bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular mechanisms underpinning favourable physiological adaptations to exercise prehabilitation for urological cancer surgery
Authors: Blackwell James E. M. , Gharahdaghi Nima , Deane Colleen S. , Brook Matthew S. , Williams John P. , Lund Jonathan N. , Atherton Philip J. , Smith Ken , Wilkinson Daniel J. , Phillips Bethan E.
Published: December 2023

Background

Surgery for urological cancers is associated with high complication rates and survivors commonly experience fatigue, reduced physical ability and quality of life. High-intensity interval training (HIIT) as surgical prehabilitation has been proven effective for improving the cardiorespiratory fitness (CRF) of urological cancer patients, however the mechanistic basis of this favourable adaptation is undefined. Thus, we aimed to assess the mechanisms of physiological responses to HIIT as surgical prehabilitation for urological cancer.

Methods

Nineteen male patients scheduled for major urological surgery were randomised to complete 4-weeks HIIT prehabilitation (71.6 ± 0.75 years, BMI: 27.7 ± 0.9 kg·m2) or a no-intervention control (71.8 ± 1.1 years, BMI: 26.9 ± 1.3 kg·m2). Before and after the intervention period, patients underwent m. vastus lateralis biopsies to quantify the impact of HIIT on mitochondrial oxidative phosphorylation (OXPHOS) capacity, cumulative myofibrillar muscle protein synthesis (MPS) and anabolic, catabolic and insulin-related signalling.

Results

OXPHOS capacity increased with HIIT, with increased expression of electron transport chain protein complexes (C)-II (p = 0.010) and III (p = 0.045); and a significant correlation between changes in C-I (r = 0.80, p = 0.003), C-IV (r = 0.75, p = 0.008) and C-V (r = 0.61, p = 0.046) and changes in CRF. Neither MPS (1.81 ± 0.12 to 2.04 ± 0.14%·day−1, p = 0.39) nor anabolic or catabolic proteins were upregulated by HIIT (p > 0.05). There was, however, an increase in phosphorylation of AS160Thr642 (p = 0.046) post-HIIT.

Conclusions

A HIIT surgical prehabilitation regime, which improved the CRF of urological cancer patients, enhanced capacity for skeletal muscle OXPHOS; offering potential mechanistic explanation for this favourable adaptation. HIIT did not stimulate MPS, synonymous with the observed lack of hypertrophy. Larger trials pairing patient-centred and clinical endpoints with mechanistic investigations are required to determine the broader impacts of HIIT prehabilitation in this cohort, and to inform on future optimisation (i.e., to increase muscle mass).
Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies
Authors: Bahar Md Entaz , Kim Hyun Joon , Kim Deok Ryong
Published: December 2023

Metastatic dissemination of solid tumors, a leading cause of cancer-related mortality, underscores the urgent need for enhanced insights into the molecular and cellular mechanisms underlying metastasis, chemoresistance, and the mechanistic backgrounds of individuals whose cancers are prone to migration. The most prevalent signaling cascade governed by multi-kinase inhibitors is the mitogen-activated protein kinase (MAPK) pathway, encompassing the RAS–RAF–MAPK kinase (MEK)–extracellular signal-related kinase (ERK) pathway. RAF kinase is a primary mediator of the MAPK pathway, responsible for the sequential activation of downstream targets, such as MEK and the transcription factor ERK, which control numerous cellular and physiological processes, including organism development, cell cycle control, cell proliferation and differentiation, cell survival, and death. Defects in this signaling cascade are associated with diseases such as cancer. RAF inhibitors (RAFi) combined with MEK blockers represent an FDA-approved therapeutic strategy for numerousRAF-mutant cancers, including melanoma, non-small cell lung carcinoma, and thyroid cancer. However, the development of therapy resistance by cancer cells remains an important barrier. Autophagy, an intracellular lysosome-dependent catabolic recycling process, plays a critical role in the development of RAFi resistance in cancer. Thus, targeting RAF and autophagy could be novel treatment strategies forRAF-mutant cancers. In this review, we delve deeper into the mechanistic insights surrounding RAF kinase signaling in tumorigenesis and RAFi-resistance. Furthermore, we explore and discuss the ongoing development of next-generation RAF inhibitors with enhanced therapeutic profiles. Additionally, this review sheds light on the functional interplay between RAF-targeted therapies and autophagy in cancer.
Simultaneously targeting extracellular vesicle trafficking and TGF-β receptor kinase activity blocks signaling hyperactivation and metastasis
Authors: Teixeira Adilson Fonseca , Wang Yanhong , Iaria Josephine , ten Dijke Peter , Zhu Hong-Jian
Published: December 2023

Metastasis is the leading cause of cancer-related deaths. Transforming growth factor beta (TGF-β) signaling drives metastasis and is strongly enhanced during cancer progression. Yet, the use of on-target TGF-β signaling inhibitors in the treatment of cancer patients remains unsuccessful, highlighting a gap in the understanding of TGF-β biology that limits the establishment of efficient anti-metastatic therapies. Here, we show that TGF-β signaling hyperactivation in breast cancer cells is required for metastasis and relies on increased small extracellular vesicle (sEV) secretion. Demonstrating sEV’s unique role, TGF-β signaling levels induced by sEVs exceed the activity of matching concentrations of soluble ligand TGF-β. Further, genetic disruption of sEV secretion in highly-metastatic breast cancer cells impairs cancer cell aggressiveness by reducing TGF-β signaling to nearly-normal levels. Otherwise, TGF-β signaling activity in non-invasive breast cancer cells is inherently low, but can be amplified by sEVs, enabling invasion and metastasis of poorly-metastatic breast cancer cells. Underscoring the translational potential of inhibiting sEV trafficking in advanced breast cancers, treatment with dimethyl amiloride (DMA) decreases sEV secretion, TGF-β signaling activity, and breast cancer progression in vivo. Targeting both the sEV trafficking and TGF-β signaling by combining DMA and SB431542 at suboptimal doses potentiated this effect, normalizing the TGF-β signaling in primary tumors to potently reduce circulating tumor cells, metastasis, and tumor self-seeding. Collectively, this study establishes sEVs as critical elements in TGF-β biology, demonstrating the feasibility of inhibiting sEV trafficking as a new therapeutic approach to impair metastasis by normalizing TGF-β signaling levels in breast cancer cells.
Targeting S100A9 protein affects mTOR-ER stress signaling and increases venetoclax sensitivity in Acute Myeloid Leukemia
Authors: Fan Rong , Satilmis Hatice , Vandewalle Niels , Verheye Emma , De Bruyne Elke , Menu Eline , De Beule Nathan , De Becker Ann , Ates Gamze , Massie Ann , Kerre Tessa , Törngren Marie , Eriksson Helena , Vanderkerken Karin , Breckpot Karine , Maes Ken , De Veirman Kim
Published: December 2023

Acute Myeloid Leukemia (AML) is a heterogeneous disease with limited treatment options and a high demand for novel targeted therapies. Since myeloid-related protein S100A9 is abundantly expressed in AML, we aimed to unravel the therapeutic impact and underlying mechanisms of targeting both intracellular and extracellular S100A9 protein in AML cell lines and primary patient samples. S100A9 silencing in AML cell lines resulted in increased apoptosis and reduced AML cell viability and proliferation. These therapeutic effects were associated with a decrease in mTOR and endoplasmic reticulum stress signaling. Comparable results on AML cell proliferation and mTOR signaling could be observed using the clinically available S100A9 inhibitor tasquinimod. Interestingly, while siRNA-mediated targeting of S100A9 affected both extracellular acidification and mitochondrial metabolism, tasquinimod only affected the mitochondrial function of AML cells. Finally, we found that S100A9-targeting approaches could significantly increase venetoclax sensitivity in AML cells, which was associated with a downregulation of BCL-2 and c-MYC in the combination group compared to single agent therapy. This study identifies S100A9 as a novel molecular target to treat AML and supports the therapeutic evaluation of tasquinimod in venetoclax-based regimens for AML patients.
Combined absence of TRP53 target genes ZMAT3, PUMA and p21 cause a high incidence of cancer in mice
Authors: Brennan Margs S. , Brinkmann Kerstin , Romero Sola Gerard , Healey Geraldine , Gibson Leonie , Gangoda Lahiru , Potts Margaret A. , Lieschke Elizabeth , Wilcox Stephen , Strasser Andreas , Herold Marco J. , Janic Ana
Published: December 2023

Transcriptional activation of target genes is essential for TP53-mediated tumour suppression, though the roles of the diverse TP53-activated target genes in tumour suppression remains poorly understood. Knockdown of ZMAT3, an RNA-binding zinc-finger protein involved in regulating alternative splicing, in haematopoietic cells by shRNA caused leukaemia only with the concomitant absence of the PUMA and p21, the critical effectors of TRP53-mediated apoptosis and cell cycle arrest respectively. We were interested to further investigate the role of ZMAT3 in tumour suppression beyond the haematopoietic system. Therefore, we generated Zmat3 knockout and compound gene knockout mice, lacking Zmat3 and p21, Zmat3 and Puma or all three genes. Puma−/−p21−/−Zmat3−/− triple knockout mice developed tumours at a significantly higher frequency compared to wild-type, Puma−/−Zmat3−/− or p21−/−Zmat3−/−deficient mice. Interestingly, we observed that the triple knockout and Puma−/−Zmat3−/− double deficient animals succumbed to lymphoma, while p21−/−Zmat3−/− animals developed mainly solid cancers. This analysis suggests that in addition to ZMAT3 loss, additional TRP53-regulated processes must be disabled simultaneously for TRP53-mediated tumour suppression to fail. Our findings reveal that the absence of different TRP53 regulated tumour suppressive processes changes the tumour spectrum, indicating that different TRP53 tumour suppressive pathways are more critical in different tissues.
Inhibition of LRRK2 kinase activity rescues deficits in striatal dopamine physiology in VPS35 p.D620N knock-in mice
Authors: Bu Mengfei , Follett Jordan , Deng Isaac , Tatarnikov Igor , Wall Shannon , Guenther Dylan , Maczis Melissa , Wimsatt Genevieve , Milnerwood Austen , Moehle Mark S. , Khoshbouei Habibeh , Farrer Matthew J.
Published: December 2023

Dysregulation of dopamine neurotransmission profoundly affects motor, motivation and learning behaviors, and can be observed during the prodromal phase of Parkinson’s disease (PD). However, the mechanism underlying these pathophysiological changes remains to be elucidated. Mutations in vacuolar protein sorting 35 (VPS35) and leucine-rich repeat kinase 2 (LRRK2) both lead to autosomal dominant PD, and VPS35 and LRRK2 may physically interact to govern the trafficking of synaptic cargos within the endo-lysosomal network in a kinase-dependent manner. To better understand the functional role of VPS35 and LRRK2 on dopamine physiology, we examined Vps35 haploinsufficient (Haplo) and Vps35 p.D620N knock-in (VKI) mice and how their behavior, dopamine kinetics and biochemistry are influenced by LRRK2 kinase inhibitors. We found Vps35 p.D620N significantly elevates LRRK2-mediated phosphorylation of Rab10, Rab12 and Rab29. In contrast, Vps35 haploinsufficiency reduces phosphorylation of Rab12. While striatal dopamine transporter (DAT) expression and function is similarly impaired in both VKI and Haplo mice, that physiology is normalized in VKI by treatment with the LRRK2 kinase inhibitor, MLi-2. As a corollary, VKI animals show a significant increase in amphetamine induced hyperlocomotion, compared to Haplo mice, that is also abolished by MLi-2. Taken together, these data show Vps35 p.D620N confers a gain-of-function with respect to LRRK2 kinase activity, and that VPS35 and LRRK2 functionally interact to regulate DAT function and striatal dopamine transmission.
Intra- and inter-individual cognitive variability in schizophrenia and bipolar spectrum disorder: an investigation across multiple cognitive domains
Authors: Haatveit Beathe , Westlye Lars T. , Vaskinn Anja , Flaaten Camilla Bärthel , Mohn Christine , Bjella Thomas , Sæther Linn Sofie , Sundet Kjetil , Melle Ingrid , Andreassen Ole A. , Alnæs Dag , Ueland Torill
Published: December 2023

There is substantial cognitive heterogeneity among patients with schizophrenia (SZ) and bipolar disorders (BD). More knowledge about the magnitude and clinical correlates of performance variability could improve our understanding of cognitive impairments. Using double generalized linear models (DGLMs) we investigated cognitive mean and variability differences between patients with SZ (n = 905) and BD spectrum disorders (n = 522), and healthy controls (HC,n = 1170) on twenty-two variables. The analysis revealed significant case-control differences on 90% of the variables. Compared to HC, patients showed larger intra-individual (within subject) variability across tests and larger inter-individual (between subject) variability in measures of fine-motor speed, mental processing speed, and inhibitory control (SZ and BD), and in verbal learning and memory and intellectual functioning (SZ). In SZ, we found that lager intra -and inter (on inhibitory control and speed functions) individual variability, was associated with lower functioning and more negative symptoms. Inter-individual variability on single measures of memory and intellectual function was additionally associated with disorganized and positive symptoms, and use of antidepressants. In BD, there were no within-subject associations with symptom severity. However, greater inter-individual variability (primarily on inhibitory control and speeded functions) was associated with lower functioning, more negative -and disorganized symptoms, earlier age at onset, longer duration of illness, and increased medication use. These results highlight larger individual differences in patients compared to controls on various cognitive domains. Further investigations of the causes and correlates of individual differences in cognitive function are warranted.
Chromosome architecture in an archaeal species naturally lacking structural maintenance of chromosomes proteins
Authors: Badel Catherine , Bell Stephen D.
Published: December 2023

Proteins in the structural maintenance of chromosomes (SMC) superfamily play key roles in chromosome organization and are ubiquitous across all domains of life. However, SMC proteins are notably absent in the Desulfurococcales of phylum Crenarchaeota. Intrigued by this observation, we performed chromosome conformation capture experiments in the model Desulfurococcales species Aeropyrum pernix. As in other archaea, we observe chromosomal interaction domains across the chromosome. The boundaries between chromosomal interaction domains show a dependence on transcription and translation for their definition. Importantly, however, we reveal an additional higher-order, bipartite organization of the chromosome—with a small high-gene-expression and self-interacting domain that is defined by transcriptional activity and loop structures. Viewing these data in the context of the distribution of SMC superfamily proteins in the Crenarchaeota, we suggest that the organization of the Aeropyrum genome represents an evolutionary antecedent of the compartmentalized architecture observed in the Sulfolobus lineage.
Functional and evolutionary significance of unknown genes from uncultivated taxa
Authors: Rodríguez del Río Álvaro , Giner-Lamia Joaquín , Cantalapiedra Carlos P. , Botas Jorge , Deng Ziqi , Hernández-Plaza Ana , Munar-Palmer Martí , Santamaría-Hernando Saray , Rodríguez-Herva José J. , Ruscheweyh Hans-Joachim , Paoli Lucas , Schmidt Thomas S. B. , Sunagawa Shinichi , Bork Peer , López-Solanilla Emilia , Coelho Luis Pedro , Huerta-Cepas Jaime
Published: December 2023

Many of the Earth’s microbes remain uncultured and understudied, limiting our understanding of the functional and evolutionary aspects of their genetic material, which remain largely overlooked in most metagenomic studies1. Here we analysed 149,842 environmental genomes from multiple habitats2–6 and compiled a curated catalogue of 404,085 functionally and evolutionarily significant novel (FESNov) gene families exclusive to uncultivated prokaryotic taxa. All FESNov families span multiple species, exhibit strong signals of purifying selection and qualify as new orthologous groups, thus nearly tripling the number of bacterial and archaeal gene families described to date. The FESNov catalogue is enriched in clade-specific traits, including 1,034 novel families that can distinguish entire uncultivated phyla, classes and orders, probably representing synapomorphies that facilitated their evolutionary divergence. Using genomic context analysis and structural alignments we predicted functional associations for 32.4% of FESNov families, including 4,349 high-confidence associations with important biological processes. These predictions provide a valuable hypothesis-driven framework that we used for experimental validatation of a new gene family involved in cell motility and a novel set of antimicrobial peptides. We also demonstrate that the relative abundance profiles of novel families can discriminate between environments and clinical conditions, leading to the discovery of potentially new biomarkers associated with colorectal cancer. We expect this work to enhance future metagenomics studies and expand our knowledge of the genetic repertory of uncultivated organisms.
Effect of viscous dissipation and induced magnetic field on an unsteady mixed convective stagnation point flow of a nonhomogenous nanofluid
Authors: Aiyashi M. A. , Abo-Dahab S. M. , Albalwi M. Daher
Published: December 2023

In the study, we investigate the numerical investigation of variable viscous dissipation and source of heat or sink in mixed convective stagnation point flow the unsteady non-homogeneous nanofluid under the induced magnetic parameter. Considering similarity conversions, the governing of fundamental boundary of layer non-linear PDEs are transformed to equations of the non-linear differential type that, under appropriate boundary conditions, are numerically solved, and the MATLAB function bvp4c is considered to solve the resulting system. The obtained results are calculated numerically for non-dimensional velocity, temperature, and volume fraction and displayed graphically. Further, numbers of Nusselt and Sherwood and local Skin of friction have been produced and displayed by graphs. A comparison with previous results obtained neglecting the new parameters has been made to show the impact of new external parametes on the phenomneon. The obtained findings agree with those introduced by others if the magnetic field and viscous dissipation are neglected. The results obtained have an important applications in diverse field as chemical engineering, agriculture, medical science, and industries.
Acidified manure and nitrogen-enriched biochar showed short-term agronomic benefits on cotton–wheat cropping systems under alkaline arid field conditions
Authors: Shah Suleman Haider , Hussain Muhammad Baqir , Haider Ghulam , Haq Tanveer Ul , Zahir Zahir Ahmad , Danish Subhan , Paray Bilal Ahamad , Kammann Claudia
Published: December 2023

Application of organic residues such as farm manure and biochar in various agricultural environments have shown positive effects on soil carbon sequestration. However, there is a lack of consensus regarding the agronomical benefits of a single and small dose of biochar and farm manure in arid alkaline soils. Therefore, a field experiment with the given treatments (1) control (no amendment), (2) acidified manure (AM) at 300 kg ha−1, (3) nitrogen (N) enriched biochar (NeB) at 3 Mg ha−1, and (4) an equal combination of AM + NeB (150 kg ha−1 AM + 1.5 Mg ha−1 NeB)) was conducted in a typical cotton–wheat cropping system. A parallel laboratory incubation study with the same amendments was carried out to account for soil carbon dioxide emission (CO2). The N enrichment of biochar and its co-application with acidified manure increased soil mineral N (NO3− and NH4+) in the topsoil (0–15 cm), and increased total N uptake (25.92% to 69.91%) in cotton over control, thus reducing N losses and increased uptake over control. Compared to the control, co-application of AM + NeB significantly improved soil N and P bioavailability, leading to increased plant biomass N, P, and K (32%, 40%, 6%, respectively) uptake over control. The plant's physiological and growth improvements [chlorophyll (+ 28.2%), height (+ 47%), leaf area (+ 17%), number of bolls (+ 7%), and average boll weight (+ 8%)] increased the agronomic yield in the first-season crop cotton by 25%. However, no positive response was observed in the second season wheat crop. This field study improved our understanding that co-application of acidified manure and N-enriched biochar in small dose can be a strategy to achieve short-term agronomic benefits and carbon sequestration in the long run.
Usability of an artificially intelligence-powered triage platform for adult ophthalmic emergencies: a mixed methods study
Authors: Jindal Anish , Sumodhee Dayyanah , Brandao-de-Resende Camilo , Melo Mariane , Neo Yan Ning , Lee Elsa , Day Alexander C.
Published: December 2023

There is growing demand for emergency-based eyecare services where the majority of those attending do not require urgent ophthalmic management. The Royal College of Ophthalmologists have recommended upskilling and supporting of allied health professionals to support eyecare delivery, where machine learning algorithms could help. A mixed methods study was conducted to evaluate the usability of an artificial intelligence (AI) powered online triage platform for ophthalmology. The interface, usability, safety and acceptability were investigated using a Think Aloud interview and usability questionnaires. Twenty participants who actively examine patients in ophthalmic triage within a tertiary eye centre or primary care setting completed the interview and questionnaires. 90% or more of participants found the platform easy to use, reflected their triage process and were able to interpret the triage outcome, 85% found it safe to use and 95% felt the processing time was fast. A quarter of clinicians reported that they have experienced some uncertainty when triaging in their career and were unsure of using AI, after this study 95% of clinicians were willing to use the platform in their clinical workflow. This study showed the platform interface was acceptable and usable for clinicians actively working in ophthalmic emergency triage.
Using spectral and temporal filters with EEG signal to predict the temporal lobe epilepsy outcome after antiseizure medication via machine learning
Authors: Shin Youmin , Hwang Sungeun , Lee Seung-Bo , Son Hyoshin , Chu Kon , Jung Ki-Young , Lee Sang Kun , Park Kyung-Il , Kim Young-Gon
Published: December 2023

Epilepsy is a neurological disorder in which the brain is transiently altered.Predicting outcomes in epilepsy is essential for providing feedback that can foster improved outcomes in the future. This study aimed to investigate whether applying spectral and temporal filters to resting-state electroencephalography (EEG) signals could improve the prediction of outcomes for patients taking antiseizure medication to treat temporal lobe epilepsy (TLE). We collected EEG data from a total of 46 patients (divided into a seizure-free group (SF, n = 22) and a non-seizure-free group (NSF, n = 24)) with TLE and retrospectively reviewed their clinical data. We segmented spectral and temporal ranges with various time-domain features (Hjorth parameters, statistical parameters, energy, zero-crossing rate, inter-channel correlation, inter-channel phase locking value and spectral information derived from Fourier transform, Stockwell transform, and wavelet transform) and compared their performance by applying an optimal frequency strategy, an optimal duration strategy, and a combination strategy. For all time-domain features, the optimal frequency and time combination strategy showed the highest performance in distinguishing SF patients from NSF patients (area under the curve (AUC) = 0.790 ± 0.159). Furthermore, optimal performance was achieved by utilizing a feature vector derived from statistical parameters within the 39- to 41-Hz frequency band with a window length of 210 s, as evidenced by an AUC of 0.748. By identifying the optimal parameters, we improved the performance of the prediction model. These parameters can serve as standard parameters for predicting outcomes based on resting-state EEG signals.
Reduced electron/hole recombination in Z-scheme nanostructure of zeolitic imidazolate framework-11/graphitic carbon nitride as photocatalyst under visible light
Authors: YarAhmadi Goli , Keramati Narjes
Published: December 2023

In this research, for the first time, the synthesis of nanostructure of zeolitic imidazolate framework-11/graphitic carbon nitride (ZIF-11/g-C3N4X) with different weight of g-C3N4(X: 0.01, 0.1, 0.3 g) is reported. Their performance was compared in photocatalytic degradation of MB under visible light. Synthetic samples were characterized by X-Ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), X-ray photoelectron spectrometer (XPS), diffused reflectance spectroscopy (DRS), Field emission scanning electron microscopy (FE-SEM), Transmission electron microscope (TEM), Brunauer–Emmett–Teller (BET), Electrochemical Impedance Spectroscopy (EIS) and Photoluminescence (PL) analysis. Based on the results, Z-scheme ZIF-11/g-C3N40.3 was selected as the best sample. FESEM and TEM images indicated that g-C3N4sheets were complicated on the surface of ZIF-11 with rhombic dodecahedron (RHO) morphology. The surface area and band gap of ZIF-11/g-C3N40.3 was determined as 174.5 m2/g and 2.58 eV, respectively. The recombination of charge carriers in the ZIF-11/g-C3N40.3 nanostructure was reduced. Photocatalytic degradation efficiency of MB (5 ppm), pH = 7, visible irradiation (120 W-60 min) using 0.1 g of ZIF-11/g-C3N40.3 was achieved 72.7% with first-order kinetic model and acceptable stability in three consecutive cycles. Further, the total organic carbon (TOC) removal rate by ZIF-11/g-C3N40.3 after 5 h were 66.5%.
Smart retail SKUs checkout using improved residual network
Authors: Wang Chunchieh , Huang Chengwei , Zhu Xiaoming , Li Zhi , Zhao Liye
Published: December 2023

Intelligent signal processing in unmanned stores enhances operational efficiency, notably through automated SKUs (Stock Keeping Units) recognition, which expedites customer checkout. Distinguishing itself from generic detection algorithms, the retail product detection algorithm addresses challenges like densely arranged items, varying scales, large quantities, and product similarities. To mitigate these challenges, firstly we propose a novel boundary regression neural network architecture, which enhances the detection of bounding box in dense arrangement, minimizing computational costs and parameter sizes. Secondly, we propose a novel loss function for hierarchical detection, addressing imbalances in positive and negative samples. Thirdly, we enhance the conventional non-maximum suppression (NMS) with weighted non-maximum suppression (WNMS), tying NMS ranking scores to candidate box accuracy. Experimental results on SKU-110K and RPC datasets, two public available databases, show that the proposed SKUs recognition algorithm provides improved reliablity and efficiency over existing methods.
Transcriptomic study reveals changes of lncRNAs in PBMCs from HIV-1 patients before and after ART
Authors: Zhou Yingying , Huang Yuqing , Chen Xiaoping , Chen Tielong , Hu Wenjia , Hou Wei , Zhang Qi , Xiong Yong
Published: December 2023

Long noncoding RNAs (lncRNAs) play important roles in regulating HIV-1 infection and virus-host interactions. However, it is unclear whether and how ART alters lncRNAs in HIV-infected patients. In the present study, we investigated changes of lncRNAs in PBMCs from HIV-1 patients pre- and post-ART. We identified a total of 974 lncRNAs whose expression was restored to normal levels after ART. Cis-acting analysis showed that six lncRNAs have cis-regulated target genes, among which RP11-290F5.1 and interferon regulatory factor 2 (IRF2) were reported to promote HIV replication. Furthermore, we found that lncRNA CTB-119C2.1, which regulates most mRNAs with differential expression in PBMCs from HIV-1 infected patients after ART, was significantly upregulated by RNA-seq and qRT-PCR assays. KEGG analysis of CTB-119C2.1-associated genes revealed that most of the genes are involved in the p53 signaling pathway and pathways related to cell cycle and DNA replication. Our findings thus reveal the dynamic change of lncRNAs in people living with HIV-1 pre- and post-ART and warrant further investigation of the role of lncRNAs in HIV-1 pathogenesis and treatment.
Influence of UV nail lamps radiation on human keratinocytes viability
Authors: Słabicka-Jakubczyk Anna , Lewandowski Miłosz , Pastuszak Paulina , Barańska-Rybak Wioletta , Górska-Ponikowska Magdalena
Published: December 2023

Ultraviolet nail lamps are becoming increasingly popular, however, the safety of their use remains controversial. The following article directly responds to recently published literature data and aims to determine the viability of human keratinocytes irradiated by a UV nail-drying machine. Cells were exposed to 365–405 nm wavelength UV light emitted by a nail drying machine in two time variants: 4 and 20 min, with and without sunscreen cream SPF50 protection, and compared to the untreated control. Compared to the control, cell viability after irradiation for 4 min decreased insignificantly (p < 0.1), however for 20 min decreased by 35% (p < 0.0001). Furthermore, cells with sunscreen protection compared to those without showed significantly increased viability, regardless of time-variant (p < 0.0001). The study shows that 4-min irradiation does not significantly reduce the viability of human keratinocytes and the time of 20 min significantly alters the research results compared to 4 min, which corresponds to real conditions. The results suggest that typical manicure exposure time does not significantly affect keratinocyte viability, which could increase the risk of developing skin cancers. Despite the above results, it is recommended to use sunscreen protection on your hands during the procedure, which significantly increases the viability of keratinocytes during ultraviolet nail lamp radiation.
Investigation of spin wave dynamics in Au/CoFeB/Au multilayers with perpendicular magnetic anisotropy
Authors: Janardhanan S. , Mielcarek S. , Głowiński H. , Kowacz M. , Kuświk P. , Krawczyk M. , Trzaskowska A.
Published: December 2023

We have carried out an experimental investigation of the spin-wave dynamics in the Au/CoFeB/Au multilayer consisting of a ferromagnetic film with thicknesses of 0.8, 0.9 and 1.0 nm. We employed the Brillouin light scattering spectroscopy to measure the frequency of the spin waves in dependence on the wave vector. Additionally, we characterized the samples by ferromagnetic resonance measurements. We found that the considered samples exhibit perpendicular magnetic anisotropy with low damping, indicating small pumping effects. Furthermore, we found a nonreciprocal dispersion relation pointing at a non-negligible Dzyaloshinskii–Moriya interaction. These results make the Au/CoFeB/Au multilayer a compelling subject for further analysis and as a potential material for future applications within magnonics.
Selection and prediction of metro station sites based on spatial data and random forest: a study of Lanzhou, China
Authors: Niu Quanfu , Wang Gang , Liu Bo , Zhang Ruizhen , Lei Jiaojiao , Wang Hao , Liu Mingzhi
Published: December 2023

Urban economic development, congestion relief, and traffic efficiency are all greatly impacted by the thoughtful planning of urban metro station layout. with the urban area of Lanzhou as an example, the suitability of the station locations of the built metro stations of the rail transit lines 1 and 2 in the study area have been evaluated using multi-source heterogeneous spatial data through data collection, feature matrix construction, the use of random forest and K-fold cross-validation, among other methods. The average Gini reduction value was used to examine the contribution rate of each feature indicator based on the examination of model truthfulness. According to the study's findings: (1) K-fold cross-validation was applied to test the random forest model that was built using the built metro stations and particular factors. The average accuracy of the tests and out-of-bag data (OOB) of tenfold cross-validation were 89.62% and 91.285%, respectively. Additionally, the AUC area under the ROC curve was 0.9823, indicating that this time, from the perspective of the natural environment, traffic location, and social factors The 19 elements selected from the views of the urban function structure, social economics, and natural environment are closely associated to the locations of the metro station in the research region, and the prediction the findings are more reliable; (2) It becomes apparent that more than half of the built station sites display excellent agreement with the predicted sites in terms of geographical location by superimposing the built metro station sites with the prediction results and tally up their cumulative prediction probability values within the 300 m buffering zone; (3) Based on the contribution rate of each indicator to the model, transport facilities, companies, population density, night lighting, science, education and culture, residential communities, and road network density are identified as the primary influential factors, each accounting for over 6.6%. Subsequently, land use, elevation, and slope are found to have relatively lower contributions. The results of the research provided important information for the local metro's best location selection and planning.
Adult attention-deficit/hyperactivity disorder traits in healthy adults associated with brain volumetric data identify precuneus involvement in traffic crashes
Authors: Putra Handityo Aulia , Park Kaechang , Oba Hikaru , Yamashita Fumio
Published: December 2023

This large-scale study including 2548 healthy adults with no clinical attention-deficit/hyperactivity disorder (ADHD) diagnosis intended to clarify the complex relationships between cerebral grey matter volumes (GMVs), ADHD traits, and driving safety behaviours. Path analysis of magnetic resonance imaging (MRI) results and questionnaires about ADHD traits and traffic crashes over the past decade revealed significant correlations of ADHD traits with different brain regions relevant to different cognitive functions. The left precuneus responsible for visuospatial cognition was the sole region correlated with all ADHD trait categories, suggesting it plays an important role in understanding driving safety and traffic crashes. For the first time, a strong relationship was found among regional GMVs, ADHD traits, and real-life traffic crashes. These insights into the complex interplay may inform the development of an effective intervention with MRI examination to prevent traffic crashes. Large-scale brain volumetric data may further open social applications of behaviour science and neuroimaging.
An observational study on salivary conductivity for fluid status assessment and clinical relevance in acute ischemic stroke during intravenous fluid hydration
Authors: Chen Chun-Hao , Lee An-Ting , Yang Jen-Tsung , Tsai Yuan-Hsiung , Lin Leng-Chieh , Huang Yen-Chu
Published: December 2023

The body fluid status in acute stroke is a crucial determinant in early stroke recovery but a real-time method to monitor body fluid status is not available. This study aims to evaluate the relationship between salivary conductivity and body fluid status during the period of intravenous fluid hydration. Between June 2020 to August 2022, patients presenting with clinical signs of stroke at the emergency department were enrolled. Salivary conductivities were measured before and 3 h after intravenous hydration. Patients were considered responsive if their salivary conductivities at 3 h decreased by more than 20% compared to their baseline values. Stroke severity was assessed using the National Institutes of Health Stroke Scale, and early neurological improvement was defined as a decrease of ≥ 2 points within 72 h of admission. Among 108 recruited patients, there were 35 of stroke mimics, 6 of transient ischemic attack and 67 of acute ischemic stroke. Salivary conductivity was significantly decreased after hydration in all patients (9008 versus 8118 µs/cm, p = 0.030). Among patients with acute ischemic stroke, the responsive group, showed a higher rate of early neurological improvement within 3 days compared to the non-responsive group (37% versus 10%, p = 0.009). In a multivariate logistic regression model, a decrease in salivary conductivity of 20% or more was found to be an independent factor associated with early neurological improvement (odds ratio 5.42, 95% confidence interval 1.31–22.5, p = 0.020). Real-time salivary conductivity might be a potential indicator of hydration status of the patient with acute ischemic stroke.
Prevalence of tuberculosis infection among patients with Takayasu arteritis: a meta-analysis of observational studies
Authors: Li Liping , Zhou Fang , Li Fen , Chen Jinwei , Xie Xi
Published: December 2023

To clarify the risk of tuberculosis (TB) infection in patients with Takayasu arteritis (TAK). In this study, we conducted a comprehensive search across multiple databases, including PubMed, Web of Science, Embase, Cochrane, and Medline, from the inception of the Literature Library to May 16, 2023. Using a specific set of keywords, including “Takayasu Arteritis”, “Tuberculosis”, and “Mycobacterium tuberculosis”, the main objective of this search was to identify all relevant observational studies, including case-control studies, cohort studies, and cross-sectional studies, that report the prevalence of TB in individuals diagnosed with TAK. Two independent evaluators rigorously screened the studies, extracted data, and assessed the study quality using the Joanna Briggs Institute (JBI) critical appraisal tools. Statistical analyses were conducted using R software version 4.3.0, which allowed for the synthesis of prevalence and subgroup analyses. Subgroup analyses were stratified based on quality scores, World Health Organization regional categorizations, and TB categories. Assessment of publication bias was performed using a funnel plot. The study included a total of 30 studies with 5548 participants. The findings showed that individuals with TAK exhibited an average prevalence of TB infection at 31.27% (95% CI 20.48–43.11%). Significantly, the prevalence of TB infection demonstrated notable regional disparities, ranging from 16.93% (95% CI 7.71–28.76%) in the Western Pacific Region to 63.58% (95% CI 35.70–87.66%) in the African Region. Moreover, the study revealed that patients with TAK displayed a high prevalence of latent TB infection (LTBI) at 50.01% (95% CI 31.25–68.77%) and active TB at 14.40% (95% CI 9.03–20.68%). The high heterogeneity observed in the data highlights significant variability in TB infection rates among the populations studied, with the African Region exhibiting the highest rates. The study concludes that there is a high prevalence of TB infection in the TAK population, with regional variations. Consideration should be given to  implementing rigorous TB screening measures and preventive interventions specifically tailored for the TAK population.
Longitudinal analysis of refraction and ocular biometrics in preschool children with early-onset high myopia
Authors: Yum Hae Ri , Park Shin Hae , Shin Sun Young
Published: December 2023

We investigated changes in refraction and ocular biometrics in preschool children with early-onset high myopia. Sixty eyes of 60 children with a mean follow-up time of 58.5 months were included in this study. At baseline, mean age of children was 55.6 ± 13.1 months, mean spherical equivalent (SE) was − 8.59 ± 2.66 D, and 25.64 ± 1.16 mm for axial length (AL). The total annual rate of myopic progression and axial elongation were − 0.37 ± 0.39 D/year and 0.33 ± 0.18 mm/year, respectively. During follow-up period, there was a trend toward less myopic progression and axial elongation over time. Of the total participants, 24 children (40%) were in the myopia progression group and the remaining 36 children (60%) were in the myopia stability group. In multiple linear regression analysis, baseline SE and AL were independently associated with myopic progression, while age, sex, and baseline AL-to-CR ratio were not related to myopic progression. According to the model, more myopic SE (β = − 0.186, P = 0.035) and longer AL (β = − 0.391, P = 0.008) at baseline were significantly associated with myopic progression. Myopia progression in preschoolers with high myopia tended to be relatively modest, with 60% of subjects exhibited myopic stability. Higher myopic SE, and longer AL at baseline were associated with myopic progression in preschool children with high myopia.
Impacts of tropical cyclones on the global water budget
Authors: Pérez-Alarcón Albenis , Coll-Hidalgo Patricia , Fernández-Alvarez José C. , Trigo Ricardo M. , Nieto Raquel , Gimeno Luis
Published: December 2023

Tropical cyclones (TCs) require substantial amounts of moisture for their genesis and development, acting as important moisture drivers from the ocean to land and from tropical to subtropical and extratropical regions. Quantifying anomalous moisture transport related to TCs is crucial for understanding long-term TC-induced changes in the global hydrological cycle. Our results highlight that, in terms of the global water budget, TCs enhance moisture transport from evaporative regions and precipitation over sink regions, leading to predominantly anomalous positive surface freshwater flux areas over the tropics and more regionally concentrated negative areas over the Intertropical Convergence Zone. Furthermore, we detected seasonal variability in the impact of TC on the hydrological cycle, which is closely related to the annual and seasonal TC frequency. Our analysis also revealed a global statistically significant drop (~40 mm year−1) in TC-induced surface freshwater fluxes from 1980 to 2018 in response to the increasing sea surface temperature and slightly decrease in global TC frequency and lifetime in the last two decades. These findings have important implications for predicting the impacts of TCs on the hydrological cycle under global warming conditions.
Structural and biochemical investigations of a HEAT-repeat protein involved in the cytosolic iron-sulfur cluster assembly pathway
Authors: Vasquez Sheena , Marquez Melissa D. , Brignole Edward J. , Vo Amanda , Kong Sunnie , Park Christopher , Perlstein Deborah L. , Drennan Catherine L.
Published: December 2023

Iron-sulfur clusters are essential for life and defects in their biosynthesis lead to human diseases. The mechanism of cluster assembly and delivery to cytosolic and nuclear client proteins via the cytosolic iron-sulfur cluster assembly (CIA) pathway is not well understood. Here we report cryo-EM structures of the HEAT-repeat protein Met18 fromSaccharomyces cerevisiae, a key component of the CIA targeting complex (CTC) that identifies cytosolic and nuclear client proteins and delivers a mature iron-sulfur cluster. We find that in the absence of other CTC proteins, Met18 adopts tetrameric and hexameric states. Using mass photometry and negative stain EM, we show that upon the addition of Cia2, these higher order oligomeric states of Met18 disassemble. We also use pulldown assays to identify residues of critical importance for Cia2 binding and recognition of the Leu1 client, many of which are buried when Met18 oligomerizes. Our structures show conformations of Met18 that have not been previously observed in any Met18 homolog, lending support to the idea that a highly flexible Met18 may be key to how the CTC is able to deliver iron-sulfur clusters to client proteins of various sizes and shapes, i.e. Met18 conforms to the dimensions needed.
Unravelling key enzymatic steps in C-ring cleavage during angucycline biosynthesis
Authors: Elsayed Somayah S. , van der Heul Helga U. , Xiao Xiansha , Nuutila Aleksi , Baars Laura R. , Wu Changsheng , Metsä-Ketelä Mikko , van Wezel Gilles P.
Published: December 2023

Angucyclines are type II polyketide natural products, often characterized by unusual structural rearrangements through B- or C-ring cleavage of their tetracyclic backbone. While the enzymes involved in B-ring cleavage have been extensively studied, little is known of the enzymes leading to C-ring cleavage. Here, we unravel the function of the oxygenases involved in the biosynthesis of lugdunomycin, a highly rearranged C-ring cleaved angucycline derivative. Targeted deletion of the oxygenase genes, in combination with molecular networking and structural elucidation, showed that LugOI is essential for C12 oxidation and maintaining a keto group at C6 that is reduced by LugOII, resulting in a key intermediate towards C-ring cleavage. An epoxide group is then inserted by LugOIII, and stabilized by the novel enzyme LugOV for the subsequent cleavage. Thus, for the first time we describe the oxidative enzymatic steps that form the basis for a wide range of rearranged angucycline natural products.
Low effective ultraviolet exposure ages for organics at the surface of Enceladus
Authors: Hendrix Amanda R. , House Christopher H.
Published: December 2023

The saturnian moon Enceladus presents a remarkable opportunity in our solar system for searching for evidence of life, given its habitable ocean and plume that deposits organic-bearing ocean material onto the surface. Organic ocean material could be sampled by a lander mission at Enceladus. It is of interest to understand the amount of relatively pristine, unaltered organics present on the surface, given the ultraviolet (UV) and plasma environment. Here, we investigate UV penetration into Enceladus’s surface and the resultant effective exposure ages for various regions, using the UV reflectance spectrum of Enceladus as measured by the Hubble Space Telescope and considering the rate of resurfacing by plume fallout. In high plume fallout regions near the south pole, plume grains are buried by fresher grains within years, resulting in low levels of exposure to solar UV, which penetrates only ~100 micrometers. Regions at latitudes south of ~40°S can have exposure ages <100 years, translating to relatively high abundances of pristine organic material preserved in the regolith.
Morphological Responses as a New Tool to Evaluate the Effects of Agrochemicals and Other Emerging Contaminants in Neotropical Frogs
Authors: Franco-Belussi Lilian , Valverde Bruno S. L. , Bach Nadia C. , Pérez-Iglesias Juan M. , de Oliveira Classius , Canevari Gabriel C. , Fernandes Carlos E.
Published: December 2023

Morphological and histological traits are good biomarkers of intermediate responses of organisms to contaminants because they integrate both biochemical and physiological responses. Morphological biomarkers describe changes and abnormalities from subcellular and cellular up to individual levels. Morphological changes in organs and tissues can be defensive or compensatory to maintain tissue and organ functions against degenerative changes. In this chapter, we present new morphological tools used in both field work and laboratory experiments to evaluate the effects of contaminants on frogs. We also provide detailed tool descriptions that include characteristics of tissue morphometric techniques, cell density and colour difference analysis. In addition, we demonstrate their applicability in different organs and tissues of Neotropical frog species.