bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low-dose metformin targets the lysosomal AMPK pathway through PEN2
Authors: Ma Teng , Tian Xiao , Zhang Baoding , Li Mengqi , Wang Yu , Yang Chunyan , Wu Jianfeng , Wei Xiaoyan , Qu Qi , Yu Yaxin , Long Shating , Feng Jin-Wei , Li Chun , Zhang Cixiong , Xie Changchuan , Wu Yaying , Xu Zheni , Chen Junjie , Yu Yong , Huang Xi , He Ying , Yao Luming , Zhang Lei , Zhu Mingxia , Wang Wen , Wang Zhi-Chao , Zhang Mingliang , Bao Yuqian , Jia Weiping , Lin Shu-Yong , Ye Zhiyun , Piao Hai-Long , Deng Xianming , Zhang Chen-Song , Lin Sheng-Cai 
Published: February 2022

AbstractMetformin, the most prescribed antidiabetic medicine, has shown other benefits such as anti-ageing and anticancer effects1–4. For clinical doses of metformin, AMP-activated protein kinase (AMPK) has a major role in its mechanism of action4,5; however, the direct molecular target of metformin remains unknown. Here we show that clinically relevant concentrations of metformin inhibit the lysosomal proton pump v-ATPase, which is a central node for AMPK activation following glucose starvation6. We synthesize a photoactive metformin probe and identify PEN2, a subunit of γ-secretase7, as a binding partner of metformin with a dissociation constant at micromolar levels. Metformin-bound PEN2 forms a complex with ATP6AP1, a subunit of the v-ATPase8, which leads to the inhibition of v-ATPase and the activation of AMPK without effects on cellular AMP levels. Knockout of PEN2 or re-introduction of a PEN2 mutant that does not bind ATP6AP1 blunts AMPK activation. In vivo, liver-specific knockout of Pen2 abolishes metformin-mediated reduction of hepatic fat content, whereas intestine-specific knockout of Pen2 impairs its glucose-lowering effects. Furthermore, knockdown of pen-2 in Caenorhabditis elegans abrogates metformin-induced extension of lifespan. Together, these findings reveal that metformin binds PEN2 and initiates a signalling route that intersects, through ATP6AP1, the lysosomal glucose-sensing pathway for AMPK activation. This ensures that metformin exerts its therapeutic benefits in patients without substantial adverse effects.
Reproducible neuroimaging features for diagnosis of autism spectrum disorder with machine learning
Authors: Mellema Cooper J. , Nguyen Kevin P. , Treacher Alex , Montillo Albert 
Published: February 2022

AbstractAutism spectrum disorder (ASD) is the fourth most common neurodevelopmental disorder, with a prevalence of 1 in 160 children. Accurate diagnosis relies on experts, but such individuals are scarce. This has led to increasing interest in the development of machine learning (ML) models that can integrate neuroimaging features from functional and structural MRI (fMRI and sMRI) to help reveal central nervous system alterations characteristic of ASD. We optimized and compared the performance of 12 of the most popular and powerful ML models. Each was separately trained using 15 different combinations of fMRI and sMRI features and optimized with an unbiased model search. Deep learning models predicted ASD with the highest diagnostic accuracy and generalized well to other MRI datasets. Our model achieves state-of-the-art 80% area under the ROC curve (AUROC) in diagnosis on test data from the IMPAC dataset; and 86% and 79% AUROC on the external ABIDE I and ABIDE II datasets (with further improvement to 93% and 90% after supervised domain adaptation). The highest performing models identified reproducible putative biomarkers for accurate ASD diagnosis in accord with known ASD markers as well as novel cerebellar biomarkers. Such reproducibility lends credence to their tremendous potential for defining and using a set of truly generalizable ASD biomarkers that will advance scientific understanding of neuronal changes in ASD.
Interventional neurorehabilitation for promoting functional recovery post-craniotomy: a proof-of-concept
Authors: Poologaindran Anujan , Profyris Christos , Young Isabella M. , Dadario Nicholas B. , Ahsan Syed A. , Chendeb Kassem , Briggs Robert G. , Teo Charles , Romero-Garcia Rafael , Suckling John , Sughrue Michael E. 
Published: February 2022

AbstractThe human brain is a highly plastic ‘complex’ network—it is highly resilient to damage and capable of self-reorganisation after a large perturbation. Clinically, neurological deficits secondary to iatrogenic injury have very few active treatments. New imaging and stimulation technologies, though, offer promising therapeutic avenues to accelerate post-operative recovery trajectories. In this study, we sought to establish the safety profile for ‘interventional neurorehabilitation’: connectome-based therapeutic brain stimulation to drive cortical reorganisation and promote functional recovery post-craniotomy. In n = 34 glioma patients who experienced post-operative motor or language deficits, we used connectomics to construct single-subject cortical networks. Based on their clinical and connectivity deficit, patients underwent network-specific transcranial magnetic stimulation (TMS) sessions daily over five consecutive days. Patients were then assessed for TMS-related side effects and improvements. 31/34 (91%) patients were successfully recruited and enrolled for TMS treatment within two weeks of glioma surgery. No seizures or serious complications occurred during TMS rehabilitation and 1-week post-stimulation. Transient headaches were reported in 4/31 patients but improved after a single session. No neurological worsening was observed while a clinically and statistically significant benefit was noted in 28/31 patients post-TMS. We present two clinical vignettes and a video demonstration of interventional neurorehabilitation. For the first time, we demonstrate the safety profile and ability to recruit, enroll, and complete TMS acutely post-craniotomy in a high seizure risk population. Given the lack of randomisation and controls in this study, prospective randomised sham-controlled stimulation trials are now warranted to establish the efficacy of interventional neurorehabilitation following craniotomy.
Coastal marshes provide valuable protection for coastal communities from storm-induced wave, flood, and structural loss in a changing climate
Authors: Peter Sheng Y. , Paramygin Vladimir A. , Rivera-Nieves Adail A. , Zou Ruizhi , Fernald Sarah , Hall Timothy , Jacob Klaus 
Published: February 2022

AbstractWetlands such as tidal marshes and mangroves are known to buffer coastal communities from wave, flood, and structural loss during storms. Coastal communities and resource managers seek to understand the ecosystem service value of coastal wetlands for reducing storm-induced flood loss in a changing climate. A recent modeling study found that a tall and dense Phragmites-dominated Piermont Marsh reduced the flood loss in the Village of Piermont, New York, U.S.A. during Superstorm Sandy and the 1% annual chance flood and wave event by 8% and 11%, respectively. Here we used the same modeling approach to examine the marsh’s buffering capacity in a changing climate (from 2020 to 2100), considering a potential marsh restoration plan (from 2020 to 2025) and potential marsh loss due to sea-level rise. Results showed that from 2020 to 2100, the 1% annual chance flood, wave, and structural loss would increase due to sea-level rise, storms, and marsh loss. However, the marsh will buffer ~ 11–12% of structural loss until 2050. Under the extreme SLR scenario of 2.89 m and a low accretion rate, Piermont Marsh is expected to lose its buffering capacity by 2080–2100 but will retain some buffering capacity with a high accretion rate of 10 mm/year and marsh growth. The marsh’s buffering capacity will remain during extra-tropical storms during winter and spring unless the wind has a significant northerly component. Lessons learned from this study can be used by coastal communities and marsh managers to develop coastal resiliency and marsh restoration plan.
Enhancing neutralization of Plasmodium falciparum using a novel monoclonal antibody against the rhoptry-associated membrane antigen
Authors: Knudsen Anne S. , Walker Melanie R. , Agullet Judit P. , Björnsson Kasper H. , Bassi Maria R. , Barfod Lea 
Published: February 2022

AbstractThe pathogenesis of malaria is associated with blood-stage infection and there is strong evidence that antibodies specific to parasite blood-stage antigens can control parasitemia. This provides a strong rational for applying blood-stage antigen components in a multivalent vaccine, as the induced antibodies in combination can enhance protection. The Plasmodium falciparum rhoptry-associated membrane antigen (PfRAMA) is a promising vaccine target, due to its fundamental role in merozoite invasion and low level of polymorphism. Polyclonal antibodies against PfRAMA are able to inhibit P. falciparum growth and interact synergistically when combined with antibodies against P. falciparum reticulocyte-binding protein 5 (PfRh5) or cysteine-rich protective antigen (PfCyRPA). In this study, we identified a novel PfRAMA-specific mAb with neutralizing activity, which in combination with PfRh5- or PfCyRPA-specific mAbs potentiated the neutralizing effect. By applying phage display technology, we mapped the protective epitope to be in the C-terminal region of PfRAMA. Our results confirmed previous finding of synergy between PfRAMA-, PfRh5- and PfCyRPA-specific antibodies, thereby paving the way of testing these antigens (or fragments of these antigens) in combination to improve the efficacy of blood-stage malaria vaccines. The results emphasize the importance of directing antibody responses towards protective epitopes, as the majority of anti-PfRAMA mAbs were unable to inhibit merozoite invasion of erythrocytes.
Linking path and filament persistence lengths of microtubules gliding over kinesin
Authors: Sweet May , Kang’iri Samuel Macharia , Nitta Takahiro 
Published: February 2022

AbstractMicrotubules and kinesin motor proteins are involved in intracellular transports in living cells. Such intracellular material transport systems can be reconstructed for utilisation in synthetic environments, and they are called molecular shuttles driven by kinesin motors. The performance of the molecular shuttles depends on the nature of their trajectories, which can be characterized by the path persistence length of microtubules. It has been theoretically predicted that the path persistence length should be equal to the filament persistence length of the microtubules, where the filament persistence length is a measure of microtubule flexural stiffness. However, previous experiments have shown that there is a significant discrepancy between the path and filament persistence lengths. Here, we showed how this discrepancy arises by using computer simulation. By simulating molecular shuttle movements under external forces, the discrepancy between the path and filament persistence lengths was reproduced as observed in experiments. Our close investigations of molecular shuttle movements revealed that the part of the microtubules bent due to the external force was extended more than it was assumed in the theory. By considering the extended length, we could elucidate the discrepancy. The insights obtained here are expected to lead to better control of molecular shuttle movements.
Relationship between continuity of care and clinical outcomes in patients with dyslipidemia in Korea: a real world claims database study
Authors: Lee Juhee , Choi Eunyoung , Choo Eunjung , Linda Siachalinga , Jang Eun Jin , Lee Iyn-Hyang 
Published: February 2022

AbstractDyslipidemia is a risk factor for atherosclerotic cardiovascular disease and requires proactive management. This study aimed to investigate the association between care continuity and the outcomes of patients with dyslipidemia. We conducted a retrospective cohort study on patients with dyslipidemia by employing the Korea National Health Insurance claims database during the period 2007–2018. The Continuity of Care Index (COCI) was used to measure continuity of care. We considered incidence of atherosclerotic cardiovascular disease as a primary outcome. A Cox's proportional hazards regression model was used to quantify risks of primary outcome. There were 236,486 patients newly diagnosed with dyslipidemia in 2008 who were categorized into the high and low COC groups depending on their COCI. The adjusted hazard ratio for the primary outcome was 1.09 times higher (95% confidence interval: 1.06–1.12) in the low COC group than in the high COC group. The study shows that improved continuity of care for newly-diagnosed dyslipidemic patients might reduce the risk of atherosclerotic cardiovascular disease.
RETRACTED ARTICLE: Type 1 diabetes and the challenges of emotional support in crisis situations: results from a randomized clinical trial of a multidisciplinary teleintervention
Authors: Alessi Janine , Becker Alice Scalzilli , Amaral Bibiana , de Oliveira Giovana Berger , Franco Debora Wilke , Knijnik Carolina Padilla , Kobe Gabriel Luiz , de Brito Ariane , de Carvalho Taíse Rosa , Telo Guilherme Heiden , Schaan Beatriz D. , Telo Gabriela Heiden 
Published: February 2022

AbstractThe association between type 1 diabetes and mental health disorders could be exacerbated in a stressful environment. This study aimed to evaluate the effectiveness of a teleguided intervention on emotional disorders in patients with type 1 diabetes during the COVID-19 outbreak. An open-label clinical trial was performed during the social distancing period in the COVID-19 outbreak in Brazil. Individuals with type 1 diabetes aged ≥ 18 years were randomized to receive a teleguided multidisciplinary intervention or the usual care plus an educational website access. The primary outcome was a positive screening for emotional disorders (Self Report Questionnaire 20) after a 16-week intervention. Secondary outcomes included evaluation of patients’ perceptions of pandemic-related changes, diabetes-related emotional distress, eating disorders, and sleep disorders. Data were analyzed with the intent‐to‐treat principle. Fifty-eight individuals (mean age, 43.8 ± 13.6 years) were included (intervention group, n = 29; control group, n = 29). The primary outcome was not different between the groups. The intervention group felt more supported in their diabetes care during the social distancing period (82.8% vs. 48.3% in the control group, P < 0.01). Both groups reported a similar self-perceived worsening of physical activity habits and mental health during the outbreak. There was no benefit to using the telehealth strategy proposed for emotional disorders in patients with type 1 diabetes during the COVID-19 outbreak. Further studies are needed to determine the impact on metabolic parameters and to understand why it is so difficult to emotionally support these patients.Trail Registration: ClinicalTrials.gov (NCT04344210), 14/04/2020.
Electrochemical evaluation of porous CaFe2O4 anode material prepared via solution combustion synthesis at increasing fuel-to-oxidizer ratios and calcination temperatures
Authors: Strimaitis Jacob , Danquah Samuel A. , Denize Clifford , Pradhan Sangram K. , Bahoura Messaoud 
Published: February 2022

AbstractThe drawbacks of common anodes in lithium-ion batteries (LIBs) and hybrid supercapacitors (HSCs), such as the high voltage plateau of Li4Ti5O12 (1.55 V vs. Li/Li+) and the moderate capacity of graphite (372 mAh-g-1), have established a need for better materials. Conversion materials, and in particular iron oxide and CaFe2O4 (CFO), have amassed recent attention as potential anode replacements. In this study, we evaluate the material and electrochemical effects of the solution combustion synthesis (SCS) of porous CFO across novel fuel-to-oxidizer ratios and calcination temperatures. We demonstrate that nearly doubling the amount of fuel used during synthesis increases capacities between 120 and 150% at high current densities (~ 1000 mA-g-1) and across 500 additional charging-discharging cycles, an effect brought on in part by enhanced compositional purity in these samples. However, in order to ensure long-term cyclic stability, it is necessary to also calcine porous CFO to 900 °C to enhance crystallite size, particle size and spacing, and compositional purity.
Confusion matrix and minimum cross-entropy metrics based motion recognition system in the classroom
Authors: Wu Ming-Te 
Published: February 2022

AbstractThis research proposes a motion recognition system for early detection of students' physical aggressive behavior in the classroom. The motion recognition system recognizes physical attacks so that teachers can resolve disputes early to reduce other greater injuries. In the beginning, cameras were used in this system to monitor students’ classroom activities and to obtain body images by removing background and saliency maps. Two angles from arm to shoulder and shoulder to the center of the body are then measured and the velocity between the two frames from the movement of the body is detected, and use these angle and velocity values as the criterion for judging whether it is a physical attack. In the end, the accuracy of the proposed algorithms is verified by using the confusion matrix based on machine learning and the minimum cross entropy based on neural networks. The simulation proves that the proposed algorithm can correctly detect the attack behavior of the collected videos.
The effect of video-assisted discharge education after total hip replacement surgery: a randomized controlled study
Authors: Cetinkaya Eren Ozum , Buker Nihal , Tonak Hasan Atacan , Urguden Mustafa 
Published: February 2022

AbstractThis study aimed to investigate the effect of a video-assisted discharge education program on activities of daily living, functionality, and patient satisfaction following total hip replacement (THR) surgery. This study included 31 patients who were randomly divided into the physiotherapy group (n = 18), and the video-assisted discharge education (VADE) group (n = 13). Both groups received a physiotherapy program. The VADE group was also received the VADE program. Face-to-face instruction was used in all of the educational programs. There was a significant difference in favor of the VADE group in Harris Hip Score, Nottingham Extended Activities of Daily Living Scale’s movement score, Tampa Scale of Kinesiophobia, Patient Satisfaction Questionnaire (p < 0.05). There was a significant difference between groups on resting pain levels in the first week and on resting and activity pain levels in the third month in favor of the VADE group (p < 0.05). The results of this study demonstrated that VADE can be effective in improving patient satisfaction and functionality, reducing pain and kinesiophobia following THR.
Clinical feasibility of a contactless multiparameter continuous monitoring technology for neonates in a large public maternity hospital in Nairobi, Kenya
Authors: Ginsburg Amy Sarah , Zandi Nia Sahar , Chomba Dorothy , Dunsmuir Dustin , Waiyego Mary , Coleman Jesse , Ochieng Roseline , Liu Sichen , Zhou Guohai , Ansermino J. Mark , Macharia William M. 
Published: February 2022

AbstractMultiparameter continuous physiological monitoring (MCPM) technologies are critical in the clinical management of high-risk neonates; yet, these technologies are frequently unavailable in many African healthcare facilities. We conducted a prospective clinical feasibility study of EarlySense’s novel under-mattress MCPM technology in neonates at Pumwani Maternity Hospital in Nairobi, Kenya. To assess feasibility, we compared the performance of EarlySense’s technology to Masimo’s Rad-97 pulse CO-oximeter with capnography technology for heart rate (HR) and respiratory rate (RR) measurements using up-time, clinical event detection performance, and accuracy. Between September 15 and December 15, 2020, we collected and analyzed 470 hours of EarlySense data from 109 enrolled neonates. EarlySense’s technology’s up-time per neonate was 2.9 (range 0.8, 5.3) hours for HR and 2.1 (range 0.9, 4.0) hours for RR. The difference compared to the reference was a median of 0.6 (range 0.1, 3.1) hours for HR and 0.8 (range 0.1, 2.9) hours for RR. EarlySense’s technology identified high HR and RR events with high sensitivity (HR 81%; RR 83%) and specificity (HR 99%; RR 83%), but was less sensitive for low HR and RR (HR 0%; RR 14%) although maintained specificity (HR 100%; RR 95%). There was a greater number of false negative and false positive RR events than false negative and false positive HR events. The normalized spread of limits of agreement was 9.6% for HR and 28.6% for RR, which met the a priori-identified limit of 30%. EarlySense’s MCPM technology was clinically feasible as demonstrated by high percentage of up-time, strong clinical event detection performance, and agreement of HR and RR measurements compared to the reference technology. Studies in critically ill neonates, assessing barriers and facilitators to adoption, and costing analyses will be key to the technology’s development and potential uptake and scale-up.
H3K27ac nucleosomes facilitate HMGN localization at regulatory sites to modulate chromatin binding of transcription factors
Authors: Zhang Shaofei , Postnikov Yuri , Lobanov Alexei , Furusawa Takashi , Deng Tao , Bustin Michael 
Published: February 2022

AbstractNucleosomes containing acetylated H3K27 are a major epigenetic mark of active chromatin and identify cell-type specific chromatin regulatory regions which serve as binding sites for transcription factors. Here we show that the ubiquitous nucleosome binding proteins HMGN1 and HMGN2 bind preferentially to H3K27ac nucleosomes at cell-type specific chromatin regulatory regions. HMGNs bind directly to the acetylated nucleosome; the H3K27ac residue and linker DNA facilitate the preferential binding of HMGNs to the modified nucleosomes. Loss of HMGNs increases the levels of H3K27me3 and the histone H1 occupancy at enhancers and promoters and alters the interaction of transcription factors with chromatin. These experiments indicate that the H3K27ac epigenetic mark enhances the interaction of architectural protein with chromatin regulatory sites and identify determinants that facilitate the localization of HMGN proteins at regulatory sites to modulate cell-type specific gene expression.
Gut microbiota-derived butyrate regulates gut mucus barrier repair by activating the macrophage/WNT/ERK signaling pathway
Authors: Liang Liping , Liu Le , Zhou Wanyan , Yang Chenghai , Mai Genghui , Li Haolin , Chen Ye 
Published: February 2022

Abstract
Ulcerative colitis (UC) is majorly associated with dysregulation of the dynamic cross-talk among microbial metabolites, intestinal epithelial cells, and macrophages. Several studies have reported the significant role of butyrate in host–microbiota communication. However, whether butyrate provides anti-inflammatory profiles in macrophages, thus contributing to UC intestinal mucus barrier protection, has currently remained elusive. In the current study, we found that butyrate increased mucin production and the proportion of mucin-secreting goblet cells in the colon crypt in a macrophage-dependent manner by using clodronate liposomes. Furthermore, in vivo and in vitro studies were conducted, validating that butyrate facilitates M2 macrophage polarization with the elevated expressions of CD206 and arginase-1 (Arg1). In macrophages/goblet-like LS174T cells co-culture systems, butyrate-primed M2 macrophages significantly enhanced the expression of mucin-2 (MUC2) and SPDEF (goblet cell marker genes) than butyrate alone, while blockade of WNTs secretion or ERK1/2 activation significantly decreased the beneficial effect of butyrate-primed macrophages on goblet cell function. Additionally, the adoptive transfer of butyrate-induced M2 macrophages facilitated the generation of goblet cells and mucus restoration following dextran sulfate sodium (DSS) insult. Taken together, our results revealed a novel mediator of macrophage–goblet cell cross-talk associated with the regulation of epithelial barrier integrity, implying that the microbial metabolite butyrate may serve as a candidate therapeutic target for UC.