bluuebunny/crossref_metadata_2025 huggingface dataset:
Primary Productivity in the Mid-Atlantic Bight: Is the Shelf Break a Location of Enhanced Productivity?
Authors: Ma Jiejie , Smith Walker O.
Published: February 2022

Estimates of primary production represent the input of carbon into food webs, as well as the initial step in the biological pump. For the past 60 years, much of the productivity information has been obtained using measurements of 14C-bicarbonate removal during simulated in situ incubations. However, such measurements often do not reflect the complexity of the environment, and also suffer from uncertainties, biases and limitations. A vertically resolved bio-optical model has been used to estimate productivity based on profiles commonly assessed in oceanographic investigations, but comparisons with simultaneous measurements of 14C-uptake are limited. We conducted three cruises off the coast of New England that included sampling continental shelf waters, the shelf-break region, and deeper waters at scales of 7 km, all of which had productivity estimated by a vertically resolved productivity model as well as by traditional 14C-uptake measurements using simulated in situ techniques. We found that the vertically resolved bio-optical model gave results that appear to be more robust and resolved productivity at smaller vertical and horizontal scales, and seem less biased by some of the uncertainties in 14C-uptake measurements. Both estimates suggest that the New England waters are highly productive due to a variety of biological and physical processes occurring at different times of the year, but there was no consistent stimulation at the shelf break over the time scales of these estimates.
Broadband Sound Absorption of Subwavelength Porous Meta-Liner
Authors: Xiao Heye , Yuan Tianyue , Song Xiang , Chen Junli , Zhou Jie , Sui Dan , Gu Jintao
Published: February 2022

This work proposes a subwavelength porous meta-liner with broadband sound absorption from 900 to 1,200 Hz. The meta-liner consists of four subunits, which are made up of porous material and hollow coiling slit embedded in it. Each subunit is designed by adjusting the length of its coiling slit to achieve resonance in the target frequency and examined by the finite element method (FEM). These subunits are arranged in an axial direction uniformly and radial direction periodically to propose a meta-liner duct. Then, the noise reduction of the propeller system with the meta-liner duct is measured by the microphone array. The result shows that the propeller with the meta-liner duct can reduce the noise level of the ducted propeller between 3.6 and 5.5 dB in the design frequency range, which also effectively reduces the noise level in the broadband frequency range. Therefore, the meta-liner shows a good application prospect in the noise reduction of the propeller.
Effects of Carbon Dioxide and Temperature on the Oxygen-Hemoglobin Dissociation Curve of Human Blood: Implications for Avalanche Victims
Authors: Woyke Simon , Brugger Hermann , Ströhle Mathias , Haller Thomas , Gatterer Hannes , Dal Cappello Tomas , Strapazzon Giacomo
Published: February 2022

Completely avalanche-buried patients are frequently exposed to a combination of hypoxia and hypercapnia with a risk of normothermic cardiac arrest. Patients with a long burial time and an air pocket are exposed to a combination of hypoxia, hypercapnia, and hypothermia which may lead to the development of the “triple H syndrome”. This specific combination has several pathophysiological implications, particularly on the cardiovascular system and oxygen transport (oxygen supply and oxygen consumption). To examine the effects on hemoglobin oxygen affinity, we investigated venous blood samples from 15 female and 15 male healthy subjects. In a factorial design of four different carbon dioxide partial pressure (PCO2) levels (20, 40, 60, and 80 mmHg) and five different temperature levels (13.7°C, 23°C, 30°C, 37°C, and 42°C), 30 unbuffered whole blood samples were analyzed in a newly developed in vitro method for high-throughput oxygen dissociation curve (ODC) measurements. P50s, Hill coefficients, CO2-Bohr coefficients, and temperature coefficients were analyzed using a linear mixed model (LMM). Mean P50 at baseline (37°C, 40 mmHg PCO2) was 27.1 ± 2.6 mmHg. Both CO2-Bohr (p < 0.001) and temperature coefficients (p < 0.001) had a significant effect on P50. The absolute CO2 effect was still pronounced at normothermic and febrile temperatures, whereas at low temperatures, the relative CO2 effect (expressed by CO2-Bohr coefficient; p < 0.001, interaction) was increased. The larger impact of PCO2 on oxygen affinity at low temperature may be caused by the competition of 2,3-BPG with PCO2 and the exothermic binding characteristic of 2,3-BPG. In a model of an avalanche burial, based on published data of CO2 levels and cooling rates, we calculated the resulting P50 for this specific condition based on the here-reported PCO2 and temperature effect on ODC. Depending on the degree of hypercapnia and hypothermia, a potentially beneficial increase in hemoglobin oxygen affinity in the hypoxic condition might ensue.
Transcriptome-Based Molecular Networks Uncovered Interplay Between Druggable Genes of CD8+ T Cells and Changes in Immune Cell Landscape in Patients With Pulmonary Tuberculosis
Authors: Alsulaimany Faten Ahmad , Zabermawi Nidal M. Omer , Almukadi Haifa , Parambath Snijesh V. , Shetty Preetha Jayasheela , Vaidyanathan Venkatesh , Elango Ramu , Babanaganapalli Babajan , Shaik Noor Ahmad
Published: February 2022

Background

Tuberculosis (TB) is a major infectious disease, where incomplete information about host genetics and immune responses is hindering the development of transformative therapies. This study characterized the immune cell landscape and blood transcriptomic profile of patients with pulmonary TB (PTB) to identify the potential therapeutic biomarkers.

Methods

The blood transcriptome profile of patients with PTB and controls were used for fractionating immune cell populations with the CIBERSORT algorithm and then to identify differentially expressed genes (DEGs) with R/Bioconductor packages. Later, systems biology investigations (such as semantic similarity, gene correlation, and graph theory parameters) were implemented to prioritize druggable genes contributing to the immune cell alterations in patients with TB. Finally, real time-PCR (RT-PCR) was used to confirm gene expression levels.

Results

Patients with PTB had higher levels of four immune subpopulations like CD8+ T cells (P = 1.9 × 10−8), natural killer (NK) cells resting (P = 6.3 × 10−5), monocytes (P = 6.4 × 10−6), and neutrophils (P = 1.6 × 10−7). The functional enrichment of 624 DEGs identified in the blood transcriptome of patients with PTB revealed major dysregulation of T cell-related ontologies and pathways (q ≤ 0.05). Of the 96 DEGs shared between transcriptome and immune cell types, 39 overlapped with TB meta-profiling genetic signatures, and their semantic similarity analysis with the remaining 57 genes, yielded 45 new candidate TB markers. This study identified 9 CD8+ T cell-associated genes (ITK, CD2, CD6, CD247, ZAP70, CD3D, SH2D1A, CD3E, and IL7R) as potential therapeutic targets of PTB by combining computational druggability and co-expression (r2 ≥ |0.7|) approaches.

Conclusion

The changes in immune cell proportion and the downregulation of T cell-related genes may provide new insights in developing therapeutic compounds against chronic TB.
Assessment of Eyelid Pressure Using a Novel Pressure Measurement Device in Patients With Moderate-to-Severe Dry Eye Disease
Authors: Wang Jingyi , Bao Jiayu , Song Wenxiu , Li Siyuan , Hao Yiran , Tian Lei , Jie Ying
Published: February 2022

Objective

To assess a novel eyelid pressure measurement device and study the relationship between eyelid pressure and ocular surface parameters of moderate-to-severe dry eye disease (DED).

Methods

The present study included 70 eyes of 35 moderate-to-severe DED patients. All subjects were subjected to the following examinations for DED assessment: Ocular Surface Disease Index (OSDI) questionnaire, tear meniscus height (TMH), lipid layer thickness (LLT), number of partial blink (PB), total blink (TB) and partial blink rate (PBR), fluorescein tear breakup time (FBUT), corneal fluorescein staining (CFS), lid margin abnormality, meibum expression assessment (meibum score), meibomian gland dropout (MGd) and Schirmer I test. Pressure of the upper eyelid was measured thrice with the novel pressure measurement device. Repeatability of the device was evaluated by intraclass correlation coefficient (ICC). Safety of the device was evaluated by observing ocular adverse reactions of each subject prior to measurement, at day 1 and day 7 following measurement. Correlations between eyelid pressure and ocular surface parameters of moderate-to-severe DED were analyzed by using Pearson correlation coefficient and Kendall's tau-b correlation coefficient.

Results

ICC of the measurement results in our study was 0.86. There was no abnormality presenting in all subjects recorded prior to measurement, 1 and 7 days following measurement. The eyelid pressure was significantly correlated with PBR (r = 0.286, P = 0.016), FBUT (r = −0.331, P = 0.005), CFS (r = 0.528, P = 0.000), lid margin abnormality (r = 0.408, P = 0.011) and MGd (r = 0.226, P = 0.016) in moderate-to-severe DED patients, but not significantly correlated with OSDI score (r = 0.016, P = 0.912), TMH (r = −0.002, P = 0.988), meibum score (r = −0.196, P = 0.317), LLT (r = 0.114, P = 0.346), PB (r = 0.116, P = 0.338), TB (r = 0.074, P = 0.544), meibum score (r = −0.196, P = 0.317) and Schirmer I test (r = 0.028, P = 0.821).

Conclusion

The novel pressure measurement device exhibited good repeatability and safety in measuring eyelid pressure. Significant correlations were noted between the eyelid pressure and PBR, FBUT, CFS, lid margin abnormality and MGd in moderate-to-severe DED. The measurement of eyelid pressure combined with ocular surface parameters may be valuable for the assessment of DED.
Analysis of SARS-CoV-2 Variants From 24,181 Patients Exemplifies the Role of Globalization and Zoonosis in Pandemics
Authors: Colson Philippe , Fournier Pierre-Edouard , Chaudet Hervé , Delerce Jérémy , Giraud-Gatineau Audrey , Houhamdi Linda , Andrieu Claudia , Brechard Ludivine , Bedotto Marielle , Prudent Elsa , Gazin Céline , Beye Mamadou , Burel Emilie , Dudouet Pierre , Tissot-Dupont Hervé , Gautret Philippe , Lagier Jean-Christophe , Million Matthieu , Brouqui Philippe , Parola Philippe , Fenollar Florence , Drancourt Michel , La Scola Bernard , Levasseur Anthony , Raoult Didier
Published: February 2022

After the end of the first epidemic episode of SARS-CoV-2 infections, as cases began to rise again during the summer of 2020, we at IHU Méditerranée Infection in Marseille, France, intensified the genomic surveillance of SARS-CoV-2, and described the first viral variants. In this study, we compared the incidence curves of SARS-CoV-2-associated deaths in different countries and reported the classification of SARS-CoV-2 variants detected in our institute, as well as the kinetics and sources of the infections. We used mortality collected from a COVID-19 data repository for 221 countries. Viral variants were defined based on ≥5 hallmark mutations along the whole genome shared by ≥30 genomes. SARS-CoV-2 genotype was determined for 24,181 patients using next-generation genome and gene sequencing (in 47 and 11% of cases, respectively) or variant-specific qPCR (in 42% of cases). Sixteen variants were identified by analyzing viral genomes from 9,788 SARS-CoV-2-diagnosed patients. Our data show that since the first SARS-CoV-2 epidemic episode in Marseille, importation through travel from abroad was documented for seven of the new variants. In addition, for the B.1.160 variant of Pangolin classification (a.k.a. Marseille-4), we suspect transmission from farm minks. In conclusion, we observed that the successive epidemic peaks of SARS-CoV-2 infections are not linked to rebounds of viral genotypes that are already present but to newly introduced variants. We thus suggest that border control is the best mean of combating this type of introduction, and that intensive control of mink farms is also necessary to prevent the emergence of new variants generated in this animal reservoir.
Delineation of ISEcp1 and IS26-Mediated Plasmid Fusion Processes by MinION Single-Molecule Long-Read Sequencing
Authors: Chen Kaichao , Xie Miaomiao , Chan Edward Wai-Chi , Chen Sheng
Published: February 2022

We recently reported the recovery of a novel IncI1 type conjugative helper plasmid which could target mobile genetic elements (MGE) located in non-conjugative plasmid and form a fusion conjugative plasmid to mediate the horizontal transfer of the non-conjugative plasmid. In this study, interactions between the helper plasmid pSa42-91k and two common MGEs, ISEcp1 and IS15DI, which were cloned into a pBackZero-T vector, were monitored during the conjugation process to depict the molecular mechanisms underlying the plasmid fusion process mediated by insertion sequence (IS) elements. The MinION single-molecule long-read sequencing technology can dynamically reveal the plasmid recombination events and produce valuable information on genetic polymorphism and plasmid heterogeneity in different multidrug resistance (MDR) encoding bacteria. Such data would facilitate the development of new strategies to control evolution and dissemination of MDR plasmids.
Emergent Virus Reactivation in SARS-CoV-2-Negative Community Acquired Pneumonia Patients During the COVID-19 Pandemic
Authors: Qu Junyan , He Fang , Li Huan , Lv Xiaoju
Published: February 2022

Emergent viruses (namely, HSV-1, CMV, and EBV) reactivation were common in critically ill patients and/or immunosuppressed patients. This study aimed to understand the clinical manifestations and reactivation of the emergent viruses in SARS-CoV-2-Negative community acquired pneumonia (CAP) patients during the COVID-19 pandemic. We retrospectively reviewed the medical records of CAP patients from January to March 2020, in our university hospital in China. The patients were divided into two groups based on the presence or absence of emergent viruses. In all patients, the positive rates of EBV, HSV, and CMV were 23.43% (15/64), 22.06% (15/68), and 12.50% (8/64), respectively. The most common presenting symptoms were fever (98, 57.99%) and dry cough (55, 32.54%). The levels of albumin, hemoglobin, lymphocyte count, and CD4 + T lymphocyte count in emergent viruses positive group were lower than those of viruses negative group (P < 0.05). The initial chest CT features of these patients were diverse. The most common manifestations were ground-glass opacity (91/169, 53.85%) and pulmonary nodule (88/169, 52.07%). More emergent viruses positive patients have bilateral upper lobes involvement than emergent viruses negative patients (P < 0.05). A total of 80.47% patients (136/169) received empirical antimicrobial treatment. The most commonly used antibiotic regimen was fluoroquinolone monotherapy (80/169, 47.34%). The emergent viruses positive patients have poorer clinical outcome (P < 0.05). In conclusion, emergent viruses reactivation was common in SARS-CoV-2-Negative CAP patients. Emergent viruses positive patients have poorer cellular immune function, more severer conditions and poorer prognosis. Fluoroquinolones may be a therapeutic option for CAP patients.
Seroprevalence, Prevalence, and Genomic Surveillance: Monitoring the Initial Phases of the SARS-CoV-2 Pandemic in Betim, Brazil
Authors: Silva Ana Valesca Fernandes Gilson , Menezes Diego , Moreira Filipe Romero Rebello , Torres Octávio Alcântara , Fonseca Paula Luize Camargos , Moreira Rennan Garcias , Alves Hugo José , Alves Vivian Ribeiro , Amaral Tânia Maria de Resende , Coelho Adriano Neves , Saraiva Duarte Júlia Maria , da Rocha Augusto Viana , de Almeida Luiz Gonzaga Paula , de Araújo João Locke Ferreira , de Oliveira Hilton Soares , de Oliveira Nova Jersey Cláudio , Zolini Camila , de Sousa Jôsy Hubner , de Souza Elizângela Gonçalves , de Souza Rafael Marques , Ferreira Luciana de Lima , Lehmkuhl Gerber Alexandra , Guimarães Ana Paula de Campos , Maia Paulo Henrique Silva , Marim Fernanda Martins , Miguita Lucyene , Monteiro Cristiane Campos , Neto Tuffi Saliba , Pugêdo Fabrícia Soares Freire , Queiroz Daniel Costa , Queiroz Damares Nigia Alborguetti Cuzzuol , Resende-Moreira Luciana Cunha , Santos Franciele Martins , Souza Erika Fernanda Carlos , Voloch Carolina Moreira , Vasconcelos Ana Tereza , de Aguiar Renato Santana , de Souza Renan Pedra
Published: February 2022

The COVID-19 pandemic has created an unprecedented need for epidemiological monitoring using diverse strategies. We conducted a project combining prevalence, seroprevalence, and genomic surveillance approaches to describe the initial pandemic stages in Betim City, Brazil. We collected 3239 subjects in a population-based age-, sex- and neighborhood-stratified, household, prospective; cross-sectional study divided into three surveys 21 days apart sampling the same geographical area. In the first survey, overall prevalence (participants positive in serological or molecular tests) reached 0.46% (90% CI 0.12–0.80%), followed by 2.69% (90% CI 1.88–3.49%) in the second survey and 6.67% (90% CI 5.42–7.92%) in the third. The underreporting reached 11, 19.6, and 20.4 times in each survey. We observed increased odds to test positive in females compared to males (OR 1.88 95% CI 1.25–2.82), while the single best predictor for positivity was ageusia/anosmia (OR 8.12, 95% CI 4.72–13.98). Thirty-five SARS-CoV-2 genomes were sequenced, of which 18 were classified as lineage B.1.1.28, while 17 were B.1.1.33. Multiple independent viral introductions were observed. Integration of multiple epidemiological strategies was able to adequately describe COVID-19 dispersion in the city. Presented results have helped local government authorities to guide pandemic management.
Bacillus spp. Probiotic Strains as a Potential Tool for Limiting the Use of Antibiotics, and Improving the Growth and Health of Pigs and Chickens
Authors: Luise Diana , Bosi Paolo , Raff Lena , Amatucci Laura , Virdis Sara , Trevisi Paolo
Published: February 2022

The pressure to increasingly optimize the breeding of livestock monogastric animals resulted in antimicrobials often being misused in an attempt to improve growth performance and counteract diseases in these animals, leading to an increase in the problem of antibiotic resistance. To tackle this problem, the use of probiotics, also known as direct in-feed microbials (DFM), seems to be one of the most promising strategies. Among probiotics, the interest inBacillusstrains has been intensively increased in recent decades in pigs and poultry. The aim of the present review was to evaluate the effectiveness ofBacillusstrains as probiotics and as a potential strategy for reducing the misuse of antibiotics in monogastric animals. Thus, the potential modes of action, and the effects on the performance and health of pigs (weaning pigs, lactation and gestation sows) and broilers are discussed. These searches yielded 131 articles (published before January 2021). The present review showed thatBacillusstrains could favor growth in terms of the average daily gain (ADG) of post-weaning piglets and broilers, and reduce the incidence of post-weaning diarrhea in pigs by 30% and mortality in broilers by 6–8%. The benefits ofBacillusstrains on these parameters showed results comparable to the benefit obtained by the use of antibiotics. Furthermore, the use ofBacillusstrains gives promising results in enhancing the local adaptative immune response and in reducing the oxidative stress of broilers. Fewer data were available regarding the effect on sows. Discordant effects have been reported regarding the effect on body weight (BW) and feed intake while a number of studies have supported the hypothesis that feeding probiotics to sows could benefit their reproductive performance, namely the BW and ADG of the litters. Taken all the above-mentioned facts together, this review confirmed the effectiveness ofBacillusstrains as probiotics in young pigs and broilers, favoring their health and contributing to a reduction in the misuse of direct in-feed antibiotics. The continuous development and research regarding probiotics will support a decrease in the misuse of antibiotics in livestock production in order to endorse a more sustainable rearing system in the near future.
Structural and Functional Diversity of Animal Toxins Interacting With GPCRs
Authors: Van Baelen Anne-Cécile , Robin Philippe , Kessler Pascal , Maïga Arhamatoulaye , Gilles Nicolas , Servent Denis
Published: February 2022

Peptide toxins from venoms have undergone a long evolutionary process allowing host defense or prey capture and making them highly selective and potent for their target. This has resulted in the emergence of a large panel of toxins from a wide diversity of species, with varied structures and multiple associated biological functions. In this way, animal toxins constitute an inexhaustible reservoir of druggable molecules due to their interesting pharmacological properties. One of the most interesting classes of therapeutic targets is the G-protein coupled receptors (GPCRs). GPCRs represent the largest family of membrane receptors in mammals with approximately 800 different members. They are involved in almost all biological functions and are the target of almost 30% of drugs currently on the market. Given the interest of GPCRs in the therapeutic field, the study of toxins that can interact with and modulate their activity with the purpose of drug development is of particular importance. The present review focuses on toxins targeting GPCRs, including peptide-interacting receptors or aminergic receptors, with a particular focus on structural aspects and, when relevant, on potential medical applications. The toxins described here exhibit a great diversity in size, from 10 to 80 amino acids long, in disulfide bridges, from none to five, and belong to a large panel of structural scaffolds. Particular toxin structures developed here include inhibitory cystine knot (ICK), three-finger fold, and Kunitz-type toxins. We summarize current knowledge on the structural and functional diversity of toxins interacting with GPCRs, concerning first the agonist-mimicking toxins that act as endogenous agonists targeting the corresponding receptor, and second the toxins that differ structurally from natural agonists and which display agonist, antagonist, or allosteric properties.
Effects of Cognitive Reserve in Alzheimer’s Disease and Cognitively Unimpaired Individuals
Authors: Lee Dong Hyuk , Seo Sang Won , Roh Jee Hoon , Oh Minyoung , Oh Jungsu S. , Oh Seung Jun , Kim Jae Seung , Jeong Yong
Published: February 2022

The concept of cognitive reserve (CR) has been proposed as a protective factor that modifies the effect of brain pathology on cognitive performance. It has been characterized through CR proxies; however, they have intrinsic limitations. In this study, we utilized two different datasets containing tau, amyloid PET, and T1 magnetic resonance imaging. First, 91 Alzheimer’s disease (AD) continuum subjects were included from Alzheimer’s Disease Neuroimaging Initiative 3. CR was conceptualized as the residual between actual cognition and estimated cognition based on amyloid, tau, and neurodegeneration. The proposed marker was tested by the correlation with CR proxy and modulation of brain pathology effects on cognitive function. Second, longitudinal data of baseline 53 AD spectrum and 34 cognitively unimpaired (CU) participants in the MEMORI dataset were analyzed. CR marker was evaluated for the association with disease conversion rate and clinical progression. Applying our multimodal CR model, this study demonstrates the differential effect of CR on clinical progression according to the disease status and the modulating effect on the relationship between brain pathology and cognition. The proposed marker was associated with years of education and modulated the effect of pathological burden on cognitive performance in the AD spectrum. Longitudinally, higher CR marker was associated with lower disease conversion rate among prodromal AD and CU individuals. Higher CR marker was related to exacerbated cognitive decline in the AD spectrum; however, it was associated with a mitigated decline in CU individuals. These results provide evidence that CR may affect the clinical progression differentially depending on the disease status.
Early Noise-Induced Hearing Loss Accelerates Presbycusis Altering Aging Processes in the Cochlea
Authors: Fetoni Anna Rita , Pisani Anna , Rolesi Rolando , Paciello Fabiola , Viziano Andrea , Moleti Arturo , Sisto Renata , Troiani Diana , Paludetti Gaetano , Grassi Claudio
Published: February 2022

Several studies identified hearing loss as a risk factor for aging-related processes, including neurodegenerative diseases, as dementia and age-related hearing loss (ARHL). Although the association between hearing impairment in midlife and ARHL has been widely documented by epidemiological and experimental studies, the molecular mechanisms underlying this association are not fully understood. In this study, we used an established animal model of ARHL (C57BL/6 mice) to evaluate if early noise-induced hearing loss (NIHL) could affect the onset or progression of age-related cochlear dysfunction. We found that hearing loss can exacerbate ARHL, damaging sensory-neural cochlear epithelium and causing synaptopathy. Moreover, we studied common pathological markers shared between hearing loss and ARHL, demonstrating that noise exposure can worsen/accelerate redox status imbalance [increase of reactive oxygen species (ROS) production, lipid peroxidation, and dysregulation of endogenous antioxidant response] and vascular dysfunction [increased expression of hypoxia-inducible factor-1alpha (HIF-1α) and vascular endothelial growth factor C (VEGFC)] in the cochlea. Unveiling the molecular mechanisms underlying the link between hearing loss and aging processes could be valuable to identify effective therapeutic strategies to limit the effect of environmental risk factors on age-related diseases.
Normal Variants, Pitfalls and Artifacts in Ga-68 DOTATATE PET/CT Imaging
Authors: Malan Nico , Vangu Mboyo-Di-Tamba
Published: February 2022

Indium 111 DTPA Octreotide (Octreoscan) has been the pillar of Somatostatin receptor (SSTRs) imaging in nuclear medicine for over three decades. The advent of PET/CT brought new analogs of somatostatin that have higher affinity and improved resolution due to their labeling to Gallium 68 for positron imaging. The most used analogs include DOTATATE, DOTATOC and DOTANOC. However, Gallium 68–1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-octreotate (DOTATATE) is probably the most common non-FDG (fluoro-2-deoxy glucose) PET tracer alongside PSMA (prostate specific membrane antigen). In contrast to F18-labeled FDG, it does not require proximity to a cyclotron due to the availability of the Ga68 generator. DOTATATE is a somatostatin analog which allows whole body imaging of somatostatin receptors on cell surfaces. 68Ga-DOTA compounds provide the imaging standard for well-differentiated (Grade 1 and low grade 2) neuro-endocrine tumors (NETs) and is utilized in the staging and characterization and restaging of patients with NETs. 68Ga DOTATATE has a complementary role with 18F-FDG where tumors may exhibit varying degrees of differentiation. It furthermore has application as a prelude to therapy in selecting patients for peptide receptor radionuclide therapy using a theranostic approach. A sound knowledge of the normal biodistribution of the radiotracer is imperative for optimal patient outcome and to avoid potential false positives such as inflammation, normal pancreatic uncinate process uptake and osteoblastic activity. In this review, we will describe the normal appearances of the 68Ga DOTATATE and the potential pitfalls with the support of images to aid in improving interpretation of this crucial innovative tool in the management of individuals with tumors expressing SSTRs.
Ferulic Acid From Plant Biomass: A Phytochemical With Promising Antiviral Properties
Authors: Antonopoulou Io , Sapountzaki Eleftheria , Rova Ulrika , Christakopoulos Paul
Published: February 2022

Plant biomass is a magnificent renewable resource for phytochemicals that carry bioactive properties. Ferulic acid (FA) is a hydroxycinnamic acid that is found widespread in plant cell walls, mainly esterified to polysaccharides. It is well known of its strong antioxidant activity, together with numerous properties, such as antimicrobial, anti-inflammatory and neuroprotective effects. This review article provides insights into the potential for valorization of FA as a potent antiviral agent. Its pharmacokinetic properties (absorption, metabolism, distribution and excretion) and the proposed mechanisms that are purported to provide antiviral activity are presented. Novel strategies on extraction and derivatization routes, for enhancing even further the antiviral activity of FA and potentially favor its metabolism, distribution and residence time in the human body, are discussed. These routes may lead to novel high-added value biorefinery pathways to utilize plant biomass toward the production of nutraceuticals as functional foods with attractive bioactive properties, such as enhancing immunity toward viral infections.
Prior Local or Systemic Treatment: A Predictive Model Could Guide Clinical Decision-Making for Locoregional Recurrent Breast Cancer
Authors: Wu Huai-liang , Lu Yu-jie , Li Jian-wei , Wu Si-yu , Chen Xiao-song , Liu Guang-yu
Published: February 2022

Introduction

Locoregional recurrent breast cancer indicates poor prognosis. No solid prediction model is available to predict prognosis and guide clinical management. Prior local treatment or systemic treatment remains controversial.

Methods

Locoregional recurrent breast cancer patients operated in Fudan University Shanghai Cancer Center were enrolled as a training cohort. An external validation cohort included breast cancer patients after locoregional recurrence from Ruijin Hospital, Shanghai Jiaotong University. A nomogram predicting overall survival after locoregional recurrence was established using multivariable Cox regression analysis while internal and external validation were performed to evaluate its calibration and discrimination.

Results

Overall, 346 and 96 breast cancer patients were included in the training cohort and the validation cohort separately. A nomogram was developed, including age, neoadjuvant chemotherapy, breast surgery, pathology type, tumor size, lymph node status, hormonal receptor and Her-2 status, disease-free interval, and sites of locoregional recurrence. It had modest calibration and discrimination in the training cohort, internal validation and external validation (concordance index: 0.751, 0.734 and 0.722, respectively). The nomogram classified 266 and 80 patients into low and high-risk subgroups with distinctive prognosis. Local treatment after locoregional recurrence was associated with improved overall survival in low-risk group (P = 0.011), while systemic therapies correlated with better outcomes only in high-risk group (P < 0.001).

Conclusion

A nomogram based on clinicopathological factors can predict prognosis and identify low and high-risk patients. Local treatment is a prior choice for low-risk patients whereas systemic treatment needs to be considered for high-risk patients, warranting further validation and exploration.
Artesunate Inhibits the Growth Behavior of Docetaxel-Resistant Prostate Cancer Cells
Authors: Vakhrusheva Olesya , Erb Holger H. H. , Bräunig Vitus , Markowitsch Sascha D. , Schupp Patricia , Baer Patrick C. , Slade Kimberly Sue , Thomas Anita , Tsaur Igor , Puhr Martin , Culig Zoran , Cinatl Jindrich , Michaelis Martin , Efferth Thomas , Haferkamp Axel , Juengel Eva
Published: February 2022

Novel therapeutic strategies are urgently needed for advanced metastatic prostate cancer (PCa). Phytochemicals used in Traditional Chinese Medicine seem to exhibit tumor suppressive properties. Therefore, the therapeutic potential of artesunate (ART) on the progressive growth of therapy-sensitive (parental) and docetaxel (DX)-resistant PCa cells was investigated. Parental and DX-resistant PCa cell lines DU145, PC3, and LNCaP were incubated with artesunate (ART) [1-100 µM]. ART-untreated and ‘non-cancerous’ cells served as controls. Cell growth, proliferation, cell cycle progression, cell death and the expression of involved proteins were evaluated. ART, dose- and time-dependently, significantly restricted cell growth and proliferation of parental and DX-resistant PCa cells, but not of ‘normal, non-cancerous’ cells. ART-induced growth and proliferation inhibition was accompanied by G0/G1 phase arrest and down-regulation of cell cycle activating proteins in all DX-resistant PCa cells and parental LNCaP. In the parental and DX-resistant PC3 and LNCaP cell lines, ART also promoted apoptotic cell death. Ferroptosis was exclusively induced by ART in parental and DX-resistant DU145 cells by increasing reactive oxygen species (ROS). The anti-cancer activity displayed by ART took effect in all three PCa cell lines, but through different mechanisms of action. Thus, in advanced PCa, ART may hold promise as a complementary treatment together with conventional therapy.
Implementation of a Delirium Bundle for Pediatric Intensive Care Patients
Authors: Michel Jörg , Schepan Elena , Hofbeck Michael , Engel Juliane , Simma Alexander , Neunhoeffer Felix
Published: February 2022

Background and Objective

Delirium represents the most common form of acute cerebral dysfunction in critical illness. The prevention, recognition, and treatment of delirium must become the focus of modern pediatric intensive care, as delirium can lead to increased morbidity and mortality. The aim of this study is to evaluate the impact of a delirium bundle consisting of mainly non-pharmacological measures.

Material and Methods

This is a pre-/post-implementation study in an interdisciplinary pediatric intensive care unit of a tertiary care university hospital. In the pre-implementation period, pediatric intensive care delirium was monitored using the Sophia Observation withdrawal Symptoms and Pediatric Delirium scale. After introduction of a delirium bundle consisting of non-pharmacological prevention and treatment measures a period of 4 months was interposed to train the PICU staff and ensure that the delirium bundle was implemented consistently before evaluating the effects in the post-implementation period. Data collection included prevalence of delirium and withdrawal, length of PICU stay, duration of mechanical ventilation, and cumulative dose of sedatives and analgesics.

Results

A total of 792 critically ill children aged 0–18 years were included in this study. An overall delirium prevalence of 30% was recorded in the pre-implementation group and 26% in the post-implementation group (p = 0.13). A significant reduction in the prevalence of pediatric delirium from was achieved in the subgroup of patients under 5 years of age (27.9 vs. 35.8%, p = 0.04) and in patients after surgery for congenital heart disease (28.2 vs. 39.5%, p = 0.04). Young age, length of PICU stay, and iatrogenic withdrawal syndrome were found to be risk factors for developing delirium.

Conclusions

Based on a validated delirium monitoring, our study gives new information regarding the prevalence of pediatric delirium and the characteristics of intensive care patients at risk for this significant complication. Especially young patients and patients after surgery for congenital heart disease seem to benefit from the implementation of non-pharmacological delirium bundles. Based on our findings, it is important to promote change in pediatric intensive care—toward a comprehensive approach to prevent delirium in critically ill children as best as possible.
Comparative Analysis of the Efficacy and Safety of Different Traditional Chinese Medicine Injections in the Treatment of Cancer-Related Pain: A Bayesian Network Meta-Analysis
Authors: Su Pengli , Leng Yuanyuan , Liu Jun , Yu Yanan , Wang Zhong , Dang Haixia
Published: February 2022

Background: Given the limitations of three-step analgesic therapy and the extensive use of traditional Chinese medicine injections (TCMIs) for cancer-related pain (CRP), this network meta-analysis (NMA) aims to compare the efficacy and safety of different regimens of TCMIs for CRP.

Methods: A literature search was conducted in seven electronic databases for all related articles published before 12 April 2021. Randomized controlled trials (RCTs) were screened by a prior eligible criteria. The quality of literature was evaluated by the Cochrane risk of bias tool. We used Stata 16.0 software to analyze data including total pain relief rate, quality of life, and the incidence of adverse reactions. The surface under the cumulative ranking curve (SUCRA) probability values were applied to rank the interventions. Radar map was used to exhibit the most outstanding regimen for a certain outcome. Synthetic sorting bubble diagram was performed to show the relatively better regimen by integrating two or three outcomes.

Results: A total of 84 RCTs involving 8,044 patients were included. The results indicated that YDZYR + AN (Yadanziyouru injection plus analgesic) ranked first for pain relief rate, closely followed by KLT + AN (Kanglaite injection plus analgesic). AD + AN (Aidi injection plus analgesic) ranked first for quality of life, KLT + AN following closely. The total adverse reaction rate of FFKS + AN (Fufangkushen injection plus analgesic) was the lowest, and the constipation rate of FFKS was the lowest. In terms of the incidence of nausea and vomiting, KLT + AN was the best choice. In the plots analysis, the results of integrated total incidence of adverse reactions and pain relief rate analysis indicated that FFKS + AN was the most appropriate regimen. Meanwhile, it had the lowest incidence of integrated constipation, nausea and vomiting, and total adverse reactions. KLT + AN was the best in alleviating pain and improving quality of life integrated outcomes.

Conclusion: In conclusion, FFKS + AN was the best treatment regimen for the pain relief rate and total adverse reaction rate, and it was also the safest regimen for CRP treatment. KLT + AN was the most effective choice. Further, compared with analgesic treatment alone for patients with CRP, TCMIs + AN combination treatment strategies are significantly more effective. However, more high-quality RCTs are required to support these conclusions.

Systematic Review Registration: (https://www.crd.york.ac.uk/prospero/#recordDetails, https://www.crd.york.ac.uk/prospero/export_details_pdf.php), identifier (ChiCTR-ONC-CRD42021267829)
Evidence Mapping of 23 Systematic Reviews of Traditional Chinese Medicine Combined With Western Medicine Approaches for COVID-19
Authors: Zhang Ting , Li Xuechao , Chen Yamin , Zhao Liang , Tian Jinhui , Zhang Junhua
Published: February 2022

Background: Coronavirus disease 2019 (COVID-19) has already spread around the world. The modality of traditional Chinese medicine (TCM) combined with Western medicine (WM) approaches is being used to treat COVID-19 patients in China. Several systematic reviews (SRs) are available highlighting the efficacy and safety of TCM combined with WM approaches in COVID-19 patients. However, their evidence quality is not completely validated.

Purpose: We aimed to assess the methodological quality and the risk of bias of the included SRs, assess the evidence quality of outcomes, and present their trends and gaps using the evidence mapping method.

Methods: PubMed, Cochrane Library, Embase, CNKI, CBM, and Wanfang Data were searched from inception until March 2021 to identify SRs pertaining to the field of TCM combined with WM approaches for COVID-19. The methodological quality of the SRs was assessed using the Assessment of Multiple Systematic Reviews 2 (AMSTAR 2), the risk of bias of the included SRs was assessed with the Risk of Bias in Systematic Review (ROBIS) tool, and the evidence quality of outcomes was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.

Results: In total, 23 SRs were found eligible. Twenty-one were rated of moderate confidence by AMSTAR 2, while 12 were rated at low risk using the ROBIS tool. In addition, most outcomes were graded as having moderate quality using the GRADE system. We found that the combined use of TCM and WM approaches could improve the CT recovery rate, effective rate, viral nucleic acid negative conversion rate, and the disappearance rate of fever, cough, and shortness of breath. Also, these approaches could decrease the conversion rate from mild to critical, white blood cell counts, and lymphocyte counts and shorten the time to viral assay conversion and the length of hospital stay.

Conclusion: TCM combined with WM approaches had advantages in efficacy, laboratory, and clinical symptom outcomes of COVID-19, but the methodological deficiencies of SRs should be taken into consideration. Therefore, to better guide clinical practice in the future, the methodological quality of SRs should still be improved, and high-quality randomized controlled trials (RCTs) and observational studies should also be carried out.
Evaluation of Bacteriophage Cocktail on Septicemia Caused by Colistin-Resistant Klebsiella pneumoniae in Mice Model
Authors: Singh Aprajita , Singh Alakh Narayan , Rathor Nisha , Chaudhry Rama , Singh Sudhir Kumar , Nath Gopal
Published: February 2022

Objective:The emergence of resistance against last-resort antibiotics, carbapenem and colistin, inKlebsiella pneumoniaehas been reported across the globe. Bacteriophage therapy seems to be one of the most promising alternatives. This study aimed to optimize the quantity and frequency of bacteriophage cocktail dosage/s required to eradicate theKlebsiella pneumoniaebacteria in immunocompetent septicemic mice.

Methods:The three most active phages ɸKpBHU4, ɸKpBHU7, and ɸKpBHU14 characterized by molecular and TEM analyses were in the form of cocktail and was given intraperitoneally to mice after inducing the septicemia mice model with a constant dose of 8 × 107colony-forming unit/mouse (CFU/mouse)Klebsiella pneumoniae. After that, the efficacy of the phage cocktail was analyzed at different dosages, that is, in increasing, variable, constant, and repeated dosages. Furthermore, interleukin-6 and endotoxin levels were estimated with variable doses of phage cocktail.

Results:We have elucidated that phage therapy is effective against theKlebsiella pneumoniaesepticemia mice model and is a promising alternative to antibiotic treatments. Our work delineates that a single dose of phage cocktail with 1 × 105plaque-forming unit/mouse (PFU/mouse) protects the mice from fatal outcomes at any stage of septicemia. However, a higher phage dosage of 1 × 1012 PFU/mice is fatal when given at the early hours of septicemia, while this high dose is not fatal at the later stages of septicemia. Moreover, multiple repeated dosages are required to eradicate the bacteria from peripheral blood. In addition, the IL-6 levels in the 1 × 105 PFU/mouse group remain lower, but in the 1 × 1012 PFU/mouse group remains high at all points, which were associated with fatal outcomes.

Conclusion:Our study showed that the optimized relatively lower and multiple dosages of phage cocktails with the strict monitoring of vitals in clinical settings might cure septicemia caused by MDR bacteria with different severity of infection.
Chemical Antioxidant Quality Markers of Chrysanthemum morifolium Using a Spectrum-Effect Approach
Authors: Lu Yi-Fan , Li Ding-Xiang , Zhang Ran , Zhao Lin-Lin , Qiu Zhen , Du Yan , Ji Shuai , Tang Dao-Quan
Published: February 2022

Traditionally, the quality evaluation of Chrysanthemum morifolium (CM) cv. (Juhua) attributes its habitats and processing methods, however, this strategy of neglecting bioactive ingredients usually results in deviation of quality evaluation. This study aims to explore the quality marker (Q-marker) based on spectrum-effect relationship and quality control strategy of CMs. The chromatographic fingerprint of 30 flower head samples of CMs from five different habitats including Hang-baiju, Gongju, Huaiju, Taiju and Boju were constructed by high performance liquid chromatography and analyzed through chemometrics methods such as similarity analysis (SA), cluster analysis (CA) and principal component analysis (PCA). The common peaks were quantified by external standard method and relative correction factor method. The in-vitro radical scavenging capacity assays of DPPH·, ·OH and ABTS were carried out. The Q-marker was explored by the correlation analysis between the contents of common peaks and in-vitro radical scavenging capacity, and then used to evaluate the quality of 30 flower head samples of CMs. A total of eight common peaks were appointed in 30 flower head samples of CMs, and their similarities ranged from 0.640 to 0.956. CA results showed that 30 flower head samples of CMs could be divided into five categories with reference to the Euclidean distance of 5. PCA results showed that common peaks played a major role in differential contribution of CMs. The quantification of common peaks hinted that their contents possessed significant variation whether for different accessions or the same accessions of CMs. The correlation analysis showed that chlorogenic acid, 3,5-O-dicaffeoylquinic acid, unknown peak 1, 4,5-O-dicaffeoylquinic acid and kaempferol-3-O-rutinoside could be used as the Q-markers for the quality evaluation of 30 flower head samples of commercially available CMs. The analysis strategy that combines chromatographic fingerprint analysis, multiple ingredients quantification, in-vitro chemical anti-oxidant activity evaluation and spectrum-effect relationship analysis clarified the therapeutic material basis and discovered the Q-markers, which possibly offers a more comprehensive quality assessment of CMs.
A New Approach of Fatigue Classification Based on Data of Tongue and Pulse With Machine Learning
Authors: Shi Yulin , Yao Xinghua , Xu Jiatuo , Hu Xiaojuan , Tu Liping , Lan Fang , Cui Ji , Cui Longtao , Huang Jingbin , Li Jun , Bi Zijuan , Li Jiacai
Published: February 2022

Background

Fatigue is a common and subjective symptom, which is associated with many diseases and suboptimal health status. A reliable and evidence-based approach is lacking to distinguish disease fatigue and non-disease fatigue. This study aimed to establish a method for early differential diagnosis of fatigue, which can be used to distinguish disease fatigue from non-disease fatigue, and to investigate the feasibility of characterizing fatigue states in a view of tongue and pulse data analysis.

Methods

Tongue and Face Diagnosis Analysis-1 (TFDA-1) instrument and Pulse Diagnosis Analysis-1 (PDA-1) instrument were used to collect tongue and pulse data. Four machine learning models were used to perform classification experiments of disease fatigue vs. non-disease fatigue.

Results

The results showed that all the four classifiers over “Tongue & Pulse” joint data showed better performances than those only over tongue data or only over pulse data. The model accuracy rates based on logistic regression, support vector machine, random forest, and neural network were (85.51 ± 1.87)%, (83.78 ± 4.39)%, (83.27 ± 3.48)% and (85.82 ± 3.01)%, and with Area Under Curve estimates of 0.9160 ± 0.0136, 0.9106 ± 0.0365, 0.8959 ± 0.0254 and 0.9239 ± 0.0174, respectively.

Conclusion

This study proposed and validated an innovative, non-invasive differential diagnosis approach. Results suggest that it is feasible to characterize disease fatigue and non-disease fatigue by using objective tongue data and pulse data.