bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Efficient and Scalable “Second Generation” Total Synthesis of the Marine Polyketide Limaol Endowed with Antiparasitic Activity
Authors: Hess Stephan N. , Fürstner Alois 
Published: May 2024

AbstractThe cluster of four skipped exo‐methylene substituents on the “northern” wing of limaol renders this dinoflagellate‐derived marine natural product unique in structural terms. This arguably non‐thermodynamic array gains kinetic stability by virtue of populating local conformations which impede isomerization to a partly or fully conjugated polyene. This analysis suggested that the difficulties encountered during the late stages of our first total synthesis of this polyketide had not been caused by an overly fragile character of this unusual substructure; rather, an unfavorable steric microenvironment about the spirotricyclic core was identified as the likely cause. To remedy the issue, the protecting groups on this central fragment were changed; in effect, this amendment allowed all strategic and practical problems to be addressed. As a result, the overall yield over the longest linear sequence was multiplied by a factor of almost five and the material throughput increased more than eighty‐fold per run. Key‐to‐success was a gold‐catalyzed spirocyclization reaction; the reasons why a Brønsted acid cocatalyst is needed and the origin of the excellent levels of selectivity were delineated. The change of the protecting groups also allowed for much improved fragment coupling processes; most notably, the sequence of a substrate‐controlled carbonyl addition reaction followed by Mitsunobu inversion that had originally been necessary to affix the southern tail to the core could be replaced by a reagent controlled asymmetric allylation. Finally, a much‐improved route to the “northern” sector was established by leveraging the power of asymmetric hydrogenation of a 2‐pyrone derivative. Limaol was found to combine appreciable antiparasitic activity with very modest cytotoxicity.
Chirality Sensing of Cryptochiral Guests with Prism[n]arenes
Authors: Della Sala Paolo , Calice Umberto , Iuliano Veronica , Geremia Silvano , Hickey Neal , Belviso Sandra , Summa Francesco F. , Monaco Guglielmo , Gaeta Carmine , Superchi Stefano 
Published: May 2024

AbstractOptical chirality sensing has gained significant attention in recent years. Within this field, the quest for stereodynamic chiroptical probes capable of detecting cryptochiral guests presents a formidable challenge. Macrocycles exhibiting planar chirality have emerged as promising candidates for amplifying the chirality of cryptochiral guests. In this study, we demonstrate that the formation of host‐guest complexes between cryptochiral molecules and planar chiral prismarenes triggers electronic circular dichroism (ECD) signals via host‐guest complexation‐induced chirality amplification. The absolute configuration of the most stable chiral macrocyclic host‐guest complex has been established by resorting to both exciton model and DFT computations. Furthermore, we demonstrated that this supramolecular chirality sensing system can be employed to determine the enantiomeric composition of scalemic mixtures by measuring the ECD bands intensity. The information described here opens the way for the use of prismarenes as stereodynamic probes for sensing of cryptochiral guests.
Ultrastructure expansion microscopy (U‐ExM) of mouse and human kidneys for analysis of subcellular structures
Authors: Langner Ewa , Puapatanakul Pongpratch , Pudlowski Rachel , Alsabbagh Dema Yaseen , Miner Jeffrey H. , Horani Amjad , Dutcher Susan K. , Brody Steven L. , Wang Jennifer T. , Suleiman Hani Y. , Mahjoub Moe R. 
Published: May 2024

AbstractUltrastructure expansion microscopy (U‐ExM) involves the physical magnification of specimens embedded in hydrogels, which allows for super‐resolution imaging of subcellular structures using a conventional diffraction‐limited microscope. Methods for expansion microscopy exist for several organisms, organs, and cell types, and used to analyze cellular organelles and substructures in nanoscale resolution. Here, we describe a simple step‐by‐step U‐ExM protocol for the expansion, immunostaining, imaging, and analysis of cytoskeletal and organellar structures in kidney tissue. We detail the critical modified steps to optimize isotropic kidney tissue expansion, and preservation of the renal cell structures of interest. We demonstrate the utility of the approach using several markers of renal cell types, centrioles, cilia, the extracellular matrix, and other cytoskeletal elements. Finally, we show that the approach works well on mouse and human kidney samples that were preserved using different fixation and embedding conditions. Overall, this protocol provides a simple and cost‐effective approach to analyze both preclinical and clinical renal samples in high detail, using conventional lab supplies and standard widefield or confocal microscopy.
Exploring the Correlation of Dynamic Surface Tension with Antimicrobial Activities of Quaternary Ammonium‐Based Disinfectants
Authors: Vargas‐Cuebas Germán G. , Sanchez Christian A. , Brayton Samantha R. , Nikoloff Alexander , Masters Ronald , Minbiole Kevin P. C. , Wuest William M. 
Published: May 2024

AbstractQuaternary ammonium compound (QAC) disinfectants represent one of our first lines of defense against pathogens. Their inhibitory and bactericidal activities are usually tested through minimum inhibitory concentration (MIC) and time‐kill assays, but these assays can become cumbersome when screening many compounds. We investigated how the dynamic surface tension (DST) measurements of QACs correlate with these antimicrobial activities by testing a panel of potent and structurally varied QACs against the gram‐positive Staphylococcus aureus and the gram‐negative Pseudomonas aeruginosa. We found that DST values correlated well with bactericidal activity in real‐world disinfection conditions but not with MIC values. Moreover, no correlation between these two antimicrobial activities of QACs (bactericidal and inhibition) was observed. In addition, we observed that the bactericidal activity of our QAC panel against the gram‐negative P. aeruginosa was severely affected in the presence of hard water. Interestingly, we found that the counterion of the QAC affects the killing of bacteria in these conditions, a phenomenon not observed in most MIC assessments. Moreover, some of our best‐in‐class QACs show enhanced bactericidal activity when combined with a commercially available QAC. In conclusion, we determined that an intrinsic physical property of QACs (DST) can be used as a technique to screen for bactericidal activity of QACs in conditions that mimic real‐world disinfection conditions.
Population‐specific validation and comparison of the performance of 77‐ and 313‐variant polygenic risk scores for breast cancer risk prediction
Authors: Hovhannisyan Milena , Zemankova Petra , Nehasil Petr , Matejkova Katerina , Borecka Marianna , Cerna Marta , Dolezalova Tatana , Dvorakova Lenka , Foretova Lenka , Horackova Klara , Jelinkova Sandra , Just Pavel , Kalousova Marta , Kral Jan , Machackova Eva , Nemcova Barbora , Safarikova Marketa , Springer Drahomira , Stastna Barbora , Tavandzis Spiros , Vocka Michal , Zima Tomas , Soukupova Jana , Kleiblova Petra , Ernst Corinna , Kleibl Zdenek , Janatova Marketa 
Published: May 2024

AbstractBackgroundThe polygenic risk score (PRS) allows the quantification of the polygenic effect of many low‐penetrance alleles on the risk of breast cancer (BC). This study aimed to evaluate the performance of two sets comprising 77 or 313 low‐penetrance loci (PRS77 and PRS313) in patients with BC in the Czech population.MethodsIn a retrospective case‐control study, variants were genotyped from both the PRS77 and PRS313 sets in 1329 patients with BC and 1324 noncancer controls, all women without germline pathogenic variants in BC predisposition genes. Odds ratios (ORs) were calculated according to the categorical PRS in individual deciles. Weighted Cox regression analysis was used to estimate the hazard ratio (HR) per standard deviation (SD) increase in PRS.ResultsThe distributions of standardized PRSs in patients and controls were significantly different (p < 2.2 × 10−16) with both sets. PRS313 outperformed PRS77 in categorical and continuous PRS analyses. For patients in the highest 2.5% of PRS313, the risk reached an OR of 3.05 (95% CI, 1.66–5.89; p = 1.76 × 10−4). The continuous risk was estimated as an HRper SD of 1.64 (95% CI, 1.49–1.81; p < 2.0 × 10−16), which resulted in an absolute risk of 21.03% at age 80 years for individuals in the 95th percentile of PRS313. Discordant categorization into PRS deciles was observed in 248 individuals (9.3%).ConclusionsBoth PRS77 and PRS313 are able to stratify individuals according to their BC risk in the Czech population. PRS313 shows better discriminatory ability. The results support the potential clinical utility of using PRS313 in individualized BC risk prediction.
Impact of HIV status on prognosis of malignancies among people living with HIV in Japan
Authors: Ando Kenju , Shimomura Akihiko , Watanabe Koji , Tsukada Kunihisa , Teruya Katsuji , Gatanaga Hiroyuki , Shimizu Chikako 
Published: May 2024

AbstractBackgroundAntiretroviral therapy has reduced the incidence and mortality of AIDS‐defining malignancies (ADM); however, non–AIDS‐defining malignancies (NADM) are a major cause of death among people living with HIV (PLWH) today. Though current guidelines suggest that PLWH should receive the same treatment as the general population, there are limited studies focused on how HIV status affects the prognosis of cancers. The present study aimed to investigate the characteristics and prognosis of malignant diseases among PLWH in Japan.MethodsPatients with HIV diagnosed with malignant diseases at our institution between 2011 and 2021 were retrospectively reviewed.ResultsThere were 205 patients who were diagnosed with malignancies. Of these, 87 (42.4%) were diagnosed with ADM and 118 (57.6%) were diagnosed with NADM. Among 69 patients who received chemotherapy for ADM, 24 (34.8%) developed AIDS‐defining opportunistic infections during treatment. In contrast, only one (1.8%) of the 56 patients administered chemotherapy for NADM developed AIDS‐defining opportunistic infections. Complications of opportunistic infections at diagnosis of malignancies, low CD4+ T‐cell count, positive HIV RNA, and nonadministration of antiretroviral therapy were associated with 5‐year overall survival among patients with malignant lymphomas. However, the variables associated with HIV did not affect NADM prognosis.ConclusionsIn this analysis, HIV status had a small impact on the prognosis of malignant diseases in PLWH. Few patients with NADM developed AIDS‐defining opportunistic infections after receiving chemotherapy.
Transcriptomic analysis revealed potential regulatory biomarkers and repurposable drugs for breast cancer treatment
Authors: Shornale Akter Most , Uddin Md. Helal , Atikur Rahman Sheikh , Hossain Md. Arju , Ashik Md. Ashiqur Rahman , Zaman Nurun Nesa , Faruk Omar , Hossain Md. Sanwar , Parvin Anzana , Rahman Md Habibur 
Published: May 2024

AbstractBreast cancer (BC) is the most widespread cancer worldwide. Over 2 million new cases of BC were identified in 2020 alone. Despite previous studies, the lack of specific biomarkers and signaling pathways implicated in BC impedes the development of potential therapeutic strategies. We employed several RNAseq datasets to extract differentially expressed genes (DEGs) based on the intersection of all datasets, followed by protein–protein interaction network construction. Using the shared DEGs, we also identified significant gene ontology (GO) and KEGG pathways to understand the signaling pathways involved in BC development. A molecular docking simulation was performed to explore potential interactions between proteins and drugs. The intersection of the four datasets resulted in 146 DEGs common, including AURKB, PLK1, TTK, UBE2C, CDCA8, KIF15, and CDC45 that are significant hub‐proteins associated with breastcancer development. These genes are crucial in complement activation, mitotic cytokinesis, aging, and cancer development. We identified key microRNAs (i.e., hsa‐miR‐16‐5p, hsa‐miR‐1‐3p, hsa‐miR‐147a, hsa‐miR‐195‐5p, and hsa‐miR‐155‐5p) that are associated with aggressive tumor behavior and poor clinical outcomes in BC. Notable transcription factors (TFs) were FOXC1, GATA2, FOXL1, ZNF24 and NR2F6. These biomarkers are involved in regulating cancer cell proliferation, invasion, and migration. Finally, molecular docking suggested Hesperidin, 2‐amino‐isoxazolopyridines, and NMS‐P715 as potential lead compounds against BC progression. We believe that these findings will provide important insight into the BC progression as well as potential biomarkers and drug candidates for therapeutic development.
Tramadol/Diclofenac Fixed‐Dose Combination for Acute Pain Management: Bioavailability Assessment of a Generic Product
Authors: da Silva Thalita Martins , Davanço Marcelo Gomes , Meulman Jessica , Vianna Débora Renz Barreto , Costa Fernando , Pacheco Fernando Bastos Canton , Carandina Silvana Aparecida Calafatti , Issa Eduardo , Vespasiano Celso Francisco Pimentel 
Published: May 2024

AbstractThe multimodal analgesia strategy for acute pain involves using 2 or more analgesic medications with distinct mechanisms of action. This study assessed the bioavailability and tolerability of 2 tramadol hydrochloride (50 mg)/diclofenac sodium (50 mg) fixed‐dose combination formulations under fed conditions to attend the Brazilian regulatory requirements for generic product registration. An open‐label, randomized, single‐dose, 2‐period, 2‐way crossover trial was conducted, including healthy subjects of both sexes. Subjects received a single dose of either the test or reference formulation of tramadol/diclofenac fixed‐dose combination tablets with a 7‐day washout period. Blood samples were collected up to 36 hours after dosing for tramadol and 12 hours for diclofenac and quantified using a validated liquid chromatography‐tandem mass spectrometry method. Of 56 subjects enrolled, 53 completed the study. The 90% confidence intervals for maximum plasma concentration and area under the concentration‐time curve from time 0 to the last quantifiable concentration were within acceptable bioequivalence limits of 80%‐125%. Considering the results presented in this study, the test formulation is bioequivalent to the reference formulation and could be interchangeable in medical practice.
Application of histogram of oriented gradient features and support vector machine models in stage lighting control in drama
Authors: Qu Shen 
Published: May 2024

SummaryThe lighting control of the theatrical stage is directly related to the presentation effect of the program and the audience's experience. With the development of intelligent control technology, the control of lighting effects has been continuously improved. However, the existing stage lighting control lacks intelligence, resulting in poor control effect and weak energy‐saving performance. Based on this, a human contour image classification model using support vector machines (SVM) based on histogram of oriented gradient (HOG) feature extraction method is constructed to achieve stage lighting control. The results show that the revised HOG feature extraction approach achieves recognition performance of 99.6% when the ratio is 0.8. The HOG‐SVM model proposed in the study has the best recognition performance, reaching 99.6%. This indicates that the stage lighting control system based on HOG‐SVM feature extraction constructed in the research can meet the actual needs of stage program performance, which can be applied to stage lighting control to effectively reduce energy consumption.
SNP‐SVant: A Computational Workflow to Predict and Annotate Genomic Variants in Organisms Lacking Benchmarked Variants
Authors: Gunasekaran Deepika , Ardell David H. , Nobile Clarissa J. 
Published: May 2024

AbstractWhole‐genome sequencing is widely used to investigate population genomic variation in organisms of interest. Assorted tools have been independently developed to call variants from short‐read sequencing data aligned to a reference genome, including single nucleotide polymorphisms (SNPs) and structural variations (SVs). We developed SNP‐SVant, an integrated, flexible, and computationally efficient bioinformatic workflow that predicts high‐confidence SNPs and SVs in organisms without benchmarked variants, which are traditionally used for distinguishing sequencing errors from real variants. In the absence of these benchmarked datasets, we leverage multiple rounds of statistical recalibration to increase the precision of variant prediction. The SNP‐SVant workflow is flexible, with user options to tradeoff accuracy for sensitivity. The workflow predicts SNPs and small insertions and deletions using the Genome Analysis ToolKit (GATK) and predicts SVs using the Genome Rearrangement IDentification Software Suite (GRIDSS), and it culminates in variant annotation using custom scripts. A key utility of SNP‐SVant is its scalability. Variant calling is a computationally expensive procedure, and thus, SNP‐SVant uses a workflow management system with intermediary checkpoint steps to ensure efficient use of resources by minimizing redundant computations and omitting steps where dependent files are available. SNP‐SVant also provides metrics to assess the quality of called variants and converts between VCF and aligned FASTA format outputs to ensure compatibility with downstream tools to calculate selection statistics, which are commonplace in population genomics studies. By accounting for both small and large structural variants, users of this workflow can obtain a wide‐ranging view of genomic alterations in an organism of interest. Overall, this workflow advances our capabilities in assessing the functional consequences of different types of genomic alterations, ultimately improving our ability to associate genotypes with phenotypes. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC.Basic Protocol: Predicting single nucleotide polymorphisms and structural variationsSupport Protocol 1: Downloading publicly available sequencing dataSupport Protocol 2: Visualizing variant loci using Integrated Genome ViewerSupport Protocol 3: Converting between VCF and aligned FASTA formats
Impact of Gender on Chronic Complications in Participants With Type 2 Diabetes: Evidence From a Cross‐Sectional Study
Authors: Mokhtarpour Kiavash , Yadegar Amirhossein , Mohammadi Fatemeh , Aghayan Seyedeh Nazanin , Seyedi Seyed Arsalan , Rabizadeh Soghra , Esteghamati Alireza , Nakhjavani Manouchehr 
Published: May 2024

ABSTRACTIntroductionThis study aimed to assess and compare the prevalence of diabetes complications between men and women with Type 2 diabetes (T2D), as well as how gender relates to these complications.MethodsIn this cross‐sectional study, complications of diabetes, including coronary artery disease (CAD), retinopathy, neuropathy and diabetic kidney disease (DKD), were evaluated in 1867 participants with T2D. Additionally, baseline characteristics of the individuals, including anthropometric measurements, metabolic parameters and the use of dyslipidaemia drugs and antihyperglycaemic agents, were assessed. Gender differences in complications were examined using the chi‐squared test. Multivariate logistic regression was employed to investigate the relationship between gender and T2D complications, with and without adjusting for the characteristics of the studied population.ResultsIn the studied population, 62.1% had at least one complication, and complications were 33.5% for DKD, 29.6% for CAD, 22.9% for neuropathy and 19.1% for retinopathy. The prevalence of CAD and neuropathy was higher in men. However, DKD and retinopathy were more prevalent among women. Odds ratios of experiencing any complication, CAD and retinopathy in men compared with women were 1.57 (95% CI: 1.27–2.03), 2.27 (95% CI: 1.72–2.99) and 0.72 (95% CI: 0.52–0.98), respectively, after adjusting for demographic factors, anthropometric measures, metabolic parameters and the consumption of dyslipidaemia drugs and antihyperglycaemic agents.ConclusionThe prevalence of diabetes complications was significantly higher in men with diabetes, highlighting the need for better treatment adherence. CAD was associated with the male gender, whereas retinopathy was associated with the female gender. Men and women with diabetes should be monitored closely for CAD and retinopathy, respectively, regardless of their age, diabetes duration, anthropometric measures, laboratory findings and medications.
Combined ultra‐microelectrode: Exploring new potentials for in vivo/in situ ascorbic acid electroanalysis
Authors: Fathi Samira , Hatamie Amir 
Published: May 2024

AbstractMiniaturized and portable analytical tools show promise for sophisticated analysis, particularly in biological systems such as fruits, and they are suitable for advanced agriculture and related food industries. In this study, we developed combined ultra‐microelectrodes (UME) by modifying a microscale carbon fiber electrode (33 μm) coated with an Au nano‐film in a micropipette‐tip system. The proposed UME@Au exhibited a linear response to AC concentrations ranging from 30 to 1400 μM, with a 16 μM limit of detection. It demonstrated the ability to perform in vivo‐in vitro AC analysis in micro‐zones and volumes, such as different points of fruit tissue (Such as lemon) and within the body of a living plant (Such as Cactus arms and trunk), serving as a tiny implanted probe.In the first part of our study, we analyzed AC levels in lemon tissue directly. Our measurements revealed that AC levels are distributed heterogeneously in a single fruit. Additionally, stored AC levels depend on the color of the lemon (yellow ones have higher levels than the green ones). Furthermore, the UME was applied to control AC levels in different storage conditions, including opened containers, airtight containers, with and without exposing daylight, etc.In the second part, the UME@Au was utilized as an implanted sensor for in vivo analysis of AC in different parts of the cactus, recognized as a source of AC. No sample preparation is needed with minimum damage. The implanted microsensor could perform electroanalysis inside the live plant and stored parenchyma cells, etc. Notably, our results showed that AC levels are higher in the younger arms compared to the older ones, and so on.Based on our findings, the miniaturized, small, cheap, user‐friendly electrode demonstrated many capabilities, such as being implantable, having satisfactory stability, and not requiring sample preparations for analysis. It can open up a new window for micro‐electroanalysis in food and analytical plant sciences. We predict that this microscale platform can be modified and used for bioanalysis of other (bio)targets, such as vitamins, ions, and even the detection of plant pathogens in plants and crops directly. This involvement in the smart and modern farming industry is anticipated in the near future.