bluuebunny/crossref_metadata_2025 huggingface dataset:
Circulating DNA in patients undergoing loco-regional treatment of colorectal cancer metastases: a systematic review and meta-analysis
Authors: Callesen Louise B. , Takacova Tana , Hamfjord Julian , Würschmidt Florian , Oldhafer Karl J. , Brüning Roland , Arnold Dirk , Spindler Karen-Lise G.
Published: November 2022

Background:

Loco-regional treatment strategies of colorectal cancer (CRC) metastases are evolving, but biological markers that can benefit patients and assist physicians in clinical decisions are lacking. The primary objective of this systematic review and meta-analysis is to investigate the current knowledge on circulating DNA and its clinical utility in predicting outcomes in patients undergoing loco-regional treatment of CRC metastases.

Methods:

A systematic search of PubMed, Embase, and Cochrane Central Register of Controlled Trials was conducted on March 22, 2022. We included studies on patients undergoing loco-regional treatment of CRC metastases reporting the predictive or prognostic value of circulating DNA in the blood. Hazard ratios (HR) were pooled in separate random-effects meta-analyses to investigate if pre- or post-ablation measurements of circulating DNA were associated with survival. The risk of bias was assessed according to the Quality in Prognosis Studies tool.

Results:

Twenty-eight studies with 2868 patients were included, of which 16 studies were eligible for meta-analyses. As expected in this new research field, a majority of included studies ( n = 21/28) had a high risk of bias in at least one domain. Circulating DNA above the cutoff in a plasma sample taken before loco-regional treatment was associated with a short recurrence-free survival [pooled HR = 2.8, 95% confidence interval (CI) 1.4–5.7, n = 162] and overall survival (pooled HR = 4.7, 95% CI 1.1–20.6, n = 105). Circulating DNA above the cutoff in a plasma sample taken after loco-regional treatment was associated with a short recurrence-free survival (pooled HR = 4.5, 95% CI 3.4–6.1, n = 569) and overall survival (pooled HR = 7.5, 95% CI 2.0–27.3, n = 161). There was limited data on the association between dynamics in circulating DNA and outcome.

Conclusions:

Measurements of circulating DNA can be valuable when selecting and monitoring patients undergoing loco-regional treatment of CRC metastases. Studies designed to investigate the true clinical utility of circulating DNA in the context of various ablation modalities are warranted. The review has been registered at PROSPERO (ID: CRD42022320032)
The short-term effects of intravitreal bevacizumab injection on intraocular pressure, cornea, iridocorneal angle, and anterior chamber
Authors: Gumus Gulsah , Berhuni Mustafa , Ozturkmen Cem
Published: November 2022

Background:

Transient increase in intraocular pressure (IOP), changes in anterior chamber parameters, and changes in aqueous humor dynamics may occur after intravitreal injections because of intravitreal volume changes.

Objective:

In this observational study, we investigated the early effects of intravitreal bevacizumab (IVB) injection on IOP, central corneal thickness (CCT), corneal volume (CV), anterior chamber depth (ACD), and iridocorneal angle (ICA).

Method:

The patients who had one single-dose IVB (2.5 mg/0.1 mL) injection were included in the study. The patients underwent IOP, CCT, CV, ACD, and ICA measurements before and 1 h and 1 day after the injection. Pre-injection and post-injection values were compared.

Results:

Forty-two eyes of 42 patients were included in the study, and the mean age of patients was 60.1 ± 7.4 years. The mean IOP measurements before and after injection at 1 h and day 1 were 15 ± 2.4, 17.4 ± 2.4, and 14.7 ± 2.3, respectively. The mean IOP, CCT, and CV values 1 h after injection were significantly higher than pre-injection values ( p < 0.05, p < 0.05, and p = 0.02, respectively). Conversely, mean ACD and ICA values 1 h after injection were significantly lower than pre-injection values ( p = 0.01 for both). There were no statistically significant differences on the first day after injection for all parameters.

Conclusion:

IVB (2.5 mg/0.1 mL) injection causes transient increases in IOP and transient decreases in ACD and ICA at the first hour after injection. Related to elevation in IOP, CCT and CV may increase transiently. These changes return to baseline values on the first day after injection.
Comparative Evaluation of Freshly Prepared Versus Freeze-Dried Human Amniotic Membrane in Intraoral Soft Tissue Defects
Authors: Mathur Mrinalini , Aurora Jitender Kumar , Tandon Parul , Chauhan Himanshu , Mishra Priyatam
Published: November 2022

Aim:

The aim of the study is to evaluate the efficacy in treatment outcome while using freshly prepared human amniotic membrane against freeze dried human amniotic membrane in intraoral soft tissue defects.

Method:

This prospective study included 20 patients having postsurgical soft tissue defect requiring primary wound coverage with human amniotic membrane. Patients were divided randomly into 2 groups. In group A, freshly prepared human amniotic membrane was placed, while in group B, freeze-dried human amniotic membrane was placed. Patients were evaluated on the basis of following parameters: postoperative pain, swelling, rate of epithelialization, and interincisal distance over a period of 6 months.

Result:

The results showed no significant difference in the mean of the pain between both the groups except on the first postoperative day. No significant difference in terms of reduction in swelling and increase in interincisal distance postoperatively was found at any point while using either fresh or freeze-dried human amniotic membrane. Significant difference was found in the mean rate of epithelialization between the groups on the 7th and the 21st postoperative days.

Conclusion:

Thus, we conclude that freshly prepared human amniotic membrane in comparison to the freeze-dried human amniotic membrane accelerates epithelialization and healing when used in the repair of postsurgical oral mucosal defects.
Multidimensional Sleep and Cardiometabolic Risk Factors for Type 2 Diabetes: Examining Self-Report and Objective Dimensions of Sleep
Authors: Matricciani Lisa , Paquet Catherine , Dumuid Dorothea , Lushington Kurt , Olds Tim
Published: November 2022

Purpose:

The purpose of the study was to determine the association between objective and self-report measures of sleep and cardiometabolic risk factors for type 2 diabetes.

Methods:

This study examines data on Australian adults, collected as part of the Child Health CheckPoint study. Sleep was examined in terms of actigraphy-derived sleep duration, timing, efficiency and variability; and self-report trouble sleeping. Cardiometabolic risk factors for type 2 diabetes were examined in terms of body mass index and biomarkers of inflammation and dyslipidemia. Generalized estimating equations, adjusted for geographic clustering, were used to determine the association between measures of sleep and cardiometabolic risk factors.

Results:

Complete case analysis was conducted for 1017 parents (87% mothers). Both objective and self-report measures of sleep were significantly but weakly associated with cardiometabolic risk factors.

Conclusion:

Both objective and self-report measures of sleep are significantly associated with cardiometabolic risk factors for type 2 diabetes. Self-report troubled sleep is associated with poorer cardiometabolic health, independent of actigraphy-derived sleep parameters.
Seeing Inside: How Stigma and Recognition Shape Community Health Worker Home Visits in São Paulo, Brazil
Authors: Pingel Emily S
Published: November 2022

Community Health Worker (CHW) home visits are central to primary care provision in São Paulo, Brazil. Yet CHWs receive little training prior to conducting these visits. In the neighborhood where I conducted ethnographic fieldwork, nearly half of patients were immigrants to Brazil, adding a layer of sociocultural and linguistic difference. I thus investigated how interactions between CHWs and patients unfolded and were shaped by cultural processes. Analyzing fieldnotes and interview data, I found that CHWs cherished relationships with older adult Portuguese-speaking patients, while expressing exasperation and even disgust with more recent immigrants and patients living with stigmatized health conditions. The cultural processes of recognition and stigma shaped CHWs’ perceptions of and interactions with patients. I ground these analyses in the history of state-sponsored discourse linking immigrants with poor hygiene, concluding that home visits deserve greater scrutiny as a public health tool that may increase access to care at the expense of health equity.
Alternative Avenues for Collaborating With Special Education Paraprofessionals
Authors: Grimsby Rachel
Published: November 2022

There are many barriers to collaborative planning between music educators and special education paraprofessionals (SEPs). While allocated collaborative planning time would be best, the reality for many music educators and SEPs is that they are not given this time. I provide three alternatives to collaborative planning that were suggested by music educators and SEPs who participated in an informal learning community. Suggestions for advocacy as well as an advocacy sidebar are provided.
Single-cell methods in myeloproliferative neoplasms: old questions, new technologies
Authors: O’Sullivan Jennifer Mary , Mead Adam J. , Psaila Bethan
Published: November 2022

Myeloproliferative neoplasms (MPN) are a group of clonal stem cell–derived hematopoietic malignancies driven by aberrant Janus kinase-signal transducer and activator of transcription proteins (JAK/STAT) signaling. Although these are genetically simple diseases, MPNs are phenotypically heterogeneous, reflecting underlying intratumoral heterogeneity driven by the interplay of genetic and nongenetic factors. Their evolution is determined by factors that enable certain cellular subsets to outcompete others. Therefore, techniques that resolve cellular heterogeneity at the single-cell level are ideally placed to provide new insights into MPN biology. With these insights comes the potential to uncover new approaches to predict the clinical course and treat these cancers, ultimately improving outcomes for patients. MPNs present a particularly tractable model of cancer evolution, because most patients present in an early disease phase and only a small proportion progress to aggressive disease. Therefore, it is not surprising that many groundbreaking technological advances in single-cell omics have been pioneered by their application in MPNs. In this review article, we explore how single-cell approaches have provided transformative insights into MPN disease biology, which are broadly applicable across human cancers, and discuss how these studies might be swiftly translated into clinical pathways and may eventually underpin precision medicine.
C1Q labels a highly aggressive macrophage-like leukemia population indicating extramedullary infiltration and relapse
Authors: Yang Li-Xue , Zhang Cheng-Tao , Yang Meng-Ying , Zhang Xue-Hong , Liu Hong-Chen , Luo Chen-Hui , Jiang Yue , Wang Zhang-Man , Yang Zhong-Yin , Shi Zhao-Peng , Yang Yi-Ci , Wei Ruo-Qu , Zhou Li , Mi Jun , Zhou Ai-Wu , Yao Zhi-Rong , Xia Li , Yan Jin-Song , Lu Ying
Published: November 2022

Extramedullary infiltration (EMI) is a concomitant manifestation that may indicate poor outcome of acute myeloid leukemia (AML). The underlying mechanism remains poorly understood and therapeutic options are limited. Here, we employed single-cell RNA sequencing on bone marrow (BM) and EMI samples from a patient with AML presenting pervasive leukemia cutis. A complement C1Q+ macrophage-like leukemia subset, which was enriched within cutis and existed in BM before EMI manifestations, was identified and further verified in multiple patients with AML. Genomic and transcriptional profiling disclosed mutation and gene expression signatures of patients with EMI that expressed high levels of C1Q. RNA sequencing and quantitative proteomic analysis revealed expression dynamics of C1Q from primary to relapse. Univariate and multivariate analysis demonstrated adverse prognosis significance of C1Q expression. Mechanistically, C1Q expression, which was modulated by transcription factor MAF BZIP transcription factor B, endowed leukemia cells with tissue infiltration ability, which could establish prominent cutaneous or gastrointestinal EMI nodules in patient-derived xenograft and cell line–derived xenograft models. Fibroblasts attracted migration of the C1Q+ leukemia cells through C1Q–globular C1Q receptor recognition and subsequent stimulation of transforming growth factor β1. This cell-to-cell communication also contributed to survival of C1Q+ leukemia cells under chemotherapy stress. Thus, C1Q served as a marker for AML with adverse prognosis, orchestrating cancer infiltration pathways through communicating with fibroblasts and represents a compelling therapeutic target for EMI.
Therapeutic activity of GARP:TGF-β1 blockade in murine primary myelofibrosis
Authors: Lecomte Sara , Devreux Julien , de Streel Grégoire , van Baren Nicolas , Havelange Violaine , Schröder David , Vaherto Noora , Vanhaver Christophe , Vanderaa Christophe , Dupuis Noémie , Pecquet Christian , Coulie Pierre G. , Constantinescu Stefan N. , Lucas Sophie
Published: November 2022

Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by the clonal expansion of myeloid cells, notably megakaryocytes (MKs), and an aberrant cytokine production leading to bone marrow (BM) fibrosis and insufficiency. Current treatment options are limited. TGF-β1, a profibrotic and immunosuppressive cytokine, is involved in PMF pathogenesis. While all cell types secrete inactive, latent TGF-β1, only a few activate the cytokine via cell type–specific mechanisms. The cellular source of the active TGF-β1 implicated in PMF is not known. Transmembrane protein GARP binds and activates latent TGF-β1 on the surface of regulatory T lymphocytes (Tregs) and MKs or platelets. Here, we found an increased expression of GARP in the BM and spleen of mice with PMF and tested the therapeutic potential of a monoclonal antibody (mAb) that blocks TGF-β1 activation by GARP-expressing cells. GARP:TGF-β1 blockade reduced not only fibrosis but also the clonal expansion of transformed cells. Using mice carrying a genetic deletion of Garp in either Tregs or MKs, we found that the therapeutic effects of GARP:TGF-β1 blockade in PMF imply targeting GARP on Tregs. These therapeutic effects, accompanied by increased IFN-γ signals in the spleen, were lost upon CD8 T-cell depletion. Our results suggest that the selective blockade of TGF-β1 activation by GARP-expressing Tregs increases a CD8 T-cell-mediated immune reaction that limits transformed cell expansion, providing a novel approach that could be tested to treat patients with myeloproliferative neoplasms.
Regulation of iron homeostasis by hepatocyte TfR1 requires HFE and contributes to hepcidin suppression in β-thalassemia
Authors: Xiao Xia , Moschetta Gillian A. , Xu Yang , Fisher Allison L. , Alfaro-Magallanes Víctor M. , Dev Som , Wang Chia-Yu , Babitt Jodie L.
Published: November 2022

Transferrin receptor 1 (TfR1) performs a critical role in cellular iron uptake. Hepatocyte TfR1 is also proposed to influence systemic iron homeostasis by interacting with the hemochromatosis protein HFE to regulate hepcidin production. Here, we generated hepatocyte Tfrc knockout mice (Tfrcfl/fl;Alb-Cre+), either alone or together with Hfe knockout or β-thalassemia, to investigate the extent to which hepatocyte TfR1 function depends on HFE, whether hepatocyte TfR1 impacts hepcidin regulation by serum iron and erythropoietic signals, and its contribution to hepcidin suppression and iron overload in β-thalassemia. Compared with Tfrcfl/fl;Alb-Cre− controls, Tfrcfl/fl;Alb-Cre+ mice displayed reduced serum and liver iron; mildly reduced hematocrit, mean cell hemoglobin, and mean cell volume; increased erythropoietin and erythroferrone; and unchanged hepcidin levels that were inappropriately high relative to serum iron, liver iron, and erythroferrone levels. However, ablation of hepatocyte Tfrc had no impact on iron phenotype in Hfe knockout mice. Tfrcfl/fl;Alb-Cre+ mice also displayed a greater induction of hepcidin by serum iron compared with Tfrcfl/fl;Alb-Cre− controls. Finally, although acute erythropoietin injection similarly reduced hepcidin in Tfrcfl/fl;Alb-Cre+ and Tfrcfl/fl;Alb-Cre− mice, ablation of hepatocyte Tfrc in a mouse model of β-thalassemia intermedia ameliorated hepcidin deficiency and liver iron loading. Together, our data suggest that the major nonredundant function of hepatocyte TfR1 in iron homeostasis is to interact with HFE to regulate hepcidin. This regulatory pathway is modulated by serum iron and contributes to hepcidin suppression and iron overload in murine β-thalassemia.
Dasatinib/prednisone induction followed by blinatumomab/dasatinib in Ph+ acute lymphoblastic leukemia
Authors: Advani Anjali S. , Moseley Anna , O’Dwyer Kristen M. , Wood Brent L. , Park Jae , Wieduwilt Matthew , Jeyakumar Deepa , Yaghmour George , Atallah Ehab L. , Gerds Aaron T. , O'Brien Susan M. , Liesveld Jane L. , Othus Megan , Litzow Mark , Stone Richard M. , Sharon Elad , Erba Harry P.
Published: November 2022

Novel treatment strategies are needed for the treatment of Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL) in older patients. This trial evaluated the feasibility and outcomes with the anti-CD19 bispecific T-cell–engaging antibody, blinatumomab, in combination with dasatinib and steroids. Patients 65 years of age or older with Ph+ or Ph-like ALL (with dasatinib-sensitive fusions/mutations) were eligible and could be newly diagnosed or relapsed/refractory. Induction therapy consisted of dasatinib/prednisone. Patients not achieving response by day 56 proceeded to blinatumomab reinduction therapy. Patients achieving response with induction or reinduction therapy proceeded to blinatumomab/dasatinib postremission therapy for 3 cycles followed by dasatinib/prednisone maintenance. All patients received central nervous system prophylaxis with intrathecal methotrexate for a total of 8 doses. Response was assessed at days 28, 56, and 84 and at additional time points based on response parameters. Measurable residual disease was assessed centrally by 8-color flow cytometry at day 28. A total of 24 eligible patients with newly diagnosed Ph+ ALL were enrolled with a median age of 73 years (range, 65-87 years). This combination was safe and feasible. With a median of 2.7 years of follow-up, 3-year overall survival and disease-free survival were 87% (95% confidence interval [CI], 64-96) and 77% (95% CI, 54-90), respectively. Although longer follow-up is needed, these results are encouraging, and future trials are building on this backbone regimen. This trial was registered at www.clinicaltrials.gov as #NCT02143414.
Clinical outcomes associated with NPM1 mutations in patients with relapsed or refractory AML
Authors: Issa Ghayas C. , Bidikian Aram , Venugopal Sangeetha , Konopleva Marina , DiNardo Courtney D. , Kadia Tapan M. , Borthakur Gautam , Jabbour Elias , Pemmaraju Naveen , Yilmaz Musa , Short Nicholas J. , Maiti Abhishek , Sasaki Koji , Masarova Lucia , Pierce Sherry , Takahashi Koichi , Tang Guilin , Loghavi Sanam , Patel Keyur , Andreeff Michael , Bhalla Kapil , Garcia-Manero Guillermo , Ravandi Farhad , Kantarjian Hagop , Daver Naval
Published: November 2022

Mutations in Nucleophosmin 1 (NPM1) are associated with a favorable prognosis in newly diagnosed acute myeloid leukemia (AML), however, their prognostic impact in relapsed/refractory (R/R) settings are unknown. In a retrospective analysis, we identified 206 patients (12%) with mutated NPM1 (NPM1c) and compared their outcomes to 1516 patients (88%) with NPM1 wild-type (NPM1wt). NPM1c was associated with higher rates of complete remission or complete remission with incomplete count recovery compared with NPM1wt following each line of salvage therapy (first salvage, 56% vs 37%; P < .0001; second salvage, 33% vs 22%; P = .02; third salvage, 24% vs 14%; P = .02). However, NPM1 mutations had no impact on relapse-free survival (RFS) and overall survival (OS) with each salvage therapy with a median OS following salvage 1, 2 or 3 therapies in NPM1c vs NPM1wt of 7.8 vs 6.0; 5.3 vs 4.1; and 3.5 vs 3.6 months, respectively. Notably, the addition of venetoclax to salvage regimens in patients with NPM1c improved RFS and OS (median RFS, 15.8 vs 4.6 months; P = .05; median OS, 14.7 vs 5.9 months; P = .02). In conclusion, NPM1 mutational status has a minimal impact on prognosis in relapsed or refractory AML; therefore, novel treatment strategies are required to improve outcomes in this entity.
The effects on asthmatics of exposure to a conventional water-based and a volatile organic compound-free paint
Authors: Beach  , Raven J , Ingram C , Bailey M , Johns D , Walters EH , Abramson M
Published: November 2022

The water-based paints now frequently used for house painting still contain small amounts of volatile organic compounds (VOCs), with the potential to exacerbate symptoms of asthma. Because of these potential problems and environmental concerns, some manufacturers have produced paints with no VOC content. We wished to compare the effects on asthmatics of conventional water-based paint and the new VOC-free paint. Seventeen asthmatics were recruited on the basis of having previously reported exacerbation of symptoms by paint or other odours. Each undertook a standard painting task with identically coloured conventional acrylic and VOC-free paints in a double-blind, crossover study. Respiratory symptoms, lung function, and airway responsiveness were measured at each visit. A significant increase in reported "wheeze" was detected during use of conventional paint (p<0.01), but not with the new paint. There was also a significantly greater increase in reported "breathlessness" whilst using conventional paint than with the new paint (p<0.05). In contrast, lung function measurements showed a small but significant increase during the use of both paints (p<0.05). There was no significant change in airway responsiveness after use of either paint. The new paint appears to be less likely to cause a worsening of respiratory symptoms than conventional acrylic paint, although this difference is not reflected in measurements of lung function or airway responsiveness. Although the benefit conferred in the majority of asthmatics is probably modest, there may be some patients with an increased sensitivity to paint odour, who would derive a useful symptomatic benefit from using the VOC-free paint.
Tuberculosis in asylum seekers in Belgium. VRGT (Flemish Lung and Tuberculosis Association)
Authors: Van den Brande P , Uydebrouck M , Vermeire P , Demedts M
Published: November 2022

Countries with a low incidence of tuberculosis have recently been faced with the problem of tuberculosis (TB) in asylum seekers from countries with a high TB prevalence. We report on the tuberculosis case notification rate (TBCNR) in Belgium in 1993, and on the results of active screening in a group of asylum seekers. The TBCNR in Belgium in 1993 increased slightly to 14.9 per 100,000, mainly due to the nonindigenous population. The highest TBCNR (312 per 100,000) was reported among the 26,882 asylum seekers staying in Belgium in 1993. Of all new asylum seekers admitted in 1993, 4,794 agreed to undergo radiographic screening for TB at entry, of whom 123 had a chest radiograph which was suspect. Among the 123, 67 could be further investigated, and, of these, 19 cases (28%) of active TB were detected; this represents a TBCNR of 396 per 100,000 when referred to the 4,794 asylum seekers screened. In addition, 56 asylum seekers with suspect chest radiograph were lost to further investigation. From the present results it appears that: 1) in Belgium, asylum seekers constitute an important risk group for TB, with a TBCNR after screening which is approximately 30 times that in the indigenous population; and 2) there is a deficient follow-up after first screening, generating the risk of transmission of TB within the community. Our recommendations are, therefore, that in all asylum seekers screening for tuberculosis should be mandatory and follow-up of active tuberculosis should be regulated.
Effect of inhaled beclomethasone dipropionate on isocapnic hyperventilation with cold air in asthmatics, measured with forced oscillation technique
Authors: Pennings HJ , Wouters EF
Published: November 2022

Isocapnic hyperventilation with cold air (IHCA) is a reliable technique for assessing indirect bronchial hyperresponsiveness in patients with asthma. Impedance measurement of the respiratory system by the forced pseudorandom noise oscillation technique is a sensitive technique to assess changes in bronchial tone after IHCA. The aim of this study was to evaluate the effect of 6 weeks of treatment with beclomethasone dipropionate, 1,000 microg x day-1, on IHCA in asthmatic patients, measured with both forced oscillation technique and flow-volume recordings. Forty patients with mild asthma were included in this double-blind, placebo-controlled parallel-group study. Stratification on the basis of sex was performed to overcome differences in airway diameter. At entry and every 2 weeks during the treatment period, IHCA was performed and patient diaries were evaluated. Characteristic changes in forced oscillation parameters after IHCA were observed in all patients. After 6 weeks of treatment, BDP-treated patients showed statistically significant differences in impedance measurements after IHCA, manifested by significant attenuation of resistance at 8 Hz (p<0.01), slope of the frequency-resistance curve (p<0.01), reactance at 8 Hz (p=0.01), and resonant frequency (f0) (p<0.02). Flow-volume recordings showed only a statistically significant change in the decrease of inspiratory vital capacity (IVC) (p=0.01). Furthermore, a significant correlation was observed between serum immunoglobulin E (IgE) levels and the effect of BDP on IHCA, measured with forced oscillation technique. In this study, beclomethasone dipropionate, 1,000 microg x day(-1) for 6 weeks, decreased indirect bronchial hyperresponsiveness as assessed by cold air bronchoprovocation in asthmatic patients. The forced oscillation technique proved a more sensitive method of detecting changes in bronchial tone than flow-volume recordings.
Effect of hyperinflation on the diaphragm
Authors: De Troyer A
Published: November 2022

Acute hyperinflation causes the inspiratory muscles to operate at shorter than normal lengths. The ability of these muscles, in particular the diaphragm, to lower intrathoracic pressure is therefore reduced. Skeletal muscles, however, adapt to chronic shortening, and animals models of emphysema have shown that with chronic hyperinflation, the diaphragmatic muscle fibres lose sacromeres. As a result, the force-generating ability of these fibres is relatively preserved. In patients with hyperinflation due to chronic obstructive pulmonary disease, the ability of the diaphragm to generate pressure is also better than anticipated on the basis of hyperinflation alone. However, the diaphragm in these patients is also lower in the chest wall than in healthy subjects. Consequently, even though the neural drive to the muscle is greater than normal, its ability to descend during inspiration is impaired. Its rib cage expanding action is also reduced; in patients with severe hyperinflation, contraction of the diaphragm even produces deflation, rather than expansion, of the rib cage. In such patients, therefore, the ability of the diaphragm to increase lung volume is reduced, and hence the act of breathing is more dependent on the rib cage inspiratory muscles.
Transudative effusions
Authors: Kinasewitz GT
Published: November 2022

Transudative pleural effusions develop because the distribution of hydrostatic and oncotic pressure across the pleura is altered, so that the rate of pleural fluid formation exceeds that of its reabsorption. They are characterized by a low cell and protein content. Congestive heart failure is the most common cause of transudative effusion. The fluid that accumulates in a hepatic hydrothorax, urinothorax, during peritoneal dialysis, and in many patients with nephrotic syndrome may also have the characteristics of a transudate. The development of a transudative effusion indicates that the pleural membranes per se are intact, so that if the underlying problem can be corrected, the effusion will be reabsorbed.
Chylothorax complicating a thoracic aortic aneurysm
Authors: Gil-Suay V , Martinez-Moragon E , de Diego A , Sanchis J
Published: November 2022

Chylothorax is an uncommon condition, usually associated with advanced malignant disease or trauma to the thoracic duct. Idiopathic chylothorax and other diverse causes have been anecdotally reported. We describe a rare case of chylothorax, developing as a result of damage to the thoracic duct by a thoracic aortic aneurysm. Tetracycline pleurodesis was successful in controlling the chylous effusion.
Effects of four different methods of sampling arterial blood and storage time on gas tensions and shunt calculation in the 100% oxygen test
Authors: Smeenk FW , Janssen JD , Arends BJ , Harff GA , van den Bosch JA , Schonberger JP , Postmus PE
Published: November 2022

At the present time, plastic syringes are most commonly used for collecting arterial blood. The oxygen tension of the arterial blood (Pa,O2) in these syringes may fall. We studied the effect of the type of syringe, metabolism, and storage time on the arterial oxygen pressures measured and on the pulmonary shunt calculated. In 10 patients, 2-3 h after aortacoronary bypass surgery, a 100% oxygen test was performed. Four arterial blood gas samples were withdrawn from each patient in random order, two in glass syringes and two in plastic syringes. One glass and one plastic syringe were stored at room temperature (RT), and the others were stored in ice-water (IW). Each sample was analysed as soon as possible, and repeated 15, 30, 60 and 120 min after sampling. The Pa,O2 measurement in blood in the glass syringe in IW measured as soon as possible after sampling was considered the "gold standard". Pulmonary shunt calculations were performed using the results of the various blood gas analyses. Compared with the "gold standard", all of the other methods showed significant deterioration in the Pa,O2 measurement. The effect due to diffusion was 0.05 kPa x min(-1), and that due to metabolism 0.11 kPa x min(-1). The Pa,O2 in the glass syringes stored in IW remained stable with time. The pulmonary shunt was significantly overestimated when the "gold standard" blood gas results were not used (range 0.8-9.9%). Glass (not plastic) syringes should be used in the 100% oxygen test. The syringe should be cooled immediately, even when the sample is analysed as soon as possible.
Prognostic factors in restoration of pulmonary flow after submassive pulmonary embolism: a multiple regression analysis
Authors: Menendez R , Nauffal D , Cremades MJ
Published: November 2022

Defects as evaluated by lung perfusion scans may persist even 6 months after pulmonary embolism (PE), when treatment is withdrawn. The aim of this study was to evaluate the effect of several potential factors on the resolution of lung perfusion defects, both during the first days and at 6 months, when patients were discharged. In a retrospective follow-up cohort study we included 102 patients with PE, diagnosed lung from a ventilation/perfusion (V'/Q') scan, following Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) criteria, together with a phlebographic study of lower extremities or angiography. Lung perfusion scan was performed at diagnosis, and in two follow-up evaluations, at 7-10 days and at 6 months. Potential factors studied were: age; sex; presence of underlying cardiac or pulmonary disease; venous insufficiency; alveolar-arterial pressure difference for oxygen; delay in diagnosis; abnormalities in electrocardiogram or chest radiograph; and the size of defects as shown in lung perfusion scans. All factors were studied with regards to the size of the defects at the two follow-up evaluations, through a univariate statistical analysis and two multiple stepwise regression analysis. Multivariate statistical analysis selected four factors: size of defects at diagnosis; prior cardiopulmonary disease; delay in diagnosis; and sex, as synergistic variables to predict defect size at 7-10 days. On the other hand, the defect size at 7-10 days was the only variable selected as a predictor of the size of defects at 6 months. Resolution of pulmonary defects during the first days after diagnosis of pulmonary embolism is influenced by the initial defect size, prior cardiopulmonary diseases and sex. The size of residual defects at 6 months depends mainly on the size of defects at 7-10 days.
Short-term effect of winter air pollution on respiratory health of asthmatic children in Paris
Authors: Segala C , Fauroux B , Just J , Pascual L , Grimfeld A , Neukirch F
Published: November 2022

There is controversy as to whether low levels of air pollution affect the symptoms and lung function in asthma. We addressed this by examining the short-term effects of winter air pollution on childhood asthma in Paris. We performed a 6 month follow-up of 84 medically diagnosed asthmatic children classified into two groups of severity. The outcomes included incidence and prevalence of asthma attacks, symptoms and use of supplementary beta2-agonists, peak expiratory flow (PEF) value and its variability. The statistical analysis controlled the lack of independence between daily health outcomes, trends and meteorology. Air pollution was associated with an increase in reports and duration of asthma attacks and asthma-like symptoms in mild asthmatic children. The strongest association was the risk of asthma attack for an increase of 50 microg x m(-3) of sulphur dioxide (SO2) on the same day (odds ratio (OR)=2.86). Maximum reduction in morning peak expiratory flow (PEF) (5%) and maximum increase in PEF variability (2%) were observed at a lag of 3 days for an increase of 50 microg x m(-3) of SO2 in the subgroup of mild asthmatics receiving no regular inhaled medication. In moderate asthmatic children, the duration of supplementary beta2-agonist use was strongly associated with air pollution. The general pattern of our results provides evidence of the effect of the low levels of air pollution encountered in Western Europe on symptoms and lung function in childhood asthma.
Acute asthma epidemics, weather and pollen in England, 1987-1994
Authors: Newson R , Strachan D , Archibald E , Emberlin J , Hardaker P , Collier C
Published: November 2022

Recent epidemics of acute asthma have caused speculation that, if their causes were known, early warnings might be feasible. In particular, some epidemics seemed to be associated with thunderstorms. We wondered what risk factors predicting epidemics could be identified. Daily asthma admissions counts during 1987-1994, for two age groups (0-14 yrs and > or = 15 yrs), were measured using the Hospital Episodes System (HES). Epidemics were defined as combinations of date, age group and English Regional Health Authority (RHA) with exceptionally high asthma admission counts compared to the predictions of a log-linear autoregression model. They were compared with control days 1 week before and afterwards, regarding seven meteorological variables and 5 day average pollen counts for four species. Fifty six asthma epidemics were identified. The mean density of sferics (lightning flashes), temperature and rainfall on epidemic days were greater than those on control days. High sferics densities were overrepresented in epidemics. Simultaneously high sferics and grass pollen further increased the probability of an epidemic, but only to 15% (95% confidence interval 2-45%). Two thirds of epidemics were not preceded by thunderstorms. Thunderstorms and high grass pollen levels precede asthma epidemics more often than expected by chance. However, most epidemics are not associated with thunderstorms or unusual weather conditions, and most thunderstorms, even following high grass pollen levels, do not precede epidemics. An early warning system based on the indicators examined here would, therefore, detect few epidemics and generate an unacceptably high rate of false alarms.
Calcium ATPase and respiratory muscle function
Authors: Aubier M , Viires N
Published: November 2022

The sarcoplasmic reticulum (SR) of striated muscle is a highly specialized intracellular membrane system that plays a key role in the contraction-relaxation cycle of muscle. Its primary function is the regulation of cytoplasmic Ca2+ concentration. A key element in this regulation is the Sarco(endo)plasmic reticulum Ca2+-adenosine triphosphatase (SERCA), which by sequestering Ca2+ into the SR, induces and maintains relaxation. It has been extensively studied with respect to structure and mechanism of action, and more recently to gene expression. Three separate genes encode five SERCA isoforms, two of which, SERCA 1 and SERCA 2, are expressed in skeletal muscle. In the first part of this review we focus on the general properties of the Ca2+ pump (structure and function and regulation of activity). In the second part we describe variations in SERCA expression in various physiological and pathological situations. These have essentially been studied in the heart and skeletal muscles, with data in respiratory muscles being very limited.
Prevalence, risk factors and treatments for post-COVID-19 breathlessness: a systematic review and meta-analysis
Authors: Zheng Bang , Daines Luke , Han Qing , Hurst John R. , Pfeffer Paul , Shankar-Hari Manu , Elneima Omer , Walker Samantha , Brown Jeremy S. , Siddiqui Salman , Quint Jennifer K. , Brightling Christopher E. , Evans Rachael A. , Wain Louise V. , Heaney Liam G. , Sheikh Aziz
Published: November 2022

Persistent breathlessness >28 days after acute COVID-19 infection has been identified as a highly debilitating post-COVID symptom. However, the prevalence, risk factors, mechanisms and treatments for post-COVID breathlessness remain poorly understood. We systematically searched PubMed and Embase for relevant studies published from 1 January 2020 to 1 November 2021 (PROSPERO registration number: CRD42021285733) and included 119 eligible papers. Random-effects meta-analysis of 42 872 patients with COVID-19 reported in 102 papers found an overall prevalence of post-COVID breathlessness of 26% (95% CI 23–29) when measuring the presence/absence of the symptom, and 41% (95% CI 34–48) when using Medical Research Council (MRC)/modified MRC dyspnoea scale. The pooled prevalence decreased significantly from 1–6 months to 7–12 months post-infection. Post-COVID breathlessness was more common in those with severe/critical acute infection, those who were hospitalised and females, and was less likely to be reported by patients in Asia than those in Europe or North America. Multiple pathophysiological mechanisms have been proposed (including deconditioning, restrictive/obstructive airflow limitation, systemic inflammation, impaired mental health), but the body of evidence remains inconclusive. Seven cohort studies and one randomised controlled trial suggested rehabilitation exercises may reduce post-COVID breathlessness. There is an urgent need for mechanistic research and development of interventions for the prevention and treatment of post-COVID breathlessness.
Onset of the COVID-19 pandemic reduced active time in patients with implanted cardiac devices
Authors: Sommers Nicholas , Berger Marcie , Rubenstein Jason C. , Roth James , Pan Amy , Thompson Colton , Widlansky Michael E.
Published: November 2022

Background

Physical inactivity and sedentary behavior are modifiable risk factors for chronic disease and all-cause mortality that may have been negatively impacted by the COVID-19 shutdowns.

Methods

Accelerometry data was retrospectively collected from 332 permanent pacemaker (PPM) and 244 implantable cardiac defibrillation (ICD) patients for 6 time points: March 15-May 15, 2020 (pandemic period), January 1-March 14, 2020, October 1-December 31, 2019, March 15-May 15, 2019, January 1-March 14, 2019, and October 1-December 31, 2018. Paired t-tests, with Bonferroni correction, were used to compare time periods.

Results

Activity significantly decreased during the pandemic period compared to one year prior by an average of 0.53 ± 1.18h/day (P < 0.001) for PPM patients and 0.51 ± 1.2h/day (P < 0.001) for ICD patients. Stratification of subjects by active time (< 2 versus ≥ 2h/day) showed patients with < 2h, particularly those with ICDs, had modestly greater activity reductions with the pandemic onset. Logistical regression analyses suggest a trend toward a greater reduction in active time at the onset of the pandemic and an increased risk of hospital or emergency department (ED) admission for PPM patients, but not ICD patients.

Conclusion

The onset of the pandemic in the United States was associated with a significant drop in PPM and ICD patient active hours that was modestly more pronounced in less active patients and cannot be explained by one year of aging or seasonal variation. If sustained, these populations may experience excess cardiovascular morbidity.
Comparative transcriptome analysis of resistant and susceptible Kentucky bluegrass varieties in response to powdery mildew infection
Authors: Zhang Yujuan , Dong Wenke , Zhao Chunxu , Ma Huiling
Published: November 2022

Background

Poa pratensis is one of the most common cold-season turfgrasses used for urban turf building, and it is also widely used in ecological environment management worldwide. Powdery mildew is a common disease of P. pratensis. To scientifically and ecologically control lawn powdery mildew, the molecular mechanism underlying the response of P. pratensis to powdery mildew infection must better understood.

Results

To explore molecular mechanism underlying the response of P. pratensis to powdery mildew infection, this study compared physiological changes and transcriptomic level differences between the highly resistant variety ‘BlackJack’ and the extremely susceptible variety ‘EverGlade’ under powdery mildew infection conditions. We analyzed DEGs using reference canonical pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, and the results showed that “starch and sucrose metabolism”, “photosynthesis” and “fatty acid metabolism”pathways were only enriched in ‘BlackJack’, and the expression of DEGs such as HXK, INV, GS, SS, AGpase and β-amylase in “starch and sucrose metabolism” pathway of ‘BlackJack’ were closely related to powdery mildew resistance. Meanwhile, compared with ‘EverGlade’, powdery mildew infection promoted synthesis of sucrose, expression of photosynthesis parameters and photosynthesis-related enzymes in leaves of ‘BlackJack’ and decreased accumulation of monosaccharides such as glucose and fructose.

Conclusions

This study identified the key metabolic pathways of a P. pratensis variety with high resistance to powdery mildew infection and explored the differences in physiological characteristics and key genes related to sugar metabolism pathways under powdery mildew stress. These findings provide important insights for studying underlying molecular response mechanism.
Plastome phylogenomic analysis reveals evolutionary divergences of Polypodiales suborder Dennstaedtiineae
Authors: Lu Jin-Mei , Du Xin-Yu , Kuo Li-Yaung , Ebihara Atsushi , Perrie Leon R. , Zuo Zheng-Yu , Shang Hui , Chang Yi-Han , Li De-Zhu
Published: November 2022

Background

Polypodiales suborder Dennstaedtiineae contain a single family Dennstaedtiaceae, eleven genera, and about 270 species, and include some groups that were previously placed in Dennstaedtiaceae, Hypolepidaceae, Monachosoraceae, and Pteridaceae. The classification and phylogenetic relationships among these eleven genera have been poorly understood. To explore the deep relationships within suborder Dennstaedtiineae and estimate the early diversification of this morphologically heterogeneous group, we analyzed complete plastomes of 57 samples representing all eleven genera of suborder Dennstaedtiineae using maximum likelihood and Bayesian inference.

Results

The phylogenetic relationships of all the lineages in the bracken fern family Dennstaedtiaceae were well resolved with strong support values. All six genera of Hypolepidoideae were recovered as forming a monophyletic group with full support, and Pteridium was fully supported as sister to all the other genera in Hypolepidoideae. Dennstaedtioideae (Dennstaedtia s.l.) fell into four clades with full support: the Microlepia clade, the northern Dennstaedtia clade, the Dennstaedtia globulifera clade, and the Dennstaedtia s.s. clade. Monachosorum was strongly resolved as sister to all the remaining genera of suborder Dennstaedtiineae. Based on the well resolved relationships among genera, the divergence between Monachosorum and other groups of suborder Dennstaedtiineae was estimated to have occurred in the Early Cretaceous, and all extant genera (and clades) in Dennstaedtiineae, were inferred to have diversified since the Late Oligocene.

Conclusion

This study supports reinstating a previously published family Monachosoraceae as a segregate from Dennstaedtiaceae, based on unique morphological evidence, the shady habitat, and the deep evolutionary divergence from its closest relatives.
The effect of varying inhaled oxygen concentrations of high-flow nasal cannula oxygen therapy during gastroscopy with propofol sedation in elderly patients: a randomized controlled study
Authors: Zhang Wenwen , Yin Hailing , Xu Yajie , Fang Zhaojing , Wang Wanling , Zhang Chen , Shi Hongwei , Wang Xiaoliang
Published: November 2022

Background

Despite evidence that high-flow nasal cannula oxygen therapy (HFNC) promotes oxygenation, its application in sedated gastroscopy in elderly patients has received little attention. This study investigated the effect of different inhaled oxygen concentrations (FiO2) of HFNC during sedated gastroscopy in elderly patients.

Methods

In a prospective randomized single-blinded study, 369 outpatients undergoing regular gastroscopy with propofol sedation delivered by an anesthesiologist were randomly divided into three groups (n = 123): nasal cannula oxygen group (Group C), 100% FiO2 of HFNC group (Group H100), and 50% FiO2 of HFNC (Group H50). The primary endpoint in this study was the incidence of hypoxia events with pulse oxygen saturation (SpO2) ≤ 92%. The secondary endpoints included the incidence of other varying degrees of hypoxia and adverse events associated with ventilation and hypoxia.

Results

The incidence of hypoxia, paradoxical response, choking, jaw lift, and mask ventilation was lower in both Group H100 and Group H50 than in Group C (P < 0.05). Compared with Group H100, Group H50 showed no significant differences in the incidence of hypoxia, jaw lift and mask ventilation, paradoxical response, or choking (P > 0.05). No patients were mechanically ventilated with endotracheal intubation or found to have complications from HFNC.

Conclusion

HFNC prevented hypoxia during gastroscopy with propofol in elderly patients, and there was no significant difference in the incidence of hypoxia when FiO2 was 50% or 100%.

Trial registration

This single-blind, prospective, randomized controlled trial was approved by the Ethics Committee of Nanjing First Hospital (KY20201102-04) and registered in the China Clinical Trial Center (20/10/2021, ChiCTR2100052144) before patients enrollment. All patients signed an informed consent form.