bluuebunny/crossref_metadata_2025_split huggingface dataset:
From organoids to bedside: Advances in modeling, decoding and targeting of colorectal cancer
Authors: Betge Johannes , Jackstadt Rene 
Published: September 2022

AbstractPatient derived organoids closely resemble the biology of tissues and tumors. They are enabling ex vivo modeling of human diseases and dissecting key features of tumor biology like anatomical diversity or inter‐ and intra‐tumoral heterogeneity. In the last years, organoids were established as models for drug discovery and explored to guide clinical decision making. In this review, we discuss the recent developments in organoid based research, elaborating on the developments in colorectal cancer as a prime example. We focus our review on the role of organoids to decode cancer cell dynamics and tumor microenvironmental complexity with the underlying bi‐directional crosstalk. Additionally, advancements in the development of living biobanks, screening approaches, organoid based precision medicine and challenges of co‐clinical trials are highlighted. We discuss ongoing efforts to overcome challenges that the field faces and indicate potential future directions.
Classification of brain hemorrhage computed tomography images using OzNet hybrid algorithm
Authors: Ozaltin Oznur , Coskun Orhan , Yeniay Ozgur , Subasi Abdulhamit 
Published: September 2022

AbstractClassification of brain hemorrhage computed tomography (CT) images provides a better diagnostic implementation for emergency patients. Attentively, each brain CT image must be examined by doctors. This situation is time‐consuming, exhausting, and sometimes leads to making errors. Hence, we aim to find the best algorithm owing to a requirement for automatic classification of CT images to detect brain hemorrhage. In this study, we developed OzNet hybrid algorithm, which is a novel convolution neural networks (CNN) algorithm. Although OzNet achieves high classification performance, we combine it with Neighborhood Component Analysis (NCA) and many classifiers: Artificial neural networks (ANN), Adaboost, Bagging, Decision Tree, K‐Nearest Neighbor (K‐NN), Linear Discriminant Analysis (LDA), Naïve Bayes and Support Vector Machines (SVM). In addition, Oznet is utilized for feature extraction, where 4096 features are extracted from the fully connected layer. These features are reduced to have significant and informative features with minimum loss by NCA. Eventually, we use these classifiers to classify these significant features. Finally, experimental results display that OzNet‐NCA‐ANN excellent classifier model and achieves 100% accuracy with created Dataset 2 from Brain Hemorrhage CT images.
Lysosomal glycogen accumulation in Pompe disease results in disturbed cytoplasmic glycogen metabolism
Authors: Canibano‐Fraile Rodrigo , Harlaar Laurike , dos Santos Carlos A. , Hoogeveen‐Westerveld Marianne , Demmers Jeroen A. A. , Snijders Tim , Lijnzaad Philip , Verdijk Robert M. , van der Beek Nadine A. M. E. , van Doorn Pieter A. , van der Ploeg Ans T. , Brusse Esther , Pijnappel W. W. M. Pim , Schaaf Gerben J. 
Published: September 2022

AbstractPompe disease is an inherited metabolic myopathy caused by deficiency of acid alpha‐glucosidase (GAA), resulting in lysosomal glycogen accumulation. Residual GAA enzyme activity affects disease onset and severity, although other factors, including dysregulation of cytoplasmic glycogen metabolism, are suspected to modulate the disease course. In this study, performed in mice and patient biopsies, we found elevated protein levels of enzymes involved in glucose uptake and cytoplasmic glycogen synthesis in skeletal muscle from mice with Pompe disease, including glycogenin (GYG1), glycogen synthase (GYS1), glucose transporter 4 (GLUT4), glycogen branching enzyme 1 (GBE1), and UDP‐glucose pyrophosphorylase (UGP2). Expression levels were elevated before the loss of muscle mass and function. For first time, quantitative mass spectrometry in skeletal muscle biopsies from five adult patients with Pompe disease showed increased expression of GBE1 protein relative to healthy controls at the group level. Paired analysis of individual patients who responded well to treatment with enzyme replacement therapy (ERT) showed reduction of GYS1, GYG1, and GBE1 in all patients after start of ERT compared to baseline. These results indicate that metabolic changes precede muscle wasting in Pompe disease, and imply a positive feedforward loop in Pompe disease, in which lysosomal glycogen accumulation promotes cytoplasmic glycogen synthesis and glucose uptake, resulting in aggravation of the disease phenotype.
Low‐field MRI: Clinical promise and challenges
Authors: Arnold Thomas Campbell , Freeman Colbey W. , Litt Brian , Stein Joel M. 
Published: September 2022

Modern MRI scanners have trended toward higher field strengths to maximize signal and resolution while minimizing scan time. However, high‐field devices remain expensive to install and operate, making them scarce outside of high‐income countries and major population centers. Low‐field strength scanners have drawn renewed academic, industry, and philanthropic interest due to advantages that could dramatically increase imaging access, including lower cost and portability. Nevertheless, low‐field MRI still faces inherent limitations in image quality that come with decreased signal. In this article, we review advantages and disadvantages of low‐field MRI scanners, describe hardware and software innovations that accentuate advantages and mitigate disadvantages, and consider clinical applications for a new generation of low‐field devices. In our review, we explore how these devices are being or could be used for high acuity brain imaging, outpatient neuroimaging, MRI‐guided procedures, pediatric imaging, and musculoskeletal imaging. Challenges for their successful clinical translation include selecting and validating appropriate use cases, integrating with standards of care in high resource settings, expanding options with actionable information in low resource settings, and facilitating health care providers and clinical practice in new ways. By embracing both the promise and challenges of low‐field MRI, clinicians and researchers have an opportunity to transform medical care for patients around the world.Level of Evidence5Technical EfficacyStage 6
Elevated serum PAR‐1 levels as an emerging biomarker of inflammation to predict the dengue infection severity
Authors: Sibia Raminderpal Singh , Sood Ankita , Subedi Arshula , Sharma Anushya , Mittal Anirudh , Singh Gaaminepreet , Singh Thakur Gurjeet , Jaura Ravinder Singh , Goyal Sanjay 
Published: September 2022

AbstractThe present study was designed to check the serum levels of protease‐activated receptor (PAR‐1) in patients during different phases of dengue severity. Moreover, a correlation between serum PAR‐1 levels and hematological parameters, inflammatory cytokine levels, and liver functional changes was also determined. Based on the World Health Organization criteria, the study population was divided into: nonsevere dengue fever (DF; n = 30), severe dengue hemorrhagic fever (DHF; n = 19), and severe dengue shock syndrome (DSS; n = 11). The platelet count (PLT) and hematocrit (HCT) were analyzed using an automated hematology analyzer and liver function enzymes aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphate (ALP), bilirubin were checked by auto‐analyzer using diagnostic kits. Moreover, the levels of inflammatory mediators C‐reactive protein (CRP), tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6), interleukin‐17 (IL‐17), and PAR‐1 were determined using respective ELISA kits. The HCT levels were elevated and platelet count decreased significantly during dengue complications (DHF and DSS) compared to the DF patients, while the levels of liver functional biomarkers AST, ALT, ALP, and bilirubin remained elevated in DHF and DSS groups than in the corresponding DF group. Similarly, the inflammatory cytokine levels of CRP, TNF‐α, IL‐6, and IL‐17 in DHF and DSS subjects were markedly increased when observed against DF subjects. Notably, the PAR‐1 levels were significantly elevated in DHF and DSS groups than in the DF group and positively correlated with changes in HCT levels, inflammatory biomarkers, and liver enzymes. Our findings conclude that PAR‐1 levels persistently increased with the severity of the dengue infection and are strongly associated with various clinical manifestations. Thus, PAR‐1 levels can be used as a diagnostic marker for assessing dengue severity.
Nonconforming finite element formulation for the simulation of impedance cardiography
Authors: Kaltebacher Manfred , Badeli Vahid , Reinbacher‐Köstinger Alice 
Published: September 2022

AbstractWe present a nonconforming Finite Element (FE) formulation for the electro‐quasistatic case. The formulation allows a grid generation for each sub‐domain individually. At the nonconforming interfaces, we apply a Nitsche‐type mortaring, which can also be interpreted as a DG‐IP (Discontinuous Galerkin‐Internal Penalty) formulation. Thereby, the continuity of the electric potential and the electric flux in the discrete setting is guaranteed. The system matrix remains symmetric, and the necessary penalty factor can be chosen in a wide range without deteriorating the numerical solution. The application to impedance cardiography demonstrates the practical applicability, especially its advantage toward simplification of the grid generation.
Local and systemic metabolic adjustments to drought in maize: Hydraulic redistribution in a split‐root system
Authors: Werner Lena Maria , Hartwig Roman Paul , Engel Isabelle , Franzisky Bastian Leander , Wienkoop Stefanie , Brenner Martin , Preiner Julian , Repper Dagmar , Hartung Jens , Zörb Christian , Wimmer Monika Andrea 
Published: September 2022

AbstractBackgroundIt is yet unknown how maize plants respond to a partial root drying under conditions of a limited total water supply, and which adaptation mechanisms are triggered under these conditions.AimsThe aims of this study were to assess whether partial root drying results in distinguishable local and systemic physiological and metabolic drought responses, and whether compensatory water uptake and/or alteration of root architecture occurs under these conditions.MethodsMaize plants were grown in a split‐root system. When plants were 20 days old, the treatments ‘well‐watered’, ‘local drought’ and ‘full drought’ were established for a period of 10 days. Shoot length and gas exchange were measured non‐destructively, root exudates were collected using a filter system and biomass, relative water content, osmolality and proline content were determined destructively at final harvest.ResultsLocal drought triggered stress responses such as reduced biomass, shoot length, relative water content and increased osmolality. Maintained root growth was systemically achieved by hydraulic redistribution rather than by altering root architecture. Local and systemic osmolyte adjustments contributed to this hydraulic redistribution.ConclusionsBoth local and systemic metabolic responses helped the plants to induce hydraulic redistribution, enhance water availability and in consequence plant water relations. This resulted in a surprisingly well‐maintained root growth even in the drought stressed root compartment.
Survival and failure modes of the Compress® spindle and expandable distal femur endoprosthesis among pediatric patients: A multi‐institutional study
Authors: Tanaka Kara S. , Andaya Veronica R. , Thorpe Steven W. , Gundle Kenneth R. , Hayden James B. , Duong Yee‐Cheen , Avedian Raffi S. , Mohler David G. , Morse Lee J. , Zimel Melissa N. , O'Donnell Richard J. , Fang Andrew , Randall Robert Lor , Tran Tina H. , New Christin , Wustrack Rosanna L. ,   other members of Study Group FORCE
Published: September 2022

AbstractBackgroundExpandable endoprostheses can be used to equalize limb length for pediatric patients requiring reconstruction following large bony oncologic resections. Outcomes of the Compress® Compliant Pre‐Stress (CPS) spindle paired with an Orthopedic Salvage System expandable distal femur endoprosthesis have not been reported.MethodsWe conducted a multi‐institutional retrospective study of pediatric patients with distal femoral bone sarcomas reconstructed with the above endoprostheses. Statistical analysis utilized Kaplan–Meier survival technique and competing risk analysis.ResultsThirty‐six patients were included from five institutions. Spindle survivorship was 86.3% (95% confidence interval [CI], 67.7–93.5) at 10 years. Two patients had a failure of osseointegration (5.7%), both within 12 months. Twenty‐two (59%) patients had 70 lengthening procedures, with mean expansions of 3.2 cm (range: 1–9) over 3.4 surgeries. The expandable mechanism failed in eight patients with a cumulative incidence of 16.1% (95% CI, 5.6–31.5) at 5 years. Twenty‐nine patients sustained International Society of Limb Salvage failures requiring 63 unplanned surgeries. Periprosthetic joint infection occurred in six patients (16.7%). Limb preservation rate was 91% at 10 years.ConclusionsThere is a high rate of osseointegration of the Compress® spindle among pediatric patients when coupled with an expandable implant. However, there is a high rate of expansion mechanism failure and prosthetic joint infections requiring revision surgery.Level of evidenceLevel IV, therapeutic study.
Evaluation and publication delay in Ibero‐American scientific journals
Authors: Zabala Jon , González‐Albo Borja , García‐García Ana , Garrido‐Domínguez Aurora , Vidal‐Liy José Ignacio , Álvarez‐Díez Luis R. , Hernando‐Tundidor Soledad , Mostazo‐Fernández Yara , Abejón Teresa 
Published: September 2022

AbstractThis article analyses the review, acceptance and publication dates of a sample of 21,890 articles from 326 Ibero‐American scientific journals from all subject areas and countries included in the Latindex Catalogue 2.0 and published between 2018 and 2020 (freely available as an open access dataset). The aim is to discover evaluation and publication times. The evaluation process takes a median of 110 days, the publication process, a median of 82 days, and the whole process, a median of 224 days. Statistical differences are found according to periodicity, subject areas, countries, existence of a printed version and article type (Call for Papers or General articles). From the data we find that the delay in publication is longer than publishers themselves report to the DOAJ. STEM areas present the most similarity in publication patterns, having a higher number of evaluation days (Ed) than publication days (Pd); Arts and Humanities present the opposite pattern, with a higher Pd than Ed. In the case of Social Sciences, the times are similar. General articles and Call for Papers articles differ in terms of Ed, but not Pd, indicating that Call for Papers revisions are faster.
Enzymatic Sialylation of Synthetic Multivalent Scaffolds: From 3′‐Sialyllactose Glycomacromolecules to Novel Neoglycosides
Authors: Konietzny Patrick B. , Peters Hannelore , Hofer Marc L. , Gerling‐Driessen Ulla I. M. , de Vries Robert P. , Peters Thomas , Hartmann Laura 
Published: September 2022

AbstractSialoglycans play a key role in many biological recognition processes and sialylated conjugates of various types have successfully been applied, e.g., as antivirals or in antitumor therapy. A key feature for high affinity binding of such conjugates is the multivalent presentation of sialoglycans which often possess synthetic challenges. Here, the combination is described of solid phase polymer synthesis and enzymatic sialylation yielding 3′‐sialyllactose‐presenting precision glycomacromolecules. CMP‐Neu5Ac synthetase from Neisseria meningitidis (NmCSS) and sialyltransferase from Pasteurella multocida (PmST1) are combined in a one‐pot reaction giving access to sequence‐defined sialylated macromolecules. Surprisingly, when employing Tris(hydroxymethyl)aminomethane (Tris) as a buffer, formation of significant amounts of α‐linked Tris‐sialoside is observed as a side reaction. Further exploring and exploiting this unusual sialylation reaction, different neoglycosidic structures are synthesized showing that PmST1 can be used to derive both, sialylation on natural carbohydrates as well as on synthetic hydroxylated scaffolds.
YAP/Smad3 promotes pathological extracellular matrix microenviroment‐induced bladder smooth muscle proliferation in bladder fibrosis progression
Authors: Di Xing‐Peng , Jin Xi , Ai Jian‐Zhong , Xiang Li‐Yuan , Gao Xiao‐Shuai , Xiao Kai‐Wen , Li Hong , Luo De‐Yi , Wang Kun‐Jie 
Published: September 2022

AbstractFibrosis is a chronic inflammation process with excess extracellular matrix (ECM) deposition that cannot be reversed. Patients suffer from bladder dysfunction caused by bladder fibrosis. Moreover, the interactive mechanisms between ECM and bladder fibrosis are still obscure. Hence, we assessed the pivotal effect of Yes‐associated protein (YAP) on the proliferation of bladder smooth muscle in fibrosis process. We identified that stiff ECM increased the expression and translocation of YAP in the nucleus of human bladder smooth muscle cell (hBdSMC). Sequencings and proteomics revealed that YAP bound to Smad3 and promoted the proliferation of hBdSMC via MAPK/ERK signaling pathway in stiff ECM. Moreover, CUT and TAG sequencing and dual‐luciferase assays demonstrated that Smad3 inhibited the transcription of JUN. The YAP inhibitor CA3 was used in a partial bladder outlet obstruction (pBOO) rat model. The results showed that CA3 attenuated bladder smooth muscle proliferation. Collectively, YAP binding with Smad3 in the nucleus inhibited the transcription of JUN, and promoted the proliferation of bladder smooth muscle through the MAPK/ERK signaling pathway. The current study identified a novel mechanism of mechanical force induced bladder fibrosis that provided insights in YAP‐associated organ fibrosis.
A physical‐based model for on‐chip double‐layer spiral inductors with a ground shield
Authors: Yang Yintang , Lan Haokun , Zhang Jianqiang , Liu Maliang 
Published: September 2022

AbstractA physical‐based analytical model for double‐layer inductors to reduce the on‐chip area occupied is presented. A simple DC inductance model is developed based on self‐inductance and mutual inductance of metal segments. A new method has been adopted to accurately estimate the nonuniform distribution of currents due to skin and proximity effects, and a ladder structure is used to characterize them. Dielectric and substrate electric effects are analyzed, and a ground shield is used to reduce losses. The effective inductance reduction due to the eddy current in the silicon substrate is modeled by a negative mutual inductance between the metal spiral lines and the substrate. All the model parameters can be calculated from the structure sizes and process parameters. On‐chip inductors with different parameters were fabricated for the verifications. The EM simulated results and measured results are in good agreement with the proposed model. Thus, it is suitable for different technologies. This model can facilitate the design and optimization of on‐chip inductors for RF IC applications.
Analysis of 3‐nitropropionic acid in Fabaceae plants by HPLC‐MS/MS
Authors: Takács Orsolya , Nagyné Nedves Andrea , Boldizsár Imre , Höhn Mária , Béni Szabolcs , Gampe Nóra 
Published: September 2022

AbstractIntroduction3‐Nitropropionic acid (3‐NPA) is a toxic compound that can accumulate in esterified form in the Fabaceae family. In the Lotae tribe, many species have been identified as 3‐NPA producers (e.g., Securigera varia), while some of the genetically close Lotae plants were formerly reported as 3‐NPA‐free (e.g., Lotus corniculatus and Anthyllis vulneraria). These plants are used as forage and have a tradition in ethnomedicine, also, the extracts of A. vulneraria are used in cosmetics.ObjectivesOur aim was to investigate the 3‐NPA content of these selected Fabaceae species and to develop a validated quantitative method to evaluate 3‐NPA concentrations in extracts of different herbal parts and cosmetic products.Materials and MethodsA UHPLC‐ESI‐Orbitrap‐MS/MS method was applied for detection and identification of 3‐NPA derivatives in the form of glucose esters. For the quantitative analysis, an optimized sample processing method was developed. The free 3‐NPA content was determined using HPLC‐ESI‐MS/MS.Results3‐NPA esters could be detected in all three species, but their quantity showed a high variation. S. varia contained 0.5–1.0 g/100 g of 3‐NPA, while in L. corniculatus samples only trace quantities were detectable, below the LOQ (25 ng/ml). Most of the A. vulneraria samples showed similarly low concentrations, but one sample had 3‐NPA levels comparable to S. varia. 3‐NPA could not be detected in the tested cosmetics containing A. vulneraria extracts.ConclusionsUsing highly sensitive analytical methods, new 3‐NPA‐containing species were identified. The developed validated quantitative method is suitable for the determination of 3‐NPA concentrations in herbal samples.
A G4 approach to computing the Hammett substituent constants σp, σm, σ−, σ+, and σ+m
Authors: Yett Ariana , Rablen Paul R. 
Published: September 2022

AbstractBy performing appropriate empirical scaling of G4 energy differences, it is possible to calculate Hammett substituent constants σp, σm, σ−, σ+, and σ+m with a typical accuracy (mean absolute error) of ±0.1. The procedure is straightforward and easily carried out by non‐experts using the Gaussian software package. Values are provided for 41 substituents of widely varying electronic character, including some reactive species for which experimental values are unavailable. Additionally, comparison of calculated and experimental values suggests that some previously published numbers might be significantly in error, particularly for some ionic, acidic, and/or basic substituents. Values are also provided for a newly defined substituent constant, σ−m.
Deciphering the role of (anti)aromaticity in cofacial excimers of linear acenes
Authors: Krishnan Akhilesh , Diaz‐Andres Aitor , Sudhakaran Keerthy P. , John Athira T. , Hariharan Mahesh , Casanova David 
Published: September 2022

AbstractExcited state aromaticity is a stimulating area of research, widely used as a probe to describe and rationalize many photochemical phenomena. Herein, we review some of the recent findings of unprecedented aromatic stabilization in spin singlet excimer and through‐space aromatic character in triplet excimers of a series of linear [n]acenes, as paramount examples of polycyclic aromatic hydrocarbons (PAHs). This review also provides insights on the aromatic stabilization profile of singlet benzene excimer formation, which can be related to antiaromaticity alleviation of the molecular (localized) S1 through exciton delocalization. The theoretical investigation of excimer stabilization using magnetic, electronic, and geometric aromatic indices manifested the presence of through‐space ring current in triplet cofacial excimers. The antiaromaticity of the sandwich (D6h) spin singlet and triplet benzene excimers was also investigated by decomposing the excimer wave function as a linear combination of local exciton (LE) and charge transfer (CT) diabats and by identifying the contribution of these terms to the nucleus independent chemical shift (NICS) of the two 6‐membered rings. These results provide a detailed description of the unique (anti)aromatic properties in PAH excimers, establishing strong connection between this important chemical concept and the electronic structure intricacies of excimers.