bluuebunny/crossref_metadata_2025_split huggingface dataset:
Measurement of the Total Lung Volume Using an Adjusted Single-Breath Helium Dilution Method in Patients With Obstructive Lung Disease
Authors: Liu Qing , Zhou Lingxiao , Feng Peiling , Liu Jinkai , Shen Bin , Huang Lili , Wang Yingying , Zou Yimin , Xia Yang , Huang Gang 
Published: September 2021

Background: Whole-body plethysmography (WBP) is the gold standard for measuring lung volume, but its clinical application is limited as it requires expensive equipment and is not simple to use. Studies have shown that the single-breath helium dilution (SBHD) method, which is commonly used in clinical practice, significantly underestimates lung volume in patients with obstructive lung disease (OLD). By comparing the differences in lung volume measured using SBHD and WBP, we aimed to establish a correction equation for the SBHD method to determine the total lung volume in patients with OLD of different severities.Methods: From 628 patients with OLD simultaneously subjected to SBHD and WBP, 407 patients enrolled between January 2018 and November 2019 were in the training group and 221 enrolled between December 2019 and December 2020 were in the prospective verification cohort. The multiple linear regression equation was used for data in the training group to establish a correction equation for SBHD to determine the total lung volume, and this was validated in the prospective validation cohort.Results: There was a moderate positive correlation between total lung capacity (TLC) determined using the SBHD [TLC (SBHD)] and WBP methods [TLC (WBP)] (r = 0.701; P &lt; 0.05), and the differences between TLC (SBHD) and TLC (WBP) (ΔTLC) were related to the severity of obstruction. As the severity of obstruction increased, the TLC was underestimated by the SBHD method. We established the following correction equation: TLC (adjusted SBHD) (L) = −0.669 + 0.756*TLC(SBHD)(L) – 0.047*FEV1FVC+0.039*height (cm)–0.009*weight(kg)(r2 = 0.753 and adjusted r2 = 0.751). Next, we validated this equation in the validation cohort. With the correction equation, no statistical difference was observed between TLC (adjusted SBHD) and TLC (WBP) among the obstruction degree groups (P &gt; 0.05).Conclusions: The SBHD method is correlated with WBP to measure the total lung volume, but the SBHD method presents limitations in determining the total lung volume in patients with obstructive lung disease. Here, we established an effective and reliable correction equation in order to accurately assess the total lung volume of patients with OLD using the SBHD method.
Design and Rationale of a Prospective International Follow-Up Study on Intensive Care Survivors of COVID-19: The Long-Term Impact in Intensive Care Survivors of Coronavirus Disease-19–AFTERCOR
Authors: Wildi Karin , Li Bassi Gianluigi , Barnett Adrian , Panigada Mauro , Colombo Sebastiano M. , Bandera Alessandra , Muscatello Antonio , McNicholas Bairbre , Laffey John G. , Battaglini Denise , Robba Chiara , Torres Antoni , Motos Ana , Luna Carlos M. , Rainieri Fernando , Hodgson Carol , Burrell Aidan J. C. , Buscher Hergen , Dalton Heidi , Cho Sung-Min , Choi Huimahn Alex , Thomson David , Suen Jacky , Fraser John F. 
Published: September 2021

Background: In a disease that has only existed for 18 months, it is difficult to be fully informed of the long-term sequelae of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Evidence is growing that most organ systems can be affected by the virus, causing severe disabilities in survivors. The extent of the aftermath will declare itself over the next 5–10 years, but it is likely to be substantial with profound socio-economic impact on society.Methods: This is an international multi-center, prospective long-term follow-up study of patients who developed severe coronavirus disease-2019 (COVID-19) and were admitted to Intensive Care Units (ICUs). The study will be conducted at international tertiary hospitals. Patients will be monitored from time of ICU discharge up to 24 months. Information will be collected on demographics, co-existing illnesses before ICU admission, severity of illness during ICU admission and post-ICU quality of life as well as organ dysfunction and recovery. Statistical analysis will consist of patient trajectories over time for the key variables of quality of life and organ function. Using latent class analysis, we will determine if there are distinct patterns of patients in terms of recovery. Multivariable regression analyses will be used to examine associations between baseline characteristics and severity variables upon admission and discharge in the ICU, and how these impact outcomes at all follow-up time points up to 2 years.Ethics and Dissemination: The core study team and local principal investigators will ensure that the study adheres to all relevant national and local regulations, and that the necessary approvals are in place before a site may enroll patients.Clinical Trial Registration:anzctr.org.au: ACTRN12620000799954.
Altered Coupling Between Resting-State Cerebral Blood Flow and Functional Connectivity Strength in Cervical Spondylotic Myelopathy Patients
Authors: Wei Wuzeng , Wang Tao , Abulizi Tuersong , Li Bing , Liu Jun 
Published: September 2021

Background: Changes in regional neural activity and functional connectivity in cervical spondylotic myelopathy (CSM) patients have been reported. However, resting-state cerebral blood flow (CBF) changes and coupling between CBF and functional connectivity in CSM patients are largely unknown.Methods: Twenty-seven CSM patients and 24 sex/age-matched healthy participants underwent resting-state functional MRI and arterial spin labeling imaging to compare functional connectivity strength (FCS) and CBF between the two groups. The CBF–FCS coupling of the whole gray matter and specific regions of interest was also compared between the groups.Results: Compared with healthy individuals, CBF–FCS coupling was significantly lower in CSM patients. The decrease in CBF–FCS coupling in CSM patients was observed in the superior frontal gyrus, bilateral thalamus, and right calcarine cortex, whereas the increase in CBF–FCS coupling was observed in the middle frontal gyrus. Moreover, low CBF and high FCS were observed in sensorimotor cortices and visual cortices, respectively.Conclusion: In general, neurovascular decoupling at cortical level may be a potential neuropathological mechanism of CSM.
The Common Neurological Presentations and Clinical Outcomes of Coronavirus Disease 2019 in Saudi Arabia
Authors: Alkeridy Walid A. , Alanazy Mohammed H. , Alamri Nada , Alqahtani Awyshah , Alhazzani Adel , Muayqil Taim 
Published: September 2021

Background: Neurological manifestations have increasingly become recognized in COVID-19. People from different ethnic backgrounds are experiencing different outcomes related to SARS-CoV-2 infection. Several cohort studies reported the common neurological manifestations and complications associated with COVID-19 disease around the world however, the prevalence of neurological complications associated with SARS-CoV-2 infection in the Arab countries and Saudi Arabia is still unknown.Objective: To study the prevalence, risk factors, and characteristics of the neurological complications associated with COVID-19 and their relationship with clinical outcomes.Methods: We conducted a prospective, single-center, observational, cohort study of consecutive hospitalized adults COVID-19 patients with and without neurological manifestation admitted between March 2020 until the end of December 2020. Data was collected prospectively using electronic medical records; Cases and controls were observed until they either get discharged from the hospital or died. The primary outcomes were death, survival, and survival with sequalae.Results: Among 497 patients with COVID-19, 118 patients (23.7%) had neurological complications, 94 patients (18.9%) had encephalopathy, and 16 patients (3.2%) had cerebrovascular accidents (CVA). Patients with COVID-19-related neurological complications were older and more likely to have a pre-existing neurological disease. The most common neurological syndrome associated with COVID-19 were encephalopathy (18.9%) and headache (13.7%). Pre-existing neurological disease and an elevated neutrophil count were the strongest predictors of developing any neurological complications. Death form COVID-19 was associated with age (OR 1.06, 95% CI 1.02–1.10, P = 0.001), invasive ventilation (OR 37.12, 95% CI 13.36–103.14), COVID-19-related-neurological complications (OR 3.24, 95% CI 1.28–8.21, P = 0.01), and elevated CRP level (OR 1.01, 95% CI 1.00–1.01, P = 0.01).Conclusions: COVID-19 is associated with a wide range of neurological manifestations in people living in Saudi Arabia, with older individuals and those with underlying neurological disorders being most at risk. The presence of neurological complications was associated with increased mortality and poor outcomes.
Eating and Lifestyle Habits in Youth With Down Syndrome Attending a Care Program: An Exploratory Lesson for Future Improvements
Authors: Roccatello Giulia , Cocchi Guido , Dimastromatteo Rosa Tullia , Cavallo Alessandra , Biserni Giovanni Battista , Selicati Mariella , Forchielli Maria Luisa 
Published: September 2021

Introduction:Children with Down Syndrome (DS) have nutritional problems with unknown implications besides increased potential for obesity. Their food habits are unknown. We aim to delineate eating and lifestyle habits of DS children attending a multispecialist program to identify the challenges they face and the potential improvements.Patients and Methods:We interacted with 34 DS children (22 males, 12 females, 2–16 years old) and their families. Food habits, medical conditions and treatments, degrees of development and physical activity, anthropometric and laboratory data were recorded over 6 months and analyzed. A 3-day food diary and a 24-h recall food frequency questionnaire were administered.Results:Twenty-nine (85%) children completed meals, only 11 (32%) received alternative food such as milk. Weaning regularly started in 25 (73%) children. Preschool children introduced adequate calories and nutrients. School children and adolescents did not reach recommendations. All age groups, as the general pediatric population, excessively ate protein and saturated fat, and preferred bread, pasta, fruit juices, meat and cold cuts. Peculiarly, pulses and fish were adequately assumed by preschool and school children, respectively. Five children (15%) were overweight/obese.Conclusions:Dietary excesses commonly found in the general pediatric population are also present in this DS group, proving a narrowing gap between the two. DS group performed better nutritionally in the early years and overweight/obesity occurrence seems contained. DS children may benefit from a practical yet professional care-program in which nutrition education may improve their growth, development and transition into adulthood.
Apigenin Inhibits the Histamine-Induced Proliferation of Ovarian Cancer Cells by Downregulating ERα/ERβ Expression
Authors: Liu Manman , Zhang Yani , Xu Qiqi , Liu Guirong , Sun Na , Che Huilian , He Tao 
Published: September 2021

BackgroundApigenin (APG), a natural flavonoid, can affect the development of a variety of tumors, but its role in ovarian cancer remains unclear. There has been an increasing amount of evidence supporting the vital role played by mast cells and the bioactive mediators they release, as components of the tumor microenvironment, in the progression of ovarian cancer (OC); however, the mechanism warrants further exploration.Methods and ResultsIn this study, a combination of transcriptomics analysis and application of TCGA database was performed, and we found that the expression of genes related to mast cell degranulation in ovarian cancer tissues changed remarkably. We then explored whether histamine, a major constituent of mast cell degranulation, could affect the development of ovarian cancer through immunohistochemistry analysis and cell proliferation assays. The results showed that a certain concentration of histamine promoted the proliferation of ovarian cancer cells by upregulating the expression of estrogen receptor α (ERα)/estrogen receptor β (ERβ). Additionally, we found that the inhibition of ERα or the activation of ERβ could inhibit the proliferation of ovarian cancer cells induced by histamine through real-time PCR and western blot assays. Finally, we demonstrated the attenuation effect imparted by apigenin in histamine-mediated ovarian cancer via the PI3K/AKT/mTOR signaling pathway.ConclusionOur research revealed that apigenin decelerated ovarian cancer development by downregulating ER-mediated PI3K/AKT/mTOR expression, thus providing evidence of its applicability as a potentially effective therapeutic agent for ovarian cancer treatment.
A Phase I Trial of Dasatinib and Osimertinib in TKI Naïve Patients With Advanced EGFR-Mutant Non-Small-Cell Lung Cancer
Authors: Kim Chul , Liu Stephen V. , Crawford Jennifer , Torres Tisdrey , Chen Vincent , Thompson Jillian , Tan Ming , Esposito Giuseppe , Subramaniam Deepa S. , Giaccone Giuseppe 
Published: September 2021

BackgroundOsimertinib is an effective first-line therapy option for EGFR-mutant NSCLC, but virtually all patients develop resistance. CRIPTO, through Src activation, has been implicated in resistance to EGFR tyrosine kinase inhibitor (EGFR-TKI) therapy. Dasatinib, a Src inhibitor, has shown preclinical synergy with EGFR-TKI therapy.MethodThis is a single-arm phase I/II trial of osimertinib and dasatinib in TKI-naïve advanced EGFR-mutant NSCLC (NCT02954523). A 3 + 3 design was used in the phase I to establish the recommended phase II dose (RP2D). Osimertinib 80 mg QD was combined with dasatinib 70 mg BID (DL2), 50 mg BID (DL1), 70 mg QD (DL-1), and 50 mg QD (DL-2).ResultsTen patients (DL2: 3, DL1: 6, DL -1: 1) were enrolled. 3 (50%) of 6 patients at DL1 experienced a DLT (grade 3 headaches/body pain, neutropenia, rash, one each). Common treatment-related adverse events included pleural effusion (n=10), diarrhea (n=8), rash (n=7), transaminitis (n=7), thrombocytopenia (n=7), and neutropenia (n=7). While the MTD was not determined by protocol-defined DLT criteria, DL-2 was chosen as the RP2D, considering overall tolerability. Nine (90%) patients had a PR, including 1 unconfirmed PR. Median PFS was 19.4 months and median OS 36.1 months. The trial was closed to accrual prematurely due to slow accrual after the approval of osimertinib as first-line therapy.ConclusionsThe combination of dasatinib and osimertinib demonstrated anticancer activity. The treatment was limited by chronic toxicities mainly attributed to dasatinib. To improve the safety and tolerability of Src and EGFR co-inhibition, Src inhibitors with a more favorable safety profile should be utilized in future studies.Clinical Trial Registrationhttps://clinicaltrials.gov/ct2/show/NCT02954523
Prolonged Slow Expiration Technique and Gastroesophageal Reflux in Infants Under the Age of 1 Year
Authors: Lievens Laure , Vandenplas Yvan , Vanlaethem Sylvie , Van Ginderdeuren Filip 
Published: September 2021

Background:The Prolonged Slow Expiration Technique (PSE) is an airway clearance technique (ACT) carried out in newborn children with bronchial obstruction and hypersecretion to clear away the mucus from the respiratory tract. Evidence about the effect of PSE on gastroesophageal reflux (GER) is currently lacking in the literature. This study aimed to evaluate the influence of PSE on GER in infants under the age of 1 year.Methods:Infants were observed using multichannel intraluminal impedance-pH monitoring (MII-pH) over 24 h. During monitoring, the participants were treated with one 20 min intervention of PSE in supine position, 2 h after feeding. In this controlled trial with intra-subject design, the number of reflux episodes (REs) during PSE were compared to 20 min before and after PSE.Results:Fifty infants younger than 1 year were screened of whom 22 had a pathological GER. For the entire group, no significant difference was seen in the total number of REs between before, during, or after the PSE treatment (P= 0.76). No significant difference in total REs was found between the three measuring points (P= 0.59) in the group of infants with an abnormal MII-pH (n= 22).Conclusion:PSE does not cause a significant difference in REs in infants younger than 1 year.Registration number:NCT03341585.
A High Performance Terahertz Photoconductive Antenna Array Detector With High Synthesis Efficiency
Authors: Shi Wei , Wang Zhiquan , Hou Lei , Wang Haiqing , Wu Meilin , Li Chaofan 
Published: September 2021

A 2 × 2 terahertz photoconductive antenna (PCA) array detector with high efficiency synthesis characteristic that improves the signal-to-noise ratio (SNR) of the detected signals has been reported in this paper. By processing the substrate material through a special micromachining process, the current signal generated by the adjacent antenna elements as opposed to that generated by the antenna gap is eliminated. Experiments show that the amplitude of the current signal output by the PCA array detector is consistent with the amplitude of the synchronous superposition of the current signals output by antenna elements, and the synthesis efficiency of the device achieves 93.7%. At the same time, the antenna array detector has low current noise, and its highest SNR is 62 dB under the excitation of different light energy, which is related to the number of antenna array elements.
Phosphorylation at Serines 157 and 161 Is Necessary for Preserving Cardiac Expression Level and Functions of Sarcomeric Z-Disc Protein Telethonin
Authors: Lewis Hannah R. , Eminaga Seda , Gautel Mathias , Avkiran Metin 
Published: September 2021

Aims:In cardiac myocytes, the sarcomeric Z-disc protein telethonin is constitutively bis-phosphorylated at C-terminal residues S157 and S161; however, the functional significance of this phosphorylation is not known. We sought to assess the significance of telethonin phosphorylationin vivo, using a novel knock-in (KI) mouse model generated to express non-phosphorylatable telethonin (TcapS157/161A).Methods and Results:TcapS157/161Aand wild-type (WT) littermates were characterized by echocardiography at baseline and after sustained β-adrenergic stimulationviaisoprenaline infusion. Heart tissues were collected for gravimetric, biochemical, and histological analyses. At baseline,TcapS157/161Amice did not show any variances in cardiac structure or function compared with WT littermates and mutant telethonin remained localized to the Z-disc. Ablation of telethonin phosphorylation sites resulted in a gene-dosage dependent decrease in the cardiac telethonin protein expression level in mice carrying the S157/161A alleles, without any alteration in telethonin mRNA levels. The proteasome inhibitor MG132 significantly increased the expression level of S157/161A telethonin protein in myocytes fromTcapS157/161Amice, but not telethonin protein in myocytes from WT mice, indicating a role for the ubiquitin–proteasome system in the regulation of telethonin protein expression level.TcapS157/161Amice challenged with sustained β-adrenergic stimulationviaisoprenaline infusion developed cardiac hypertrophy accompanied by mild systolic dysfunction. Furthermore, the telethonin protein expression level was significantly increased in WT mice following isoprenaline stimulation but this response was blunted inTcapS157/161Amice.Conclusion:Overall, these data reveal that telethonin protein turnoverin vivois regulated in a novel phosphorylation-dependent manner and suggest that C-terminal phosphorylation may protect telethonin against proteasomal degradation and preserve cardiac function during hemodynamic stress. Given that human telethonin C-terminal mutations have been associated with cardiac and skeletal myopathies, further research on their potential impact on phosphorylation-dependent regulation of telethonin protein expression could provide valuable mechanistic insight into those myopathies.
Predictive Models of Maternal Harsh Parenting During COVID-19 in China, Italy, and Netherlands
Authors: Riem Madelon M. E. , Lodder Paul , Guo Jing , Vrielink-Verpaalen Michelle , van IJzendoorn Marinus H. , Bakermans-Kranenburg Marian J. , De Carli Pietro 
Published: September 2021

Background: The COVID-19 pandemic drastically impacted on family life and may have caused parental distress, which in turn may result in an overreliance on less effective parenting practices.Objective: The aim of the current study was to identify risk and protective factors associated with impaired parenting during the COVID-19 lockdown. Key factors predicting maternal harsh discipline were examined in China, Italy, and the Netherlands, using a cross-validation approach, with a particular focus on the role of allomaternal support from father and grandparents as a protective factor in predicting maternal harshness.Methods: The sample consisted of 900 Dutch, 641 Italian, and 922 Chinese mothers (age M = 36.74, SD = 5.58) who completed an online questionnaire during the lockdown.Results: Although marital conflict and psychopathology were shared risk factors predicting maternal harsh parenting in each of the three countries, cross-validation identified a unique risk factor model for each country. In the Netherlands and China, but not in Italy, work-related stressors were considered risk factors. In China, support from father and grandparents for mothers with a young child were protective factors.Conclusions: Our results indicate that the constellation of factors predicting maternal harshness during COVID-19 is not identical across countries, possibly due to cultural variations in support from fathers and grandparents. This information will be valuable for the identification of at-risk families during pandemics. Our findings show that shared childrearing can buffer against risks for harsh parenting during COVID-19. Hence, adopting approaches to build a pandemic-proof community of care may help at-risk parents during future pandemics.