bluuebunny/crossref_metadata_2025 huggingface dataset:
Regional (south‐eastern Pacific Ocean) population genetics and global phylogeography of two endangered highly migratory pelagic sharks, the blue shark Prionace glauca and shortfin mako Isurus oxyrinchus
Authors: González M. Teresa , Leiva Natalia V. , Zárate Patricia M. , Baeza J. Antonio
Published: July 2023

The blue shark Prionace glauca and the shortfin mako Isurus oxyrinchus are two large and highly migratory sharks inhabiting temperate and tropical waters worldwide that are heavily targeted by artisanal and industrial fisheries. The International Union for Nature Conservation classifies the blue shark and shortfin mako as ‘Near Threatened’ and ‘Vulnerable’, respectively, in the Nature Red List of Threatened Species v. 2019‐2.

This study examined the population genetics of the shortfin mako and blue sharks at a regional (south‐eastern Pacific Ocean) and global scale. The null hypothesis of no genetic discontinuities among ocean basins and/or between hemispheres was tested using two mitochondrial markers suitable for population genetics inference in these species: the non‐coding control region and the protein‐coding gene cytochrome c oxidase I in I. oxyrinchus, and the control region and cytochrome b in P. glauca.

Spatial genetic analyses suggested a single and two genetic clusters co‐occurring along the south‐eastern Pacific Ocean in the shortfin mako and blue shark, respectively. Phylogeographic analyses, migration estimates, haplotype networks and AMOVAs demonstrated that the two species exhibit an overall pattern of high genetic connectivity among hemispheres and across ocean basins with a signature of shallow genetic structuring worldwide.

This study has generated valuable information for the management and conservation of heavily exploited sharks and highlights the need for additional inclusive research programmes assessing inter‐regional genomic discontinuities using more statistically powerful genetic markers to determine with precision population genetic discontinuities (if any) in these and other highly migratory sharks.
The archaeoastronomy of Tikal: A reanalysis
Authors: Layser Christopher A. , Gullberg Steven R.
Published: July 2023

At the great city of Tikal, the ancient Maya placed and oriented their ceremonial architecture and monuments in accordance with cosmological principles. Its earliest ceremonial plaza, the Mundo Perdido, is one of the oldest pre‐Classic E‐Groups of the Petén, the astronomical utility of which has been a topic of debate by archeologists and archaeoastronomers alike over the past century. In 1988, Aveni and Hartung surveyed the great temples of Tikal and revealed the relationship between their astronomical and dynastic aspects. Yet, over the intervening decades breakthroughs in the decipherment of the Maya glyphs have greatly increased our understanding of Tikal's dynastic history while interpretations in the field of archaeoastronomy have become more rigorous. For instance, more recent surveys and interpretations by Ŝprajc (2021a, 2021b) have demonstrated the importance of the Maya ritual calendar in the placement and orientation of ceremonial public architecture. The aim of this paper is to reassess this earlier fieldwork in archaeoastronomy, provide recent corroborative measurements of the orientation of key buildings, and provide a cohesive summation of the cosmological principles found in the design and construction of the city of Tikal.
Characterizing the autism spectrum phenotype in DYRK1A‐related syndrome
Authors: Kurtz‐Nelson Evangeline C. , Rea Hannah M. , Petriceks Aiva C. , Hudac Caitlin M. , Wang Tianyun , Earl Rachel K. , Bernier Raphael A. , Eichler Evan E. , Neuhaus Emily
Published: July 2023

Likely gene‐disrupting (LGD) variants in DYRK1A are causative of DYRK1A syndrome and associated with autism spectrum disorder (ASD) and intellectual disability (ID). While many individuals with DYRK1A syndrome are diagnosed with ASD, they may present with a unique profile of ASD traits. We present a comprehensive characterization of the ASD profile in children and young adults with LGDs in DYRK1A. Individuals with LGD variants in DYRK1A (n = 29) were compared to children who had ASD with no known genetic cause, either with low nonverbal IQ (n = 14) or average or above nonverbal IQ (n = 41). ASD was assessed using the ADOS‐2, ADI‐R, SRS‐2, SCQ, and RBS‐R. Quantitative score comparisons were conducted, as were qualitative analyses of clinicians' behavioral observations. Diagnosis of ASD was confirmed in 85% and ID was confirmed in 89% of participants with DYRK1A syndrome. Individuals with DYRK1A syndrome showed broadly similar social communication behaviors to children with idiopathic ASD and below‐average nonverbal IQ, with specific challenges noted in social reciprocity and nonverbal communication. Children with DYRK1A syndrome also showed high rates of sensory‐seeking behaviors. Phenotypic characterization of individuals with DYRK1A syndrome may provide additional information on mechanisms contributing to co‐occurring ASD and ID and contribute to the identification of genetic predictors of specific ASD traits.
Correlating MRI‐based brain volumetry and cognitive assessment in people with Down syndrome
Authors: Hamadelseed Osama , Skutella Thomas
Published: July 2023

Introduction

Down syndrome (DS) is the most common genetic cause of intellectual disability. Children and adults with DS show deficits in language performance and explicit memory. Here, we used magnetic resonance imaging (MRI) on children and adults with DS to characterize changes in the volume of specific brain structures involved in memory and language and their relationship to features of cognitive‐behavioral phenotypes.

Methods

Thirteen children and adults with the DS phenotype and 12 age‐ and gender‐matched healthy controls (age range 4–25) underwent an assessment by MRI and a psychological evaluation for language and cognitive abilities.

Results

The cognitive profile of people with DS showed deficits in different cognition and language domains correlating with reduced volumes of specific regional and subregional brain structures, confirming previous related studies. Interestingly, in our study, people with DS also showed more significant parahippocampal gyrus volumes, in agreement with the results found in earlier reports.

Conclusions

The memory functions and language skills affected in studied individuals with DS correlate significantly with the reduced volume of specific brain regions, allowing us to understand DS's cognitive‐behavioral phenotype. Our results provide an essential basis for early intervention and the design of rehabilitation management protocols.
Circulating hsa_circ_0072309, acting via the miR‐100/ACKR3 pathway, maybe a potential biomarker for the diagnosis, prognosis, and treatment of brain metastasis from non‐small‐cell lung cancer
Authors: Zhang Xiao‐Qiang , Song Qian , Zeng Lin‐Xiang
Published: July 2023

Background

One of the main causes of lung cancer‐related death is brain metastasis (BM). Finding early indicators of BM derived from lung cancer is crucial. Therefore, this study was designed to determine if serum hsa_circ_0072309 may be employed as a potential biomarker for BM induced by non‐small‐cell lung cancer (NSCLC) and to understand its possible underlying mechanism.

Methods

Primary lung cancer and healthy neighboring tissues were obtained from all patients, while BM tissues were taken from BM+ patients. Serum specimens were collected from all patients and healthy volunteers. Hsa_circ_001653, miR‐100, and ACKR3 RNA expressions were analyzed by quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR), and atypical chemokine receptor 3 (ACKR3) protein expression by western blotting (WB), immunohistochemistry (IHC), and enzyme‐linked immunosorbent assay (ELISA). In order to examine the effect of serum hsa_circ_0072309 and its relevant mechanism on BM development, an NSCLC‐associated BM model in mice was established.

Results

According to the results, miR‐100 expression was down‐regulated in primary lung cancer tissues compared to healthy lung tissues in all NSCLC patients, and circ_0072309 and ACKR3 expression were up‐regulated. In BM tissues compared with primary lung tumors of BM+ patients, in serum samples from all patients compared to healthy volunteers, and in lung tumors of BM+ patients compared to those from BM− patients. Patients' serum exhibits the same level of hsa_circ_0072309/miR‐100/ACKR3 expression as in BM samples. Advanced tumor‐node‐metastasis (TNM) stage, higher BM, shorter post‐operative overall survival (OS), and progression‐free survival (PFS) are all substantially associated with increased serum circ_0072309 levels in BM+ patients. In animal models, serum owning hsa_circ_0072309 from BM+ patients facilitates BM formation by regulating the miR‐100/ACKR3 pathway.

Conclusions

The current preliminary research reveals serum hsa_circ_0072309 as a possible biomarker and target for early diagnosis, prognosis, and therapy of NSCLC‐derived BM and suggests a substantial role for the hsa_circ_0072309/miR‐100/ACKR3 axis in the formation of BM from NSCLC.
Propolis Enhances 5‐Fluorouracil Mediated Antitumor Efficacy and Reduces Side Effects in Colorectal Cancer: An in Vitro and in Vivo Study
Authors: Kocyigit Abdurrahim , Guler Eray Metin , Durmus Ezgi , Yenigun Vildan Betul , Kanimdan Ebru , Ozman Zeynep , Yasar Oznur , Goren Ahmet Ceyhan , Hekimoglu Emine Rumeysa , Oruc Hasan Huseyin , Aydogdu Gokhan
Published: July 2023

In this study, we investigated the combined treatment of 5‐fluorouracil (5‐FU) and Anatolian propolis extract (PE) on colorectal cancer (CRC)using in vitro and in vivo studies. We exposed luciferase‐transfected (Lovo‐Luc CRC) cells and healthy colon cells (CCD‐18Co) to varying concentrations of 5‐FU and PE to assess their genotoxic, apoptotic, and cytotoxic effects, as well as their intracellular reactive oxygen species (iROS) levels. We also developed a xenograft model in nude mice and evaluated the anti‐tumor effects of PE and 5‐FU using various methods. Our findings showed that the combination of PE and 5‐FU had selectivity against cancer cells, particularly at higher doses, and enhanced the anti‐tumor effectiveness of 5‐FU against colon CRC. The results suggest that PE can reduce side effects and increase the effectiveness of 5‐FU through iROS generation in a dose‐dependent manner.
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

In 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

Alzheimer'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

PROTACs (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

The 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

Racemic 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

Microscopy‐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

In 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

The 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.
Energy Management Strategy Optimization for a Novel Electric‐hydraulic Power Coupling Vehicle Considering the Influence of Multiple Driving Cycles
Authors: Jia Qingxiao , Zhang Hongxin , Liu Shuo , Chen Hao
Published: July 2023

Hydraulic hybrid technology can further improve the economy of electric vehicles (EV). In this article, a novel electric‐hydraulic power coupling vehicle (EHPCV), which is endowed with multiple drive modes and energy regenerative braking modes, is investigated. The electric‐hydraulic power coupler (EHPC) is an innovative device for realizing power coupling and conversion. The design and optimization of the energy management strategy (EMS) are key to ensuring the efficient and stable operation of the hybrid electric vehicle. Based on the analysis of energy flow, a rule‐based EMS (RB‐EMS) is built. To achieve more reasonable energy management of the EHPCV in random driving environments, the article proposes an optimization framework for the EMS based on multiple driving cycles. More precisely, a multiobjective optimization mathematical model is established with the goal of maximizing the battery state of charge and minimizing velocity error. Moreover, the optimal Latin hypercube design is used to select the design variables that have a significant impact on the optimization objective. Definitively, the nondominated sorting genetic algorithm II algorithm combines with RB‐EMS to optimize the control parameters. The verification results show that the optimized EMS enables the EHPCV to have superior economic advantages.
Review of the charring rates of different timber species
Authors: Liu Julie , Fischer Erica C.
Published: July 2023

During 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

Resting‐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

Objective

This 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).

Methods

First, 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.

Results

In 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.

Conclusion

Knockdown 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

Objective

In 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).

Methods

We 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.

Results

Our 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.

Conclusions

In 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

Breast 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

Background and Aim

Long‐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.

Methods

This 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.

Results

Twenty‐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).

Conclusion

Outpatient 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

In 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 .
A new l‐serine binding orphan SerBP affects indole synthesis in Pantoea ananatis
Authors: Zhang Lei , Yu Jiajia , Zheng Jing , Wu Liqing , Zhou Xinyi , Ban Yali , Sun Yuanhao , Zhang Haotian , Feng Yongjun
Published: July 2023

Indole is traditionally known as a metabolite of l‐tryptophan and now as an important signaling molecule in bacteria, however, the understanding of its upstream synthesis regulation is very limited. Pantoea ananatis YJ76, a predominant diazotrophic endophyte isolated from rice (Oryza sativa), can produce indole to regulate various physiological and biochemical behaviors. We constructed a mutant library of YJ76 using the mTn5 transposon insertion mutation method, from which an indole‐deficient mutant was screened out. Via high‐efficiency thermal asymmetric interlaced PCR (hiTAIL‐PCR), the transposon was determined to be inserted in a gene (RefSeq: WP014605468.1) of unknown function that is highly conserved at the intraspecific level. Bioinformatics analysis implied that the protein (Protein ID: WP089517194.1) encoded by the mutant gene is most likely to be a new orphan substrate‐binding protein (SBP) for amino acid ABC transporters. Amino acid supplement cultivation experiments and surface plasmon resonance revealed that the protein could bind to l‐serine (KD = 6.149 × 10−5 M). Therefore, the SBP was named as SerBP. This is the first case that a SBP responds to l‐serine ABC transports. As a precursor of indole synthesis, the transmembrane transported l‐serine was directly correlated with indole signal production and the mutation of serBP gene weakened the resistance of YJ76 to antibiotics, alkali, heavy metals, and starvation. This study provided a new paradigm for exploring the upstream regulatory pathway for indole synthesis of bacteria.
Diurnal to interannual variability of low‐level cloud cover over western equatorial Africa in May–October
Authors: Moron Vincent , Camberlin P. , Aellig R. , Champagne O. , Fink A. H. , Knippertz P. , Philippon N.
Published: July 2023

This study examines the diurnal to interannual variations of the stratiform cloud cover in May–October (1971–2019) from a 3‐hourly station database and from ERA5 reanalyses over western equatorial Africa (WEA). The main diurnal variations of the local‐scale fraction and genus of stratiform clouds are synthesized into three canonical diurnal types (i.e., “clear,” “clear afternoon,” “cloudy” days). The interannual variations of frequencies of the three diurnal types during the cloudiest months (JJAS) are mostly associated with two main mechanisms: a meridional shallow overturning cell associating more “cloudy” and less “clear” and “clear afternoon” days to anomalous southerlies below 900 hPa over and around WEA, anomalous ascent around 5°–7°N, anomalous northerlies between 875 and 700 hPa, and anomalous subsidence over the equatorial Atlantic. This circulation is strongly related to interannual variations of the equatorial Atlantic upwelling (i.e., more clouds when the upwelling is strong) associated with a meridional shift of the Intertropical Convergence Zone over the Tropical Atlantic and adjacent continents. The second mechanism operates mostly in the zonal direction and involves again the coupled ocean–atmosphere system over the equatorial Atlantic, but also the remote El Niño–Southern Oscillation (ENSO). An anomalously cold equatorial Atlantic drives increased low‐level westerlies toward the Congo Basin. Warm ENSO events promote broad warm and easterly anomalies in the middle and upper troposphere, which increase the local static stability, and thus the local stratiform cloud cover over WEA. The present study suggests new mechanisms responsible for interannual variations of stratiform clouds in WEA, thus providing avenues of future research regarding the stability of the stratiform cloud deck under the ongoing differential warming of tropical ocean and land masses.
Effects of elevated nitrogen fertilizer on the multi‐level structure and thermal properties of rice starch granules and their relationship with chalkiness traits
Authors: Guo Changchun , Wuza Riqu , Tao Ziling , Yuan Xiaojuan , Luo Yinghan , Li Feijie , Yang Guotao , Chen Zongkui , Yang Zhiyuan , Sun Yongjian , Ma Jun
Published: July 2023

BACKGROUND

Chalkiness in rice reduces its market value and affects consumer acceptance. Research on the mechanism of chalkiness formation has focused primarily on the activity of key enzymes of carbon metabolism and starch accumulation. The relationship between the formation of chalkiness induced by N fertilizer and rice starch's multi‐level structure and thermal properties still needs to be fully elucidated.

RESULTS

In this study, the rates of chalky grains and degree of chalkiness decreased with the increase in N fertilizer dosage. This was attributed to an increased proportion of short chains, ordered structure carbon chains, small starch granules, and branched starches, and a higher degree of crystallinity and ΔHg in protein, and a decreased proportion of amylose, large starch granules, and weighted average diameter of starch granule surface area and volume. Application of N fertilizer promoted an increased proportion of short‐branched chain amylopectin to develop a more ordered carbohydrate structure and crystalline lamella. These effects enhanced the normal development and compactness of starch granules in grains, and improved their arrangement morphology, thereby reducing the chalkiness in rice.

CONCLUSION

These changes in starch multi‐level structure and protein improve the physicochemical characteristics of starch and enhance the fullness, crystallinity and compactness of starch granules, while synergistically increasing the regularity and homogeneity of starch granules and thus optimizing the stacking pattern of starch granules, leading to a reduction in rice chalkiness under nitrogen fertilization and thus improving the appearance of rice. © 2023 Society of Chemical Industry.
What is the extension of bench terrace construction for forest plantations? The case of North Central Portugal
Authors: Martins Martinho A. S. , Parente Joana , Keizer Jan J. , Vieira Diana C. S.
Published: July 2023

Over the last decades, the establishment of new fast‐growing forest plantations has been prospering. Although the European continent has the lowest share worldwide of forest plantations out of its total forest area, the Portuguese reality contrasts this. Since the last century, eucalypt plantations have increased widely in Portugal, and nowadays, it represents 36% of the total country's forests. Consequently, the soils of these plantations are commonly targeted with intensive soil mobilization by heavy machinery before planting, which in the case of sloped areas, frequently results in bench terracing. This study aims to quantify the widespread bench terracing implementation over the last 20 years in the Caramulo Mountains in north central Portugal. To do so, an analysis of satellite imagery was performed with Google Earth Pro, which allowed determining the coverage of forest areas where new terraces have been implemented, and their respective temporal dynamics. These results were then compared with additional spatiotemporal databases on land cover, topography, and bedrock, in order to understand the drivers of terrace implementation. Till date, 15% of the forest area in the mountains of Caramulo is under terraces, and over the last 20 years, the construction rate of new terraced land decreased in time, from 4% between 2000 and 2004 to 2% between 2015 and 2019. Among the two bedrock types existent in the area, terracing was found nearly exclusive over schist bedrock type (97%), while few areas were implemented over granites (3%). Their distribution was found limited above 30° of slope angle while 39% were found implemented below 15° of slope angle, conflicting with literature recommendations. Terracing was also found to be a driver of land cover change in 12% of the newly constructed terraces, whereas 8% were constructed over previous pine plantations and 4% on shrublands. This study allowed identifying several knowledge gaps associated with terracing implementation. Therefore, the authors of this work suggest a multidisciplinary approach when planning new terraces for a better assessment of the benefits and impacts of such land management practices.
Quantity or quality? Policy effects on innovations in the wind power industry in China
Authors: Jiang Zihao , Shi Jiarong
Published: July 2023

This study evaluates the effects of policy on the quantity and quality of innovations based on microdata collected from Chinese enterprises from 2006 to 2020 and then identifies the moderating effect of technological opportunity. The results indicate that while policy significantly increases the quantity of innovation, it inhibits its quality, and when technological opportunities are added to this mix, it does not significantly moderate the impact of policy on innovation quantity but does weaken its negative effect on innovation quality.
Null controllability of a retarded population dynamics model with interior degeneracy
Authors: Diao Boubacar , Echarroudi Younes , Khalil Kamal
Published: July 2023

In this work, we establish a null controllability property of a dispersive age‐structured population dynamics model with finite‐time delay on the mortality rate term. We assume that the dispersion term includes an interior degeneracy satisfying some suitable assumptions. To achieve our main results, we act according to the classical procedure, which is the Carleman estimates of a suitable adjoint system, and then its associated observability inequality. It is well known that the basis of Carleman's estimates is an adjusted weight function and one of the originalities of our article is the expression of the function as a function of age and time variables.
Children's Oncology Group's 2023 blueprint for research: Liver tumors
Authors: O'Neill Allison F. , Meyers Rebecka L. , Katzenstein Howard M. , Geller James I. , Tiao Greg M. , López‐Terrada Dolores , Malogolowkin Marcio ,   the Liver Tumor Committee
Published: July 2023

Liver tumors account for approximately 1%–2% of all pediatric malignancies, with the two most common tumors being hepatoblastoma (HB) and hepatocellular carcinoma (HCC). Previous Children's Oncology Group studies have meaningfully contributed to the current understanding of disease pathophysiology and treatment, laying groundwork for the ongoing prospective international study of both HB and HCC. Future work is focused on elucidating the biologic underpinnings of disease to support an evolution in risk categorization, advancements in the multidimensional care required to treat these patients, and the discovery of novel therapies.
Effect of hybridization and stacking sequences on mechanical properties and thermal stability of aloe vera‐roselle‐glass fiber reinforced polymer composites
Authors: Vijayan R. , Natarajan Elango , Palanikumar K. , Krishnamoorthy A. , Markandan Kalaimani , Ramesh S.
Published: July 2023

Environment friendly polymer composites made of plant based natural fibers such as bamboo fiber, roselle fiber (RF), aloe vera fiber (AF) oil, or kenaf fiber are cardinal of the current world toward sustainability. They offer lower carbon footprint, higher biodegradability, higher specific strength, higher thermal, and acoustic characteristics. On the other hand, properties of synthetic glass fibers (GFs) such as high specific strength to weight ratio, great resistance during impact, and high durability extend their application perspective for various engineering materials. As such, in the present study, mechanical properties and thermal stability of hybrid laminate comprising of natural fiber (i.e., AF and RF) and synthetic fiber (i.e., GF) fabricated using hand layup process were investigated. Experimental findings reveal that sequencing of the fibers significantly affects properties of the composite. Introducing a layer of AF between RF increased the tensile strength by 30.2% respectively while hybrid laminates composed of three successive layers of RF exhibited 12.6% higher impact strength compared to hybrid laminate composed of AF. Besides, the thermal stability of hybrid laminates was higher (i.e., minimal weight loss of <6.1% when heated up to 800°) compared to neat polymer or laminates with single reinforcement. The enhanced thermal stability, mechanical properties, and tribological properties of the “greener” hybrid laminates can be employed in various structural or lightweight industrial applications.

Highlights

Hybridization using natural fibers and synthetic fibers are attempted and investigated.

Fiber sequencing significantly affects mechanical properties of the composite.

Higher thermal stability of hybrid laminates, that is, minimal weight loss of <6.1% when heated up to 800°.

Laminated composed of AF in between RF exhibited lowest frictional coefficient.

“Green” hybrid polymer laminate suitable for various structural and lightweight industrial applications is identified.