bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bulk and single‐cell spatial transcriptomic analysis reveals cuproptosis‐related molecular subtypes characterized by distinct tumour microenvironment infiltrates in colorectal cancer
Authors: Luo Wenqin , Gu Ruiqi , Fang Hongsheng , Zhang Ruijia , Gan Lu , Mo Shaobo , Li Qingguo 
Published: February 2023

AbstractBackgroundThe association between tumour microenvironment (TME) in colorectal cancer (CRC) and cell death patterns requires further exploration. Cuproptosis may provide new insight into analyzing CRC's TME.MethodsWe used cuproptosis‐related genes (CRGs) to stratify the meta‐Gene‐Expression Omnibus cohort by the “non‐negative matrix factorization” consistency matrix algorithm. To clarify the relative abundance of different cells in TME, CIBERSORT and single‐sample gene set enrichment methods were performed. Then, CRGs’ transcription in different cell types and the spatial position of CRGs’ enrichment were demonstrated through single‐cell spatial transcriptomics (STs) analysis. Prediction of clinical outcomes and response rate of immunotherapy was also conducted by constructing CRG_score.ResultsThree cuproptosis‐related TME phenotypes were figured out in CRC with distinctive clinicopathological and prognostic features. Three phenotypes were identical to immune‐inflamed, immune‐desert and immune‐excluded profiles, respectively. Interestingly, cuproptosis‐related cluster 3 (CPRC3) phenotype‐related gene_score was predominantly upregulated in the fibroblast region, consisting of stromal cells. This result was in line with CPRC3's immune‐excluded profile. Based on the robust cuproptosis‐related risk_score and nomogram, CRC patients’ clinical outcome and response to PD1/PD‐L1 immunotherapy can be well predicted.ConclusionsThis study characterized three cuproptosis‐related TME patterns with unique immune infiltration and prognosis in both bulk and single‐cell ST profiling. Risk_score was also built to help clinicians decide on personalized anticancer treatment and immunotherapy applications for CRC patients.
Comparison of fine‐needle aspiration and core‐needle biopsy in the pathological evaluation on thyroid lesions: A single‐center experience on 407 Chinese patients
Authors: Li Wei , Han Ya‐Ting , Hu Zhandong , Zhang Yujie , Zhao Xin , Guo Xuexi , Cai Wenjuan , Zhang Mingfang 
Published: February 2023

AbstractBackgroundThe object of this study was to compare the diagnosis performance of US‐guided fine‐needle aspiration (FNA) and core‐needle biopsy (CNB) for patients with thyroid nodules, in aspects of sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV).Materials and MethodsFour hundred seven Chinese patients from July 2019 to June 2022 were retrospectively recruited in this study. Cytological diagnoses were categorized into six categories based on the 2017 Bethesda System for Reporting Thyroid Cytopathology (BSRTC), and histological specimens were drawn a diagnosis by means of an analogy with the Bethesda system.ResultsAll patients incorporated were proceed with surgical excision (SE) and received final surgical diagnoses. The rate of malignancy (ROM) was comparable between two methods, with the exception that the test‐negative category of the FNA group was significantly higher than that of the CNB group (39.25% vs. 23.86%, p = .022). Sensitivity and accuracy were higher in CNB group (82.50% and 87.83%, respectively) than that in FNA group (72.00% and 79.36%, respectively), as well as NPV (76.14% in CNB vs. 60.75% in FNA), but not in terms of the specificity and PPV (95.59% and 97.30% in FNA vs. 97.10% and 98.02% in CNB).ConclusionCNB displayed a higher sensitivity and accuracy than FNA in malignant lesions of thyroid. Both FNA and CNB exhibit excellent performance with the understanding that both need to be applied under the most appropriate conditions to maximize their benefits.
Shikonin potentiates therapeutic efficacy of oxaliplatin through reactive oxygen species‐mediated intrinsic apoptosis and endoplasmic reticulum stress in oxaliplatin‐resistant colorectal cancer cells
Authors: Zhang Zhengguang , Shen Cunsi , Zhou Fuqiong , Zhang Yajie 
Published: February 2023

AbstractOxaliplatin (OXA) has been recognized as a third‐generation platinum‐based chemotherapeutic agent with stellar therapeutic efficacy in managing colorectal cancer (CRC). Nevertheless, resistance to OXA in CRC patients hinders its effectiveness. Shikonin (SHI), a natural naphthoquinone derived from Arnebia euchroma (Royle) Johnst., features a broad pharmacological profile and minimal toxicities. To assess the synergism of SHI and OXA towards OXA‐resistant CRC cells (HCT116R), we employed in vitro and in vivo pharmacological assays. Our experiments provided evidence that SHI, either alone or in combination with OXA, considerably reduced cell proliferation, triggered apoptosis, and induced the generation of reactive oxygen species (ROS) in HCT116R cells. Furthermore, the combination of SHI and OXA dramatically curbed the extent of HCT116R‐initiated xenograft growth in mouse models. Bioinformatics, western blot, and ROS assays highlighted that the mechanisms of SHI against OXA‐resistant CRC cells may involve the induction of cellular responses to chemical stress, intrinsic apoptosis, as well as endoplasmic reticulum stress pathways mediated by ROS. Notably, the synergism of SHI+OXA was partially abrogated by an ROS inhibitor N‐acetyl cysteine. Our findings imply the potential of SHI to boost the sensitivity of OXA to CRC, offering promising benefits for clinical strategies to combat OXA resistance.
Diastereoselective Synthesis of Camptothecin‐like Scaffolds: Construction of a New Class of Pseudo‐natural Products
Authors: Srikanth Gourishetty , Ravi Anil , Sebastian Anusha , Joseph Jobi , Khanfar Monther A. , El‐Gamal Mohammed I. , Al‐Qawasmeh Raed A. , Shehadi Ihsan A. , McN. Sieburth Scott , Abu‐Yousef Imad A. , Majdalawieh Amin F. , Al‐Tel Taleb H. 
Published: February 2023

AbstractThe discovery of novel small molecules endowed with high 3D‐content remains a powerful tool for interrogating underrepresented biological space. To this end, the pseudo‐natural products (pseudo‐NP) strategy has become one of the most important tools to deliver biologically significant chemical probes. In this article, we describe the development of a new class of pseudo‐NP collection, through connecting tryptamines with a furanose derivative followed by subjecting the product from this operation to a ring distortion strategy that led to diastereoselective synthesis of camptothecin‐like compounds. This process is driven by a cascade that unites Pictet–Spengler reaction with Michael addition reaction, followed by oxidative‐ring enlargement and subsequent transannular aldol cyclization delivering camptothecin‐like architectures. The obtained diastereoselectivity was verified using density functional theory (DFT) calculations.
A Modeling Approach for Assessing Ecological Risks of Neonicotinoid Insecticides from Emission to Nontarget Organisms: A Case Study of Cotton Plant
Authors: Li Zijian , Li Minmin , Niu Shan 
Published: February 2023

Abstract
The use of neonicotinoid insecticides in agriculture has posed threats to ecological systems, and there is a need to assess the ecological risks of neonicotinoids from emission to nontarget organisms. We introduced a modeling approach to assess the ecological risks of neonicotinoids using honeybee and earthworm as model organisms, and the simulation was flexible under different environmental conditions. Using the cotton plant as an example, the simulation results demonstrated that under current recommended application rates, the use of common neonicotinoid insecticides posed no threat to earthworms, with the simulated risk quotients (RQs) much lower than 1. However, the simulation for some neonicotinoid insecticides (e.g., acetamiprid) indicated that using these insecticides on cotton plants could threaten honeybees, with simulated RQs higher than 1. The variability analysis showed that in high-latitude regions, the unacceptable risk to honeybees posed by insecticide application can be further elevated due to cold, wet weather that results in relatively high insecticide levels in pollen and nectar. The model evaluation showed large overlaps of simulated risk intervals between the proposed and existing (BeeREX) models. Because the proposed and existing models have different simulation mechanisms, we recommend that these two models be used together to complement each other in future studies. Environ Toxicol Chem 2023;42:928–938. © 2023 SETAC
Cell‐instructive biomaterials in tissue engineering and regenerative medicine
Authors: Adhikari Bikram , Stager Michael A. , Krebs Melissa D. 
Published: February 2023

AbstractThe field of biomaterials aims to improve regenerative outcomes or scientific understanding for a wide range of tissue types and ailments. Biomaterials can be fabricated from natural or synthetic sources and display a plethora of mechanical, electrical, and geometrical properties dependent on their desired application. To date, most biomaterial systems designed for eventual translation to the clinic rely on soluble signaling moieties, such as growth factors, to elicit a specific cellular response. However, these soluble factors are often limited by high cost, convoluted synthesis, low stability, and difficulty in regulation, making the translation of these biomaterials systems to clinical or commercial applications a long and arduous process. In response to this, significant effort has been dedicated to researching cell‐directive biomaterials which can signal for specific cell behavior in the absence of soluble factors. Cells of all tissue types have been shown to be innately in tune with their microenvironment, which is a biological phenomenon that can be exploited by researchers to design materials that direct cell behavior based on their intrinsic characteristics. This review will focus on recent developments in biomaterials that direct cell behavior using biomaterial properties such as charge, peptide presentation, and micro‐ or nano‐geometry. These next generation biomaterials could offer significant strides in the development of clinically relevant medical devices which improve our understanding of the cellular microenvironment and enhance patient care in a variety of ailments.
Thioredoxin 1 overexpression attenuated diabetes‐induced endoplasmic reticulum stress in Müller cells via apoptosis signal‐regulating kinase 1
Authors: Yu Xuebin , Teng Qiufeng , Bao Kaimin , Chudhary Maryam , Qi Hui , Zhou Wenying , Che Hongxin , Liu Junli , Ren Xiang , Kong Li 
Published: February 2023

AbstractAs one of the common and serious chronic complications of diabetes mellitus (DM), the related mechanism of diabetic retinopathy (DR) has not been fully understood. Müller cell reactive gliosis is one of the early pathophysiological features of DR. Therefore, exploring the manner to reduce diabetes‐induced Müller cell damage is essential to delay DR. Thioredoxin 1 (Trx1), one of the ubiquitous redox enzymes, plays a vital role in redox homeostasis via protein–protein interactions, including apoptosis signal‐regulating kinase 1 (ASK1). Previous studies have shown that upregulation of Trx by some drugs can attenuate endoplasmic reticulum stress (ERS) in DR, but the related mechanism was unclear. In this study, we used DM mouse and high glucose (HG)‐cultured human Müller cells as models to clarify the effect of Trx1 on ERS and the underlying mechanism. The data showed that the diabetes‐induced Müller cell damage was increased significantly. Moreover, the expression of ERS and reactive gliosis was also upregulated in diabetes in vivo and in vitro. However, it was reversed after Trx1 overexpression. Besides, ERS‐related protein expression, reactive gliosis, and apoptosis were decreased after transfection with ASK1 small‐interfering RNA in stable Trx1 overexpression Müller cells after HG treatment. Taken together, Trx1 could protect Müller cells from diabetes‐induced damage, and the underlying mechanism was related to inhibited ERS via ASK1.
Characteristics of adult hospital medicine fellowships in the United States: A cross‐sectional survey study
Authors: Felde Lanna , Burden Marisha , Shah Nainesh , Ramos Pedro , Chu Eugene S. 
Published: February 2023

AbstractBackgroundHospitalists who seek academic careers are interested in developing skills in research, education, and quality improvement (QI). Since these are not major foci of residency programs, hospitalists may pursue a hospital medicine fellowship to acquire these skill sets.ObjectiveWe sought to characterize the current state of hospital medicine fellowships in the United States, including demographics, clinical requirements, curricular focus, financial structure, and scholarly outputs.Designs, Settings, and ParticipantsThis was a cross‐sectional study of 32 hospital medicine fellowship programs across the United States in 2020–2021. An electronic survey was emailed to program leaders.ResultsOut of 32 eligible programs contacted, 19 (59.4%) programs responded, representing 22 fellowship tracks. Most (63.2%) programs have been in existence for 5 years or less. Fourteen (63.6%) of the tracks had multiple focus areas, while 8 (36.4%) had a single focus. Of the 14 fellowship tracks with multiple focus areas, 6 (42.8%) reported research, QI and medical education as curricular elements. All 14 reported research as one of the curricular elements. The majority (68.4%) of programs offered opportunities to obtain a master's degree, though the field of degree varied widely. A median of 50% (IQR 0) of fellows' time was spent in clinical activities. Considerable heterogeneity exists among adult hospital medicine fellowship programs. The majority focus on research, QI, and/or medical education. Hospital medicine fellowships offer opportunities for intesive faculty development and unique career pathways.
Diagnostic delays among COVID‐19 patients with a second concurrent diagnosis
Authors: Freund Ophir , Azolai Lee , Sror Neta , Zeeman Idan , Kozlovsky Tom , Greenberg Sharon A. , Epstein Weiss Tali , Bornstein Gil , Tchebiner Joseph Zvi , Frydman Shir 
Published: February 2023

AbstractBackgroundLittle is known about the effect of a new pandemic on diagnostic errors.ObjectiveWe aimed to identify delayed second diagnoses among patients presenting to the emergency department (ED) with COVID‐19.DesignsAn observational cohort Study.Settings and ParticipantsConsecutive hospitalized adult patients presenting to the ED of a tertiary referral center with COVID‐19 during the Delta and Omicron variant surges. Included patients had evidence of a second diagnosis during their ED stay.Main Outcome and MeasuresThe primary outcome was delayed diagnosis (without documentation or treatment in the ED). Contributing factors were assessed using two logistic regression models.ResultsAmong 1249 hospitalized COVID‐19 patients, 216 (17%) had evidence of a second diagnosis in the ED. The second diagnosis of 73 patients (34%) was delayed, with a mean (SD) delay of 1.5 (0.8) days. Medical treatment was deferred in 63 patients (86%) and interventional therapy in 26 (36%). The probability of an ED diagnosis was the lowest for Infection‐related diagnoses (56%) and highest for surgical‐related diagnoses (89%). Evidence for the second diagnosis by physical examination (adjusted odds ratios [AOR] 2.35, 95% confidence interval [CI] 1.20–4.68) or by imaging (AOR 2.10, 95% CI 1.16–3.79) were predictors for ED diagnosis. Low oxygen saturation (AOR 0.38, 95% CI 0.18–0.79) and cough or dyspnea (AOR 0.48, 95% CI 0.25–0.94) in the ED were predictors of a delayed second diagnosis.
Long‐term outcomes of pacemaker implantation in children with univentricular versus complex biventricular surgical repair
Authors: Spentzou Georgia , Taylor Luke , Zhang Yiyan , D'Udekem Yves , Zannino Diana , Davis Andrew , Pflaumer Andreas 
Published: February 2023

AbstractObjectivePacing in a univentricular circulation has been associated with worsened outcomes. We investigated the long‐term outcomes of pacing in children with a univentricular circulation compared to a complex biventricular circulation. We also identified predictors of adverse outcomes.MethodsA retrospective study of all children with major congenital heart disease who underwent pacemaker implantation under the age of 18 years between November 1994 and October 2017.ResultsEighty‐nine patients were included; 19 with a univentricular and 70 with a complex biventricular circulation. A total of 96% of pacemaker systems were epicardial. Median follow up was 8.3 years. The incidence of adverse outcome was similar between the two groups. Five (5.6%) patients died and two (2.2%) underwent heart transplantation. Most adverse events occurred within the first 8 years after pacemaker implantation. Univariate analysis identified five predictors of adverse outcomes in the patients in the biventricular but none in the univentricular group. The predictors of adverse outcome in the biventricular circulation were a right morphologic ventricle as the systemic ventricle, age at first congenital heart disease (CHD) operation, number of CHD operations, and female gender. The nonapical lead position was associated with a much higher risk of an adverse outcome.ConclusionsChildren with a pacemaker and a complex biventricular circulation have similar survival to the ones with a pacemaker and a univentricular circulation. The only modifiable predictor was the epicardial lead position on the paced ventricle, emphasizing the importance of apical placement of the ventricular lead.
The future of scientific journals: The rise of UniAI
Authors: Habibzadeh Farrokh 
Published: February 2023

Key points
The enormous amount of scientific data produced each second will make it difficult to analyze them.
In near future, a universal AI‐based (UniAI) system with ready access to a collective database will be formed to analyze the gigantic amount of data being created.
There will be no ready articles, no scientific journal, no indexing system, no peer review, no research or publication ethical concerns, and no editor.
UniAI, a self‐organized self‐sufficient AI system will assume most part of the research and its publication.
Intraputaminal Gene Delivery in Two Patients with Aromatic L‐Amino Acid Decarboxylase Deficiency
Authors: François‐Heude Marie‐Céline , Poulen Gaetan , Flamand Roze Emmanuel , Nguyen Morel Marie‐Ange , Gras Domitille , Roch‐Toreilles Isabelle , Quintard Adeline , Baroux Gaelle , Meyer Pierre , Coubes Philippe , Milesi Christophe , Cambonie Gilles , Baleine Julien , Sola Chrystelle , Delye Bénédicte , Dimopoulou Evgenia , Sanchez Stéphanie , Gasnier Mathieu , Touati Souad , Zamora Alberto , Pontal Daniel , Leboucq Nicolas , Kouyoumdjian Virginie , Lebasnier Adrien , Sanquer Sylvia , Mariano‐Goulart Denis , Roujeau Thomas , Roubertie Agathe 
Published: February 2023

ABSTRACTBackgroundAromatic l‐amino acid decarboxylase deficiency (AADCD) is a rare, early‐onset, dyskinetic encephalopathy mostly reflecting a defective synthesis of brain dopamine and serotonin. Intracerebral gene delivery (GD) provided a significant improvement among AADCD patients (mean age, ≤6 years).ObjectiveWe describe the clinical, biological, and imaging evolution of two AADCD patients ages >10 years after GD.MethodsEladocagene exuparvovec, a recombinant adeno‐associated virus containing the human complimentary DNA encoding the AADC enzyme, was administered into bilateral putamen by stereotactic surgery.ResultsEighteen months after GD, patients showed improvement in motor, cognitive and behavioral function, and in quality of life. Cerebral l‐6‐[18F] fluoro‐3, 4‐dihydroxyphenylalanine uptake was increased at 1 month, persisting at 1 year compared to baseline.ConclusionTwo patients with a severe form of AADCD had an objective motor and non‐motor benefit from eladocagene exuparvovec injection even when treated after the age of 10 years, as in the seminal study.
Full modulation transfer functions of thick parallel‐ and focused‐element scintillator arrays obtained by a Monte Carlo optical transport model
Authors: Zarrini‐Monfared Zinat , Karbasi Sareh , Zamani Ali , Mosleh‐Shirazi Mohammad Amin 
Published: February 2023

AbstractBackgroundArrays of thick segmented crystalline scintillators are useful x‐ray converters for image‐guided radiation therapy using electronic portal imaging (EPI) and megavoltage cone‐beam computed tomography (MV‐CBCT). Ionizing‐radiation‐only simulations previously showed relatively low modulation transfer function (MTF) in parallel‐element arrays because of beam divergence. Hence, a focused‐element geometry (matching the beam divergence) has been proposed. The “full” (ionizing and optical) MTF performance of such a focused geometry compared to its radiation‐only MTF has, however, not been fully investigated.PurposeTo study the full MTF performance of such arrays in a more realistic situation in which optical characteristics are also included using an in‐house detector model that supports light transport, and quantify the errors in MTF estimation when the optical stage is ignored.MethodsFirst, radiation (x‐ray and electron) transport was simulated. Then, transport of the generated optical photons was modeled using ScintSim2, an optical Monte Carlo (MC) code developed in MATLAB for simulation of two‐dimensional (2D) parallel‐ and focused‐element scintillator arrays. The full‐MTF responses of focused‐ and parallel‐element geometries, for a large array of 3 × 3 mm2 CsI:Tl detector elements of 10, 40, and 60 mm thicknesses, were examined. For each configuration, a composite line spread function (LSF) was calculated to obtain the MTF.ResultsAt the Nyquist frequency, for 10 mm‐thick central elements and 60 mm‐thick peripheral parallel elements, full‐MTF exhibited a drop of up to 15 and 79 times, respectively, compared with radiation‐only MTF. This was found to be partly attributable to the angular distribution of the light emerging from the detector‐element exit face and the dependence on its aspect ratio, since the light exiting thicker scintillators exhibited a more forward‐directed distribution. Focused elements provided an increase of up to nine times in peripheral‐area full MTF values.ConclusionsFull MTF was up to 79 times lower than radiation‐only MTF. Focused arrays preserved full MTF by up to nine times compared to parallel elements. The differences in the results obtained with and without inclusion of optical photons emphasize the need to include light transport when optimizing thick segmented scintillation detectors. Besides their application in detector optimization for radiotherapy megavoltage photon imaging, these findings can also be useful for other segmented‐scintillator‐based imaging systems, for example, in nuclear medicine, or in 2D detection systems for quality assurance of MR‐linacs.