bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of dietary supplementation with chokeberry (Aronia melanocarpa, Michx.) on tetrachloride‐induced liver injury in Wistar rats: Hematological and biochemical implication
Authors: Suljević Damir , Mitrašinović‐Brulić Maja , Klepo Lejla , Škrijelj Rifat , Fočak Muhamed 
Published: July 2023

AbstractIn the current study, we assessed the hematological/biochemical alterations, histopathological changes in the liver, and blood cell disorders in Wistar rats exposed to a toxic concentration of carbon tetrachloride (CCl4) and the potential protective effect of a 30‐day oral extract of chokeberry (Aronia melanocarpa, AM). The concentration of AM (3.38 mg/kg) obtained by quantitative purification from AM fruit showed the highest antioxidant activity (AOA) in vitro and was used for oral ingestion. In addition to high AOA, high values of total phenols (85.334 mg/g), total phenolic acid (606.95 mg/g), total flavonids (22.10 mg/g), and total anthocyanins (11.01 mg/g) were recorded in chokeberry extract. CCl4 treatment caused serious liver injury, hepatocyte and blood cell impairment. AM extract given to rats before CCl4 application had a moderate hepatoprotective effect in comparison to after CCl4 application. White blood count and leukocytes were significantly altered by CCl4, however, the protective role of AM in leukocyte disorders was not established. A high number of microcytes, stomatocytes, anisocytes, and hemolyzed erythrocytes during CCl4 exposure was reduced by AM extract. Flower erythrocytes in the AM + CCl4 group were recorded. Supplementation with chokeberry extract without CCl4 caused hyperproteinemia and hyperalbuminemia. Although the results indicate a weak protective role for AM, it is nevertheless important for improved erythropoiesis and regulation of the development of anemia. The hepatoprotective role of AM was moderate, and the immune response was not proven. Daily consumption of chokeberry extract can improve health. However, the results of our study showed that the ingestion of AM extract at this dose with the highest AOA would have more effective effects if the supplementation were significantly increased.
Failure, Success, and Future Direction of Alzheimer Drugs Targeting Amyloid‐β Cascade: Pros and Cons of Chemical and Biological Modalities
Authors: Kim JiMin , Jeon Hanna , Yun Kim Hye , Kim YoungSoo 
Published: July 2023

AbstractAlzheimer's disease (AD) is the most prevalent cause of dementia and has become a health concern worldwide urging for an effective therapeutic. The amyloid hypothesis, currently the most pursued basis of AD drug discovery, points the cause of AD to abnormal production and ineffective removal of pathogenic aggregated amyloid‐β (Aβ). AD therapeutic research has been focused on targeting different species of Aβ in the amyloidogenic process to control Aβ content and recover cognitive decline. Among the different processes targeted, the clearance mechanism has been found to be the most effective, supported by the recent clinical approval of an Aβ‐targeting immunotherapeutic drug which significantly slowed cognitive decline. Although the current AD drug discovery field is extensively researching immunotherapeutic drugs, there are numerous properties of immunotherapy in need of improvements that could be overcome by an equally performing chemical drug. Here, we review chemical and immunotherapy drug candidates, based on their mechanism of modulating the amyloid cascade, selected from the AlzForum database. Through this review, we aim to summarize and evaluate the prospect of Aβ‐targeting chemical drugs.
Delivering on Cell‐Selective Protein Degradation Using Chemically Tailored PROTACs
Authors: Yao Rui , Luo Tianli , Wang Ming 
Published: July 2023

AbstractPROTACs (Proteolysis‐Targeting Chimeras) have emerged as a groundbreaking class of chemical tools that facilitate the degradation of target proteins by leveraging the ubiquitin‐proteasome system (UPS). However, the effective utilization of PROTACs in chemical biology studies and therapeutics encounters significant challenges when it comes to achieving cell‐selective protein degradation and in vivo applications. This review article aims to shed light on recent advancements in the development of Pro‐PROTACs, which exhibit controlled protein degradation capabilities in response to external stimuli or disease‐related endogenous biochemical signals. The article delves into the specific chemical strategies employed to regulate the interaction between PROTACs and E3 ubiquitin ligases or target proteins. These strategies enable spatial and temporal control over the protein degradation potential of Pro‐PROTACs. Furthermore, the review summarizes recent investigations regarding the delivery of PROTACs using biodegradable nanoparticles for in vivo applications and targeted protein degradation. Such delivery systems hold great promise for enabling efficient and selective protein degradation in vivo. Lastly, the article provides a perspective on the future design of multifunctional PROTACs and their intracellular delivery mechanisms, with a particular focus on achieving cell‐selective protein degradation.
A Photo‐degradable Crosslinker for the Development of Light‐responsive Protocell Membranes
Authors: Grimes Patrick J. , Jenkinson‐Finch Mary , Symons Henry E. , Briscoe Wuge H. , Rochat Sebastien , Mann Stephen , Gobbo Pierangelo 
Published: July 2023

AbstractThe achievement of light‐responsive behaviours is an important target for protocell engineering to allow control of fundamental protocellular processes such as communication via diffusible chemical signals, shape changes or even motility at the flick of a switch. As a step towards this ambitious goal, here we describe the synthesis of a novel poly(ethylene glycol)‐based crosslinker, reactive towards nucleophiles, that effectively degrades with UV light (405 nm). We demonstrate its utility for the fabrication of the first protocell membranes capable of light‐induced disassembly, for the photo‐generation of patterns of protocells, and for the modulation of protocell membrane permeability. Overall, our results not only open up new avenues towards the engineering of spatially organised, communicating networks of protocells, and of micro‐compartmentalised systems for information storage and release, but also have important implications for other research fields such as drug delivery and soft materials chemistry.
Resolution by diastereomeric salts: Access to both enantiomers of racemic acid using the same enantiomer of resolving base
Authors: Kovalenko Vitaly , Císařová Ivana 
Published: July 2023

AbstractRacemic carboxylic acid, a Diels‐Alder cycloadduct derived from 5‐bromo‐3‐phenyl‐α‐pyrone and acrylate dienophile, was resolved into enantiomers by diastereomeric salt crystallization. Quinidine was used as a sole resolving base. The salt of (+)‐acid crystallized from aqueous acetonitrile solution. Once this salt was separated by filtration, quinidine salt with (−)‐acid crystallized from mother liquor. As a result, both enantiomers of Diels‐Alder cycloadduct were isolated in high enantiomeric purity.
Basic Image Analysis and Manipulation in ImageJ/Fiji
Authors: Stossi Fabio , Singh Pankaj K. 
Published: July 2023

AbstractMicroscopy‐generated images contain quantitative information that can be extracted using a variety of analysis methods and automated pipelines. In this protocol, basic aspects of image analysis are outlined, including software installation, data import, image processing functions, and analytical tools that can be used to extract information from microscopy data using the open‐source software ImageJ/Fiji. Step‐by‐step protocols for analyzing objects (i.e., nuclei) in a fluorescence image are included, focusing on segmentation routines. © 2023 Wiley Periodicals LLC.
Superacid Resin‐Based Heterogeneous Catalysts for the Selective Acylation of 1,2‐Methylenedioxybenzene
Authors: Schiaroli Nicola , Allegri Alessandro , Eberle Martina , Billi Stefano , Guerrini Alberto , Albonetti Stefania , Vaccari Angelo , Tabanelli Tommaso , Lucarelli Carlo 
Published: July 2023

AbstractIn this work, we firstly report on the use of highly active and selective Aquivion superacid resins as heterogeneous catalysts for the acylation of 1,2‐methylenedioxybenzene (MDB) with propionic anhydride (AP). The reaction was investigated and optimized using solvent‐free conditions to selectively produce 3,4‐methylenedioxypropiophenone (MDP1P), a key intermediate for the manufacture of active ingredients used in insecticide formulations with a volume of production of roughly 3000 t/y. Interestingly, Aquivion‐based catalysts allows to work in mild reaction conditions (i. e. 80 °C), obtaining MDP1P yields as high as 44 % after only 1 h of reaction (selectivity 83 %). A detailed study of the AP reactivity demonstrated its tendency to promote oligomerization reactions that, as confirmed by ex‐situ and in‐situ FT‐ATR analyses, caused the deactivation of the catalyst forming surficial carbonaceous residues. In this context, a fast oxidation of the resin surface organic residues using a diluted HNO3 (or H2O2) solution was proven to be an efficient method to regenerate the catalyst, which can be reused for several reaction cycles. The results obtained in preliminary scale‐up tests were basically unaffected by the reaction volume (up to 800 mL), paving the way for possible future applications of the process.
Exploring the impact of design technique on usability: A case study on designing the eHealth websites using card sorting and interactive dialogue model
Authors: Munim Kazi Md. , Islam Iyolita , Milton Md. Musfiqur Rahman , Ara Laila Arzuman , Faisal Faiz Al , Islam Muhammad Nazrul 
Published: July 2023

AbstractThe design and info‐architecture of the web content contribute significantly to achieving better usability and user experience as well as to adopting a website to its intended end‐users. Although several design techniques exist, choosing a suitable one for designing a particular type of website is difficult and needs further investigation. Thus, the objective of this research is to explore the impact of a design technique on web usability and to find out the best suitable design technique for a particular type of website. To achieve these objectives, two separate websites for providing electronic health services named Citizen Health Service portal were developed using the two mostly used design techniques, namely card sorting and interactive dialogue model (IDM). The usability of both websites was evaluated through a laboratory‐based usability testing approach with 20 participants. The study result showed that the IDM performs better in designing such an information‐intensive website.
Review of the charring rates of different timber species
Authors: Liu Julie , Fischer Erica C. 
Published: July 2023

AbstractDuring a fire, the load‐carrying cross section of timber members will reduce due to charring. This article summarizes experimental investigations into the charring rate of different timber species under standard fire conditions, identifies material properties that contribute to the variations of char rates across the different species, and evaluates the applicability of prescribed charring rates to solid timber, cross‐laminated timber (CLT), and glulam exposed to standard fires. Data from the literature showed that density had the greatest impact on charring rate. The charring rate of timber decreased with increasing density, particularly timber densities >700 kg/m3. Prescribed charring rates from current design standards provide reasonable estimates of the average charring rate of timber with densities <700 kg/m3 exposed to standard fire curves. A linear charring rate of 0.65 mm/min was found to be suitable for CLT and glulam exposed to a standard fire for up to 180 min if the CLT did not experience char fall‐off. The National Design Specification nonlinear charring model may underestimate the char depth of glulam exposed to standard fire curves for longer than 60 min; however, the percent underestimation was small and limited data was available. The review demonstrated the need for data on the char depths of glulam and CLT exposed to standard fire curves for longer than 60 min and particularly for longer than 120 min.
Modeling venous bias in resting state functional MRI metrics
Authors: Huck Julia , Jäger Anna‐Thekla , Schneider Uta , Grahl Sophia , Fan Audrey P. , Tardif Christine , Villringer Arno , Bazin Pierre‐Louis , Steele Christopher J. , Gauthier Claudine J. 
Published: July 2023

AbstractResting‐state (rs) functional magnetic resonance imaging (fMRI) is used to detect low‐frequency fluctuations in the blood oxygen‐level dependent (BOLD) signal across brain regions. Correlations between temporal BOLD signal fluctuations are commonly used to infer functional connectivity. However, because BOLD is based on the dilution of deoxyhemoglobin, it is sensitive to veins of all sizes, and its amplitude is biased by draining veins. These biases affect local BOLD signal location and amplitude, and may also influence BOLD‐derived connectivity measures, but the magnitude of this venous bias and its relation to vein size and proximity is unknown. Here, veins were identified using high‐resolution quantitative susceptibility maps and utilized in a biophysical model to investigate systematic venous biases on common local rsfMRI‐derived measures. Specifically, we studied the impact of vein diameter and distance to veins on the amplitude of low‐frequency fluctuations (ALFF), fractional ALFF (fALFF), Hurst exponent (HE), regional homogeneity (ReHo), and eigenvector centrality values in the grey matter. Values were higher across all distances in smaller veins, and decreased with increasing vein diameter. Additionally, rsfMRI values associated with larger veins decrease with increasing distance from the veins. ALFF and ReHo were the most biased by veins, while HE and fALFF exhibited the smallest bias. Across all metrics, the amplitude of the bias was limited in voxel‐wise data, confirming that venous structure is not the dominant source of contrast in these rsfMRI metrics. Finally, the models presented can be used to correct this venous bias in rsfMRI metrics.
Knockdown of KLF5 ameliorates renal fibrosis in MRL/lpr mice via inhibition of MX1 transcription
Authors: Tao Shanshan , Tan Xiao , Chai Wen , Peng Xiaojie , Zheng Weimin , Fu Rui , Deng Meihui 
Published: July 2023

AbstractObjectiveThis study aims to elucidate the role of Kruppel‐like factor (KLF5) and myxovirus resistance 1 (MX1) in the progression of renal fibrosis in lupus nephritis (LN).MethodsFirst, the expression of KLF5 and MX1 was assessed in the peripheral blood of LN patients and healthy participants. Next, the pathological changes in renal tissues were evaluated and compared in BALB/c and MRL/lpr mice, by detecting the expression of fibrosis marker proteins (transforming growth factor‐β [TGF‐β] and CTGF) and α‐SMA, the content of urine protein, and the levels of serum creatinine, blood urea nitrogen, and serum double‐stranded DNA antibody. In TGF‐β1‐induced HK‐2 cells, the messenger RNA levels of KLF5 and MX1 were tested by qRT‐PCR, and the protein expression of α‐SMA, type I collagen (Col I), fibronectin (FN), and matrix metalloproteinase 9 (MMP9) was measured by western blot analysis. Moreover, the relationship between KLF5 and MX1 was predicted and verified.ResultsIn renal tissues of MRL/lpr mice and the peripheral blood of LN patients, KLF5 and MX1 were highly expressed. Pearson analysis revealed that KLF5 was positively correlated with MX1. Furthermore, KLF5 bound to MX1 promoter and promoted its transcription level. MRL/lpr mice showed substantial renal injury, accompanied by increased expression of α‐SMA, TGF‐β, CTGF, Col I, FN, and MMP9. Injection of sh‐KLF5 or sh‐MX1 alone in MRL/lpr mice reduced renal fibrosis in LN, while simultaneous injection of sh‐KLF5 and ad‐MX1 exacerbated renal injury and fibrosis. Furthermore, we obtained the same results in TGF‐β1‐induced HK‐2 cells.ConclusionKnockdown of KLF5 alleviated renal fibrosis in LN through repressing the transcription of MX1.
Efficacy and safety of belimumab therapy for patients with lupus nephritis: A meta‐analysis and a propensity score‐matched case–control study
Authors: Zhang Kai , Qi Tiening , Guo Donghua , Liu Youxia 
Published: July 2023

AbstractObjectiveIn this study, we performed a meta‐analysis and a propensity score‐matched case–control study to evaluate the efficacy and safety of belimumab in patients with lupus nephritis (LN).MethodsWe analyzed the data from three randomized controlled trials (RCTs) to assess the effects of belimumab treatment on renal improvement and adverse effects. Our study included a total of six LN patients who received belimumab treatment and an additional six LN patients who received standard therapy. All participants were followed up for a duration exceeding 96 weeks to evaluate the outcomes of the treatments.ResultsOur meta‐analysis incorporated data from three articles involving a total of 666 patients. The results of the analysis revealed that a higher proportion of patients who received belimumab treatment experienced renal improvement compared to those in the control group. The patients in belimumab group had a higher renal complete response rate and proteinuria improvement rate compared to the control group. However, belimumab treatment did not increase the renal partial response rate compared to the control group. The belimumab group also exhibited a higher proportion of patients who achieved normalization of antidouble‐stranded DNA, as well as normalization of low C3 and C4 levels. In our case–control study, significant improvement in proteinuria was demonstrated with belimumab at Week 48 (p = 0.037) and at all subsequent time points (all p < 0.05). Over the course of 96 weeks, belimumab treatment was associated with renal function stabilization and an increase in C3 and C4 levels. Moreover, the use of belimumab resulted in a reduction in glucocorticoid dosage at Week 24 (p = 0.02). Additionally, patients receiving belimumab treatment had a lower risk of severe treatment‐emergent adverse events, and no other significant adverse effects were observed between the two groups.ConclusionsIn patients with LN, the utilization of belimumab therapy has demonstrated notable improvements in renal response rates. Additionally, it has shown a decreased likelihood of serious treatment‐related adverse events and a diminished need for glucocorticoid dosage when compared to the active control group.
Fiber optic probe‐based ATR‐FTIR spectroscopy for rapid breast cancer detection: A pilot study
Authors: Zhang Shuyan , Vasudevan Swetha , Tan Sonia Peng Hwee , Olivo Malini 
Published: July 2023

AbstractBreast cancer diagnosis is crucial for timely treatment and improved outcomes. This paper proposes a novel approach for rapid breast cancer diagnosis using optical fiber probe‐based attenuated total reflectance Fourier transform infrared (ATR‐FTIR) spectroscopy from 750 to 4000 cm−1. The technique enables direct analysis of tissue samples, eliminating the need for microtome sectioning and staining, thus saving time and resources. By capturing molecular fingerprint information, various machine‐learning models were used to analyze the spectroscopic data to classify cancerous and non‐cancerous tissues accurately. Comparing deparaffinized and paraffinized samples reveals the impact of sample preparation and experimental methods. The study demonstrates a strong correlation between the cancerous nature of a sample and its ATR‐FTIR spectrum, suggesting its potential for breast cancer diagnosis (sensitivity of 74.2% and specificity of 78.3%). The proposed approach holds promise for integration into clinical operations, providing a rapid method for preliminary breast cancer diagnosis.
Outpatient albumin infusions reduce hospitalizations and improve outcomes in decompensated cirrhosis: A real‐world cohort study
Authors: Hannah Nicholas , Tjandra Douglas , Patwardhan Ashwin , Rutland Kelsey , Halliday John , Sood Siddharth 
Published: July 2023

AbstractBackground and AimLong‐term human albumin (HA) infusions improve survival in cirrhotic patients with diuretic resistant ascites. We aimed to determine whether there is a significant benefit in a more unwell real‐world cohort.MethodsThis is a single‐center retrospective cohort study. Patients received outpatient HA between April 2017 and June 2021. Inclusion criteria were age ≥18 years, cirrhosis with ascites, and received at least 1 month of HA. Patients with significant comorbidities and ongoing alcohol use were not excluded. Outcomes assessed were transjugular intrahepatic portosystemic shunt (TIPS)/transplant‐free survival (TTFS), and biochemical and prognostic outcomes.ResultsTwenty‐four patients were included. Median age was 59.5 years. Seven were female (29.2%). Etiology included were alcohol (50%), non‐alcoholic steatohepatitis (16.7%), and viral/alcohol (12.5%). Median model for end‐stage liver disease‐sodium (MELD‐Na) was 18.5, with Child–Pugh scores (CPS) A (4.2%), B (50%), and C (45.8%). Improvements in serum sodium (P = 0.014), albumin (P = 0.003), and CPS (P = 0.017) were observed. Reduction in hospitalizations (P = 0.001), particularly portal hypertensive related admissions was observed (relative risk 0.39; 95% confidence interval [CI] 0.21–0.69, P = 0.003), needed to treat 2.09 (95% CI 1.25–3.67). There was a reduction in total paracentesis requirements (P = 0.005). On multivariate analysis, type 2 diabetes mellitus significantly increased risk of TIPS/transplant/death (hazard ratio 6.16; 95% CI 1.23–30.84, P = 0.027). Median TTFS improved in patients with a change in MELD‐Na ≤1 at 1 month: 29.4 months versus 7.7 months (P = 0.011).ConclusionOutpatient HA infusions decrease portal hypertensive related hospital admissions, improve serum sodium, albumin levels, and CPS. Type 2 diabetes mellitus and change in MELD‐Na score help discriminate those likely to benefit most.
Subdigraphs of prescribed size and out‐degree
Authors: Steiner Raphael 
Published: July 2023

AbstractIn 2006, Noga Alon raised the following open problem: Does there exist an absolute constant such that every ‐vertex digraph with minimum out‐degree at least contains an ‐vertex subdigraph with minimum out‐degree at least ? In this note, we answer this natural question in the negative, by showing that for arbitrarily large values of there exists a ‐vertex tournament with minimum out‐degree , in which every ‐vertex subdigraph contains a vertex of out‐degree at most .