3), irregular contours (OR=7.47; p < 10−3), taller‐than‐wide shape (OR=3.58; p = 0.02), microcalcifications (OR=3.02; p = .006) and the presence of cervical adenopathy (OR=3.89; p = .006). The prevalence of malignancy was 15.5%, 69% and 76.9% for EU TI‐RADS categories 3, 4 and 5, respectively. It was 33.3%, 57% and 91.1% for ACR TI‐RADS categories 3, 4 and 5, respectively. For category 5, EU TI‐RADS and ACR TI‐RADS had sensitivities of 60% and 41%, specificities of 82% and 96%, respectively. For categories 4 and 5 combined, the diagnostic performance of these two classification systems became comparable with a sensitivity of 89% and 86% for EU‐TIRADS and ACR‐TIRADS, respectively. The area under the ROC curve was 0.81 for the EU TI‐RADS classification and 0.82 for the ACR TI‐RADS classification.ConclusionsEU TI‐RADS and ACR TI‐RADS scoring systems seem to be comparable in predicting malignancy in thyroid nodules.
Gastrointestinal bleeding on continuous‐flow left ventricular assist device therapy
Authors: Hammer Yoav , Bitar Abbas , Aaronson Keith D. 
Published: June 2023

AbstractWhile technological advances in the field of continuous‐flow left ventricular assist device (CF‐LVAD) are constantly being made, CF‐LVAD recipients are still subjected to a relatively high rate of LVAD‐related adverse events, with post‐LVAD gastrointestinal bleeding (GIB) being the most common one. GIB is associated with a significant impairment in quality of life, multiple hospital admissions, blood transfusion requirements and possibly death. Furthermore, of those patients who bled once, many will experience recurrent GIB events, which further aggravates their discomfort. While some medical and endoscopic treatment options are available, evidence regarding their benefit remains largely equivocal, with all related studies based on data from registries rather than clinical trials. Although having a major impact on LVAD recipients, an effective and validated pre‐implant screening options to predict GIB events post‐implant are scarce. This review focuses on the aetiology, incidence, risk factors, treatment options and the effect of new generation devices on post‐LVAD GIB.
NR1D1::MAML1 epithelioid and spindle cell sarcoma mimicking pseudomyogenic hemangioendothelioma in core biopsy: A case report and review of the literature
Authors: Warmke Laura M. , Collier Christopher D. , Davis Jessica L. 
Published: June 2023

AbstractEpithelioid and spindle cell sarcomas with NR1D1::MAML1/2 gene fusions are rare and emerging entities. Only six cases of NR1D1‐rearranged mesenchymal tumors have previously been reported in the literature; they are often characterized by an epithelioid morphology, at least focal pseudogland formation, prominent cytoplasmic vacuoles, and focal to diffuse immunohistochemical expression of keratin. We herein report the first case of an NR1D1::MAML1 epithelioid and spindle cell sarcoma with dual immunohistochemical expression of ERG and FOSB, mimicking a pseudomyogenic hemangioendothelioma (PHE) on core biopsy. The sarcoma arose in the left forearm of a 64‐year‐old man. Initial biopsy showed a mesenchymal neoplasm composed of epithelioid and spindle cells dispersed in myxoid stroma with scattered stromal neutrophils. The morphologic features, combined with the dual immunohistochemical expression of ERG and FOSB, initially mimicked PHE, representing an important potential diagnostic pitfall. The patient subsequently underwent a radical resection, which showed a much more diffuse epithelioid appearance with nested architecture and pseudogland formation. Next‐generation sequencing was performed on the resection specimen, which revealed an NR1D1::MAML1 gene fusion, confirming the final diagnosis. Given the fully malignant potential of this tumor, knowledge and recognition of this rare entity are essential to ensure proper management, prevent misdiagnosis, and further characterize the clinical course of this emerging entity. Comprehensive molecular testing can help to identify these rare tumors and exclude the possibility of epithelioid mimics, including PHE.
Quality of life burden on United States infants and caregivers due to lower respiratory tract infection and adjusting for selective testing: Pilot prospective observational study
Authors: Hariharan Dhwani , Kumar V. S. Senthil , Glaser Elizabeth L , Crown William H. , Wolf Zachary A. , Fisher Kimberley A. , Wood Charles T. , Malcolm William F. , Nelson Christopher B. , Shepard Donald S. 
Published: June 2023

AbstractBackground and AimsPolicymakers need data about the burden of respiratory syncytial virus (RSV) lower respiratory tract infections (LRTI) among infants. This study estimates quality of life (QoL) for otherwise healthy term US infants with RSV‐LRTI and their caregivers, previously limited to premature and hospitalized infants, and corrects for selective testing.MethodsThe study enrolled infants <1 year with a clinically diagnosed LRTI encounter between January and May 2021. Using an established 0–100 scale, the 36 infants’ and caregivers’ QoL at enrollment and quality‐adjusted life year losses per 1000 LRTI episodes (quality‐adjusted life years [QALYs]/1000) were validated and analyzed. Regression analyses examined predictors of RSV‐testing and RSV‐positivity, creating modeled positives.ResultsMean QoL at enrollment in outpatient (n = 11) LRTI‐tested infants (66.4) was lower than that in not‐tested LRTI infants (79.6,p = 0.096). For outpatient LRTI infants (n = 23), median QALYs/1000 losses were 9.8 and 0.25 for their caregivers. RSV‐positive outpatient LRTI infants (n = 6) had significantly milder QALYs/1000 losses (7.0) than other LRTI‐tested infants (n = 5)(21.8,p = 0.030). Visits earlier in the year were more likely to be RSV‐positive than later visits (p = 0.023). Modeled RSV‐positivity (51.9%) was lower than the observed rate (55.0%). Infants’ and caregivers’ QALYs/1000 loss were positively correlated (rho = 0.34,p = 0.046), indicating that infants perceived as sicker imposed greater burdens on caregivers.ConclusionsThe overall median QALYs/1000 losses for LRTI (9.0) and RSV‐LRTI (5.6) in US infants are substantial, with additional losses for their caregivers (0.25 and 0.20, respectively). These losses extend equally to outpatient episodes. This study is the first reporting QALY losses for infants with LRTI born at term or presenting in nonhospitalized settings, and their caregivers.