bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydrogen peroxide formation in carbon clothes for enhancement of an electro-oxidation tertiary treatment for tequila vinasse wastewater
Authors: Covarrubias-Del-Toro Rafael , Huerta-Rocha Marisol , Lezama Luis , García Edith Xio Mara , Estrada-Vargas Arturo
Published: May 2023

Carbon-based electrodes have been extensively used as cathodes for the electro-generation of H₂O₂, which is used in the production of the hydroxyl radical •OH to mineralize organic compounds in several types of wastewater. Carbon cloth has been also used in combination with activated carbon for the combined adsorption and oxidation of persistent organic compounds present in tequila vinasse wastewater. Whereas most of the works regarding the H₂O₂ electro-generation involve relatively complex processes to enhance the catalytic activity or the electrochemically active area of these electrodes, calcination by itself represents a simple and low-cost option to enhance these cathodic and anodic functions, especially in the fabrication of large area electrodes that could be needed to treat the large amount of tequila vinasse wastewater that is produced daily. In this work, the effect of calcination at 300°C and 600°C of carbon clothes in the oxidation current and H₂O₂ production at different potentials in H₂SO₄ was studied. Oxidation current increased 700% upon calcination at 600°C, compared to no calcination. H₂O₂ was produced only in a narrow range of polarizations, whereas calcination at 600 °C increased the generation rate from 7.1 ± 0.3 to 17.8 ± 0.4 mg L⁻1 h⁻1.
Analysis of trade-offs/synergies in land use function changes in Bin County, China
Authors: Ning Jing , Zhang Huimei , Shi Dongwei , Du Guoming
Published: May 2023

Land use function has become an important part in land change science. More attention should be given to multifunctional land to achieve land structure optimization and sustainable land use. This study takes Bin County in Heilongjiang province of China as the research area and investigates the spatiotemporal pattern and trade-off synergistic relationship of land functions from 2000 to 2020. Land functions were quantitatively measured by the spatiotemporal method of statistical data, INVEST model, CASA, RUSLE, and other models. The results showed that 1) during 2000–2020, the production function showed an overall trend of enhancement. Living function remained enhanced except in the southeast and north. The water conservation function was weakened in most areas, while the carbon fixation function was strengthened in the southeast and weakened in the central and northern parts. Soil conservation function decreased first and then increased significantly in the southwest. 2) There was a synergistic relationship between production and living functions and trade-off relationships between ecology and production functions and ecology and living functions from 2000 to 2020. 3) The production and living functions are mainly coordinated in space, and the collaborative agglomeration types are mainly distributed in Tangfang town, Manjing town, and other areas. The spatial distribution of trade-offs and synergies between ecological and productive functions and ecological and living functions was similar. The trade-off and agglomeration types were scattered, and the synergies were distributed in Binxi town and Juren town.
SARS-CoV-2 Omicron variants: burden of disease, impact on vaccine effectiveness and need for variant-adapted vaccines
Authors: Pather Shanti , Madhi Shabir A. , Cowling Benjamin J. , Moss Paul , Kamil Jeremy P. , Ciesek Sandra , Muik Alexander , Türeci Özlem
Published: May 2023

The highly transmissible Omicron (B.1.1.529) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first detected in late 2021. Initial Omicron waves were primarily made up of sub-lineages BA.1 and/or BA.2, BA.4, and BA.5 subsequently became dominant in mid-2022, and several descendants of these sub-lineages have since emerged. Omicron infections have generally caused less severe disease on average than those caused by earlier variants of concern in healthy adult populations, at least, in part, due to increased population immunity. Nevertheless, healthcare systems in many countries, particularly those with low population immunity, have been overwhelmed by unprecedented surges in disease prevalence during Omicron waves. Pediatric admissions were also higher during Omicron waves compared with waves of previous variants of concern. All Omicron sub-lineages exhibit partial escape from wild-type (Wuhan-Hu 1) spike-based vaccine-elicited neutralizing antibodies, with sub-lineages with more enhanced immuno-evasive properties emerging over time. Evaluating vaccine effectiveness (VE) against Omicron sub-lineages has become challenging against a complex background of varying vaccine coverage, vaccine platforms, prior infection rates, and hybrid immunity. Original messenger RNA vaccine booster doses substantially improved VE against BA.1 or BA.2 symptomatic disease. However, protection against symptomatic disease waned, with reductions detected from 2 months after booster administration. While original vaccine-elicited CD8+ and CD4+ T-cell responses cross-recognize Omicron sub-lineages, thereby retaining protection against severe outcomes, variant-adapted vaccines are required to expand the breadth of B-cell responses and improve durability of protection. Variant-adapted vaccines were rolled out in late 2022 to increase overall protection against symptomatic and severe infections caused by Omicron sub-lineages and antigenically aligned variants with enhanced immune escape mechanisms.
Autoimmune/inflammatory syndrome induced by adjuvants in a woman with Hashimoto thyroiditis and familial autoimmunity—a case report and literature review
Authors: Plavsic Aleksandra , Arandjelovic Snezana , Dimitrijevic Milan , Kusic Natasa , Tomic Spiric Vesna , Popovic Bojana , Jovicic Zikica , Peric Popadic Aleksandra , Miskovic Rada
Published: May 2023

Introduction

Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) consists of a wide spectrum of symptoms and immunological features that are believed to develop in predisposed individuals after exposure to an adjuvant, including a silicone breast implant (SBI). Different autoimmune diseases (AIDs) have been associated with ASIA, but ASIA development after SBI in women with Hashimoto thyroiditis (HT) and familial autoimmunity has rarely been described.

Case report

A 37-year-old woman presented in 2019 with arthralgia, sicca symptoms, fatigue, + antinuclear antibody (ANA), + anti SSA, and + anticardiolipin Immunoglobulin G (IgG) antibodies. She was diagnosed with HT and vitamin D deficiency in 2012. The familial autoimmunity was present: the patient’s mother had been diagnosed with systemic lupus erythematosus and secondary Sjogren’s syndrome and her grandmother with cutaneous lupus and pernicious anemia. In 2017, the patient had a cosmetic SBI procedure that was complicated by repeated right breast capsulitis. After 2 years of irregular visits due to COVID-19, she presented with + ANA, + anticentromere antibodies both in sera and seroma, sicca syndrome, arthralgias, twinkling in extremities, abnormal capillaroscopic findings, and reduced diffusing capacity of the lungs for carbon monoxide. She was diagnosed with ASIA, and antimalarial and corticosteroid therapy were introduced.

Conclusion

In patients with HT and familial autoimmunity, SBI should be carefully considered due to the possibility of ASIA development. Hashimoto thyroiditis, familial autoimmunity, and ASIA seem to be interconnected in the complex mosaic of autoimmunity in predisposed individuals.
cGAMP the travelling messenger
Authors: Blest Henry T. W. , Chauveau Lise
Published: May 2023

2’3’-cGAMP is a key molecule in the cGAS-STING pathway. This cyclic dinucleotide is produced by the cytosolic DNA sensor cGAS in response to the presence of aberrant dsDNA in the cytoplasm which is associated with microbial invasion or cellular damage. 2’3’-cGAMP acts as a second messenger and activates STING, the central hub of DNA sensing, to induce type-I interferons and pro-inflammatory cytokines necessary for responses against infection, cancer or cellular stress. Classically, detection of pathogens or danger by pattern recognition receptors (PRR) was thought to signal and induce the production of interferon and pro-inflammatory cytokines in the cell where sensing occurred. These interferon and cytokines then signal in both an autocrine and paracrine manner to induce responses in neighboring cells. Deviating from this dogma, recent studies have identified multiple mechanisms by which 2’3’-cGAMP can travel to neighboring cells where it activates STING independent of DNA sensing by cGAS. This observation is of great importance, as the cGAS-STING pathway is involved in immune responses against microbial invaders and cancer while its dysregulation drives the pathology of a wide range of inflammatory diseases to which antagonists have been elusive. In this review, we describe the fast-paced discoveries of the mechanisms by which 2’3’-cGAMP can be transported. We further highlight the diseases where they are important and detail how this change in perspective can be applied to vaccine design, cancer immunotherapies and treatment of cGAS-STING associated disease.
Serum proteomics in giant cell arteritis in response to a three-day pulse of glucocorticoid followed by tocilizumab monotherapy (the GUSTO trial)
Authors: Christ Lisa , Gloor Andrea D. , Kollert Florian , Gaber Timo , Buttgereit Frank , Reichenbach Stephan , Villiger Peter M.
Published: May 2023

Objective

Proteome analyses in patients with newly diagnosed, untreated giant cell arteritis (GCA) have not been reported previously, nor are changes of protein expression upon treatment with glucocorticoids (GC) and/or tocilizumab (TCZ) known. The GUSTO trial allows to address these questions, provides the opportunity to learn about the differential effects of GC and TCZ on proteomics and may help to identify serum proteins to monitor disease activity.

Methods

Serum samples obtained from 16 patients with new-onset GCA at different time points (day 0, 3, 10, and week 4, 24, 52) during the GUSTO trial (NCT03745586) were examined for 1436 differentially expressed proteins (DEPs) based on proximity extension assay technology. The patients received 500 mg methylprednisolone intravenously for 3 consecutive days followed by TCZ monotherapy.

Results

When comparing day 0 (before the first GC infusion) with week 52 (lasting remission), 434 DEPs (213↑, 221↓) were identified. In response to treatment, the majority of changes occurred within 10 days. GC inversely regulated 25 proteins compared to remission. No difference was observed between weeks 24 and 52 during established remission and ongoing TCZ treatment. Expression of CCL7, MMP12, and CXCL9 was not regulated by IL6.

Conclusion

Disease-regulated serum proteins improved within 10 days and were normalized within 24 weeks, showing a kinetic corresponding to the gradual achievement of clinical remission. The proteins inversely regulated by GC and TCZ shed light on the differential effects of the two drugs. CCL7, CXCL9, and MMP12 are biomarkers that reflect disease activity despite normalized C-reactive protein levels.
Targeting NETs using dual-active DNase1 variants
Authors: Englert Hanna , Göbel Josephine , Khong Danika , Omidi Maryam , Wolska Nina , Konrath Sandra , Frye Maike , Mailer Reiner K. , Beerens Manu , Gerwers Julian C. , Preston Roger J. S. , Odeberg Jacob , Butler Lynn M. , Maas Coen , Stavrou Evi X. , Fuchs Tobias A. , Renné Thomas
Published: May 2023

Background

Neutrophil Extracellular Traps (NETs) are key mediators of immunothrombotic mechanisms and defective clearance of NETs from the circulation underlies an array of thrombotic, inflammatory, infectious, and autoimmune diseases. Efficient NET degradation depends on the combined activity of two distinct DNases, DNase1 and DNase1-like 3 (DNase1L3) that preferentially digest double-stranded DNA (dsDNA) and chromatin, respectively.

Methods

Here, we engineered a dual-active DNase with combined DNase1 and DNase1L3 activities and characterized the enzyme for its NET degrading potential in vitro. Furthermore, we produced a mouse model with transgenic expression of the dual-active DNase and analyzed body fluids of these animals for DNase1 and DNase 1L3 activities. We systematically substituted 20 amino acid stretches in DNase1 that were not conserved among DNase1 and DNase1L3 with homologous DNase1L3 sequences.

Results

We found that the ability of DNase1L3 to degrade chromatin is embedded into three discrete areas of the enzyme's core body, not the C-terminal domain as suggested by the state-of-the-art. Further, combined transfer of the aforementioned areas of DNase1L3 to DNase1 generated a dual-active DNase1 enzyme with additional chromatin degrading activity. The dual-active DNase1 mutant was superior to native DNase1 and DNase1L3 in degrading dsDNA and chromatin, respectively. Transgenic expression of the dual-active DNase1 mutant in hepatocytes of mice lacking endogenous DNases revealed that the engineered enzyme was stable in the circulation, released into serum and filtered to the bile but not into the urine.

Conclusion

Therefore, the dual-active DNase1 mutant is a promising tool for neutralization of DNA and NETs with potential therapeutic applications for interference with thromboinflammatory disease states.
Integrating fishers’ knowledge with oceanographic observations to understand changing ocean conditions in the Northeast United States
Authors: Olsen Noelle A. , Bahr Frank , Bethoney N. David , Mercer Anna M. , Gawarkiewicz Glen
Published: May 2023

Recent warming in the Northeast United States continental shelf ecosystem has raised several concerns about the impacts on the ecosystem and commercial fisheries. In 2014, researchers from the Commercial Fisheries Research Foundation and Woods Hole Oceanographic Institution founded the Shelf Research Fleet to involve fishers in monitoring the rapidly changing ocean environment and encourage sharing of ecological knowledge. The Shelf Research Fleet is a transdisciplinary, cooperative program that trains commercial fishers to collect oceanographic information by deploying conductivity, temperature, and depth (CTD) instruments while commercially fishing. A total of 806 CTD profiles have been collected by the Shelf Research Fleet through December 2022. Participating vessels can view the conductivity and temperature water column profiles they collect in real-time. These profiles help inform their fishing practices and give insights when unexpected species appear in their gear or if their catch composition changes from previous years. The data collected by the Shelf Research Fleet are shared with and processed by researchers from numerous partnering institutions. The Shelf Research Fleet data have been used by researchers to better understand oceanographic phenomena including marine heatwaves, shelf-break exchange processes, warm core rings, and salinity maximum intrusions onto the continental shelf. The scope of the Shelf Research Fleet has grown over time to include efforts to more directly link oceanographic results with biological observations to better understand how changing ocean conditions are affecting commercially important species. This article describes the approach, successes, challenges, and future directions of the Shelf Research Fleet and aims to outline a framework for a cost-effective research program that engages fishers in the collection of oceanographic data, strengthening partnerships between fishing industry members and the scientific community.
Reconstructing past fisheries catches for large pelagic species in the Indian Ocean
Authors: Heidrich Kristina N. , Meeuwig Jessica J. , Zeller Dirk
Published: May 2023

Comprehensive catch data are fundamental to support the sustainable management of large pelagic fisheries. However, catch data reported by the Indian Ocean Tuna Commission (IOTC) on behalf of its member countries currently under-represent the extent of these fisheries in the Indian Ocean. We reconstructed fisheries catches of large pelagic species for the Indian Ocean from 1950 to 2020, aiming to improve the comprehensiveness of existing reported data and to provide more ecologically relevant datasets for research and management uses. We reconstructed catches for 42 countries operating five major gear groups (longline, purse seine, gillnet, pole-and-line, and other gears) in the large pelagic fisheries. Reconstructed catches were 30% higher than the data reported by the IOTC. We demonstrated that distant-water fishing fleets historically dominated large-scale industrial fishing but were gradually replaced by fleets flagged to Indian Ocean rim countries. Our results also indicated an average discard rate of ~14% over the 1950-2020 period, primarily attributable to extensive discarding practices associated with longline and gillnet vessels. Reporting over time has improved only for tunas, whereas shark catches still remain under-reported, accounting for 51% of total unreported landings and discards in 2020. We confirmed substantial taxonomic aggregation in the data reported by the IOTC on behalf of its member countries, masking important patterns and trends and further complicating the sustainable management of exploited species in the Indian Ocean. We recommend substantially increased observer coverage and far better and stronger support by all member countries to improve the fisheries statistics in the IOTC.
Sustainability assessment for an offshore coral reef island based on scenario simulation and emergy analysis
Authors: Wu Wenzhou , Zhang Peng , Jiang Huiping , Su Fenzhen
Published: May 2023

As the intensity of ocean spatial exploitation increases, the offshore island tourism has been thriving, and the utilization of uninhabited islands is attracting more and more attention. In order to achieve the sustainable development of offshore island tourism resources, it is important to evaluate population carrying capacity and conduct sustainability assessment for uninhabited islands. To this end, we proposed a quantitative evaluation method for the sustainable development of offshore coral reef islands based on the combination of scenario simulation and emergy analysis. This method was tested on a coral reef island in the South China Sea, namely Lingyang Reef. The dynamics in emergy related structures and indicators of Lingyang Reef system were revealed under different scenarios, providing decision-making references for the pre-development sustainability assessment of an uninhabited coral reef island. The evaluation results showed that (1) when accommodating 2000 persons, the island system was in a low-load state, with sustainable values in terms of renewable energy input percentage, environmental load ratio, and emergy sustainability index, except for the critical state of emergy yield ratio; (2) when accommodating 5000 persons, the emergy yield ratio was in an unsustainable state, with the emergy sustainability index in a critical state, and both of the renewable energy input percentage and environmental load ratio in sustainable states, indicating that socioeconomic activities were not beyond the carrying capacity, and the development and utilization intensity was moderate; (3) when accommodating 10000 persons, the renewable energy input percentage and emergy sustainability index were in critical states, and the emergy yield ratio and environmental load ratio were in unsustainable states, indicating that the corresponding human activities had exceeded the carrying capacity.
Compounding deep sea physical impacts on marine microbial motility
Authors: Mullane Kelli K. , Nishiyama Masayoshi , Kurihara Tatsuo , Bartlett Douglas H.
Published: May 2023

Introduction

Approximately three-fourths of all pelagic marine prokaryotes live in the deep sea, an environment characterized by high hydrostatic pressure and, in most cases, low temperature. Labile organic matter is often scarce within these settings, providing a competitive advantage to motile cells that can access the nutrients within a greater seawater volume. Because many cells present at depth are shallow water-adapted microbes descending from more productive surface waters, deep-sea conditions could significantly reduce their motility and, consequently, their biogeochemical activities.

Methods

In this study, we address this possibility by examining the impact of deep-sea physical conditions on the motility of three representative marine microbes belonging to the cosmopolitan genera Halomonas, Alcanivorax, and Shewanella. Growth-dependent motility agar assays and growth-independent microscopy assays were employed at four pressures and two temperatures.

Results

At pressures equivalent to bathyal and abyssal depths (10 – 50 Megapascals), decreases in temperature (30°C – 4°C or 23°C – 7°C depending on the assay) had a greater negative impact on motility than pressure. In addition, the high-pressure and low-temperature impacts were additive. Exposure to high pressure and/or low temperature had varying degrees of effect on flagellar function, depending on the strain and the magnitude of the applied stress. These ranged from short-term impacts that were quickly reversible to long-term impacts that were detrimental to the function of the flagellum, leading to complete loss of motility.

Discussion

These findings highlight the sensitivity of motility systems of piezosensitive mesophilic marine bacteria to the combined pressure/temperature conditions present in the deep sea, phenotypes that in situ are likely to manifest themselves in the modulation of diverse microbial activities.
Rare case of pulmonary fat embolism and acute respiratory distress syndrome after liposuction and fat grafting: a case report
Authors: Gai Xiaoyan , Sun Xiaoyan , Zhu Xiang , Zhou Qingtao , Sun Yongchang
Published: May 2023

Background

Pulmonary fat embolism usually occurs after fracture, yet rarely observed after liposuction and fat grafting.

Case presentation

We describe a 19-year-old female patient who presented with acute respiratory failure and diffuse pulmonary opacities on chest radiographic image shortly after liposuction and fat grafting. Bronchoalveolar lavage was performed and lipid content in alveolar cells contribute to the diagnosis of the fat embolism syndrome. The patient was successfully treated with noninvasive mechanical ventilation and a short course of glucocorticoids.

Conclusions

Early recognition and appropriate treatment are very important to improve the outcome of pulmonary fat embolism. Considering that liposuction and fat grafting are increasingly common cosmetic surgeries, our aim is to raise awareness for this rare adverse event.
Hazara orthonairovirus nucleoprotein facilitates viral cell-to-cell spread by modulating tight junction protein, claudin-1
Authors: Ohta Keisuke , Saka Naoki , Fukasawa Masayoshi , Nishio Machiko
Published: May 2023

Background

Tight junctions act as a barrier that prevents invasion of pathogens through epithelial cells. This study aims to elucidate the correlation between tight junctions and nairoviruses using Hazara orthonairovirus (HAZV) as a surrogate model for Crimean-Congo hemorrhagic fever virus.

Methods

mRNA, total protein, and cell surface protein levels of tight junction proteins were examined by quantitative real-time reverse transcription polymerase chain reaction, immunoblot and flow cytometry, respectively. HAZV growth was measured by plaque assay. Immunofluorescence assay was used to examine viral cell-to-cell spread. The interaction between HAZV nucleoprotein and claudin-1 was analyzed by immunoprecipitation.

Results

HAZV infection induced mRNA of several tight junction proteins, especially claudin-1. HAZV infection also induced cell surface expression of claudin-1 protein. Claudin-1 overexpression inhibited the growth of HAZV by blocking its cell-to-cell spread. In contrast, HAZV nucleoprotein completely inhibited HAZV-induced cell surface expression of claudin-1, and this inhibition required interaction between HAZV nucleoprotein and claudin-1.

Conclusion

HAZV nucleoprotein was shown to bind to claudin-1 to negatively regulate its cell surface expression, and so can promote cell-to-cell spread of HAZV. This is the first presentation of a possible mechanism behind how nairoviruses counteract tight junction barrier function.
DPP-4 inhibitors for treating T2DM - hype or hope? an analysis based on the current literature
Authors: Saini Kunika , Sharma Smriti , Khan Yousuf
Published: May 2023

DPP-4 inhibition is an interesting line of therapy for treating Type 2 Diabetes Mellitus (T2DM) and is based on promoting the incretin effect. Here, the authors have presented a brief appraisal of DPP-4 inhibitors, their modes of action, and the clinical efficiency of currently available drugs based on DPP-4 inhibitors. The safety profiles as well as future directions including their potential application in improving COVID-19 patient outcomes have also been discussed in detail. This review also highlights the existing queries and evidence gaps in DPP-4 inhibitor research. Authors have concluded that the excitement surrounding DPP-4 inhibitors is justified because in addition to controlling blood glucose level, they are good at managing risk factors associated with diabetes.
Microbial inulinase promotes fructan hydrolysis under simulated gastric conditions
Authors: Guice Justin L. , Hollins Morgan D. , Farmar James G. , Tinker Kelly M. , Garvey Sean M.
Published: May 2023

Fermentable oligo-, di-, monosaccharides and polyols (FODMAPs) have emerged as key contributors to digestive discomfort and intolerance to certain vegetables, fruits, and plant-based foods. Although strategies exist to minimize FODMAP consumption and exposure, exogenous enzyme supplementation targeting the fructan-type FODMAPs has been underexploited. The objective of this study was to test the hydrolytic efficacy of a food-grade, non-genetically engineered microbial inulinase preparation toward inulin-type fructans in the INFOGEST in vitro static simulation of gastrointestinal (GI) digestion. Purified inulin was shown to undergo acid-mediated hydrolysis at high gastric acidity as well as predominantly inulinase-mediated hydrolysis at lower gastric acidity. Inulinase dose-response simulations of inulin, garlic, and high-fructan meal digestion in the gastric phase suggest that as little as 50 inulinase units (INU) and up to 800 INU per serving promote fructan hydrolysis better than the control simulations without inulinase. Liquid chromatography-mass spectrometry (LC-MS) profiling of fructo-oligosaccharides (FOS) in the gastric digestas following inulinase treatment confirms the fructolytic activity of inulinase under simulated digestive conditions. Altogether, these in vitro digestion data support the use of microbial inulinase as an exogenous enzyme supplement for reducing dietary fructan-type FODMAP exposure.
Localized chemotherapy approaches and advanced drug delivery strategies: a step forward in the treatment of peritoneal carcinomatosis from ovarian cancer
Authors: Breusa Silvia , Zilio Serena , Catania Giuseppina , Bakrin Naoual , Kryza David , Lollo Giovanna
Published: May 2023

Peritoneal carcinomatosis (PC) is a common outcome of epithelial ovarian carcinoma and is the leading cause of death for these patients. Tumor location, extent, peculiarities of the microenvironment, and the development of drug resistance are the main challenges that need to be addressed to improve therapeutic outcome. The development of new procedures such as HIPEC (Hyperthermic Intraperitoneal Chemotherapy) and PIPAC (Pressurized Intraperitoneal Aerosol Chemotherapy) have enabled locoregional delivery of chemotherapeutics, while the increasingly efficient design and development of advanced drug delivery micro and nanosystems are helping to promote tumor targeting and penetration and to reduce the side effects associated with systemic chemotherapy administration. The possibility of combining drug-loaded carriers with delivery via HIPEC and PIPAC represents a powerful tool to improve treatment efficacy, and this possibility has recently begun to be explored. This review will discuss the latest advances in the treatment of PC derived from ovarian cancer, with a focus on the potential of PIPAC and nanoparticles in terms of their application to develop new therapeutic strategies and future prospects.
5-aminolevulinic acid, fluorescein sodium, and indocyanine green for glioma margin detection: analysis of operating wide-field and confocal microscopy in glioma models of various grades
Authors: Belykh Evgenii , Bardonova Liudmila , Abramov Irakliy , Byvaltsev Vadim A. , Kerymbayev Talgat , Yu Kwanha , Healey Debbie R. , Luna-Melendez Ernesto , Deneen Benjamin , Mehta Shwetal , Liu James K. , Preul Mark C.
Published: May 2023

Introduction

Surgical resection remains the first-line treatment for gliomas. Several fluorescent dyes are currently in use to augment intraoperative tumor visualization, but information on their comparative effectiveness is lacking. We performed systematic assessment of fluorescein sodium (FNa), 5-aminolevulinic acid (5-ALA)–induced protoporphyrin IX (PpIX), and indocyanine green (ICG) fluorescence in various glioma models using advanced fluorescence imaging techniques.

Methods

Four glioma models were used: GL261 (high-grade model), GB3 (low-grade model), and an in utero electroporation model with and without red fluorescence protein (IUE +RFP and IUE -RFP, respectively) (intermediate-to-low-grade model). Animals underwent 5-ALA, FNa, and ICG injections and craniectomy. Brain tissue samples underwent fluorescent imaging using a wide-field operative microscope and a benchtop confocal microscope and were submitted for histologic analysis.

Results

Our systematic analysis showed that wide-field imaging of highly malignant gliomas is equally efficient with 5-ALA, FNa, and ICG, although FNa is associated with more false-positive staining of the normal brain. In low-grade gliomas, wide-field imaging cannot detect ICG staining, can detect FNa in only 50% of specimens, and is not sensitive enough for PpIX detection. With confocal imaging of low-intermediate grade glioma models, PpIX outperformed FNa.

Discussion

Overall, compared to wide-field imaging, confocal microscopy significantly improved diagnostic accuracy and was better at detecting low concentrations of PpIX and FNa, resulting in improved tumor delineation. Neither PpIX, FNa, nor ICG delineated all tumor boundaries in studied tumor models, which emphasizes the need for novel visualization technologies and molecular probes to guide glioma resection. Simultaneous administration of 5-ALA and FNa with use of cellular-resolution imaging modalities may provide additional information for margin detection and may facilitate maximal glioma resection.
Enhanced recovery of postoperative nursing for single-port thoracoscopic surgery in lung cancer patients
Authors: Hu Xiufen , He Xiaodan
Published: May 2023

Lung cancer is a common clinical malignant tumor, and the number of new lung cancer patients is increasing year by year. With the advancement of thoracoscopy technology and equipment, the scope of application of minimally invasive surgery has expanded to almost all types of lung cancer resection, making it the mainstream lung cancer resection surgery. Single-port thoracoscopic surgery provides evident advantages in terms of postoperative incision pain since only a single incision is required, and the surgical effect is similar to those of multi-hole thoracoscopic surgery and traditional thoracotomy. Although thoracoscopic surgery can effectively remove tumors, it nevertheless induces variable degrees of stress in lung cancer patients, which eventually limit lung function recovery. Rapid rehabilitation surgery can actively improve the prognosis of patients with different types of cancer and promote early recovery. This article reviews the research progress on rapid rehabilitation nursing in single-port thoracoscopic lung cancer surgery.
Could the tumor-associated microbiota be the new multi-faceted player in the tumor microenvironment?
Authors: Goubet Anne-Gaëlle
Published: May 2023

Microorganisms have been identified in tumor specimens for over a century. It is only in recent years that tumor-associated microbiota has become a rapidly expanding field. Assessment techniques encompass methods at the frontiers of molecular biology, microbiology, and histology, requiring a transdisciplinary process to carefully decipher this new component of the tumor microenvironment. Due to the low biomass, the study of tumor-associated microbiota poses technical, analytical, biological, and clinical challenges and must be approached as a whole. To date, several studies have begun to shed light on the composition, functions, and clinical relevance of the tumor-associated microbiota. This new piece of the tumor microenvironment puzzle could potentially change the way we think about and treat patients with cancer.
Establishment and validation of a ferroptosis-related signature predicting prognosis and immunotherapy effect in colon cancer
Authors: Li Zhufeng , Yuan Fang , Liu Xin , Wei Jianming , Liu Tong , Li Weidong , Li Chuan
Published: May 2023

Background

Ferroptosis, a novel form of regulating cell death, is related to various cancers. However, the role of ferroptosis-related genes (FRGs) on the occurrence and development of colon cancer (CC) needs to be further elucidated.

Method

CC transcriptomic and clinical data were downloaded from TCGA and GEO databases. The FRGs were obtained from the FerrDb database. The consensus clustering was performed to identify the best clusters. Then, the entire cohort was randomly divided into the training and testing cohorts. Univariate Cox, LASSO regression and multivariate Cox analyses were used to construct a novel risk model in training cohort. The testing and the merged cohorts were performed to validate the model. Moreover, CIBERSORT algorithm analyze TIME between high- and low- risk groups. The immunotherapy effect was evaluated by analyzing the TIDE score and IPS between high- and low- risk groups. Lastly, RT-qPCR were performed to analyze the expression of the three prognostic genes, and the 2-years OS and DFS between the high- and low- risk groups of 43 clinical CC samples to further validate the value of the risk model.

Results

SLC2A3, CDKN2A, and FABP4 were identified to construct a prognostic signature. Kaplan–Meier survival curves showed that OS between the high- and low-risk groups were statistically significant (pmerged<0.001, ptraining<0.001, ptesting<0.001). TIDE score and IPS were higher in the high-risk group (pTIDE<0.005, pDysfunction<0.005, pExclusion<0.001, pmAb-CTLA-4 = 3e-08, pmAb-PD-1 = 4.1e-10). The clinical samples were divided into high- and low- risk groups according to the risk score. There was a statistical difference in DFS (p=0.0108).

Conclusion

This study established a novel prognostic signature and provided more insight into the immunotherapy effect of CC.
Supervised interprofessional student pain clinic program - efficacy with the utilization of zoom
Authors: Dao Brandon , Cao Ling
Published: May 2023

Introduction

Current medical education curricula in pain management are insufficient to match the prevalence of chronic pain and the needs of patient populations. The Supervised Student Inter-professional Pain Clinic Program (SSIPCP) aims to train healthcare professional students to improve their abilities in chronic pain management in interprofessional (IP) teams. Due to the COVID-19 pandemic, Zoom was employed to allow the program to continue. In this study, survey data from students who participated during and before the COVID-19 pandemic were compared to determine if the program carried out via Zoom can maintain its effectiveness.

Methods

Student pre- and post-program survey data were entered into Microsoft Excel spreadsheet and then graphed and analyzed with Sigma Plot. Surveys assessed knowledge in chronic pain physiology and management, attitude towards IP practice, and perceived team skills in the form of questionnaires and open-ended questions. Paired t-tests and Wilcoxon Signed-rank tests were used for two-group comparisons and two-way repeated ANOVA followed by the Holm-Sidak post-hoc tests were used for multiple group comparisons.

Results

Overall, students continued to exhibit significant improvement in major areas assessed even with the use of Zoom. Strengths of the programs were also shared across student cohorts regardless of Zoom usage. However, despite their improvements, students who utilized Zoom stated that they would have preferred in-person program activities.

Conclusion

Although students prefer in-person activities, the SSIPCP successfully trained healthcare students in chronic pain management and working in an IP team through Zoom.
Case report: Fatal lung hyperinflammation in a preterm newborn with SARS-CoV-2 infection
Authors: Aguilar-Caballero Daniela , Capcha Jose M. C. , Caballero Veronica , Young Karen C. , Duara Shahnaz , Borchetta Michael , Gonzalez Ivan , Saad Ali G. , Webster Keith A. , Shehadeh Lina A. , Bandstra Emmalee S. , Schmidt Augusto F.
Published: May 2023

Vertical transmission of SARS-CoV-2 from mother to fetus is widely accepted. Whereas most infected neonates present with mild symptoms or are asymptomatic, respiratory distress syndrome (RDS) and abnormal lung images are significantly more frequent in COVID-19 positive neonates than in non-infected newborns. Fatality is rare and discordant meta-analyses of case reports and series relating perinatal maternal COVID-19 status to neonatal disease severity complicate their extrapolation as prognostic indicators. A larger database of detailed case reports from more extreme cases will be required to establish therapeutic guidelines and allow informed decision making. Here we report an unusual case of a 28 weeks' gestation infant with perinatally acquired SARS-CoV-2, who developed severe protracted respiratory failure. Despite intensive care from birth with first line anti-viral and anti-inflammatory therapy, respiratory failure persisted, and death ensued at 5 months. Lung histopathology showed severe diffuse bronchopneumonia, and heart and lung immunohistochemistry confirmed macrophage infiltration, platelet activation and neutrophil extracellular trap formation consistent with late multisystem inflammation. To our knowledge, this is the first report of SARS CoV-2 pulmonary hyperinflammation in a preterm newborn with fatal outcome.
Toxicokinetics of recombinant human fibroblast growth factor 21 for injection in cynomolgus monkey for 3 months
Authors: Lu Chao , Jin Lei , Bi Jianing , Jin Hongyi , You Xinyi , Peng Lulu , Fan Haibing , Wang Huan , Wang Liangshun , Fan Zhengkai , Wang Xiaojie , Liu Baohua
Published: May 2023

Introduction: Recombinant human fibroblast growth factor 21 (FGF-21) is a potential therapeutic agent for multiple metabolic diseases. However, little is known about the toxicokinetic characteristics of FGF-21.

Methods: In the present study, we investigated the toxicokinetics of FGF-21 delivered via subcutaneous injection in vivo. Twenty cynomolgus monkeys were injected subcutaneously with different doses of FGF-21 for 86 days. Serum samples were collected at eight different time points (0, 0.5, 1.5, 3, 5, 8, 12, and 24 h) on day 1, 37 and 86 for toxicokinetic analysis. The serum concentrations of FGF-21 were measured using a double sandwich Enzyme-linked immunosorbent assay. Blood samples were collected on day 0, 30, 65, and 87 for blood and blood biochemical tests. Necropsy and pathological analysis were performed on d87 and d116 (after recovery for 29 days).

Results: The average AUC(0-24h) values of low-dose FGF-21 on d1, d37, and d86 were 5253, 25268, and 60445 μg h/L, and the average AUC(0–24h) values of high-dose FGF-21 on d1, d37, and d86 were 19964, 78999, and 1952821 μg h/L, respectively. Analysis of the blood and blood biochemical indexes showed that prothrombin time and AST content in the high-dose FGF-21 group increased. However, no significant changes in other blood and blood biochemical indexes were observed. The anatomical and pathological results showed that continuous subcutaneous injection of FGF-21 for 86 days did not affect organ weight, the organ coefficient, and histopathology in cynomolgus monkeys.

Discussion: Our results have guiding significance for the preclinical research and clinical use of FGF-21.
Characterization of 15 CYP2J2 variants identified in the Chinese Han population on the metabolism of ebastine and terfenadine in vitro
Authors: Zou Li-Li , Zhao Fang-Ling , Qi Yu-Ying , Wang Shuang-Hu , Zhou Quan , Geng Pei-Wu , Zhou Yun-Fang , Zhang Qing , Chen Hao , Dai Da-Peng , Cai Jian-Ping , Ji Fu-Sui
Published: May 2023

Genetic polymorphism of the cytochrome P450 (CYP) gene can significantly influence the metabolism of endogenous and xenobiotic compounds. However, few studies have focused on the polymorphism of CYP2J2 and its impact on drug catalytic activity, especially in the Chinese Han population. In this study, we sequenced the promoter and exon regions of CYP2J2 in 1,163 unrelated healthy Chinese Han individuals using the multiplex PCR amplicon sequencing method. Then, the catalytic activities of the detected CYP2J2 variants were evaluated after recombinant expression in S. cerevisiae microsomes. As a result, CYP2J2*7, CYP2J2*8, 13 variations in the promoter region and 15 CYP2J2 nonsynonymous variants were detected, of which V15A, G24R, V68A, L166F and A391T were novel missense variations. Immunoblotting results showed that 11 of 15 CYP2J2 variants exhibited lower protein expression than wild-type CYP2J2.1. In vitro functional analysis results revealed that the amino acid changes of 14 variants could significantly influence the drug metabolic activity of CYP2J2 toward ebastine or terfenadine. Specifically, 4 variants with relatively higher allele frequencies, CYP2J2.8, 173_173del, K267fs and R446W, exhibited extremely low protein expression and defective catalytic activities for both substrates. Our results indicated that a high genetic polymorphism of CYP2J2 could be detected in the Chinese Han population, and most genetic variations in CYP2J2 could influence the expression and catalytic activity of CYP2J2. Our data significantly enrich the knowledge of genetic polymorphisms in CYP2J2 and provide new theoretical information for corresponding individualized medication in Chinese and other Asian populations.
Toll-like receptor 4 deletion partially protects mice from high fat diet-induced arterial stiffness despite perturbation to the gut microbiota
Authors: Ecton Kayl E. , Graham Elliot L. , Risk Briana D. , Brown Gabriele D. , Stark Grace C. , Wei Yuren , Trikha S. Raj J. , Weir Tiffany L. , Gentile Christopher L.
Published: May 2023

The present study aimed to determine the effects of toll-like receptor 4 (TLR4) deletion on high fat diet-induced aortic stiffness and gut microbiota alterations. We hypothesized that a high fat diet would result in perturbation of the gut microbiota in both control and TLR4 knockout mice (TLR4-/-), but that the absence of TLR4 signaling would protect mice from downstream vascular consequences of the high fat diet. Male control mice (CON, n=12) and TLR4-/- mice (KO, n=12) were fed either a standard low-fat diet (SD) or a high fat diet (HFD) (60% kcals from fat) for 6 months, after which time measurements of aortic stiffness (via pulse wave velocity [aPWV]) and gut microbiota composition (16S rRNA sequencing) were determined. Compared to the SD, HFD reduced microbial variability, promoted perturbation of the gut microbiota, and increased intestinal permeability in both CON and KO mice, with no effect of genotype. This increased intestinal permeability in HFD mice was accompanied by increases in plasma lipopolysaccharide binding protein (LBP) levels, an indicator of circulating endotoxin (p<0.05 for all comparisons between HFD and SD groups). aPWV was increased in CON+HFD mice (CON+HFD vs CON+SD: 525.4 ± 16.5 cm/sec vs. 455.2 ± 16.5 cm/sec; p<0.05), whereas KO+HFD mice displayed partial protection from HFD-induced arterial stiffening (KO+HFD vs. CON+SD: 488.2 ± 16.6 cm/sec vs. 455.2 ± 16.5 cm/sec; p=0.8) (KO+HFD vs. CON+HFD: 488.2 ± 16.6 cm/sec vs. 525.4 ± 16.5 cm/sec; p=0.1). In summary, TLR4 KO mice are not protected from deleterious alterations in gut microbial composition or intestinal permeability following a HFD, but are partially protected from the downstream arterial stiffening, suggesting that TLR4 signaling is not required for HFD-mediated intestinal disturbances, but is an important determinant of downstream vascular consequences.
Oralność gwar i ich leksyka
Authors: Sierociuk Jerzy
Published: May 2023

This article discusses the issue of a relationship between oral characteristics of dialects with the functioning of the lexis that is specific to them. A dialect, as a speech of an oral community, functions based on an intergenerational message. This influences the “storage” of a significant portion of the local lexis in the sphere close to passive command. This property determines, to a large extent, the limited resource of lexicographic materials, since a considerable portion of the vocabulary is provided by respondents only after a straightforward intervention of the explorer.
Wielość gwar śląskich źródłem bogactwa regionu
Authors: Nowakowska-Kempna Iwona
Published: May 2023

The diversity of the contemporary Silesian dialects corresponds to the division adopted by K. Nitsch (1960), apart from the non-existence of the Lach dialects that are extinct in this area. However, the dialects present in Silesia have become richer by the Southern Borderlands dialect, which is used mainly by repatriates living in villages (and small towns) in the area stretching from the Katowice to the Wrocław regions. The linguistic analysis of a given dialect is still determined based on the inhabitants’ speech, that is relying on the usage and function criterion. This opens the prospect of studying language by means of the paradigms applying the usage-based models of language, such as cognitivism, sociolinguistics, and dialectology. The most commonly used
variation of Polish is mixed, where the dialect intertwines with the general language and which is characterised by stylistic diversity (e.g. the colloquial and scientific styles); hence, the application of language usage-based paradigms, which enable the presentation of language in sociocultural processes (e.g. dromology, mediamorphosis, and glocalisation, i.e. globalisaƟ on and localisation combined) is important in the research of this kind. When determining dialectal characteristics, E. Rosch’s prototype theory is also useful, as it permits the detection of canonical (prototypical) features of a given dialect, usually phonetic ones, which allow its distinction from another dialect by criteria. This is because the traditional division of Silesian dialects has undergone certain transformations concerned with a shift of Silesian dialects’ influences with respect to
Lesser and Greater Polish ones, expansion of the mixed area at the borderline between dialects, establishment of mixed Polish, and reduction of the number of people speaking a dialect only. The diversity of dialects as a prestigious variation of Polish in Silesia attests to the abundance of regional experiences of the lands and requires a further holistic research of the language transformations occurring in Silesia