bluuebunny/crossref_metadata_2025 huggingface dataset:
Sampling Constraints and Variability in the Analysis of Bacterial Community Structures in the Sea Surface Microlayer
Authors: Wong Shu-Kuan , Suzuki Shotaro , Cui Yingshun , Kaneko Ryo , Kogure Kazuhiro , Hamasaki Koji
Published: June 2021

The sea surface microlayer (SML) is a thin surface film located at the interface between oceans and the atmosphere. In this study, three SML samplers—polycarbonate membrane (PC), glass plate (GP), and drum sampler (DS)—were used to collect microbiological DNA samples for molecular analysis. Among the three samplers, DS only took half the time to sample the SML compared to GP while PC were able to sample the thinnest SML depth. Biological matter and distinct bacterial communities in the SML were apparent during low wind conditions in samples collected by three samplers. Signs of biological matter [transparent exopolymer particles (TEP) and chlorophyll-a concentrations] depletion, and an increased similarity in the biological communities of the SML and underlying water (UW), were more pronounced during high wind speed conditions in samples collected by GP and DS. GP samples had lower biological matter enrichment than DS samples compared with UW. The depletion of biological matter in GP samples were more apparent during periods of high chl-a concentrations in the SML. In contrast, PC was able to consistently sample an SML community distinct from that of the UW, regardless of wind conditions. Bacterial community DNA samples obtained by the three SML samplers showed relatively consistent patterns of community structure, despite large fluctuations between seasons (summer vs. winter) and layers (SML vs. UW) being observed. Although no SML-specific taxon was detected in this study, a comparison of the representation of taxonomic groups in each sample suggested that certain taxa (15 orders) were specifically enriched or depleted in the SML, especially taxa belonging to Actinobacteria, Cyanobacteria, Deferribacteria, and Proteobacteria. This trend was consistent regardless of sampling method, implying that these bacterial groups are key taxa in the biogeochemical processes occurring at the air-sea interface.
Characterizing Biaxially Stretched Polypropylene / Graphene Nanoplatelet Composites
Authors: Mayoral B. , Menary G , Martin P , Garrett G , Millar B , Douglas P , Khanam N. , AlMaadeed M. A. , Ouederni M. , Hamilton A. , Sun D.
Published: June 2021

In this work, polypropylene (PP) nanocomposites containing different weight concentration of graphene nanoplatelets (GNP) were prepared by melt-mixing using an industrial-scale, co-rotating, intermeshing, twin-screw extruder. The materials were then compression moulded into sheets, and biaxially stretched at different stretching ratios (SRs) below the PP melting temperature. The effects of GNP content and biaxial stretching on the bulk properties of unfilled PP and PP/GNP nanocomposites have been investigated in details. Results show that the addition of GNP (>5wt%) can lead to electrically conductive composites due to the formation of percolation network. The GNP have led to increased polymer crystallinity and enhanced materials stiffness and strength. Biaxial stretching process further enhances the materials mechanical properties but has slightly decreased the composites electrical conductivity. The PP/GNP nanocomposites were also processed into 3D demonstrator parts using vacuum forming, and the properties of which were comparable with biaxially stretched composites.
Mesoporous Silica Based Nanostructures for Bone Tissue Regeneration
Authors: Ghosh Sougata , Webster Thomas J.
Published: June 2021

Porous nano-scaffolds provide for better opportunities to restore, maintain, and improve functions of damaged tissues and organs by facilitating tissue regeneration. Various nanohybrids composed of mesoporous silica nanoparticles (MSNs) are being widely explored for tissue engineering. Since biological activity is enhanced by several orders of magnitude in multicomponent scaffolds, remarkable progress has been observed in this field, which has aimed to develop the controlled synthesis of multifunctional MSNs with tuneable pore size, efficient delivering capacity of bioactive factors, as well as enhanced biocompatibility and biodegradability. In this review, we aim to provide a broad survey of the synthesis of multifunctional MSN based nanostructures with exotic shapes and sizes. Further, their promise as a novel nanomedicine is also elaborated with respect to their role in bone tissue engineering. Also, recent progress in surface modification and functionalization with various polymers like poly (l-lactic acid)/poly (ε-caprolactone), polylysine-modified polyethylenimine, poly (lactic-co-glycolic acid), and poly (citrate-siloxane) and biological polymers like alginate, chitosan, and gelatine are also covered. Several attempts for conjugating drugs like dexamethasone and β–estradiol, antibiotics like vancomycin and levofloxaci, and imaging agents like fluorescein isothiocyanate and gadolinium, on the surface modified MSNs are also covered. Finally, the scope of developing orthopaedic implants and potential trends in 3D bioprinting applications of MSNs are also discussed. Hence, MSNs based nanomaterials may serve as improved candidate biotemplates or scaffolds for numerous bone tissue engineering, drug delivery and imaging applications deserving our full attention now.
The Scientific and Clinical Case for Reviewing Diagnostic Radiopharmaceutical Extravasation Long-Standing Assumptions
Authors: Osborne Dustin , Lattanze Ronald , Knowland Josh , Bryant Tonia E. , Barvi Iryna , Fu Yitong , Kiser Jackson W.
Published: June 2021

Background:The patient benefit from a diagnostic nuclear medicine procedure far outweighs the associated radiation risk. This benefit/risk ratio assumes a properly administered radiopharmaceutical. However, a significant diagnostic radiopharmaceutical extravasation can confound the procedure in many ways. We identified three current extravasation hypotheses espoused by medical societies, advisory committees, and hundreds of individual members of the nuclear medicine community: diagnostic extravasations do not cause harm, do not result in high absorbed dose to tissue, and require complex dosimetry methods that are not readily available in nuclear medicine centers. We tested these hypotheses against a framework of current knowledge, recent developments, and original research. We conducted a literature review, searched regulatory databases, examined five clinical cases of extravasated patients, and performed dosimetry on those extravasations to test these globally accepted hypotheses.

Results:A literature review found 58 peer-reviewed documents suggesting patient harm. Adverse event/vigilance report database reviews for extravasations were conducted and revealed 38 adverse events which listed diagnostic radiopharmaceutical extravasation as a factor, despite a regulatory exemption for required reporting. In our own case material, assessment of care was evaluated for five extravasated patients who underwent repeat imaging. Findings reflected results of literature review and included mis- or non-identification of lesions, underestimation of Standardized Uptake Values (SUVs) by 19–73%, classification of scans as non-diagnostic, and the need to repeat imaging with the associated additional radiation exposure, inconvenience, or delays in care. Dosimetry was performed for the same five cases of diagnostic radiopharmaceutical extravasation. Absorbed doses to 5 cm3of tissue were between 1.1 and 8.7 Gy, and shallow dose equivalent for 10 cm2of skin was as high as 4.2 Sv.

Conclusions:Our findings suggest that significant extravasations can or have caused patient harm and can irradiate patients' tissue with doses that exceed medical event reporting limits and deterministic effect thresholds. Therefore, diagnostic radiopharmaceutical injections should be monitored, and dosimetry of extravasated tissue should be performed in certain cases where thresholds are thought to have been exceeded. Process improvement efforts should be implemented to reduce the frequency of extravasation in nuclear medicine.
Dermoscopic Features Summarization and Comparison of Four Types of Cutaneous Vascular Anomalies
Authors: Gao Jing , Fei Wenmin , Shen Changbing , Shen Xue , Sun Minghui , Xu Ning , Li Qing , Huang Cong , Zhang Tingfang , Ko Randy , Cui Yong , Yang Chunjun
Published: June 2021

Objective: Dermoscopic features of cutaneous vascular anomalies have been reported, but the described features currently known are limited and not well-understood. The aim of this study is to comprehensively summarize and compare the dermoscopic features of the four different types of cutaneous vascular anomalies [infantile hemangiomas (IH), cherry angioma (CA), angiokeratomas (AK), and pyogenic granuloma (PG)] in the Chinese Han population.

Materials and Methods: Dermoscopic features of 31 IH, 172 CA, 31 AK, and 45 PG were collected based on the contact non-polarized mode of dermoscopy at 20-fold magnification. Dermoscopic features including background, lacunae, vessel morphology and distribution were collected and summarized. Additionally, we compared these features by age stage, gender, and anatomical locations in CA.

Results: The dermoscopic features of IH included the red lacunae, red/red-blue/red-white backgrounds, and vessel morphology such as linear curved vessels, serpiginous vessels, coiled vessels. For CA, the lacunae appeared reddish brown to reddish blue or only red. In terms of vascular morphology, serpentine vessels, coiled vessels, looped vessels, and curved vessels could be seen in the lesions. A few lesions were black or presented with a superficial white veil. There were statistical differences in red background (P = 0.021), unspecific vessel distribution (P = 0.030), black area (P = 0.029), and white surface (P = 0.042) among different age groups. Red-brown lacunae (P = 0.039), red-blue (P = 0.013), red-white background (P = 0.015), black area (P = 0.016), and white surface (P = 0.046) were of statistical difference in terms of the locations of lesions. Lacunae were also observed in AK, which presented with red, dark purple, dark blue, black. Global dermoscopic patterns that were characterized by a homogeneous area were obvious in all PG lesions, among which 30 (66.7%) were red-white and 15 (33.3%) were red. As for local features, “white rail” lines were detected in 19 (42.2%) lesions and white collarette was seen in 34 (75.6%) lesions.

Conclusions: Dermoscopy is an applicable diagnostic tool for the diagnosis of cutaneous vascular anomalies. It is necessary to take into account the age stage and lesion location when we diagnose CA using dermoscopy.
Identification of Microbiological Activities in Wet Flue Gas Desulfurization Systems
Authors: Martin Gregory , Sharma Shagun , Ryan William , Srinivasan Nanda K. , Senko John M.
Published: June 2021

Thermoelectric power generation from coal requires large amounts of water, much of which is used for wet flue gas desulfurization (wFGD) systems that minimize sulfur emissions, and consequently, acid rain. The microbial communities in wFGDs and throughout thermoelectric power plants can influence system performance, waste processing, and the long term stewardship of residual wastes. Any microorganisms that survive in wFGD slurries must tolerate high total dissolved solids concentrations (TDS) and temperatures (50–60°C), but the inocula for wFGDs are typically from fresh surface waters (e.g., lakes or rivers) of low TDS and temperatures, and whose activity might be limited under the physicochemically extreme conditions of the wFGD. To determine the extents of microbiological activities in wFGDs, we examined the microbial activities and communities associated with three wFGDs. O2 consumption rates of three wFGD slurries were optimal at 55°C, and living cells could be detected microscopically, indicating that living and active communities of organisms were present in the wFGD and could metabolize at the high temperature of the wFGD. A 16S rRNA gene-based survey revealed that the wFGD-associated microbial communities included taxa attributable to both thermophilic and mesophilic lineages. Metatranscriptomic analysis of one of the wFGDs indicated an abundance of active Burholderiaceae and several Gammaproteobacteria, and production of transcripts associated with carbohydrate metabolism, osmotic stress response, as well as phage, prophages, and transposable elements. These results illustrate that microbial activities can be sustained in physicochemically extreme wFGDs, and these activities may influence the performance and environmental impacts of thermoelectric power plants.
The Role of OmpR in Bile Tolerance and Pathogenesis of Adherent-Invasive Escherichia coli
Authors: Lucchini Valentina , Sivignon Adeline , Pieren Michel , Gitzinger Marc , Lociuro Sergio , Barnich Nicolas , Kemmer Christian , Trebosc Vincent
Published: June 2021

Gut microbiota dysbiosis toward adherent-invasive Escherichia coli (AIEC) plays an important role in Crohn’s disease (CD). The OmpR transcriptional regulator is required for the AIEC LF82 prototype strain to adhere and invade intestinal epithelial cells. In this study, we explored the role of OmpR in AIEC pathogenesis using a panel of eight Escherichia coli strains isolated from CD patients and identified as AIEC. The deletion of ompR together with the implementation of two cell-based assays revealed that the role of OmpR in adhesion in vitro was not conserved in AIEC clinical strains. Nevertheless, we showed that OmpR was required for robust gut colonization of transgenic mice expressing human CEACAM receptors, suggesting that OmpR is involved in alternative virulence mechanisms in AIEC strains. We found that deletion of ompR compromised the ability of AIEC strains to cope with the stress induced by bile salts, which may be key for AIEC pathogenesis. More specifically, we demonstrated that OmpR was involved in a tolerance mechanism toward sodium deoxycholate (DOC), one of bile salts main component. We showed that the misregulation of OmpF or the loss of outer membrane integrity are not the drivers of OmpR-mediated DOC tolerance, suggesting that OmpR regulates a specific mechanism enhancing AIEC survival in the presence of DOC. In conclusion, the newly discovered role of OmpR in AIEC bile tolerance suggests that OmpR inhibition would interfere with different aspects of AIEC virulence arsenal and could be an alternative strategy for CD-treatment.
Analysis of the Prognostic Value and Gene Expression Mechanism of SHOX2 in Lung Adenocarcinoma
Authors: Li Nanhong , Zeng Yu , Tai Min , Lin Biyun , Zhu Di , Luo Yi , Ren Xinle , Zhu Xiaoying , Li Lanlan , Wu Hongrong , Huang Jian
Published: June 2021

Background: Detection of SHOX2 methylation has been used to assist in the early diagnosis of lung cancer in many hospitals as SHOX2 may be important in the tumorigenesis of lung cancer. However, there are few studies on the mRNA expression, methylation, and molecular mechanism of SHOX2 in lung cancer. We aimed to explore the role of SHOX2 in lung adenocarcinoma (LUAD).

Methods: First, we examined the differential expression of SHOX2 mRNA and methylation in cancerous and normal tissues using databases. Second, we analyzed the relationship between SHOX2 expression and common clinical parameters in LUAD patients. Third, we further explored the methylated level and its specific location of SHOX2 and the mainly factors of SHOX2 gene expression. Finally, we screened the correlatively expressed genes to analyze the pathways from the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes using DAVID.

Results: We found that the mRNA expression of SHOX2 was higher in multiple cancers, including LUAD and lung squamous cell carcinoma (LUSC), than in normal tissues. Among LUAD patients, SHOX2 expression was higher in patients of middle–young age, with smoking history, in advanced stages, and with nodal distant metastasis. In addition, our results showed that patients with high expression of SHOX2 are prone to recurrence, poor differentiation, and poor prognosis. Thus, we identified that SHOX2 might be an oncogene for LUAD progression. The main factor influencing the high expression of SHOX2 mRNA may be DNA methylation, followed by copy number variation (CNV), but not by gene mutations in LUAD. Unexpectedly, we found that SHOX2 undergoes hypomethylation in the gene body instead of hypermethylation in the promoter. Additionally, SHOX2 has cross talk in the PI3K–Akt signaling pathway and ECM–receptor interaction.

Conclusion:SHOX2 is highly expressed in most cancers. SHOX2 gene expression might be mainly regulated by methylation of its gene body in LUAD, and its high expression or hypomethylation indicates poor differentiation and poor prognosis. SHOX2 could be involved in PI3K–Akt and other important cancer-related signaling pathways to promote tumorigenesis.
Early Findings in Neonatal Cases of RYR1–Related Congenital Myopathies
Authors: Mauri Eleonora , Piga Daniela , Govoni Alessandra , Brusa Roberta , Pagliarani Serena , Ripolone Michela , Dilena Robertino , Cinnante Claudia , Sciacco Monica , Cassandrini Denise , Nigro Vincenzo , Bresolin Nereo , Corti Stefania , Comi Giacomo P. , Magri Francesca
Published: June 2021

Ryanodine receptor type 1-related congenital myopathies are the most represented subgroup among congenital myopathies (CMs), typically presenting a central core or multiminicore muscle histopathology and high clinical heterogeneity. We evaluated a cohort of patients affected with Ryanodine receptor type 1-related congenital myopathy (RYR1-RCM), focusing on four patients who showed a severe congenital phenotype and underwent a comprehensive characterization at few months of life. To date there are few reports on precocious instrumental assessment. In two out of the four patients, a muscle biopsy was performed in the first days of life (day 5 and 37, respectively) and electron microscopy was carried out in two patients detecting typical features of congenital myopathy. Two patients underwent brain MRI in the first months of life (15 days and 2 months, respectively), one also a fetal brain MRI. In three children electromyography was performed in the first week of life and neurogenic signs were excluded. Muscle MRI obtained within the first years of life showed a typical pattern of RYR1-CM. The diagnosis was confirmed through genetic analysis in three out of four cases using Next Generation Sequencing (NGS) panels. The development of a correct and rapid diagnosis is a priority and may lead to prompt medical management and helps optimize inclusion in future clinical trials.
Music Therapy Alleviates Motor Dysfunction in Rats With Focal Cerebral Ischemia–Reperfusion Injury by Regulating BDNF Expression
Authors: Chen Weiguan , Zheng Jiaxuan , Shen Guangyu , Ji Xin , Sun Linlin , Li Xia , Xu Feng , Gu Jin-hua
Published: June 2021

Background/Aim: Music-based therapy plays a role in central nervous system diseases. We aimed to explore the effect of different doses and durations of music therapy on motor function recovery after stroke and the underlying molecular mechanisms.

Methods: Adult male Sprague–Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 1 h, which was followed by reperfusion. In experiment 1, the rats that survived 1 week after MCAO surgery were randomly allocated into four groups (n = 10 per group): MCAO group, 1 h music group (Mozart K.448 music therapy 1 h per day for 2 weeks), 12 h music group (Mozart K.448 music therapy 12 h/day for 2 weeks), and accelerated music group (reversely accelerated music therapy 12 h for 2 weeks, AM group). In experiment 2, the survived rats were randomly divied into three groups: MCAO group, 12 h music group (music therapy 12 h/day for 3 weeks), and 12 h music-R group (music therapy 12 h/day for 2 weeks and rest for 1 week). Three neuroscores were evaluated daily, starting on the first day after surgery until the end of the experiment. The rats were killed 3 weeks after MCAO surgery in experiment 1 or 4 weeks after surgery in experiment 2. Nissl staining of infart core, peri-infarct zone, and motor cortex was performed to assess neuronal survival and regeneration. Western blot and immunofluorescence were used to detect the expression and distribution of brain-derived neurotrophic factor (BDNF) and glial fibrillary acidic protein (GFAP) in ipsilateral hemispheres.

Results: In the experiment of different music therapy doses, the motor function in the 12-h music group but not in the 1-h music group and AM group was significantly improved compared with that of the MCAO group. The BDNF protein level of the ipsilateral hemisphere motor cortex in the 12-h music group and the 1-h music group was higher than that of the MCAO group. The neurons and Nissl bodies were more in the 12-h music group than in the MCAO group. Immunofluorescence assay showed that a 12 h music therapy induces BDNF and GFAP accumulation at the damage boundary. In the experiment of different music therapy durations, 3 weeks music therapy (12 h music group) induced more longer cell synapses and more clearer cell-to-cell connections than 2 weeks music intervention (12 h music-R group). Moreover, the GFAP morphology in the 12-h music group was more similar to mature activated astrocytes than that in the 12-h music-R group.

Conclusions: Music therapy may improve poststroke motor function and promote neuronal repair in the long term. The mechanism may be through stimulating BDNF and GFAP secretion in the injured motor cortex.
The Resting-State Electroencephalogram Microstate Correlations With Empathy and Their Moderating Effect on the Relationship Between Empathy and Disgust
Authors: Zhang Meng , Li Zhaoxian , Wang Li , Yang Shiyan , Zou Feng , Wang Yufeng , Wu Xin , Luo Yanyan
Published: June 2021

Humans have a natural ability to understand the emotions and feelings of others, whether one actually witnesses the situation of another, perceives it from a photograph, reads about it in a fiction book, or merely imagines it. This is the phenomenon of empathy, which requires us to mentally represent external information to experience the emotions of others. Studies have shown that individuals with high empathy have high anterior insula and adjacent frontal operculum activation when they are aware of negative emotions in others. As a negative emotion, disgust processing involves insula coupling. What are the neurophysiological characteristics for regulating the levels of empathy and disgust? To answer this question, we collected electroencephalogram microstates (EEG-ms) of 196 college students at rest and used the Disgust Scale and Interpersonal Reactivity Index. The results showed that: (1) there was a significant positive correlation between empathy and disgust sensitivity; (2) the empathy score and the intensity of transition possibility between EEG-ms C and D were significantly positively correlated; and (3) the connection strength between the transition possibility of EEG-ms C and D could adjust the relationship between the disgust sensitivity score and the empathy score. This study provides new neurophysiological characteristics for an understanding of the regulate relationship between empathy and disgust and provides a new perspective on emotion and attention.
The Role of White Matter in the Neural Control of Swallowing: A Systematic Review
Authors: Alvar Ann , Hahn Arkenberg Rachel , McGowan Bethany , Cheng Hu , Malandraki Georgia A.
Published: June 2021

Background: Swallowing disorders (dysphagia) can negatively impact quality of life and health. For clinicians and researchers seeking to improve outcomes for patients with dysphagia, understanding the neural control of swallowing is critical. The role of gray matter in swallowing control has been extensively documented, but knowledge is limited regarding the contributions of white matter. Our aim was to identify, evaluate, and summarize the populations, methods, and results of published articles describing the role of white matter in neural control of swallowing.

Methods: We completed a systematic review with a multi-engine search following PRISMA-P 2015 standards. Two authors screened articles and completed blind full-text review and quality assessments using an adapted U.S. National Institute of Health's Quality Assessment. The senior author resolved any disagreements. Qualitative synthesis of evidence was completed.

Results: The search yielded 105 non-duplicate articles, twenty-two of which met inclusion criteria. Twenty were rated as Good (5/22; 23%) or Fair (15/22; 68%) quality. Stroke was the most represented diagnosis (n = 20; 91%). All studies were observational, and half were retrospective cohort design. The majority of studies (13/22; 59%) quantified white matter damage with lesion-based methods, whereas 7/22 (32%) described intrinsic characteristics of white matter using methods like fractional anisotropy. Fifteen studies (68%) used instrumental methods for swallowing evaluations. White matter areas commonly implicated in swallowing control included the pyramidal tract, internal capsule, corona radiata, superior longitudinal fasciculus, external capsule, and corpus callosum. Additional noteworthy themes included: severity of white matter damage is related to dysphagia severity; bilateral white matter lesions appear particularly disruptive to swallowing; and white matter adaptation can facilitate dysphagia recovery. Gaps in the literature included limited sample size and populations, lack of in-depth evaluations, and issues with research design.

Conclusion: Although traditionally understudied, there is sufficient evidence to conclude that white matter is critical in the neural control of swallowing. The reviewed studies indicated that white matter damage can be directly tied to swallowing deficits, and several white matter structures were implicated across studies. Further well-designed interdisciplinary research is needed to understand white matter's role in neural control of normal swallowing and in dysphagia recovery and rehabilitation.
Norms for Automatic Estimation of Hippocampal Atrophy and a Step Forward for Applicability to the Italian Population
Authors: De Francesco Silvia , Galluzzi Samantha , Vanacore Nicola , Festari Cristina , Rossini Paolo Maria , Cappa Stefano F. , Frisoni Giovanni B. , Redolfi Alberto
Published: June 2021

Introduction

Hippocampal volume is one of the main biomarkers of Alzheimer’s Dementia (AD). Over the years, advanced tools that performed automatic segmentation of Magnetic Resonance Imaging (MRI) T13D scans have been developed, such as FreeSurfer (FS) and ACM-Adaboost (AA). Hippocampal volume is considered abnormal when it is below the 5th percentile of the normative population. The aim of this study was to set norms, established from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) population, for hippocampal volume measured with FS v.6.0 and AA tools in the neuGRID platform (www.neugrid2.eu) and demonstrate their applicability for the Italian population.

Methods

Norms were set from a large group of 545 healthy controls belonging to ADNI. For each pipeline, subjects with segmentation errors were discarded, resulting in 532 valid segmentations for FS and 421 for AA (age range 56–90 years). The comparability of ADNI and the Italian Brain Normative Archive (IBNA), representative of the Italian general population, was assessed testing clinical variables, neuropsychological scores and normalized hippocampal volumes. Finally, percentiles were validated using the Italian Alzheimer’s disease Repository Without Borders (ARWiBo) as external independent data set to evaluate FS and AA generalizability.

Results

Hippocampal percentiles were checked with the chi-square goodness of fit test. P-values were not significant, showing that FS and AA algorithm distributions fitted the data well. Clinical, neuropsychological and volumetric features were similar in ADNI and IBNA (p > 0.01). Hippocampal volumes measured with both FS and AA were associated with age (p < 0.001). The 5th percentile thresholds, indicating left/right hippocampal atrophy were respectively: (i) below 3,223/3,456 mm3 at 56 years and 2,506/2,415 mm3 at 90 years for FS; (ii) below 4,583/4,873 mm3 at 56 years and 3,831/3,870 mm3 at 90 years for AA. The average volumes computed on 100 cognitively intact healthy controls (CN) selected from ARWiBo were close to the 50th percentiles, while those for 100 AD patients were close to the abnormal percentiles.

Discussion

Norms generated from ADNI through the automatic FS and AA segmentation tools may be used as normative references for Italian patients with suspected AD.
Therapeutic and Industrial Applications of Curdlan With Overview on Its Recent Patents
Authors: Chaudhari Vinay , Buttar Harpal Singh , Bagwe-Parab Siddhi , Tuli Hardeep Singh , Vora Amisha , Kaur Ginpreet
Published: June 2021

Curdlan is an exopolysaccharide, which is composed of glucose linked with β-(1,3)-glycosidic bond and is produced by bacteria, such as Alcaligenes spp., Agrobacterium spp., Paenibacillus spp., Rhizobium spp., Saccharomyces cerevisiae, Candida spp., and fungal sources like Aureobasidium pullulan, Poria cocos, etc. Curdlan has been utilized in the food and pharmaceutical industries for its prebiotic, viscosifying, and water-holding properties for decades. Recently, the usefulness of curdlan has been further explored by the pharmaceutical industry for its potential therapeutic applications. Curdlan has exhibited immunoregulatory and antitumor activity in preclinical settings. It was observed that curdlan can prevent the proliferation of malarial merozoites in vivo; therefore, it may be considered as a promising therapy for the treatment of end-stage malaria. In addition, curdlan has demonstrated potent antiviral effects against human immunodeficiency virus (HIV) and Aedes aegypti virus. It has been suggested that the virucidal properties of curdlans should be extended further for other deadly viruses, such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and the current severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2/COVID-19). The prebiotic property of curdlan would confer beneficial effects on the host by promoting the growth of healthy microbiota in the gut and consequently help to reduce gastrointestinal disorders. Therefore, curdlan can be employed in the manufacture of prebiotics for the management of various gastrointestinal dysbiosis problems. Studies on the mechanism of action of curdlan-induced suppression in microbial and tumor cells at the cellular and molecular levels would not only enhance our understanding regarding the therapeutic effectiveness of curdlan but also help in the discovery of new drugs and dietary supplements. The primary focus of this review is to highlight the therapeutic interventions of curdlan as an anticancer, anti-malaria, antiviral, and antibacterial agent in humans. In addition, our review provides the latest information about the chemistry and biosynthesis of curdlan and its applications for making novel dairy products, functional foods, and nutraceuticals and also details about the recent patents of curdlan and its derivatives.
Biosynthesis of a Novel Antibacterial Dipeptide, Using Proteases From South American Native Fruits, Useful as a Food Preservative
Authors: Adaro Mauricio , Bersi Grisel , Talia Juan Manuel , Bernal Claudia , Guzmán Fanny , Vallés Diego , Barberis Sonia
Published: June 2021

Antiacanthainandgranulosainare the partially purified proteolytic extracts from the South American native fruits ofBromelia antiacantha(Bertol. ) andSolanum granuloso leprosum, respectively. The aim of this work was to compare the ability of both soluble and immobilizedantiacanthainandgranulosain for the synthesis of Z-Tyr-Val-OH, a novel antibacterial dipeptide, in different reaction systems formed by almost anhydrous organic solvents (Xw: 1 × 10−5) and several percentages of immiscible organic solvents in 100 mM Tris(hydroxymethyl)aminomethane hydrochloride buffer pH 8.0. Soluble antiacanthain in half of the 24 different organic biphasic media showed higher catalytic potential than in 100 mM Tris(hydroxymethyl)aminomethane hydrolchloride buffer pH 8.0. Soluble granulosain showed lower catalytic potential in all liquid-liquid biphasic media than in the same buffer. However, 50% (v/v) ethyl ethanoate in 100 mM Tris(hydroxymethyl)aminomethane hydrolchloride buffer pH 8.0 allowed to express the highest catalytic potential of both soluble enzymes. In 50% v/v ethyl ethanoate, soluble antiacanthain and granulosain catalyzed the synthesis of Z-Tyr-Val-OH with 72 ± 0.15 and 60 ± 0.10% maximal peptide yields, respectively. Multi-point immobilization in glyoxyl-silica did not lead to better peptide yields than soluble enzymes, in that liquid-liquid biphasic medium under the same reaction conditions. Soluble and glyoxyl-silica immobilized antiacanthain in almost anhydrous ethyl ethanoate (Xw: 1 × 10−5) were able to retain 17.3 and 45% of the initial proteolytic activity of antiacanthain in 100 mM Tris hydrolchloride buffer pH 8.0, respectively, at 40°C under agitation (200 rpm). Soluble and glyoxyl-silica immobilized granulosain were inactivated under the same reaction conditions. Glyoxyl-silica immobilized antiacanthain showed to be a robust biocatalyst in almost anhydrous ethyl ethanoate (Xw: 1 × 10−5), eliciting the best peptide yield (75 ± 0.13%). The synthesis reaction of Z-Tyr-Val-OH could not proceed when soluble antiacanthain was used under the same conditions. Both peptidases only catalyzed the synthesis reaction under kinetic control, using activated acyl donor substrates. Finally, this work reports a novel broad-spectrum antibacterial peptide that significantly decreased (p≤ 0.05) the specific growth rates of Gram positive and Gram negative microorganisms at very low concentrations (≥15 and 35 μg/ml, respectively); contributing with a new safe food preservative of applying for different food systems.
Probiotic Effects of Lactobacillus fermentum ZJUIDS06 and Lactobacillus plantarum ZY08 on Hypercholesteremic Golden Hamsters
Authors: Yang Dongting , Lyu Wentao , Hu Ziyi , Gao Jiting , Zheng Zhiyao , Wang Weijun , Firrman Jenni , Ren Daxi
Published: June 2021

Hypercholesteremia or high cholesterol is one of the important factors leading to atherosclerosis and other cardiovascular diseases. The application of probiotics with cholesterol-lowering characteristics has become increasingly popular over the past decade due to their contribution to human health. This study aimed to evaluate the probiotic effects of Lactobacillus fermentum ZJUIDS06 and Lactobacillus plantarum ZY08 on hyperlipidemic golden hamsters. A hyperlipidemic model was established through a high cholesterol diet in golden hamsters, after which lyophilized Lactobacillus fermentum ZJUIDS06 and Lactobacillus plantarum ZY08 were orally administered individually for 8 weeks. The physiological characteristics of golden hamsters and short chain fatty acid (SCFA) in the colon were assessed by automatic Biochemical Analyzer and gas choromatograph, respectively. A MiSeq sequencing-based analysis of the bacterial 16S rRNA gene (V3–V4 region) in the cecum content was performed to analyze the cecum microbiota. Correlations between sets of these variables were also investigated using the R package “corrplot.” Results showed that neither Lactobacillus fermentum ZJUIDS06 nor Lactobacillus plantarum ZY08 inhibited body weight increase. However, supplementation with Lactobacillus fermentum ZJUIDS06 for 8 weeks increased colon SCFA levels (P < 0.05), decreased serum low-density lipoprotein, total cholesterol, and triglycerides levels, and also induced changes in the cecum microbiota of hyperlipidemic golden hamsters. Remarkably, oral administration of Lactobacillus fermentum ZJUIDS06 increased the relative abundance of Parabacteroides in the cecum, which served as a biomarker for colon SCFA production and improvement of serum cholesterol levels. In a word, Lactobacillus fermentum ZJUIDS06 improved hyperlipidemia in golden hamsters, which correlated with an increase in SCFA levels and relative abundance of Parabacteroides, indicating its potential importance in functional foods that can help lower cholesterol.
Tumor Microenvironment Alters Chemoresistance of Hepatocellular Carcinoma Through CYP3A4 Metabolic Activity
Authors: Özkan Alican , Stolley Danielle L. , Cressman Erik N. K. , McMillin Matthew , DeMorrow Sharon , Yankeelov Thomas E. , Rylander Marissa Nichole
Published: June 2021

Variations in tumor biology from patient to patient combined with the low overall survival rate of hepatocellular carcinoma (HCC) present significant clinical challenges. During the progression of chronic liver diseases from inflammation to the development of HCC, microenvironmental properties, including tissue stiffness and oxygen concentration, change over time. This can potentially impact drug metabolism and subsequent therapy response to commonly utilized therapeutics, such as doxorubicin, multi-kinase inhibitors (e.g., sorafenib), and other drugs, including immunotherapies. In this study, we utilized four common HCC cell lines embedded in 3D collagen type-I gels of varying stiffnesses to mimic normal and cirrhotic livers with environmental oxygen regulation to quantify the impact of these microenvironmental factors on HCC chemoresistance. In general, we found that HCC cells with higher baseline levels of cytochrome p450-3A4 (CYP3A4) enzyme expression, HepG2 and C3Asub28, exhibited a cirrhosis-dependent increase in doxorubicin chemoresistance. Under the same conditions, HCC cell lines with lower CYP3A4 expression, HuH-7 and Hep3B2, showed a decrease in doxorubicin chemoresistance in response to an increase in microenvironmental stiffness. This differential therapeutic response was correlated with the regulation of CYP3A4 expression levels under the influence of stiffness and oxygen variation. In all tested HCC cell lines, the addition of sorafenib lowered the required doxorubicin dose to induce significant levels of cell death, demonstrating its potential to help reduce systemic doxorubicin toxicity when used in combination. These results suggest that patient-specific tumor microenvironmental factors, including tissue stiffness, hypoxia, and CYP3A4 activity levels, may need to be considered for more effective use of chemotherapeutics in HCC patients.
How the COVID-19 Pandemic Impacted on Integrated Care Pathways for Lung Cancer: The Parallel Experience of a COVID-Spared and a COVID-Dedicated Center
Authors: Pasello Giulia , Menis Jessica , Pilotto Sara , Frega Stefano , Belluomini Lorenzo , Pezzuto Federica , Caliò Anna , Sepulcri Matteo , Cernusco Nunzia Luna Valentina , Schiavon Marco , Infante Maurizio Valentino , Damin Marco , Micheletto Claudio , Del Bianco Paola , Giovannetti Riccardo , Bonanno Laura , Fantoni Umberto , Guarneri Valentina , Calabrese Fiorella , Rea Federico , Milella Michele , Conte PierFranco
Published: June 2021

Introduction

The COVID-19 pandemic has proved to be a historic challenge for healthcare systems, particularly with regard to cancer patients. So far, very limited data have been presented on the impact on integrated care pathways (ICPs).

Methods

We reviewed the ICPs of lung cancer patients who accessed the Veneto Institute of Oncology (IOV)/University Hospital of Padua (Center 1) and the University Hospital of Verona (Center 2) before and after the COVID-19 pandemic, through sixteen indicators chosen by the members of a multidisciplinary team (MDT).

Results

Two window periods (March and April 2019 and 2020) were chosen for comparison. Endoscopic diagnostic procedures and major resections for early stage NSCLC patients increased at Center 1, where a priority pathway with dedicated personnel was established for cancer patients. A slight decrease was observed at Center 2 which became part of the COVID unit. Personnel shortage and different processing methods of tumor samples determined a slightly longer time for diagnostic pathway completion at both Centers. Personnel protection strategies led to a MDT reshape on a web basis and to a significant selection of cases to be discussed in both Centers. The optimization of patient access to healthcare units reduced first outpatient oncological visits, patient enrollment in clinical trials, and end-of-life cancer systemic treatments; finally, a higher proportion of hypofractionation was delivered as a radiotherapy approach for early stage and locally advanced NSCLC.

Conclusions

Based on the experience of the two Centers, we identified the key steps in ICP that were impacted by the COVID-19 pandemic so as to proactively put in place a robust service provision of thoracic oncology.
The Proton-Boron Reaction Increases the Radiobiological Effectiveness of Clinical Low- and High-Energy Proton Beams: Novel Experimental Evidence and Perspectives
Authors: Bláha Pavel , Feoli Chiara , Agosteo Stefano , Calvaruso Marco , Cammarata Francesco Paolo , Catalano Roberto , Ciocca Mario , Cirrone Giuseppe Antonio Pablo , Conte Valeria , Cuttone Giacomo , Facoetti Angelica , Forte Giusi Irma , Giuffrida Lorenzo , Magro Giuseppe , Margarone Daniele , Minafra Luigi , Petringa Giada , Pucci Gaia , Ricciardi Valerio , Rosa Enrico , Russo Giorgio , Manti Lorenzo
Published: June 2021

Protontherapy is a rapidly expanding radiotherapy modality where accelerated proton beams are used to precisely deliver the dose to the tumor target but is generally considered ineffective against radioresistant tumors. Proton-Boron Capture Therapy (PBCT) is a novel approach aimed at enhancing proton biological effectiveness. PBCT exploits a nuclear fusion reaction between low-energy protons and 11B atoms, i.e. p+11B→ 3α (p-B), which is supposed to produce highly-DNA damaging α-particles exclusively across the tumor-conformed Spread-Out Bragg Peak (SOBP), without harming healthy tissues in the beam entrance channel. To confirm previous work on PBCT, here we report new in-vitro data obtained at the 62-MeV ocular melanoma-dedicated proton beamline of the INFN-Laboratori Nazionali del Sud (LNS), Catania, Italy. For the first time, we also tested PBCT at the 250-MeV proton beamline used for deep-seated cancers at the Centro Nazionale di Adroterapia Oncologica (CNAO), Pavia, Italy. We used Sodium Mercaptododecaborate (BSH) as 11B carrier, DU145 prostate cancer cells to assess cell killing and non-cancer epithelial breast MCF-10A cells for quantifying chromosome aberrations (CAs) by FISH painting and DNA repair pathway protein expression by western blotting. Cells were exposed at various depths along the two clinical SOBPs. Compared to exposure in the absence of boron, proton irradiation in the presence of BSH significantly reduced DU145 clonogenic survival and increased both frequency and complexity of CAs in MCF-10A cells at the mid- and distal SOBP positions, but not at the beam entrance. BSH-mediated enhancement of DNA damage response was also found at mid-SOBP. These results corroborate PBCT as a strategy to render protontherapy amenable towards radiotherapy-resilient tumor. If coupled with emerging proton FLASH radiotherapy modalities, PBCT could thus widen the protontherapy therapeutic index.
Clinical, Radiometabolic and Immunologic Effects of Olaparib in Locally Advanced Triple Negative Breast Cancer: The OLTRE Window of Opportunity Trial
Authors: Schettini Francesco , Corona Silvia Paola , Giudici Fabiola , Strina Carla , Sirico Marianna , Bernocchi Ottavia , Milani Manuela , Ziglioli Nicoletta , Aguggini Sergio , Azzini Carlo , Barbieri Giuseppina , Cervoni Valeria , Cappelletti Maria Rosa , Molteni Alfredo , Lazzari Maria Chiara , Ferrero Giuseppina , Ungari Marco , Marasco Elena , Bruson Alice , Xumerle Luciano , Zago Elisa , Cerra Davide , Loddo Marco , Williams Gareth H. , Paris Ida , Scambia Giovanni , Generali Daniele
Published: June 2021

Introduction

Olaparib is effective in metastatic triple negative breast cancer (TNBC) carrying germline mutations in DNA damage repair (DDR) genes BRCA1/2 (gBRCA-mut). The OLTRE window-of-opportunity trial preliminarily investigated potential pathologic, radiometabolic and immune biomarkers of early-response to olaparib in gBRCA-wild-type (wt) TNBC and, as proof-of-concept in gBRCA-mut HER2-negative BC.

Methods

Patients received olaparib for 3 weeks (3w) before standard neoadjuvant chemotherapy and underwent multiple FDG18-PET/CT scan (basal, after olaparib), clinical assessments (basal, every 3w), tumor biopsies and blood samplings (baseline, after olaparib). Clinical and radiometabolic responses were evaluated according to RECIST1.1 and PERCIST criteria.

Results

27 patients with gBRCA-wt TNBC and 8 with gBRCA-mut BC (6 TNBC, 2 HR+/HER2-negative) were enrolled. Three (11.1%) patients showed mutations in non-BRCA1/2 DDR genes and 4 (14.8%) in other genes. 3w olaparib induced 16/35 and 15/27 partial clinical and radiometabolic responses, including in 40.7% and 50.0% gBRCA-wt patients. gBRCA-mut tumors presented numerically higher tumor-infiltrating lymphocytes (TILs) levels and PD-L1 positive tumors. Clinical responders experienced a reduction in T-regs/T-eff ratio (p=0.05), B and NK lymphocytes (p=0.003 both), with an average increase in T-helpers rate (p<0.001) and CD4/CD8 ratio (p=0.02). Ki67% and TILs did not vary significantly (p=0.67 and p=0.77). A numerical increase in PD-L1 positive cases after olaparib was observed, though non-significant (p=0.134). No differences were observed according to gBRCA status and type of response.

Conclusions

Early-stage TNBC might be a target population for olaparib, irrespective of gBRCA mutations. Future trials should combine TILs, PD-L1 and gBRCA status to better identify candidates for escalated/de-escalated treatment strategies including olaparib.
Prognostic Value of Peripheral Whole Blood Cell Counts Derived Indexes in Gallbladder Carcinoma: A Systematic Review and Meta-Analysis
Authors: Xu Bowen , Chen Zhiqiang , Zhang Jing , Chang Jianhua , Zhao Wei , Dong Zhaoru , Zhi Xuting , Li Tao
Published: June 2021

Background

Gallbladder carcinoma (GBC) is a rare gastrointestinal malignancy with poor prognosis. Adequate pre-treatment prediction of survival is essential for risk stratification and patient selection for aggressive surgery or adjuvant therapeutic strategy. Whole blood cell count (WBCC) derived indexes are broadly used as prognosticative biomarkers in various cancer types, but their utility in GBC needs to be validated.

Methods

An extensive literature review was conducted in line with PRISMA guideline until June 31 2020, to identify original studies concerning WBCC-derived indexes as prognostic indicators in GBC. All relative parameters were extracted and pooled for statistical analyses.

Results

Fourteen studies incorporating 2,324 patients were included with a high quality and low risk of biases. All 14 studies evaluated the prognostic value of NLR showing a significant correlation with OS in GBC patients (HR = 1.94, P <0.001). Elevated NLR was revealed to correlate with TNM stage (stages III and IV, OR = 4.65, P <0.001), tumor differentiation (OR = 2.37, P <0.042), CA 19-9 (SMD = 0.47, P = 0.01), but no significance was found with age, sex and CEA. Positive indicative value of MLR and PLR were also confirmed with a HR of 2.06 (P <0.001) and 1.34 (P <0.001), respectively.

Conclusion

The WBCC-derived indexes including NLR, MLR/LMR and PLR were validated to be useful prognostic parameters for predicting survival outcomes in GBC patients. These series of indexes, especially NLR, could improve risk stratification and facilitate better patient selection for surgical resection or aggressive chemotherapy in the decision making of GBC patients.