bluuebunny/crossref_metadata_2025 huggingface dataset:
Validation of newly derived polygenic risk scores for dementia in a prospective study of older individuals
Authors: Yu Chenglong , Ryan Joanne , Orchard Suzanne G. , Robb Catherine , Woods Robyn L. , Wolfe Rory , Renton Alan E. , Goate Alison M. , Brodtmann Amy , Shah Raj C. , Chong Trevor T.‐J. , Sheets Kerry , Kyndt Christopher , Sood Ajay , Storey Elsdon , Murray Anne M. , McNeil John J. , Lacaze Paul
Published: May 2023

INTRODUCTION

Recent genome‐wide association studies identified new dementia‐associated variants. We assessed the performance of updated polygenic risk scores (PRSs) using these variants in an independent cohort.

METHODS

We used Cox models and area under the curve (AUC) to validate new PRSs (PRS‐83SNP, PRS‐SBayesR, and PRS‐CS) compared with an older PRS‐23SNP in 12,031 initially‐healthy participants ≥70 years of age. Dementia was rigorously adjudicated according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM‐IV) criteria.

RESULTS

PRS‐83SNP, PRS‐SBayesR, and PRS‐CS were associated with incident dementia, with fully adjusted (including apolipoprotein E [APOE] ε4) hazard ratios per standard deviation (SD) of 1.35 (1.23–1.47), 1.37 (1.25–1.50), and 1.42 (1.30–1.56), respectively. The AUC of a model containing conventional/non‐genetic factors and APOE was 74.7%. This was improved to 75.7% (p = 0.007), 76% (p = 0.004), and 76.1% (p = 0.003) with addition of PRS‐83SNP, PRS‐SBayesR, and PRS‐CS, respectively. The PRS‐23SNP did not improve AUC (74.7%, p = 0.95).

CONCLUSION

New PRSs for dementia significantly improve risk‐prediction performance, but still account for less risk than APOE genotype overall.
Markers of Vitamin B12 Status in Relation to Cerebrospinal Fluid Biomarkers of Alzheimer's Disease and Cognitive Performance
Authors: Hooshmand Babak , Appold Franziska , Fissler Patrick , Perneczky Robert , Otto Markus , Tumani Hayrettin , Kivipelto Miia , von Arnim Christine A. F.
Published: May 2023

Background

The association between markers of vitamin B12 status and cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD), which precede cognitive impairment, has been investigated by only a few small studies and results have been inconsistent.

Aim

The aim of this study was to investigate the associations of vitamin B12‐related markers with CSF biomarkers of AD and cognitive performance.

Methods

Data included 462 patients aged 40 to 94 years referred to the Memory Clinic of the Ulm University Hospital, Ulm, Germany. Vitamin B12, holotranscobalamin (HoloTC), homocysteine (tHcy), and methylmalonic acid (MMA) have been measured. CSF values of amyloid β42 (Aβ42) and total‐tau have been assessed in 227 participants. CERAD battery was administered to examine the cognitive status, and different domains were derived. Regression models were used to investigate the associations.

Results

In the multi‐adjusted model, higher levels of MMA were associated with raised CSF total‐tau values: the odds ratios (ORs) 95% confidence intervals (CIs) were 3.25 (95% CI = 1.35–7.76) for the highest quartile of MMA compared to the lowest. Furthermore, moderately increased MMA were related to lower Aβ42 levels: the ORs and 95% CIs were 3.06 (95% CI = 1.22–7.67) for the third quartile of MMA compared to the lowest. All B12 indicators except B12 itself were related to several cognitive domains, such as episodic memory and executive functioning.

Conclusions

Markers of vitamin B12 may be independent predictors of CSF biomarkers of AD and cognitive functioning, with MMA showing the most consistent effects. Randomized controlled trials are needed to determine the importance of vitamin B12 supplementation on slowing structural brain changes and cognitive decline. ANN NEUROL 2023;94:223–231
Associations of VGF with Neuropathologies and Cognitive Health in Older Adults
Authors: Yu Lei , Petyuk Vladislav A. , Lopes Katia de Paiva , Tasaki Shinya , Menon Vilas , Wang Yanling , Schneider Julie A. , De Jager Philip L. , Bennett David A.
Published: May 2023

Objective

VGF is proposed as a potential therapeutic target for Alzheimer's (AD) and other neurodegenerative conditions. The cell‐type specific and, separately, peptide specific associations of VGF with pathologic and cognitive outcomes remain largely unknown. We leveraged gene expression and protein data from the human neocortex and investigated the VGF associations with common neuropathologies and late‐life cognitive decline.

Methods

Community‐dwelling older adults were followed every year, died, and underwent brain autopsy. Cognitive decline was captured via annual cognitive testing. Common neurodegenerative and cerebrovascular conditions were assessed during neuropathologic evaluations. Bulk brain RNASeq and targeted proteomics analyses were conducted using frozen tissues from dorsolateral prefrontal cortex of 1,020 individuals. Cell‐type specific gene expressions were quantified in a subsample (N = 424) following single nuclei RNASeq analysis from the same cortex.

Results

The bulk brain VGF gene expression was primarily associated with AD and Lewy bodies. The VGF gene association with cognitive decline was in part accounted for by neuropathologies. Similar associations were observed for the VGF protein. Cell‐type specific analyses revealed that, while VGF was differentially expressed in most major cell types in the cortex, its association with neuropathologies and cognitive decline was restricted to the neuronal cells. Further, the peptide fragments across the VGF polypeptide resembled each other in relation to neuropathologies and cognitive decline.

Interpretation

Multiple pathways link VGF to cognitive health in older age, including neurodegeneration. The VGF gene functions primarily in neuronal cells and its protein associations with pathologic and cognitive outcomes do not map to a specific peptide. ANN NEUROL 2023;94:232–244
Colossal Anisotropic Thermal Expansion through Coupling Spin Crossover and Rhombus Deformation in a Hexanuclear {FeIII4FeII2} Compound
Authors: Sun Hui‐Ying , Meng Yin‐Shan , Zhao Liang , Yao Nian‐Tao , Mao Pan‐Dong , Liu Qiang , Yan Fei‐Fei , Oshio Hiroki , Liu Tao
Published: May 2023

Colossal and anisotropic thermal expansion is a key function for microscale or nanoscale actuators in material science. Herein, we present a hexanuclear compound of [(Tp*)FeIII(CN)3]4[FeII(Ppmp)]2⋅2 CH3OH (1, Tp*=hydrotris(3,5‐dimethyl‐pyrazol‐1‐yl)borate and Ppmp=2‐[3‐(2′‐pyridyl)pyrazol‐1‐ylmethyl]pyridine), which has a rhombic core structure abbreviated as {FeIII2FeII2}. Magnetic susceptibility measurements and single‐crystal X‐ray diffraction analyses revealed that 1 underwent thermally‐induced spin transition with the thermal hysteresis. The FeII site in 1 behaved as a spin crossover (SCO) unit, and significant deformation of its octahedron was observed during the spin transition process. Moreover, the distortion of the FeII centers actuated anisotropic deformation of the rhombic {FeIII2FeII2} core, which was spread over the whole crystal through the subsequent molecular rearrangements, leading to the colossal anisotropic thermal expansion. Our results provide a rational strategy for realizing the colossal anisotropic thermal expansion and shape memory effects by tuning the magnetic bistability.
Birefringence Regulation by Clarifying the Relationship Between Stereochemically Active Lone Pairs and Optical Anisotropy in Tin‐based Ternary Halides
Authors: Guo Jingyu , Huang Junben , Tudi Abudukadi , Hou Xueling , Han Shujuan , Yang Zhihua , Pan Shilie
Published: May 2023

It is important to establish and clarify the relationship between stereochemically active lone pairs and birefringence, since it is one of the significantly effective routes to explore birefringent crystals by introducing Sn‐centered polyhedra with stereochemically active lone pairs. Herein, four tin(II)‐based ternary halides A3SnCl5 and ASn2Cl5 (A=NH4 and Rb) have been synthesized successfully. The experimental birefringence of Rb3SnCl5 and RbSn2Cl5 is larger than or equal to 0.046 and 0.123@546 nm, respectively. Through investigating the alkali or alkaline‐earth metal tin(II)‐based ternary halides, the structure‐performance relationship has been concluded between stereochemically active lone pairs and optical anisotropy. It is beneficial to the analysis and prediction of birefringence in tin‐based halides and provides a guide for exploring tin(II)‐based optoelectronic functional materials.
Synthesis of a Blue‐Emissive Azaborathia[9]helicene by Silicon‐Boron Exchange from Unusual Atropisomeric Teraryls
Authors: Volland Daniel , Niedens Jan , Geppert Patrick T. , Wildervanck Martijn J. , Full Felix , Nowak‐Król Agnieszka
Published: May 2023

We report the concise synthesis and chir(optical) properties of an azaborathia[9]helicene consisting of two thienoazaborole motifs. The key intermediate, a highly congested teraryl with nearly parallel isoquinoline moieties, was generated as a mixture of atropisomers upon fusion of the central thiophene ring of the dithienothiophene moiety. These diastereomers were characterized by single crystal X‐ray analysis revealing intriguing interactions in the solid state. Subsequent insertion of boron into the aromatic scaffold via silicon‐boron exchange involving triisopropylsilyl groups fixed the helical geometry, thereby establishing a novel method for the preparation of azaboroles. The ligand exchange at boron in the final step afforded the blue emitter displaying a fluorescence quantum yield of 0.17 in CH2Cl2 and excellent configurational stability. Detailed structural and theoretical investigation of unusual atropisomers and the helicene provide insights into their isomerization processes.
Guiding Principles for the Rational Design of Hybrid Materials: Use of DFT Methodology for Evaluating Non‐Covalent Interactions in a Uranyl Tetrahalide Model System
Authors: Rajapaksha Harindu , Augustine Logan J. , Mason Sara E. , Forbes Tori Z.
Published: May 2023

Together with the synthesis and experimental characterization of 14 hybrid materials containing [UO2X4]2− (X=Cl− and Br−) and organic cations, we report on novel methods for determining correlation trends in their formation enthalpy (ΔHf) and observed vibrational signatures. ΔHf values were analyzed through isothermal acid calorimetry and a Density Functional Theory+Thermodynamics (DFT+T) approach with results showing good agreement between theory and experiment. Three factors (packing efficiency, cation protonation enthalpy, and hydrogen bonding energy [
]) were assessed as descriptors for trends in ΔHf. Results demonstrated a strong correlation between
and ΔHf, highlighting the importance of hydrogen bonding networks in determining the relative stability of solid‐state hybrid materials. Lastly, we investigate how hydrogen bonding networks affect the vibrational characteristics of uranyl solid‐state materials using experimental Raman and IR spectroscopy and theoretical bond orders and find that hydrogen bonding can red‐shift U≡O stretching modes. Overall, the tightly integrated experimental and theoretical studies presented here bridge the trends in macroscopic thermodynamic energies and spectroscopic features with molecular‐level details of the geometry and electronic structure. This modeling framework forms a basis for exploring 3D hydrogen bonding as a tunable design feature in the pursuit of supramolecular materials by rational design.
Introduction to Dinosaurs: New Ideas from Old Bones papers honoring Peter Dodson
Authors: Fiorillo Anthony R. , Forster Catherine A. , Weishampel David B.
Published: May 2023

This special volume of The Anatomical Record honors the life‐long commitment to anatomy and paleontology by Professor Peter Dodson (Emeritus, University of Pennsylvania). Peter's legacy is not only rooted in his own research interests, but also in the wealth of former students he mentored over his career, many of whom have made their own new contributions to the fields of anatomy and paleontology through original scientific investigation. Within these 18 scientific papers, which cover multiple taxa, multiple continents, and multiple methodologies, each of the contributors brought to this volume their own unique work that can be traced back to some form of inspiration by the honoree.
Development of heterodimeric estrogen receptor alpha antagonists to target simultaneously the ligand and coactivator binding site
Authors: Hörmann Nikolas , Kalchschmid Christina , Grabher Patricia , Grassmayr Isabella , Kapitza Paul , Kaserer Teresa , Gust Ronald
Published: May 2023

One‐third of breast cancer patients will develop recurrent cancer within 15 years of endocrine treatment. Notably, tumor growth in a hormone‐refractory state still relies on the interaction between estrogen receptor alpha (ERα) and upregulated coactivators. Herein, we suggest that simultaneous targeting of the primary ligand binding site (LBS) and the coactivator binding site (CABS) at ERα represents a promising alternative therapeutic strategy to overcome mutation‐driven resistance in breast cancer. We synthesized two series of compounds that connect the LBS‐binder (E)−3‐{4‐[8‐fluoro‐4‐(4‐hydroxyphenyl)‐2,3‐dihydrobenzo[b]oxepin‐5‐yl]phenyl}acrylic acid 8 with the coactivator binding site inhibitors (CBIs) 4,6‐bis(isobutyl(methyl)amino)pyrimidine or 3‐(5‐methoxy‐1H‐benzo[d]imidazol‐2‐yl)propanoic acid via covalent linkage. The most active benzoxepine‐pyrimidine conjugate 31 showed strong inhibition of estradiol‐induced transactivation (IC50 =  18.2 nM (ERα) and 61.7 nM (ERβ)) in a luciferase reporter gene assay as well as high antiproliferative effects in MCF‐7 (IC50 = 65.9 nM) and tamoxifen‐resistant MCF‐7/TamR (IC50 = 88.9 nM) breast cancer cells. All heterodimers exhibited two‐ to sevenfold higher antagonism at ERα (compared with ERβ) and were superior to the acrylic acid precursor 8 in terms of ER antagonism and antiproliferative activity. It was demonstrated on the example of 31 that the compounds did not influence the ERα content in MCF‐7 cells and therefore act as pure antiestrogens without downregulating potency. Possible interactions of the CBI at the receptor surface, which enhanced the biological activities, were evaluated using molecular docking studies.
Molecular Principles of the Excited‐State Intramolecular Thiol Proton Transfers in 3‐thiolflavone Derivatives
Authors: Sun Pingping , Kripalani Devesh R. , Chi Weijie
Published: May 2023

The excited‐state intramolecular proton transfer (ESIPT) effect has attracted considerable attention due to its potential applications in photoluminescent materials. However, only a few theoretical reports have investigated the ESIPT process involving sulfur‐hydrogen bonds. Herein, we systematically investigated the ESIPT effect of three 3‐thiolflavone derivatives containing sulfur‐hydrogen bonds with M06‐2X functional combined Def2‐TZVP basis set. The intramolecular sulfur‐hydrogen bonds were confirmed in the ground and excited states via analyzing the bond lengths, interaction energies, and infrared vibrational spectra. Besides, we demonstrated that the electron‐withdrawing group led to a more stable tautomer compared to the electron‐donating group. Conversely, the electron‐donating group played a crucial role in reducing the energy barrier of the ESIPT reaction due to the strengthening of the hydrogen bond in the excited state. Interestingly, the substituent group can determine the excited‐state electronic properties of keto tautomers. Specifically, the electron‐withdrawing group caused significant improvement in the nπ* transition configuration, significantly reducing the radiation rate. The electron‐donating group increased the proportion of the ππ* transition configuration, thus, the keto tautomer had bright emission. We expect these findings to open new avenues for designing potential luminescent materials.
A brief history of image sensors in the optical
Authors: Roth Martin M.
Published: May 2023

Image sensors, most notably the Charge Coupled Device (CCD), have revolutionized observational astronomy as perhaps the most important innovation after photography. Since the 50th anniversary of the invention of the CCD has passed in 2019, it is time to review the development of detectors for the visible wavelength range, starting with the discovery of the photoelectric effect and the first experiments to utilize it for the photometry of stars at Sternwarte Babelsberg in 1913, over the invention of the CCD, its development at the Jet Propulsion Laboratory, to the high‐performance CCD and complementary metal‐oxide‐semiconductor imagers that are available off‐the‐shelf today.
A randomised trial of [18F]PSMA‐1007‐PET/CT versus NaF‐PET/CT for staging primary prostate cancer: A trial protocol
Authors: Buch‐Olsen Karen Middelbo , Poulsen Mads Hvid , Hansen Steinbjørn , Vilstrup Mie Holm , Holm Jorun , Hess Søren , Holdgaard Paw Christian , Zieger Karsten Egbert Arnold , Madsen Søren Sørensen , Gerke Oke , Pedersen Kasper Tholstrup , Dam Johan Hygum , Langkjær Niels , Østergaard Louise Dorner , Asmussen Jon Thor , Braad Poul Erik , Nørgaard Birgitte , Eiber Matthias , Hildebrandt Malene Grubbe
Published: May 2023

Background

Prostate‐specific membrane antigen (PSMA)‐positron emission tomography/contrast‐enhanced computed tomography (PET/CT) is a sensitive imaging modality for prostate cancer (PCa). Due to lack of knowledge of the patient benefit, PSMA‐PET/CT is not yet recommended in the European guidelines for staging and treatment planning of patients with newly diagnosed PCa. We will investigate the potential difference in progression‐free survival (PFS) and quality of life (QoL) of using PSMA‐PET/CT versus sodium fluoride (NaF)‐PET/CT for staging and treatment planning in patients with newly diagnosed PCa.

Study Design

This is a prospective randomised controlled multicentre trial carried out at three centres in the Region of Southern Denmark.

Endpoints

The primary endpoint is PFS. Secondary endpoints are residual disease, stage migration, impact on treatment strategies, stage distribution, QoL and diagnostic accuracy measures.

Patients and Methods

Patients eligible for the study have newly diagnosed unfavourable intermediate‐ or high‐risk PCa. A total of 448 patients will be randomised 1:1 into two groups: (A) a control group staged with Na[18F]F‐PET/CT and (B) an intervention group staged with [18F]PSMA‐1007‐PET/CT. A subgroup in the intervention group will have a supplementary blinded Na[18F]F‐PET/CT performed for the purpose of performing accuracy analyses. QoL will be assessed at baseline and with regular intervals (3–12 months) during the study period. Treatment decisions are achieved at multidisciplinary team conferences based on the results of the respective scans and according to current Danish guidelines.

Trial Registration

The Regional Committees on Health Research Ethics for Southern Denmark (S‐20190161) and the Danish Medicines Agency (EudraCT Number 2021‐000123‐12) approved the study, and it has been registered on clinicaltrials.gov (Record 2020110469).
MosSCI‐mediated exogenous gene expression is modulated by genomic positioning
Authors: Chen Yuzhi , Arlt Volker M. , Stürzenbaum Stephen R.
Published: May 2023

Although the Mos1‐mediated single‐copy insertion (MosSCI) technique has been widely used to generate stable transgenic Caenorhabditis elegans strains, the link between stability of expression and integration site still needs to be explored. Here, experimental evidence is provided that transgenes are not able to match the level of transcription of their native counterpart, and that insertions at certain locations can result in an external stress‐mediated increase in expression. Insertion site ttTi5605 on chromosome II was shown to be a superior location, at least when introducing reproduction related genes. Thus, this study provides a reference for the selection of an optimal site for MosSCI which provides acceptable expression performance whilst minimizing undesirable secondary effects.
Mapping the field of responsible sourcing: Topic modeling through bibliometric analysis
Authors: Cherkaoui Adil , Aliat Marouane
Published: May 2023

Academic interest concerning inclusion of sustainability principles in the field of procurement has been in steady increase over the last 20 years. However, there is an apparent void in bibliometric analyses in this field. To address this gap, VosViewer is used in this study to examine the academic literature on responsible sourcing. 575 peer‐reviewed papers from Scopus were analyzed to reveal important topics, authors, and publications connected to the subject in hand. The first part of the analysis analyzed publication activity and listed all high impact journals covering the topic. Geographical distribution of findings showed that developed countries are the most productive in the field, in addition to an increasing interest from developing countries over the last decade. Keyword analysis generated from Vosviewer yielded to four main clusters covering the topic and shaping the intellectual structure of the study: (1) sustainable development & supply chain management, (2) environmental impact of procurement, (3) lifecycle analysis, (4) social responsibility and ethical sourcing. The article discusses the four main clusters and ends with concluding remarks encompassing six knowledge gaps and potential future research fields.
Adapting corporations to climate change: How decarbonization impacts the business strategy–performance nexus
Authors: França Alexandra , López‐Manuel Lucas , Sartal Antonio , Vázquez Xosé H.
Published: May 2023

Today's conventional wisdom on competitive strategies advanced at a time when climate change was not an issue. However, increasing requirements for decarbonization may be affecting the soundness of well‐established knowledge, which includes the effect of competitive strategies on performance. Based on 15 years (2005–2019) of panel data on 1264 publicly traded corporations from 34 countries, we find that carbon abatement positively moderates the relation between the intensity of a cost‐leadership strategy and ROA, ROE, and Tobin's Q. A post hoc analysis also reveals, nevertheless, that this requires firms to show a minimum level of cost‐reduction expertise before they can consider harnessing decarbonization for the same purposes. By contrast, the effect of decarbonization on the differentiation–performance nexus only improves for Tobin's Q, thus reflecting their difficulty to monetize climate change efforts in the short term. Overall, these findings not only allow revitalizing a rather stuck literature on competitive strategies and performance but also inform managers about when and why they can expect to achieve decarbonization for free with current competitive strategies.
A high‐throughput microfluidic mechanoporation platform to enable intracellular delivery of cyclic peptides in cell‐based assays
Authors: Kasper Stephen H. , Otten Stephanie , Squadroni Brian , Orr‐Terry Cionna , Kuang Yi , Mussallem Lily , Ge Lan , Yan Lin , Kannan Srinivasaraghavan , Verma Chandra S. , Brown Christopher J. , Johannes Charles W. , Lane David P. , Chandramohan Arun , Partridge Anthony W. , Roberts Lee R. , Josien Hubert , Therien Alex G. , Hett Erik C. , Howell Bonnie J. , Peier Andrea , Ai Xi , Cassaday Jason
Published: May 2023

Cyclic peptides are poised to target historically difficult to drug intracellular protein–protein interactions, however, their general cell impermeability poses a challenge for characterizing function. Recent advances in microfluidics have enabled permeabilization of the cytoplasmic membrane by physical cell deformation (i.e., mechanoporation), resulting in intracellular delivery of impermeable macromolecules in vector‐ and electrophoretic‐free approaches. However, the number of payloads (e.g., peptides) and/or concentrations delivered via microfluidic mechanoporation is limited by having to pre‐mix cells and payloads, a manually intensive process. In this work, we show that cells are momentarily permeable (t1/2 = 1.1–2.8 min) after microfluidic vortex shedding (μVS) and that lower molecular weight macromolecules can be cytosolically delivered upon immediate exposure after cells are processed/permeabilized. To increase the ability to screen peptides, we built a system, dispensing‐microfluidic vortex shedding (DμVS), that integrates a μVS chip with inline microplate‐based dispensing. To do so, we synced an electronic pressure regulator, flow sensor, on/off dispense valve, and an x‐y motion platform in a software‐driven feedback loop. Using this system, we were able to deliver low microliter‐scale volumes of transiently mechanoporated cells to hundreds of wells on microtiter plates in just several minutes (e.g., 96‐well plate filled in <2.5 min). We validated the delivery of an impermeable peptide directed at MDM2, a negative regulator of the tumor suppressor p53, using a click chemistry‐ and NanoBRET‐based cell permeability assay in 96‐well format, with robust delivery across the full plate. Furthermore, we demonstrated that DμVS could be used to identify functional, low micromolar, cellular activity of otherwise cell‐inactive MDM2‐binding peptides using a p53 reporter cell assay in 96‐ and 384‐well format. Overall, DμVS can be combined with downstream cell assays to investigate intracellular target engagement in a high‐throughput manner, both for improving structure–activity relationship efforts and for early proof‐of‐biology of non‐optimized peptide (or potentially other macromolecular) tools.
In vitro culture of reptile PGCS to preserve endangered species
Authors: Golkar‐Narenji Afsaneh , Dziegiel Piotr , Kempisty Bartosz , Petitte James , Mozdziak Paul Edward , Bryja Artur
Published: May 2023

Primordial germ cells (PGCs), are the source of gametes in vertebrates. There are similarities in the development of PGCs of reptiles with avian and mammalian species PGCs development. PGCs culture has been performed for avian and mammalian species but there is no report for reptilian PGCs culture. In vitro culture of PGCs is needed to produce transgenic animals, preservation of endangered animals and for studies on cell behaviour and research on fertility. Reptiles are traded as exotic pets and a source of food and they are valuable for their skin and they are useful as model for medical research. Transgenic reptile has been suggested to be useful for pet industry and medical research. In this research different aspects of PGCs development was compared in three main classes of vertebrates including mammalian, avian and reptilian species. It is proposed that a discussion on similarities between reptilian PGCs development with avian and mammalian species helps to find clues for studies of reptilian PGCs development details and finding an efficient protocol for in vitro culture of reptilian PG.
Sheep‐derived cell immortalization through the expression of cell cycle regulators and biological characterization using transcriptomes
Authors: Kikuchi Noe , Matsusaka Himari , Bai Lanlan , Sano Hiroaki , Eitsuka Takahiro , Nakagawa Kiyotaka , Sugano Eriko , Ozaki Taku , Tomita Hiroshi , Kiyono Tohru , Fukuda Tomokazu
Published: May 2023

Sheep are important domestic animals for the production of wool and meat. Although numerous cultured cell lines from humans and mice have been established, the number of cell lines derived from sheep is limited. To overcome this issue, the efficient establishment of a sheep‐derived cell line and its biological characterization is reported. Mutant cyclin‐dependent kinase 4, cyclin D1, and telomerase reverse transcriptase were introduced into sheep muscle‐derived cells in an attempt to immortalize primary cells using the K4DT method. Furthermore, the SV40 large T oncogene was introduced into the cells. The successful immortalization of sheep muscle‐derived fibroblasts was shown using the K4DT method or SV40 large T antigen. Furthermore, the expression profile of established cells showed close biological characteristics of ear‐derived fibroblasts. This study provides a useful cellular resource for veterinary medicine and cell biology.
Three‐year outcomes for transcatheter repair in patients with mitral regurgitation from the CLASP study
Authors: Spargias Konstantinos , Lim D. Scott , Makkar Raj , Kar Saibal , Kipperman Robert M. , O′Neill William W. , Ng Martin K. C. , Smith Robert L. , Fam Neil P. , Rinaldi Michael J. , Raffel Christopher O. , Walters Darren L. , Levisay Justin , Montorfano Matteo , Latib Azeem , Carroll John D. , Nickenig Georg , Windecker Stephan , Marcoff Leo , Cohen Gideon N. , Schäfer Ulrich , Webb John G. , Szerlip Molly
Published: May 2023

Background

Mitral valve transcatheter edge‐to‐edge repair (M‐TEER) is an effective option for treatment of mitral regurgitation (MR). We previously reported favorable 2‐year outcomes for the PASCAL transcatheter valve repair system.

Objectives

We report 3‐year outcomes from the multinational, prospective, single‐arm CLASP study with analysis by functional MR (FMR) and degenerative MR (DMR).

Methods

Patients with core‐lab determined MR ≥ 3+ were deemed candidates for M‐TEER by the local heart team. Major adverse events were assessed by an independent clinical events committee to 1 year and by sites thereafter. Echocardiographic outcomes were evaluated by the core laboratory to 3 years.

Results

The study enrolled 124 patients, 69% FMR; 31% DMR (60% NYHA class III‐IVa, 100% MR ≥ 3+). The 3‐year Kaplan−Meier estimate for survival was 75% (66% FMR; 92% DMR) and freedom from heart failure hospitalization (HFH) was 73% (64% FMR; 91% DMR), with 85% reduction in annualized HFH rate (81% FMR; 96% DMR) (p < 0.001). MR ≤ 2+ was achieved and maintained in 93% of patients (93% FMR; 94% DMR) and MR ≤ 1+ in 70% of patients (71% FMR; 67% DMR) (p < 0.001). The mean left ventricular end‐diastolic volume (181 mL at baseline) decreased progressively by 28 mL [p < 0.001]. NYHA class I/II was achieved in 89% of patients (p < 0.001).

Conclusions

The 3‐year results from the CLASP study demonstrated favorable and durable outcomes with the PASCAL transcatheter valve repair system in patients with clinically significant MR. These results add to the growing body of evidence establishing the PASCAL system as a valuable therapy for patients with significant symptomatic MR.
Hoarseness as the initial presentation of multiple myeloma
Authors: Colebunders Jules , Hellemans Stig , Ahmed Melek , Libbrecht Sasha , de Bruijn Sévérine
Published: May 2023

Key Clinical Message

Myeloma of the thyroid cartilage is a rare but important differential diagnosis of a laryngeal mass. Although hoarseness as the initial presenting symptom in multiple myeloma is extremely rare, a clinician should always consider it.

Multiple myeloma (MM) is a malignant plasma cell disorder characterized by an uncontrolled proliferation of monoclonal plasma cells. Although the clinical presentation at diagnosis can be quite variable, thyroid cartilage infiltration in MM is rare. Here we discuss a 65‐year‐old Caucasian male presenting to the ENT doctor with continuous hoarseness for 3 months. The initial clinical examination showed a tangible mass at the left lymph node level II–III. Further examination with fiber‐optic laryngoscopy showed a bulging of the aryepiglottic and ventricular fold. Neck and chest CT scan revealed multiple osteolytic bone lesions in addition to the large lesion in the left thyroid cartilage. Laboratory work‐up, PET‐CT scan and biopsy of the thyroid cartilage were performed and eventually all confirmed the presence of a new diagnosis of IgA kappa MM. The patient was referred to the department of hematology to start with chemotherapy.
Platelet‐rich plasma in the treatment of alopecia areata after COVID‐19 vaccination
Authors: Teng Hsiang‐Chiun , Chen Hsin‐Hsu
Published: May 2023

Key Clinical Message

Alopecia areata may develop in patients after COVID‐19 vaccination. Platelet‐rich plasma (PRP) has an outstanding anti‐inflammatory effect and could be an alternative treatment for alopecia patients who are refractory or intolerant to corticosteroids.

A 34‐year‐old female with no systemic illness presented with non‐scarring hair loss after the second COVID‐19 vaccination shot 4 weeks ago. The hair loss worsened and progressed to severe alopecia areata. We started double‐spin PRP therapy. Her hair recovered completely after six courses of PRP treatment.
Dedicated to Edmund R. Malinowski. Secondary, model‐based examination of model‐free analysis results: Making the most of soft‐modelling outcomes
Authors: Maeder Marcel
Published: May 2023

Edmund R. Malinowski is well known for his factor analysis‐based work; he is clearly less well known for his chemical model‐based analyses of chemical data. In this contribution, we discuss the, at the time innovative, idea of subjecting the primary model‐free analysis results to a secondary quantitative model‐based evaluation. Two examples from his research serve as illustrations: the complexation of Cu2+ with cyclodextrin and the dimerisation and trimerisation of methylene blue. In both examples, the spectrophotometric titration data are first analysed by window factor analysis, WFA, resulting in the concentration profiles. These primary, model‐free results allowed Malinowski to gain qualitative insight in the chemical processes. Additional quantitative analyses of the concentration profiles, based on the previously obtained reaction model, resulted in the numerical values of the underlying equilibrium constants. This contribution relates and compares this methodology with alternative ways of analysing the same data.
Smart Temperature‐Gating and Ion Conductivity Control of Grafted Anodic Aluminum Oxide Membranes
Authors: Lee Min‐Jie , Chen Yi‐Fan , Lee Lin‐Ruei , Lin Yu‐Liang , Zheng Sheng , Chang Ming‐Hsuan , Chen Jiun‐Tai
Published: May 2023

Over the past few decades, stimuli‐responsive materials have been widely applied to porous surfaces. Permeability and conductivity control of ions confined in nanochannels modified with stimuli‐responsive materials, however, have been less investigated. In this work, the permeability and conductivity control of ions confined in nanochannels of anodic aluminum oxide (AAO) templates modified with thermo‐responsive poly(N‐isopropylacrylamide) (PNIPAM) brushes are demonstrated. By surface‐initiated atom transfer radical polymerization (SI‐ATRP), PNIPAM brushes are successfully grafted onto the hexagonally packed cylindrical nanopores of AAO templates. The surface hydrophilicities of the membranes can be reversibly altered because of the lower critical solution temperature (LCST) behavior of the PNIPAM polymer brushes. From electrochemical impedance spectroscopy (EIS) analysis, the temperature‐gating behaviors of the AAO‐g‐PNIPAM membranes exhibit larger impedance changes than those of the pure AAO membranes at higher temperatures because of the aggregation of the grafted PNIPAM chains. The reversible surface properties caused by the extended and collapsed states of the polymer chains are also demonstrated by dye release tests. The smart thermo‐gated and ion‐controlled nanoporous membranes are suitable for future smart membrane applications.
Synthesis of Tetrathiophosphates from White Phosphorus
Authors: He Jiali , Shi Shanshan , Zhang Yumeng , Zhang Yang , Xu Pengxiang , Tang Guo , Zhao Yufen
Published: May 2023

Comprehensive Summary

A transition‐metal‐free one‐pot direct synthesis of tetrathiophosphates (R1S)2P(S)SR2 from white phosphorus (P4), through intermediate sodium alkyltetrathiophosphates (R1S)2P(S)SNa, is presented. In the presence of NaSH, various disulfides such as diaryl disulfidbges and dialkyl disulfides are easily coupled with P4 to give sodium alkyltetrathiophosphates (R1S)2P(S)SNa in almost quantitative yield, which react with alkyl halides in one pot to generate (R1S)2P(S)SR2. Furthermore, S‐(2‐cyanoethyl)‐substituted tetrathiophosphates (R1S)2P(S)SCH2CH2CN are successfully designed as a kind of tetrathiophosphorylation reagent to react with diaryl iodonium salts involving deprotection‐dealkylation process.
Identification of m6A‐related lncRNAs as prognostic signature within colon tumor immune microenvironment
Authors: Cao Lichao , Zhang Shenrui , Ba Ying , Zhang Hezi
Published: May 2023

Background

The current study probed prognosis‐related potential for m6A‐related lncRNAs signatures within colon tumor immune microenvironment (TIM).

Methods

After downloading transcriptomic datasets for colon cancer (CC) patients from The Cancer Genome Atlas (TCGA), they were divided, in a 1:1 ratio, within training or test datasets. m6A‐related lncRNAs were then scrutinized across such dataset using Pearson correlation assessment before generating a m6A‐related lncRNAs prognosis‐related model using the training dataset. The latter was then validated with the test and the whole dataset. In addition, we compared the differences of TIM and the estimated IC50 of drug response between the high‐ and low‐risk groups.

Results

Overall survival (OS) resulted as linked with 11 m6A‐related lncRNAs, while within the developed prognosis‐related model, areas‐under‐curves were as follows: within training dataset, values at 3‐, 4‐, and 5‐years were 0.777, 0.819, and 0.805, accordingly, and for test one, they were 0.697, 0.682, and 0.706, respectively. Finally, the values for the whole dataset were 0.675 (3‐year), 0.682 (4‐years), and 0.679 (5‐years), accordingly. Moreover, CC cases categorized within low‐risk cohort demonstrated enhanced OS (p < .0001), lower metastasis (p = 2e‐06) and lower T stage (p = .0067), more instability for microsatellite status (p = .012), and downregulation for PD‐L1, PD‐1, CTLA‐4, LAG3, and HAVCR2 (p < .05). In addition, risk scorings were significantly linked to the degree of infiltrative intensity for CD8 and CD4 (memory resting) T‐cells, T‐regulatory (Tregs), and Mast cells triggering (p < .05). Patients with low infiltrative propensity for CD4 T‐cells also had better OS (p = .016). Moreover, six representative drugs were found to be sensitive for treating CC patients.

Conclusion

A robust m6A‐related prognostic model with great performances was developed before exploring the TIM characteristics and its potential therapeutic drugs, which might improve the prognosis and therapeutic efficacy.
Testing methods to estimate spectral reflectance using datasets under different illuminants
Authors: Xu Jinghong , Luo Ming Ronnier , Fan Hui
Published: May 2023

With the rapid development of mobile imaging devices, there is a strong desire for accurate image reconstruction. However, the conventional colorimetry system is often related to environmental illuminations. Spectral reflectance is the fingerprint of color and is invariant with environmental illuminations. Therefore, the goal of the present study is to verify different algorithms to reconstruct the spectral reflectance from the camera red, green, and blue responses. In this research, the weighted local sample selection method was first combined with pseudo inverse matrix method (PI) and Wiener estimation method (WE) to investigate the optimal sample number on the model accuracy. The optimum local sample numbers of the two combination methods were established. The performance of five methods was evaluated, including PI, WE, smoothing constraint method, weighted pseudo inverse matrix method (WPI) and weighted Wiener estimation method (WWE) under lightings varying a wide range of correlated color temperature (CCT) from 3000 to 10 000 K. The best algorithm (WPI) in different lighting environments was established. The metamerism of different materials was revealed, the impact of materials on training and testing samples was reported. Finally, the methods' performance under different CCTs was revealed in terms of root mean square error and CIEDE2000, and the results from the theoretical simulation and real camera capturing were compared.
Strain‐Tunable Photocatalytic Performance in Two‐Dimensional Janus In2S2X (X=Se,Te) Monolayer as Photocatalyst for CO2 Reduction
Authors: Chen Zhengnan , Chi YuHua , Ma Hao , Yuan Saifei , Hao Chunlian , Ren Hao , Zhao Wen , Zhu HouYu , Guo Wenyue
Published: May 2023

Strain engineering has been widely used in the study of two‐dimensional semiconductors in recent years, because it can improve catalytic performance by changing the structural characteristics of materials. In this work, we systematically investigate the effects of biaxial strain on the electronic structure, band‐edge positions, and optical absorption of perfect Janus In2S2X (X=Se, Te) particles and vacancy In2S2X (V‐In2S2X). Biaxial strain enables In2S2X to achieve a transition between indirect and direct band gaps. Tensile strain reduces the band‐edge potential of the conduction band minimum (CBM), but compressive strain increases it and then tends to stabilize the material. In V‐In2S2X, the tensile strain makes the top bands of the bandgap overlap with the CBM and moves the bottom band of the bandgap down, reducing the bandgap, which makes the light absorption range redshift. Most importantly, we demonstrate that V‐In2S2X obtains excellent photocatalytic CO2 reduction performance under 4 % tensile strain, broadening its practical applications in many fields.
Analysis of repeated measures data through mixed models: An application in Theobroma grandiflorum breeding
Authors: Chaves Saulo F. S. , Alves Rodrigo S. , Dias Luiz A. S. , Alves Rafael M. , Dias Kaio O. G. , Evangelista Jeniffer S. P. C.
Published: May 2023

Theobroma grandiflorum is a perennial fruit tree native to the Amazon region. As a perennial species with continuous production throughout the years, breeders should seek well‐conducted trials, accurate phenotyping and adequate statistical models for genetic evaluation and selection that can leverage the information provided by the repeated measures. We evaluated 13 models with different covariance structures for genetic and residual effects for T. grandiflorum evaluation, using an unbalanced dataset with 34 hybrids from the triple‐crossing of nine parents, planted in a randomized complete block design. For nine consecutive years, the fruit yield of these hybrids was evaluated. Each model had its goodness‐of‐fit tested by the Akaike information criterion. The most adequate model for estimating the variance components and the breeding values were modelled with the first‐order heterogeneous autoregressive for residual effects and third‐order factor analytic for genetic effects. From this model, we used the factor analytic selection tools for selecting the top 10 families, providing a genetic gain of 10.42%. These results are important not only for T. grandiflorum breeding but also to show that in any repeated measures' data from fruit‐bearing perennial species the modelling of genetic and residual effects should not be neglected.
Design and development of dynamic Agri‐ontology for IoT interoperability
Authors: Khatoon P Salma , Ahmed Muqeem
Published: May 2023

In recent years, the usage and applications of Internet of Things (IoT) have increased exponentially. IoT connects multiple heterogeneous devices like sensors, micro controllers, actuators, smart devices like mobiles, watches, etc. IoT contributes the data produced in the context of data collection, including the domains like military, agriculture, healthcare, etc. The diversity of possible applications at the intersection of the IoT and the web semantics has prompted many research teams to work at the interface between these two disciplines. This makes it possible to collect data and control various objects in transparent way. The challenge lies in the use of this data. Ontologies address this challenge to meet specific data needs in the IoT field. This paper presents the implementation of a dynamic agriculture ontology‐building tool that parses the ontology files to extract full data and update it based on the user needs. The technology is used to create the angular library for parsing the OWL files. The proposed ontology framework would accept user‐defined ontologies and provide an interface for an online updating of the owl files to ensure the interoperability in the agriculture IoT.
THIP: A trajectory history‐based indoor positioning algorithm using stress‐free floor plan for patient monitoring
Authors: Jalali Mohammad Reza , Kheirabadi Mohammad Taghi
Published: May 2023

The Internet of Things (IoT) is a novel paradigm that consists of a wide network of machines and intelligent devices with the capability of communication and interaction with each other. One of the significant issues for the IoT is its healthcare applications. The positioning systems based on their environment can be classified into two main categories: Indoor and outdoor. Recently, IoT indoor positioning attracts too much attention among researchers for patient monitoring. Hence, in this paper, a stress‐free floor plan indoor positioning algorithm for patient monitoring is proposed, called THIP. The history of the patient's movement is stored in a trajectory history, and this information is employed to estimate the patient's more accurate position. The proposed THIP algorithm is simulated in MATLAB software. Several experiments are conducted to evaluate the performance of the proposed algorithm. Simulation results show that the proposed THIP algorithm raises patient positioning accuracy and declines the distance error cumulative compared to LiFS by about 4.68% and 60.6 m, respectively. Moreover, it can identify the floor level of the moving user.
The use of nitrous oxide whippets as a recreational drug: Hidden health risks
Authors: Desmedt Bart , Verleysen Eveline , Demaegdt Heidi , van Campenhout Peter , van Miert Erik , Deconinck Eric
Published: May 2023

Whipped cream canisters, also known as nitrous oxide whippets, are traditionally used in the culinary arts to prepare food foams. In recent years, however, these gas canisters have been cracked open and inhaled to produce a “legal” high. Users of these whippets have reported the presence of an oily residue containing metallic particles. This contamination was investigated using liquid chromatography‐, gas chromatography‐ and inductively coupled plasma‐mass spectrometry (ICP‐MS) and optical emission spectrometry (ICP‐OES). The particulate matter was also analyzed by scanning transmission electron microscopy (STEM) combined with energy‐dispersive X‐ray spectroscopy (EDX). The presence of cyclohexyl isothiocyanate was confirmed at a maximum concentration of 67 μg per whippet. ICP‐MS and ICP‐OES analysis revealed the presence of mainly iron and zinc, but also, traces of aluminum, chromium, cobalt, nickel, and lead were found. STEM‐EDX analysis confirmed the presence of nano‐sized particles containing iron and zinc. When simulating inhalation, using the multiple path particle dosimetry model, it was confirmed that these nano‐sized particles can reach the deeper parts of the lungs. Most users assume that inhaling a food‐grade nitrous oxide whippet for a “legal” high poses no risks. However, this research shows that users are exposed to cyclohexyl isothiocyanate, a substance classified as a respiratory sensitizer. The presence of zinc in the particulate matter could potentially be linked to lung lesions.