bluuebunny/crossref_metadata_2025 huggingface dataset:
Red mark syndrome: Is the aquaculture water microbiome a keystone for understanding the disease aetiology?
Authors: Bruno Antonia , Cafiso Alessandra , Sandionigi Anna , Galimberti Andrea , Magnani Davide , Manfrin Amedeo , Petroni Giulio , Casiraghi Maurizio , Bazzocchi Chiara
Published: February 2023

Aquaculture significantly contributes to the growing demand for food worldwide. However, diseases associated with intensive aquaculture conditions, especially the skin related syndromes, may have significant implications on fish health and industry. In farmed rainbow trout, red mark syndrome (RMS), which consists of multiple skin lesions, currently lacks recognized aetiological agents, and increased efforts are needed to elucidate the onset of these conditions. Most of the past studies were focused on analyzing skin lesions, but no study focused on water, a medium constantly interacting with fish. Indeed, water tanks are environmental niches colonized by microbial communities, which may be implicated in the onset of the disease. Here, we present the results of water and sediment microbiome analyses performed in an RMS-affected aquaculture facility, bringing new knowledge about the environmental microbiomes harbored under these conditions. On the whole, no significant differences in the bacterial community structure were reported in RMS-affected tanks compared to the RMS-free ones. However, we highlighted significant differences in microbiome composition when analyzing different samples source (i.e., water and sediments). Looking at the finer scale, we measured significant changes in the relative abundances of specific taxa in RMS-affected tanks, especially when analyzing water samples. Our results provide worthwhile insight into a mostly uncharacterized ecological scenario, aiding future studies on the aquaculture built environment for disease prevention and monitoring.
Inhibitory effect and underlying mechanism of cinnamon and clove essential oils on Botryosphaeria dothidea and Colletotrichum gloeosporioides causing rots in postharvest bagging-free apple fruits
Authors: Wang Dan , Wang Guiping , Wang Jinzheng , Zhai Hao , Xue Xiaomin
Published: February 2023

Bagging-free apple is more vulnerable to postharvest disease, which severely limits the cultivation pattern transformation of the apple industry in China. This study aimed to ascertain the dominant pathogens in postharvest bagging-free apples, to evaluate the efficacy of essential oil (EO) on inhibition of fungal growth, and to further clarify the molecular mechanism of this action. By morphological characteristics and rDNA sequence analyses, Botryosphaeria dothidea (B. dothidea) and Colletotrichum gloeosporioides (C. gloeosporioides) were identified as the main pathogens isolated from decayed bagging-free apples. Cinnamon and clove EO exhibited high inhibitory activities against mycelial growth both in vapor and contact phases under in vitro conditions. EO vapor at a concentration of 60 μL L−1 significantly reduced the incidence and lesion diameter of inoculated decay in vivo. Observations using a scanning electron microscope (SEM) and transmission electron microscope (TEM) revealed that EO changed the mycelial morphology and cellular ultrastructure and destroyed the integrity and structure of cell membranes and major organelles. Using RNA sequencing and bioinformatics, it was demonstrated that clove EO treatment impaired the cell membrane integrity and biological function via downregulating the genes involved in the membrane component and transmembrane transport. Simultaneously, a stronger binding affinity of trans-cinnamaldehyde and eugenol with CYP51 was assessed by in silico analysis, attenuating the activity of this ergosterol synthesis enzyme. Moreover, pronounced alternations in the oxidation/reduction reaction and critical materials metabolism of clove EO-treated C. gloeosporioides were also observed from transcriptomic data. Altogether, these findings contributed novel antimicrobial cellular and molecular mechanisms of EO, suggesting its potential use as a natural and useful preservative for controlling postharvest spoilage in bagging-free apples.
Evaluation of the lignocellulose degradation potential of Mediterranean forests soil microbial communities through diversity and targeted functional metagenomics
Authors: Kalntremtziou Maria , Papaioannou Ioannis A. , Vangalis Vasileios , Polemis Elias , Pappas Katherine M. , Zervakis Georgios I. , Typas Milton A.
Published: February 2023

The enzymatic arsenal of several soil microorganisms renders them particularly suitable for the degradation of lignocellulose, a process of distinct ecological significance with promising biotechnological implications. In this study, we investigated the spatiotemporal diversity and distribution of bacteria and fungi with 16S and Internally Trascribed Spacer (ITS) ribosomal RNA next-generation-sequencing (NGS), focusing on forest mainland Abies cephalonica and insular Quercus ilex habitats of Greece. We analyzed samples during winter and summer periods, from different soil depths, and we applied optimized and combined targeted meta-omics approaches aiming at the peroxidase-catalase family enzymes to gain insights into the lignocellulose degradation process at the soil microbial community level. The microbial communities recorded showed distinct patterns of response to season, soil depth and vegetation type. Overall, in both forests Proteobacteria, Actinobacteria, Acidobacteria were the most abundant bacteria phyla, while the other phyla and the super-kingdom of Archaea were detected in very low numbers. Members of the orders Agaricales, Russulales, Sebacinales, Gomphales, Geastrales, Hysterangiales, Thelephorales, and Trechisporales (Basidiomycota), and Pezizales, Sordariales, Eurotiales, Pleosporales, Helotiales, and Diaporthales (Ascomycota) were the most abundant for Fungi. By using optimized “universal” PCR primers that targeted the peroxidase-catalase enzyme family, we identified several known and novel sequences from various Basidiomycota, even from taxa appearing at low abundance. The majority of the sequences recovered were manganese peroxidases from several genera of Agaricales, Hysterangiales, Gomphales, Geastrales, Russulales, Hymenochaetales, and Trechisporales, while lignin -and versatile-peroxidases were limited to two to eight species, respectively. Comparisons of the obtained sequences with publicly available data allowed a detailed structural analysis of polymorphisms and functionally relevant amino-acid residues at phylogenetic level. The targeted metagenomics applied here revealed an important role in lignocellulose degradation of hitherto understudied orders of Basidiomycota, such as the Hysterangiales and Gomphales, while it also suggested the auxiliary activity of particular members of Proteobacteria, Actinobacteria, Acidobacteria, Verrucomicrobia, and Gemmatimonadetes. The application of NGS-based metagenomics approaches allows a better understanding of the complex process of lignocellulolysis at the microbial community level as well as the identification of candidate taxa and genes for targeted functional investigations and genetic modifications.
Marine-derived fungi as biocatalysts
Authors: Virués-Segovia Jorge R. , Muñoz-Mira Salvador , Durán-Patrón Rosa , Aleu Josefina
Published: February 2023

Marine microorganisms account for over 90% of ocean biomass and their diversity is believed to be the result of their ability to adapt to extreme conditions of the marine environment. Biotransformations are used to produce a wide range of high-added value materials, and marine-derived fungi have proven to be a source of new enzymes, even for activities not previously discovered. This review focuses on biotransformations by fungi from marine environments, including bioremediation, from the standpoint of the chemical structure of the substrate, and covers up to September 2022.
Aculeaxanthones A–E, new xanthones from the marine-derived fungus Aspergillus aculeatinus WHUF0198
Authors: Wu Jun , Shui Hua , Zhang Mengke , Zeng Yida , Zheng Mingxin , Zhu Kong-Kai , Wang Shou-Bao , Bi Hongkai , Hong Kui , Cai You-Sheng
Published: February 2023

Introduction

Dimeric natural products are widespread in plants and microorganisms, which usually have complex structures and exhibit greater bioactivities than their corresponding monomers. In this study, we report five new dimeric tetrahydroxanthones, aculeaxanthones A−E (4−8), along with the homodimeric tetrahydroxanthone secalonic acid D (1), chrysoxanthones B and C (2 and 3), and 4−4’-secalonic acid D (9), from different fermentation batches of the title fungus.

Methods

A part of the culture was added to a total of 60 flasks containing 300 ml each of number II fungus liquid medium and culture 4 weeks in a static state at 28˚C. The liquid phase (18 L) and mycelia was separated from the fungal culture by filtering. A crude extract was obtained from the mycelia by ultrasound using acetone. To obtain a dry extract (18 g), the liquid phase combined with the crude extract were further extracted by EtOAc and concentrated in vacuo. The MIC of anaerobic bacteria was examined by a broth microdilution assay. To obtain MICs for aerobic bacteria, the agar dilution streak method recommended in Clinical and Laboratory Standards Institute document (CLSI) M07-A10 was used. Compounds 1−9 was tested against the Bel-7402, A-549 and HCT-116 cell lines according to MTT assay.

Results and Discussion

The structures of these compounds were elucidated on the base of 1D and 2D NMR and HR-ESIMS data, and the absolute configurations of the new xanthones 4−8 were determined by conformational analysis and time-dependent density functional theory-electronic circular dichroism (TDDFT-ECD) calculations. Compounds 1–9 were tested for cytotoxicity against the Bel-7402, A549, and HCT-116 cancer cell lines. Of the dimeric tetrahydroxanthone derivatives, only compound 6 provided cytotoxicity effect against Bel-7402 cell line (IC50, 1.96 µM). Additionally, antimicrobial activity was evaluated for all dimeric tetrahydroxanthones, including four Gram-positive bacteria including Enterococcus faecium ATCC 19434, Bacillus subtilis 168, Staphylococcus aureus ATCC 25923 and MRSA USA300; four Gram-negative bacteria, including Helicobacter pylori 129, G27, as well as 26,695, and multi drug-resistant strain H. pylori 159, and one Mycobacterium M. smegmatis ATCC 607. However, only compound 1 performed activities against H. pylori G27, H. pylori 26695, H. pylori 129, H. pylori 159, S. aureus USA300, and B. subtilis 168 with MIC values of 4.0, 4.0, 2.0, 2.0, 2.0 and 1.0 μg/mL, respectively.
Exploring the active ingredients and potential mechanisms of action of sinomenium acutum in the treatment of rheumatoid arthritis based on systems biology and network pharmacology
Authors: Gong Nan , Wang Lin , An Lili , Xu YuanKun
Published: February 2023

Objective: To investigate and predict the targets and signaling pathways of sinomenium acutum (SA) in the treatment of rheumatoid arthritis (RA) through systems biology and network pharmacology, and to elucidate its possible mechanisms of action.

Methods: We screened the active ingredients and corresponding target proteins of SA in Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Traditional Chinese Medicines Integrated Database (TCMID) and Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine (BATMAN); and obtained the targets of rheumatoid arthritis diseases in a database of gene-disease associations (DisGeNET), Online Mendelian Inheritance in Man (OMIM) database. The two targets were mapped by Venn diagram and the intersection was taken. The intersecting targets were used to construct protein-protein interaction (PPI) network maps in the String database, and Metascape was used for Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Finally, the molecular docking technique was applied to validate and further clarify the core target of SA for the treatment of rheumatoid arthritis.

Results: A total of six active ingredients and 217 potential targets were obtained after screening; 2,752 rheumatoid arthritis-related targets and 66 targets common to RA and SA. GO function and KEGG pathway enrichment analysis yielded 751 GO function entries (652 GO biological processes, 59 GO molecular functions and 40 GO cellular components) and 77 KEGG signaling pathways. It mainly involves pathways related to neural activity ligand-receptor interaction pathways, cancer pathways, calcium signaling channels, Th17 cell differentiation and others, which are mainly classified into four categories, including regulation of immunity, anti-inflammation, regulation of cell growth and apoptosis, and signaling. The molecular docking results showed that the binding energy of PTGS2, CASP3, JUN and PPARG to the key components beta-sitosterol, 16-epi-Isositsirikine, Sinomenine and Stepholidine were ≤ −6.5 kcal/mol, suggesting the existence of molecular binding sites.

Conclusion: SA acts on key targets such as PTGS2, CASP3, JUN, and PPARG to modulate signaling pathways such as neural activity ligand-receptor interaction, cancer, calcium ion, NF-κB, and Th17 cell differentiation to regulate immunity, anti-inflammation, modulation of cell cycle, bone metabolism, and signaling for the treatment of RA. It was also confirmed that the treatment of RA with SA has multi-component, multi-target, multi-pathway and multi-mechanism characteristics.
Protective effects of isoflavones on alcoholic liver diseases: Computational approaches to investigate the inhibition of ALDH2 with isoflavone analogues
Authors: Lee Wook , Kim Seung-Jin
Published: February 2023

Excessive and chronic alcohol intake can lead to the progression of alcoholic liver disease (ALD), which is a major cause of morbidity and mortality worldwide. ALD encompasses a pathophysiological spectrum such as simple steatosis, alcoholic steatohepatitis (ASH), fibrosis, alcoholic cirrhosis, and hepatocellular carcinoma (HCC). Aldehyde dehydrogenase (ALDH2) is the most vital enzyme that produces acetate from acetaldehyde and is expressed at high levels in the liver, kidneys, muscles, and heart. The ALDH2*2 allele is found in up to 40% of East Asian populations, and has a significant impact on alcohol metabolism. Interestingly, several studies have shown that individuals with ALDH2 deficiency are more susceptible to liver inflammation after drinking alcohol. Furthermore, there is growing evidence of an association between ALDH2 deficiency and the development of cancers in the liver, stomach, colon, and lung. Isoflavone analogues are low molecular-weight compounds derived from plants, similar in structure and activity to estrogen in mammals, known as phytoestrogens. Recent studies have reported that isoflavone analogues have beneficial effects on the progression of ALD. This mini-review summarizes the current knowledge about the roles of isoflavone analogues in ALD and discusses the therapeutic potential of isoflavone analogues in liver pathophysiology. In particular, we highlight the significance of computational approaches in this field.
Revitalizing an important field in biophysics: The new frontiers of molecular crowding
Authors: Cammarata Marco , Piazza Francesco , Rivas Germán , Schirò Giorgio , Temussi Piero Andrea , Pastore Annalisa
Published: February 2023

Taking into account the presence of the crowded environment of a macromolecule has been an important goal of biology over the past 20 years. Molecular crowding affects the motions, stability and the kinetic behaviour of proteins. New powerful approaches have recently been developed to study molecular crowding, some of which make use of the synchrotron radiation light. The meeting “New Frontiers in Molecular Crowding” was organized in July 2022at the European Synchrotron Radiation facility of Grenoble to discuss the new frontiers of molecular crowding. The workshop brought together researchers from different disciplines to highlight the new developments of the field, including areas where new techniques allow the scientists to gain unprecedently expected information. A key conclusion of the meeting was the need to build an international and interdisciplinary research community through enhanced communication, resource-sharing, and educational initiatives that could let the molecular crowding field flourish further.
Sleep staging in the ICU with heart rate variability and breathing signals. An exploratory cross-sectional study using deep neural networks
Authors: Ganglberger Wolfgang , Krishnamurthy Parimala Velpula , Quadri Syed A. , Tesh Ryan A. , Bucklin Abigail A. , Adra Noor , Da Silva Cardoso Madalena , Leone Michael J. , Hemmige Aashritha , Rajan Subapriya , Panneerselvam Ezhil , Paixao Luis , Higgins Jasmine , Ayub Muhammad Abubakar , Shao Yu-Ping , Coughlin Brian , Sun Haoqi , Ye Elissa M. , Cash Sydney S. , Thompson B. Taylor , Akeju Oluwaseun , Kuller David , Thomas Robert J. , Westover M. Brandon
Published: February 2023

Introduction: To measure sleep in the intensive care unit (ICU), full polysomnography is impractical, while activity monitoring and subjective assessments are severely confounded. However, sleep is an intensely networked state, and reflected in numerous signals. Here, we explore the feasibility of estimating conventional sleep indices in the ICU with heart rate variability (HRV) and respiration signals using artificial intelligence methods

Methods: We used deep learning models to stage sleep with HRV (through electrocardiogram) and respiratory effort (through a wearable belt) signals in critically ill adult patients admitted to surgical and medical ICUs, and in age and sex-matched sleep laboratory patients

Results: We studied 102 adult patients in the ICU across multiple days and nights, and 220 patients in a clinical sleep laboratory. We found that sleep stages predicted by HRV- and breathing-based models showed agreement in 60% of the ICU data and in 81% of the sleep laboratory data. In the ICU, deep NREM (N2 + N3) proportion of total sleep duration was reduced (ICU 39%, sleep laboratory 57%, p < 0.01), REM proportion showed heavy-tailed distribution, and the number of wake transitions per hour of sleep (median 3.6) was comparable to sleep laboratory patients with sleep-disordered breathing (median 3.9). Sleep in the ICU was also fragmented, with 38% of sleep occurring during daytime hours. Finally, patients in the ICU showed faster and less variable breathing patterns compared to sleep laboratory patients

Conclusion: The cardiovascular and respiratory networks encode sleep state information, which, together with artificial intelligence methods, can be utilized to measure sleep state in the ICU
The role of the gut-microbiome-brain axis in metabolic remodeling amongst children with cerebral palsy and epilepsy
Authors: Peng Ye , Chiu Annie T. G. , Li Vivien W. Y. , Zhang Xi , Yeung Wai L. , Chan Sophelia H. S. , Tun Hein M.
Published: February 2023

Background

Epilepsy-associated dysbiosis in gut microbiota has been previously described, but the mechanistic roles of the gut microbiome in epileptogenesis among children with cerebral palsy (CP) have yet to be illustrated.

Methods

Using shotgun metagenomic sequencing coupled with untargeted metabolomics analysis, this observational study compared the gut microbiome and metabolome of eight children with non-epileptic cerebral palsy (NECP) to those of 13 children with cerebral palsy with epilepsy (CPE). Among children with CPE, 8 had drug-sensitive epilepsy (DSE) and five had drug-resistant epilepsy (DRE). Characteristics at enrollment, medication history, and 7-day dietary intake were compared between groups.

Results

At the species level, CPE subjects had significantly lower abundances of Bacteroides fragilis and Dialister invisus but higher abundances of Phascolarctobacterium faecium and Eubacterium limosum. By contrast, DRE subjects had a significantly higher colonization of Veillonella parvula. Regarding microbial functional pathways, CPE subjects had decreased abundances of pathways for serine degradation, quinolinic acid degradation, glutamate degradation I, glycerol degradation, sulfate reduction, and nitrate reduction but increased abundances of pathways related to ethanol production. As for metabolites, CPE subjects had higher concentrations of kynurenic acid, 2-oxindole, dopamine, 2-hydroxyphenyalanine, 3,4–dihydroxyphenylglycol, L-tartaric acid, and D-saccharic acid; DRE subjects had increased concentrations of indole and homovanilic acid.

Conclusions

In this study, we found evidence of gut dysbiosis amongst children with cerebral palsy and epilepsy in terms of gut microbiota species, functional pathways, and metabolites. The combined metagenomic and metabolomic analyses have shed insights on the potential roles of B. fragilis and D. invisus in neuroprotection. The combined analyses have also provided evidence for the involvement of GMBA in the epilepsy-related dysbiosis of kynurenine, serotonin, and dopamine pathways and their complex interplay with neuroimmune and neuroendocrinological pathways.
Sleep matters: Neurodegeneration spectrum heterogeneity, combustion and friction ultrafine particles, industrial nanoparticle pollution, and sleep disorders—Denial is not an option
Authors: Calderón-Garcidueñas Lilian , Torres-Jardón Ricardo , Greenough Glen P. , Kulesza Randy , González-Maciel Angélica , Reynoso-Robles Rafael , García-Alonso Griselda , Chávez-Franco Diana A. , García-Rojas Edgar , Brito-Aguilar Rafael , Silva-Pereyra Héctor G. , Ayala Alberto , Stommel Elijah W. , Mukherjee Partha S.
Published: February 2023

Sustained exposures to ubiquitous outdoor/indoor fine particulate matter (PM2.5), including combustion and friction ultrafine PM (UFPM) and industrial nanoparticles (NPs) starting in utero, are linked to early pediatric and young adulthood aberrant neural protein accumulation, including hyperphosphorylated tau (p-tau), beta-amyloid (Aβ1 − 42), α-synuclein (α syn) and TAR DNA-binding protein 43 (TDP-43), hallmarks of Alzheimer's (AD), Parkinson's disease (PD), frontotemporal lobar degeneration (FTLD), and amyotrophic lateral sclerosis (ALS). UFPM from anthropogenic and natural sources and NPs enter the brain through the nasal/olfactory pathway, lung, gastrointestinal (GI) tract, skin, and placental barriers. On a global scale, the most important sources of outdoor UFPM are motor traffic emissions. This study focuses on the neuropathology heterogeneity and overlap of AD, PD, FTLD, and ALS in older adults, their similarities with the neuropathology of young, highly exposed urbanites, and their strong link with sleep disorders. Critical information includes how this UFPM and NPs cross all biological barriers, interact with brain soluble proteins and key organelles, and result in the oxidative, endoplasmic reticulum, and mitochondrial stress, neuroinflammation, DNA damage, protein aggregation and misfolding, and faulty complex protein quality control. The brain toxicity of UFPM and NPs makes them powerful candidates for early development and progression of fatal common neurodegenerative diseases, all having sleep disturbances. A detailed residential history, proximity to high-traffic roads, occupational histories, exposures to high-emission sources (i.e., factories, burning pits, forest fires, and airports), indoor PM sources (tobacco, wood burning in winter, cooking fumes, and microplastics in house dust), and consumption of industrial NPs, along with neurocognitive and neuropsychiatric histories, are critical. Environmental pollution is a ubiquitous, early, and cumulative risk factor for neurodegeneration and sleep disorders. Prevention of deadly neurological diseases associated with air pollution should be a public health priority.
Interdisciplinary views of fNIRS: Current advancements, equity challenges, and an agenda for future needs of a diverse fNIRS research community
Authors: Doherty Emily J. , Spencer Cara A. , Burnison Jeremy , Čeko Marta , Chin Jenna , Eloy Lucca , Haring Kerstin , Kim Pilyoung , Pittman Daniel , Powers Shannon , Pugh Samuel L. , Roumis Demetris , Stephens Jaclyn A. , Yeh Tom , Hirshfield Leanne
Published: February 2023

Functional Near-Infrared Spectroscopy (fNIRS) is an innovative and promising neuroimaging modality for studying brain activity in real-world environments. While fNIRS has seen rapid advancements in hardware, software, and research applications since its emergence nearly 30 years ago, limitations still exist regarding all three areas, where existing practices contribute to greater bias within the neuroscience research community. We spotlight fNIRS through the lens of different end-application users, including the unique perspective of a fNIRS manufacturer, and report the challenges of using this technology across several research disciplines and populations. Through the review of different research domains where fNIRS is utilized, we identify and address the presence of bias, specifically due to the restraints of current fNIRS technology, limited diversity among sample populations, and the societal prejudice that infiltrates today's research. Finally, we provide resources for minimizing bias in neuroscience research and an application agenda for the future use of fNIRS that is equitable, diverse, and inclusive.
Cell therapy for neuropathic pain
Authors: Yin QingHua , Zou TianHao , Sun ShuJun , Yang Dong
Published: February 2023

Neuropathic pain (NP) is caused by a lesion or a condition that affects the somatosensory system. Pathophysiologically, NP can be ascribed to peripheral and central sensitization, implicating a wide range of molecular pathways. Current pharmacological and non-pharmacological approaches are not very efficacious, with over half of NP patients failing to attain adequate pain relief. So far, pharmacological and surgical treatments have focused primarily on symptomatic relief by modulating pain transduction and transmission, without treating the underlying pathophysiology. Currently, researchers are trying to use cell therapy as a therapeutic alternative for the treatment of NP. In fact, mounting pre-clinical and clinical studies showed that the cell transplantation-based therapy for NP yielded some encouraging results. In this review, we summarized the use of cell grafts for the treatment of NP caused by nerve injury, synthesized the latest advances and adverse effects, discussed the possible mechanisms to inform pain physicians and neurologists who are endeavoring to develop cell transplant-based therapies for NP and put them into clinical practice.
PET tracers in glioblastoma: Toward neurotheranostics as an individualized medicine approach
Authors: Dadgar Habibullah , Jokar Narges , Nemati Reza , Larvie Mykol , Assadi Majid
Published: February 2023

Over the past decade, theragnostic radiopharmaceuticals have been used in nuclear medicine for both diagnosis and treatment of various tumors. In this review, we carried out a literature search to investigate and explain the role of radiotracers in the theragnostic approach to glioblastoma multiform (GBM). We primarily focused on basic and rather common positron emotion tomography (PET) radiotracers in these tumors. Subsequently, we introduced and evaluated the preclinical and clinical results of theranostic-based biomarkers including integrin receptor family, prostate-specific membrane antigen (PSMA), fibroblast activated protein (FAP), somatostatin receptors (SRS), and chemokine receptor-4 (CXCR4) for patients with GBM to confer the benefit of personalized therapy. Moreover, promising research opportunities that could have a profound impact on the treatment of GBM over the next decade are also highlighted. Preliminary results showed the potential feasibility of the theragnostic approach using theses biomarkers in GBM patients.
Radiomics insight into the neurodegenerative “hot” brain: A narrative review from the nuclear medicine perspective
Authors: Aghakhanyan Gayane , Di Salle Gianfranco , Fanni Salvatore Claudio , Francischello Roberto , Cioni Dania , Cosottini Mirco , Volterrani Duccio , Neri Emanuele
Published: February 2023

The application of radiomics for non-oncologic diseases is currently emerging. Despite its relative infancy state, the evidence highlights the potential of radiomics approaches to serve as neuroimaging biomarkers in the field of the neurodegenerative brain. This systematic review presents the last progress and potential application of radiomics in the field of neurodegenerative nuclear imaging applied to positron-emission tomography (PET) and single-photon emission computed tomography (SPECT) by focusing mainly on the two most common neurodegenerative disorders, Alzheimer's (AD) and Parkinson's disease (PD). A comprehensive review of the current literature was performed using the PubMed and Web of Science databases up to November 2022. The final collection of eighteen relevant publications was grouped as AD-related and PD-related. The main efforts in the field of AD dealt with radiomics-based early diagnosis of preclinical AD and the prediction of MCI to AD conversion, meanwhile, in the setting of PD, the radiomics techniques have been used in the attempt to improve the assessment of PD diagnosis, the differential diagnosis between PD and other parkinsonism, severity assessment, and outcome prediction. Although limited evidence with relatively small cohort studies, it seems that radiomics-based analysis using nuclear medicine tools, mainly [18F]Fluorodeoxyglucose (FDG) and β-amyloid (Aβ) PET, and dopamine transporter (DAT) SPECT, can be used for computer-aided diagnoses in AD-continuum and parkinsonian disorders. Combining nuclear radiomics analysis with clinical factors and introducing a multimodality approach can significantly improve classification and prediction efficiency in neurodegenerative disorders.
The comparison of manual and mechanical anastomosis after total pharyngolaryngoesophagectomy
Authors: Wang Kexi , He Xiaotian , Wu Duoguang , Wang Kefeng , Li Yuquan , Wang Wenjian , Hu Xueting , Lei Kai , Tan Binghua , Liang Ruihao , Cai Qian , Wang Minghui
Published: February 2023

Background

Total pharyngolaryngoesophagectomy (TPLE) is considered as a curative treatment for hypopharynx cancer and cervical esophageal carcinomas (HPCECs). Traditional pharyngo-gastric anastomosis is usually performed manually, and postoperative complications are common. The aim of this study was to introduce a new technique for mechanical anastomosis and to evaluate perioperative outcomes and prognosis.

Methods

From May 1995 to Nov 2021, a series of 75 consecutive patients who received TPLE for a pathological diagnosis of HPCECs at Sun Yat-sen Memorial Hospital were evaluated. Mechanical anastomosis was performed in 28 cases and manual anastomosis was performed in 47 cases. The data from these patients were retrospectively analyzed.

Results

The mean age was 57.6 years, and 20% of the patients were female. The rate of anastomotic fistula and wound infection in the mechanical group were significantly lower than that in the manual group. The operation time, intraoperative blood loss and postoperative hospital stays were significantly higher in the manual group than that in the mechanical group. The R0 resection rate and the tumor characteristics were not significantly different between groups. There was no significant difference in overall survival and disease-free survival between the two groups.

Conclusion

The mechanical anastomosis technology adopted by this study was shown to be a safer and more effective procedure with similar survival comparable to that of manual anastomosis for the HPCECs patients.
The gene regulatory molecule GLIS3 in gastric cancer as a prognostic marker and be involved in the immune infiltration mechanism
Authors: Ding Yi , Wang Zehua , Chen Chen , Wang Chenxu , Li Dongyu , Qin Yanru
Published: February 2023

Background

Gastric cancer is the most prevalent solid tumor form. Even after standard treatment, recurrence and malignant progression are nearly unavoidable in some cases of stomach cancer. GLIS Family Zinc Finger 3 (GLIS3) has received scant attention in gastric cancer research. Therefore, we sought to examine the prognostic significance of GLIS3 and its association with immune infiltration in gastric cancer.

Method

Using public data from The Cancer Genome Atlas (TCGA), we investigated whether GLIS3 gene expression was linked with prognosis in patients with stomach cancer (STAD). The following analyses were performed: functional enrichment analysis (GSEA), quantitative real-time PCR, immune infiltration analysis, immunological checkpoint analysis, and clinicopathological analysis. We performed functional validation of GLIS3 in vitro by plate cloning and CCK8 assay. Using univariate and multivariate Cox regression analyses, independent prognostic variables were identified. Additionally, a nomogram model was built. The link between OS and subgroup with GLIS3 expression was estimated using Kaplan-Meier survival analysis. Gene set enrichment analysis utilized the TCGA dataset.

Result

GLIS3 was significantly upregulated in STAD. An examination of functional enrichment revealed that GLIS3 is related to immunological responses. The majority of immune cells and immunological checkpoints had a positive correlation with GLIS3 expression. According to a Kaplan-Meier analysis, greater GLIS3 expression was related to adverse outcomes in STAD. GLIS3 was an independent predictive factor in STAD patients, as determined by Cox regression (HR = 1.478, 95%CI = 1.478 (1.062-2.055), P=0.02)

Conclusion

GLIS3 is considered a novel STAD patient predictive biomarker. In addition, our research identifies possible genetic regulatory loci in the therapy of STAD.
Clinicopathological characteristics and treatment outcome of resectable gastric cancer patients with small para-aortic lymph node
Authors: Yao Zhendan , Yang Hong , Cui Ming , Xing Jiadi , Zhang Chenghai , Zhang Nan , Chen Lei , Tan Fei , Xu Kai , Liu Maoxing , Su Xiangqian
Published: February 2023

Background

Resectable gastric cancer (GC) patients with small para-aortic lymph node (smaller than 10mm in diameter, sPAN) were seldom reported, and existing guidelines did not provide definite treatment recommendation for them.

Methods

A total of 667 consecutive resectable GC patients were enrolled. 98 patients were in the sPAN group, and 569 patients without enlarged para-aortic lymph node were in the nPAN group. Standard D2 lymphadenectomy was performed. Neoadjuvant and adjuvant chemotherapy were administrated according to the cTNM and pTNM stage, respectively. Clinicopathological features and prognosis were compared between these two groups.

Results

The median size of sPAN was 6 (range, 2−9) mm and the distribution was prevalent in No. 16b1. cN stage (p=0.001) was significantly related to the presence of sPAN. sPAN was both independent risk factor for OS (p=0.031) and RFS (p=0.046) of all patients. The prognosis of patients with sPAN was significantly worse than that of patients with nPAN (OS: p=0.008; RFS: p=0.007). Preoperative CEA and CA19-9 were independent risk factors for prognosis of patients with sPAN. Furthermore, patients in the sPAN group with normal CEA and CA19-9 exhibited acceptable prognosis (5-year OS: 67%; RFS: 64%), while those with elevated CEA or CA19-9 suffered significantly poorer prognosis (5-year OS: 17%; RFS: 17%) than patients in the nPAN group (5-year OS: 64%; RFS 62%) (both p < 0.05).

Conclusions

Standard D2 lymphadenectomy should be considered a valid approach for GC patients with sPAN associate to normal preoperative CEA and CA19-9 levels. Patients with sPAN associated to elevated CEA or CA19-9 levels could benefit from a multimodal approach: neoadjuvant chemotherapy; radical surgery with D2 plus lymph nodal dissection extended to No. 16 station.
Integrative population pharmacokinetic/pharmacodynamic analysis of nemonoxacin capsule in Chinese patients with community-acquired pneumonia
Authors: Chen Yuancheng , Wu Xiaojie , Tsai Chengyuan , Chang Liwen , Yu Jicheng , Cao Guoying , Guo Beining , Shi Yaoguo , Zhu Demei , Hu Fupin , Yuan Jinyi , Liu Yang , Zhao Xu , Zhang Yingyuan , Wu Jufang , Zhang Jing
Published: February 2023

Introduction: Nemonoxacin is an innovative quinolone antibiotic for treatment of community-acquired pneumonia (CAP). As more data are available from clinical studies, it is necessary to perform an integrative pharmacokinetic/pharmacodynamic (PK/PD) analysis to support and justify the optimal dosing regimen of nemonoxacin in clinical practice.

Methods and Results: We developed a population PK model using non-linear mixed effect model based on the data of 195 Chinese subjects receiving nemonoxacin in phase I to III clinical trials. The base model was a standard two-compartment PK model defined by clearance (12 L/h) and central volume of distribution (86 L). Covariates included creatinine clearance (CLcr), body weight (BW), sex, disease status and food. Compared to the subject with BW 60 kg, Cmax and AUC0‐24, ss reduced by 24% and 19% in the subject with BW 80 kg, respectively. Compared to the subject with CLcr 150 ml/min, AUC0‐24, ss and T1/2 increased by 28% and 24%, respectively in the subject with CLcr 30 ml/min. Compared to the fasted status, Tmax of nemonoxacin increased by 1.2 h in the subject with fed status. Effects of sex and disease status on PK parameters were small (change of PK parameters ≤19%). AUC0–24/MIC and %T > MIC were identified as the optimal PK/PD indices for predicting clinical efficacy. The AUC0-24/MIC target was 63.3, 97.8, and 115.7 against Streptococcus pneumoniae, Staphylococcus aureus, and Haemophilus influenzae, respectively. The %T > MIC target was 7.96% against Klebsiella pneumoniae. Monte Carlo simulation showed that treatment with nemonoxacin 500 mg q24 h could attain a PK/PD cutoff value higher than the MIC90 against S. pneumoniae and S. aureus. The corresponding cumulative fraction of response (CFR) was greater than 93%, while nemonoxacin 750 mg q24 h would provide higher PK/PD cutoff value against Haemophilus parainfluenzae, and higher CFR (83%) than 500 mg q24 h.

Conclusion: Integrative PK/PD analysis justifies the reliable clinical and microbiological efficacy of nemonoxacin 500 mg q24 h in treating CAP caused by S. pneumoniae, S. aureus, and K. pneumoniae, irrespective of patient sex, mild renal impairment, empty stomach or not. However, nemonoxacin 750 mg q24 h would provide better efficacy than 500 mg q24 h for the CAP caused by H. parainfluenzae in terms of CFR.
Studies of different kernel functions in nuclear mass predictions with kernel ridge regression
Authors: Wu X. H.
Published: February 2023

The kernel ridge regression (KRR) approach has been successfully applied in nuclear mass predictions. Kernel function plays an important role in the KRR approach. In this work, the performances of different kernel functions in nuclear mass predictions are carefully explored. The performances are illustrated by comparing the accuracies of describing experimentally known nuclei and the extrapolation abilities. It is found that the accuracies of describing experimentally known nuclei in the KRR approaches with most of the adopted kernels can reach the same level around 195 keV, and the performance of the Gaussian kernel is slightly better than other ones in the extrapolation validation for the whole range of the extrapolation distances.
Parameterizations of immiscible two-phase flow in porous media
Authors: Pedersen Håkon , Hansen Alex
Published: February 2023

A fundamental variable characterizing immiscible two-phase flow in porous media is the wetting saturation, which is the ratio between the pore volume filled with wetting fluid and the total pore volume. More generally, this variable comes from a specific choice of coordinates on some underlying space, the domain of variables that can be used to express the volumetric flow rate. The underlying mathematical structure allows for the introduction of other variables containing the same information, but which are more convenient from a theoretical point of view. We introduce along these lines polar coordinates on this underlying space, where the angle plays a role similar to the wetting saturation. We derive relations between these new variables based on the Euler homogeneity theorem. We formulate these relations in a coordinate-free fashion using differential forms. Finally, we discuss and interpret the co-moving velocity in terms of this coordinate-free representation.
The effect of Tabata-style functional high-intensity interval training on cardiometabolic health and physical activity in female university students
Authors: Lu Yining , Wiltshire Huw D. , Baker Julien Steven , Wang Qiaojun , Ying Shanshan
Published: February 2023

Introduction: The increasing prevalence of metabolic syndrome and physical inactivity enhances exposure to cardiometabolic risk factors in university students. High-intensity interval training (HIIT) improved cardiometabolic health in clinical adults but the evidence in the university setting is limited. Furthermore, few studies examined the effect of low-volume HIIT on habitual physical activity (PA). Therefore, the primary aim of this study was to evaluate the efficacy of 12-week Tabata-style functional HIIT for improving multiple cardiometabolic health outcomes and habitual PA. We also investigated whether changes in habitual PA over the intervention period had an impact on exercise-induced health outcomes.

Methods: 122 female freshmen were randomized into the Tabata group (n = 60) and the control (n = 62). The Tabata training protocol involved 8 × 20 s maximal repeated functional exercises followed by 10 s rest with a frequency of 3 times per week for 12 weeks. Body composition, maximal oxygen uptake (VO2max), blood pressure (BP), blood lipids, fasting glucose and insulin, C-reactive protein and PA were objectively measured using standardized methods. Dietary intake was measured using a valid food frequency questionnaire. All variables were measured pre- and post-intervention.

Results: Mixed linear modelling results showed that there were large intervention effects on VO2max (p < 0.001, d = 2.53, 95% CI: 2.03 to 3.00 for relative VO2max; p < 0.001, d = 2.24, 95% CI: 1.76 to 2.68 for absolute VO2max), resting heart rate (p < 0.001, d = −1.82, 95% CI: −2.23 to −1.37), systolic BP (p < 0.001, d = −1.24, 95% CI: −1.63 to −0.84), moderate-to-vigorous intensity physical activity (MVPA) (p < 0.001, d = 2.31, 95% CI: 1.83 to 2.77), total PA (p < 0.001, d = 1.98, 95% CI: 1.53 to 2.41); moderate effects on %BF (p < 0.001, d = -1.15, 95% CI: −1.53 to −0.75), FM (p < 0.001, d = −1.08, 95% CI: −1.46 to −0.69), high-density lipoprotein (HDL) (p < 0.001, d = 1.04, 95% CI: 0.65 to 1.42), total cholesterol (p = 0.001, d = −0.64, 95% CI: −1.00 to −0.26); small effects on BMI (p = 0.011, d = −0.48, 95% CI: −0.84 to 0.11), WC (p = 0.043, d = −0.37, 95% CI: −0.74 to −0.01), low-density lipoprotein (p = 0.003, d = −0.57, 95% CI: −0.93 to −0.19), HOMA-IR (p = 0.026, d = −0.42, 95% CI: −0.78 to −0.05) and fasting insulin (p = 0.035, d = −0.40, 95% CI: −0.76 to −0.03). Regression analysis showed that only the percentage change of HDL was associated with the change of MVPA (b = 0.326, p = 0.015) and TPA (b = 0.480, p = 0.001).

Conclusion: From the findings of the study we can conclude that 12-week low-volume Tabata-style functional HIIT was highly effective for university female students to improve cardiorespiratory fitness, body fat, some cardiometabolic health outcomes and habitual PA.
A real-time and convex model for the estimation of muscle force from surface electromyographic signals in the upper and lower limbs
Authors: Shirzadi Mehdi , Marateb Hamid Reza , Rojas-Martínez Mónica , Mansourian Marjan , Botter Alberto , Vieira dos Anjos Fabio , Martins Vieira Taian , Mañanas Miguel Angel
Published: February 2023

Surface electromyography (sEMG) is a signal consisting of different motor unit action potential trains and records from the surface of the muscles. One of the applications of sEMG is the estimation of muscle force. We proposed a new real-time convex and interpretable model for solving the sEMG—force estimation. We validated it on the upper limb during isometric voluntary flexions-extensions at 30%, 50%, and 70% Maximum Voluntary Contraction in five subjects, and lower limbs during standing tasks in thirty-three volunteers, without a history of neuromuscular disorders. Moreover, the performance of the proposed method was statistically compared with that of the state-of-the-art (13 methods, including linear-in-the-parameter models, Artificial Neural Networks and Supported Vector Machines, and non-linear models). The envelope of the sEMG signals was estimated, and the representative envelope of each muscle was used in our analysis. The convex form of an exponential EMG-force model was derived, and each muscle’s coefficient was estimated using the Least Square method. The goodness-of-fit indices, the residual signal analysis (bias and Bland-Altman plot), and the running time analysis were provided. For the entire model, 30% of the data was used for estimation, while the remaining 20% and 50% were used for validation and testing, respectively. The average R-square (%) of the proposed method was 96.77 ± 1.67 [94.38, 98.06] for the test sets of the upper limb and 91.08 ± 6.84 [62.22, 96.62] for the lower-limb dataset (MEAN ± SD [min, max]). The proposed method was not significantly different from the recorded force signal (p-value = 0.610); that was not the case for the other tested models. The proposed method significantly outperformed the other methods (adj. p-value < 0.05). The average running time of each 250 ms signal of the training and testing of the proposed method was 25.7 ± 4.0 [22.3, 40.8] and 11.0 ± 2.9 [4.7, 17.8] in microseconds for the entire dataset. The proposed convex model is thus a promising method for estimating the force from the joints of the upper and lower limbs, with applications in load sharing, robotics, rehabilitation, and prosthesis control for the upper and lower limbs.
Diverse functions of the inward-rectifying potassium channel Kir5.1 and its relationship with human diseases
Authors: Zhang Chaojie , Guo Jia
Published: February 2023

The inward-rectifying potassium channel subunit Kir5.1, encoded by Kcnj16, can form functional heteromeric channels (Kir4.1/5.1 and Kir4.2/5.1) with Kir4.1 (encoded by Kcnj10) or Kir4.2 (encoded by Kcnj15). It is expressed in the kidneys, pancreas, thyroid, brain, and other organs. Although Kir5.1 cannot form functional homomeric channels in most cases, an increasing number of studies in recent years have found that the functions of this subunit should not be underestimated. Kir5.1 can confer intracellular pH sensitivity to Kir4.1/5.1 channels, which can act as extracellular potassium sensors in the renal distal convoluted tubule segment. This segment plays an important role in maintaining potassium and acid-base balances. This review summarizes the various pathophysiological processes involved in Kir5.1 and the expression changes of Kir5.1 as a differentially expressed gene in various cancers, as well as describing several other disease phenotypes caused by Kir5.1 dysfunction.