bluuebunny/crossref_metadata_2025 huggingface dataset:
A Method to Evaluated Gas Content with Coalbed Methane Reservoir Based on Adsorption Theory and Production Analysis
Authors: Feng Ruyong
Published: June 2022

In the process of coalbed methane development, the gas content not only determines the reserves of methane in coal reservoir but also is the most important geological parameter affecting the production of coalbed methane. The gas content directly determines whether coalbed methane can be developed efficiently. However, in the current development evaluation process, it is very difficult to accurately predict the gas content in coal seams. An efficient and accurate method to predict gas content has not been found yet. This is mainly restricted by the development mode and technology of coalbed methane. In the current low-cost development model, gas content test data are relatively scarce. Under such circumstances, it is difficult to accurately evaluate the distribution of CBM gas content in the whole area. At the same time, the gas content of coalbed is the key parameter for efficient development of coalbed methane. Under normal circumstances, gas content heterogeneity will result in a large gap between development effects in different regions. At present, there is no evaluation method for gas content parameters of coal reservoir. Under this background, the key parameters of coalbed methane development in southern Qinshui Basin were evaluated. On the basis of systematically summarizing and understanding the development law of coalbed methane in different types of coal reservoirs, a gas content evaluation method based on adsorption theory and production dynamic analysis is proposed. Combined with the coalbed methane production model and isothermal adsorption model, the critical desorption pressure can be calculated accurately by using the bottom hole pressure when casing pressure occurs in production wells. The critical desorption pressure correction model of coalbed methane was innovatively established. Langmuir equation was used to accurately characterize the adsorption characteristics of coalbed methane. Forming a new method for gas content prediction in the case of fewer coring wells. The gas content evaluation technology coupled with isothermal adsorption theory and production dynamic analysis saves the development cost of coalbed methane and improves the prediction accuracy of coal seam gas content in noncoring wells. At the same time, there is a good relationship between the predicted results and the measured gas content at well points. The coincidence rate reached 97.37%. This technology can effectively improve the prediction accuracy of coal seam gas content. This technique is suitable for the productivity evaluation of coalbed methane reservoir. It can also provide scientific basis for the development and reserve evaluation of coalbed methane reservoirs at home and abroad.
Rhodotorula mucilaginosa Fungemia, a Rare Opportunistic Infection without Central Venous Catheter Implantation, Successfully Treated by Liposomal Amphotericin B
Authors: Hirano Ryuichi , Mitsuhashi Tatsuro , Osanai Katsuyoshi
Published: June 2022

Background. Fungemia due to Rhodotorula mucilaginosa is rare and highly resistance to antifungal therapy. Since most cases of R. mucilaginosa fungemia are attributed to medical devices, limited information is currently available on infection without central venous catheter (CVC) implantation. We herein report a case of R. mucilaginosa fungemia without implantation of CVC, successfully treated by liposomal amphotericin B (L-AMB). Case Presentation. An 81-year-old man with a history of chronic obstructive lung disease and rheumatoid arthritis was admitted with dyspnea and fever. The present case had no previous history of CVC implantation. Candidemia was suspected based on yeast and salmon-pink colonies in blood cultures, and thus, micafungin (MCFG) was administered. The isolated yeast was identified as R. mucilaginosa, which exhibited resistance to MCFG. Therefore, antifungal therapy was changed to L-AMB. The sterile blood culture and defervescence were observed from the initiation of L-AMB. Conclusion. Although the obvious entry point was unclear, long-term immunosuppressive therapy for RA may have damaged the gastrointestinal tract, which leading to the bacterial translocation of R. mucilaginosa. An early class switch to L-AMB was effective. Physicians need to consider the administration of L-AMB in cases suspected of R. mucilaginosa fungemia following the detection of salmon-pink colonies in blood cultures.
Characterization of Cold Bituminous Mastics Prepared with Different Active Fillers at High and Intermediate Temperature
Authors: Bérubé Marc-André , Carter Alan , Singh Dharamveer
Published: June 2022

Cold recycling of asphalt mixes is becoming a usual pavement rehabilitation technique. The use of active fillers in conjunction with bituminous emulsion changes the properties of the mixes, mainly on the mastic characteristics. The use of active filler can make the mastic more brittle, but limited data are available on this aspect. In this study, emulsion-active filler mastics were prepared with two different mixing methods. Two different active fillers, ordinary Portland cement and fly ash, were used at four different contents with a single emulsion and an inert filler. Once cured, the mastics were tested with a dynamic shear rheometer (DSR) to get the viscoelastic properties at high temperature and with the double-edge-notched tension (DENT) test to look at the cracking potential at intermediate temperature. The results show that the order that the materials are incorporated during the mixing of the mastics does have a significant effect on the properties. Also, in terms of stiffness, the optimum amount of active filler is different for the cement than for the fly ash. For the cracking resistance, the results have shown that the addition of both active fillers does have an impact on the cracking resistance, but in the amount tested, no brittle fracture was observed. The results have shown that the type and quantity of active filler are important since it changes the fracture performance and the viscoelastic properties of bituminous mastic.
Evaluation of the Property of Axillary Lymph Nodes and Analysis of Lymph Node Metastasis Factors in Breast Cancer by Ultrasound Elastography
Authors: Zhou Jia , Zhang Qingyu , Zhang Qi , Yan Lei , Gao Qing
Published: June 2022

This research was aimed at investigating the role of ultrasound elastography (UE) in evaluating the properties of axillary lymph nodes in breast cancer and exploring the influencing factors of lymph node metastasis in breast cancer patients. Routine ultrasonography (US) and UE were performed for 160 breast cancer patients. 80 cases were in the group with lymph node metastasis, and the other 80 were in the nonlymph node metastasis group. The sensitivity, specificity, and accuracy of the two ultrasound examinations were compared, the receiver-operator characteristic (ROC) curves were drawn, and the influencing factors of lymph node metastasis were analyzed. The sensitivity, specificity, and accuracy of UE in diagnosing axillary lymph nodes of breast cancer were 97.22%, 95.45%, and 96.25%, respectively, which were markedly higher than those of routine US (

P
<
0.05

). Cortical thickness, blood flow grade, blood flow type, and elasticity score had a greater impact on axillary lymph node metastasis of breast cancer. When

cortical
 
thickness
≥
3
 
cm

, blood flow was of 2-3 grades, blood flow was the peripheral/mixed type, and elasticity score was 3-4 points, these became risk factors for lymph node metastasis in breast cancer patients. UE was effective in diagnosing the property of lymph nodes and could evaluate lymph node metastasis in breast cancer patients. It had a good clinical value and was worthy of popularization and application.
Graphic Perception System for Visually Impaired Groups
Authors: Wen Jingzi
Published: June 2022

In the age of internet, the demand of visually impaired groups to perceive graphic images through tactile sense is becoming stronger and stronger. Image object recognition is a basic task in the field of computer vision. In recent years, deep neural networks have promoted the development of image object recognition. However, existing methods generally have problems of image details’ loss and edge refinement, which cannot improve the accuracy rate of object recognition for visually impaired groups. In order to solve this problem, this study proposes a graphic perception system, which improves the attention mechanism. This system mainly consists of three modules: mixing attention module (MAM), enhanced receptive field module (ERFM), and multilevel fusion module (MLAM). MAM can generate better semantic features, which can be used to guide feature fusion in the decoding process, so that the aggregated features can better locate significant objects. ERFM can enrich the context information of low-level features and input the enhanced features into MLAM. MLAM uses the semantic information generated by MAM to guide the fusion of the current decoded features and the low-level features’ output by ERFM, and gradually recover boundary details in a cascading manner. Finally, the proposed algorithm is compared with other algorithms on PASCAL VOC and MS-COCO data. Experimental results show that the proposed method can effectively improve the accuracy of graphic object recognition.
Days of Flooding Associated with Increased Risk of Influenza
Authors: Kontowicz Eric , Brown Grant , Torner James , Carrel Margaret , Baker Kelly K. , Petersen Christine A.
Published: June 2022

Influenza typically causes mild infection but can lead to severe outcomes for those with compromised lung health. Flooding, a seasonal problem in Iowa, can expose many Iowans to molds and allergens shown to alter lung inflammation, leading to asthma attacks and decreased viral clearance. Based on this, the hypothesis for this research was that there would be geographically specific positive associations in locations with flooding with influenza diagnosis. An ecological study was performed using influenza diagnoses and positive influenza polymerase chain reaction tests from a de‐identified large private insurance database and Iowa State Hygienic Lab. After adjustment for multiple confounding factors, Poisson regression analysis resulted in a consistent 1% associated increase in influenza diagnoses per day above flood stage (95% confidence interval: 1.00–1.04). This relationship remained after removal of the 2009–2010 influenza pandemic year. There was no associated risk between flooding and influenza‐like illness as a nonspecific diagnosis. Associated risks between flooding and increased influenza diagnoses were geographically specific, with the greatest risk in the most densely populated areas. This study indicates that populations who live, work, or volunteer in flooded environments should consider preventative measures to avoid environmental exposures to mitigate illness from influenza in the following year.
Online Learning for DNN Training: A Stochastic Block Adaptive Gradient Algorithm
Authors: Liu Jianghui , Li Baozhu , Zhou Yangfan , Zhao Xuhui , Zhu Junlong , Zhang Mingchuan
Published: June 2022

Adaptive algorithms are widely used because of their fast convergence rate for training deep neural networks (DNNs). However, the training cost becomes prohibitively expensive due to the computation of the full gradient when training complicated DNN. To reduce the computational cost, we present a stochastic block adaptive gradient online training algorithm in this study, called SBAG. In this algorithm, stochastic block coordinate descent and the adaptive learning rate are utilized at each iteration. We also prove that the regret bound of

O

T

can be achieved via SBAG, in which

T

is a time horizon. In addition, we use SBAG to train ResNet-34 and DenseNet-121 on CIFAR-10, respectively. The results demonstrate that SBAG has better training speed and generalized ability than other existing training methods.
Lumbar Canal Stenosis Caused by Marked Bone Overgrowth after Decompression Surgery
Authors: Shimauchi-Ohtaki Hiroya , Minami Manabu , Takahashi Toshiyuki , Kanematsu Ryo , Honda Fumiaki , Hanakita Junya
Published: June 2022

Narrowing of the lumbar canal due to bone regrowth after lumbar decompression surgery generally occurs at the facet joint; it is exceedingly rare for this phenomenon to occur at the laminar arch. Herein, we describe a case of restenosis caused by marked bone overgrowth at the facet joints and laminar arch after lumbar decompression surgery. A 64-year-old man underwent partial hemilaminectomy for lumbar canal stenosis at the L3/L4 level 12 years ago. His symptoms recurred 7 years after the first surgery. Overgrowth of the laminar arch and facet joints was observed at the decompression site. Thus, partial laminectomy of L3 and L4 was performed as a second surgery. Four years after the second surgery, a laminectomy of L3-L4 was performed for bone restenosis and disc herniation. The underlying mechanism of the remarkable overgrowth of the removed lamina remains unclear. Endochondral ossification signals and mechanosignals should be comprehensively examined.
Selective Vulnerability of Senescent Glioblastoma Cells to BCL-XL Inhibition
Authors: Rahman Masum , Olson Ian , Mansour Moustafa , Carlstrom Lucas P. , Sutiwisesak Rujapope , Saber Rehan , Rajani Karishma , Warrington Arthur E. , Howard Adam , Schroeder Mark , Chen Sisi , Decker Paul A. , Sananikone Eliot F. , Zhu Yi , Tchkonia Tamar , Parney Ian F. , Burma Sandeep , Brown Desmond , Rodriguez Moses , Sarkaria Jann N. , Kirkland James L. , Burns Terry C.
Published: June 2022

Glioblastoma (GBM) is a rapidly fatal malignancy typically treated with radiation and temozolomide (TMZ), an alkylating chemotherapeutic. These cytotoxic therapies cause oxidative stress and DNA damage, yielding a senescent-like state of replicative arrest in surviving tumor cells. Unfortunately, recurrence is inevitable and may be driven by surviving tumor cells eventually escaping senescence. A growing number of so-called “senolytic” drugs have been recently identified that are defined by their ability to selectively eliminate senescent cells. A growing inventory of senolytic drugs is under consideration for several diseases associated with aging, inflammation, DNA damage, as well as cancer. Ablation of senescent tumor cells after radiation and chemotherapy could help mitigate recurrence by decreasing the burden of residual tumor cells at risk of recurrence. This strategy has not been previously explored for GBM. We evaluated a panel of 10 previously described senolytic drugs to determine whether any could exhibit selective activity against human GBM persisting after exposure to radiation or TMZ. Three of the 10 drugs have known activity against BCL-XL and preferentially induced apoptosis in radiated or TMZ-treated glioma. This senolytic activity was observed in 12 of 12 human GBM cell lines. Efficacy could not be replicated with BCL-2 inhibition or senolytic agents acting against other putative senolytic targets. Knockdown of BCL-XL decreased survival of radiated GBM cells, whereas knockdown of BCL-2 or BCL-W yielded no senolytic effect.

Implications:

These findings imply that molecularly heterogeneous GBM lines share selective senescence-induced BCL-XL dependency increase the significance and translational relevance of the senolytic therapy for latent glioma.
Vitamin D Receptor Activation Attenuates Hippo Pathway Effectors and Cell Survival in Metastatic Neuroblastoma
Authors: Ladumor Yagnesh , Seong Bo Kyung Alex , Hallett Robin , Valencia-Sama Ivette , Adderley Teresa , Wang Yingying , Kee Lynn , Gont Alexander , Kaplan David R. , Irwin Meredith S.
Published: June 2022

Survival for high-risk neuroblastoma remains poor. Most patients who recur, present with metastatic disease, and few targetable pathways that govern spread to distant sites are currently known. We previously developed a metastatic mouse model to select cells with enhanced ability to spread to the bone and brain and identified a signature based on differentially expressed genes, which also predicted patient survival. To discover new neuroblastoma therapies, we utilized the Connectivity Map to identify compounds that can reverse this metastatic transcriptional signature and found calcipotriol, a vitamin D3 analog, to be a compound that selectively targets cell lines with enhanced metastatic potential. Calcipotriol treatment of enhanced metastatic, but not parental, cells reduces proliferation and survival via vitamin D receptor (VDR) signaling, increases the expression of RASSF2, a negative regulator of the Hippo signaling pathway, and reduces the levels of the Hippo pathway effectors YAP and TAZ. RASSF2 is required for the effects of calcipotriol and for the reduction of levels and nuclear localization of YAP/TAZ. Migration of the enhanced metastatic cells and YAP/TAZ levels are reduced after calcipotriol treatment and YAP overexpression reduces calcipotriol sensitivity. Furthermore, metastatic cells that overexpress VDR also showed lower tumor burden in vivo.

Implications:

This newly identified link between VDR signaling and the Hippo pathway could inform treatment strategies for metastatic neuroblastoma.
Inhibiting WEE1 and IKK-RELA Crosstalk Overcomes TNFα Resistance in Head and Neck Cancers
Authors: Hu Zhengbo , Viswanathan Ramya , Cheng Hui , Chen Jianghong , Yang Xinping , Huynh Angel , Clavijo Paul , An Yi , Robbins Yvette , Silvin Christopher , Allen Clint , Ormanoglu Pinar , Martin Scott , Cornelius Shaleeka , Saleh Anthony , Chen Zhong , Van Waes Carter , Morgan Ethan L.
Published: June 2022

TNFα is a key mediator of immune and radiotherapy-induced cytotoxicity, but many cancers, including head and neck squamous cell carcinomas (HNSCC), display TNF resistance due to activation of the canonical IKK–NF-κB/RELA pro-survival pathway. However, toxicities associated with direct targeting of the canonical pathway point to the need to identify mechanism(s) contributing to TNFα resistance and synthetic lethal targets to overcome such resistance in cancer cells. Here, RNAi screening for modulators of TNFα–NF-κB reporter activity and cell survival unexpectedly implicated the WEE1 and CDC2 G2–M checkpoint kinases. The IKKα/β-RELA and WEE1-CDC2 signaling pathways are activated by TNFα and form a complex in cell lines derived from both human papillomavirus (−) and (+) subtypes of HNSCC. WEE1 inhibitor AZD1775 reduced IKK/RELA phosphorylation and the expression of NF-κB–dependent pro-survival proteins Cyclin D1 and BCL2. Combination of TNFα and AZD1775 enhanced caspase-mediated apoptosis in vitro, and combination treatment with radiotherapy and AZD1775 potentiated inhibition of HNSCC tumor xenograft growth in vivo, which could be significantly attenuated by TNFα depletion. These data offer new insight into the interplay between NF-κB signaling and WEE1-mediated regulation of the G2–M cell-cycle checkpoint in HNSCC.

Implications:

Inhibiting WEE1 and IKK-RELA crosstalk could potentially enhance the effects of therapies mediated by TNFα with less systemic immune suppression and toxicity than observed with direct interruption of IKK-NF-κB/RELA signaling.
Diurnal Expression of PD-1 on Tumor-Associated Macrophages Underlies the Dosing Time-Dependent Antitumor Effects of the PD-1/PD-L1 Inhibitor BMS-1 in B16/BL6 Melanoma-Bearing Mice
Authors: Tsuruta Akito , Shiiba Yuki , Matsunaga Naoya , Fujimoto Marina , Yoshida Yuya , Koyanagi Satoru , Ohdo Shigehiro
Published: June 2022

Cancer cells have acquired several pathways to escape from host immunity in the tumor microenvironment. Programmed death 1 (PD-1) receptor and its ligand PD-L1 are involved in the key pathway of tumor immune escape, and immune checkpoint therapy targeting PD-1 and PD-L1 has been approved for the treatment of patients with certain types of malignancies. Although PD-1 is a well-characterized receptor on T cells, the immune checkpoint receptor is also expressed on tumor-associated macrophages (TAM), a major immune component of the tumor microenvironment. In this study, we found significant diurnal oscillation in the number of PD-1–expressing TAMs collected from B16/BL6 melanoma-bearing mice. The levels of Pdcd1 mRNA, encoding PD-1, in TAMs also fluctuated in a diurnal manner. Luciferase reporter and bioluminescence imaging analyses revealed that a NF-κB response element in the upstream region of the Pdcd1 gene is responsible for its diurnal expression. A circadian regulatory component, DEC2, whose expression in TAMs exhibited diurnal oscillation, periodically suppressed NF-κB–induced transactivation of the Pdcd1 gene, resulting in diurnal expression of PD-1 in TAMs. Furthermore, the antitumor efficacy of BMS-1, a small molecule inhibitor of PD-1/PD-L1, was enhanced by administering it at the time of day when PD-1 expression increased on TAMs. These findings suggest that identification of the diurnal expression of PD-1 on TAMs is useful for selecting the most appropriate time of day to administer PD-1/PD-L1 inhibitors.

Implications:

Selecting the most appropriate dosing time of PD-1/PD-L1 inhibitors may aid in developing cancer immunotherapy with higher efficacy.
EML4-ALK Variant 3 Promotes Mitotic Errors and Spindle Assembly Checkpoint Deficiency Leading to Increased Microtubule Poison Sensitivity
Authors: Lucken Kellie , O'Regan Laura , Choi Jene , Sampson Josephina , Pashley Sarah L. , Bayliss Richard , Khan Sam , Fry Andrew M.
Published: June 2022

EML4-ALK is an oncogenic fusion protein present in approximately 5% of non–small cell lung cancers (NSCLC). Alternative breakpoints in the gene encoding EML4 result in distinct variants that are linked to markedly different patient outcomes. Patients with EML4-ALK variant 3 (V3) respond poorly to ALK inhibitors and have lower survival rates compared with patients with other common variants, such as V1. Here, we use isogenic Beas-2B bronchial epithelial cell lines expressing EML4-ALK V1 or V3, as well as ALK-positive NSCLC patient cells that express V1 (H3122 cells) or V3 (H2228 cells), to show that EML4-ALK V3 but not V1 leads to hyperstabilized K-fibers in mitosis, as well as errors in chromosome congression and segregation. This is consistent with our observation that EML4-ALK V3 but not V1 localizes to spindle microtubules and that wild-type EML4 is a microtubule stabilizing protein. In addition, cells expressing EML4-ALK V3 exhibit loss of spindle assembly checkpoint control that is at least in part dependent on ALK catalytic activity. Finally, we demonstrate that cells expressing EML4-ALK V3 have increased sensitivity to microtubule poisons that interfere with mitotic spindle assembly, whereas combination treatment with paclitaxel and clinically approved ALK inhibitors leads to a synergistic response in terms of reduced survival of H2228 cells.

Implications:

This study suggests that combining the microtubule poison, paclitaxel, with targeted ALK inhibitors may provide an effective new treatment option for patients with NSCLC with tumors that express the EML4-ALK V3 oncogenic fusion.
Das Beste aus zwei Welten: Eine systematische Übersicht zu Faktoren der Implementierung einer “Blended Therapy” (Gemischte Therapie) in der Psychotherapeutischen Routineversorgung
Authors: Dech Mayra , Klawohn Julia , Romanczuk-Seiferth Nina
Published: June 2022

Ziel: Diese Arbeit gibt einen Überblick über bisherige wissenschaftliche Empfehlungen zur Implementierung der blended therapy, d.h. der Kombination von Therapien in Präsenz und via digitaler Medien. Die Empfehlungen um­fassen die Themen: (1) wahrgenommene Barrieren von Psychotherapeut*innen, (2) Format der blended therapy und (3) Indikationen für Patient*innen. In diesem Rahmen werden Faktoren aufgezeigt, die Akteur*innen im Gesundheitssystem als Orientierung dienen können, welche Determinanten bei der Implementierung in die Routineversorgung zu berücksichtigen sind. Methodik: Die systematische Suche erfolgte in den Datenbanken PsycArticles, PsycInfo, PSYNDEX und PubMed. Ergebnisse: Die Publikationen umfassen vier quantitative, neun qualitative sowie drei Mixed-Methods-Studien. Die bisherigen Arbeiten kommen zu dem Ergebnis, dass Psychotherapeut*innen frühzeitig in den Implementierungsprozess einbezogen und langfristige supportive Maßnahmen für die Umstrukturierung der bisherigen Arbeitsroutine geschaffen werden sollten. Das Format der blended therapy sollte nicht standardisiert angewandt, sondern vielmehr individuell an die Patient*innen angepasst werden. Hinsichtlich möglicher Indikationen werden verschiedene Einflussfaktoren der Patient*innen diskutiert, die bisher jedoch nur unzureichend untersucht wurden. Diskussion: Bisherige Studien weisen größtenteils homogene Charakteristika und Ergebnisse auf. Forschungslücken bestehen hinsichtlich der Frage, inwieweit sich die Ergebnisse auf andere Therapieschulen, Berufsgruppen und Störungsbilder übertragen lassen. Schlussfolgerung: Das Review veranschaulicht, dass es wichtiger Vorarbeit hinsichtlich der Anwendungsunterstützung für Psychotherapeut*innen sowie weiterer Forschungsaktivität bedarf, um die Implementierung von blended therapy im Sinne einer möglichen Verbesserung der psychotherapeutischen Versorgung voranzutreiben.
miR-146a-5p Attenuates Allergic Airway Inflammation by Inhibiting the NLRP3 Inflammasome Activation in Macrophages
Authors: Yang Yanping , Huang Guandong , Xu Qing , Zhao Gang , Jiang Jiamei , Li Yongxia , Guo Zhong
Published: June 2022

Objective: Asthma is a common inflammatory respiratory disease with increasing incidence worldwide. This study aimed to investigate the mechanism of miR-146a-5p in reducing allergic airway inflammation by inhibiting NLRP3 inflammasome activation in macrophages. Methods: Allergic mouse models were established by ovalbumin stimulation, and mice were treated with miR-146a-5p agomir and oe-TIRAP 3 h before OVA stimulation. The pathological changes of lung tissues were observed by hematoxylin-eosin staining. The airway hyperresponsiveness of mice were examined. The miR-146a-5p level was detected by RT-qPCR. The inflammatory cytokines (IL-18/TNF-α) and anti-inflammatory cytokine IL-10 levels in bronchoalveolar lavage fluid and serum IgE levels were examined by ELISA. Airway inflammation in mice was detected after miR-146a-5p overexpression. The levels of NLRP3/ASC/caspase1 proteins and macrophage M1/M2 surface markers in mouse lung tissues were examined using immunohistochemistry, Western blot, and flow cytometry. The targeting relationship between miR-146a-5p and TIRAP was verified by dual-luciferase assay. The p65 levels in the cytoplasm/nucleus of mouse lung tissue were measured. Results: miR-146a-5p was downregulated in the lung tissues of allergic mice, and miR-146a-5p overexpression alleviated airway inflammation in asthmatic mice. miR-146a-5p suppressed NLRP3 inflammasome activation in macrophages of allergic mice, reduced NLRP3/ASC/caspase1 protein levels in lung tissues, blocked M1 polarization, and promoted M2 polarization. miR-146a-5p targeted TIRAP. TIRAP overexpression partially reversed the promoting effect of miR-146a-5p on M2 polarization. miR-146a-5p can inhibit the activation of the TIRAP/NF-κB pathway. Conclusion: miR-146a-5p inhibited NLRP3 inflammasome activation in macrophages in the lung tissue of allergic mice, prevented pro-inflammatory phenotype M1 polarization, and promoted anti-inflammatory phenotype M2 polarization by targeting the TIRAP/NF-κB pathway, thus alleviating airway inflammation in allergic asthma.
Reversibility of Hypercapnia after an Acute Exacerbation of COPD
Authors: Bräunlich Jens , Turba Kristin , Wirtz Hubert
Published: June 2022

Background: After an episode of hypercapnic AECOPD, some patients show reversible, prolonged or persistent hypercapnic respiratory failure. However, at the time of patient discharge, it is uncertain whether patients will remain hypercapnic or may return to a physiologic gas status. Methods: Data were retrospectively collected from COPD patients with an acute hypercapnic exacerbation (AECOPD). Out of 143 total COPD inpatients, complete data set was available for 82 patients in stable condition. According to the first available capillary or arterial pCO2, patients were divided into those with persistent hypercapnia (PHG) and those with reversible hypercapnia. Results: In this study, 51% of patients with acute hypercapnic AECOPD and follow-up (FUP) visits developed normocapnia after a time period of several weeks. These patients were characterized by lower carbon dioxide partial pressure (PaCO2), HCO3−, and BE levels prior to the AECOPD event, at discharge and at FUP. pH was higher at discharge and FUP in this group. Greater disease severity and lower forced vital capacity were prominent in patients with PHG. Binary logistic regression revealed GOLD D and higher PaCO2 at discharge as predicting factors for PHG. Conclusions: A large percentage of patients has prolonged hypercapnia following acute hypercapnic COPD exacerbation. The risk profile of patients with irreversible hypercapnia should be carefully evaluated following AECOPD in order to choose selected patients for home-noninvasive ventilation.
Vitamin D Improves the Effect of Glucocorticoids on Attenuating Lipopolysaccharide-Induced IL-6 Production via TLR4/NF-κB Pathway in Human Respiratory Epithelial Cells
Authors: Wang Li , Zhao Yan , Yao Shuang , Lou Hongfei , Zhang Luo
Published: June 2022

Background: Glucocorticoid (GC) resistance results in unsatisfactory outcomes in chronic rhinosinusitis with nasal polyps (CRSwNP) patients. Previous studies have shown that calcitriol, the active form of vitamin D, alone or in combination with corticosteroids, exerts crucial immunomodulatory effects on inflammatory responses. However, whether vitamin D can improve the effect of GCs to attenuate inflammation in the epithelium of CRSwNP remains unclear. Methods: A human bronchial epithelial cell line (Beas-2B) and primary human nasal epithelial cells (HNECs) obtained from 10 patients with CRSwNP were exposed to lipopolysaccharide (LPS) for 24 h to establish an inflammation model. LPS-stimulated HNECs and Beas-2B cells were treated with/without dexamethasone in the presence or absence of calcitriol pretreatment for 24 h. The expression levels of interleukin-6 (IL-6) mRNA and protein were determined by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Toll-like receptor 4 (TLR4)/NF-κB pathway related markers were examined by western blotting. One-way ANOVA or the Kruskal-Wallis test with post hoc analysis were used for multiple comparisons among groups. Results: The production of IL-6 in Beas-2B cells and primary HNECs after LPS stimulation was significantly increased, which could be inhibited by dexamethasone or calcitriol alone. However, significant inhibition of IL-6 production was observed in the calcitriol plus dexamethasone group. Further analysis showed that calcitriol could enhance the effect of dexamethasone in inhibiting LPS-induced overexpression of TLR4, Myd88, and phosphorylation of p65. Conclusion: Our findings demonstrated that vitamin D could improve the effect of GCs to alleviate the level of IL-6 induced by LPS via the TLR4/NF-κB pathway in human respiratory epithelial cells.
Mucolytic and Antioxidant Effects of Intranasal Acetylcysteine Use on Acute Rhinosinusitis in Rats with an Acute Rhinosinusitis Model
Authors: Savran Fatih , Karabulut Burak , Yılmaz Aslı Sahin , Surmeli Mehmet , Guler Eray Metin , Genc Semra , Ihvan Aysenur
Published: June 2022

Introduction: The aim of this study was to investigate whether N-acetylcysteine (NAC) is effective in the treatment murine model of acute rhinosinusitis in rats. Materials and Methods: Twelve rats were included in the study. The left nasal cavity of all rats was infected with Streptococcus pneumoniae. Group 1 was the group in which NAC was administered into the left nasal cavity twice daily. Group 2 was selected as the control group. All rats were then sterilely sacrificed under anesthesia after intracardiac blood sampling. After sacrifice, sterile culture samples were collected from the posterior nasal cavity. Results: Total oxidant status and oxidative stress index (OSI), interleukin 1β, interleukin 6, and tumor necrosis factor α levels decreased significantly in the treatment group. Total antioxidant status was significantly increased. There was a statistically significant increase in total serum thiol levels and native thiol levels. Histopathologic evaluation showed a statistically significant decrease in submucosal gland hypertrophy in the treatment group. Conclusion: According to our study, intranasal application of NAC can decrease the inflammatory findings in murine acute rhinosinusitis.
Automated CT Perfusion Detection of the Acute Infarct Core in Ischemic Stroke: A Systematic Review and Meta-Analysis
Authors: Lim Nicholas E. , Chia Benjamin , Bulsara Max K. , Parsons Mark , Hankey Graeme J. , Bivard Andrew
Published: June 2022

Introduction: In patients with acute ischemic stroke, the location and volume of an irreversible infarct core determine prognosis and treatment. We aimed to determine if automated CT perfusion (CTP) is non-inferior to diffusion-weighted imaging (DWI) or fluid-attenuated inversion recovery (FLAIR) in predicting the acute infarct core. Methods: In this systematic review and meta-analysis, we searched MEDLINE and EMBASE from 1960 to December 2020. Five outcome measures were examined: volumetric difference, volumetric correlation, sensitivity and specificity at the patient level, Dice coefficient, and sensitivity and specificity at the voxel level. A random-effects meta-analysis was performed for volumetric difference and correlation. Results: From 3,986 studies retrieved, 48 studies met our inclusion criteria with 46 studies on anterior circulation, one study on posterior circulation, and one study on lacunar infarct strokes. In anterior circulation stroke, there were no significant mean volumetric differences between CTP and acute DWI (cerebral blood flow [CBF] 0.52 mL, 95% CI [−0.07, 1.11], I2 0.0%; relative CBF [rCBF] 3.01 mL, 95% CI [−0.46, 6.48], I2 82.6%; relative cerebral blood volume [rCBV] −12.84 mL, 95% CI [−38.56, 12.88], I2 96.2%) and between CTP and delayed DWI or FLAIR (rCBF −1.29 mL, 95% CI [−6.49, 3.92], I2 91.8%; rCBV −5.80 mL, 95% CI [−16.20, 4.60], I2 84.2%). Mean correlation between CTP and acute DWI was 0.90 (95% CI [0.80, 0.95], I2 60.0%) for rCBF and 0.84 (95% CI [0.58, 0.94], I2 93.5%) for rCBV. Mean correlation between CTP and delayed DWI or FLAIR was 0.74 (95% CI [0.57, 0.85], I2 94.6%) for rCBF and 0.90 (95% CI [0.69, 0.97], I2 93.1%) for rCBV. Sensitivity and specificity at the patient level were reported by three studies and Dice coefficient by four studies. Statistical analysis could not be performed for sensitivity and specificity at the voxel level. Limited evidence was available for posterior circulation or lacunar infarct strokes. Conclusion: Due to significant heterogeneity and insufficient high-quality studies reporting each outcome, there is insufficient evidence to reliably determine the accuracy of CTP prediction of the infarct core compared to DWI or FLAIR.
The Contribution of Complement Protein C1q in COVID-19 and HIV Infection Comorbid with Preeclampsia: A Review
Authors: Govender Sumeshree , Naicker Thajasvarie
Published: June 2022

Dysregulation in component 1q (C1q) levels is associated with weak placental development in preeclampsia (PE). Human immunodeficiency virus infection (HIV-1) triggers the C1q complex, resulting in opsonization of healthy host cells, contributing to their removal, and augmented progression of HIV disease. In coronavirus disease 2019 (COVID-19)-infected patients, the deposition of C1q activates the complement. Considering the paucity of data, this review highlights a significant gap in the potential of C1q in the immunocompromised state of preeclamptic HIV-infected women and COVID-19 infection. In PE, C1q is downregulated; while in antiretroviral treatment-treated HIV/COVID-19 infected patients, C1q is upregulated. It is plausible that C1q is augmented in the triad and may exacerbate severity of disease. This thereby provides a foundation for future intended research which involves the investigation of single nucleotide polymorphism expression of the C1q gene, specifically in these diseases.
The Impact of Radiofrequency Wide Circumferential Pulmonary Vein Isolation on Left Atrial Geometry in Patients with Recurrent Atrial Fibrillation
Authors: Iliodromitis Konstantinos E. , Silva Etel , Van Camp Guy , Geelen Peter , De Potter Tom
Published: June 2022

Purpose: The aim of the study was to investigate the effect of wide area circumferential radiofrequency catheter ablation (WACA) pulmonary vein isolation on left atrium (LA) geometry. Methods: Seventy-one patients underwent WACA, for recurrent paroxysmal (n = 31) and persistent (n = 40) atrial fibrillation (AF). A three-dimension rotational angiography of the LA was obtained immediately prior to index and repeat procedure. Results: Significant reduction of LA volume (65.6 ± 14 mL/m2 vs. 62.2 ± 15 mL/m2, p < 0.001) and surface (74.4 ± 11.2 vs. 70.4 ± 11.2 cm2/m2, p < 0.001) was noted. LA sphericity increased significantly (82 ± 2% vs. 83 ± 2%, p = 0.004) in all 71 patients. Patients with paroxysmal AF showed significant reduction of LA volume (121.8 ± 25.7 vs. 116 ± 32 mL, p = 0.008) and increase of LA sphericity (82.3 ± 2.1 vs. 83.1 ± 2%, p = 0.009). Patients with persistent AF showed significant decrease of LA volume (133.5 ± 32 vs. 126 ± 32 mL, p = 0.005) and LA surface area (76.3 ± 12.3 vs. 71.8 ± 12.4 cm2/m2, p = 0.005). LA sphericity (82.4 ± 2.8 vs. 83 ± 2.4%, p = ns) remained unchanged. Conclusions: WACA results into significant reduction of LA volume and surface area. Increased LA sphericity is observed in paroxysmal AF only.
Identification of a Novel Mutation in Patients with Type A Insulin Resistance Syndrome
Authors: Zhao Liling , Dai Hongmei , Zhang Qin , Hu Wenmu , Jin Ping
Published: June 2022

Introduction: Type A insulin resistance syndrome is a rare type of congenital insulin resistance often caused by heterozygous mutations in the insulin receptor gene (INSR). The aim of this study was to explore the clinical and genetic characteristics of three patients with type A insulin resistance syndrome from two Chinese families. Methods: The peripheral blood samples were collected from each family member. Whole-exome sequencing was performed on three patients. Results: Patient #1 was diagnosed with hyperinsulinemia at the age of 11 years and presented with hirsutism, acanthosis nigricans, and polycystic ovaries by 13 years. A heterozygous c.3470A>G mutation in the INSR gene was identified in patient #1. Patient #2 was a 13-year-old girl who presented with insulin resistance, polycystic ovary, and hyperandrogenemia. A novel c.3601C>G INSR mutation was identified in patient #2. Co-segregated analysis showed that the c.3601C>G mutation was also found in her father, who had hyperinsulinemia and diabetes mellitus, which was consistent with autosomal dominant inheritance. SIFT and PolyPhen-2 predicted that the c.3470A>G and c.3601C>G mutations in INSR had damaging effects. Conclusion: Our study expands the genotypic and phenotypic spectrum of type A insulin resistance syndrome. Awareness of the clinical features coupled with INSR gene screening is key to early detection and active intervention.
Lack of Prognostic Value of Pretreatment Neutrophil-to-Lymphocyte Ratio in Early Breast Cancer
Authors: Sifón Maria del Rosario , Marcolini Nicolas , Barber Maria Julia , Mclean Ignacio , Rizzo Manglio , Rivero Sergio , Costanzo Maria Victoria , Nervo Adrian , Crimi Gabriel , Perazzo Florencia , Levy Estrella Mariel , Mandó Pablo
Published: June 2022

Background: Breast cancer is a highly heterogeneous disease with large differences in the risk of recurrence. An elevated neutrophil-to-lymphocyte ratio (NLR) is correlated with a poor prognosis in a variety of tumors, and although it is still controversial in breast cancer, there are multiple studies, including meta-analysis, suggesting this. The purpose of this study was to analyze the prognostic value of preoperative NLR in an Argentine population of patients with nonmetastatic breast cancer, not exposed to neoadjuvant treatment. Methods: Retrospective multicenter cohort study that includes patients over 18 years of age from three centers in the city and province of Buenos Aires who have had surgery for early breast cancer between January 1, 1999, and December 31, 2014. Based on the previous literature, a cutoff value of 2.0 was defined. Results: A total of 791 patients were eligible for the analysis. Median age was 55 years (IQR 45–65). Median NLR was 1.92 (IQR 1.50–2.56). The distribution of groups according to the 8th edition of the AJCC was 54.1% for stage I, 35.6% stage II, and 10.4% stage III. Among the different tumor phenotypes, 79.0% were HR+/HER2−, 11.4% were HR+ or−/HER2+, and 9.2% were HR−/HER2−. With a median follow-up of 5.3 years, 112 patients (14.2%) had disease recurrence. Stage III patients had a higher NLR than stage I and stage II patients (p = 0.002). The rest of the clinical and pathological characteristics did not show differences in the groups according to NLR. There were no differences in relapse-free survival according to the NLR (p = 0.37), and itdid not change after adjusting for other prognostic variables. Conclusion: We consider it is important to determine the efficacy of prognostic markers that are easily accessible and of simple, systematic application. However, NLR does not appear to be an independent prognostic factor for recurrence in our population. In this sense, we consider it is important to publish negative results in order to avoid publication bias.
Development and Preliminary Validation of the Questionnaire “Evaluation of the Constitution of Social Circles” in Patients Treated for Cancer of the Upper Aerodigestive Tract
Authors: Balaguer Mathieu , Pommée Timothy , Pinquier Julien , Farinas Jérôme , Woisard Virginie , Sordes Florence
Published: June 2022

Purpose: The constitution of social circles around patients treated for cancer of the upper aerodigestive tract (UADT) has a major influence on factors that affect quality of life (QOL) but is poorly assessed, mainly due to a lack of tools. The objective of this study is to develop a questionnaire that assesses the constitution of social circles in a population treated for UADT cancer and to analyze the construct (structural and clinical validity) and criterion validity. Methods: The Evaluation of the Constitution of Social Circles (ECSC) questionnaire was developed in French by a committee of experts. Structural validity was analyzed using inter-item correlations. The scores of a group of patients treated for UADT cancer were compared with those of a group of healthy subjects (clinical validity). For criterion validity, the ECSC scores were compared to those from various questionnaires that assess social functioning (QFS), psychological status (HAD), perceived speech impairment (PHI), and QOL (EORTC QLQ-H&N35) in patients. Results: Structural validity shows low to moderate inter-item correlations which is consistent with the construction of the questionnaire not assessing underlying concepts. Clinical validity was satisfactory regarding the frequency of contact (p = 0.01), satisfaction with the frequency of contact in the private circle (p = 0.03), and the size of the social circles of family and friends (p ≤ 0.01). Criterion validity was adequate with moderate correlations between the ECSC scores and the QFS sub-scores of interest (rs > 0.56, p < 0.05). Anxiety (HAD) had a low correlation (|rs| = 0.46, p < 0.05) with satisfaction with exchanges and the frequency of contact with family. Satisfaction with exchanges with the private circle was moderately correlated with the EORTC QLQ-H&N35 score (rs = 0.56, p = 0.01) and showed a negative trend on the PHI (rs < −0.39, p ≥ 0.05). Conclusion: While the test-retest reliability is yet to be evaluated and the sample size should be increased, this preliminary study shows that the ECSC is a valid tool for assessing the constitution of social circles in patients treated for UADT cancer. It highlights the links between social circles and their functional impact on communication and QOL.
Ambientalismo e desenvolvimento sustentado, nova ideologia/utopia do desenvolvimento
Authors: Ribeiro Gustavo Lins
Published: June 2022

Este artigo busca interpretações alternativas adequadas para a compreensão de problemas contemporâneos, tais como o ambientalismo. A noção de desenvolvimento, uma das idéias básicas da cultura moderna europeia ocidental, tem se mostrado tão elástica que se tornou vazia. Este trabalho procura analisar as mudanças da noção de desenvolvimento que se fizeram sob o influxo das transformações econômicas, sociais e políticas da contemporaneidade.
Predictors of Recurrent Stroke After Embolic Stroke of Undetermined Source in the RE‐SPECT ESUS Trial
Authors: Del Brutto Victor J. , Diener Han‐Christoph , Easton J. Donald , Granger Christopher B. , Cronin Lisa , Kleine Eva , Grauer Claudia , Brueckmann Martina , Toyoda Kazunori , Schellinger Peter D. , Lyrer Philippe , Molina Carlos A. , Chutinet Aurauma , Bladin Christopher F. , Estol Conrado J. , Sacco Ralph L.
Published: June 2022

Background

We sought to determine recurrent stroke predictors among patients with embolic strokes of undetermined source (ESUS).

Methods and Results

We applied Cox proportional hazards models to identify clinical features associated with recurrent stroke among participants enrolled in RE‐SPECT ESUS (Randomized, Double‐Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source) trial, an international clinical trial evaluating dabigatran versus aspirin for patients with ESUS. During a median follow‐up of 19 months, 384 of 5390 participants had recurrent stroke (annual rate, 4.5%). Multivariable models revealed that stroke or transient ischemic attack before the index event (hazard ratio [HR], 2.27 [95% CI, 1.83–2.82]), creatinine clearance <50 mL/min (HR, 1.69 [95% CI, 1.23–2.32]), male sex (HR, 1.60 [95% CI, 1.27–2.02]), and CHA
2
DS
2
‐VASc ≥4 (HR, 1.55 [95% CI, 1.15–2.08] and HR, 1.66 [95% CI, 1.21–2.26] for scores of 4 and ≥5, respectively) versus CHA
2
DS
2
‐VASc of 2 to 3, were independent predictors for recurrent stroke.

Conclusions

In RE‐SPECT ESUS trial, expected risk factors previously linked to other common stroke causes were associated with stroke recurrence. These data help define high‐risk groups for subsequent stroke that may be useful for clinicians and for researchers designing trials among patients with ESUS.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT02239120.