bluuebunny/crossref_metadata_2025 huggingface dataset:
Anomalous Reduction of the Total Suspended Matter During the COVID-19 Lockdown in the Hooghly Estuarine System
Authors: Jayaram Chiranjivi , Roy Rajdeep , Chacko Neethu , Swain Debadatta , Punnana Ramunaidu , Bandyopadhyay S. , Choudhury S. B. , Dutta Dibyendu
Published: May 2021

The impact of the coronavirus disease 2019 (COVID-19) lockdown in the Hooghly estuarine region, India is assessed using the total suspended matter (TSM) concentration. The estimation of TSM is performed using Landsat-8/operational land imager (OLI), and an intercomparison of TSM load during the pre-lockdown and lockdown periods is done. It is observed that during the lockdown period, TSM reduced by 30–50%. This is a significant observation considering the ecological balance of the region and the fact that it is home to the largest mangroves in the world. This change in suspended matter presumably reflects the influence of reduction in anthropogenic activities owing to the COVID-19 lockdowns, such as industries, closure of shipping activities (through less dredging), and brick kilns (through less sediment removal), which are generally the primary contributors in this region. Even though these observed changes are representative of the positive influence of the COVID-19 lockdown, its implications in estuarine biogeochemistry still remain poorly quantified. The decrease in TSM content may increase light penetration, thereby increasing the primary productivity. In addition, low sediment load reaching the Bay of Bengal could influence the carbon export due to reduction in ballasting effect as reported from this region. In summary, the influence of the COVID-19 lockdown on the biogeochemistry of the aquatic ecosystem appears rather complex than thought earlier and may vary regionally based on local hydrodynamics. The analysis elucidates the complex interplay of regional lockdown and its implication in modulation of local biogeochemistry. However, the relative importance of each process in the Hooghly estuary remains to be fully evaluated.
Musical Chairs on Temperate Reefs: Species Turnover and Replacement Within Functional Groups Explain Regional Diversity Variation in Assemblages Associated With Honeycomb Worms
Authors: Muller Alexandre , Poitrimol Camille , Nunes Flávia L. D. , Boyé Aurélien , Curd Amelia , Desroy Nicolas , Firth Louise B. , Bush Laura , Davies Andrew J. , Lima Fernando P. , Marzloff Martin P. , Meneghesso Claudia , Seabra Rui , Dubois Stanislas F.
Published: May 2021

Reef-building species are recognized as having an important ecological role and as generally enhancing the diversity of benthic organisms in marine habitats. However, although these ecosystem engineers have a facilitating role for some species, they may exclude or compete with others. The honeycomb worm Sabellaria alveolata (Linnaeus, 1767) is an important foundation species, commonly found from northwest Ireland to northern Mauritania, whose reef structures increase the physical complexity of the marine benthos, supporting high levels of biodiversity. Local patterns and regional differences in taxonomic and functional diversity were examined in honeycomb worm reefs from 10 sites along the northeastern Atlantic to explore variation in diversity across biogeographic regions and the potential effects of environmental drivers. While taxonomic composition varied across the study sites, levels of diversity remained relatively constant along the European coast. Assemblages showed high levels of species turnover compared to differences in richness, which varied primarily in response to sea surface temperatures and sediment content, the latter suggesting that local characteristics of the reef had a greater effect on community composition than the density of the engineering species. In contrast, the functional composition of assemblages was similar regardless of taxonomic composition or biogeography, with five functional groups being observed in all sites and only small differences in abundance in these groups being detected. Functional groups represented primarily filter-feeders and deposit-feeders, with the notable absence of herbivores, indicating that the reefs may act as biological filters for some species from the local pool of organisms. Redundancy was observed within functional groups that may indicate that honeycomb worm reefs can offer similar niche properties to its associated assemblages across varying environmental conditions. These results highlight the advantages of comparing taxonomic and functional metrics, which allow identification of a number of ecological processes that structure marine communities.
Self-Supported Smart Bacterial Nanocellulose–Phosphotungstic Acid Nanocomposites for Photochromic Applications
Authors: Santos Moliria V. , Barud Hernane S. , Alencar Monica A. S. , Nalin Marcelo , Toma Sérgio H. , Araki Koiti , Benedetti Assis V. , Maciel Indhira O. , Fragneaud Benjamin , Legnani Cristiano , Molina Celso , Cremona Marco , Ribeiro Sidney J. L.
Published: May 2021

Bacterial nanocellulose (BNC) is a natural biopolymer obtained by gram-negative bacteria by means of a green and inexhaustible biotechnological process using glucose as producing source. BCN hydrogels is formed by cellulose nanofibrils that maintain an open network structure, an ideal matrix to produce new class of organic-inorganic nanocomposites (OIN) for multifunctional applications. The polyoxometalates (POMs) are complex molecules with several metallic ions sharing oxide ions, forming a highly symmetrical metal oxide cluster. Phosphotungstic acid (PWA), H3PW12O40 photoreduction process activated under ultraviolet irradiation, promoting color change. In this work, photochromic organic-inorganic nanocomposites were prepared by soaking phosphotungstic acid (H3PW12O40) in wet BNC membranes mats at room temperature. Semi-transparent and free-standing BNC/PWA nanocomposite with paper-like aspect were obtained. BNC network was able to control, stabilize and disperse PWA particles in a narrow nanometric distribution, and FTIR spectra indicated that the primary Keggin structure was also preserved in the nanocomposites, independently on the PWA content. The nanoparticles present a narrow distribution of around 16 nm, independently on the PWA concentration. BNC/PWA nanocomposites showed reversible photochromic behavior characteristic of the equilibrium between different tungsten oxidation states. PWA reduction (W6+→ W5+) and organic matrix oxidation is proposed to occur through a radical process involving the interaction of one electron from the oxygen atom of the PWA and one hydrogen from BNC matrix. The photochromic effect vanishes almost completely after 5 h. This mechanism is real in the presence of oxygen, however, if the membranes are left in nitrogen or under vacuum the blue color remains longer than 45 days. Photo-electrochemical behavior was studied by spectroelectrochemistry measurements. It is worth noting that all processes were still reversible in the timescale of the experiment and color changes were observed in several cycles.
Protein Extraction From FFPE Kidney Tissue Samples: A Review of the Literature and Characterization of Techniques
Authors: García-Vence Maria , Chantada-Vazquez Maria del Pilar , Sosa-Fajardo Ana , Agra Rebeca , Barcia de la Iglesia Ana , Otero-Glez Alfonso , García-González Miguel , Cameselle-Teijeiro José M. , Nuñez Cristina , Bravo Juan J. , Bravo Susana B.
Published: May 2021

Most tissue biopsies from patients in hospital environments are formalin-fixed and paraffin-embedded (FFPE) for long-term storage. This fixation process produces a modification in the proteins called “crosslinks”, which improves protein stability necessary for their conservation. Currently, these samples are mainly used in clinical practice for performing immunohistochemical analysis, since these modifications do not suppose a drawback for this technique; however, crosslinks difficult the protein extraction process. Accordingly, these modifications make the development of a good protein extraction protocol necessary. Due to the specific characteristics of each tissue, the same extraction buffers or deparaffinization protocols are not equally effective in all cases. Therefore, it is necessary to obtain a specific protocol for each tissue. The present work aims to establish a deparaffinization and protein extraction protocol from FFPE kidney samples to obtain protein enough of high quality for the subsequent proteomic analysis. Different deparaffination, protocols and protein extraction buffers will be tested in FFPE kidney samples. The optimized conditions will be applied in the identification by LC-MS/MS analysis of proteins extracted from 5, 10, and 15 glomeruli obtained through the microdissection of FFPE renal samples.
Update of Clown Nose-Like Lesion, a Underrecognized Manifestation of Metastatic Malignancies and Genetic Cancer Predisposition Syndromes
Authors: Zhao Bei , Chen Ling , Liao Jinfeng , Xie Zhen , Lei Xia , Shen Zhu
Published: May 2021

Clown nose-like lesion refers to the manifestation of a reddish or skin-colored bulge on the tip of the nose or the manifestation of bulbous tip of the nose. More and more clinical cases show that clown nose-like lesion can also be the indication of some genetic syndromes, not just the manifestation of metastatic visceral tumor as it initially proposed. However, the clinical features of clown nose-like lesion indicated by metastatic malignancies, genetic cancer predisposition syndromes or primary diseases involving the nasal tip are lacking. In this study, patients with clown nose-like lesion in our clinical practices and from published literatures were collected and reviewed. We found that clown nose-like lesions caused by metastatic malignancies including lung cancer are often solitary and more common in male (24/31) older individuals (average age 62.3, ranging 40–78 years old). In addition, they usually appear for a short time, and are prone to be misdiagnosed as primary nasal diseases, leading to a poor prognosis (all patients with data available died within 4 months). Clown nose-like lesions associated with genetic cancer predisposition syndromes usually develop at a young age (mean age 15.3) with female preference (9/10). They are accompanied by multiple-systemic involvements, including low hair volume, developmental delay, cancer predisposition or neurological diseases. They show slow development and often positive family history (6/10). These two kinds of clown nose-like lesions are often asymptomatic, which delays the diagnosis and treatment of underlying malignancies or syndromes. In brief, the term of clown nose-like lesion is underrecognized, and should be updated. Clown nose-like lesions can serve as indicators to at least three categories of clinical issues: metastatic visceral tumors, genetic syndromes, and primary diseases involving the nasal tip. Increased awareness of clinical features of updated clown nose-like lesions can alert physicians to these underlying malignancies or syndromes, render earlier detection of associated medical issues, and allow for genetic counseling of family members.
Vegetative Insecticidal Protein (Vip): A Potential Contender From Bacillus thuringiensis for Efficient Management of Various Detrimental Agricultural Pests
Authors: Gupta Mamta , Kumar Harish , Kaur Sarvjeet
Published: May 2021

Bacillus thuringiensis (Bt) bacterium is found in various ecological habitats, and has natural entomo-pesticidal properties, due to the production of crystalline and soluble proteins during different growth phases. In addition to Cry and Cyt proteins, this bacterium also produces Vegetative insecticidal protein (Vip) during its vegetative growth phase, which is considered an excellent toxic candidate because of the difference in sequence homology and receptor sites from Cry proteins. Vip proteins are referred as second-generation insecticidal proteins, which can be used either alone or in complementarity with Cry proteins for the management of various detrimental pests. Among these Vip proteins, Vip1 and Vip2 act as binary toxins and have toxicity toward pests belonging to Hemiptera and Coleoptera orders, whereas the most important Vip3 proteins have insecticidal activity against Lepidopteran pests. These Vip3 proteins are similar to Cry proteins in terms of toxicity potential against susceptible insects. They are reported to be toxic toward pests, which can’t be controlled with Cry proteins. The Vip3 proteins have been successfully pyramided along with Cry proteins in transgenic rice, corn, and cotton to combat resistant pest populations. This review provides detailed information about the history and importance of Vip proteins, their types, structure, newly identified specific receptors, and action mechanism of this specific class of proteins. Various studies conducted on Vip proteins all over the world and the current status have been discussed. This review will give insights into the significance of Vip proteins as alternative promising candidate toxic proteins from Bt for the management of pests in most sustainable manner.
Phylogeny- and Abundance-Based Metrics Allow for the Consistent Comparison of Core Gut Microbiome Diversity Indices Across Host Species
Authors: Risely Alice , Gillingham Mark A. F. , Béchet Arnaud , Brändel Stefan , Heni Alexander C. , Heurich Marco , Menke Sebastian , Manser Marta B. , Tschapka Marco , Wasimuddin  , Sommer Simone
Published: May 2021

The filtering of gut microbial datasets to retain high prevalence taxa is often performed to identify a common core gut microbiome that may be important for host biological functions. However, prevalence thresholds used to identify a common core are highly variable, and it remains unclear how they affect diversity estimates and whether insights stemming from core microbiomes are comparable across studies. We hypothesized that if macroecological patterns in gut microbiome prevalence and abundance are similar across host species, then we would expect that increasing prevalence thresholds would yield similar changes to alpha diversity and beta dissimilarity scores across host species datasets. We analyzed eight gut microbiome datasets based on 16S rRNA gene amplicon sequencing and collected from different host species to (1) compare macroecological patterns across datasets, including amplicon sequence variant (ASV) detection rate with sequencing depth and sample size, occupancy-abundance curves, and rank-abundance curves; (2) test whether increasing prevalence thresholds generate universal or host-species specific effects on alpha and beta diversity scores; and (3) test whether diversity scores from prevalence-filtered core communities correlate with unfiltered data. We found that gut microbiomes collected from diverse hosts demonstrated similar ASV detection rates with sequencing depth, yet required different sample sizes to sufficiently capture rare ASVs across the host population. This suggests that sample size rather than sequencing depth tends to limit the ability of studies to detect rare ASVs across the host population. Despite differences in the distribution and detection of rare ASVs, microbiomes exhibited similar occupancy-abundance and rank-abundance curves. Consequently, increasing prevalence thresholds generated remarkably similar trends in standardized alpha diversity and beta dissimilarity across species datasets until high thresholds above 70%. At this point, diversity scores tended to become unpredictable for some diversity measures. Moreover, high prevalence thresholds tended to generate diversity scores that correlated poorly with the original unfiltered data. Overall, we recommend that high prevalence thresholds over 70% are avoided, and promote the use of diversity measures that account for phylogeny and abundance (Balance-weighted phylogenetic diversity and Weighted Unifrac for alpha and beta diversity, respectively), because we show that these measures are insensitive to prevalence filtering and therefore allow for the consistent comparison of core gut microbiomes across studies without the need for prevalence filtering.
Silencing of circRNA circ_0001666 Represses EMT in Pancreatic Cancer Through Upregulating miR-1251 and Downregulating SOX4
Authors: Zhang Rundong , Zhu Wanli , Ma Chenchao , Ai Kaixing
Published: May 2021

Background

Pancreatic cancer (PC) is an aggressive malignancy and has a poor prognosis. Although emerging research has revealed that circular RNAs (circRNAs) are crucial modulators that control tumor development and metastasis, their functional involvement in PC has not been well characterized. Here, we examined whether and how circRNA circ_0001666 governs epithelial-mesenchymal transition (EMT) in PC.

Methods

We investigated the effects of circ_0001666 on EMT and PC cell invasion by gain- and loss-of-function assays. We also explored the mechanisms underlying the functions of circ_0001666 in PC cells.

Results

We found that circ_0001666 is highly expressed in PC tissues and PC cell lines. Patients with high circ_0001666 expression had shorter survival times. In vitro and in vivo experiments have demonstrated that upregulation of circ_0001666 facilitates PC cell proliferation, EMT and invasiveness, whereas knockdown of circ_0001666 exhibits opposite functions. Moreover, circ_0001666 is able to bind to miR-1251, thus increasing the expression of SOX4, which is a direct downstream effector of miR-1251. The oncogenic effects of circ_0001666 on EMT and PC cell invasion were rescued by miR-1251 overexpression.

Conclusions

These results suggested that circ_0001666 acts as an oncogenic circRNA to promote EMT and invasion of PC cells through sponging miR-1251, and indicated that circ_0001666 could be explored as a potential therapeutic target for PC.
Longitudinal Assessment of Working Memory Performance in the APPswe/PSEN1dE9 Mouse Model of Alzheimer’s Disease Using an Automated Figure-8-Maze
Authors: van Heusden Fran C. , Palacín i Bonsón Sara , Stiedl Oliver , Smit August B. , van Kesteren Ronald E.
Published: May 2021

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder, with a long preclinical and prodromal phase. To enable the study of disease mechanisms, AD has been modeled in many transgenic animal lines and cognitive functioning has been tested using several widely used behavioral tasks. These tasks, however, are not always suited for repeated longitudinal testing and are often associated with acute stress such as animal transfer, handling, novelty, or stress related to the task itself. This makes it challenging to relate cognitive dysfunction in animal models to cognitive decline observed in AD patients. Here, we designed an automated figure-8-maze (F8M) to test mice in a delayed alternation task (DAT) in a longitudinal manner. Mice were rewarded when they entered alternate sides of the maze on subsequent trials. Automation as well as connection of the F8M set-up with a home cage reduces experimenter interference and minimizes acute stress, thus making it suitable for longitudinal testing and facilitating clinical translation. In the present study, we monitored cognitive functioning of 2-month-old APPswe/PSEN1dE9 (APP/PS1) mice over a period of 4 months. The percentage of correct responses in the DAT did not differ between wild-type and transgenic mice from 2 to 6 months of age. However, 6-month-old mice displayed an increase in the number of consecutive incorrect responses. These results demonstrate the feasibility of longitudinal testing using an automated F8M and suggest that APP/PS1 mice are not impaired at delayed spatial alternation until 6 months of age under the current experimental conditions.
sTWEAK as Predictor of Stroke Recurrence in Ischemic Stroke Patients Treated With Reperfusion Therapies
Authors: Hervella Pablo , Pérez-Mato María , Rodríguez-Yáñez Manuel , López-Dequidt Iria , Pumar José M. , Sobrino Tomás , Campos Francisco , Castillo José , da Silva-Candal Andrés , Iglesias-Rey Ramón
Published: May 2021

Aim: The purpose of this study was to investigate clinical and neuroimaging factors associated with stroke recurrence in reperfused ischemic stroke patients, as well as the influence of specific biomarkers of inflammation and endothelial dysfunction.

Methods: We conducted a retrospective analysis on a prospectively registered database. Of the 875 patients eligible for this study (53.9% males; mean age 69.6 ± 11.8 years vs. 46.1% females; mean age 74.9 ± 12.6 years), 710 underwent systemic thrombolysis, 87 thrombectomy and in 78, systemic or intra-arterial thrombolysis together with thrombectomy was applied. Plasma levels of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFα) were analyzed as markers of inflammation, and soluble tumor necrosis factor-like inducer of apoptosis (sTWEAK) as an endothelial dysfunction marker. The main outcome variables of the study were the presence and severity of leukoaraiosis (LA) and stroke recurrence.

Results: The average follow-up time of the study was 25 ± 13 months, during which 127 patients (14.5%) showed stroke recurrence. The presence and severity of LA was more severe in the second stroke episode (Grade III of the Fazekas 28.3 vs. 52.8%; p < 0.0001). IL-6 levels at the first admission and before reperfusion treatment in patients with and without subsequent recurrence were similar (9.9 ± 10.4 vs. 9.1 ± 7.0 pg/mL, p = 0.439), but different for TNFα (14.7 ± 5.6 vs. 15.9 ± 5.7 pg/mL, p = 0.031) and sTWEAK (5,970.8 ± 4,330.4 vs. 8,660.7 ± 5,119.0 pg/mL, p < 0.0001). sTWEAK values ≥7,000 pg/mL determined in the first stroke were independently associated to recurrence (OR 2.79; CI 95%: 1.87–4.16, p < 0.0001).

Conclusions: The severity and the progression of LA are the main neuroimaging factors associated with stroke recurrence. Likewise, sTWEAK levels were independently associated to stroke recurrence, so further studies are necessary to investigate sTWEAK as a therapeutic target.
Pembrolizumab-Induced Isolated Cranial Neuropathy: A Rare Case Report and Review of Literature
Authors: Bruno Francesco , Palmiero Rosa Antonietta , Ferrero Bruno , Franchino Federica , Pellerino Alessia , Milanesi Enrica , Soffietti Riccardo , Rudà Roberta
Published: May 2021

Introduction: Anti-PD1 agents are widely used in the treatment of solid tumors. This has prompted the recognition of a class of immune-related adverse events (irAEs), due to the activation of autoimmune T-cells. Pembrolizumab is an anti-PD1 agent, which has been related to an increased risk of various neurological irAE (n-irAEs). Here, we present a rare case of pembrolizumab-induced neuropathy of cranial nerves.

Case Report: A 72-year-old patient was diagnosed with a lung adenocarcinoma in February 2018 (EGFR–, ALK–, and PDL1 90%). According to the molecular profile, pembrolizumab was started. After three administrations, the patient developed facial paresis, ptosis, ophthalmoplegia, and dysphonia. As brain metastases and paraneoplastic markers were excluded, a drug-related disorder was suspected and pembrolizumab was discontinued. A nerve conduction study and electromyography excluded signs of neuropathy and myopathy at four limbs, and repetitive nerve stimulation was negative. However, altered blink reflex and nerve facial conduction were consistent with an acute neuropathy of the cranial district. Thus, the patient was treated with two cycles of intravenous immunoglobulins (IVIg), which rapidly allowed improvement of both symptoms and neurophysiological parameters. However, the patient died in October 2018 for a progression of lung tumor.

Discussion: Only 16 cases of pembrolizumab-related neuropathies have been described so far. Our case is of particular interest for the isolated involvement of cranial nerves and the prompt response to IVIg.

Conclusion: N-irAEs are insidious conditions that require solid knowledge of onco-immunotherapy complications: it is mandatory not to delay any treatment that would potentially modify the course of a neurological complication.
Automated Analysis of Risk Factors for Postictal Generalized EEG Suppression
Authors: Zhao Xiuhe , Vilella Laura , Zhu Liang , Rani M. R. Sandhya , Hampson Johnson P. , Hampson Jaison , Hupp Norma J. , Sainju Rup K. , Friedman Daniel , Nei Maromi , Scott Catherine , Allen Luke , Gehlbach Brian K. , Schuele Stephan , Harper Ronald M. , Diehl Beate , Bateman Lisa M. , Devinsky Orrin , Richerson George B. , Zhang Guo-Qiang , Lhatoo Samden D. , Lacuey Nuria
Published: May 2021

Rationale: Currently, there is some ambiguity over the role of postictal generalized electro-encephalographic suppression (PGES) as a biomarker in sudden unexpected death in epilepsy (SUDEP). Visual analysis of PGES, known to be subjective, may account for this. In this study, we set out to perform an analysis of PGES presence and duration using a validated signal processing tool, specifically to examine the association between PGES and seizure features previously reported to be associated with visually analyzed PGES.

Methods: This is a prospective, multicenter epilepsy monitoring study of autonomic and breathing biomarkers of SUDEP in adult patients with intractable epilepsy. We studied videoelectroencephalogram (vEEG) recordings of generalized convulsive seizures (GCS) in a cohort of patients in whom respiratory and vEEG recording were carried out during the evaluation in the epilepsy monitoring unit. A validated automated EEG suppression detection tool was used to determine presence and duration of PGES.

Results: We studied 148 GCS in 87 patients. PGES occurred in 106/148 (71.6%) seizures in 70/87 (80.5%) of patients. PGES mean duration was 38.7 ± 23.7 (37; 1–169) seconds. Presence of tonic phase during GCS, including decerebration, decortication and hemi-decerebration, were 8.29 (CI 2.6–26.39, p = 0.0003), 7.17 (CI 1.29–39.76, p = 0.02), and 4.77 (CI 1.25–18.20, p = 0.02) times more likely to have PGES, respectively. In addition, presence of decerebration (p = 0.004) and decortication (p = 0.02), older age (p = 0.009), and hypoxemia duration (p = 0.03) were associated with longer PGES durations.

Conclusions: In this study, we confirmed observations made with visual analysis, that presence of tonic phase during GCS, longer hypoxemia, and older age are reliably associated with PGES. We found that of the different types of tonic phase posturing, decerebration has the strongest association with PGES, followed by decortication, followed by hemi-decerebration. This suggests that these factors are likely indicative of seizure severity and may or may not be associated with SUDEP. An automated signal processing tool enables objective metrics, and may resolve apparent ambiguities in the role of PGES in SUDEP and seizure severity studies.
Analgesic and Antidepressant Effects of the Clinical Glutamate Modulators Acetyl-L-Carnitine and Ketamine
Authors: Freo Ulderico , Brugnatelli Viola , Turco Fabio , Zanette Gastone
Published: May 2021

Pain and depression are leading causes of disability and of profound social and economic burden. Their impact is aggravated by their chronicity and comorbidity and the insufficient efficacy of current treatments. Morphological and functional metabolism studies link chronic pain and depressive disorders to dysfunctional neuroplastic changes in fronto-limbic brain regions that control emotional responses to painful injuries and stressful events. Glutamate modulators are emerging new therapies targeting dysfunctional brain areas implicated in the generation and maintenance of chronic pain and depression. Here, we report the effects of two clinically approved glutamate modulators: acetyl-L-carnitine (ALCAR) and S, R(±)ketamine (KET). ALCAR is a natural neurotrophic compound currently marketed for the treatment of neuropathies. KET is the prototypical non-competitive antagonist at N-methyl-D-aspartate glutamate receptors and a clinically approved anesthetic. Although they differ in pharmacological profiles, ALCAR and KET both modulate aminergic and glutamatergic neurotransmissions and pain and mood. We assessed in rats the effects of ALCAR and KET on cerebral metabolic rates for glucose (rCMRglc) and assessed clinically the effects of ALCAR in chronic pain and of KET in post-operative pain. ALCAR and KET increased rCMRglc at similar degrees in prefrontal, somatosensory, and cingulate cortices, and KET increased rCMRglc at a different, much larger, degree in limbic and dopaminergic areas. While rCMRglc increases in prefrontal cortical areas have been associated with analgesic and antidepressant effects of ALCAR and KET, the marked metabolic increases KET induces in limbic and dopaminergic areas have been related to its psychotomimetic and abuse properties. In patients with chronic neuropathic pain, ALCAR (1,000 mg/day) yielded to a fast (2 weeks) improvement of mood and then of pain and quality of life. In day-surgery patients, KET improved dischargeability and satisfaction. In obese patients undergoing bariatric surgery, a single, low dose of KET (0.5 mg/kg) at induction of anesthesia determined a very fast (hours) amelioration of post-operative depression and pain and an opioid-sparing effect. These findings indicate that ALCAR and KET, two non-selective glutamate modulators, still offer viable therapeutic options in comorbid pain and depression.
Gene-Based Tests of a Genome-Wide Association Study Dataset Highlight Novel Multiple Sclerosis Risk Genes
Authors: Li He , Hou Xiaodan , Liang Yan , Xu Fang , Zhang Xiyue , Cui Pan , Xing Gebeili , Wang Xuejiao , Jiang Wei
Published: May 2021

Multiple sclerosis (MS) is an autoimmune disorder influenced by genetic and environmental factors. Many studies have provided insights into genetic factors’ contribution to MS via large-scale genome-wide association study (GWAS) datasets. However, genetic variants identified to date do not adequately explain genetic risks for MS. This study hypothesized that novel MS risk genes could be identified by analyzing the MS-GWAS dataset using gene-based tests. We analyzed a GWAS dataset consisting of 9,772 MS cases and 17,376 healthy controls of European descent. We performed gene-based tests of 464,357 autosomal single nucleotide polymorphisms (SNPs) using two methods (PLINK and VEGAS2) and identified 28 shared genes satisfied p-value < 4.56 × 10–6. In further gene expression analysis, ten of the 28 genes were significantly differentially expressed in the MS case-control gene expression omnibus (GEO) database. GALC and HLA-DOB showed the most prominent differences in gene expression (two- and three-fold, respectively) between MS patients and healthy controls. In conclusion, our results reveal more information about MS hereditary characteristics and provide a basis for further studies.
Poor Eating Habits and Selected Determinants of Food Choice Were Associated With Ultraprocessed Food Consumption in Brazilian Women During the COVID-19 Pandemic
Authors: Smaira Fabiana Infante , Mazzolani Bruna Caruso , Esteves Gabriel Perri , André Heloisa C. Santo , Amarante Milla Cordeiro , Castanho Daniela Fernandes , Campos Karen Jennifer de , Benatti Fabiana Braga , Pinto Ana Jéssica , Roschel Hamilton , Gualano Bruno , Nicoletti Carolina Ferreira
Published: May 2021

Background: The aim of this study was to investigate possible associations between food consumption and eating habits and food choice determinants in women during COVID-19 pandemic.

Methods: This is a cross-sectional survey conducted in Brazil between June and September, 2020, during which time social distancing measures were in place.

Results: Participants (n = 629) were aged 34.0 years and mostly within normal weight according to BMI (60.4%). “Snacking” and “liking” associated with increased energy (β = 164.27 and β = 110.24) and carbohydrate intake (β = 1.97 and β = 1.80), and with reduced protein intake (β = −1.54 and β = −1.18). In contrast, “dieting” and “weight control” associated with reduced energy (β = −162.57 and β = −111.49) and carbohydrate intake (β = −2.78 and β = −2.07), and with increased protein intake (β = 3.78 and β = 1.65). “Dieting” (β = 7.27), “need and hunger” (β = 3.34), and “health” (β = 4.94) associated with an increased consumption of unprocessed and minimally processed foods, whereas “replacing main meals with snacks” (β = −8.98), “snacking” (β = −6.92) and binge eating symptoms (β = −0.34) associated with reduced consumption of foods within this processing level. In contrast, “use of delivery services” (β = 3.39), “replacing main meals with snacks” (β = 5.49), “visual appeal” (β = 2.17), “social norms” (β = 2.19) and “affect regulation” (β = 2.01) associated with increased ultraprocessed food consumption. Overall, associations were more frequent and pronounced when analyzing food consumption by processing level rather than by macronutrient intake.

Conclusion: Some eating habits and food choice determinants (“snacking,” “replacing meals with snacks,” “use of delivery services”) observed during the COVID-19 pandemic were associated with an unhealthy diet (high energy and carbohydrate consumption, increased ultraprocessed food consumption and reduced unprocessed/minimally processed foods consumption) in Brazilian women.
The Choice of Candidates in Survival Markers Based on Coordinated Gene Expression in Renal Cancer
Authors: Apanovich Natalya , Apanovich Pavel , Mansorunov Danzan , Kuzevanova Anna , Matveev Vsevolod , Karpukhin Alexander
Published: May 2021

We aimed to identify and investigate genes that are essential for the development of clear cell renal cell carcinoma (ccRCC) and sought to shed light on the mechanisms of its progression and create prognostic markers for the disease. We used real-time PCR to study the expression of 20 genes that were preliminarily selected based on their differential expression in ccRCC, in 68 paired tumor/normal samples. Upon ccRCC progression, seven genes that showed an initial increase in expression showed decreased expression. The genes whose expression levels did not significantly change during progression were associated mainly with metabolic and inflammatory processes. The first group included CA9, NDUFA4L2, EGLN3, BHLHE41, VWF, IGFBP3, and ANGPTL4, whose expression levels were coordinately decreased during tumor progression. This expression coordination and gene function is related to the needs of tumor development at different stages. Specifically, the high correlation coefficient of EGLN3 and NDUFA4L2 expression may indicate the importance of the coordinated regulation of glycolysis and mitochondrial metabolism. A panel of CA9, EGLN3, BHLHE41, and VWF enabled the prediction of survival for more than 3.5 years in patients with ccRCC, with a probability close to 90%. Therefore, a coordinated change in the expression of a gene group during ccRCC progression was detected, and a new panel of markers for individual survival prognosis was identified.
Cardiovascular Death Risk in Primary Central Nervous System Lymphoma Patients Treated With Chemotherapy: A Registry-Based Cohort Study
Authors: Guan Tianwang , Qiu Zicong , Su Miao , Yang Jinming , Tang Yongshi , Jiang Yanting , Yao Dunchen , Lai Yanxian , Li Yanfang , Liu Cheng
Published: May 2021

Purpose

To study the cardiovascular death (CVD) risk in primary central nervous system lymphoma (PCNSL) patients with chemotherapy.

Methods

We obtained 2,020 PCNSL participants and 88,613 non-central nervous system lymphoma (NCNSL) participants with chemotherapy from Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2015. A 1:3 propensity score matching (PSM) was used to reduce the imbalance between PCNSL participants with and without chemotherapy, as well as the imbalance between PCNSL and NCNSL participants with chemotherapy. Competing risks regressions were conducted to evaluate the independent influence of chemotherapy on CVD.

Results

After 1:3 PSM, the CVD risk in PCNSL patients with chemotherapy was lower than those without chemotherapy [decreased 53%, adjusted HR, 0.469 (95% CI, 0.255–0.862; P = 0.015)] as well as NCNSL patients with chemotherapy [decreased 36%, adjusted HR in model 1, 0.636 (95% CI, 0.439–0.923; P = 0.017)]. The CVD risk of chemotherapy decreased in PCNSL patients with age at diagnosis >60 years old [adjusted HR, 0.390 (95% CI, 0.200–0.760; P = 0.006)], and those patients diagnosed at 2010 to 2015 [adjusted HR, 0.339 (95% CI, 0.118–0.970; P = 0.044)].

Conclusion

PCNSL patients with chemotherapy are associated with lower CVD risk. Our findings may provide new foundations for that chemotherapy is the first-line treatment for PCNSL patients, according to a cardiovascular risk perspective.
Predicting Adverse Pathologic Features and Clinical Outcomes of Resectable Pancreas Cancer With Preoperative CA 19-9
Authors: Kowalchuk Roman O. , Lester Scott C. , Graham Rondell P. , Harmsen William S. , Zhang Lizhi , Halfdanarson Thorvardur R. , Smoot Rory L. , Gits Hunter C. , Ma Wen Wee , Owen Dawn , Mahipal Amit , Miller Robert C. , Wittich Michelle A. Neben , Cleary Sean P. , McWilliams Robert R. , Haddock Michael G. , Hallemeier Christopher L. , Truty Mark J. , Merrell Kenneth W.
Published: May 2021

Background

We evaluated preoperative CA 19-9 levels in patients with resected pancreatic cancer to analyze whether they were predictive of clinical outcomes and could help select patients for additional therapy. We hypothesized that elevated CA 19-9 would be associated with worse pathologic findings and oncologic outcomes.

Methods

This study assessed 509 patients with non-metastatic pancreatic adenocarcinoma who underwent resection at our institution from 1995-2011 and had preoperative CA 19-9 recorded. No patients received neoadjuvant therapy. CA 19-9 level was analyzed as a continuous and a dichotomized (> vs. ≤ 55 U/mL) variable using logistic and Cox models.

Results

Median follow-up was 7.8 years, and the median age was 66 years (33-90). 64% of patients had elevated preoperative CA 19-9 (median: 141 U/mL), that did not correlate with bilirubin level or tumor size. Most patients had ≥ T3 tumors (72%) and positive lymph nodes (62%). The rate of incomplete (R1 or R2) resection was 19%. Increasing preoperative CA 19-9 was associated with extra-pancreatic extension (p=0.0005), lymphovascular space invasion (p=0.0072), incomplete resection [HR (95% CI) 2.0 (1.2-3.5)], and lower OS [HR = 1.6 (1.3-2.0)]. Each doubling in preoperative CA 19-9 value was associated with an 8.3% increased risk of death [HR = 1.08 (1.02-1.15)] and a 10.0% increased risk of distant recurrence [HR = 1.10 (1.02-1.19)]. Patients classified as non-secretors had comparable outcomes to patients with normal CA 19-9.

Conclusions

Elevated preoperative CA 19-9 level was associated with adverse pathologic features, incomplete resection, and inferior clinical outcomes. Neither tumor size nor bilirubin confound an elevated CA 19-9 level. Preoperative CA 19-9 level may help select patients for additional therapy.
A Novel Ferroptosis Related Gene Signature for Prognosis Prediction in Patients With Colon Cancer
Authors: Nie Jianhua , Shan Dan , Li Shun , Zhang Shuyuan , Zi Xiaolin , Xing Fan , Shi Jiaqi , Liu Caiqi , Wang Tianjiao , Sun Xiaoyuan , Zhang Qian , Zhou Meng , Luo Shengnan , Meng Hongxue , Zhang Yanqiao , Zheng Tongsen
Published: May 2021

Purpose

Colon cancer (CC) is a serious disease burden. The prognosis of patients with CC is different, so looking for effective biomarkers to predict prognosis is vitally important. Ferroptosis is a promising therapeutic and diagnosis strategy in CC. However, the role of ferroptosis in prognosis of CC has not been studied. The aim of the study is to build a prognosis model related ferroptosis, and provide clues for further therapy of CC.

Methods

The RNA-seq data were from TCGA (training group) and GEO (testing group). The R language and Perl language were used to process and analyze data. LASSO regression analysis was used to build the prognosis model. ssGSEA was used to compare the immune status between two groups. Immunohistochemistry was used to detect expression of AKR1C1 and CARS1 in colon cancer tissues and adjacent tissues.

Results

The prognosis model consisted of five ferroptosis related genes (AKR1C1, ALOX12, FDFT1, ATP5MC3, and CARS1). The area under curve (AUC) at 1-, 2-, and 3-year were 0.668, 0.678, and 0.686, respectively. The high- and low-risk patients had significant survival probability and could be clearly distinguished by the PCA and t-SNE analysis. The multivariate cox regression analysis also showed the riskscore is an independent prognosis factor. Importantly, we found that the immune status between high- and low-risk patients were different obviously, such as CD8+T cells. And STING, a new promising immune target, was also correlated to our signature genes statistically significantly.

Conclusion

Our ferroptosis prognosis signature could predict survival of CC patients to a certain degree. And the crosstalk between ferroptosis and immune, especially STING need further studies.
Prognosis and Immune Infiltration of Chromobox Family Genes in Sarcoma
Authors: Zhou Jian , Chen Ziyuan , Zou Ming , Wan Rongjun , Wu Tong , Luo Yingquan , Wu Gen , Wang Wanchun , Liu Tang
Published: May 2021

Background

Chromobox family genes (CBXs) are known to play roles in numerous modifications of the chromatin in order to inhibit the transcription of target genes. CBXs have been shown to be expressed at high levels in many types of cancer and can also serve as a target gene for therapeutic purposes. However, little is known about the expression and prognostic value of CBXs in human sarcomas.

Methods

The transcription level of CBXs was analyzed using the Oncomine dataset, and the differential expression of CBXs in sarcoma was reported by the Gene Expression Profiling Interactive Analysis (GEPIA) dataset. We also used the CCLE dataset to evaluate the expression of CBXs in a sarcoma cell line. The prognostic value of CBXs was analyzed using GEPIA and Kaplan–Meier analysis. In addition, the corrections between CBXs and their co-expressed genes were reported using Oncomine and GEPIA datasets. DAVID was used to perform GO function enrichment analysis for the CBXs and their co-expression genes. Finally, TIMER was used to analyze the immune cell infiltration of CBXs in patients with sarcoma.

Results

HP1-α/β/γ (CBX1/3/5) and CBX4/6/8 were found to be overexpressed in human sarcoma, and CBXs were upregulated in almost all the sarcoma cell line. The expression levels of HP1-α/β/γ (CBX1/3/5) and CBX7 were associated with overall survival (OS) in patients with sarcoma, while high expression levels of CBX7 were related to disease-free survival (DFS). In addition, the expression levels of CBX2/6/7 were related to recurrence-free survival (RFS). We also found that the CBX family was positively correlated with the infiltration of immune cells, including CD8+ T cells, CD4+ T cells, B cells, macrophages, neutrophils, and dendritic cells, in sarcoma.

Conclusions

The results from the present study indicated that CBXs were significantly associated with prognosis and immunological status in sarcoma. These data suggest that CBXs could serve as potential biomarkers for prognosis and immune infiltration in human sarcoma.
Establishment and Initial Experience of Clinical FLASH Radiotherapy in Canine Cancer Patients
Authors: Konradsson Elise , Arendt Maja L. , Bastholm Jensen Kristine , Børresen Betina , Hansen Anders E. , Bäck Sven , Kristensen Annemarie T. , Munck af Rosenschöld Per , Ceberg Crister , Petersson Kristoffer
Published: May 2021

FLASH radiotherapy has emerged as a treatment technique with great potential to increase the differential effect between normal tissue toxicity and tumor response compared to conventional radiotherapy. To evaluate the feasibility of FLASH radiotherapy in a relevant clinical setting, we have commenced a feasibility and safety study of FLASH radiotherapy in canine cancer patients with spontaneous superficial solid tumors or microscopic residual disease, using the electron beam of our modified clinical linear accelerator. The setup for FLASH radiotherapy was established using a short electron applicator with a nominal source-to-surface distance of 70 cm and custom-made Cerrobend blocks for collimation. The beam was characterized by measuring dose profiles and depth dose curves for various field sizes. Ten canine cancer patients were included in this initial study; seven patients with nine solid superficial tumors and three patients with microscopic disease. The administered dose ranged from 15 to 35 Gy. To ensure correct delivery of the prescribed dose, film measurements were performed prior to and during treatment, and a Farmer-type ion-chamber was used for monitoring. Treatments were found to be feasible, with partial response, complete response or stable disease recorded in 11/13 irradiated tumors. Adverse events observed at follow-up ranging from 3-6 months were mild and consisted of local alopecia, leukotricia, dry desquamation, mild erythema or swelling. One patient receiving a 35 Gy dose to the nasal planum, had a grade 3 skin adverse event. Dosimetric procedures, safety and an efficient clincal workflow for FLASH radiotherapy was established. The experience from this initial study will be used as a basis for a veterinary phase I/II clinical trial with more specific patient inclusion selection, and subsequently for human trials.
Sars-Cov2 Not Detected in a Pediatric Population With Acute Respiratory Infection in Primary Care in Central and Southern Italy From November 2019 to Early March 2020
Authors: Rizzo Caterina , Loconsole Daniela , Pandolfi Elisabetta , Ciofi Degli Atti Marta Luisa , van Summeren Jojanneke , Paget John , Russo Luisa , Campagna Ilaria , Croci Ileana , Gesualdo Francesco , Concato Carlo , Linardos Giulia , Bartolucci Veronica , Ciampini Sara , Muda Andrea Onetti , Raponi Massimiliano , Chironna Maria
Published: May 2021

Background: In December 2019, a novel coronavirus named SARS-CoV-2 started circulating in China and this led to a major epidemic in Northern Italy between February and May 2020. Young children (aged <5 years) seem to be less affected by this coronavirus disease (COVID-19) compared to adults, although there is very little information on the circulation of this new virus among children in Italy. We retrospectively tested nasopharyngeal swabs for SARS-CoV-2 in samples collected in young children between November, 2019 and March, 2020 in the context of the RSV ComNet study.

Methods: Two networks of primary care pediatricians in Lazio (Central Italy) and Puglia (Southern Italy) collected nasopharyngeal swabs from children, aged <5 years, presenting with symptoms for an acute respiratory infection (ARI). The RSV ComNet study is a multicenter study implemented to estimate the burden of RSV in young children (aged <5 years) in the community. Swabs were sent to a central reference laboratory and tested for 14 respiratory viruses through RT-PCR. All collected samples were retrospectively tested for SARS-CoV-2 using RT-PCR (Istituto Superiore di Sanità protocol).

Results: A total of 293 children with ARI were identified in the two participating networks. The highest number of cases were recruited in weeks 51/2019 and 3/2020. The majority of patients (57%) came from the Lazio region. All of the 293 samples tested negative for SARS-Cov2. Rhinovirus was the most frequently detected virus (44%), followed by RSV (41%) and influenza viruses (14%).

Conclusions: Our study shows that in Lazio (a region of intermediate SARS-COV-2 incidence) and Puglia (a region of low incidence), the SARS-Cov2 virus did not circulate in a sample of ARI pediatric cases consulting primary care pediatricians between November 2019 and March 2020.