bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytokine Hemoadsorption As Rescue Therapy for Critically Ill Patients with SARS-CoV-2 Pneumonia with Severe Respiratory Failure and Hypercytokinemia
Authors: Ruiz-Rodríguez Juan Carlos , Chiscano-Camón Luis , Ruiz-Sanmartin Adolf , Palmada Clara , Plata-Menchaca Erika Paola , Franco-Jarava Clara , Pérez-Carrasco Marcos , Hernandez-Gonzalez Manuel , Ferrer Ricard
Published: June 2021

Background : A dysregulated inflammatory response, known as “cytokine storm”, plays an important role in the pathophysiology of coronavirus 2019 disease (COVID-19). There is a subgroup of patients who develop a hyperinflammatory response with severe respiratory failure and organ dysfunction with high mortality. Identifying these patients is outstanding as they could benefit from specific therapies, such as cytokine removal by hemoadsorption. Methods: Single-center, observational and prospective study of critically ill patients with SARS-CoV-2 pneumonia, severe acute respiratory failure and hypercytokinemia. All patients received cytokine hemoadsorption using Cytosorb® (Cytosorbents Europe, Berlin, Germany). The indication for treatment was acute respiratory failure, inadequate prone response, and hypercytokinemia. Results : A total of 343 patients were admitted to the ICU due to SARS-Cov-2 infection between March 3, 2020, to June 22, 2020. Of these, six patients [5 (83.3%) men; mean age 57 (10.5) years; SOFA 5 (1.4); mean Acute Physiology And Chronic Health Evaluation (APACHE) II score 19.5 (6)] underwent hemoadsorption with Cytosorb®. All patients fulfilled the Berlin criteria for severe acute respiratory distress syndrome (ARDS), underwent prone positioning, and were on mechanical ventilation for 15.2 (7.2) days. One session of 16 (9.0) hours duration was performed. IL-6 levels were significantly reduced [(pre- hemoadsorption levels 17.367 (4.539– 22.532) pg/ml; post-hemoadsorption levels 2.403 (917 – 3.724) pg/ml, p = 0.043], and improvements in oxygenation were observed [pre-hemoadsorption PaO 2 /FiO 2 ratio was 103 (18.4), post- hemoadsorption PaO2/FiO2 ratio was 222 (20.9), p = 0.029]. We documented the clinical improvement and rapid reversal of organ dysfunction [pre-hemoadsorption Sequential Organ Failure Assessment (SOFA) score 9 (4.7); post- hemoadsorption SOFA score 7.7 (5.4), p = 0.046]. Inflammatory markers (C-reactive protein, D-dimer, and ferritin) also improved significantly. Mean ICU stay was 17.2 (8.0) days. ICU and in-hospital mortality was 33.7%. Conclusions : In our cohort, patients with SARS-CoV-2 pneumonia and severe acute respiratory failure and hypercytokinemia who received cytokine hemoadsorption, an important reduction in IL-6 levels and improvements in oxygenation and SOFA score were observed.
Characterization Of a G Protein α Subunit Encoded Gene From The Dimorphic Fungus-Tremella Fuciformis
Authors: Zhu Hanyu , Liu Dongmei , Zheng Liesheng , Chen Liguo , Ma Aimin
Published: June 2021

Tremella fuciformis is a dimorphic fungus which can undertake the reversible transition between yeast and pseudohypha forms. G protein α subunit (Gα) carries different signals to regulate a variety of biological processes in eukaryotes, including fungal dimorphism. In this study, a novel Gα subunit encoded gene, TrGpa1, was firstly cloned from T. fuciformis. The TrGpa1 open reading frame has 1059 nucleotides, and encodes a protein which belongs to the group I of Gαi superfamily. Furthermore, the role of TrGpa1 in the T. fuciformis dimorphism was analysed by gene overexpression and knockdown. Stable integration of the target gene into the genome was confirmed by PCR and Southern blot hybridization. Transformants with the highest and lowest TrGpa1 expression levels were selected via quantitative real-time PCR analysis and Western blot. Each transformant was compared with the wild-type strain about the morphological change under different environmental factors, including pH values, temperature, cultural time, inoculum size, and quorum-sensing molecules (farnesol and tyrosol). Comparing with the wild-type strain, the overexpression transformant always had higher ratios of pseudohyphae, while the knockdown transformant had less proportions of pseudohyphae. Therefore, the TrGpa1 involves in the dimorphism of T. fuciformis and plays a positive role in promoting pseudohyphal growth.
Establishment of Reference Intervals of Monomeric Prolactin To Identify Macroprolactinemia in Chinese Patients with Increased Total Prolactin
Authors: Hu Yao , Ni Jiajin , Zhang Buyue , Cheng Wei , Zhang Huating , Ye Hongying , Ji Lijin , Lu Bin , Guan Ming
Published: June 2021

Background

Macroprolactin is responsible for pseudohyperprolactinemia and is a common pitfall of the prolactin immunoassay. We aimed to determine the frequency of macroprolactinemia in Chinese hyperprolactinemic patients using monomeric prolactin discriminated by precipitation with polyethylene glycol (PEG).
Methods

Post-PEG monomeric prolactin gender-specific reference intervals were established for the Elecsys immunoassay method (Roche Diagnostics) using sera from healthy female (n = 120) and male (n = 120) donors. The reference intervals were validated using 20 macroprolactinemic (as assessed by gel filtration chromatography (GFC)) sera samples, and presence of monomeric prolactin was discriminated by GFC. Patients with high total prolactin were then screened by PEG precipitation to analyze macroprolactin. The demographic and biochemical details of patients with true hyperprolactinemia and macroprolactinemia were compared.
Results

Reference intervals for monomeric prolactin in females and males were 3.4–18.5 and 2.7–13.1 ng/mL, respectively. Among 1140 hyperprolactinemic patients, macroprolactinemia was identified in 261 (22.9%) patients while the other 879 (77.1%) patients were diagnosed with true hyperprolactinemia. Menstrual disturbances were the most common clinical feature in both groups. Galactorrhea, amenorrhea, and visual disturbances occurred more frequently in true hyperprolactinemic patients (P < 0.05).
Conclusions

The prevalence of macroprolactin in Chinese patients with hyperprolactinemia was described for the first time. Monomeric prolactin concentration, along with a reference interval screening with PEG precipitation, provides a diagnostic approach for hyperprolactinemia with improved accuracy.
Stereotactic Body Radiation Therapy For The Treatment of Localized Prostate Cancer In Men With Underlying Inflammatory Bowel Disease
Authors: Lischalk Jonathan W. , Blacksburg Seth , Mendez Christopher , Repka Michael , Sanchez Astrid , Carpenter Todd , Witten Matthew , Garbus Jules E. , Evans Andrew , Collins Sean , Katz Aaron , Haas Jonathan
Published: June 2021

BackgroundHistorically, IBD has been thought to increase the underlying risk of radiation related toxicity in the treatment of prostate cancer. In the modern era, contemporary radiation planning and delivery may mitigate radiation related toxicity in this theoretically high-risk cohort. This is the first manuscript to report clinical outcomes for men diagnosed with prostate cancer and underlying IBD curatively treated with stereotactic body radiation therapy (SBRT). MethodsA large institutional database of patients (n = 4,245) treated with SBRT for adenocarcinoma of the prostate was interrogated to identify patients who were diagnosed with underlying IBD prior to treatment. All patients were treated with SBRT over five treatment fractions using a robotic radiosurgical platform and fiducial tracking. Baseline IBD characteristics including IBD subtype, pre-SBRT IBD medications, and EPIC bowel questionnaires were reviewed for the IBD cohort. Acute and late toxicity was evaluated using the CTCAE version 5.0. ResultsA total of 31 patients were identified who had underlying IBD prior to SBRT for the curative treatment of prostate cancer. The majority (n = 18) were diagnosed with ulcerative colitis and the majority were being treated local steroid suppositories for IBD. No biochemical relapses were observed in the IBD cohort with early follow up. High-grade acute and late toxicities were rare (n = 1, grade 3 proctitis) with a median time to any GI toxicity of 22 months. Hemorrhoidal flare was the most common low-grade toxicity observed (n = 3). ConclusionTo date, this is one of the largest groups of patients with IBD treated safely and effectively with radiation for prostate cancer and the only review of patients treated with SBRT. Caution is warranted when delivering therapeutic radiation to patients with IBD, however modern radiation techniques appear to have mitigated the risk of GI side effects.
Efficacy of the CoronaVac® Vaccine in a Region of the Colombian Amazon, Was Herd Immunity Achieved?
Authors: Mattar Salim , Serrano-Coll Héctor , Miller Hollman , Guzmán Camilo , Rivero Ricardo , Gastelbondo Bertha , Miranda Jorge , Galeano Ketty , Montaña-Restrepo Jhon
Published: June 2021

Introduction. Currently, more than 1.8 billion doses of SARS-CoV-2 vaccines have been applied worldwide. However, some developing countries are still a long way from achieving herd immunity through vaccination. In some territories, such as the Colombian Amazon, mass immunization strategies have been implemented with the CoronaVac® vaccine. Due to its proximity to Brazil, where one of the variants of interest of SARS-CoV-2 circulates. Objective. To determine the efficacy of the CoronaVac® vaccine in a population of the Colombian Amazon. Methods. Between February 24, 2021, and May 19, 2021, a descriptive observational study was carried out in which a population of individuals over 18 years of age immunized with two doses of the CoronaVac® vaccine was evaluated. The study site was in the municipality of Mitú, Vaupés, in southeastern Colombia, a region located in the Amazon bordering Brazil. Results. 87% of the urban population of the Mitú municipality were vaccinated with CoronaVac®. To date, 2.1% of vaccinated individuals have become ill, and only 0.1% of these require hospitalization. No deaths attributable to COVID-19 have been reported among vaccinated individuals, and the vaccine has shown 97% efficacy against mild disease and 100% against severe infection. Conclusions. The herd immunity achieved through mass vaccination in this population has made it possible to reduce the rate of complicated cases and mortality from COVID-19 in this region of the Colombian Amazon.
Development of an Anti-infective Coating on the Surface of Intraosseous Implants Responsive to Enzymes and Bacteria
Authors: Liao Xin , Yu Xingfang , Yu Haiping , Huang Jiaqi , Zhang Bi , Xiao Jie
Published: June 2021

BackgroundBacterial proliferation on the endosseous implants surface presents a new threat to the using of the bone implants. Unfortunately, there is no effective constructed antibacterial coating which is bacterial anti-adhesion substrate-independent or have long-term biofilm inhibition functions. MethodsDrug release effect was tested in CMS solution and S. aureus. We used bacterial inhibition rate assays and protein leakageexperiment to analyze the in vitro antibacterial effect of (MMT/PLL-CHX)10 multilayer film. We used the CCK-8 assay to analyze the effect of (MMT/PLL-CHX)10 multilayer films on the growth and proliferation of rat osteoblasts. Rat orthopaedic implant-related infections model was constructed to test the antimicrobial activity effect of (MMT/PLL-CHX)10 multilayer films in vivo.ResultsIn this study, the (MMT/PLL-CHX)10 multilayer films structure were progressively degraded and showed well concentration-dependent degradation characteristics following incubation with Staphylococcus aureus and CMS solution. Bacterial inhibition rate assays and protein leakageexperiment showed high levels of bactericidal activity. While the CCK-8 analysis proved that the (MMT/PLL-CHX)10 multilayer films possess perfect biocompatibility. It is somewhat encouraging that in the in vivo antibacterial tests, the K-wires coated with (MMT/PLL-CHX)10 multilayer films showed lower infections incidence and inflammation than the unmodified group, and all parameters are close to SHAM group. Conclusion﻿(MMT/PLL-CHX)10 multilayer films provides a potential therapeutic method for orthopaedic implant-related infections.
The Effect of Slow-grown in Vitro Storage Under Different Light Spectra on Banana Plantlets Cv. Prata Catarina (AAB).
Authors: Rodrigues Paulo Hercilio Viegas , Oliveira Emerson , Demetrio Christian , Ambrosano Guilherme , Piedade Sônia Maria Stefano
Published: June 2021

Maintaining updated in vitro plant subcultures is essential for commercial micropropagation and tissue culture research. In unusual situations, the subcultures can be delay and the slow-growth in vitro storage technic could be applied to reduce the loss of plant material. The present study aimed to evaluate the slow-growth in vitro storage of banana plantlets (‘Prata Catarina’; group AAB) under different light spectra. Shoot cultures in MS medium without plant growth regulators were maintained under blue (B), red (R), red plus blue (R2B), and white (CW) light spectra (25°C ± 2°C; 50 µmol m -2 s -1 ) for up to 140 days. The plantlets maintained under the R, CW, and R2B spectra did not survive after 140 days of in vitro slow-growth storage. The plantlets maintained under the B spectrum survived after 140 days of in vitro slow-growth storage and showed little browning.
Thirty-day Hospital Readmission Prediction Model Based on Common Data Model with Weather and Air Quality Data
Authors: Ryu Borim , Yoo Sooyoung , Kim Seok , Choi Jinwook
Published: June 2021

Many epidemiological studies have established an association between environmental exposure and clinical outcome for hospital admissions. However, few studies have explored the impact of environmental factors, such as ambient air pollution and meteorological factors, on hospital readmissions using predictive analysis. In this study, we aimed to develop a model to predict unplanned hospital readmissions within 30 days of discharge based on the common data model considering weather and air quality factors. Moreover, we validated the proposed model externally. We developed and compared the following machine learning methods: decision tree, random forest, AdaBoost, and gradient boosting machine–based models. We performed 10-fold cross-validation for internal validation, and external validation was performed by applying the model to unseen data. The performance of the prediction model was evaluated using the area under the receiver operating characteristic curve. PM10, rainfall, and maximum temperature were the weather and air quality variables that most impacted the model. Among the four machine learning models, the AdaBoost-based model demonstrated the best performance and was the most accurate in predicting the readmission of patients with musculoskeletal diseases. External validation demonstrated that the model based on weather and air quality factors is transportable.
The Impact of COVID-19 on Surgical Education: A Monocentric Survey of Residents Training in Surgical Specialties
Authors: Tassé Nicolas , Auger-Dufour Etienne
Published: June 2021

BACKGROUND: This study aims to identify the effects of the COVID-19 on surgical resident education at University Laval during first wave of the pandemic of spring 2020.METHODS: We conducted a web-based survey study to all residents training within one of the ten surgical specialties at University Laval, Quebec City. The survey focused on clinical teaching hours, appreciation of activities and novelties experienced and the impacts of virtual teaching. Descriptive statistical analysis was performed to summarize the data.RESULTS: There were 48 surgical residents who responded to our survey. There were participants from ten specialties. During the pandemic the mean number of weekly teaching hours dropped from 4.31 to 3.69 hours. The most appreciated activity was teaching sessions lead by a staff surgeon. More than 80% of respondents reported having partaken in other activities at some time during an online class while over 70% expressed retaining less when material was taught online rather than in person.CONCLUSION: Our survey provides insight for surgical programs to improve resident teaching and illustrates the necessity to optimize teaching schedules rapidly in times of pandemic. Even though the appreciation of virtual learning seems unsatisfactory by certain residents, trainees still require and appreciate teaching by their mentors.
Targeted Phototherapy by Niobium Carbide for Mammalian Tumor Models Similar to Human Being
Authors: Liu Zhao , Tian Yuhang , Jiang Shan , Shang Haitao , Chen Kexin , Tan Haoyan , Zhang Lei , Guo Chongshen , Jing Hui , Cheng Wen
Published: June 2021

BackgroundAlthough nanomaterial-mediated phototherapy has been extensively studied, the major antitumor success is limited to treating subcutaneous tumor on nude, lacking of clinically-relevant big animal study. Therefore, it is urgent to make further investigation on the typical big model, which is more closely related to the human body. ResultsIn this work, niobium carbide (NbC) is selected as photoactive substance in virtue of its outstanding near infrared (NIR) absorption properties and resultantly NIR-triggered hyperthemia and reactive oxygen species generation for the synergetic photothermal and photodynamic effect. Moreover, macrophage is used as bio-carrier for the targeted delivery of NbC and the phagocytosis of macrophages is proved to be able to retain the photothermal/photodynamic effect of NbC. Resultantly, macrophage loaded NbC could realize complete removal of solid tumor on both of nude mice and big animal of rabbits. Meanwhile, two-dimensional ultrasound, shave wave elastography (SWE) and contrast-enhanced ultrasound (CEUS) have been applied for monitoring the physiological evolutions of in vivo tumor post treatment, which clearly disclose the photoablation process of tumor and provide a new way for the surveillance of tumor on the big animal study. Conclusion﻿Hence, large animal model study in this work presents higher clinical significance than the previous studies.
Suboptimal Immune Recovery Despite Sustained HIV Suppression Among a Yi Ethnic Population in Southwest China
Authors: Chen Liyu , Liu Chang-Hai , Kang Shuang , Du Lingyao , Ma Fanghua , Li Changmin , Bai Lang , Li Hong , Tang Hong
Published: June 2021

Objectives: Despite sustained viral suppression with effective antiretroviral therapy (ART), HIV-infected patients with suboptimal immune recovery are still at high risk of non-AIDS-related and AIDS-related events. The aim of this study was to investigate the potential determinants associated with suboptimal CD4+ T cell count recovery during free ART with sustained viral suppression among a HIV-infected Yi ethnic population in Liangshan Prefecture, an area with high HIV prevalence in China.Method: This retrospective study included all HIV-infected Yi adults (≥ 18 years and with baseline CD4+ T cell count less than 500 cells/μL) who initiated ART supported by NFATP between January 2015 and December 2018 in Zhaojue county, Liangshan Prefecture (Figure 1), and achieved virological suppression (viral load < 50 copies/mL) within 12 months after ART initiation and maintained sustained virological suppression. Univariate and multivariate log-binomial regression models were used to assess determinants of suboptimal immune recovery, producing adjusted odds ratios (aORs) and confidence intervals (CIs).Results: A total of 277 HIV-infected Yi patients (male/female, 140/137) with a mean age of 36.57 ± 7.63 years and a mean baseline CD4+ T cell count of 284.49 ± 117.11 cells/μL were included. Nearly half of the Yi patients were infected through injection drug use (48.7%, 135/277), and the prevalence of anti-HCV antibody was high (43.7%, 121/277). The free ART regimens were 91% efavirenz-based, 5.1% nevirapine-based, and 3.9% lopinavir/ritonavir-based. After a mean 3.77 ± 1.21 years of ART, optimal immune recovery (CD4+ T cell count ≥ 500 cells/μL), intermediate immune recovery (350≤CD4 < 500 cells/μL), and suboptimal immune recovery (CD4 < 350 cells/μL) occurred in 32.9%, 31%, and 36.2% of the included patients, respectively. After adjustments, multivariable analysis revealed that low pre-ART CD4+ cell count, WHO clinical stage III and IV, and coinfection with HCV were associated with suboptimal immune recovery. Conclusions: Our study support prompt ART initiation after HIV diagnosis, and curative HCV treatment in HCV/HIV co-infected patients for improving the immunological effectiveness of ART among HIV-infected Yi patients in Liangshan Prefecture.Trial registration: None
Efficacy of Single-site Radiotherapy Plus PD-1 Inhibitors vs PD-1 Inhibitors for Oligometastatic Non-Small Cell Lung Cancer
Authors: Wang Peiliang , Yin Tianwen , Zhao Kaikai , Yu Jinming , Teng Feifei
Published: June 2021

Purpose: Growing numbers of clinical trials test the efficacy of radiotherapy (RT) plus immune checkpoint inhibitors (ICIs), but the number of irradiated sites is not uniform. We aim to evaluate the efficacy of single-site RT plus immunotherapy in oligometastatic non-small cell lung cancer (NSCLC) with smaller disease burdens and low tumor heterogeneity. Methods: We retrospectively identified oligometastatic NSCLC (≤4 metastatic sites) patients treated with PD-1 pathway inhibitors with or without RT to a single lesion in our institution between 2018 and 2020. The primary endpoints were the best objective response rate (ORR) and progression-free survival (PFS) . Results: Of the 152 patients enrolled, 93 and 59 were identified as the ICI alone group and the ICI plus RT group, respectively. The addition of radiotherapy to ICI therapy significant increased the best ORR from 31.2% to 50.8%, p=0.015). The out-of-field (abscopal`) response rate could reach 41.3% (95% CI, 26.5%-56.1%) in the ICI plus RT group. Median progression-free survival was 8.9 months (95%CI, 4.7-13.1 months) with ICI alone versus 13.8 months (95% CI, 9.5-18.1 months) with ICI plus radiotherapy (hazard ratio [HR] 0.568; p=0.035). In an exploratory subgroup analysis of PFS, the addition of RT brought greater benefits in patients with aged <65 years (p=0.016), patients with ECOG PS=0 (p=0.048), patients with 1-2 metastatic sites (p=0.024). No unexpected adverse events or significantly increased toxicities were observed in the experimental arm.Conclusion: Single-site RT plus anti-PD-1 inhibitors significantly increased systemic responses and improved survival outcomes in oligometastatic NSCLC patients.
A375 Melanoma Cells are Sensitized to Cisplatin-Induced Toxicity by a Synthetic Nitro-Flavone Derivative 2-(4-Nitrophenyl)-4H-Chromen-4-one Through Inhibition of PARP1
Authors: Mitra Anindita , Ghosh Rita
Published: June 2021

Background: Cisplatin has been extensively used in therapeutics for its broad-spectrum anticancer activity and frequently used for the treatment of solid tumors. However, it presents several side-effects and several cancers develop resistance. Combination therapy of cisplatin with poly (ADP-ribose) polymerase 1 (PARP1) inhibitors has been effective in increasing its efficacy at lower doses. Methods and Results: In this work, we have shown that the nitro-flavone derivative, 2-(4-Nitrophenyl)-4H-chromen-4-one (4NCO), can improve the sensitivity of cancer cells to cisplatin through inhibition of PARP1. The effect of 4NCO on cisplatin toxicity was studied through combination therapy in both exponential and density inhibited A375 melanoma cells. Combination index (CI) was determined from isobologram analysis. The mechanism of cell killing was assessed by lactate dehydrogenase (LDH) assay. Temporal nicotinamide adenine dinucleotide (NAD+) assay was done to show the inhibition of PARP1. We also performed in silico molecular modeling studies to know the binding mode of 4NCO to a modeled PARP1-DNA complex containing cisplatin-crosslinked adduct. The results from both in silico and in cellulo studies confirmed that PARP1 inhibition by 4NCO was most effective in sensitizing A375 melanoma cells to cisplatin. Isobologram analysis revealed that 4NCO reduced cell viability both in exponential and density inhibited A375 cells synergistically. The combination led to cell death through apoptosis. Conclusion: The synthetic nitro-flavone derivative 4NCO effectively inhibited the important nuclear DNA repair enzyme PARP1 and therefore, could complement the DNA-damaging anticancer drug cisplatin in A375 cells and thus, could act as a potential adjuvant to cisplatin in melanoma therapy.
A New Hendra Virus Genotype Found in Australian Flying Foxes
Authors: Wang Jianning , Anderson Danielle E , Halpin Kim , Hong Xiao , Chen Honglei , Walker Som , Valdeter Stacey , Heide Brenda van der , Neave Matthew J , Bingham John , O’Brien Dwane , Eagles Debbie , Wang Lin-Fa , Williams David T
Published: June 2021

Background

Hendra virus (HeV) has caused lethal disease outbreaks in humans and horses in Australia. Pteropid bats (flying foxes) are the wildlife reservoir from which the virus was first isolated in 1996. Following a heat stress mortality event in Australian flying foxes in 2013, a novel HeV variant was discovered. This study describes the subsequent surveillance of Australian flying foxes for this novel virus over a nine year period using qRT-PCR testing of bat tissues submitted primarily for Australian bat lyssavirus (ABLV) diagnosis. Genome sequencing and characterisation of the novel HeV variant was also undertaken.
Methods

Spleen and kidney samples harvested from flying fox carcasses were initially screened with two real-time qRT-PCR assays specific for the prototype HeV. Two additional qRT-PCR assays were developed specific for the HeV variant first detected in samples from a flying fox in 2013. Next-generation sequencing and virus isolation was attempted from selected samples to further characterise the new virus.
Results

Since 2013, 98 flying foxes were tested and 11 were positive for the new HeV variant. No samples were positive for the original HeV. Ten of the positive samples were from grey-headed flying foxes (GHFF, Pteropus poliocephalus), however this species was over-represented in the opportunistic sampling (83% of bats tested were GHFF). The positive GHFF samples were collected from Victoria and South Australia and one positive Little red flying fox (LRFF, Pteropus scapulatus) was collected from Western Australia. Immunohistochemistry (IHC) confirmed the presence of henipavirus antigen, associated with an inflammatory lesion in cardiac blood vessels of one GHFF. Positive samples were sequenced and the complete genome was obtained from three samples. When compared to published HeV genomes, there was 84% sequence identity at the nucleotide level. Based on phylogenetic analyses, the newly detected HeV belongs to the HeV species but occupies a distinct lineage. We have therefore designated this virus HeV genotype 2 (HeV-G2). Attempts to isolate virus from PCR positive samples have not been successful.
Conclusions

A novel HeV genotype (HeV-G2) has been identified in two flying fox species submitted from three states in Australia, indicating that the level of genetic diversity for HeV is broader than first recognised. Given its high genetic relatedness to HeV, HeV-G2 should be considered a zoonotic pathogen.
Blinking Patterns in Calves and Changes Following Restraint and Disbudding
Authors: Ugwu Nnenna , Love Emma , Murrell Jo , Whay Helen R. , Knowles Toby G , Hockenhull Jo
Published: June 2021

The use of spontaneous eye blink rate [EBR] as a non-invasive stress measure is well documented in humans and is gleaning research attention in animal studies. Thus, this study investigated the EBR patterns and changes associated with two known stressful conditions, crush-restraint and disbudding, in dairy calves. Fifty-four female Holstein dairy calves were studied. EBR patterns were assessed in two separate studies (n = 10 in first study; n = 25 in replicate study) four times daily for 4-5 days. Additionally, the EBR of 19 calves divided into two groups (disbudded group = 13; sham group = 6) was recorded following crush-restraint and disbudding (under anaesthesia)/sham-disbudding (without anaesthesia). EBR was consistent across days and times in the first study but in the replicate study, it varied across days. The disbudded group had lower EBR following crush-restraint but was comparable with the sham group following disbudding. Findings suggest that spontaneous blinking may potentially serve as an instant measure of stress in dairy calves based on the elevations associated with crush-restraint and disbudding. However, blink rates may vary across days, and this should be considered when utilizing this measure to assess stress.
Comparison of Endoscopic Brush And Net Catheters As Sampling Tools To Analyze Lower Rectum Intestinal Mucus Samples of Patients With Ulcerative Colitis
Authors: Nakamura Masanao , Maeda Keiko , Yamamoto Kenta , Yamamura Takeshi , Sawada Tsunaki , Mizutani Yasuyuki , Ishikawa Eri , Kakushima Naomi , Furukawa Kazuhiro , Iida Tadashi , Ishikawa Takuya , Ohno Eizaburo , Honda Takashi , Kawashima Hiroki , Ishigami Masatoshi , Fujishiro Mitsuhiro
Published: June 2021

Background and aims: The pathophysiology of ulcerative colitis remains unclear, but early lesions on the colorectal mucosal surface may play an important role in its etiology. Intestinal mucus samples, including inner and outer layers, are collected by net or brush catheters, but the quality of the samples obtained by each method has not been fully investigated. The aim of this study was to compare the microbiome and protein content of Intestinal mucus collected by net and brush catheters during colonoscopy.Methods: Intestinal mucus samples from the lower rectum of four patients with ulcerative colitis were collected using a net catheter, a brush catheter, and intestinal fluid suction. Microbiome and protein content were analyzed using 16S rRNA gene sequencing and mass spectrometry.Results: The patients demonstrated significant differences in microbiome alpha diversity (p <0.05), but this difference was not observed between the sampling methods. Net catheter samples demonstrated higher total protein concentrations than brush catheter samples. Mucus-associated proteins (Mucin-2, Mucin-5B, Mucin-13, and IgGFc-binding protein) were more abundantly collected by nets in three patients with active ulcerative colitis, but more abundant by brushes in patients with inactive ulcerative colitis.　Bifidobacterium and some oral bacteria were similarly associated with ulcerative colitis activity.Conclusions: Brush catheters are more likely to collect the intestinal mucus of inner layer, whereas net catheters are more likely to collect larger samples that include the outer mucus layer, as well as intestinal fluid. Two sampling methods with different types of work on the mucosa may lead different results among patients with mucosal vulnerabilities.
Multiple Bronchiolar Adenomas With Malignant Transformation and CCNE1 Mutation: a Case Report and Literature Review
Authors: Li Xiaojun , Wu Yonghui , Hui Dayang , Luo Xiaoxuan , Wu Weibin , Zhang Jian , Chen Huiguo
Published: June 2021

Background: Bronchiolar adenoma (BA) is a recently proposed diagnostic terminology, which is considered as the expansion of the concept of ciliated muconodular papillary tumors (CMPT). BA is considered to be a benign neoplasm, but a few previous cases have been reported with the possibility of malignant transformation. Therefore，the genetic and histological nature of BA is controversial so far. We describe a rare case of multiple BAs with malignant transformation and CCNE1（cyclin E1）mutation to increase the understanding of this disease.Case description: A 56-year-old woman was admitted to our hospital due to two ground-glass nodules (GGNs) in the left lung detected by chest CT without symptom. The pure GGN located in the upper lingual segment about 6 mm in diameter and another mixed GGN located in the dorsal segment about 7 mm. The two GGNs have been found a year ago without treatment, and the mixed GGN become larger to 8 mm with vacuole sign in the next year health checkup. We performed a wedge resection of the two nodules completely by video-assisted thoracoscopy (VATS). Postoperative pathology indicated that the pure GGN was atypical bronchial adenoma, while the mixed GGN was atypical bronchial adenoma with malignant transformation which was missed in frozen section. Gene mutations analysis by next-generation sequencing (NGS) showed CCNE1 gene mutation in both lesions, and her-2 mutation was identified in the mixed GGN. The programmed cell death 1 ligand 1 (PD-L1) expression analysis of tumor cells showed 0% and less than 1% in the pure GGN and the mixed GGN, respectively. Conclusion: BA is generally considered to be a benign tumor. The present study indicated that BA may be carcinogenic in atypical cases with some driver genes mutation and we should be vigilant for its potentiality of malignant transformation in clinical practice.
Coarsening Behavior of Bulk Nanobubbles in Water
Authors: Lee Jeong Il , Huh Han Sol , Park Joong Yull , Han Jung-Geun , Kim Jong-Min
Published: June 2021

In recent years, extremely small gas bubbles called bulk nanobubbles (BNBs) have drawn great attention due to their impressive effects and their wide applicability in a variety of technological fields, including biomedical engineering, water treatment, and nanomaterials. However, unsolved questions remain regarding the stability and behavior of BNBs. In the present work, BNBs were generated in water using a gas-liquid mixing method. To investigate the coarsening behavior of BNBs in water over time, particle analysis was performed using a nanoparticle tracking analysis (NTA) method. Over time, the BNB diameter continuously increased (from 88.50 nm to 201.00 nm), and its cubic radius increased linearly (r3 ~ t). While the concentration of BNBs decreased (from 3.47 ×108 particles/mL to 0.61 ×108 particles/mL), the total volume of BNBs remained the same. Moreover, the size distribution broadened over time, and the concentration of larger BNBs gradually increased over time. These results indicate that relatively small BNBs disappear and larger BNBs grow through mass transfer between BNBs instead of dissolution of the gas and coalescence. In other words, BNBs underwent Oswald ripening; that is, gas molecules detached from smaller BNBs, diffused into the continuous phase, and then were absorbed into larger BNBs.
An in vitro study regarding an animal model for the attenuation of SARS-CoV-2: Are cats possible candidates?
Authors: Oguzoglu Tuba Cigdem , Hanifehnezhad Alireza , Özkul Aykut
Published: June 2021

Although the origin of the SARS-CoV-2 pandemic is not definitively known, this virus is seen that adapted to human. It is known yet, several animal species are naturally susceptible for SARS-CoV-2, including pets. In this in vitro study, it was investigated whether cats could have a host status in this infection. It was also following questioned, whether cats could be an animal model for vaccine attenuation. Felis catus whole fetus 4 (FCWF-4) and Vero cells were used in this study for propagation of SARS-CoV-2-Ank1 strain. Virus replication was controlled by immunohistochemistry and real time pcr techniques. While an increase in virus titer was detected in the serious passages made in Vero cells, no increase was observed in the FCWF-4 cell. The results were confirmed by immunohistochemistry. Due to the fact that SARS CoV 2 is a zoonotic potential, its presence in domestic animals frequently investigated in current studies. Cats can get this virus from infected owners with whom they share the same habitat. The results of this study also showed that cats are not candidates to be a natural source of infection for SARS-CoV-2.
Using the QI Maturity Tool – Modified Ontario Version to Assess the State of QI Maturity in Ontario’s Public Health Units
Authors: Law Madelyn , Berry Alex , Clarke Nicole , Hay Graham , Muhl Caitlin , Pilato Kelly , Hunter Danielle , Larson Anna
Published: June 2021

Background

Implementation of quality improvement (QI) practices varies considerably among public health units (PHUs) in Ontario. With the emphasis on continuous quality improvement (CQI) in the revised Ontario Public Health Standards (OPHS), there is a need to understand the level of quality improvement (QI) maturity in Ontario’s PHUs. The objective of this research was to establish a baseline understanding of QI maturity in Ontario’s PHUs.
Methods

The QI Maturity Tool - Modified Ontario Version was used to assess the state of QI maturity in 34 PHUs across Ontario. QI maturity was assessed through 23 questions across three dimensions: QI Organizational Culture; QI Capacity and Competency; and QI Perceived Value. QI maturity scores were classified into five stages: Beginning; Emerging; Progressing; Achieving; and Excelling. QI maturity scores were calculated for each of the 34 participating PHUs to determine their stage of QI maturity. Each PHU’s score was then used to determine the provincial average for QI maturity. Participants were also asked to answer three questions related to core CQI organizational structures.
Results

Across the 34 PHUs, 3,503 staff participated in the survey. A review of individual PHU scores indicates that Ontario’s PHUs are at varying stages of QI maturity. The average QI maturity score of 4.94 for the 34 participating PHUs places the provincial average in the “Emerging” stage of QI maturity. By QI dimensions, the participating PHUs scored in the “Emerging” stage for QI Organizational Culture (5.09), the “Beginning” stage for QI Competency and Capacity (4.58), and the “Achieving” stage for QI Perceived Value (6.00).
Conclusion

There is an urgent need for Ontario’s PHUs to progress to higher stages of QI maturity. Participants place a high value on QI, but collectively are at less “mature” stages of QI in relation to QI organizational culture and the competency and capacity to engage in QI activities. PHUs should leverage the value that staff place on QI to foster the development of a culture of QI and provide staff with relevant knowledge and skills to engage in QI activities.
A Novel Three-MicroRNA Signature for Predicting Survival in Patients with Nasopharyngeal Carcinoma
Authors: Zhang Shan-Qiang , Liu Jun , Chen Hai-Bin , Dai Wen-Jie , Zhou Li-Qing , Xie Chong-Wei , LI Ji-Cheng
Published: June 2021

This study aims to use integrated bioinformatics technology to dig a predictive miRNA-signature correlated with the prognosis of Nasopharyngeal carcinoma (NPC). Initially, 94 up-regulated and 91 down-regulated differentially expressed microRNAs (DEMs) of NPC were identified in the GEO dataset, and univariate COX regression analysis showed their abnormal expression were significantly associated with poor prognosis of NPC, respectively (P=0.002, P<0.001 and P<0.001). Subsequently, hsa-miR-29c, hsa-miR-30e and hsa-miR-93 identified by random forest algorithm were used to construct a predictive signature through multivariate COX regression analysis. Moreover, PCA, Kaplan-Meier analysis, time-dependent ROC analysis, and univariate and multivariate COX regression analysis demonstrated that there were significant differences in risk score, survival time and the expression of 3 DEMs between the high-risk group and the low-risk group (P< 0.001), and the high-risk group had worse OS (P<0.001). Furthermore, the average AUC values of 1- to 5-year OS, DFS and DMFS predicted by the signature were all above 0.7, and showed better clinical independence than other commonly used indexes. Eventually, 295 differentially expressed mRNAs were obtained by the intersection of the predicted results of TargetScan and the differentially expressed mRNAs in the datasets. Among them, 56 differentially expressed mRNAs were related to PFS. GO and KEGG enrichment analysis indicated that the poor prognosis of NPC was related to the abnormality of chromosomes, cytokines, and chemokines. Collectively, we constructed a 3-miRNA signature with better independent performance in predicting the prognosis for NPC, which may provide a basis for finding new therapeutic targets of NPC patients.
Appropriateness of using vitamin K for the correction of INR elevation secondary to hepatic disease in critically ill patients: An Observational Study
Authors: Sulaiman Khalid Al , Mutairi Mashael Al , Harbi Omar Al , Duraihim Alanoud Al , Aldosary Sara , Khalil Haifa Al , Shaya Abdulrahman Al , Harbi Shmeylan Al , Alotaibi Nouf , Aamer Kholoud Al , Vishwakarma Ramesh , Katheri Abdulmalik Al , Bekairy Abdulkareem M. Al
Published: June 2021

Background: Hepatic diseases have been associated with an increased risk of coagulopathy and increased odds of secondary thrombosis and bleeding. Using vitamin K for correction of coagulopathy in critically ill patients is controversial with limited evidence.Objective: To evaluate the efficacy as well as safety of vitamin K in correction of international normalized ratio (INR) elevation secondary to liver disease in critically ill patients.Setting: Tertiary teaching hospital in Saudi Arabia.Method: A retrospective case-control study of adult ICU patients with coagulopathy secondary to liver disease. A total of 98 patients were included in the study. Patients were divided into two groups based on vitamin K administration to correct INR elevation. differences. The propensity score was generated based on disease severity scores to adjust group.Main outcomes: The primary outcome was to evaluate the association between vitamin K administration and the incidence of new bleeding events in critically ill patients with INR elevation secondary to liver disease. Secondary outcomes were to evaluate the incidence of a new thrombotic event and the degree of INR correction with vitamin K. Results: Forty-seven patients (48%) received vitamin K during the study period. The incidence of the new bleeding event was not statistically different between groups (OR 2.4, 95% CI 0.28-21.67, P=0.42). Delta of INR reduction was observed with a median of 0.63 when the first dose is given (p-value: <.0001). However, other subsequent doses of vitamin K were not statistically significant.Conclusion: Using vitamin K for INR correction in critically ill patients with coagulopathy secondary to liver disease was not associated with a lower incidence of new bleeding events. Vitamin K was efficient in reducing INR level at the first dose, other subsequent doses were not.Impacts on practice: 1. Routine use of vitamin K to correct PT/INR in critically ill patients with liver disease may need be re-evaluated.2. If the initial dose of vitamin K does not reverse INR elevation, subsequent doses may not have any effect.3. Using vitamin K to correct INR was not associated with a lower incidence of new bleeding events nor RBCs/Platelets transfusion than patients who did not receive it.
Environmental Radioactivity evaluation and its health-related effects using gamma spectrometry in Delanta-Dawunt, Wollo District, Ethiopia
Authors: Legasu Mekuanint Lemlem , Chaubey Ashok K
Published: June 2021

Background & Methodology : The specific activity concentration of naturally occurring radionuclides 226Ra, 232Th, 40K and their health related effects were determined in different environmental samples(gemstones) collected from Delanta-Dawunt. Which is one of the mining place in Ethiopia to extract mainly opals (gemstones). Sample collection and the gamma spectroscopic analysis followed the recommended international procedures for such type of research. Gamma-ray spectrometry was applied using HPGe gamma-ray detector and PC-based MCA. The Purpose of this research: to determine the activity concentrations of the radionuclides U/Th series and K of gemstones(opals), to determine life time cancer risk of radionuclide in the environment , to assess the hazard and risk to the public associated with these dose values , to conduct the geochemical studies by quantifying the levels of trace gemstones as well as the physical parameters in soil samples within and around it, and To determine the radiation doses from these activity concentrations and compare with international recommended dose limits. Results: The results of the activity concentration on our research work showed significant variations from 11.97 ± 2.46 to 62.44 ± 14.99 Bq kg-1 for 226Ra, 25.69 ± 3.69 to 137.84 ± 13.23 Bq kg-1 for 232Th and 184.84 ± 3.59 to 969.56 ±18.16 Bq kg-1 for 40K. The mean radioactivity concentration of 226Ra, 232Th, and 40K was found to be around 29.84 ± 6.53, 68.44 ± 18.94, 390.87 ± 6.09 Bk kg-1 respectively. Conculsion: The mean values of Radium equivalent activity (Raeq), absorbed dose, annual effective dose equivalent, external and internal radiation hazard (Hex and Hin) index ,and activity utilization index is 151.68±19.46 Bq kg-1, 72.19 ± 8.48 nGy h-1, 0.07 ± 0.01mSv y-1,0.43, 0.51, 0.57 ± 0.08 and 0.29 ± 0.03 respectively. The specific activity of 232Th is higher than the world mean value and 40K is the same as the world mean value. The radiation hazard indices, ELCR values found in this study are lower than the world mean values. However, the absorbed dose is higher than the world means value. This is due to the reason of high thorium concentration existence and opal mining is highly explored on such study areas.
Can serum autoantibodies be a potential early detection biomarker for breast cancer in women? a diagnostic test accuracy review and meta-analysis
Authors: Kathrikolly Thejas , Nair Sreekumaran , Mathew Aju , Saxena Prakash , Nair Suma
Published: June 2021

Background

The increasing incidence of breast cancer necessitates the need to explore alternate screening strategies that circumvent the setbacks of conventional techniques specially among population that report earlier age at diagnosis. Serum autoantibodies is one such potential area of interest. However, their ubiquitous presence across cancer types limits its applicability to any one specific type of cancer. This review was therefore carried out to explore and consolidate available evidence on autoantibodies for early detection of breast cancer and to identify those that demonstrated a higher sensitivity.
Methods

A diagnostic test accuracy (DTA) review was carried out to ascertain serum autoantibodies that could be used for early detection of breast cancer among women. All relevant articles that investigated the role of autoantibodies in early detection of breast cancer were included for the review. MEDLINE, Scopus, ProQuest, Ovid SP and Cochrane Library were searched extensively for eligible studies. Quality of the included studies was assessed using Quality Assessment of Diagnostic Accuracy Studies (QUADAS) -2 tool. RevMan 5.3 was used for exploratory and MetaDTA 2019 for hierarchical analyses. The review helped identify the most frequently investigated autoantibodies and a meta-analysis further consolidated the findings.
Results

A total of 53 articles were included for the final analysis that reported over a 100 autoantibodies that were studied for early detection of breast cancer in women. P53, MUC1, HER2, HSP60, P16, Cyclin B1 and c-Myc were the most frequently investigated autoantibodies. Of these P53, MUC1, HER2 and HSP60 exhibited higher summary sensitivity measures. While the individual pooled sensitivity estimates ranged between 10–56%, the panel sensitivity values reported across studies were higher with an estimated range of 60–87%.
Conclusion

Findings from the review indicate a higher sensitivity for an autoantibody panel in comparison to individual assays. A panel comprising of P53, MUC1, HER2 and HSP60 autoantibodies has the potential to be investigated as an early detection biomarker for breast cancer.