bluuebunny/crossref_metadata_2025 huggingface dataset:
The exogenous surfactant Curosurf enhances phosphatidylcholine content in isolated type II cells
Authors: Bourbon  , Chailley-Heu B , Gautier B
Published: November 2022

The exogenous surfactant, Curosurf, contains proteins as well as phospholipids. We investigated the possibility that these might affect the reutilization of exogenous phospholipid by type II alveolar cells isolated from rat lung. The time course of incorporation into lamellar bodies of radioactivity from tritiated dipalmitoyl-phosphatidylcholine (DPPC) contained within liposomes was studied. Rates of uptake were compared between liposomes prepared from pure phospholipids and from Curosurf. The incorporation of labelled choline into newly synthesized phosphatidylcholine was also determined in the presence of both preparations. The rate of DPPC incorporation over the first 4 h was the same, but, after 6 and 8 h, the radioactivity associated with lamellar bodies was about 40% higher from Curosurf liposomes. By contrast, both Curosurf and the phospholipid mixture enhanced choline incorporation into phosphatidylcholine to the same extent. We conclude that Curosurf enhances the surfactant-related phosphatidylcholine content of type II cells by two mechanisms, one of which depends on the presence of proteins in exogenous surfactant. The difference in incorporation of radioactivity from liposome-associated labelled dipalmitoyl-phosphatidylcholine cannot be explained just by an increase in reutilization of choline from degraded dipalmitoyl-phosphatidylcholine.
Changes in lung lymphocyte populations reflect those seen in peripheral blood in HIV-1 positive individuals
Authors: Bofill M , Lipman M , McLaughlin JE , Johnson MA , Poulter LW
Published: November 2022

We have investigated the level of lymphocytosis present in the lung of human immunodeficiency virus (HIV)-1+ infected patients with and without pulmonary disease and how changes in natural killer (NK), B and T-cells seen in peripheral blood (PB) compare with those seen in bronchoalveolar lavage fluid (BALF). Lymphocyte subpopulations and their expression of activation, cytotoxic markers and memory status were characterized by triple immunofluorescence. Macrophages accounted for over 80% of the BAL cells. Only three out of 72 patients had a lymphocyte percentage >30%. No statistically significant differences in the relative proportions of NK, CD4 and CD8 populations were seen in BALF when compared to PB, except for a twofold increase in the percentage of activated CD8 cells in BALF. The only differences in BALF populations between the HIV-1+ groups were a lower percentage of CD4+ cells, and a higher percentage of activated CD8+ cells in the patients with pneumonitis. In the present cohort of patients there was little evidence for an overall lymphocytosis in bronchoalveolar lavage fluid of HIV-1+ subjects. Changes observed in lymphocyte subsets of bronchoalveolar lavage fluid populations reflected those in peripheral blood, and were similar for patients with and without pneumonitis. Evidence of increased CD8 subset activity in bronchoalveolar lavage fluid did, however, emerge.
Platelet-derived growth factor expression in primary pulmonary hypertension: comparison of HIV seropositive and HIV seronegative patients
Authors: Humbert M , Monti G , Fartoukh M , Magnan A , Brenot F , Rain B , Capron F , Galanaud P , Duroux P , Simonneau G , Emilie D
Published: November 2022

Primary pulmonary hypertension (PPH) is characterized by intimal fibrosis and cell proliferation (including fibroblasts, smooth muscle and endothelial cells) in the distal pulmonary arterial tree. Considerable interest has been generated by recent reports of PPH in human immunodeficiency virus (HIV)-1-infected individuals. Although the lack of evidence for a pulmonary artery infection has suggested that in such cases HIV may act through mediator release rather than by direct endothelial infection, the mechanisms underlying HIV-associated PPH remain poorly defined. Platelet-derived growth factor (PDGF) has the ability to induce smooth muscle cell and fibroblast proliferation and migration. Given these considerations, we have attempted to document a possible role for PDGF in PPH occurring in HIV seropositive and seronegative patients. Using semiquantitative polymerase chain reaction (PCR), PDGF A-chain messenger ribonucleic acid (mRNA) expression was analysed in surgical lung biopsies from 13 HIV seronegative patients and one HIV seropositive patient, all displaying severe PPH. In parallel, lung samples from two patients with HIV-1-associated PPH were studied by immunohistochemistry and in situ hybridization. Results were compared to those obtained in three HIV-1-infected individuals with no pulmonary complication (as demonstrated by clinical, radiological, bacteriological, and necropsy findings) and five control lung biopsies. As compared to controls, PDGF A-chain mRNA expression is elevated in lung biopsies from patients displaying PPH (p=0.029). In HIV-1-associated PPH, interstitial perivascular cells expressing PDGF A-chain mRNA and protein could be detected by in situ hybridization and immunohistochemistry, respectively. Platelet-derived growth factor expression is elevated in lung biopsies of patients displaying primary pulmonary hypertension. Growth factors such as platelet-derived growth factor may play a part in the initiation and/or progression of primary pulmonary hypertension.
Regulation of adrenergic nerve-mediated contraction of canine pulmonary artery by K+ channels
Authors: Tagaya E , Tamaoki J , Takemura H , Nagai A
Published: November 2022

The aim of the present study was to investigate the role of certain subtypes of K+ channels in nerve-evoked contractions of pulmonary artery in vitro. The lobar or segmental pulmonary arteries were dissected from dogs, cut into ring segments, and the contractile responses to electrical field stimulation (EFS) and noradrenaline were measured under isometric conditions. Addition of iberiotoxin, a big conductance Ca2+-activated K+ channel blocker, and apamin, a small conductance Ca2+-activated K+ channel blocker, did not change the resting tension but augmented the contractile responses to EFS, so that the electric stimulus frequency required to produce a half-maximal contraction (ES50) was decreased from 18.2+/-3.5 to 7.4+/-2.3 Hz (p<0.01) and from 16.8+/-2.2 to 11.4+/-2.0 Hz (p<0.05), respectively, whereas glibenclamide, an adenosine triphosphate (ATP)-sensitive K+ channel blocker, had no effect. In contrast, none of the K+ channel blockers altered the contractile response to noradrenaline. Incubation of tissues with iberiotoxin and apamin increased the release of 3H-noradrenaline evoked by EFS. We conclude that big conductance Ca2+-activated K+ channels and small conductance Ca2+-activated K+ channels may play a role in the regulation of adrenergic neurotransmission in the pulmonary artery, probably by inhibiting the exocytotic release of noradrenaline from the adrenergic nerve terminals.
Leucocyte kinesis in blood, bronchoalveoli and nasal cavities during late asthmatic responses in guinea-pigs
Authors: Nabe T , Shinoda N , Yamashita K , Yamamura H , Kohno S
Published: November 2022

Recently, we reported a reproducible model of asthma in guinea-pigs in vivo, which developed a late asthmatic response (LAR) as well as an early response. In this study, time-related changes in the occurrence of the LAR and leucocyte kinesis were assessed. Furthermore, the state of the activation of eosinophils that migrated into the lower airways was characterized in vitro. Guinea-pigs were alternately sensitized/challenged by inhalation with aerosolized ovalbumin adsorbed on aluminium hydroxide and ovalbumin alone, once every 2 weeks. At defined times before and after the fifth challenge, airway resistance was measured, blood was drawn and bronchoalveolar lavage (BAL) and nasal cavity lavage (NCL) were performed. Superoxide anion (.O2-) production of eosinophils was measured with cytochrome c. Occurrence of LAR and considerable increases in circulating eosinophils coincided with each other 5-7 h after the challenge. After 7 h, eosinophil infiltrations into bronchoalveolar spaces were observed. The capacity of eosinophils from the sensitized animals to produce .O2- was higher than those from the non-sensitized ones, when eosinophils were stimulated by platelet-activating factor. Although an increased number of eosinophils in the NCL fluid was observed, it was much less than that in the BAL fluid. Thus, it has been concluded that eosinophilia in the blood and the lung may participate in the occurrence of the late asthmatic response, which is thought to be preferentially evoked in the lower airways in guinea-pigs in vivo.
The association of respiratory symptoms and lung function with the use of gas for cooking. European Community Respiratory Health Survey
Authors: Jarvis D , Chinn S , Sterne J , Luczynska C , Burney P
Published: November 2022

The association of respiratory symptoms and lung function with the use of gas for cooking was examined using data collected as part of the European Community Respiratory Health Survey, an international multicentre study. Associations between gas cooking and respiratory symptoms and respiratory function were assessed by logistic and multiple regression models. Tests for interaction were used to examine whether the effect of gas cooking varied between centres and, as there was evidence for this, the average effects were estimated using standard methods for random effects meta-analysis. Data from 5,561 males and 6,029 females living in 23 centres in 11 countries were analysed. There was no significant association found between respiratory symptoms and gas cooking in males. In females the association between some respiratory symptoms and gas cooking varied between centres with an overall positive association with "wheeze in the last 12 months" (odds ratio (OR) 1.24: 95% confidence interval (95% CI) 1.00-1.54) and "wheeze with breathlessness in the last 12 months" (OR 1.33: 95% CI 1.06-1.69). There was no evidence that atopy modified this association. Cooking with gas was associated with airways obstruction in both males and females although the differences failed to reach statistical significance. In some countries the use of gas for cooking is associated with respiratory symptoms suggestive of airways obstruction in females.
The effect of latent adenovirus 5 infection on cigarette smoke-induced lung inflammation
Authors: Vitalis TZ , Kern I , Croome A , Behzad H , Hayashi S , Hogg JC
Published: November 2022

The aim of this study was to test the hypothesis that latent adenovirus (Ad) 5 infection increases the lung inflammation that follows a single acute exposure to cigarette smoke. A recently developed model of latent adenoviral infection in guinea-pigs was used. Twelve animals were infected with Ad5 (10(8) plaque-forming units) and 12 animals were sham-infected. Thirty five days later six Ad5-infected and six sham-infected animals were exposed to the smoke from five cigarettes. The remaining animals were used as controls for both infection and smoking. As markers of inflammation, the volume fraction of macrophages, T-lymphocytes, neutrophils and eosinophils were measured by quantitative histology. We found that latent Ad5-infection alone, doubled the number of macrophages in the lung parenchyma and that smoking alone, doubled the volume fraction of neutrophils in the airway wall and the volume fraction of macrophages in the lung parenchyma. Neither viral infection nor smoking, alone, had an effect on T-lymphocytes or eosinophils. However, the combination of viral infection and smoking doubled the T-lymphocyte helper cells and quadrupled the volume fraction of macrophages in the lung parenchyma. We conclude that in guinea-pigs, latent adenovirus 5 infection increases the inflammation that follows a single acute exposure to cigarette smoke, by increasing the volume fraction of macrophages and T-lymphocyte helper cells.
Blood gas measurement during exercise: a comparative study between arterialized earlobe sampling and direct arterial puncture in adults
Authors: Fajac I , Texereau J , Rivoal V , Dessanges JF , Dinh-Xuan AT , Dall'Ava-Santucci J
Published: November 2022

Sampling arterialized earlobe blood is thought to be easier and less painful than direct arterial puncture, and to allow measurement of blood gas values during exercise without the need to insert an arterial cannula. However, arterialized earlobe oxygen tension (PO2) often underestimates arterial PO2 at rest, and is not fully validated during exercise. We have therefore conducted a prospective study to compare values of PO2 and carbon dioxide tension (PCO2) and the discomfort experienced by adult subjects undergoing the two methods of blood sampling during exercise. Seventy consecutive adult patients were studied. Blood samples were drawn simultaneously from the radial artery and arterialized earlobe of each patient during the last minute of an 8 min exercise. Values of PO2 and PCO2 were measured by means of blood gas electrodes. The correlation coefficients between the two samples were 0.92 for PO2 and 0.91 for PCO2. However, the bias and the limits of agreement between the two methods were wide for PO2 (mean+/-2SD of the differences between the two methods: 0.63+/-1.50 kPa (4.7+/-11.2 mmHg)). The bias and the limits of agreement were smaller for PCO2. Patients felt that the earlobe method was not associated with less discomfort than radial artery puncture. We conclude that arterialized earlobe blood oxygen tension is not a good substitute for arterial oxygen tension during exercise, and should not be used to assess arterial oxygen tension in adults during exercise.
Eosinophil cationic protein in sputum is dependent on temperature and time
Authors: Grebski E , Graf C , Hinz G , Wuthrich B , Medici TC
Published: November 2022

Eosinophil cationic protein (ECP) in sputum may be used to estimate the severity of bronchial inflammation and obstruction in asthmatics as well as to monitor asthma drug therapy. For this purpose, standardized processing of sputum is important. The aim of our study was to determine whether time and temperature influence the ECP concentration in the sputum of asthmatics. The samples of induced sputum obtained from 12 patients with stable asthma were homogenized using ultrasonification, and centrifuged. Supernatants were evenly divided and stored for 1, 6, 24 or 72 h at either 4 or 25 degrees C, then frozen at -80 degrees C. The ECP concentrations were determined using fluoroimmunoassay and compared with the immediately frozen samples. After storing at 4 degrees C, the ECP levels at the four time points were 101.2, 96.0, 98.2 and 90.6% of the initial concentration, respectively. When sputum specimens were stored at 25 degrees C, ECP levels decreased to 96.1, 94.4, 90.7 and 87.7%, respectively. The influence of time on ECP concentrations in sputa was statistically significant (p=0.02). A significant temperature effect was found when comparing the specimens stored at 4 degrees C with those at 25 degrees C (p=0.03). Looking at individual time points, a significant decrease in ECP concentration was only seen at 25 degrees C after 24 and 72 h. We conclude that eosinophilic cationic protein in the sputum of asthmatics decreases in a time- and temperature-dependent process. If sputa cannot be processed after obtaining the specimens, they should be stored in a refrigerator at 4 degrees C, until eosinophilic cationic protein is measured.
Lung transplantation for pulmonary sarcoidosis
Authors: Judson MA
Published: November 2022

Patients with end-stage sarcoidosis have now undergone lung transplantation successfully with good short-term and intermediate-term results. Lung transplantation for sarcoidosis requires several considerations unique to this disease. Selection of pulmonary sarcoidosis patients for transplantation requires that medical therapy has been exhausted. This may involve the use of corticosteriods and alternative medications. Causes of pulmonary dysfunction other than pulmonary sarcoidosis, such as bronchiectasis and myocardial sarcoidosis, must be excluded before candidates are considered for transplantation. The extent and severity of extrapulmonary disease must also be assessed and may preclude lung transplantation. The presence of mycetomas is considered a relative contra-indication by some transplant centres and an absolute contra-indication by others. Relatively few patients with pulmonary sarcoidosis have undergone transplantation and, therefore, there are few data on outcome. Sarcoidosis frequently recurs in the allograft, but rarely causes symptoms or pulmonary dysfunction. More severe acute rejection episodes may occur in sarcoidosis transplant recipients, although at present there is no evidence of an increased risk of obliterative bronchiolitis or increased mortality.
Recurrent varicella pneumonia complicating an endogenous reactivation of chickenpox in an HIV-infected adult patient
Authors: Fraisse P , Faller M , Rey D , Labouret N , Partisani M , Stoll-Keller F , Lang JM , Weitzenblum E
Published: November 2022

We report the case of an adult patient with acquired immune deficiency syndrome (AIDS) presenting with acute dyspnoea and cutaneous disseminated lesions suggestive of an atypical varicella. The chest radiograph and the computed tomography (CT)-scan revealed a miliary pneumonia. On a previous serum sample varicella-zoster (VZV)-specific serum immunoglobulin (Ig)G titre was 1/200. A high dose acyclovir treatment was effective, but recurrences occurred twice when the treatment was discontinued. During the first recurrence the polymerase chain reaction (PCR) detected the presence of VZV in the bronchoalveolar lavage (BAL) sample. These findings confirmed the diagnosis of secondary varicella with pulmonary involvement. Secondary varicella pneumonia has not been reported in a human immunodeficiency virus (HIV)-infected adult until now. The use of PCR on a BAL sample was very useful in this case because viral culture remained negative. Recurrences of the varicella pneumonia suggested that a maintenance treatment was required in this deeply immunocompromised patient.
Reproducibility of lung volume measurements
Authors: Hankinson JL , Stocks J , Peslin R
Published: November 2022

Test reproducibility is an important consideration when interpreting results and should be set as a goal during data collection. Reproducibility criteria may need to be different for different subject groups and are instrument and procedure-dependent. Ideally, the within-subject variability for each lung volume and measurement technique used should be established for each laboratory. These values also need to be established for each different subject group (age and disease). At a minimum, test reproducibility should be monitored and controlled and each laboratory should define their between-day reproducibility of measurements on at least one "reference" subject from ongoing periodic (e.g., weekly or monthly) measurements as part of their laboratory's quality control programme. For plethysmographic measurements functional residual capacity (FRC)pleth multiple determinations and a corresponding test reproducibility criteria is probably justified.
Clinical significance of the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in acute exacerbations of COPD: present and future
Authors: Zinellu Angelo , Zinellu Elisabetta , Mangoni Arduino A. , Pau Maria Carmina , Carru Ciriaco , Pirina Pietro , Fois Alessandro G.
Published: November 2022

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are a leading cause of hospitalisation and death in COPD patients. In addition to the identification of better strategies to prevent AECOPD, there is an intense focus on discovering novel markers of disease severity that enhance risk stratification on hospital admission for the targeted institution of aggressiveversussupportive treatments. In the quest for such biomarkers, an increasing body of evidence suggests that specific indexes derived from routine complete blood counts,i.e.the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR), can significantly predict adverse outcomes in AECOPD. This narrative review discusses the current evidence regarding the association between the NLR and the PLR on admission and several clinical end-points (need for invasive ventilation, noninvasive mechanical ventilation failure, admission to an intensive care unit, pulmonary hypertension, length of hospitalisation, and mortality) in AECOPD. Future research directions and potential clinical applications of these haematological indexes in this patient group are also discussed.
GMMchi: gene expression clustering using Gaussian mixture modeling
Authors: Liu Ta-Chun , Kalugin Peter N. , Wilding Jennifer L. , Bodmer Walter F.
Published: November 2022

Background

Cancer evolution consists of a stepwise acquisition of genetic and epigenetic changes, which alter the gene expression profiles of cells in a particular tissue and result in phenotypic alterations acted upon by natural selection. The recurrent appearance of specific genetic lesions across individual cancers and cancer types suggests the existence of certain “driver mutations,” which likely make up the major contribution to tumors’ selective advantages over surrounding normal tissue and as such are responsible for the most consequential aspects of the cancer cells’ gene expression patterns and phenotypes. We hypothesize that such mutations are likely to cluster with specific dichotomous shifts in the expression of the genes they most closely control, and propose GMMchi, a Python package that leverages Gaussian Mixture Modeling to detect and characterize bimodal gene expression patterns across cancer samples, as a tool to analyze such correlations using 2 × 2 contingency table statistics.

Results

Using well-defined simulated data, we were able to confirm the robust performance of GMMchi, reaching 85% accuracy with a sample size of n = 90. We were also able to demonstrate a few examples of the application of GMMchi with respect to its capacity to characterize background florescent signals in microarray data, filter out uninformative background probe sets, as well as uncover novel genetic interrelationships and tumor characteristics. Our approach to analysing gene expression analysis in cancers provides an additional lens to supplement traditional continuous-valued statistical analysis by maximizing the information that can be gathered from bulk gene expression data.

Conclusions

We confirm that GMMchi robustly and reliably extracts bimodal patterns from both colorectal cancer (CRC) cell line-derived microarray and tumor-derived RNA-Seq data and verify previously reported gene expression correlates of some well-characterized CRC phenotypes.

Availability

The Python package GMMchi and our cell line microarray data used in this paper is available for downloading on GitHub athttps://github.com/jeffliu6068/GMMchi.
Species and genetic diversity relationships in benthic macroinvertebrate communities along a salinity gradient
Authors: Petersen H. Cecilie , Hansen Benni W. , Knott K. Emily , Banta Gary T.
Published: November 2022

Background

Species- and genetic diversity can change in parallel, resulting in a species-genetic diversity correlation (SGDC) and raising the question if the same drivers influence both biological levels of diversity. The SGDC can be either positive or negative, depending on whether the species diversity and the genetic diversity of the measured species respond in the same or opposite way to drivers. Using a traditional species diversity approach together with ultra-conserved elements and high throughput sequencing, we evaluated the SGDCs in benthic macrofauna communities in the Baltic Sea, a geologically young brackish water sea characterised by its steep salinity gradient and low species richness. Assessing SGDCs from six focal marine invertebrate species from different taxonomic groups and with differing life histories and ecological functions on both a spatial and temporal scale gives a more comprehensive insight into the community dynamics of this young ecosystem and the extrinsic factors that might drive the SGDCs.

Results

No significant correlations between species diversity and genetic diversity were found for any of the focal species. However, both negative and positive trends of SGDCs for the individual focal species were observed. When examining the environmental drivers, no common trends between the species were found, even when restricting the analysis to specific taxonomic classes. Additionally, there were no common environmental factors driving the diversity relationships for species sharing the same SGDC trend (positive or negative). Local population dynamics, together with the invasion history of the individual species and their unique adaptation to the distinctive environment of the Baltic Sea, are expected to be of major influence on the outcome of the SGDCs.

Conclusions

The present results highlight the importance of assessing SGDCs using multiple species, not just a single indicator species. This emphasises a need to pay attention to the ecology and life history of the focal species. This study also provides insight into the large differences in both patterns and drivers of genetic diversity, which is important when including genetic biodiversity in conservation plans. We conclude that the effects of environmental and biological factors and processes that affects diversity patterns at both the community and genetic levels are likely species dependent, even in an environment such as the Baltic Sea with strong environmental gradients.
Genome-wide characterization and expression analysis of the growth-regulating factor family in Saccharum
Authors: Wu Zilin , Chen Xinglong , Fu Danwen , Zeng Qiaoying , Gao Xiaoning , Zhang Nannan , Wu Jiayun
Published: November 2022

Background

Growth regulating factors (GRFs) are transcription factors that regulate diverse biological and physiological processes in plants, including growth, development, and abiotic stress. Although GRF family genes have been studied in a variety of plant species, knowledge about the identification and expression patterns of GRFs in sugarcane (Saccharum spp.) is still lacking.

Results

In the present study, a comprehensive analysis was conducted in the genome of wild sugarcane (Saccharum spontaneum) and 10 SsGRF genes were identified and characterized. The phylogenetic relationship, gene structure, and expression profiling of these genes were analyzed entirely under both regular growth and low-nitrogen stress conditions. Phylogenetic analysis suggested that the 10 SsGRF members were categorized into six clusters. Gene structure analysis indicated that the SsGRF members in the same group were greatly conserved. Expression profiling demonstrated that most SsGRF genes were extremely expressed in immature tissues, implying their critical roles in sugarcane growth and development. Expression analysis based on transcriptome data and real-time quantitative PCR verification revealed that GRF1 and GRF3 were distinctly differentially expressed in response to low-nitrogen stress, which meant that they were additional participated in sugarcane stress tolerance.

Conclusion

Our study provides a scientific basis for the potential functional prediction of SsGRF and will be further scrutinized by examining their regulatory network in sugarcane development and abiotic stress response, and ultimately facilitating their application in cultivated sugarcane breeding.
The impact of COVID-19 on an Irish Emergency Department (ED): a cross-sectional study exploring the factors influencing ED utilisation prior to and during the pandemic from the patient perspective
Authors: Cummins Niamh M. , Garavan Carrie , Barry Louise A. , Devlin Collette , Corey Gillian , Cummins Fergal , Ryan Damien , McCarthy Gerard , Galvin Rose
Published: November 2022

Background

The collateral damage of SARS-CoV-2 is a serious concern in the Emergency Medicine (EM) community, specifically in relation to delayed care increasing morbidity and mortality in attendances unrelated to COVID-19. The objectives of this study are to describe the profile of patients attending an Irish ED prior to, and during the pandemic, and to investigate the factors influencing ED utilisation in this cohort.

Methods

This was a cross-sectional study with recruitment at three time-points prior to the onset of COVID-19 in December 2019 (n = 47) and February 2020 (n = 57) and post-Lockdown 1 in July 2020 (n = 70). At each time-point all adults presenting over a 24 h period were eligible for inclusion. Clinical data were collected via electronic records and a questionnaire provided information on demographics, healthcare utilisation, service awareness and factors influencing the decision to attend the ED. Data analysis was performed in SPSS and included descriptive and inferential statistics.

Results

The demographic and clinical profile of patients across time-points was comparable in terms of age (p = 0.904), gender (p = 0.584) and presenting complaint (p = 0.556). Median length of stay in the ED decreased from 7.25 h (IQR 4.18–11.22) in February to 3.86 h (IQR 0.41–9.14) in July (p ≤ 0.005) and differences were observed in disposition (p ≤ 0.001). COVID-19 influenced decision to attend the ED for 31% of patients with 9% delaying presentation. Post-lockdown, patients were less likely to attend the ED for reassurance (p ≤ 0.005), for a second opinion (p ≤ 0.005) or to see a specialist (p ≤ 0.05).

Conclusions

Demographic and clinical presentations of ED patients prior to the first COVID-19 lockdown and during the reopening phase were comparable, however, COVID-19 significantly impacted health-seeking behaviour and operational metrics in the ED at this phase of the pandemic. These findings provide useful information for hospitals with regard to pandemic preparedness and also have wider implications for planning of future health service delivery.
Clinical application of artificial neural network (ANN) modeling to predict BRCA1/2 germline deleterious variants in Chinese bilateral primary breast cancer patients
Authors: Li Yan , Chen Lili , Lv Jinxing , Chen Xiaobin , Zeng Bangwei , Chen Minyan , Guo Wenhui , Lin Yuxiang , Yu Liuwen , Hou Jialin , Li Jing , Zhou Peng , Zhang Wenzhe , Li Shengmei , Jin Xuan , Cai Weifeng , Zhang Kun , Huang Yeyuan , Wang Chuan , Fu Fangmeng
Published: November 2022

Background

Bilateral breast cancer (BBC), as well as ovarian cancer, are significantly associated with germline deleterious variants in BRCA1/2, while BRCA1/2 germline deleterious variants carriers can exquisitely benefit from poly (ADP-ribose) polymerase (PARP) inhibitors. However, formal genetic testing could not be carried out for all patients due to extensive use of healthcare resources, which in turn results in high medical costs. To date, existing BRCA1/2 deleterious variants prediction models have been developed in women of European or other descent who are quite genetically different from Asian population. Therefore, there is an urgent clinical need for tools to predict the frequency of BRCA1/2 deleterious variants in Asian BBC patients balancing the increased demand for and cost of cancer genetics services.

Methods

The entire coding region of BRCA1/2 was screened for the presence of germline deleterious variants by the next generation sequencing in 123 Chinese BBC patients. Chi-square test, univariate and multivariate logistic regression were used to assess the relationship between BRCA1/2 germline deleterious variants and clinicopathological characteristics. The R software was utilized to develop artificial neural network (ANN) and nomogram modeling for BRCA1/2 germline deleterious variants prediction.

Results

Among 123 BBC patients, we identified a total of 20 deleterious variants in BRCA1 (8; 6.5%) and BRCA2 (12; 9.8%). c.5485del in BRCA1 is novel frameshift deleterious variant. Deleterious variants carriers were younger at first diagnosis (P = 0.0003), with longer interval between two tumors (P = 0.015), at least one medullary carcinoma (P = 0.001), and more likely to be hormone receptor negative (P = 0.006) and HER2 negative (P = 0.001). Area under the receiver operating characteristic curve was 0.903 in ANN and 0.828 in nomogram modeling individually (P = 0.02).

Conclusion

This study shows the spectrum of the BRCA1/2 germline deleterious variants in Chinese BBC patients and indicates that the ANN can accurately predict BRCA deleterious variants than conventional statistical linear approach, which confirms the BRCA1/2 deleterious variants carriers at the lowest costs without adding any additional examinations.
The predictive value of fibrinogen in the occurrence of mild cognitive impairment events in patients with diabetic peripheral neuropathy
Authors: Zhuang Yong , Huang Huibin , Fu Zhenfei , Zhang Jinying , Cai Qingyan
Published: November 2022

Background

Research suggests that fibrinogen (Fib) is related to mild cognitive impairment (MCI) and diabetic peripheral neuropathy (DPN) and the risk of MCI in patients with DPN is greatly increased, although no studies have evaluated the predictive value of Fib for the risk of MCI in patients with DPN.

Methods

This prospective observational clinical study enrolled 207 type 2 diabetes mellitus (T2DM) patients, who were divided into diabetes with no neuropathy (102 cases) and diabetes with neuropathy (105 cases) groups. Meanwhile, 90 healthy unrelated subjects were recruited as controls. The incidence of MCI in the DPN patients was followed up for 2 years. Divide patients in the DPN group into subgroups according to whether MCI occur, use multivariate logistic regression to analyze independent factors of MCIs in DPN patients within 2 years, and use ROC curve to analyze the predictive value of Fib for MCI in DPN patients.

Results

Fib levels were significantly higher in diabetic subjects with neuropathy compared with those without (P < 0.001). In further subgroup analysis of DPN patients who were divided according to the occurrence of MCI, baseline data of the MCI subgroup showed Fib levels were higher than that in the non-MCI group while education levels declined (P < 0.001). The education level and increased Fib levels were independent factors for the occurrence of MCI within 2 years after the onset of DPN (OR = 0.769, 95% CI: 0.605 ~ 0.968, P = 0.037; OR = 2.674, 95% CI: 1.094 ~ 3.168, P = 0.002). The ROC curve indicated that the predictive value of Fib was (AUC = 0.764, 95% CI: 0.671 ~ 0.842, P < 0.001).

Conclusions

Fib may function as a predictor for assessing the risk of MCI in DPN patients.
“I wouldn’t have joined if it wasn’t online”: understanding older people’s engagement with teleyoga classes for fall prevention
Authors: Haynes Abby , Gilchrist Heidi , Oliveira Juliana S , Sherrington Catherine , Tiedemann Anne
Published: November 2022

Background

Yoga-based exercise is a promising strategy for promoting healthy ageing, with the potential to reduce falls and increase physical, cognitive and psychological wellbeing. Teleyoga (real-time yoga provided via interactive videoconferencing) can deliver yoga programs at scale, potentially reducing costs, increasing convenience, and reaching people who cannot attend studio-based classes. But better understanding of how older people perceive and engage with teleyoga is needed to optimise its design, implementation and promotion.

Methods

This study built on a previous realist process evaluation of the SAGE yoga trial which is testing the effect of a yoga-based exercise program on falls among 700 community-dwelling people aged 60 + years. In this second phase of evaluation we conducted focus groups with participants who had completed the SAGE program online and with the yoga instructors who were delivering it. We also conducted interviews with participants who had withdrawn from the trial. Six program theories developed in the earlier evaluation provided a framework for data analysis, supplemented by inductive coding and an analytical workshop.

Results

Participants described physical and psychological benefits from the SAGE teleyoga program. While noting that teleyoga cannot facilitate hands-on correction or the same quality of observation or interaction as studio classes, participants were highly appreciative of their yoga instructors’ strategies for optimising visibility, instruction, social connection and therapeutic alliance, and for adapting to constrained home environments. Some participants argued that teleyoga was superior to studio classes due to its accessibility and convenience, its lower exposure to potential embarrassment about physical appearance or capabilities, and a reduced sense of peer competition and distraction. Our program theories applied across studio and online modes of delivery.

Conclusion

Teleyoga increases accessibility for people in diverse locations and circumstances; it provides a psychologically safer space which combats self-consciousness and unwanted competitiveness; it may enhance embodiment and mindfulness for some; and it has the potential to be offered relatively cheaply at scale which could support free or reduced price classes for people on low incomes and pensions, thereby encouraging a wider population to engage in yoga for healthy ageing and fall prevention.
Targeting hypoxia in solid and haematological malignancies
Authors: Harris Bill , Saleem Sana , Cook Natalie , Searle Emma
Published: November 2022

Tumour hypoxia is a known and extensively researched phenomenon that occurs in both solid and haematological malignancies. As cancer cells proliferate, demand for oxygen can outstrip supply reducing tumour oxygenation. In solid tumours this is contributed to by disorganized blood vessel development. Tumour hypoxia is associated with resistance to treatment, more aggressive disease behaviour and an increased likelihood of metastatic progression. It can be measured using both invasive and non-invasive methods to varying degrees of accuracy. The presence of hypoxia stimulates a complex cellular network of downstream factors including Hypoxia Inducible Factor 1 (HIF1), C-X-C motif chemokine 4 (CXCR4) and Hypoxia‐inducible glycolytic enzyme hexokinase‐2 (HK2) amongst many others. They work by affecting different mechanisms including influencing angiogenesis, treatment resistance, immune surveillance and the ability to metastasize all of which contribute to a more aggressive disease pattern. Tumour hypoxia has been correlated with poorer outcomes and worse prognosis in patients. The correlation between hypoxic microenvironments and poor prognosis has led to an interest in trying to therapeutically target this phenomenon. Various methods have been used to target hypoxic microenvironments. Hypoxia-activated prodrugs (HAPs) are drugs that are only activated within hypoxic environments and these agents have been subject to investigation in several clinical trials. Drugs that target downstream factors of hypoxic environments including HIF inhibitors, mammalian target of rapamycin (mTOR) inhibitors and vascular endothelial growth factor (anti-VEGF) therapies are also in development and being used in combination in clinical trials. Despite promising pre-clinical data, clinical trials of hypoxia targeting strategies have proven challenging. Further understanding of the effect of hypoxia and related molecular mechanisms in human rather than animal models is required to guide novel therapeutic strategies and future trial design. This review will discuss the currently available methods of hypoxia targeting and assessments that may be considered in planning future clinical trials. It will also outline key trials to date in both the solid and haemato-oncology treatment spheres and discuss the limitations that may have impacted on clinical success to date.
Analysis of N7-(2-carbamoyl-2-hydroxyethyl)guanine in dried blood spot after food exposure by Ultra High Performance Liquid Chromatography–Tandem Mass Spectrometry
Authors: Harahap Yahdiana , Safitri Winning Bekti , Sunarsih Sunarsih
Published: November 2022

N7-(2-carbamoyl-2-hydroxyethyl)guanine (N7-CAG) is a DNA adduct formed by glycidamide, which is the metabolite of acrylamide. Acrylamide can be found in foods containing reducing sugars and asparagine that are heated at high temperatures. Analysis of N7-CAG was performed in Dried Blood Spot (DBS) samples from 25 subjects of group test who consumed a lot of acrylamide-containing foods and 25 subjects of negative control group. This study aimed to determine whether there is a significant difference in the levels of N7-CAG between the two groups. DBS samples were extracted using the QIAamp DNA Mini Blood Kit and analyzed using Ultra High Performance Liquid Chromatography–Tandem Mass Spectrometry (UHPLC-MS/MS). Separation was performed using an Acquity UPLC BEH C18 column (2.1 mm × 100 mm; 1.7 μm), eluted a flow rate of 0.1 ml/min under an isocratic of mobile phase of 0.1% formic acid and acetonitrile. The bioanalytical method of N7-CAG in DBS with allopurinol as the internal standard by using UHPLC-MS/MS has been validated. The calibration curve range of N7-CAG obtained was 10–300 ng/ml with a coefficient of correlation of 0.997. The results of the analysis on 25 test group subjects showed that the concentration of N7-CAG ranged from 1.87 to 23.71 ng/ml, while the 25 subjects in the negative group ranged from 1.18 to 8.47 ng/ml. The results of the Mann Whitney test showed that there was a significant difference in the levels of N7-CAG between the test group and the negative control group with p value less than 0.001.
In-vivo recording of sensory signals from peripheral nerves using flexible 3D neural electrodes
Authors: Park Byungwook , Jang Jae-Won , Kim Sohee
Published: November 2022

To overcome the limitations of muscle-based prostheses, studies on nerve-based prostheses for sensory feedback have recently been reported. To develop such prostheses, intrafascicular electrodes, a type of peripheral nerve interface, are essentially used to connect the nervous system and external systems. Through these electrodes, sensory feedback to induce sensations in patients is possible. To evoke natural sensations, precise recordings of nerve signals should precede sensory feedback, in order to identify patterns of sensory signals in the nerve and to mimic these patterns in stimulating the nerve. For this purpose, we previously developed a PDMS-based flexible penetrating microelectrode array (FPMA). In the current study, we verified the ability of the FPMA to record sensory nerve signals. The FPMA implanted in the rabbit sciatic nerve was able to record spontaneous neural signals, and the recorded signals were separated into action potential units. In addition, sensory nerve signals synchronized with ankle movement were successfully recorded, demonstrating that the FPMA is a useful peripheral neural interface capable of recording high-resolution sensory signals.
Bionic design based on micro-nano structure of osteon and its low-velocity impact damage behavior
Authors: Liu Yuxi , Li Aihua , Li Yanhua , Chen Song
Published: November 2022

It is found that the osteon is composed of thin and thick lamellae which are periodic and approximately concentric, every 5 lamellae is a cycle, the periodic helix angle of mineralized collagen fibers in two adjacent sub-lamellae is 30°. Four bionic composite models with different fiber helix angles were established and fabricated according to the microstructure of mineralized collagen fibers in osteon. Based on the impact analysis of four kinds of bionic composite models, the effects of the fiber periodic spiral structure on the impact resistance and energy dissipation of multi-layer bionic composite were investigated. The analysis results show that the fiber helix angle affects the impact damage resistance and energy dissipation of multi-layer fiber reinforced composites. Among the 4 kinds of multi-layer composite models, the composite model with helix angle of 30° has better comprehensive ability to resist impact damage. The test results show that the impact damage area of the specimen with 30° helix angle is smallest among the 4 types of bionic specimens, which is consistent with the results of finite-element impact analysis. Furthermore, in the case of without impact damage, the smaller the fiber helix angle is, the more uniform the stress distribution is and more energy is dissipated in the impact process. The periodic spiral structure of mineralized collagen fibers in osteon are the result of natural selection of biological evolution. This structure can effectively improve the ability of cortical bone to resist external impact. The research results can provide useful guidance for the design and manufacture of high-performance and strong impact resistant bionic composites.

Graphical Abstract
Are immediate postoperative X-Rays valuable in evaluating complications of primary total hip arthroplasty?
Authors: Brown Matthew L. , Michel David , Narayanan Arvind , McCauley Julie C. , Bugbee William D.
Published: November 2022

Purpose

This study aimed to investigate the complications of primary total hip arthroplasty based on immediate postoperative X-rays. The overall quality and cost of X-rays were assessed.

Methods

The institutional database was queried to identify all patients who underwent total hip arthroplasty in a single institution between January 1, 2018, and December 31, 2018. Immediate postoperative X-rays were reviewed to identify the complications such as periprosthetic fractures, dislocation, and fixation failure. The quality and cost of X-ray were assessed. The complications were categorized as "known" and "unknown" according to the intraoperative fluoroscopic results.

Results

A total of 518 total hip arthroplasties were included in this study. Based on intraoperative fluoroscopy, periprosthetic fractures were found in 10 (2%) THAs. Compared to the X-rays taken immediately after surgery, 9 periprosthetic fractures (recorded as "known") were found and 1 was not (recorded as "unknown"). There was no significant difference between intraoperative fluoroscopy and X-rays (P > 0.05). Of the 518 X-rays, 225 (43%) were of suboptimal quality. The cost of a single portable pelvic X-ray was $647.

Conclusion

In total hip arthroplasty, X-rays taken immediately after surgery rarely reveal unknown complications. The X-rays are often of suboptimal quality, have minimal clinical utility, and are less cost-effective.