bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Outcomes of Very Short Term Dual Antiplatelet Therapy in Patients With or Without Diabetes Undergoing Second-Generation Drug-Eluting Stents: A Systematic Review and Meta-Analysis of Randomized Clinical Trials
Authors: Liang Xi-Ying , Li Yan , Qiao Xuan , Zhang Wen-Jiao , Wang Zhi-Lu
Published: July 2021

Background: Patients with diabetes represent 20–30% of the population considered for percutaneous coronary intervention (PCI) and associate with more deleterious clinical outcome, which requires the optimal strategy of dual antiplatelet therapy (DAPT). The meta-analysis aims to compare clinical outcomes between very short (1–3 months) and standard (12 months) DAPT after implanting the second-generation drug-eluting stents in patients with or without diabetes following PCI.

Methods and Analysis: PubMed, Embase, Web of Science, Ovid, Cochrane Library, and ClinicalTrials.gov were searched for studies comparing the very short term and standard DAPT in patients with or without diabetes following PCI. Risk ratio with 95% confidence intervals was used to evaluate the pooled effect of discontinuous variables, and the pooled analyses were performed with RevMan 5.3 and Stata SE 14.0 software.

Results: A total of 38,864 patients were randomized to the very short term DAPT (N = 19,423) vs. standard DAPT (N = 19,441). Among them, 11,476 patients were diabetes and 27,388 patients were non-diabetes. The primary outcome of the net adverse clinical event (NACE) was significantly lower in diabetic patients with very short term DAPT (risk ratio 0.72, 95% CI 0.60–0.88, p = 0.0009). The same result was also found in the major cardiac or cerebrovascular events (MACCEs) (0.87, 0.78–0.98, p = 0.03). The risk of major or minor bleeding was significantly reduced in very short term DAPT regardless of the diabetes statue (0.69, 0.52–0.93, p = 0.01 in the diabetic group, and 0.50, 0.39–0.63, p <0.0001 in the non-diabetic group). There was no statistical difference in the incidence of major bleeding, all-cause death, cardiac death, myocardial infarction, definite or probable stent thrombosis, and stroke between the very short term DAPT (1–3 months) and standard DAPT (12 months) in patients with or without diabetes.

Conclusion: The very short term DAPT can significantly reduce the risk of the NACE and MACCE in patients with diabetes compared to standard DAPT. Meanwhile, the very short term DAPT can also reduce the incidence of major and minor bleeding without increasing the risk of ischemia in patients with or without diabetes (Registered by PROSPERO, CRD42020192133).

Systematic Review Registration:https://www.crd.york.ac.uk/prospero/, Identifier: CRD42020192133.
Comparing the Performance of Regional Earthquake Early Warning Algorithms in Europe
Authors: Zuccolo Elisa , Cremen Gemma , Galasso Carmine
Published: July 2021

Several earthquake early warning (EEW) algorithms have been developed worldwide for rapidly estimating real-time information (i.e., location, magnitude, ground shaking, and/or potential consequences) about ongoing seismic events. This study quantitatively compares the operational performance of two popular regional EEW algorithms for European conditions of seismicity and network configurations. We specifically test PRobabilistic and Evolutionary early warning SysTem (PRESTo) and the implementation of the Virtual Seismologist magnitude component within SeisComP, VS(SC), which we use jointly with the SeisComPscanlocmodule for locating events. We first evaluate the timeliness and accuracy of the location and magnitude estimates computed by both algorithms in real-time simulation mode, accounting for the continuous streaming of data and effective processing times. Then, we focus on the alert-triggering (decision-making) phase of EEW and investigate both algorithms’ ability to yield accurate ground-motion predictions at the various temporal instances that provide a range of warning times at target sites. We find that the two algorithms show comparable performances in terms of source parameters. In addition, PRESTo produces better rapid estimates of ground motion (i.e., those that facilitate the largest lead times); therefore, we conclude that PRESTo may have a greater risk-mitigation potential than VS(SC) in general. However, VS(SC) is the optimal choice of EEW algorithm if shorter warning times are permissible. The findings of this study can be used to inform current and future implementations of EEW systems in Europe.
Novel Bathymetry of Lake Afdera Reveals Fault Structures and Volcano-Tectonic Features of an Incipient Transform Zone (Afar, Ethiopia)
Authors: Schaegis Jean-Charles , Rime Valentin , Kidane Tesfaye , Mosar Jon , Gebru Ermias Filfilu , Atnafu Balemwal , Foubert Anneleen
Published: July 2021

Lake Afdera is a hypersaline endorheic lake situated at 112 m below sea-level in the Danakil Depression. The Danakil Depression is located in the northern part of the Ethiopian Afar and features an advanced stage of continental rifting. The remoteness and inhospitable environment explain the limited scientific research and knowledge about this lake. Bathymetric data were acquired during 2 weeks expeditions in January/February 2016 and 2017 using an easily deployable echosounder system mounted on an inflatable motorized boat. This study presents the first complete bathymetric map of the lake Afdera. Bathymetric results show that the lake has an average depth of 20.9 m and a total volume of 2.4 km3. The maximum measured depth is 80 m, making Lake Afdera the deepest known lake in Afar and the lowest elevation of the Danakil Depression. Comparison with historical reports shows that the lake level did not fluctuate significantly during the last 50 years. Two distinct tectonic basins to the north and the south are recognized. Faults of different orientations control the morphology of the northern basin. In contrast, the southern basin is affected by volcano-tectonic processes, unveiling a large submerged caldera. Comparison between the orientation of faults throughout the lake with the regional fault pattern indicates that the lake is part of two transfer zones: the major Alayta–Afdera Transfer Zone and the smaller Erta Ale–Tat’Ali Transfer Zone. The interaction between these Transfer Zones and the rift axis forms the equivalent of a developing nodal basin which explains the lake’s position as the deepest point of the depression. This study provides evidence for the development of an incipient transform fault on the floor of the Afar depression.
AID and APOBECs as Multifaceted Intrinsic Virus-Restricting Factors: Emerging Concepts in the Light of COVID-19
Authors: Meshcheryakova Anastasia , Pietschmann Peter , Zimmermann Philip , Rogozin Igor B. , Mechtcheriakova Diana
Published: July 2021

The AID (activation-induced cytidine deaminase)/APOBEC (apolipoprotein B mRNA editing enzyme catalytic subunit) family with its multifaceted mode of action emerges as potent intrinsic host antiviral system that acts against a variety of DNA and RNA viruses including coronaviruses. All family members are cytosine-to-uracil deaminases that either have a profound role in driving a strong and specific humoral immune response (AID) or restricting the virus itself by a plethora of mechanisms (APOBECs). In this article, we highlight some of the key aspects apparently linking the AID/APOBECs and SARS-CoV-2. Among those is our discovery that APOBEC4 shows high expression in cell types and anatomical parts targeted by SARS-CoV-2. Additional focus is given by us to the lymphoid structures and AID as the master regulator of germinal center reactions, which result in antibody production by plasma and memory B cells. We propose the dissection of the AID/APOBECs gene signature towards decisive determinants of the patient-specific and/or the patient group-specific antiviral response. Finally, the patient-specific mapping of the AID/APOBEC polymorphisms should be considered in the light of COVID-19.
Supporting Spatial Management of Data-Poor, Small-Scale Fisheries With a Bayesian Approach
Authors: Rehren Jennifer , Pennino Maria Grazia , Coll Marta , Jiddawi Narriman , Muhando Christopher
Published: July 2021

Marine conservation areas are an important tool for the sustainable management of multispecies, small-scale fisheries. Effective spatial management requires a proper understanding of the spatial distribution of target species and the identification of its environmental drivers. Small-scale fisheries, however, often face scarcity and low-quality of data. In these situations, approaches for the prioritization of conservation areas need to deal with scattered, biased, and short-term information and ideally should quantify data- and model-specific uncertainties for a better understanding of the risks related to management interventions. We used a Bayesian hierarchical species distribution modeling approach on annual landing data of the heavily exploited, small-scale, and data-poor fishery of Chwaka Bay (Zanzibar) in the Western Indian Ocean to understand the distribution of the key target species and identify potential areas for conservation. Few commonalities were found in the set of important habitat and environmental drivers among species, but temperature, depth, and seagrass cover affected the spatial distribution of three of the six analyzed species. A comparison of our results with information from ecological studies suggests that our approach predicts the distribution of the analyzed species reasonably well. Furthermore, the two main common areas of high relative abundance identified in our study have been previously suggested by the local fisher as important areas for spatial conservation. By using short-term, catch per unit of effort data in a Bayesian hierarchical framework, we quantify the associated uncertainties while accounting for spatial dependencies. More importantly, the use of accessible and interpretable tools, such as the here created spatial maps, can frame a better understanding of spatio-temporal management for local fishers. Our approach, thus, supports the operability of spatial management in small-scale fisheries suffering from a general lack of long-term fisheries information and fisheries independent data.
Soundscapes in the German Baltic Sea Before and During the Covid-19 Pandemic
Authors: Basan Fritjof , Fischer Jens-Georg , Kühnel Dennis
Published: July 2021

Anthropogenic underwater noise has been identified as one of the main pressures on the marine environment. Considerable research efforts have been made to quantify acoustic soundscapes on different spatial and temporal scales in order to identify trends and investigate how this may impact the marine environment. Measures to reduce noise input into the seas from anthropogenic sources are under discussion, including the reduction of vessel speed or re-routing of shipping lanes. The decline in maritime transport as a consequence of the Covid-19 pandemic provides an opportunity to examine the associated extent of noise reduction. Here, we present the results of a “Before-After-Control-Impact” study where we analyzed acoustic data sets from two monitoring stations in the German Baltic Sea. Data were collected between 2013 and 2020. As part of an international initiative, coordinated by the International Quiet Ocean Experiment, monthly statistics (20 average sound pressure levels per 1/3 octave bands) were calculated from acoustic data collected during the pre-pandemic period (2013–2019), and were compared with data from the year 2020, during the Covid-19 pandemic. To account for varying natural conditions the measurements were sorted into categories of same prevailing sea state. Through this approach, measurements with equivalent natural noise impact are compared and any resulting differences are likely due to the variability in the anthropogenic noise. A decline in sound pressure of 13% (1.2 dB) for low frequencies (10 Hz–1 kHz) was observed at both stations, which corresponds to the reduced level of shipping activity.
Structures, and Thermophysical Properties Characterizations of (La1-xHox)3NbO7 Solid Solutions as Thermal Barrier Coatings
Authors: Chen Lin , Wang Yitao , Zheng Qi , Feng Jing
Published: July 2021

A sequence of (La1-xHox)3NbO7 solid solutions were fabricated in this work, which were studied as candidate for thermal insulation materials. The lattices were identified via XRD, when SEM and EDS were used to characterize the microstructures and element distributions. The results showed that the highest modulus, hardness, and toughness of (La1-xHox)3NbO7 were 196 GPa, 9.2 GPa, and 1.6 MPa m1/2, respectively, and they accorded with the mechanical property requirements. Also, a low thermal conductivity (1.06 W m−1 K−1) and high thermal expansion coefficients (TECs: 11.3 × 10−6 K−1) were simultaneously realized in (La3/6Ho3/6)3NbO7, at high temperatures. No phase transition was detected up to 1,200°C, which proved their good high-temperature lattice stability. The intense anharmonic lattice vibrations might contribute to the outstanding thermal properties of (La1-xHox)3NbO7 ceramics. The suitable modulus, high hardness, low thermal conductivity, and high TECs of (La1-xHox)3NbO7 solid solutions proclaimed that they were exceptional thermal insulation ceramics.
Machine Learning Prediction Models for Mechanically Ventilated Patients: Analyses of the MIMIC-III Database
Authors: Zhu Yibing , Zhang Jin , Wang Guowei , Yao Renqi , Ren Chao , Chen Ge , Jin Xin , Guo Junyang , Liu Shi , Zheng Hua , Chen Yan , Guo Qianqian , Li Lin , Du Bin , Xi Xiuming , Li Wei , Huang Huibin , Li Yang , Yu Qian
Published: July 2021

Background: Mechanically ventilated patients in the intensive care unit (ICU) have high mortality rates. There are multiple prediction scores, such as the Simplified Acute Physiology Score II (SAPS II), Oxford Acute Severity of Illness Score (OASIS), and Sequential Organ Failure Assessment (SOFA), widely used in the general ICU population. We aimed to establish prediction scores on mechanically ventilated patients with the combination of these disease severity scores and other features available on the first day of admission.

Methods: A retrospective administrative database study from the Medical Information Mart for Intensive Care (MIMIC-III) database was conducted. The exposures of interest consisted of the demographics, pre-ICU comorbidity, ICU diagnosis, disease severity scores, vital signs, and laboratory test results on the first day of ICU admission. Hospital mortality was used as the outcome. We used the machine learning methods of k-nearest neighbors (KNN), logistic regression, bagging, decision tree, random forest, Extreme Gradient Boosting (XGBoost), and neural network for model establishment. A sample of 70% of the cohort was used for the training set; the remaining 30% was applied for testing. Areas under the receiver operating characteristic curves (AUCs) and calibration plots would be constructed for the evaluation and comparison of the models' performance. The significance of the risk factors was identified through models and the top factors were reported.

Results: A total of 28,530 subjects were enrolled through the screening of the MIMIC-III database. After data preprocessing, 25,659 adult patients with 66 predictors were included in the model analyses. With the training set, the models of KNN, logistic regression, decision tree, random forest, neural network, bagging, and XGBoost were established and the testing set obtained AUCs of 0.806, 0.818, 0.743, 0.819, 0.780, 0.803, and 0.821, respectively. The calibration curves of all the models, except for the neural network, performed well. The XGBoost model performed best among the seven models. The top five predictors were age, respiratory dysfunction, SAPS II score, maximum hemoglobin, and minimum lactate.

Conclusion: The current study indicates that models with the risk of factors on the first day could be successfully established for predicting mortality in ventilated patients. The XGBoost model performs best among the seven machine learning models.
Neurological Complications of Veno-Arterial Extracorporeal Membrane Oxygenation: A Retrospective Case-Control Study
Authors: Luo Yinan , Gu Qiao , Wen Xin , Li Yiwei , Peng Weihua , Zhu Ying , Hu Wei , Xi Shaosong
Published: July 2021

Background: To explore the epidemiology, clinical features, risk indicators, and long-term outcomes of neurological complications caused by veno-arterial extracorporeal membrane oxygenation (V-A ECMO).

Methods: We retrospectively analyzed 60 adult patients who underwent V-A ECMO support in our unit from February 2012 to August 2020. These patients were separated into the neurological complications group (NC group) and the non-neurological complications group (nNC group). The differences in basic data and ECMO data between the two groups were compared. The data of long-term neurological prognosis were collected by telephone follow-up.

Results: Thirty-nine patients (65.0%) had neurological complications. There were significant differences between the two groups in terms of median age, hypertension, median blood urea nitrogen, median troponin I (TNI), median lactic acid, pre-ECMO percutaneous coronary intervention, continuous renal replacement therapy (CRRT), median Sequential Organ Failure Assessment score, median Acute Physiology and Chronic Health Evaluation II score, median peak inspiratory pressure, median positive end expiratory pressure, and median fresh frozen plasma (P < 0.05). The median Intensive Care Unit length of stay (ICU LOS), 28-day mortality, median post-ECMO vasoactive inotropic score, non-pulsate perfusion (NP), and median ECMO duration of the NC group were significantly higher than those of the nNC group (P < 0.05). Furthermore, multiple logistic regression analysis revealed that TNI (P = 0.043), CRRT (P = 0.047), and continuous NP > 12 h (P = 0.043) were independent risk indicators for neurological complications in patients undergoing ECMO. Forty-four patients (73.3%) survived after discharge, and 38 patients (63.3%) had Cerebral Performance Category score of 1–2. And there were significant differences between the two groups in long-term neurological outcomes after discharge for 6 months (P < 0.05).

Conclusion: The incidence of neurological complications was higher in patients undergoing V-A ECMO and was closely related to adverse outcomes (including ICU LOS and 28-day mortality). TNI, CRRT, and continuous NP > 12 h were independent risk indicators for predicting neurological complications in ECMO supporting patients. And the neurological complications of patients during ECMO support had significant adverse effect on long-term surviving and neurological outcomes of patients after discharge for 6 months.
Management and Thinking on the Treatment of Cancer Patients During the COVID-19
Authors: Pan Shuangyue , Jiang Jiahong , Chen Zheling , Yang Liu
Published: July 2021

Coronavirus disease-2019 (COVID-19) has spread rapidly around the world and has become a public health emergency of international concern. The weekly epidemiological report issued by the WHO pointed out that new coronavirus variants have appeared in 131 countries and regions, which demonstrates that the current epidemic situation is still severe. As of now, the severe acute respiratory syndrome coronavirus (SARS-CoV-2) has been widespread worldwide for more than one year and poses a serious threat to the health of vulnerable groups such as those with malignancies, the elderly, and the immunocompromised. Compared with the general population, cancer patients with COVID-19 infection are more likely to have serious clinical adverse events, leading to higher mortality. There is no doubt that during the COVID-19 epidemic, whether it is with regards to how to prevent infection or how to continue anti-tumor treatment, cancer patients are in a difficult situation. Meanwhile, an international patient with malignant Hodgkin’s lymphoma who was cured after being infected with the new coronavirus surprised us, and it inspires more scientists to explore the relationship between infection, immunity, and tumors. Relevantly, through multi-disciplinary discussion, scientists put forward more new perspectives on the treatment of future tumors and the management of SARS-CoV-2 diseases. In this review, the impact of COVID-19 on cancer patients is discussed in detail and the recommendations for the diagnosis, treatment and management of cancer patients will be put forward under the challenge of the COVID-19 epidemic. Furthermore, the safety and effectiveness of the SARS-CoV-2 vaccine will be discussed, and we will also put forward our insights on cancer immunity.
Circulating CircRNAs Panel Acts as a Biomarker for the Early Diagnosis and Severity of Parkinson’s Disease
Authors: Zhong Lingling , Ju KeJu , Chen Ainian , Cao Hua
Published: July 2021

Parkinson’s disease (PD) is a chronic and progressive degenerative disease of the central nervous system. Degenerative neuropathy can occur in patients with PD even before typical clinical symptoms appear in the preclinical stage. Therefore, if the early diagnosis of degenerative diseases can be timely and the correlation with the disease progression can be explored, the disease progression will be slowed down and the quality of life of patients will be improved. In this study, the circRNA microarray was employed to screen the dysregulated circRNA in plasma samples of PD. Four circRNAs (circ_0085869, circ_0004381, circ_0017204, and circ_0090668) were obtained with increased levels in PD patients by cross comparison and preliminary verification in PD comparing with healthy controls. Further validation found the circRNA panel was consistent with the training set. The ROC curve also revealed a high diagnostic ability of circ_0004381 and circ_0017204 in predicting the early stage of PD from healthy controls. circ_0085869, circ_0004381, circ_0017204, and circ_0090668 also presented a high ability to distinguish the late stage of PD from early stage. In conclusion, circulating circRNA panel might be a potential fingerprint for predicting the early diagnosis of PD and may act as a biomarker for disease progression.
Can Task Specificity Impact tDCS-Linked to Dual Task Training Gains in Parkinson's Disease? A Protocol for a Randomized Controlled Trial
Authors: Costa-Ribeiro Adriana , Andrade Suellen Mary Marinho dos Santos , Férrer Mayane Laís Veloso , Silva Ozair Argentille Pereira Da , Salvador Maiara Llarena Silva , Smaili Suhaila , Lindquist Ana Raquel Rodrigues
Published: July 2021

Patients with Parkinson's disease (PD) have difficulties while performing dual-task activities, a condition present in everyday life. It is possible that strategies such as transcranial Direct Current Stimulation (tDCS) can be associated with motor training enriched with dual-task training to improve the performance of two concurrent tasks. Currently, it is unclear whether specific tasks and clinical conditions of PD patients have different results after the intervention. Therefore, the proposed randomized controlled trial will examine task-dependency in enhancing the effects of tDCS-linked rehabilitation training on PD and the relationships between baseline outcomes in responders and non-responders to therapy. Fifty-six patients with Parkinson's disease will be recruited to participate in this controlled, double-blind randomized multicentric clinical trial. Patients in modified Hoehn & Yahr stage 1.5–3, age between 40 and 70 years will be included. Subjects will be randomly assigned to an experimental group (EG) and a control group (CG). The EG will perform treadmill gait training associated with dual task exercises+tDCS, while the CG will only engage in treadmill gait training+tDCS. Blinded testers will assess patients before and after 12 intervention sessions and after a 4-week follow-up period. All patients will undergo a screening and an initial visit before being assessed for primary and secondary outcomes. The primary outcome measure is functional mobility measured by Timed Up and Go Test. Secondary outcomes include cognitive function, participation, motor function and body function and structure. This study will evaluate the effectiveness of an intervention protocol with tDCS, dual-task training and gait training in patients with PD. The study will also highlight the clinical factors and variability between individuals that could interfere in the training of a specific task and influence the therapeutic effect.

Clinical Trial registration: www.ClinicalTrials.gov, identifier NCT04581590.
Learning Then, Learning Now, and Every Second in Between: Lifelong Learning With a Simulated Humanoid Robot
Authors: Logacjov Aleksej , Kerzel Matthias , Wermter Stefan
Published: July 2021

Long-term human-robot interaction requires the continuous acquisition of knowledge. This ability is referred to as lifelong learning (LL). LL is a long-standing challenge in machine learning due to catastrophic forgetting, which states that continuously learning from novel experiences leads to a decrease in the performance of previously acquired knowledge. Two recently published LL approaches are the Growing Dual-Memory (GDM) and the Self-organizing Incremental Neural Network+ (SOINN+). Both are growing neural networks that create new neurons in response to novel sensory experiences. The latter approach shows state-of-the-art clustering performance on sequentially available data with low memory requirements regarding the number of nodes. However, classification capabilities are not investigated. Two novel contributions are made in our research paper: (I) An extended SOINN+ approach, called associative SOINN+ (A-SOINN+), is proposed. It adopts two main properties of the GDM model to facilitate classification. (II) A new LL object recognition dataset (v-NICO-World-LL) is presented. It is recorded in a nearly photorealistic virtual environment, where a virtual humanoid robot manipulates 100 different objects belonging to 10 classes. Real-world and artificially created background images, grouped into four different complexity levels, are utilized. The A-SOINN+ reaches similar state-of-the-art classification accuracy results as the best GDM architecture of this work and consists of 30 to 350 times fewer neurons, evaluated on two LL object recognition datasets, the novel v-NICO-World-LL and the well-known CORe50. Furthermore, we observe an approximately 268 times lower training time. These reduced numbers result in lower memory and computational requirements, indicating higher suitability for autonomous social robots with low computational resources to facilitate a more efficient LL during long-term human-robot interactions.
Revisiting the Examination of Sharp/Dull Discrimination as Clinical Measure of Spinothalamic Tract Integrity
Authors: Heutehaus Laura , Schuld Christian , Solinas Daniela , Hensel Cornelia , Kämmerer Till , Weidner Norbert , Rupp Rüdiger , Franz Steffen
Published: July 2021

Objective: Revisiting the sharp/dull discrimination as clinical measure of spinothalamic tract function considering the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI). Three clinically relevant factors were evaluated as to their impact on reliability: (1) the localization of dermatomes in relation to the sensory level, (2) the examination tool, and (3) the threshold of correct answers for grading of a preserved sharp/dull discrimination.

Design: Prospective monocentric psychometric study.

Setting: Spinal Cord Injury Center, Heidelberg University Hospital, Germany.

Participants: Convenient sample of 21 individuals with subacute spinal cord injury (age: 31–82 years) and 20 individuals without spinal cord injury (age: 24–63 years).

Assessment: All participants underwent three assessments for sharp/dull discrimination, applying five commonly used examination tools in seven dermatomes, performed by three trained examiners under conditions in accordance with ISNCSCI.

Main Outcome Measures: Assessment of interrater reliability by determining both the Fleiss kappa (κ) coefficient and the percentage agreement between raters. Data were dichotomized regarding the ISNCSCI threshold.

Results: Interrater reliability in individuals with SCI was overall substantial (κ = 0.68; CI 0.679–0.681) and moderate (κ = 0.54; CI 0.539–0.543) in dermatomes below the sensory level. All applied tools led to at least moderate reliability below the sensory level (lowest κ = 0.44; CI 0.432–0.440), with the officially endorsed safety pin achieving the highest (substantial) reliability (κ = 0.64; CI 0.638–0.646). Percentage agreement differed between non-SCI (97.3%) and formally intact above level dermatomes in SCI (89.2%).

Conclusions: Sharp/dull discrimination as a common clinical examination technique for spinothalamic tract function is a reliable assessment. Independent from the used examination tools, reliability was substantial, with the medium-sized safety pin delivering the most favorable results. Notwithstanding this, all other tools could be considered if a safety pin is not available. Regarding interrater reliability and guessing probability, a threshold of 80% correct responses for preserved sharp/dull discrimination appears to be most suitable, which is in line with current clinical approaches and ISNCSCI. The causal attribution of the identified differences in sharp/dull discrimination between clinically intact dermatomes of individuals with SCI and unaffected dermatomes of individuals without SCI requires future work.

Clinical Trial Registration Number (German Clinical Trials Register): DRKS00015334 (https://www.drks.de).
Connectivity Measures Differentiate Cortical and Subcortical Sub-Acute Ischemic Stroke Patients
Authors: Fanciullacci Chiara , Panarese Alessandro , Spina Vincenzo , Lassi Michael , Mazzoni Alberto , Artoni Fiorenzo , Micera Silvestro , Chisari Carmelo
Published: July 2021

Brain lesions caused by cerebral ischemia lead to network disturbances in both hemispheres, causing a subsequent reorganization of functional connectivity both locally and remotely with respect to the injury. Quantitative electroencephalography (qEEG) methods have long been used for exploring brain electrical activity and functional connectivity modifications after stroke. However, results obtained so far are not univocal. Here, we used basic and advanced EEG methods to characterize how brain activity and functional connectivity change after stroke. Thirty-three unilateral post stroke patients in the sub-acute phase and ten neurologically intact age-matched right-handed subjects were enrolled. Patients were subdivided into two groups based on lesion location: cortico-subcortical (CS, n = 18) and subcortical (S, n = 15), respectively. Stroke patients were evaluated in the period ranging from 45 days since the acute event (T0) up to 3 months after stroke (T1) with both neurophysiological (resting state EEG) and clinical assessment (Barthel Index, BI) measures, while healthy subjects were evaluated once. Brain power at T0 was similar between the two groups of patients in all frequency bands considered (δ, θ, α, and β). However, evolution of θ-band power over time was different, with a normalization only in the CS group. Instead, average connectivity and specific network measures (Integration, Segregation, and Small-worldness) in the β-band at T0 were significantly different between the two groups. The connectivity and network measures at T0 also appear to have a predictive role in functional recovery (BI T1-T0), again group-dependent. The results obtained in this study showed that connectivity measures and correlations between EEG features and recovery depend on lesion location. These data, if confirmed in further studies, on the one hand could explain the heterogeneity of results so far observed in previous studies, on the other hand they could be used by researchers as biomarkers predicting spontaneous recovery, to select homogenous groups of patients for the inclusion in clinical trials.
A Meta-Analysis of the Effect of Subthalamic Nucleus-Deep Brain Stimulation in Parkinson's Disease-Related Pain
Authors: Diao Yu , Bai Yutong , Hu Tianqi , Yin Zixiao , Liu Huangguang , Meng Fangang , Yang Anchao , Zhang Jianguo
Published: July 2021

Pain from Parkinson's disease (PD) is a non-motor symptom affecting the quality of life and has prevalence of 20–80%. However, it is unclear whether subthalamic nucleus deep brain stimulation (STN–DBS), a well-established treatment for PD, is effective forPD-related pain. Thus, the objective of this meta-analysis was to investigate the efficacy of STN-DBS on PD-related pain and explore how its duration affects the efficacy of STN-DBS. A systematic search was performed using PubMed, Embase, and the Cochrane Library. Nine studies included numerical rating scale (NRS), visual analog scale (VAS), or non-motor symptom scale (NMSS) scores at baseline and at the last follow-up visit and therefore met the inclusion criteria of the authors. These studies exhibited moderate- to high-quality evidence. Two reviewers conducted assessments for study eligibility, risk of bias, data extraction, and quality of evidence rating. Random effect meta-analysis revealed a significant change in PD-related pain as assessed by NMSS, NRS, and VAS (P <0.01). Analysis of the short and long follow-up subgroups indicated delayed improvement in PD-related pain. These findings (a) show the efficacy of STN-DBS on PD-related pain and provide higher-level evidence, and (b) implicate delayed improvement in PD-related pain, which may help programming doctors with supplement selecting target and programming.

Systematic Review Registration: This study is registered in Open Science Framework (DOI: 10.17605/OSF.IO/DNM6K).
Purinergic Signaling in the Pathophysiology and Treatment of Huntington’s Disease
Authors: Wiprich Melissa Talita , Bonan Carla Denise
Published: July 2021

Huntington’s disease (HD) is a devastating, progressive, and fatal neurodegenerative disorder inherited in an autosomal dominant manner. This condition is characterized by motor dysfunction (chorea in the early stage, followed by bradykinesia, dystonia, and motor incoordination in the late stage), psychiatric disturbance, and cognitive decline. The neuropathological hallmark of HD is the pronounced neuronal loss in the striatum (caudate nucleus and putamen). The striatum is related to the movement control, flexibility, motivation, and learning and the purinergic signaling has an important role in the control of these events. Purinergic signaling involves the actions of purine nucleotides and nucleosides through the activation of P2 and P1 receptors, respectively. Extracellular nucleotide and nucleoside-metabolizing enzymes control the levels of these messengers, modulating the purinergic signaling. The striatum has a high expression of adenosine A2A receptors, which are involved in the neurodegeneration observed in HD. The P2X7 and P2Y2 receptors may also play a role in the pathophysiology of HD. Interestingly, nucleotide and nucleoside levels may be altered in HD animal models and humans with HD. This review presents several studies describing the relationship between purinergic signaling and HD, as well as the use of purinoceptors as pharmacological targets and biomarkers for this neurodegenerative disorder.
The Long Noncoding RNA LINC00665 Facilitates c-Myc Transcriptional Activity via the miR-195-5p MYCBP Axis to Promote Progression of Lung Adenocarcinoma
Authors: Wang Anpeng , Zhang Te , Wei Wei , Wang Hui , Zhang Zeyu , Yang Wenming , Xia Wenjie , Mao Qixing , Xu Lin , Jiang Feng , Dong Gaochao
Published: July 2021

Long noncoding RNAs (lncRNAs) have recently received growing substantial attention in cancer research due to their important roles in various cancer types. However, the underlying mechanisms and functions of lncRNAs, especially in lung adenocarcinoma (LUAD), remain elusive. Based on pan-cancer screening analyses, we identified that the noncoding RNA LINC00665 was up-regulated in lung adenocarcinoma, which was subsequently confirmed in clinical samples and cell lines. Higher expression of LINC00665 was positively associated with poor prognosis and advanced T stage. Next, using gain- and loss- of function approaches, we revealed that LINC00665 promotes cell proliferation, cell migration, invasion, and suppresses cell apoptosis in LUAD through in vitro and in vivo experiments. Additionally, our findings showed that LINC00665 was predominately localized in the cytoplasm so as to interact with Ago2 protein, which could function as miRNA sponges. The results of bioinformatics prediction and RNA pull-down assay indicated that LINC00665 directly interacted with miR-195-5p. This was also confirmed by fluorescence colocalization. Furthermore, luciferase reporter assay demonstrated that Myc binding protein (MYCBP, also called AMY-1), which enhanced c-Myc transcriptional activity, was the target gene of LINC00665 dependent on miR-195-5p. Finally, rescue functional assay results uncovered that the oncogenic capability of LINC00665 was dependent on miR-195-5p and c-Myc transcriptional activity. In summary, this work elucidates that LINC00665 accelerates LUAD progression via the miR-195-5p/MYCBP axis by acting as a competing endogenous RNA (ceRNA), suggesting that LINC00665 may represent a potential therapeutic target for clinical intervention of LUAD.
Computed Tomography-Based Radiomics Model to Preoperatively Predict Microsatellite Instability Status in Colorectal Cancer: A Multicenter Study
Authors: Li Zhi , Zhong Qi , Zhang Liang , Wang Minhong , Xiao Wenbo , Cui Feng , Yu Fang , Huang Chencui , Feng Zhan
Published: July 2021

Objectives

To establish and validate a combined radiomics model based on radiomics features and clinical characteristics, and to predict microsatellite instability (MSI) status in colorectal cancer (CRC) patients preoperatively.

Methods

A total of 368 patients from four hospitals, who underwent preoperative contrast-enhanced CT examination, were included in this study. The data of 226 patients from a single hospital were used as the training dataset. The data of 142 patients from the other three hospitals were used as an independent validation dataset. The regions of interest were drawn on the portal venous phase of contrast-enhanced CT images. The filtered radiomics features and clinical characteristics were combined. A total of 15 different discrimination models were constructed based on a feature selection strategy from a pool of 3 feature selection methods and a classifier from a pool of 5 classification algorithms. The generalization capability of each model was evaluated in an external validation set. The model with high area under the curve (AUC) value from the training set and without a significant decrease in the external validation set was final selected. The Brier score (BS) was used to quantify overall performance of the selected model.

Results

The logistic regression model using the mutual information (MI) dimensionality reduction method was final selected with an AUC value of 0.79 for the training set and 0.73 for the external validation set to predicting MSI. The BS value of the model was 0.12 in the training set and 0.19 in the validation set.

Conclusion

The established combined radiomics model has the potential to predict MSI status in CRC patients preoperatively.
Preoperative Immunotherapy in the Multidisciplinary Management of Oral Cavity Cancer
Authors: Philips Ramez , Han Chihun , Swendseid Brian , Curry Joseph , Argiris Athanassios , Luginbuhl Adam , Johnson Jennifer
Published: July 2021

Despite advances in multimodal treatment for oral cavity squamous cell carcinoma, recurrence rates remain high, providing an opportunity for new therapeutic modalities that may improve oncologic outcomes. Much recent attention has been paid to the molecular interactions between the tumor cells with the adjacent peritumoral microenvironment, in which immunosuppressive molecular changes create a landscape that promotes tumor progression. The rationale for the introduction of immunotherapy is to reverse the balance of these immune interactions in a way that utilizes the host immune system to attack tumor cells. In the preoperative setting, immunotherapy has the advantage of priming the unresected tumor and the associated native immune infiltration, supercharging the adaptive anti-tumor immune response. It also provides the basis for scientific discovery where the molecular profile of responders can be interrogated to elucidate prognostic markers to aid in future patient selection. Preoperative immunotherapy is not without limitations. The risk of surgical delay due to immune adverse events must be carefully discussed by members of a multidisciplinary treatment team and patient selection will be critical. One day, the discovery of predictive biomarkers may allow for algorithms where pre-surgical immunotherapy decreases the size of surgical defect and impacts the intensity of adjuvant therapy leading to improved patient survival and decreased morbidity. With further study, immunotherapy could become a key component of future treatment algorithm.
NR5A2 Is One of 12 Transcription Factors Predicting Prognosis in HNSCC and Regulates Cancer Cell Proliferation in a p53-Dependent Manner
Authors: Zhang Kun , Xiao Ming , Jin Xin , Jiang Hongyan
Published: July 2021

Head and neck squamous cell carcinoma (HNSCC) rank seventh among the most common type of malignant tumor worldwide. Various evidences suggest that transcriptional factors (TFs) play a critical role in modulating cancer progression. However, the prognostic value of TFs in HNSCC remains unclear. Here, we identified a risk model based on a 12-TF signature to predict recurrence-free survival (RFS) in patients with HNSCC. We further analyzed the ability of the 12-TF to predict the disease-free survival time and overall survival time in HNSCC, and found that only NR5A2 down-regulation was strongly associated with shortened overall survival and disease-free survival time in HNSCC. Moreover, we systemically studied the role of NR5A2 in HNSCC and found that NR5A2 regulated HNSCC cell growth in a TP53 status-dependent manner. In p53 proficient cells, NR5A2 knockdown increased the expression of TP53 and activated the p53 pathway to enhance cancer cells proliferation. In contrast, NR5A2 silencing suppressed the growth of HNSCC cells with p53 loss/deletion by inhibiting the glycolysis process. Therefore, our results suggested that NR5A2 may serve as a promising therapeutic target in HNSCC harboring loss-of-function TP53 mutations.
Factors Influencing the Discordancy Between Intraoperative Frozen Sections and Final Paraffin Pathologies in Ovarian Tumors
Authors: Shen Hung , Hsu Heng-Cheng , Tai Yi-Jou , Kuo Kuan-Ting , Wu Chia-Ying , Lai Yen-Ling , Chiang Ying-Cheng , Chen Yu-Li , Cheng Wen-Fang
Published: July 2021

Aim

To retrospectively investigate the pre-operative clinical factors and ultrasonographic features that influence the accuracy of the intraoperative frozen section (IFS) of ovarian tumors.

Patients and methods

Women with ovarian tumors that underwent IFS in one tertiary medical center were recruited from January 2010 to December 2018. Demographic and clinical data of these women were retrieved from medical records in the hospital’s centralized database.

Results

A total of 903 ovarian tumors were enrolled, including 237 (26.2%) benign, 150 (16.6%) borderline tumor, and 516 (57.2%) malignant. The overall accuracy of IFS among all specimens was 89.9%. The sensitivities of IFS in diagnosing borderline tumors (82.0%) and malignant tumors (88.2%) were lower than in diagnosing benign tumors (98.7%, p <0.001, Z-test). The specificity of diagnosing malignant tumors (99.7%) was significantly higher than that of diagnosing benign tumors (94.7%, p <0.001, Z-test). The group with discordant IFS and final paraffin pathology (FPP) had younger age (47.2 ± 14.0 vs. 51.5 ± 11.8 years, p = 0.013, Mann–Whitney U test), and higher percentage of early-stage disease (85.2% vs. 65.1%, p = 0.001, chi-square test) and mucinous (39.3% vs. 3.3%) and endometrioid histologic types (34.4% vs. 20.2%) than the concordant group (all by chi-square test). Menopause (OR 0.34, 95% CI 0.15–0.76, p = 0.009), multicystic tumor in ultrasound (OR 2.14, 95% CI 1.14–4.01, p = 0.018), and ascites existence (OR 0.33, 95% CI 0.14–0.82, p = 0.016) were factors related to the discordant IFS by multivariate analysis.

Conclusions

IFS has good accuracy in the diagnosis of ovarian tumors. We recommend more frozen tissue sampling for sonographic multicystic tumors in premenopausal women to improve the accuracy of IFS.
Case Report: m.13513 G>A Mutation in a Chinese Patient With Both Leigh Syndrome and Wolff-Parkinson-White Syndrome
Authors: Liang Jian-Min , Xin Cui-Juan , Wang Guang-Liang , Wu Xue-Mei
Published: July 2021

A number of causative mutations in mitochondrial and nuclear DNA have been identified for Leigh syndrome, a neurodegenerative encephalopathy, including m. 8993 T>G, m.8993 T>C, and m.3243A>G mutations in the MTATP6, MTATP6, and MT-TL1 genes, respectively, which have been reported in Leigh syndrome patients in China. The m.13513 G>A mutation has been described only a few times in the literature and not previously reported in China. Here we report the case of a 15-month-old boy who presented with ptosis and developmental delay and was diagnosed with Leigh syndrome and well as Wolff-Parkinson-White (WPW) syndrome. The m.13513 G>A mutation was found in DNA from blood. He was intubated due to respiratory failure and died at 23 months of age. The m.13513 G>A mutation in the ND5 gene of mitochondrial DNA is associated with Leigh syndrome and WPW syndrome; however, this is the first report of this mutation in a patient in China, highlighting the geographical and racial variability of Leigh syndrome.
Traditional Chinese Medicine and Colorectal Cancer: Implications for Drug Discovery
Authors: Sun Qiang , He Man , Zhang Meng , Zeng Sha , Chen Li , Zhao Hui , Yang Han , Liu Maolun , Ren Shan , Xu Haibo
Published: July 2021

As an important part of complementary and alternative medicine, traditional Chinese medicine (TCM) has been applied to treat a host of diseases for centuries. Over the years, with the incidence rate of human colorectal cancer (CRC) increasing continuously and the advantage of TCM gradually becoming more prominent, the importance of TCM in both domestic and international fields is also growing with each passing day. However, the unknowability of active ingredients, effective substances, and the underlying mechanisms of TCM against this malignant tumor greatly restricts the translation degree of clinical products and the pace of precision medicine. In this review, based on the characteristics of TCM and the oral administration of most ingredients, we herein provide beneficial information for the clinical utilization of TCM in the prevention and treatment of CRC and retrospect the current preclinical studies on the related active ingredients, as well as put forward the research mode for the discovery of active ingredients and effective substances in TCM, to provide novel insights into the research and development of innovative agents from this conventional medicine for CRC treatment and assist the realization of precision medicine.