bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of YAP1 by N6-Methyladenosine–Modified circCPSF6 Drives Malignancy in Hepatocellular Carcinoma
Authors: Chen Yunhao , Ling Zhenan , Cai Xianlei , Xu Yongfang , Lv Zhen , Man Da , Ge Jiangzhen , Yu Chengkuan , Zhang Deguo , Zhang Yanpeng , Xie Haiyang , Zhou Lin , Wu Jian , Zheng Shusen 
Published: December 2021

Abstract

Circular RNAs (circRNA) and N6-methyladenosine (m6A) modification are extensively involved in the progression of diverse tumors, including hepatocellular carcinoma (HCC). However, the cross-talk between circRNAs and m6A remains elusive in the pathogenesis of HCC. Here we investigated m6A-mediated regulation of circRNAs in HCC. m6A-related circRNAs were identified by integrating information from two published studies, revealing circular cleavage and polyadenylation specific factor 6 (circCPSF6) as a novel m6A-modified circRNA. circCPSF6 was dominated by ALKBH5-mediated demethylation, followed by the recognization and destabilization by YTHDF2. Meanwhile, circCPSF6 was upregulated in HCC specimens, and elevated circCPSF6 expression served as an independent prognostic factor for worse survival of patients with HCC. Loss-of-function assays demonstrated that circCPSF6 maintained cell proliferation and tumorigenicity and reinforced cell motility and tumor metastasis. circCPSF6 triggered expression of YAP1, further activating its downstream cascade. Mechanistically, circCPSF6 competitively bound PCBP2, blunting its binding to YAP1 mRNA, thereby sustaining the stability of YAP1. Functionally, removal of YAP1 reversed the effects of circCPSF6 in vitro and in vivo. Aberrant activation of the circCPSF6-YAP1 axis promoted HCC malignancy. These findings offer novel insights into the regulation of circRNAs by m6A modifications and the role of this epigenetic reprogramming in HCC.

Significance:
This study advances the understanding of the interplay between m6A methylation and circRNAs in hepatocellular carcinoma, highlighting the potential of circCPSF6 as a therapeutic target.
Abstract 13649: Asymmetric Cerebral Perfusion in Comatose Extracorporeal Membrane Oxygenation Patients
Authors: Khan Imad , Johnson Thomas , Dar Irfaan , Donohue Kelly , Xu Yan , Santiago Esmeralda , Loose Emily , Selioutski Olga , Marinescu Mark 
Published: December 2021

Asymmetric cerebral perfusion can occur when extracorporeal membrane oxygenation (ECMO) flow competes with native cardiac circulation. It is unclear whether this phenomenon associates with brain injury. Diffuse correlation spectroscopy (DCS) provides continuous, laser-based, non-invasive, bedside monitoring of relative cerebral blood flow (rCBF). This study measured rCBF in ECMO patients via DCS to determine whether comatose patients experience asymmetric cerebral perfusion.
Adults receiving ECMO for any indication were prospectively recruited from 12/2019-3/2021. Patients with prior neurologic injury, scalp/facial lacerations, and SARS-CoV-2 infection were excluded. DCS monitoring was performed daily during ECMO support with sensors placed on bilateral foreheads. Mean arterial pressure (MAP) was continuously recorded from the bedside monitor. The Glasgow Coma Scale (GCS) was assessed by clinical staff multiple times daily with sedation pauses, if possible, per standard of care. rCBF was calculated by comparing continuous cerebral blood flow (CBF) measurements to the daily median CBF, then averaged at each MAP value. Daily rCBF asymmetry was calculated by summing the absolute difference of rCBF between the two hemispheres at each MAP value, normalized for the total MAP range experienced by the patient that day.
Twelve subjects were enrolled in this study (ages 21-78, 6 with cardiac arrest, 4 with acute heart failure, 2 with ARDS) and grouped by maximum GCS motor (GCS-M) score during ECMO, with 3 “comatose” subjects (GCS-M ≤ 4), and 9 “awake” subjects (GCS-M > 4). DCS was performed over 66 sessions with a mean duration of 131.83 ± 1.13 minutes. Comatose subjects exhibited more rCBF asymmetry than awake subjects (0.28 ± 0.06 mmHg-1 vs. 0.10 ± 0.001 mmHg-1, p=0.045). No difference in asymmetry was noted between patients with or without cardiac arrest.
We found that comatose ECMO subjects exhibited higher inter-hemispheric rCBF asymmetry over a range of blood pressures than awake subjects. Though our comatose sample is small, further validation of this finding and its causes, such as cerebrovascular dysregulation, is warranted.
Long-Term Outcomes in Adult Patients With Pulmonary Hypertension After Percutaneous Closure of Atrial Septal Defects
Authors: Akseer Selai , Abrahamyan Lusine , Lee Douglas S. , Huszti Ella , Meier Lukas M. , Osten Mark , Benson Lee , Horlick Eric 
Published: December 2021

Background:

Pulmonary hypertension (PH), recently redefined as mean pulmonary arterial pressure >20 mm Hg (PH
20
), may be observed in patients with atrial septal defects (ASD). We aimed to determine the effect of preprocedural PH
20
status on outcomes among patients undergoing ASD closure.

Methods:
Study population was selected from a retrospective registry of adult patients who underwent percutaneous ASD closure from 1998 to 2016 from a single center and had right heart catheterizations during the procedure. The clinical registry was linked to administrative databases to capture short- and long-term outcomes.

Results:

We included a total of 632 ASD closure patients of whom 359 (56.8%) had PH
20
. The mean follow-up length was 7.6±4.6 years. Patients with PH
20
were older (mean age 56.5 versus 43.1 years,
P
<0.001) and a higher prevalence of comorbidities including hypertension (54.3% versus 21.6%,
P
<0.001) and diabetes (18.1% versus 5.9%,
P
<0.001) than those without PH. In a Cox proportional hazards model after covariate adjustment, patients with PH had a significantly higher risk of developing major adverse cardiac and cerebrovascular events (heart failure, stroke, myocardial infarction, or cardiovascular mortality), with hazards ratio 2.45 (95% CI, 1.4–4.4). When applying the prior, mean pulmonary arterial pressure ≥25 mm Hg (PH
25
) cutoff, a significantly higher hazard of developing major adverse cardiac and cerebrovascular events was observed in PH versus non-PH patients.

Conclusions:

ASD patients with PH undergoing closure suffer from more comorbidities and worse long-term major adverse cardiac and cerebrovascular events outcomes, compared with patients without PH. The use of the new PH
20
definition potentially dilutes the effect of this serious condition on outcomes in this population.
Cardiac Risk Factors for Stroke: A Comprehensive Mendelian Randomization Study
Authors: Frerich Simon , Malik Rainer , Georgakis Marios K. , Sinner Moritz F. , Kittner Steven J. , Mitchell Braxton D. , Dichgans Martin 
Published: December 2021

Background:
Observational studies suggest an association of stroke with cardiac traits beyond atrial fibrillation, the leading source of cardioembolism. However, controversy remains regarding a causal role of these traits in stroke pathogenesis. Here, we leveraged genetic data to systematically assess associations between cardiac traits and stroke risk using a Mendelian Randomization framework.

Methods:
We studied 66 cardiac traits including cardiovascular diseases, magnetic resonance imaging–derived cardiac imaging, echocardiographic imaging, and electrocardiographic measures, as well as blood biomarkers in a 2-sample Mendelian Randomization approach. Genetic predisposition to each trait was explored for associations with risk of stroke and stroke subtypes in data from the MEGASTROKE consortium (40 585 cases/406 111 controls). Using multivariable Mendelian Randomization, we adjusted for potential pleiotropic or mediating effects relating to atrial fibrillation, coronary artery disease, and systolic blood pressure.

Results:
As expected, we observed strong independent associations between genetic predisposition to atrial fibrillation and cardioembolic stroke and between genetic predisposition to coronary artery disease as a proxy for atherosclerosis and large-artery stroke. Our data-driven analyses further indicated associations of genetic predisposition to both heart failure and lower resting heart rate with stroke. However, these associations were explained by atrial fibrillation, coronary artery disease, and systolic blood pressure in multivariable analyses. Genetically predicted P-wave terminal force in V1, an electrocardiographic marker for atrial cardiopathy, was inversely associated with large-artery stroke.

Conclusions:
Available genetic data do not support substantial effects of cardiac traits on the risk of stroke beyond known clinical risk factors. Our findings highlight the need to carefully control for confounding and other potential biases in studies examining candidate cardiac risk factors for stroke.
Implicit Contact Dynamics Modeling With Explicit Inertia Matrix Representation for Real-Time, Model-Based Control in Physical Environment
Authors: Itoh Takeshi D. , Ishihara Koji , Morimoto Jun 
Published: December 2021

Abstract
Model-based control has great potential for use in real robots due to its high sampling efficiency. Nevertheless, dealing with physical contacts and generating accurate motions are inevitable for practical robot control tasks, such as precise manipulation. For a real-time, model-based approach, the difficulty of contact-rich tasks that requires precise movement lies in the fact that a model needs to accurately predict forthcoming contact events within a limited length of time rather than detect them afterward with sensors. Therefore, in this study, we investigate whether and how neural network models can learn a task-related model useful enough for model-based control, that is, a model predicting future states, including contact events. To this end, we propose a structured neural network model predictive control (SNN-MPC) method, whose neural network architecture is designed with explicit inertia matrix representation. To train the proposed network, we develop a two-stage modeling procedure for contact-rich dynamics from a limited number of samples. As a contact-rich task, we take up a trackball manipulation task using a physical 3-DoF finger robot. The results showed that the SNN-MPC outperformed MPC with a conventional fully connected network model on the manipulation task.
Distributed Phase Oscillatory Excitation Efficiently Produces Attractors Using Spike-Timing-Dependent Plasticity
Authors: Wong Eric C. 
Published: December 2021

Abstract
The brain is thought to represent information in the form of activity in distributed groups of neurons known as attractors. We show here that in a randomly connected network of simulated spiking neurons, periodic stimulation of neurons with distributed phase offsets, along with standard spike-timing-dependent plasticity (STDP), efficiently creates distributed attractors. These attractors may have a consistent ordered firing pattern or become irregular, depending on the conditions. We also show that when two such attractors are stimulated in sequence, the same STDP mechanism can create a directed association between them, forming the basis of an associative network. We find that for an STDP time constant of 20 ms, the dependence of the efficiency of attractor creation on the driving frequency has a broad peak centered around 8 Hz. Upon restimulation, the attractors self-oscillate, but with an oscillation frequency that is higher than the driving frequency, ranging from 10 to 100 Hz.
“Killing for Show”: A Conversation with Julian Stallabrass
Authors: Nixon Mignon 
Published: December 2021

Abstract
In this conversation prompted by the publication of Julian Stallabrass's Killing for Show: Photography, War and the Media in Vietnam and Iraq (Rowman & Littlefield, 2021), Stallabrass and Mignon Nixon discuss the roles played by photography in two wars that, Stallabrass contends, were simultaneously staged for, and concealed from, the camera. The discussion encompasses diverse modes of war photography, from photojournalism and official military photography to amateur and trophy images, aftermath photographs, and found images used by contemporary artists. It dwells on questions of memory, systemic cruelty, trauma, and melancholy, and on shifts in technology, media, and social relations that have altered the dynamics of killing for show over time, without eliminating the imperative.
Increase in cartilage degeneration in all knee compartments after failed ACL reconstruction at 4 years of follow-up
Authors: Andrä Kathleen , Prill Robert , Kayaalp Enes , Irlenbusch Lars , Liesaus Eckehard , Trommer Tilo , Ullmann Peter , Becker Roland 
Published: December 2021

Abstract
Purpose
Degeneration of the cartilage after anterior cruciate ligament reconstruction (ACL-R) is known, and further deterioration can be expected in patients with tunnel malplacement or partial meniscal resection. It was hypothesized that there is a significant increase in cartilage degeneration after failed ACL-R.

Material and methods
Isolated ACL revision surgery was performed in 154 patients at an interval of 46 ± 33 months (5–175 months) between primary and revision surgery. Cartilage status at the medial, lateral femorotibial, and patellofemoral compartments were assessed arthroscopically during primary and revision ACL-R in accordance with the Outerbridge classification. Tunnel placement, roof angle, and tibial slope was measured using anteroposterior and lateral radiographic views.

Results
Cartilage degeneration increased significantly in the medial femorotibial compartment, followed by the lateral and patellofemoral compartments. There was a correlation between both cartilage degeneration in the patellofemoral compartment (PFC) (rs = 0.28, p = 0.0012) and medial tibial plateau (Rs = 0.24, p = 0.003) in relation to the position of tibial tunnel in the frontal plane. Worsening of the cartilage status in the medial femorotibial compartment, either femoral or tibial, was correlated with the tibial aperture site in the lateral view (Rs = 0.28, p < 0.001). Cartilage degeneration in the lateral compartment of the knee, on both femoral or tibial side, was inversely correlated with the femoral roof angle (Rs = −0.1985, p = 0.02). Meniscal tears, either at the medial or lateral site or at both, were found in 93 patients (60%) during primary ACL-R and increased to 132 patients (86%) during revision ACL-R.

Discussion
Accelerated cartilage degeneration and high prevalence of meniscal lesions are seen in failed ACL-R. Tunnel placement showed significant impact on cartilage degeneration and may partially explain the increased risk of an inferior outcome when revision surgery is required after failed primary ACL-R.
Level of evidence: Level IV—retrospective cohort study.
Proteomics and functional study reveal kallikrein-6 enhances communicating hydrocephalus
Authors: Yuan Lei , Zou Dongdong , Yang Xia , Chen Xin , Lu Youming , Zhang Aijun , Zhang Pengqi , Wei Fance 
Published: December 2021

Abstract
Background
Communicating hydrocephalus (CH) is a common neurological disorder caused by a blockage of cerebrospinal fluid. In this study, we aimed to explore the potential molecular mechanism underlying CH development.

Methods
Quantitative proteomic analysis was performed to screen the differentially expressed proteins (DEPs) between patients with and without CH. A CH rat model was verified by Hoechst staining, and the co-localization of the target protein and neuron was detected using immunofluorescence staining. Loss-of-function experiments were performed to examine the effect of KLK6 on the synapse structure.

Results
A total of 11 DEPs were identified, and kallikrein 6 (KLK6) expression was found to be significantly upregulated in patients with CH compared with that in patients without CH. The CH rat model was successfully constructed, and KLK6 was found to be co-localized with neuronal nuclei in brain tissue. The expression level of IL-1β, TNF-α, and KLK6 in the CH group was higher than that in the control group. After knockdown of KLK6 expression using small-interfering RNA (siRNA), the expression levels of synapsin-1 and PSD95 in neuronal cells were increased, and the length, number, and structure of synapses were significantly improved. Following siRNA interference KLK6 expression, 5681 differentially expressed genes (DEGs) were identified in transcriptome profile. The upregulated DEGs of Appl2, Nav2, and Nrn1 may be involved in the recovery of synaptic structures after the interference of KLK6 expression.

Conclusions
Collectively, KLK6 participates in the development of CH and might provide a new target for CH treatment.
The gut microbiome as an indicator of habitat disturbance in a Critically Endangered lemur
Authors: McManus Nicolette , Holmes Sheila M. , Louis Edward E. , Johnson Steig E. , Baden Andrea L. , Amato Katherine R. 
Published: December 2021

AbstractBackgroundHabitat disturbance affects the biology and health of animals globally. Understanding the factors that contribute to the differential responses of animals to habitat disturbance is critical for conservation. The gut microbiota represents a potential pathway through which host responses to habitat disturbance might be mediated. However, a lack of quantitative environmental data in many gut microbiome (GM) studies of wild animals limits our ability to pinpoint mechanisms through which habitat disturbance affects the GM. Here, we examine the impact of anthropogenic habitat disturbance on the diet and GM of the Critically Endangered black-and-white ruffed lemur (Varecia variegata editorum). We collected fecal samples and behavioral data fromVareciaoccupying habitats qualitatively categorized as primary forest, moderately disturbed forest, and heavily disturbed forest.ResultsVareciadiet and GM composition differed substantially across sites. Dietary richness predicted GM richness across sites, and overall GM composition was strongly correlated to diet composition. Additionally, the consumption of three specific food items positively correlated to the relative abundances of five microbial strains and one microbial genus across sites. However, diet did not explain all of the GM variation in our dataset, and differences in the GM were detected that were not correlated with diet, as measured.ConclusionsOur data suggest that diet is an important influence on theVareciaGM across habitats and thus could be leveraged in novel conservation efforts in the future. However, other factors such as contact with humans should also be accounted for. Overall, we demonstrate that quantitative data describing host habitats must be paired with GM data to better target the specific mechanisms through which environmental change affects the GM.
Isolation and functional characterization of a glucose-6-phosphate/phosphate translocator (IbG6PPT1) from sweet potato (Ipomoea batatas (L.) Lam.)
Authors: Wu Zhengdan , Wang Zhiqian , Zhang Kai 
Published: December 2021

AbstractSweet potato (Ipomoea batatas (L.) Lam.) is a good source of carbohydrates, an excellent raw material for starch-based industries, and a strong candidate for biofuel production due to its high starch content. However, the molecular basis of starch biosynthesis and accumulation in sweet potato is still insufficiently understood. Glucose-6-phosphate/phosphate translocators (GPTs) mediate the import of glucose-6-phosphate (Glc6P) into plastids for starch synthesis. Here, we report the isolation of a GPT-encoding gene, IbG6PPT1, from sweet potato and the identification of two additional IbG6PPT1 gene copies in the sweet potato genome. IbG6PPT1 encodes a chloroplast membrane–localized GPT belonging to the GPT1 group and highly expressed in storage root of sweet potato. Heterologous expression of IbG6PPT1 resulted in increased starch content in the leaves, root tips, and seeds and soluble sugar in seeds of Arabidopsis thaliana, but a reduction in soluble sugar in the leaves. These findings suggested that IbG6PPT1 might play a critical role in the distribution of carbon sources in source and sink and the accumulation of carbohydrates in storage tissues and would be a good candidate gene for controlling critical starch properties in sweet potato.
A prospective observational real world feasibility study assessing the role of app-based remote patient monitoring in reducing primary care clinician workload during the COVID pandemic
Authors: Shah Sachin Shailendra , Safa Afsana , Johal Kuldhir , Obika Dillon , Valentine Sophie 
Published: December 2021

AbstractBackgroundThe novel coronavirus disease in 2019 (COVID-19) has placed unprecedented strain on healthcare providers, in particular, primary care services. General practitioners (GP) have to effectively manage patients remotely preserving social distancing. We aim to assess an app-based remote patient monitoring solution in reducing the workload of a clinician and reflect this as time-saved in an economic context. Primary care COVID patients in West London deemed medium risk were recruited into the virtual ward. Patients were monitored for 14 days by telephone or by both the Huma app and telephone. Information on number of phone calls, duration of phone calls and duration of time spent reviewing the app data was recorded.ResultsThe amount of time spent reviewing one patient in the telephone only arm of the study was 490 min, compared with 280 min spent reviewing one patient who was monitored via both the Huma app and telephone. Based on employed clinicians monitoring patients, this equates to a 0.04 reduction of full-time equivalent staffing I.e. for every 100 patients, it would require 4 less personnel to remotely monitor them. There was no difference in mortality or adverse events between the two groups.ConclusionApp-based remote patient monitoring potentially holds large economic benefit to COVID-19 patients. In wake of further waves or future pandemics, and even in routine care, app-based remote monitoring patients could free up vital resources in terms of clinical team’s time, allowing a better reallocation of services.
Over-the-scope clip-assisted endoscopic full-thickness resection has potential to treat complex nonampullary duodenal lesions: a single-center case series
Authors: Wei Yongqiu , Zhou Qiaozhi , Ji Ming , Zhang Shutian , Li Peng 
Published: December 2021

Abstract
Background and aims
The duodenum is considered a challenging area for the endoscopic resection of lesions. This study aimed to evaluate the efficacy and safety of over-the-scope clip (OTSC)-assisted endoscopic full-thickness resection (EFTR) for complex nonampullary duodenal lesions unsuitable for conventional resection techniques.

Methods and patients

We conducted a retrospective case review of 13 consecutive patients with complex nonampullary duodenal tumors that were unsuitable for conventional resection techniques; these patients underwent EFTR assisted with OTSC at Beijing Friendship Hospital, Capital Medical University from September 2015 to September 2020. The OTSC device was placed, and tumors were resected after the lesions were identified. Data were abstracted for demographics, lesion features, histopathologic diagnoses, technical success rates, complete resection (R0 resection) rates, and complications.

Results
Thirteen patients with duodenal lesions (6 adenomas and 7 submucosal tumors with nonlifting signs, incomplete lifting signs, difficult locations, failed ESD/EMR attempts or suspected origin in the muscularis propria) subjected to EFTR were included. The sizes of all the lesions evaluated by endoscopy were smaller than 20 mm, and most of them (84.6%, 11/13) were smaller than 12 mm. All 13 applications of the clips, endoscopic resection and full-thickness resection were successful (13/13, 100%). Complete resection was achieved in 12 patients (12/13, 92.3%). There were no immediate or delayed complications, including bleeding, infection and perforation.

Conclusions
OTSC -assisted EFTR appears to be effective and safe for complex nonampullary duodenal lesions smaller than 20 mm (particularly those ≤ 10–12 mm) that are unsuitable for conventional resection techniques.