bluuebunny/crossref_metadata_2025 huggingface dataset:
Older people with severe loneliness have an atrophied thalamus, hippocampus, and entorhinal cortex
Authors: Imai Ayu , Matsuoka Teruyuki , Narumoto Jin
Published: November 2022

Objectives

Loneliness has been shown to increase the risk of dementia. However, it is unclear why greater loneliness is associated with greater susceptibility to dementia. Herein, we aimed to examine the morphological characteristics of the brain associated with loneliness in older people concerned about cognitive dysfunction.

Methods

In this retrospective study, 110 participants (80 with amnestic mild cognitive impairment, and 30 cognitively healthy individuals) were included. Participants were assessed using the revised University of California at Los Angeles (UCLA) loneliness scale and had undergone magnetic resonance imaging. Spearman correlation analysis and Mann–Whitney U tests were used to examine the clinical factors associated with loneliness. Multiple regression was performed to examine the relationship between the revised UCLA loneliness scale score and regional gray matter (GM) volume on voxel‐based morphometry.

Results

The revised UCLA loneliness scale scores were not significantly correlated with age, sex, or mini‐mental state examination (MMSE) scores. Multiple regression using age, sex, MMSE score, and total brain volume as covariates showed negative correlations of the revised UCLA loneliness scale scores with the grey matter volume in regions centered on the bilateral thalamus, left hippocampus and left parahippocampal gyrus, and left entorhinal area.

Conclusions

Subjective loneliness was associated with decreased GM volume in the bilateral thalamus, left hippocampus, and left entorhinal cortex of the brain in the older people, thereby providing a morphological basis for the increased risk of dementia associated with greater loneliness.
Impact of soil texture and salt type on salt precipitation and evaporation under different hydraulic conditions
Authors: Li Xinhu , Guo Min , Wang Hongchao
Published: November 2022

Salt precipitation and evaporation in porous media is an important research topic. However, several aspects remain controversial; notably, whether efflorescence inhibits evaporation in wet soil, the influence of soil texture on salt crust formation and the effect of sulphate precipitation on evaporation under changing hydraulic conditions. Therefore, this study investigates the influence of salt type (NaCl and Na2SO4) and soil texture (sandy soil, sandy loam and silt loam) on salt precipitation and evaporation under different hydraulic conditions (with and without fixed groundwater). Our results demonstrated that a NaCl salt crust strongly inhibited evaporation, even from wet soil (with groundwater), owing to its denser salt structure, which inhibited fluid flow. Moreover, the salt crust pattern differed based on soil texture. Relatively thin, flat and uniform salt crusts were developed in finer soils (silt loam), with greater evaporation resistance, whereas thick and rough salt crusts were developed in coarser soil (sandy soil), with less evaporation resistance. Na2SO4 was precipitated as subflorescence in drying soil, whereas wet soils exhibited a mixed salt precipitation pattern including both efflorescence and subflorescence. Notably, evaporation was primarily inhibited by efflorescence, rather than subflorescence. Our research provides novel insights into the dynamics of salt precipitation and evaporation in natural soils.
Suppression of SAMSN1 contributes to neuroprotection in neonatal rats suffering from hypoxic–ischemic encephalopathy injury
Authors: Wang Yi‐Bo , Gan Zong‐Jin , Zhang Jun‐Yan , Wanchana Somjit , Guo Xi‐Liang
Published: November 2022

This article aims to detect the effect of SAM domain, SH3 domain, and nuclear localization signal 1 (SAMSN1) in neonatal rats with neurological dysfunction induced by hypoxia and ischemia (HI). The HI model was created using 7‐day postnatal rats. Zea‐longa score was utilized to validate the neurological injury after HI. Then, the differentially expressed genes (DEGs) were detected by gene sequencing and bioinformatics analysis methods. The oxygen and glucose deprivation (OGD) models were established in the SY5Y cells and fetal human cortical neurons. In addition, SAMSN1‐small interfering RNA, methyl thiazolyl tetrazolium assay, and cell growth curve were employed to evaluate the cell viability variation. Obviously, Zea‐longa scores increased in rats with HI insult. Subsequently, SAMSN1 was screened out, and it was found that SAMSN1 was strikingly upregulated in SY5Y cells and fetal neurons post‐OGD. Interestingly, we found that SAMSN1 silencing could markedly enhance cell viability and cell growth after OGD. These data suggested that downregulation of SAMSN1 may exert a neuroprotective effect on damaged neurons after HI by improving cell viability and cell survival, which provides a potential theoretical basis for clinical trials in the future to treat neonatal hypoxic–ischemic encephalopathy.
Could platelet indices have diagnostic properties in children with COVID‐19?
Authors: Dobrijević Dejan , Antić Jelena , Rakić Goran , Andrijević Ljiljana , Katanić Jasmina , Pastor Kristian
Published: November 2022

Introduction

Viral infections are often accompanied by reactive thrombocytosis, that is, increased activity of platelets, which is especially common in infants and children.

Objective

This study aimed to test the diagnostic properties of platelet indices, plateletcrit (PCT), mean platelet volume (MPV) and platelet distribution width (PDW), in children with beta corona virus 2 (SARS‐CoV‐2) infection.

Methods

The study included 232 patients below the age of 18 admitted to the coronavirus disease (COVID‐19) isolation wards at the Institute for Child and Youth Health Care of Vojvodina. PCT, MPV and PDW values on the day of admission were recorded. In total, 245 controls were selected from those treated for SARS‐CoV‐2 negative respiratory infections. Descriptive and inferential statistical analyses were performed.

Results

MPV and PDW were found important as independent predictors for COVID‐19 in children. Furthermore, the joint effect of MPV and PDW for predicting COVID‐19 was confirmed. The parameters showed better sensitivity than specificity.

Conclusion

Our study showed that PCT is not clinically significant, while MPV and PDW have diagnostic value in predicting COVID‐19 in children. In perspective, these parameters could be implemented in the various learning algorithms in order to achieve earlier diagnosis and treatment.
A candidate reference method and multiple commutable control materials for serum 25‐hydroxyvitamin D measurement
Authors: Zhang Li , Long Qichen , Zhang Jiangtao , Zeng Qingzhang , Zhao Haijian , Chen Wenxiang , Zhang Tianjiao , Zhang Chuanbao
Published: November 2022

Objectives

The aim of the current study was to establish a reliable candidate reference method for serum 25‐hydroxyvitamin D [25(OH)D] measurement and to assess the commutability of multiple control materials among liquid chromatography–tandem mass spectrometry (LC–MS/MS) methods.

Methods

Serum 25‐hydroxyvitamin D2 [25(OH)D2] and 25‐hydroxyvitamin D3 [25(OH)D3] together with spiked internal standards were extracted with a one‐step approach and then analyzed by LC–MS/MS. The commutability assessment for 25(OH)D was conducted according to the Clinical and Laboratory Standards Institute (CLSI) EP14‐A3 protocol. 25(OH)D concentrations in 5 levels of unprocessed serum pools, 7 levels of serum pools spiked with 25(OH)D3 or 25(OH)D2, 3 levels of commercial control materials, 2 levels of spiked bovine serum, and 4 levels of external quality assessment (EQA) materials were measured along with 30 single‐donor samples using the candidate reference method and two routine LC–MS/MS methods.

Results

The candidate reference method could separate 25(OH)D2 and 25(OH)D3 from 14 potential interfering compounds completely within a 9‐min analysis time. Good method precision was obtained, and measurement results on certified reference material NIST SRM 972a were within the uncertainty of the certified values. All candidate materials were assessed commutable for LC–MS/MS methods.

Conclusions

The candidate reference method for serum 25(OH)D measurement is precise, accurate, and robust against interferences and can provide an accuracy base for routine methods. The multiple alternative control materials with commutability among LC–MS/MS methods will facilitate the further standardization for serum 25(OH)D measurement.
LINC00511 aggravates the malignancy of lung adenocarcinoma through sponging microRNA miR‐4739 to regulate pyrroline‐5‐carboxylate reductase 1 expression
Authors: Ye Lu , Wang Linxiu , Zeng Yu
Published: November 2022

Background

Long non‐coding RNA LINC00511 is known to exacerbate lung adenocarcinoma (LUAD) progression. However, the specific mechanism by which LINC00511 affects LUAD progression has not been investigated as yet, and we aimed to elucidate the same in the present study.

Methods

The expression levels of LINC00511, microRNA miR‐4739, and pyrroline‐5‐carboxylate reductase 1 (PYCR1) were determined by quantitative reverse transcription PCR and Western blotting. The Cell Counting Kit‐8 and bromodeoxyuridine assays were used to evaluate cell proliferation. Apoptosis was evaluated by flow cytometry, and Bax and Bcl‐2 protein levels were determined by western blotting. Cell migration was assessed using transwell assay. The interaction between LINC00511, miR‐4739, and PYCR1 was analyzed using luciferase, RNA immunoprecipitation, and RNA pull‐down assays.

Results

The expression levels of LINC00511 and PYCR1 in LUAD were downregulated, whereas that of miR‐4739 was upregulated. Functional studies showed that knockdown of LINC00511 or PYCR1 suppressed the proliferation and migration of LUAD cells, and promoted apoptosis. On the contrary, knockdown of miR‐4739 had tumor‐promoting effects. Mechanistically, LINC00511 prevented the miR‐4739 led inhibition of PYCR1, resulting in PYCR1 overexpression.

Conclusion

This study demonstrates for the first time that LINC00511 aggravates the malignancy of LUAD by sponging miR‐4739 to upregulate PYCR1 expression.
Accompanying a semi‐nested PCR assay to support histopathology findings of fungal keratitis in formalin‐fixed paraffin‐embedded corneal samples
Authors: Ashraf Mohammad Javad , Shamsizadeh Foroogh , Morovati Hamid , Hejazinia Safoora , Kord Mohammad , Ansari Saham , Pakshir Keyvan , Shekarkhar Golsa , Zomorodian Kamiar
Published: November 2022

Background

Fungal species are responsible for 40%–50% of all microbial keratitis cases. Due to the low amount of extracted DNA in ocular Formalin‐fixed Paraffin‐embedded (FFPE) samples, selecting a reliable molecular method is a substantial issue in this field.

Methods

Sixty‐six samples were collected via the penetrating keratoplasty (PK) technique. Histopathology assays were performed using hematoxylin–eosin (H&E) and periodic acid Schiff (PAS) staining methods. The ITS1/ITS4 and ITS1/ITS2 primer pairs were used in a semi‐nested polymerase chain reaction (PCR) to target the universal internal transcribed spacer (ITS) region. Some PCR results were validated through sequencing.

Results

Fungal DNA was detected in 44 of 66 samples (66.7%), and histopathology was positive for 41 of 66 samples (62.1%). Of 41 histopathologically proven fungal‐positive cases, 39 were PCR‐positive (95%). Moreover, of 44 PCR‐positive samples, 39 (88.6%) were histopathology‐positive, and 5 (11.3%) were histopathology‐negative. Totally in 39 cases (59%), both histopathology and PCR yielded positive results. The Kappa agreement rate between the two diagnostic methods, including histopathology and PCR, was 0.77. Sensitivity, specificity, positive predictive value, and false predictive value were reported as 88.64%, 90.9%, 95.12%, and 80%, respectively.

Conclusion

As we reached the acceptable Kappa agreement rate, we concluded that applying the semi‐nested PCR assay is a promising method for supporting the evidence by histopathology. Finally, we suggest targeting more specific gene regions using primer pairs that amplify smaller amplicon sizes and surveying novel molecular methods such as NGS to achieve higher sensitivity and Kappa agreement rates.
Diisobutylaluminium hydride mediated efficient synthesis of Morita–Baylis–Hilman adducts through α‐functionalization of alkyl propiolates
Authors: Gogula Sailam Sri , Konakalla Ramakrishna , Kamireddy Kamalaker Reddy , Puchakayala Muralidar Reddy , Lincoln Ch. Abraham , Basireddy Venkata Subba Reddy
Published: November 2022

Generally, oxindole derivatives are biologically important molecules and valuable building blocks in organic synthesis. Herein, we report a diisobutylaluminium hydride mediated efficient one‐pot synthesis of oxindole derivatives using N‐substituted isatins with methyl or ethyl propiolates at lower temperature (−78°C) through Morita‐Baylis‐Hillman (MBH) reaction. Within a short reaction time, a wide range of N‐alkyl or N‐aryl 3‐hydroxy oxindole derivatives (MBH adducts) were easily accessed in excellent yields under mild reaction conditions.
Cellular and computational models reveal environmental and metabolic interactions in MMUT‐type methylmalonic aciduria
Authors: Ramon Charlotte , Traversi Florian , Bürer Céline , Froese D. Sean , Stelling Jörg
Published: November 2022

Methylmalonyl‐coenzyme A (CoA) mutase (MMUT)‐type methylmalonic aciduria is a rare inherited metabolic disease caused by the loss of function of the MMUT enzyme. Patients develop symptoms resembling those of primary mitochondrial disorders, but the underlying causes of mitochondrial dysfunction remain unclear. Here, we examined environmental and genetic interactions in MMUT deficiency using a combination of computational modeling and cellular models to decipher pathways interacting with MMUT. Immortalized fibroblast (hTERT BJ5ta) MMUT‐KO (MUTKO) clones displayed a mild mitochondrial impairment in standard glucose‐based medium, but they did not to show increased reliance on respiratory metabolism nor reduced growth or viability. Consistently, our modeling predicted MUTKO specific growth phenotypes only for lower extracellular glutamine concentrations. Indeed, two of three MMUT‐deficient BJ5ta cell lines showed a reduced viability in glutamine‐free medium. Further, growth on 183 different carbon and nitrogen substrates identified increased NADH (nicotinamide adenine dinucleotide) metabolism of BJ5ta and HEK293 MUTKO cells compared with controls on purine‐ and glutamine‐based substrates. With this knowledge, our modeling predicted 13 reactions interacting with MMUT that potentiate an effect on growth, primarily those of secondary oxidation of propionyl‐CoA, oxidative phosphorylation and oxygen diffusion. Of these, we validated 3‐hydroxyisobutytyl‐CoA hydrolase (HIBCH) in the secondary propionyl‐CoA oxidation pathway. Altogether, these results suggest compensation for the loss of MMUT function by increasing anaplerosis through glutamine or by diverting flux away from MMUT through the secondary propionyl‐CoA oxidation pathway, which may have therapeutic relevance.
GLIM‐defined malnutrition and overall survival in cancer patients: A meta‐analysis
Authors: Yin Liangyu , Chong Feifei , Huo Zhenyu , Li Na , Liu Jie , Xu Hongxia
Published: November 2022

Background

Malnutrition defined by the Global Leadership Initiative on Malnutrition (GLIM) has been associated with cancer mortality, but the effect is limited and inconsistent. We performed this meta‐analysis aiming to assess this relationship in patients with cancer.

Methods

We systematically searched Embase, PubMed, Web of Science, Cochrane, CINAHL, CNKI, Wanfang, and VIP databases from January 1, 2019, to July 1, 2022. Studies evaluating the prognostic effect of GLIM‐defined malnutrition on cancer survival were included. A fixed‐effect model was fitted to estimate the combined hazard ratio (HR) with a 95% CI. Heterogeneity of studies was analyzed using the I2 statistic. Quality assessment were performed using the Newcastle‐Ottawa Scale (NOS) and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool.

Results

The search strategy identified 4378 articles in all databases combined. Nine studies (8829 patients) meeting the inclusion criteria were included for quantitative analysis. Meta‐analysis revealed significant associations between GLIM‐defined pooled malnutrition (HR = 1.75; 95% CI, 1.43–2.15), moderate malnutrition (HR = 1.44; 95% CI, 1.29–1.62), and severe malnutrition (HR = 1.79; 95% CI, 1.58–2.02) with all‐cause mortality. Sensitivity analysis supported the robustness of these associations. The between‐study heterogeneity was low (all I2 < 50%), and study quality assessed with NOS was high (all scores > 6). The evidence quality according to the GRADE tool was very low.

Conclusions

Our meta‐analysis suggests a significant negative association of malnutrition, as defined by the GLIM, with overall survival in patients with cancer. However, definitive conclusions cannot be made, owing to the low quality of the source data.
Bacterial biomarkers are linked more closely to wheat yield formation than overall bacteria in fertilized soil
Authors: Ma Li , Niu Wenquan , Li Guochun , Zhang Erxin , Sun Jun , Zhang Qian , Siddique Kadambot H. M.
Published: November 2022

Soil bacteria play pivotal roles in agroecosystem functioning. However, the immense diversity of soil bacterial communities masks the effects of some species, such as bacterial biomarkers, on soil nutrient cycling and crop growth. We analyzed biological and chemical soil parameters of five fertilization treatments (CK, LN, CN, HN, LNM: 0, 150, 200, 250 kg N hm−2, 150 kg N hm−2 + 15,000 kg hm−2 sheep manure). The random forest models were used to select bacterial biomarkers and assess the contributions of bacterial biomarkers and overall bacteria to wheat yield. Moreover, we used a partial least squares path modelling to explore the relationship between fertilization, bacterial biomarkers, carbon (C) and nitrogen (N) cycling functions, soil nutrients, and wheat yield. The results showed that bacterial biomarkers are better predictors of wheat yield than overall bacteria, explaining 52.54% and 16.00% of the variation in yield, respectively. Bacterial biomarkers affected wheat production by increasing soil organic carbon, and available nitrogen content. The LNM treatment significantly improved the relative abundance of beneficial biomarkers, such as Sphingomonadales, Xanthomonadaceae, Lysobacter, and Streptomyces, compared to the LN treatment. In addition, the LNM treatment promoted chitinlysis, cellulolysis, xylanolysis, aromatic hydrocarbon degradation, and aerobic ammonia oxidation, relative to the other inorganic N treatments (LN, CN, and HN). Our results emphasize the role of bacterial biomarkers in wheat yield formation, providing new insights into maintaining agricultural productivity by taking advantage of soil bacterial biomarkers.
Targeting intra‐tumoral heterogeneity of human brain tumors with in vivo imaging: A roadmap for imaging genomics from multiparametric MR signals
Authors: Parker Jason G. , Servati Mahsa , Diller Emily E. , Cao Sha , Ho Chang , Lober Robert , Cohen‐Gadol Aaron
Published: November 2022

Resistance of high grade tumors to treatment involves cancer stem cell features, deregulated cell division, acceleration of genomic errors, and emergence of cellular variants that rely upon diverse signaling pathways. This heterogeneous tumor landscape limits the utility of the focal sampling provided by invasive biopsy when designing strategies for targeted therapies. In this roadmap review paper, we propose and develop methods for enabling mapping of cellular and molecular features in vivo to inform and optimize cancer treatment strategies in the brain. This approach leverages (1) the spatial and temporal advantages of in vivo imaging compared with surgical biopsy, (2) the rapid expansion of meaningful anatomical and functional magnetic resonance signals, (3) widespread access to cellular and molecular information enabled by next‐generation sequencing, and (4) the enhanced accuracy and computational efficiency of deep learning techniques. As multiple cellular variants may be present within volumes below the resolution of imaging, we describe a mapping process to decode micro‐ and even nano‐scale properties from the macro‐scale data by simultaneously utilizing complimentary multiparametric image signals acquired in routine clinical practice. We outline design protocols for future research efforts that marry revolutionary bioinformation technologies, growing access to increased computational capability, and powerful statistical classification techniques to guide rational treatment selection.
Implicit dynamic buckling analysis of thin‐shell isogeometric structures considering geometric imperfections
Authors: Guo Yujie , Pan Maodong , Wei Xiaohui , Luo Fei , Sun Fangbin , Ruess Martin
Published: November 2022

In continuation of our previous work on nonlinear stability analysis of trimmed isogeometric thin shells, this contribution is an extension to dynamic buckling analyses for predicting reliably complex snap‐through and mode‐jumping behavior. Specifically, a modified generalized‐ time integration scheme is used and combined with a nonlinear isogeometric Kirchhoff–Love shell element to provide second‐order accuracy while introducing controllable high‐frequency dissipation. In addition, a weak enforcement of essential boundary conditions based on a penalty approach is considered with a particular focus on the inhomogeneous case of imposed prescribed displacements. Moreover, we propose a least‐squares B‐spline surface fitting approach and corresponding error measures to model both eigenmode based and measured geometric imperfections. The imperfect geometries thus obtained can be naturally integrated into the framework of isogeometric nonlinear dynamic shell analysis. Based on this idea, the different modeling methods and the influence of the appropriately considered geometric imperfections on the dynamic buckling behavior can be investigated systematically. Both perfect and geometrically imperfect shell models are considered to assess the performance of the proposed method. We compare our method with established developments in this field and demonstrate superior achievements with regard to solution quality and robustness.
Resolving vibro‐acoustics in poroelastic media via a multiscale virtual element method
Authors: Sreekumar Abhilash , Triantafyllou Savvas P. , Chevillotte Fabien , Bécot François‐Xavier
Published: November 2022

We introduce a novel heterogeneous multi‐scale method for the frequency response analysis of waves propagating in porous domains with a complex micro‐structure. In this, the domain is decomposed onto polygonal coarse elements each clustering its local micro‐structure. The micro‐structure is resolved using the virtual element method hence providing ample flexibility into capturing fine scale heterogeneities of arbitrary polygonal shapes. The upscaling is performed through a set of numerically evaluated multi‐scale basis functions. Rather than evaluating the basis for a broad band set of frequencies, a reduced order modeling approach is opted for. In this, the basis is evaluated for a select subset of frequencies, that is used as a basis for the evaluation of the remaining set through a proper orthogonal decomposition procedure. The solution of the coupled governing equations is then performed at the coarse‐scale at a reduced computational cost. The performance of the method in terms of accuracy and computational efficiency is evaluated through a set of numerical examples for poro‐elastic materials with heterogeneities of various shapes.
Technology‐based Comprehensive Cardiac Rehabilitation Therapy (TaCT) for women with cardiovascular disease in a middle‐income setting: A randomized controlled trial protocol
Authors: Menezes Henita Joshna , D' Souza Sonia R. B. , Padmakumar Ramachandran , Babu Abraham Samuel , Rao Rohini R. , Kamath Veena G. , Kamath Asha , Grace Sherry L.
Published: November 2022

Women are underrepresented in cardiac rehabilitation (CR) despite the benefits, and this is exacerbated in lower‐resource settings where CR is insufficiently available. In this randomized controlled trial, the effectiveness of the Technology‐based Comprehensive Cardiac Rehabilitation Therapy (TaCT) electronic cardiac rehabilitation (eCR) intervention on functional capacity, risk factors, quality of life, heart‐health behaviors, symptoms, and morbidity will be tested among women with CVD in a middle‐income country. Following a pilot study, a single‐center, single‐blinded, 2 parallel‐arm (1:1 SNOSE) superiority trial comparing an eCR intervention (TaCT) to usual care, with assessments pre‐intervention and at 3 and 6 months will be undertaken. One hundred adult women will be recruited. Permuted block (size 10) randomization will be applied. The 6‐month intervention comprises an app, website, SMS texts with generic heart‐health management advice, and bi‐weekly 1:1 telephone calls with a nurse trainee. Individualized exercise prescriptions will be developed based on an Incremental Shuttle Walk Test (primary outcome) and dietary plans based on 24 h dietary recall. A yoga/relaxation video will be provided via WhatsApp, along with tobacco cessation support and a moderated group chat. At 3 months, intervention engagement and acceptability will be assessed. Analyses will be conducted based on intent‐to‐treat. If results of this novel trial of women‐focused eCR in a middle‐income country demonstrate clinically‐significant increases in functional capacity, this could represent an important development for the field considering this would be an important outcome for women and would translate to lower mortality.
Integrated molecular characterization of esophageal basaloid squamous cell carcinoma: a subtype with distinct RNA expression pattern and immune characteristics, but no specific genetic mutations
Authors: Li Yan , Liu Linxiu , Pan Yi , Fang Fang , Xie Tongji , Cheng Na , Guo Changyuan , Xue Xuemin , Zeng Hua , Xue Liyan
Published: November 2022

Esophageal basaloid squamous cell carcinoma (bSCC) is a subtype of squamous cell carcinoma (SCC) with a different behavior and poor prognosis. Exploring bSCC's molecular characteristics and treatment strategies are of great clinical significance. We performed multi‐omics analysis of paired bSCC and common SCC (cSCC) using whole exome sequencing and a NanoString nCounter gene expression panel. Immunohistochemistry was used for verification of candidate biomarkers. Different treatment response was analyzed on both patients receiving neoadjuvant treatment and late‐stage patients. The common genetically‐clonal origin of bSCC and cSCC was confirmed. No significant differences between their genetic alterations or mutation spectra were observed. Mutation signature 15 (associated with defective DNA damage repair) was less prominent, and tumor mutational burden (TMB) was lower in bSCC. bSCC with an RNA expression pattern resembling cSCC had a better survival than other bSCCs. Moreover, bSCC showed significant upregulation of expression of genes associated with angiogenesis response, basement membranes, and epithelial–mesenchymal transition, and downregulation of KRT14 (squamous differentiation) and CCL21 (associated with immune response). Immunohistochemistry for SFRP1 was shown to be highly sensitive and specific for bSCC diagnosis (p < 0.001). In addition, bSCC receiving neoadjuvant immuno‐chemotherapy had a worse pathological response than bSCC receiving neoadjuvant chemotherapy (but without statistical significance), even in bSCC positive for PD‐L1. Our results demonstrated the molecular characteristics of esophageal bSCC as a subtype with a distinct RNA expression pattern and immune characteristics, but no specific genetic mutations. We provided a useful biomarker, SFRP1, for diagnosis. After outcome analysis for six bSCCs with neoadjuvant immunotherapy treatment and four late‐stage bSCCs with immunotherapy, we found that immunotherapy may not be an effective treatment option for most bSCCs. This may also provide a clue for the same subtypes of lung and head and neck cancer. Our study highlighted the heterogeneity among bSCC patients, and might explain the conflicting results of bSCC outcomes in existing studies. © 2022 The Pathological Society of Great Britain and Ireland.
Do reproductive history and information given through genetic counselling influence patients' decisions on mosaic embryo transfer?
Authors: Coll Lluc , Parriego Mònica , Palacios Gabriela , Garcia Sandra , Boada Montserrat , Coroleu Buenaventura , Polyzos Nikolaos P. , Vidal Francesca , Veiga Anna
Published: November 2022

Objective

To assess patients' and embryonic characteristics that may have an influence on the decision to transfer a mosaic embryo.

Method

Single centre retrospective cohort study including 1247 PGT‐A cycles. Demographic and clinical factors associated with a decision to transfer a mosaic embryo were studied. Female age, number of previous cycles, previous availability of euploid embryos, history of miscarriages and parity as well as percentage of mosaicism, type of anomaly and chromosome risk were studied in relation to decision‐making. Outcomes after mosaic embryo transfer were assessed.

Results

To date, in 7.9% of cycles (99/1247), patients have had to make a decision on the fate of their mosaic embryos. In 23.2% of cycles (23/99), patients decided to transfer. In most cases (79.8%; 79/99), patients underwent genetic counselling before the decision. None of the variables analysed were associated with the patients' decision, although parity and the high‐degree mosaicism (>50%) seemed to be negatively associated with the decision to transfer (18.2% vs. 29.8%, p = 0.294; 10% vs. 32.2%, p = 0.052).

Conclusions

Neither reproductive history nor information on mosaic embryo characteristics through counselling seems to be determinative for patients when deciding to transfer a mosaic embryo. Promising and increasing data on clinical outcomes after mosaic embryo transfer will be of utmost importance to soften risk perception regarding mosaic embryos and give a better, simplified and more evidence‐based counselling.
Vancomycin plus ceftaroline for persistent methicillin‐resistant Staphylococcus aureus bacteremia
Authors: Kufel Wesley D. , Parsels Katie A. , Blaine Bruce E. , Steele Jeffrey M. , Mahapatra Rahul , Paolino Kristopher M. , Thomas Stephen J.
Published: November 2022

Study Objective

The preferred antibiotic salvage regimen for persistent methicillin‐resistant Staphylococcus aureus bacteremia (MRSAB) is unclear. We sought to evaluate the effectiveness and safety of vancomycin plus ceftaroline for persistent MRSAB. The primary outcome was time to MRSAB clearance post‐ceftaroline initiation. Secondary outcomes included microbiological cure, hospital length of stay, 90‐day readmission for MRSAB, 90‐day all‐cause mortality, MRSAB‐related mortality, and incidence of antibiotic‐associated adverse effects.

Design

Single‐center, retrospective cohort study between January 1, 2016, and December 31, 2021.

Setting

State University of New York Upstate University Hospital, a 748‐bed tertiary care, academic medical center in Syracuse, NY.

Patients

Adult patients were included if they had blood cultures positive for MRSA ≥72 h, received vancomycin monotherapy initially, and received vancomycin plus ceftaroline for ≥24 h. Patients were excluded if they received other anti‐MRSA antibiotics, were pregnant, or were incarcerated. Of the 178 patients identified, 30 unique patients were evaluated.

Measurements and Main Results

Patients were medically complex with a median Pitt bacteremia score of 3, 63.3% (19/30) were admitted to the intensive care unit, and 66.7% (20/30) had infective endocarditis. Vancomycin‐associated acute kidney injury was observed in 10% (3/30) of patients, which resulted in dose adjustments. No patients experienced ceftaroline‐associated neutropenia or Clostridioides difficile infection, but 6.7% (2/30) developed a rash attributed to ceftaroline. Median time to MRSAB clearance post‐ceftaroline initiation was 2.6 days. Microbiologic cure occurred in nearly all patients 96.7% (29/30). Median hospital length of stay was 19.5 days, and 6.7% (2/30) of patients had 90‐day readmission for MRSAB. 90‐day all‐cause mortality and MRSAB‐related mortality occurred in 26.7% (8/30) and 13.3% (4/30) of patients, respectively.

Conclusions

Vancomycin plus ceftaroline may represent an effective and well‐tolerated salvage regimen option for persistent MRSAB.
Proxy ratings of psychological well‐being in patients with primary brain tumors: A systematic review
Authors: Sannes Timothy S. , Yusufov Miryam , Amonoo Hermioni L. , Broden Elizabeth G. , Burgers Darcy E. , Bain Paul , Pozo‐Kaderman Cristina , Miran Damien M. , Smith Timothy S. , Braun Ilana M. , Pirl William F.
Published: November 2022

Objective

This systematic review examined the agreement of proxy ratings of depression and anxiety in neuro‐oncology patients.

Methods

Searches were conducted across 4 databases (MEDLINE, Embase, PsycINFO, CINAHL, and Web of Science) to identify studies that compared proxy ratings (non‐health care providers) of anxiety and depression in patients with brain cancer. Methodological quality and potential risk of bias were evaluated using the Joanna Briggs Institute Critical Appraisal Checklist.

Results

Out of the 936 studies that were screened for inclusion, 6 were included for review. The findings were mixed in terms of whether patient and proxy ratings were accurate (e.g., deemed equivalent), with many of the selected studies suggesting moderate level of agreement for several of the selected studies and, when both depression and anxiety were included, depression ratings from proxy raters were more accurate than for anxiety. We identified important limitations across the selected articles, such as low sample size, clarity on defining proxy raters and the different instructions that proxy raters are given when asked to assess patients' mood symptoms.

Conclusions

Our findings suggest that proxy ratings of depression and anxiety should be interpreted with caution. While there is some agreement in proxy and patients with brain cancer ratings of depression and anxiety (greater agreement for depression), future work should recruit larger samples, while also remaining mindful of defining proxy raters and the instructions given in collecting these ratings.
Biophysical characterization of full‐length TAR DNA‐binding protein (TDP‐43) phase separation
Authors: Staderini Tommaso , Bigi Alessandra , Mongiello Daniele , Cecchi Cristina , Chiti Fabrizio
Published: November 2022

Amyotrophic lateral sclerosis and frontotemporal lobar degeneration with ubiquitin‐positive inclusions are associated with deposition of cytosolic inclusion bodies of TAR DNA‐binding protein 43 (TDP‐43) in brain and motor neurons. We induced phase separation of purified full‐length TDP‐43 devoid of large tags using a solution‐jump method, and monitored it with an array of biophysical techniques. The tetramethylrhodamine‐5‐maleimide‐ or Alexa488‐labeled protein formed rapidly (<1 min) apparently round, homogeneous and 0.5–1.0 μm wide assemblies, when imaged using confocal fluorescence, bright‐field, and stimulated emission depletion microscopy. The assemblies, however, had limited internal diffusion, as assessed with fluorescence recovery after photobleaching, and did not coalesce, but rather clustered into irregular bunches, unlike those formed by the C‐terminal domain. They were enriched with α‐helical structure, with minor contributions of β‐sheet/random structure, had a red‐shifted tryptophan fluorescence and did not bind thioflavin T. By monitoring with turbidimetry both the formation of the spherical species and their further clustering under different experimental conditions, we carried out a multiparametric analysis of the two phenomena. In particular, both processes were found to be promoted by high protein concentrations, salts, crowding agents, weakly by reducing agents, as the pH approached a value of 6.0 from either side (corresponding to the TDP‐43 isoionic point), and as the temperature approached a value of 31°C from either side. Important differences were found with respect to the TDP‐43 C‐terminal domain. Our multiparametric results also provide explanations to some of the solubility data obtained on full‐length TDP‐43 that were difficult to explain following the multiparametric analysis acquired on the C‐terminal domain.
Design, synthesis, and biological activity of novel spiro‐pyrazolo[1,5‐a]quinazolines derivatives as potential insecticides
Authors: Yao Guangkai , Wang Mengfan , Li Benjie , Peng Hongxiang , Yang Shuai , Zhao Chen , Xu Hanhong
Published: November 2022

BACKGROUND

Arylpyrazole insecticides display broad‐spectrum insecticidal activity against insect pests. However, the high toxicity toward honeybees associated with fipronil prohibits its agronomic utility. To explore reducing the toxicity of aryl pyrazole analogs to bees, a series of new spiro‐pyrazolo[1,5‐a]quinazoline derivatives were designed and synthesized.

RESULTS

Bioassay results showed that these compounds exhibited good insecticidal activity. In particular, the insecticidal activity of compound 5f against Plutella xylostella larvae (median lethal contentration, LC50 = 1.43 mg L−1) was equivalent to that of fipronil. Moreover, some compounds also showed good insecticidal activity against Solenopsis invicta. Importantly, the bee toxicity study confirmed that compound 5f had much lower acute oral toxicity, with a median lethal dose (LD50) = 1.15 μg bee−1 that was three to four orders of magnitude greater than that of fipronil (0.0012 μg bee−1). Electrophysiological studies were conducted using honeybee γ‐aminobutyric acid receptor heterologously expressed in Xenopus oocytes to explain the reduced bee toxicity of compound 5f. The inhibitory effect of compound 5f (16.29 μmol L−1) was determined to be approximately 700‐fold lower than that of fipronil (0.023 μmol L−1).

CONCLUSION

These spiro‐pyrazolo[1,5‐a]quinazoline derivatives could be potential candidates and lead structures for the discovery of novel insecticides with low bee toxicity. © 2022 Society of Chemical Industry.
Developing a systems‐based approach to research use in education
Authors: Maxwell Bronwen , Sharples Jonathan , Coldwell Mike
Published: November 2022

Models of research use in education tend to focus on specific elements of education systems or underplay the complexity of system change. Within other public policy areas, notably health, more work has been undertaken to integrate systems thinking when considering knowledge mobilisation and research use. In this paper, we survey public policy system change literature to develop a set of system dimensions. We use these to examine models relating to research use that are widely referenced in education. We then apply these dimensions to the work of the Education Endowment Foundation (EEF), the UK's What Works Centre for Education, which aims to support evidence‐informed practice at all levels of the education system. We focus on its work to embed research‐informed practices in regional school systems, through a case analysis of two ‘scale‐up campaigns’ to mobilise evidence relating to the effective deployment of teaching assistants (educational support paraprofessionals). The findings highlight the value of using the system dimensions framework as a diagnostic tool to understand how to effect system change, highlighting the key role of brokerage and system leadership at different system levels; school‐level capacity to implement change; and system relationships.

Context and implications

Rationale for this study

Current approaches to supporting research use in education underplay the complexity of system change. Failure to acknowledge the complexity of research‐use systems is likely to result in less‐than‐optimal approaches and interventions to improve research use.

Why the new findings matter

By applying a systems perspective, we explore how research use can be more effectively supported.

Implications for educational researchers and policymakers

Research use emerges as a myriad of interconnected ‘moving parts’ that need to function optimally and be aligned. Weakness in any area of the system, or interactions between system actors and activities across system levels, can potentially impede research use.

A systems perspective, using the dimensions table presented in the paper, can be used to examine the functioning of existing systems and make informed decisions on where best to intervene to support practitioners’ use of research.

There is value in exploring multi‐stranded mobilisation strategies that work together at different levels of the system e.g. school, regional policy, national.
Combating coxsackievirus B infections
Authors: Alhazmi Abdulaziz , Nekoua Magloire Pandoua , Mercier Ambroise , Vergez Ines , Sane Famara , Alidjinou Enagnon Kazali , Hober Didier
Published: November 2022

Coxsackieviruses B (CVB) are small, non‐enveloped, single‐stranded RNA viruses belonging to the Enterovirus genus of the Picornaviridae family. They are common worldwide and cause a wide variety of human diseases ranging from those having relatively mild symptoms to severe acute and chronic pathologies such as cardiomyopathy and type 1 diabetes. The development of safe and effective strategies to combat these viruses remains a challenge. The present review outlines current approaches to control CVB infections and associated diseases. Various drugs targeting viral or host proteins involved in viral replication as well as vaccines have been developed and shown potential to prevent or combat CVB infections in vitro and in vivo in animal models. Repurposed drugs and alternative strategies targeting miRNAs or based on plant extracts and probiotics and their derivatives have also shown antiviral effects against CVB. In addition, clinical trials with vaccines and drugs are underway and offer hope for the prevention or treatment of CVB‐induced diseases.
Using a surrogate with heterogeneous utility to test for a treatment effect
Authors: Parast Layla , Cai Tianxi , Tian Lu
Published: November 2022

The primary benefit of identifying a valid surrogate marker is the ability to use it in a future trial to test for a treatment effect with shorter follow‐up time or less cost. However, previous work has demonstrated potential heterogeneity in the utility of a surrogate marker. When such heterogeneity exists, existing methods that use the surrogate to test for a treatment effect while ignoring this heterogeneity may lead to inaccurate conclusions about the treatment effect, particularly when the patient population in the new study has a different mix of characteristics than the study used to evaluate the utility of the surrogate marker. In this article, we develop a novel test for a treatment effect using surrogate marker information that accounts for heterogeneity in the utility of the surrogate. We compare our testing procedure to a test that uses primary outcome information (gold standard) and a test that uses surrogate marker information, but ignores heterogeneity. We demonstrate the validity of our approach and derive the asymptotic properties of our estimator and variance estimates. Simulation studies examine the finite sample properties of our testing procedure and demonstrate when our proposed approach can outperform the testing approach that ignores heterogeneity. We illustrate our methods using data from an AIDS clinical trial to test for a treatment effect using CD4 count as a surrogate marker for RNA.
Critical regularity issues for the compressible Navier–Stokes system in bounded domains
Authors: Danchin Raphaël , Tolksdorf Patrick
Published: November 2022

We are concerned with the barotropic compressible Navier–Stokes system in a bounded domain of $$\mathbb {R}^d$$

R

d

(with $$d\ge 2$$

d
≥
2

). In a critical regularity setting, we establish local well-posedness for large data with no vacuum and global well-posedness for small perturbations of a stable constant equilibrium state. Our results rely on new maximal regularity estimates—of independent interest—for the semigroup of the Lamé operator, and of the linearized compressible Navier–Stokes equations.
Effective Mass of the Polaron: A Lower Bound
Authors: Betz Volker , Polzer Steffen
Published: November 2022

We show that the effective mass of the Fröhlich Polaron is bounded below by $$c \alpha ^{2/5}$$

c

α

2
/
5

for some constant $$c>0$$

c
>
0

and for all coupling constants $$\alpha $$
α
. The proof uses the point process representation of the path measure of the Fröhlich Polaron.
Resuscitative Endovascular Balloon Occlusion of the Aorta is Associated with Increased Risk of Extremity Compartment Syndrome
Authors: Wu Yu‐Tung , Lewis Meghan R. , Arase Miharu , Demetriades Demetrios
Published: November 2022

Background

Resuscitative endovascular balloon occlusion of the aorta (REBOA) has been used as a temporizing procedure to control intra‐abdominal or pelvic bleeding. Theoretically, occlusion of the aorta and the resulting ischemia–reperfusion of the lower extremities may increase the risk of extremity compartment syndrome (CS). To date, no study has addressed systematically the incidence and risk factors of CS following REBOA intervention. The purpose of this study was to address this knowledge gap.

Methods

Adult trauma patients from the American College of Surgeons Trauma Quality Improvement Program (ACS‐TQIP) database (2016–2019) were included. Patients who received REBOA within 4 h of admission were compared to patients without REBOA after propensity score matching for demographics, vital signs on admission, comorbidities, injury severity of different body regions, pelvic and lower extremity fractures, vascular trauma to the lower extremities, fixation for fractures, angioembolization (AE) for pelvis, preperitoneal pelvic packing (PPP), laparotomy, and venous thromboembolism (VTE) prophylaxis. The primary outcomes were rates of lower extremity CS and fasciotomy and acute kidney injury (AKI). Secondary outcomes included mortality.

Results

There were 534 patients who received REBOA matched with 1043 patients without REBOA. Overall, patients in the REBOA group had significantly higher rates of CS than no REBOA patients [5.4% vs 1.1%, p < 0.001, OR: 5.39]. The risk of CS remained significantly higher in the subgroups of patients with or without pelvic or lower extremity fractures, as well as in the subgroup of patients with associated extremity vascular injury [11.2% vs 1.5%, p < 0.001, OR: 8.12].The fasciotomy and AKI rates were significantly higher in the REBOA group (5.8% vs 1.2%, p < 0.001 and 12.9% vs 7.4%, p< 0.001 respectively).

Conclusion

REBOA use is associated with a higher risk of lower extremity CS, fasciotomy and AKI, especially in patients with associated lower extremity vascular injuries. These complications should be taken into account when considering REBOA use, and close observation for this complication should always be part of the routine monitoring.