bluuebunny/crossref_metadata_2025 huggingface dataset:
The influence of sources and solid phase extraction criteria on dissolved organic matter optical properties in aquatic systems
Authors: Chuang Chia-Ying Anderin , Ho Yun-Hsuan
Published: May 2023

The integrity of studies investigating the composition of dissolved organic matter (DOM) is heavily dependent on the sampling and instrumental techniques employed. In this study, we aimed to assess the impacts of both the source of the DOM and the solid phase extraction (SPE) criteria on changes to the optical properties of DOM. Samples were collected from various aquatic environments, ranging from headwaters to the open ocean. The extraction kinetics of DOM were monitored throughout the SPE process, with alterations to the DOM verified using optical properties derived from chromophoric dissolved organic matter (CDOM), including absorbance and fluorescence measurements. The fluorescence excitation-emission matrices (EEMs) were further analyzed using PARAllel FACtor analysis (PARAFAC) to resolve the underlying chemical components. Results indicate that the reaction of DOM to acidification required for polystyrene-divinylbenzene polymer sorbent SPE varies across samples. And this variability may stem from differences in functional groups and DOM sources. The maximum carbon loading observed was 9.7 mg C per 1 g PPL, which is a widely used styrene-divinylbenzene polymer sorbent, and no overloading was noted. The dissolved organic carbon (DOC) extraction efficiency (EE) ranged from 51.5-61.5% and 27.6-40.0% for post- and extract- calculations, respectively, with no significant differences in DOC EE observed among different initial DOC concentrations, salinities, and flowrates. The differences in DOC EE across diverse sources and changes in optical proxies resulting from PPL extraction were mainly due to the heterogeneity of DOM. PPL extraction altered the overall molecular characteristics of DOM from more labile to more refractory or degraded in the open ocean and headwater source samples. Notably, high and low flowrates yielded identical SPE-DOM extraction and alterations. The results indicate that DOM sources primarily control SPE EE rather than methodological or other environmental factors. PPL SPE results in a convergence of DOM variability. These findings provide crucial insights into inter-study comparisons and the interpretability of SPE-derived DOM data from samples across diverse aquatic environments.
Effect of perioperative acupuncture-assisted general anesthesia on the anesthetic dosage required in adult surgical patients: a network meta-analysis of randomized controlled trials
Authors: Qiu Meihua , Li Chuanxiong , Sun Tong , Ruan Qianwen
Published: May 2023

Objective

To determine the comparative effects of acupuncture and related techniques-assisted general anesthesia (GA) on the total dosage of main anesthetic drugs administered during surgery.

Methods

The following data bases were searched on June 30, 2022: Embase, Cochrane, PubMed, Web of Science, CBM, CNKI, WANFANG and VIP to find randomized controlled trials (RCTs). A random-effects Bayesian network meta-analysis and subgroup analysis were employed. The GRADE system was applied to make evidence quality assessments. The intraoperative total doses of propofol and remifentanil were the primary and secondary outcomes, respectively. The weighted mean difference (WMD) with 95% confidence intervals (CI) were determined to measure the size of any potential effect.

Results

Seventy-six RCTs that involved 5,877 patients were included in the analysis. Compared with GA, a significant decrease in the total dose of propofol was found for manual acupuncture (MA) assisted GA (WMD = −101.26 mg, 95% CI [−172.98, −27.06]) with moderate quality, electroacupuncture (EA) assisted GA (WMD = −54.25 mg, 95% CI [−87.25, −22.37]) with moderate quality and transcutaneous electrical acupoint stimulation (TEAS) assisted GA (WMD = −39.99 mg, 95% CI [−57.96, −22.73]) with moderate quality, respectively. A significant reduction in the total dose of remifentanil was found in favor of EA-assisted GA (WMD = −372.33 μg, 95% CI [−558.44, −196.43]) with low quality and TEAS-assisted GA (WMD = −215.77 μg, 95% CI [−305.23, −128.04]) with low quality. According to the surface under cumulative ranking area (SUCRA), MA-assisted GA and EA-assisted GA ranked first in the reduction of the total dosage of propofol and remifentanil administered, with a probability of 0.85 and 0.87, respectively.

Conclusions

Both EA- and TEAS-assisted GA significantly reduced the intraoperative total dosage of propofol and remifentanil administered. EA produced the greatest reduction in these two outcomes compared to TEAS. Although all the comparisons are low to moderate based on GRADE evidence, EA seems to be an advisable acupuncture technique to reduce the dosage of anesthetic drugs required in surgical patients under GA.
Primary synovial sarcoma of the thyroid gland: a CARE compliant case report and literature review
Authors: Ren Chutong , Li Yashan , Huang Jiangsheng , Liu Sushun , Cao Zhexu , Jiang Qin , Lin Xiang , Ye Fei , Gong Yi
Published: May 2023

Rationale

Synovial sarcoma is a subtype of soft tissue sarcoma. Synovial sarcoma in the head and neck region is relatively unusual. Primary synovial sarcoma of the thyroid gland (PSST) is first reported in 2003 by Inako Kikuchi. PSST is extremely rare with only 15 cases documented globally. PSST shows rapid disease progression and a relatively poor prognosis. However, diagnosis and therapy are challenging for clinical surgeons. In this article, we reported the 16th PSST case and reviewed the PSST cases globally for further clinical application.

Patient concerns

The patient was referred to us because of gradually worsened dyspnea and dysphagia for 20 days. Physical examination showed a 5 × 4 cm mass with a clear boundary and good mobility. Contrast-enhanced ultrasonography (CEUS) and computed tomography (CT) showed a mass in the isthmus of the thyroid gland. The imageology diagnosis tends to be a benign thyroid nodule.

Diagnosis

After surgery, histopathology, immunohistochemistry, and fluorescence, in situ hybridization indicated the mass to be primary synovial sarcoma of the thyroid gland with no local and distant metastasis.

Interventions

The patient underwent total thyroidectomy and dissected the lymph nodes in the central compartment. This patient received postoperative chemotherapy (a combination of ifosfamide and epirubicin for five cycles). Patients tolerated chemotherapy well. No recurrence was found during the 9-month follow-up.

Lessons

Although PSST is an extremely rare disease, we should raise our awareness when we encounter a rapidly growing, cystic-solid mixed thyroid mass with neck compression symptoms to avoid misdiagnosis. Intraoperatively, surgeons should refine surgical procedures to avoid capsular rupture and tumor local implantation metastasis. Intraoperative frozen section pathology is necessary sometimes, especially when the diagnosis could not be established before surgery.
Management of heterotopic pregnancy: clinical analysis of sixty-five cases from a single institution
Authors: Ge Feng , Ding Wei , Zhao Kun , Qu Pengpeng
Published: May 2023

Objective

This retrospective study aims to analyze the influence of different treatment modalities on viable intrauterine pregnancy and to summarize the clinical features of heterotopic pregnancy (HP) patients.

Material and methods

All patients diagnosed with HP between January 2012 and December 2022 in Tianjin Central Obstetrics and Gynecology Hospital were reviewed retrospectively.

Results

This study diagnosed 65 patients using transvaginal ultrasound (TVS), including two cases of natural pregnancy, seven cases of ovulation induction pregnancy, and 56 cases after in vitro fertilization and embryo transfer (IVF-ET). The gestational age was 50.2 ± 13.0 days at the time of diagnosis. The most frequent manifestations were abdominal pain (61.5%) and vaginal bleeding (55.4%), while 11 patients (16.9%) had no symptoms before the diagnosis. The primary treatment was expectant and surgical management, including laparotomy and laparoscopic surgery. In the expectant management group, four patients were transferred to surgery due to rupture of ectopic pregnancy or ectopic pregnancy mass gradually enlarged. In the surgical management group, 53 patients underwent laparoscopic surgery, and six underwent laparotomy. The laparoscopic group's mean operation time was 51.3 ± 14.2 min (range: 15–140 min), and the median intraoperative blood loss was 20 mL (range 5–200 mL). In contrast, the laparotomy group's mean operation time was 80.0 ± 25.3 min (range 50–120 min), and the median intraoperative blood loss was 22.5 mL (range 20–50 mL). Four patients had postoperative abortions. Sixty-one newborns had no birth abnormalities, and no developmental malformations were discovered after a median follow-up of 32 months.

Conclusion

Expectant treatment has a high failure rate in HP, and laparoscopic surgery is a safe and effective treatment for removing ectopic pregnancy without increasing the risk of abortion or newborn birth defects.
From Karl Wurm and Guy Scadding's staging to 18F-FDG PET/CT scan phenotyping and far beyond: perspective in the evading history of phenotyping in sarcoidosis
Authors: Papiris Spyros A. , Kolilekas Lykourgos , Rivera Natalia , Spanos Michail , Li Guoping , Gokulnath Priyanka , Chatterjee Emeli , Georgakopoulos Alexandros , Kallieri Maria , Papaioannou Andriana I. , Raptakis Thomas , Apollonatou Vasiliki , Antonogiannaki Elvira-Markela , Gialafos Elias , Chatziioannou Sofia , Grunewald Johan , Manali Effrosyni D.
Published: May 2023

Sarcoidosis is an inflammatory granulomatous disease of unknown etiology involving any organ or tissue along with any combination of active sites, even the most silent ones clinically. The unpredictable nature of the sites involved in sarcoidosis dictates the highly variable natural history of the disease and the necessity to cluster cases at diagnosis based on clinical and/or imaging common characteristics in an attempt to classify patients based on their more homogeneous phenotypes, possibly with similar clinical behavior, prognosis, outcome, and therefore with therapeutic requirements. In the course of the disease's history, this attempt relates to the availability of a means of detection of the sites involved, from the Karl Wurm and Guy Scadding's chest x-ray staging through the ACCESS, the WASOG Sarcoidosis Organ Assessment Instruments, and the GenPhenReSa study to the 18F-FDG PET/CT scan phenotyping and far beyond to new technologies and/or the current “omics.” The hybrid molecular imaging of the 18F-FDG PET/CT scan, by unveiling the glucose metabolism of inflammatory cells, can identify high sensitivity inflammatory active granulomas, the hallmark of sarcoidosis—even in clinically and physiologically silent sites—and, as recently shown, is successful in identifying an unexpected ordered stratification into four phenotypes: (I) hilar–mediastinal nodal, (II) lungs and hilar–mediastinal nodal, (III) an extended nodal supraclavicular, thoracic, abdominal, inguinal, and (IV) all the above in addition to systemic organs and tissues, which is therefore the ideal phenotyping instrument. During the “omics era,” studies could provide significant, distinct, and exclusive insights into sarcoidosis phenotypes linking clinical, laboratory, imaging, and histologic characteristics with molecular signatures. In this context, the personalization of treatment for sarcoidosis patients might have reached its goal.
Analysis of the microbial content of probiotic products commercialized worldwide and survivability in conditions mimicking the human gut environment
Authors: Ghelardi Emilia , Mazzantini Diletta , Celandroni Francesco , Calvigioni Marco , Panattoni Adelaide , Lupetti Antonella , Bois De Fer Beatrice , Perez Marcos
Published: May 2023

Introduction

Probiotics are living microorganisms that, when administered in adequate amounts, confer a health benefit on the host. Adequate number of living microbes, the presence of specific microorganisms, and their survival in the gastrointestinal (GI) environment are important to achieve desired health benefits of probiotic products. In this in vitro study, 21 leading probiotic formulations commercialized worldwide were evaluated for their microbial content and survivability in simulated GI conditions.

Methods

Plate-count method was used to determine the amount of living microbes contained in the products. Culture-dependent Matrix-Assisted Laser Desorption/Ionization–Time of Flight Mass Spectrometry and culture-independent metagenomic analysis through 16S and 18S rDNA sequencing were applied in combination for species identification. To estimate the potential survivability of the microorganisms contained in the products in the harsh GI environment, an in vitro model composed of different simulated gastric and intestinal fluids was adopted.

Results

The majority of the tested probiotic products were concordant with the labels in terms of number of viable microbes and contained probiotic species. However, one product included fewer viable microbes than those displayed on the label, one product contained two species that were not declared, and another product lacked one of the labeled probiotic strains. Survivability in simulated acidic and alkaline GI fluids was highly variable depending on the composition of the products. The microorganisms contained in four products survived in both acidic and alkaline environments. For one of these products, microorganisms also appeared to grow in the alkaline environment.

Conclusion

This in vitro study demonstrates that most globally commercialized probiotic products are consistent with the claims described on their labels with respect to the number and species of the contained microbes. Evaluated probiotics generally performed well in survivability tests, although viability of microbes in simulated gastric and intestinal environments showed large variability. Although the results obtained in this study indicate a good quality of the tested formulations, it is important to stress that stringent quality controls of probiotic products should always be performed to provide optimal health benefits for the host.
Virulence-related factors and antimicrobial resistance in Proteus mirabilis isolated from domestic and stray dogs
Authors: Liu Lijuan , Dong Zhiyou , Ai Shengquan , Chen Shanyu , Dong Mengyao , Li Qianlan , Zhou Ziyao , Liu Haifeng , Zhong Zhijun , Ma Xiaoping , Hu Yanchun , Ren Zhihua , Fu Hualin , Shu Gang , Qiu Xianmeng , Peng Guangneng
Published: May 2023

Introduction

Proteus mirabilis is a multi-host pathogen that causes diseases of varying severity in a wide range of mammals, including humans. Proteus mirabilis is resistant to multiple antibiotics and has acquired the ability to produce expanded spectrum of β-lactamases, leading to serious public health problems. However, the available information on P. mirabilis isolated from feces of dogs, is still poorly understood, as is the correlation between its virulence-associated genes (VAGs) and antibiotic resistance genes (ARGs).

Method

In this study, we isolated 75 strains of P. mirabilis from 241 samples, and investigated the swarming motility, biofilm formation, antimicrobial resistance (AMR), distribution of VAGs and ARGs, as well as the presence of class 1, 2, and 3 integrons in these isolates.

Results

Our findings suggest a high prevalence of intensive swarming motility and strong biofilm formation ability among P. mirabilis isolates. Isolates were primarily resistant to cefazolin (70.67%) and imipenem (70.67%). These isolates were found to carry ureC, FliL, ireA, zapA, ptA, hpmA, hpmB, pmfA, rsbA, mrpA, and ucaA with varying prevalence levels of 100.00, 100.00, 100.00, 98.67, 98.67, 90.67, 90.67, 90.67, 90.67, 89.33, and 70.67%, respectively. Additionally, the isolates were found to carry aac(6′)-Ib, qnrD, floR, blaCTX-M, blaCTX-M-2, blaOXA-1, blaTEM, tetA, tetB and tetM with varying prevalence levels of 38.67, 32.00, 25.33, 17.33, 16.00, 10.67, 5.33, 2.67, 1.33, and 1.33%, respectively. Among 40 MDR strains, 14 (35.00%) were found to carry class 1 integrons, 12 (30.00%) strains carried class 2 integrons, while no class 3 integrons was detected. There was a significant positive correlation between the class 1 integrons and three ARGs: blaTEM, blaCTX-M, and blaCTX-M-2. This study revealed that P. mirabilis strains isolated from domestic dogs exhibited a higher prevalence of MDR, and carried fewer VAGs but more ARGs compared to those isolated from stay dogs. Furthermore, a negative correlation was observed between VAGs and ARGs.

Discussion

Given the increasing antimicrobial resistance of P. mirabilis, veterinarians should adopt a prudent approach towards antibiotics administration in dogs to mitigate the emergence and dissemination of MDR strains that pose a potential threat to public health.
Phenotypes controlled by the Brucella abortus two component system BvrR/BvrS are differentially impacted by BvrR phosphorylation
Authors: Altamirano-Silva Pamela , Meza-Torres Jazmín , Zúñiga-Pereira Ana Mariel , Zamora-Jaen Sigrid , Pietrosemoli Natalia , Cantos Gabriela , Peltier Johann , Pizarro-Cerdá Javier , Moreno Edgardo , Chacón-Díaz Carlos , Guzmán-Verri Caterina , Chaves-Olarte Esteban
Published: May 2023

Brucella abortus is a zoonotic pathogen whose virulence depends on its ability to survive intracellularly at the endoplasmic reticulum derived compartment. The two-component system BvrR/BvrS (BvrRS) is essential for intracellular survival due to the transcriptional control of the type IV secretion system VirB and its transcriptional regulator VjbR. It is a master regulator of several traits including membrane homeostasis by controlling gene expression of membrane components, such as Omp25. BvrR phosphorylation is related to DNA binding at target regions, thereby repressing or activating gene transcription. To understand the role of BvrR phosphorylation we generated dominant positive and negative versions of this response regulator, mimicking phosphorylated and non-phosphorylated BvrR states and, in addition to the wild-type version, these variants were introduced in a BvrR negative background. We then characterized BvrRS-controlled phenotypes and assessed the expression of proteins regulated by the system. We found two regulatory patterns exerted by BvrR. The first pattern was represented by resistance to polymyxin and expression of Omp25 (membrane conformation) which were restored to normal levels by the dominant positive and the wild-type version, but not the dominant negative BvrR. The second pattern was represented by intracellular survival and expression of VjbR and VirB (virulence) which were, again, complemented by the wild-type and the dominant positive variants of BvrR but were also significantly restored by complementation with the dominant negative BvrR. These results indicate a differential transcriptional response of the genes controlled to the phosphorylation status of BvrR and suggest that unphosphorylated BvrR binds and impacts the expression of a subset of genes. We confirmed this hypothesis by showing that the dominant negative BvrR did not interact with the omp25 promoter whereas it could interact with vjbR promoter. Furthermore, a global transcriptional analysis revealed that a subset of genes responds to the presence of the dominant negative BvrR. Thus, BvrR possesses diverse strategies to exert transcriptional control on the genes it regulates and, consequently, impacting on the phenotypes controlled by this response regulator.
Identification of novel anti-amoebic pharmacophores from kinase inhibitor chemotypes
Authors: Ferrins Lori , Buskes Melissa J. , Kapteyn Madison M. , Engels Hannah N. , Enos Suzanne E. , Lu Chenyang , Klug Dana M. , Singh Baljinder , Quotadamo Antonio , Bachovchin Kelly , Tear Westley F. , Spaulding Andrew E. , Forbes Katherine C. , Bag Seema , Rivers Mitch , LeBlanc Catherine , Burchfield Erin , Armand Jeremy R. , Diaz-Gonzalez Rosario , Ceballos-Perez Gloria , García-Hernández Raquel , Pérez-Moreno Guiomar , Bosch-Navarrete Cristina , Gómez-Liñán Claudia , Ruiz-Pérez Luis Miguel , Gamarro Francisco , González-Pacanowska Dolores , Navarro Miguel , Mensa-Wilmot Kojo , Pollastri Michael P. , Kyle Dennis E. , Rice Christopher A.
Published: May 2023

Acanthamoeba species, Naegleria fowleri, and Balamuthia mandrillaris are opportunistic pathogens that cause a range of brain, skin, eye, and disseminated diseases in humans and animals. These pathogenic free-living amoebae (pFLA) are commonly misdiagnosed and have sub-optimal treatment regimens which contribute to the extremely high mortality rates (>90%) when they infect the central nervous system. To address the unmet medical need for effective therapeutics, we screened kinase inhibitor chemotypes against three pFLA using phenotypic drug assays involving CellTiter-Glo 2.0. Herein, we report the activity of the compounds against the trophozoite stage of each of the three amoebae, ranging from nanomolar to low micromolar potency. The most potent compounds that were identified from this screening effort were: 2d (A. castellanii EC50: 0.92 ± 0.3 μM; and N. fowleri EC50: 0.43 ± 0.13 μM), 1c and 2b (N. fowleri EC50s: <0.63 μM, and 0.3 ± 0.21 μM), and 4b and 7b (B. mandrillaris EC50s: 1.0 ± 0.12 μM, and 1.4 ± 0.17 μM, respectively). With several of these pharmacophores already possessing blood–brain barrier (BBB) permeability properties, or are predicted to penetrate the BBB, these hits present novel starting points for optimization as future treatments for pFLA-caused diseases.
Evolutionary pathways for deep-sea adaptation in marine planktonic Actinobacteriota
Authors: Roda-Garcia Juan J. , Haro-Moreno Jose M. , López-Pérez Mario
Published: May 2023

The deep ocean, one of the largest ecosystems on earth, is dominated by microorganisms that are keystones in the regulation of biogeochemical cycles. However, the evolutionary pathways underlying the specific adaptations required (e.g., high pressure and low temperature) by this unique niche remain understudied. Here, we analyzed the first representatives belonging to the order Acidimicrobiales, a group of marine planktonic Actinobacteriota, that specifically inhabits the aphotic zone of the oceanic water column (>200 m). Compared with their epipelagic counterparts, deep-sea representatives showed the same evolution in genome architecture with higher GC content, longer intergenic spaces as well as higher nitrogen (N-ARSC) and lower carbon (C-ARSC) content in encoded amino acid residue side chains consistent with the higher nitrogen concentration and lower carbon concentration in deep waters compared to the photic zone. Metagenomic recruitment showed distribution patterns that allowed the description of different ecogenomic units within the three deep water-associated genera defined by our phylogenomic analyses (UBA3125, S20-B6 and UBA9410). The entire genus UBA3125 was found exclusively associated with oxygen minimum zones linked to the acquisition of genes involved in denitrification. Genomospecies of genus S20-B6 recruited in samples from both mesopelagic (200–1,000 m) and bathypelagic (1000–4,000 m) zones, including polar regions. Diversity in the genus UBA9410 was higher, with genomospecies widely distributed in temperate zones, others in polar regions, and the only genomospecies associated with abyssal zones (>4,000 m). At the functional level, groups beyond the epipelagic zone have a more complex transcriptional regulation including in their genomes a unique WhiB paralog. In addition, they showed higher metabolic potential for organic carbon and carbohydrate degradation as well as the ability to accumulate glycogen as a source of carbon and energy. This could compensate for energy metabolism in the absence of rhodopsins, which is only present in genomes associated with the photic zone. The abundance in deep samples of cytochrome P450 monooxygenases associated with the genomes of this order suggests an important role in remineralization of recalcitrant compounds throughout the water column.
Causal effects of gut microbiota on sepsis: a two-sample Mendelian randomization study
Authors: Chen Jie-Hai , Zeng Li-Ying , Zhao Yun-Feng , Tang Hao-Xuan , Lei Hang , Wan Yu-Fei , Deng Yong-Qiang , Liu Ke-Xuan
Published: May 2023

Background

Recent studies had provided evidence that the gut microbiota is associated with sepsis. However, the potential causal relationship remained unclear.

Methods

The present study aimed to explore the causal effects between gut microbiota and sepsis by performing Mendelian randomization (MR) analysis utilizing publicly accessible genome-wide association study (GWAS) summary-level data. Gut microbiota GWAS (N= 18,340) were obtained from the MiBioGen study and GWAS-summary-level data for sepsis were gained from the UK Biobank (sepsis, 10,154 cases; 452,764 controls). Two strategies were used to select genetic variants, i.e., single nucleotide polymorphisms (SNPs) below the locus-wide significance level (1 × 10−5) and the genome-wide statistical significance threshold (5 × 10−8) were chosen as instrumental variables (IVs). The inverse variance weighted (IVW) was used as the primary method for MR study, supplemented by a series of other methods. Additionally, a set of sensitivity analysis methods, including the MR-Egger intercept test, Mendelian randomized polymorphism residual and outlier (MR-PRESSO) test, Cochran’s Q test, and leave-one-out test, were carried out to assess the robustness of our findings.

Results

Our study suggested that increased abundance ofDeltaproteobacteria, Desulfovibrionales, Catenibacterium, andHungatellawere negatively associated with sepsis risk, whileClostridiaceae1, Alloprevotella, LachnospiraceaeND3007group, andTerrisporobacterwere positively correlated with the risk of sepsis. Sensitivity analysis revealed no evidence of heterogeneity and pleiotropy.

Conclusion

This study firstly found suggestive evidence of beneficial or detrimental causal associations of gut microbiota on sepsis risk by applying MR approach, which may provide valuable insights into the pathogenesis of microbiota-mediated sepsis and strategies for sepsis prevention and treatment.
Characterization of BoHV-4 ORF45
Authors: Russo Luca , Capra Emanuele , Franceschi Valentina , Cavazzini Davide , Sala Roberto , Lazzari Barbara , Cavirani Sandro , Donofrio Gaetano
Published: May 2023

Bovine herpesvirus 4 (BoHV-4) is a Gammaherpesvirus belonging to the Rhadinovirus genus. The bovine is BoHV-4's natural host, and the African buffalo is BoHV-4's natural reservoir. In any case, BoHV-4 infection is not associated with a specific disease. Genome structure and genes are well-conserved in Gammaherpesvirus, and the orf 45 gene and its product, ORF45, are one of those. BoHV-4 ORF45 has been suggested to be a tegument protein; however, its structure and function have not yet been experimentally characterized. The present study shows that BoHV-4 ORF45, despite its poor homology with other characterized Rhadinovirus ORF45s, is structurally related to Kaposi's sarcoma-associated herpesvirus (KSHV), is a phosphoprotein, and localizes in the host cell nuclei. Through the generation of an ORF45-null mutant BoHV-4 and its pararevertant, it was possible to demonstrate that ORF45 is essential for BoHV-4 lytic replication and is associated with the viral particles, as for the other characterized Rhadinovirus ORF45s. Finally, the impact of BoHV-4 ORF45 on cellular transcriptome was investigated, an aspect poorly explored or not at all for other Gammaherpesvirus. Many cellular transcriptional pathways were found to be altered, mainly those involving p90 ribosomal S6 kinase (RSK) and signal-regulated kinase (ERK) complex (RSK/ERK). It was concluded that BoHV-4 ORF45 has similar characteristics to those of KSHV ORF45, and its unique and incisive impact on the cell transcriptome paves the way for further investigations.
The use of nitrogen-15 in microbial natural product discovery and biosynthetic characterization
Authors: Morgan Kalindi D.
Published: May 2023

This mini-review covers the use of nitrogen-15 in bacterial and fungal natural product discovery and biosynthetic characterization from 1970 to 2022. Nitrogen is an important element in a number of bioactive and structurally intriguing natural products including alkaloids, non-ribosomal peptides, and hybrid natural products. Nitrogen-15 can be detected at natural abundance utilizing two-dimensional nuclear magnetic resonance and mass spectrometry. Additionally, it is a stable isotope that can be added to growth media for both filamentous fungi and bacteria. With stable isotope feeding, additional two-dimensional nuclear magnetic resonance and mass spectrometry strategies have become available, and there is a growing trend to use nitrogen-15 stable isotope feeding for the biosynthetic characterization of natural products. This mini-review will catalog the use of these strategies, analyze the strengths and weaknesses of the different approaches, and suggest future directions for the use of nitrogen-15 in natural product discovery and biosynthetic characterization.
pH-dependent endocytosis mechanisms for influenza A and SARS-coronavirus
Authors: Aganovic Amar
Published: May 2023

The ongoing SARS-CoV-2 pandemic and the influenza epidemics have revived the interest in understanding how these highly contagious enveloped viruses respond to alterations in the physicochemical properties of their microenvironment. By understanding the mechanisms and conditions by which viruses exploit the pH environment of the host cell during endocytosis, we can gain a better understanding of how they respond to pH-regulated anti-viral therapies but also pH-induced changes in extracellular environments. This review provides a detailed explanation of the pH-dependent viral structural changes preceding and initiating viral disassembly during endocytosis for influenza A (IAV) and SARS coronaviruses. Drawing upon extensive literature from the last few decades and latest research, I analyze and compare the circumstances in which IAV and SARS-coronavirus can undertake endocytotic pathways that are pH-dependent. While there are similarities in the pH-regulated patterns leading to fusion, the mechanisms and pH activation differ. In terms of fusion activity, the measured activation pH values for IAV, across all subtypes and species, vary between approximately 5.0 to 6.0, while SARS-coronavirus necessitates a lower pH of 6.0 or less. The main difference between the pH-dependent endocytic pathways is that the SARS-coronavirus, unlike IAV, require the presence of specific pH-sensitive enzymes (cathepsin L) during endosomal transport. Conversely, the conformational changes in the IAV virus under acidic conditions in endosomes occur due to the specific envelope glycoprotein residues and envelope protein ion channels (viroporins) getting protonated by H+ ions. Despite extensive research over several decades, comprehending the pH-triggered conformational alterations of viruses still poses a significant challenge. The precise mechanisms of protonation mechanisms of certain during endosomal transport for both viruses remain incompletely understood. In absence of evidence, further research is needed.
Early-life stress affects Mongolian gerbil interactions with conspecific vocalizations in a sex-specific manner
Authors: Hardy Kate A. , Hart Denise M. , Rosen Merri J.
Published: May 2023

During development, early-life stress (ELS) impairs cognition, learning, and emotional regulation, in part by disrupting neural circuitry in regions underlying these higher-order functions. In addition, our recent work indicates that ELS also alters simple sensory perception: ELS impaired auditory perception and neural encoding of short gaps in sounds, which are essential for vocal communication. The combination of higher-order and basic sensory disruption suggests that ELS is likely to affect both the perception and interpretation of communication signals. We tested this hypothesis by measuring behavioral responses to conspecific vocalizations (those emitted by other gerbils) in ELS and untreated Mongolian gerbils. Because stress effects often differ by sex, we separately examined females and males. To induce ELS, pups were intermittently maternally separated and restrained from post-natal days (P) 9–24, a time window when the auditory cortex is most sensitive to external disruption. We measured the approach responses of juvenile (P31–32) gerbils to two types of conspecific vocalizations: an alarm call, which is emitted to alert other gerbils of a potential threat, and the prosocial contact call, which is emitted near familiar gerbils, especially after separation. Control males, Control females, and ELS females approached a speaker emitting pre-recorded alarm calls, while ELS males avoided this source, suggesting that ELS affects the response to alarm calls in male gerbils. During playback of the pre-recorded contact call, Control females and ELS males avoided the sound source, while Control males neither approached nor avoided, and ELS females approached the sound. These differences cannot be accounted for by changes in locomotion or baseline arousal. However, ELS gerbils slept more during playback, suggesting that ELS may reduce arousal during vocalization playback. Further, male gerbils made more errors than females on a measure of working memory, but the sex difference of cognition in this context may stem from novelty aversion rather than impaired memory. These data indicate that ELS influences behavioral responses to ethologically relevant communication sounds in a sex-specific manner, and are among the first to demonstrate an altered response to auditory stimuli following ELS. Such changes may arise from differences in auditory perception, cognition, or a combination of factors, and suggest that ELS may affect auditory communication in human adolescents.
Phantom limb therapy improves cortical efficiency of the sensorimotor network in a targeted muscle reinnervation amputee: a case report
Authors: Borrell Jordan A. , Manattu Arun Karumattu , Copeland Christopher , Fraser Kaitlin , D’Ovidio Andrew , Granatowicz Zach , Lesiak Alex C. , Figy Sean C. , Zuniga Jorge M.
Published: May 2023

Targeted muscle reinnervation (TMR) surgery involves the coaptation of amputated nerves to nearby motor nerve branches with the purpose of reclosing the neuromuscular loop in order to reduce phantom limb pain. The purpose of this case study was to create a phantom limb therapy protocol for an amputee after undergoing TMR surgery, where the four main nerves of his right arm were reinnervated into the chest muscles. The goal of this phantom limb therapy was to further strengthen these newly formed neuromuscular closed loops. The case participant (male, 21- years of age, height = 5′8″ and weight = 134 lbs) presented 1- year after a trans-humeral amputation of the right arm along with TMR surgery and participated in phantom limb therapy for 3 months. Data collections for the subject occurred every 2 weeks for 3 months. During the data collections, the subject performed various movements of the phantom and intact limb specific to each reinnervated nerve and a gross manual dexterity task (Box and Block Test) while measuring brain activity and recording qualitative feedback from the subject. The results demonstrated that phantom limb therapy produced significant changes of cortical activity, reduced fatigue, fluctuation in phantom pain, improved limb synchronization, increased sensory sensation, and decreased correlation strength between intra-hemispheric and inter-hemispheric channels. These results suggest an overall improved cortical efficiency of the sensorimotor network. These results add to the growing knowledge of cortical reorganization after TMR surgery, which is becoming more common to aid in the recovery after amputation. More importantly, the results of this study suggest that the phantom limb therapy may have accelerated the decoupling process, which provides direct clinical benefits to the patient such as reduced fatigue and improved limb synchronization.
Validation of a pharmacological imaging challenge using 11C-buprenorphine and 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography to study the effects of buprenorphine to the rat brain
Authors: Soyer Amélie , Leterrier Sarah , Breuil Louise , Goislard Maud , Leroy Claire , Saba Wadad , Thibault Karine , Bo Gregory Dal , Bottlaender Michel , Caillé Fabien , Goutal Sébastien , Tournier Nicolas
Published: May 2023

Aim

Buprenorphine mainly acts as an agonist of mu-opioid receptors (mu-OR). High dose buprenorphine does not cause respiratory depression and can be safely administered to elicit typical opioid effects and explore pharmacodynamics. Acute buprenorphine, associated with functional and quantitative neuroimaging, may therefore provide a fully translational pharmacological challenge to explore the variability of response to opioids in vivo. We hypothesized that the CNS effects of acute buprenorphine could be monitored through changes in regional brain glucose metabolism, assessed using 18F-FDG microPET in rats.

Materials and methods

First, level of receptor occupancy associated with a single dose of buprenorphine (0.1 mg/kg, s.c) was investigated through blocking experiments using 11C-buprenorphine PET imaging. Behavioral study using the elevated plus-maze test (EPM) was performed to assess the impact of the selected dose on anxiety and also locomotor activity. Then, brain PET imaging using 18F-FDG was performed 30 min after injection of unlabeled buprenorphine (0.1 mg/kg, s.c) vs. saline. Two different 18F-FDG PET acquisition paradigms were compared: (i) 18F-FDG injected i.v. under anesthesia and (ii) 18F-FDG injected i.p. in awake animals to limit the impact of anesthesia.

Results

The selected dose of buprenorphine fully blocked the binding of 11C-buprenorphine in brain regions, suggesting complete receptor occupancy. This dose had no significant impact on behavioral tests used, regardless of the anesthetized/awake handling paradigm. In anesthetized rats, injection of unlabeled buprenorphine decreased the brain uptake of 18F-FDG in most brain regions except in the cerebellum which could be used as a normalization region. Buprenorphine treatment significantly decreased the normalized brain uptake of 18F-FDG in the thalamus, striatum and midbrain (p < 0.05), where binding of 11C-buprenorphine was the highest. The awake paradigm did not improve sensitivity and impact of buprenorphine on brain glucose metabolism could not be reliably estimated.

Conclusion

Buprenorphine (0.1 mg/kg, s.c) combined with 18F-FDG brain PET in isoflurane anesthetized rats provides a simple pharmacological imaging challenge to investigate the CNS effects of full receptor occupancy by this partial mu-OR agonist. Sensitivity of the method was not improved in awake animals. This strategy may be useful to investigate de desensitization of mu-OR associated with opioid tolerance in vivo.
Identification of biomarkers differentiating Alzheimer’s disease from other neurodegenerative diseases by integrated bioinformatic analysis and machine-learning strategies
Authors: Jin Boru , Fei Guoqiang , Sang Shaoming , Zhong Chunjiu
Published: May 2023

Background

Alzheimer’s disease (AD) is the most common neurodegenerative disease, imposing huge mental and economic burdens on patients and society. The specific molecular pathway(s) and biomarker(s) that distinguish AD from other neurodegenerative diseases and reflect the disease progression are still not well studied.

Methods

Four frontal cortical datasets of AD were integrated to conduct differentially expressed genes (DEGs) and functional gene enrichment analyses. The transcriptional changes after the integrated frontal cortical datasets subtracting the cerebellar dataset of AD were further compared with frontal cortical datasets of frontotemporal dementia and Huntingdon’s disease to identify AD-frontal-associated gene expression. Integrated bioinformatic analysis and machine-learning strategies were applied for screening and determining diagnostic biomarkers, which were further validated in another two frontal cortical datasets of AD by receiver operating characteristic (ROC) curves.

Results

Six hundred and twenty-six DEGs were identified as AD frontal associated, including 580 downregulated genes and 46 upregulated genes. The functional enrichment analysis revealed that immune response and oxidative stress were enriched in AD patients. Decorin (DCN) and regulator of G protein signaling 1 (RGS1) were screened as diagnostic biomarkers in distinguishing AD from frontotemporal dementia and Huntingdon’s disease of AD. The diagnostic effects of DCN and RGS1 for AD were further validated in another two datasets of AD: the areas under the curve (AUCs) reached 0.8148 and 0.8262 in GSE33000, and 0.8595 and 0.8675 in GSE44770. There was a better value for AD diagnosis when combining performances of DCN and RGS1 with the AUCs of 0.863 and 0.869. Further, DCN mRNA level was correlated to CDR (Clinical Dementia Rating scale) score (r = 0.5066, p = 0.0058) and Braak staging (r = 0.3348, p = 0.0549).

Conclusion

DCN and RGS1 associated with the immune response may be useful biomarkers for diagnosing AD and distinguishing the disease from frontotemporal dementia and Huntingdon’s disease. DCN mRNA level reflects the development of the disease.
Dry heating affects the multi-structures, physicochemical properties, and in vitro digestibility of blue highland barley starch
Authors: Liu Shuang , Liu Hang , Gao Shanshan , Guo Shang , Zhang Cheng
Published: May 2023

As a physical method for starch modification, dry heating treatment (DHT) at high temperatures (150 and 180°C, respectively) was applied to blue highland barley (BH) starch with different durations (2 and 4 h). The effects on its multi-structures, physicochemical properties, and in vitro digestibility were investigated. The results showed that DHT had changed the morphology of BH starch, and the diffraction pattern remained an “A”-type crystalline structure. However, with an extension of DHT temperature and time, the amylose content, gelatinization temperature, enthalpy value, swelling power, and pasting viscosity of modified starches decreased, while the light transmittance, solubility, and water and oil absorption capacities increased. Additionally, compared with native starch, the content of rapidly digestible starch in modified samples increased after DHT, whereas those of slowly digestible starch and RS decreased. Based on these results, the conclusion could be drawn that DHT is an effective and green way to transform multi-structures, physicochemical properties, and in vitro digestibility of BH starch. This fundamental information might be meaningful to enrich the theoretical basis of physical modification on BH starch and extend the applications of BH in the food industry.
The prognostic value of 18F-PSMA-1007 PET/CT in predicting pathological upgrading of newly diagnosed prostate cancer from systematic biopsy to radical prostatectomy
Authors: Zheng Anqi , Wang Zhuonan , Luo Liang , Chang Ruxi , Gao Jungang , Wang Bo , Duan Xiaoyi
Published: May 2023

Objective

This study aimed to evaluate predictors for upgrading of newly diagnosed prostate cancer from systematic biopsy (SB) to radical prostatectomy (RP) using fluorine-18 prostate-specific membrane antigen 1007 (18F-PSMA-1007) positron emission tomography/computed tomography (PET/CT) and association with clinical parameters.

Materials and methods

We retrospectively collected data from biopsy-confirmed prostate cancer (PCa) patients who underwent 18F-PSMA-1007 PET/CT prior to RP from July 2019 and October 2022. Imaging characteristics derived from 18F-PSMA-1007 PET/CT and clinical parameters were compared in patients of pathological upgrading and concordance subgroups. Univariable and multivariable logistic regressions were performed to analyze factors predicting histopathological upgrading from SB to RP specimens. Discrimination ability of independent predictors was further evaluated by receiver operating characteristic (ROC) analysis with corresponding area under the curve (AUC).

Results

Pathological upgrading occurred in 26.97% (41/152) PCa patients, and 23.03% (35/152) of all patients experienced pathological downgrading. Concordance rate reached 50% (76/152). International Society of Urological Pathology grade group (ISUP GG) 1(77.78%) and ISUP GG 2 (65.22%) biopsies were related with the highest rate of upgrading. Multivariable logistic regression analyses showed that prostate volume (OR= 0.933; 95% CI, 0.887–0.982; p = 0.008), ISUP GG 1 vs. 4 (OR= 13.856; 95% CI: 2.467–77.831; p = 0.003), and total uptake of PSMA-avid lesions (PSMA-TL) (OR = 1.003; 95% CI, 1.000–1.006; p = 0.029) were found to be independent risk factors of pathological upgrading after RP. The AUCs and corresponding sensitivity and specificity of the independent predictors of synthesis for upgrading were 0.839, 78.00%, and 83.30% respectively, which showed good discrimination capacity.

Conclusion

18F-PSMA-1007 PET/CT may help to predict pathological upgrading between biopsy and RP specimens, particularly for ISUP GG 1 and ISUP GG 2 patients with higher PSMA-TL and smaller prostate volume.
Global trends and hotspots on childhood obstructive sleep apnea: a 10-year bibliometric analysis
Authors: Wang Chao , Sun Kai , Zhang Siyao , Hu Huiying , Lu Yuanyuan , Liu Kai , Yu Zhenkun
Published: May 2023

Background

Obstructive sleep apnea (OSA) is children's most common sleep-related breathing disorder. It may develop a wide range of severe complications if not diagnosed promptly and treated effectively. However, Childhood OSA has not specifically been analyzed using a bibliometric approach.

Methods

We respectively collected the research results of childhood OSA from 2013 to 2022 through Web of Science and PubMed. Vosviewer, CiteSpace, and bibliometric online analysis platforms were used for visualizing and analyzing the literature. The MeSH terms were bi-clustered using the Bibliographic Item co-occurrence Matrix Builder (BICOMB) and graph clustering toolkit (gCLUTO) to identify the hotspots.

Results

4022 publications were finally identified on childhood OSA from 2013 to 2022. The United States has the largest number of publications (1902), accounting for 47.29%. University of Cincinnati is the most productive organization (196), followed by the University of Pennsylvania (151). The most prolific journal was the International Journal of Pediatric Otorhinolaryngology, with 311 documents published. In comparison, Pediatrics is the most cited journal (6936). Gozal D ranked highest among all authors in publication (192). Burst detection shows continuous positive airway pressure, Robin sequence, and nocturnal oximetry are recent keywords of great interest to researchers. Five hotspots were identified by co-word biclustering.

Conclusion

Research over the past ten years has been fruitful, establishing the foundation for childhood OSA. Clusters (0-4) of high-frequency Major Mesh topics have attracted extensive attention. Evaluation and treatment methods of childhood OSA remain major focuses. We believe this article will provide other researchers with new directions and may contribute to a future breakthrough in this field.