bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of Dust Aerosols on Snow Cover Over the Tibetan Plateau
Authors: Zhao Dan , Chen Siyu , Chen Yu , Gong Yongqi , Lou Gaotong , Cheng Shanling , Bi Hongru 
Published: May 2022

Dust in the atmosphere and snow on the Tibetan Plateau (TP) remarkably influence the Asian climate, which can influence snow cover by changing radiative forcing. In this study, we investigated the spatial and temporal distributions of dust and snow cover over the TP from 2009 to 2018 and estimated the relative contributions of atmospheric dust and dust-on-snow to the change in snow cover over the northern TP through the use of reanalysis datasets and satellite retrievals. The results show that the high and low centers of aerosol and dust aerosol optical depth (AOD) are roughly similar. Dust concentrations over the TP generally decrease from north to south and from west to east, showing decreasing trends in the winter half-year (December to May). The correlation coefficients between the dust concentration and snow cover over the northern TP are −0.6 in spring. Dust in the atmosphere and on snow over the TP could significantly influence snow cover by changing the radiative forcing, and the influence of dust deposited on snow is greater than that in the atmosphere. Atmospheric dust reduces the surface net solar radiation by −3.84 W m−2 by absorbing shortwave radiation, decreasing the surface temperature by −2.27°C, and finally increasing the snow cover by 1.04%. However, dust deposited on snow can decrease the surface albedo by −0.004 by reducing the surface optical properties, induce surface warming at 0.42°C, and reduce snow cover by −2.00% by rapid snowmelt in the northern TP.
The Significance of Transarterial Chemo(Embolization) Combined With Tyrosine Kinase Inhibitors and Immune Checkpoint Inhibitors for Unresectable Hepatocellular Carcinoma in the Era of Systemic Therapy: A Systematic Review
Authors: Ke Qiao , Xin Fuli , Fang Huipeng , Zeng Yongyi , Wang Lei , Liu Jingfeng 
Published: May 2022

Background and AimsRegardless of great progress in early detection of hepatocellular carcinoma (HCC), unresectable HCC (uHCC) still accounts for the majority of newly diagnosed HCC with poor prognosis. With the promising results of a double combination of transarterial chemo(embolization) and tyrosine kinase inhibitors (TKIs), and TKIs and immune checkpoint inhibitors (ICIs), a more aggressive strategy, a triple combination of transarterial chemo(embolization), TKIs, and ICIs has been tried in the recent years. Hence, we aimed to conduct a systematic review to verify the safety and efficacy of the triple therapy for uHCC.MethodsPubMed, MedLine, Embase, the Cochrane Library, and Web of Knowledge were used to screen the eligible studies evaluating the clinical efficacy and safety of triple therapy for patients with uHCC up to April 25th 2022, as well as Chinese databases. The endpoints were the complete response (CR), objective response rate (ORR), disease control rate (DCR), conversion rate, progression-free survival (PFS) rate, overall survival (OS) rate, and the incidence of adverse events (AEs).ResultsA total of 15 studies were eligible with 741 patients receiving transarterial chemoembolization (TACE) or hepatic arterial infusion chemotherapy (HAIC) combined with TKIs and ICIs. The pooled rate and 95% confidence interval (CI) for CR, ORR, and DCR were 0.124 (0.069–0.190), 0.606 (0.528–0.682), and 0.885 (0.835–0.927). The pooled rates for PFS at 0.5 years and 1 year were 0.781 (0.688–0.862) and 0.387 (0.293–0.486), respectively. The pooled rates for OS at 1, 2, and 3 years were 0.690 (0.585–0.786), 0.212 (0.117–0.324), and 0.056 (0.028–0.091), respectively. In addition, the pooled rate and 95%CI for the conversion surgery was 0.359 (0.153–0.595). The subgroup analysis of control studies showed that triple therapy was superior to TACE+TKIs, TKIs+ICIs, and TKIs in CR, ORR, and DCR, conversion rate; PFS; and OS. No fatal AEs were reported, and the top three most common AEs were elevated ALT, elevated AST, and hypertension, as well as severe AEs (grading ≥3).ConclusionWith the current data, we concluded that the triple therapy of TACE/HAIC, TKIs, and ICIs would provide a clinical benefit for uHCC both in short- and long-term outcomes without increasing severe AEs, but the conclusion needs further validation.Systematic Review Registrationhttp://www.crd.york.ac.uk/PROSPERO/, Review registry: CRD42022321970.
Comparison of Global and Regional Compliance-Guided Positive End-Expiratory Pressure Titration on Regional Lung Ventilation in Moderate-to-Severe Pediatric Acute Respiratory Distress Syndrome
Authors: Ren Hong , Xie Li , Wang Zhulin , Tang Xiaoliao , Ning Botao , Teng Teng , Qian Juan , Wang Ying , Fu Lijun , Zhao Zhanqi , Xiang Long 
Published: May 2022

PurposeTo investigate the difference in the positive end-expiratory pressure (PEEP) selected with chest electrical impedance tomography (EIT) and with global dynamic respiratory system compliance (Crs) in moderate-to-severe pediatric acute respiratory distress syndrome (pARDS).MethodsPatients with moderate-to-severe pARDS (PaO2/FiO2 &lt; 200 mmHg) were retrospectively included. On the day of pARDS diagnosis, two PEEP levels were determined during the decremental PEEP titration for each individual using the best compliance (PEEPC) and EIT-based regional compliance (PEEPEIT) methods. The differences of global and regional compliance (for both gravity-dependent and non-dependent regions) under the two PEEP conditions were compared. In addition, the EIT-based global inhomogeneity index (GI), the center of ventilation (CoV), and standard deviation of regional delayed ventilation (RVDSD) were also calculated and compared.ResultsA total of 12 children with pARDS (5 with severe and 7 with moderate pARDS) were included. PEEPC and PEEPEIT were identical in 6 patients. In others, the differences were only ± 2 cm H2O (one PEEP step). There were no statistical differences in global compliance at PEEPC and PEEPEIT [28.7 (2.84–33.15) vs. 29.74 (2.84–33.47) ml/cm H2O median (IQR), p = 0.028 (the significant level after adjusted for multiple comparison was 0.017)]. Furthermore, no differences were found in regional compliances and other EIT-based parameters measuring spatial and temporal ventilation distributions.ConclusionAlthough EIT provided information on ventilation distribution, PEEP selected with the best Crs might be non-inferior to EIT-guided regional ventilation in moderate-to-severe pARDS. Further study with a large sample size is required to confirm the finding.
Accelerating GPCR Drug Discovery With Conformation-Stabilizing VHHs
Authors: Laeremans Toon , Sands Zara A. , Claes Pieter , De Blieck Ann , De Cesco Stephane , Triest Sarah , Busch Andreas , Felix David , Kumar Abhinav , Jaakola Veli-Pekka , Menet Christel 
Published: May 2022

The human genome encodes 850 G protein-coupled receptors (GPCRs), half of which are considered potential drug targets. GPCRs transduce extracellular stimuli into a plethora of vital physiological processes. Consequently, GPCRs are an attractive drug target class. This is underlined by the fact that approximately 40% of marketed drugs modulate GPCRs. Intriguingly 60% of non-olfactory GPCRs have no drugs or candidates in clinical development, highlighting the continued potential of GPCRs as drug targets. The discovery of small molecules targeting these GPCRs by conventional high throughput screening (HTS) campaigns is challenging. Although the definition of success varies per company, the success rate of HTS for GPCRs is low compared to other target families (Fujioka and Omori, 2012; Dragovich et al., 2022). Beyond this, GPCR structure determination can be difficult, which often precludes the application of structure-based drug design approaches to arising HTS hits. GPCR structural studies entail the resource-demanding purification of native receptors, which can be challenging as they are inherently unstable when extracted from the lipid matrix. Moreover, GPCRs are flexible molecules that adopt distinct conformations, some of which need to be stabilized if they are to be structurally resolved. The complexity of targeting distinct therapeutically relevant GPCR conformations during the early discovery stages contributes to the high attrition rates for GPCR drug discovery programs. Multiple strategies have been explored in an attempt to stabilize GPCRs in distinct conformations to better understand their pharmacology. This review will focus on the use of camelid-derived immunoglobulin single variable domains (VHHs) that stabilize disease-relevant pharmacological states (termed ConfoBodies by the authors) of GPCRs, as well as GPCR:signal transducer complexes, to accelerate drug discovery. These VHHs are powerful tools for supporting in vitro screening, deconvolution of complex GPCR pharmacology, and structural biology purposes. In order to demonstrate the potential impact of ConfoBodies on translational research, examples are presented of their role in active state screening campaigns and structure-informed rational design to identify de novo chemical space and, subsequently, how such matter can be elaborated into more potent and selective drug candidates with intended pharmacology.
Impact of APOE ε4 Carrier Status on Associations Between Subthreshold, Positive Amyloid-β Deposition, Brain Function, and Cognitive Performance in Cognitively Normal Older Adults: A Prospective Study
Authors: Kang Dong Woo , Wang Sheng-Min , Um Yoo Hyun , Kim Nak-Young , Lee Chang Uk , Lim Hyun Kook 
Published: May 2022

BackgroundA growing body of evidence suggests a deteriorating effect of subthreshold amyloid-beta (Aβ) accumulation on cognition before the onset of clinical symptoms of Alzheimer's disease (AD). Despite the association between the Aβ-dependent pathway and the APOE ε4 allele, the impact of this allele on the progression from the subthreshold Aβ deposits to cognitive function impairment is unclear. Furthermore, the comparative analysis of positive Aβ accumulation in the preclinical phase is lacking.ObjectiveThis study aimed to explore the differential effect of the APOE ε4 carrier status on the association between Aβ deposition, resting-state brain function, and cognitive performance in cognitively normal (CN) older adults, depending on the Aβ burden status.MethodsOne hundred and eighty-two older CN adults underwent resting-state functional magnetic resonance imaging, [18F] flutemetamol (FMM) positron emission tomography, a neuropsychological battery, and APOE genotyping. We evaluated the resting-state brain function by measuring the local and remote functional connectivity (FC) and measured the remote FC in the default-mode network (DMN), central-executive network (CEN), and salience network (SN). In addition, the subjects were dichotomized into those with subthreshold and positive Aβ deposits using a neocortical standardized uptake value ratio with the cut-off value of 0.62, which was calculated with respect to the pons.ResultsThe present result showed that APOE ε4 carrier status moderated the relationship between Aβ deposition, local and remote resting-state brain function, and cognitive performance in each CN subthreshold and positive Aβ group. We observed the following: (i) the APOE ε4 carrier status-Aβ deposition and APOE ε4 carrier status-local FC interaction for the executive and memory function; (ii) the APOE ε4 carrier status-regional Aβ accumulation interaction for the local FC; and (iv) the APOE ε4 carrier status-local FC interaction for the remote inter-network FC between the DMN and CEN, contributing higher cognitive performance in the APOE ε4 carrier with higher inter-network FC. Finally, these results were modulated according to Aβ positivity.ConclusionThis study is the first attempt to thoroughly examine the influence of the APOE ε4 carrier status from the subthreshold to positive Aβ accumulation during the preclinical phase.
Motor Training After Stroke: A Novel Approach for Driving Rehabilitation
Authors: Lodha Neha , Patel Prakruti , Casamento-Moran Agostina , Christou Evangelos A. 
Published: May 2022

BackgroundA key component of safe driving is a well-timed braking performance. Stroke-related decline in motor and cognitive processes slows braking response and puts individuals with stroke at a higher risk for car crashes. Although the impact of cognitive training on driving has been extensively investigated, the influence of motor interventions and their effectiveness in enhancing specific driving-related skills after stroke remains less understood. We compare the effectiveness of two motor interventions (force-control vs. strength training) to facilitate braking, an essential skill for safe driving.MethodsTwenty-two stroke survivors were randomized to force-control training or strength training. Before and after training, participants performed a braking task during car-following in a driving simulator. We quantified the cognitive and motor components of the braking task with cognitive processing time and movement execution time.ResultsThe cognitive processing time did not change for either training group. In contrast, the movement execution became significantly faster (14%) following force-control training but not strength training. In addition, task-specific effects of training were found in each group. The force-control group showed improved accuracy and steadiness of ankle movements, whereas the strength training group showed increased dorsiflexion strength following training.ConclusionMotor intervention that trains ankle force control in stroke survivors improves the speed of movement execution during braking. Driving rehabilitation after stroke might benefit from incorporating force-control training to enhance the movement speed for a well-timed braking response.
A Preliminary Study on Change of Serum Immunoglobulin G Glycosylation in Patients With Migraine
Authors: Xu Jingwei , Wang Yuan , Han Yating , Liu Ningfeng , Liu Zhenming , Guo Huailian , Zou Xiajuan , Zhang Jun 
Published: May 2022

Background and ObjectiveMigraine is a common neurological disease, but its pathogenesis is still unclear. Previous studies suggested that migraine was related to immunoglobulin G (IgG). We intended to analyze the immune characteristics of migraine from the perspective of IgG glycosylation and provide theoretical assistance for exploring its pathogenesis.MethodsThe differences in the serum level of IgG glycosylation and glycopeptides between patients with episodic migraine and healthy controls were analyzed by applying the poly(glycerol methacrylate)@chitosan (PGMA@CS) nanomaterial in combination with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). We constructed a binary classification model with a feedforward neural network using PyTorch 1.6.0 in Python 3.8.3 to classify the episodic migraine and healthy control groups.ResultsTwenty patients with migraine and 20 healthy controls were enrolled and the blood samples and clinical information were collected. Forty-nine IgG N-glycopeptides were detected in the serum of the subjects. The serum level of N-glycopeptide IgG1 G0-NF (p = 0.012) was increased in patients with migraine. The serum level of N-glycopeptide IgG3/4 G2FS (p = 0.041) was decreased in patients with migraine with family history of headache. It was found that the serum level of the IgG1 G1 (p = 0.004) and IgG2 G0 (p = 0.045) was increased in patients with migraine with aura, while the serum level of IgG2 G0N (p = 0.043) in patients with migraine with aura was significantly lower than that in patients with migraine without aura. In addition, a linear feedforward neural network (FFNN) was used to construct a binary classification model by detected IgG N-glycopeptides. The area under the curve (AUC) value of the binary classification model, which was constructed with 7 IgG N-glycopeptides, was 0.857, suggesting a good prediction performance. Among these IgG N-glycopeptides that were constructed the model, IgG1 G0-NF was overlapped with the differential IgG N-glycopeptide between patients with migraine and healthy controls detected with MALDI-TOF-MS.ConclusionOur results indicated that the serum level of N-glycopeptides IgG1 G0-NF might be one of the important biomarkers for the diagnosis of migraine. To the best of our knowledge, this is the first study about the changes of IgG N-glycosylation in patients with migraine by the method of MALDI-TOF-MS. The results indicated a relationship between the migraine and immune response.
Impact of Early Rehabilitation on Outcomes in Patients With Acute Ischemic Stroke After Endovascular Treatment
Authors: He Yi , Nie Ximing , He Tao , Qi Xiao , Chen Zhenzhen , Duan Wei , Wei Yufei , Liu Xiran , Liu Yong 
Published: May 2022

BackgroundThis study aims to examine the effects of early rehabilitation on functional outcomes in patients with acute ischemic stroke treated with endovascular treatment (EVT).MethodsEligible patients with large vessel occlusion stroke treated with EVT, who received early rehabilitation or standard care treatment during hospitalization, were enrolled in a multicenter registration, prospective observational study, a registration study for Critical Care of Acute Ischemic Stroke After Recanalization. Early rehabilitation was defined as rehabilitation interventions initiated within 1 week after acute stroke. The primary outcome was the favorable functional outcome (defined as modified Rankin Scale scores of 0 to 2) at 90 days. Independent association between early rehabilitation and the primary outcome was investigated using multivariable logistic regression in the entire sample and in subgroups.ResultsA total of 1,126 patients (enrolled from July 2018 to May 2019) were included in the analyses, 273 (24.2%) in the early rehabilitation group and 853 (75.8%) in the standard care group. There was no significant difference in favorable functional outcomes at 90 days between the two groups (45.4 vs. 42.6%, p = 0.41). Patients in the early rehabilitation group had a lower death rate within 90 days compared with the standard care group (6.2 vs. 20.5%, p &lt; 0.01). The multivariable logistic regression analyses showed that the early rehabilitation was not significantly associated with the favorable functional outcome at 90 days (adjusted odds ratio, 1.01 [95% CI, 0.70–1.47]; p = 0.95). There was no significant difference between subgroups in the favorable functional outcome at 90 days. No significant interaction was found between subgroups.ConclusionsPatients with stroke receiving early rehabilitation had a lower death rate. However, these clinically meaningful effects of early rehabilitation did not show on functional outcome at 90 days in patients with large vessel occlusion stroke treated with EVT.RegistrationURL: http://www.chictr.org.cn; Unique identifier: ChiCTR1900022154.
The Association of Nocturnal Blood Pressure Patterns and Other Influencing Factors With Lacunes and Enlarged Perivascular Spaces in Hypertensive Patients
Authors: Gao Yang , Deng Weiping , Sun Jialan , Yue Dongqi , Zhang Bei , Feng Yulan , Han Jun , Shen Fanxia , Hu Jin , Fu Yi 
Published: May 2022

PurposeNocturnal blood pressure dipping patterns have been associated with an increased risk of Cerebral Small Vessel Disease (CSVD), which has not been well-studied. This study is aimed to explore the association of dipping patterns and other factors with lacunes and enlarged perivascular spaces (EPVS) in patients with hypertension.MethodsWe enrolled a total of 1,322 patients with essential hypertension in this study. Magnetic resonance imaging (MRI) scans and 24-h ambulatory blood pressure (BP) monitoring were completed. Nocturnal BP decline was calculated, and then dipping patterns were classified. Patients were classified into four groups according to the performance of lacunes and EPVS in the MRI scan for statistical analysis.Results(1) Nocturnal BP decline showed independent negative correlation with both lacunes and EPVS while mean systolic BP (mSBP) level showed an independent positive correlation with them (P &lt; 0.05). (2) The frequency of reverse-dippers in the control group was significantly lower than that in other groups; the frequency of non-dippers in the lacunes group and EPVS group was significantly lower than that in the control group; the frequency of extreme-dippers in the EPVS group was significantly higher than that in the mixed (lacunes with EPVS) group (P &lt; 0.05).ConclusionsBoth mSBP and dipping patterns might play an important role in developing lacunes and EPVS in patients with hypertension.
Minimal Manifestation Status Indicates a Stable State in Myasthenia Gravis: A Quantitative Study
Authors: Jiang Ping , Li Jie , Li Hong-Yan , Zhang Bin , Yue Yao-Xian , Wang Su-Yun , Zi Xi-Cun , Liu Shuang-Shuang , Li Yi-Fan , Jiao Li-Dong , Li Hai-Feng 
Published: May 2022

IntroductionMinimal manifestation (MM) or better was recommended as the treatment goal for myasthenia gravis (MG). The sustainability of this status has not been described quantitatively in patients who had attained or are close to it.MethodsPatients who were with no or slight impact on daily living were recruited and followed at baseline and 3, 6, and 12 months. The included patients were classified into 3 post-intervention status (PIS) categories: remission (R), MM, and slight impact (SI). The proportion of patients belonging to real-time (not considering the intervals between assessments) and sustained (considering the intervals between assessments) PIS categories was compared at each follow-up. A sensitivity analysis (SA) cohort was established by including patients with PIS categories in all four follow-ups. The QMGS, MG-ADL, and MG-QOL15 scores in patients belonging to each PIS category at each follow-up were compared. The sustainability of the R/MM status was examined and correlated with real-time R/MM status at follow-ups.ResultsAt baseline, 376 patients could be classified, including 55 as R (14.2%), 209 as MM (54.0%), and 112 as SI (28.9%). In the whole cohort, 68.8–89.7%, 71–76.7% and 19.8–77.1% of the patients classified into real-time R, MM, and SI categories remained unchanged in each follow-up compared with the previous follow-up. The proportion of patients belonging to each real-time or sustained R/MM status at the three follow-ups was 89.7–92.1 or 60.8–67. In the SA cohort, at least 86.4% of the baseline R/MM patients remained in R/MM status till 12 months. There were no differences in keeping real-time R/MM status at 6 or 12 months between patients with and without sustained R/MM status at 3 and 6 months. There were differences in the QMGS, MG-ADL, and MG-QOL15 scores among patients belonging to each real-time category at baseline and follow-ups, ranking as R &lt; MM &lt; SI. The same trend was observed in patients belonging to each sustained PIS category with smaller scores than the same items of real-time categories.ConclusionThe sustainability of the R/MM status was confirmed. The R/MM status indicated a stable state of MG. The QMGS, MG-ADL, and MG-QOL15 scores may provide a quantitative reference for these PIS.