bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Kaposi’s sarcoma-associated herpes virus-encoded microRNA contributes to dilated cardiomyopathy
Authors: Zhao Yanru , Li Huaping , Du Hengzhi , Yin Zhongwei , He Mengying , Fan Jiahui , Nie Xiang , Sun Yang , Hou Huiying , Dai Beibei , Zhang Xudong , Cai Yuanyuan , Jin Kunying , Ding Nan , Wen Zheng , Chang Jiang , Chen Chen , Wang Dao Wen 
Published: June 2023

AbstractDilated cardiomyopathy (DCM) is the leading cause of heart transplantation. By microRNA (miRNA) array, a Kaposi’s sarcoma-associated herpes virus (KSHV)-encoded miRNA, kshv-miR-K12-1-5p, was detected in patients with DCM. The KSHV DNA load and kshv-miR-K12-1-5p level in plasma from 696 patients with DCM were measured and these patients were followed-up. Increased KSHV seropositivity and quantitative titers were found in the patients with DCM compared with the non-DCM group (22.0% versus 9.1%, p < 0.05; 168 versus 14 copies/mL plasma, p < 0.05). The risk of the individual end point of death from cardiovascular causes or heart transplantation was increased among DCM patients with the KSHV DNA seropositivity during follow-up (adjusted hazard ratio 1.38, 95% confidence interval 1.01–1.90; p < 0.05). In heart tissues, the KSHV DNA load was also increased in the heart from patients with DCM in comparison with healthy donors (1016 versus 29 copies/105 cells, p < 0.05). The KSHV and kshv-miR-K12-1-5p in DCM hearts were detected using immunofluorescence and fluorescence staining in situ hybridization. KSHV itself was exclusively detectable in CD31-positive endothelium, while kshv-miR-K12-1-5p could be detected in both endothelium and cardiomyocytes. Moreover, kshv-miR-K12-1-5p released by KSHV-infected cardiac endothelium could disrupt the type I interferon signaling pathway in cardiomyocytes. Two models of kshv-miR-K12-1-5p overexpression (agomiR and recombinant adeno-associated virus) were used to explore the roles of KSHV-encoded miRNA in vivo. The kshv-miR-K12-1-5p aggravated known cardiotropic viruses-induced cardiac dysfunction and inflammatory infiltration. In conclusion, KSHV infection was a risk factor for DCM, providing developmental insights of DCM involving virus and its miRNA (https://clinicaltrials.gov. Unique identifier: NCT03461107).
Brain connectivity in major depressive disorder: a precision component of treatment modalities?
Authors: Tura Asude , Goya-Maldonado Roberto 
Published: June 2023

AbstractMajor depressive disorder (MDD) is a very prevalent mental disorder that imposes an enormous burden on individuals, society, and health care systems. Most patients benefit from commonly used treatment methods such as pharmacotherapy, psychotherapy, electroconvulsive therapy (ECT), and repetitive transcranial magnetic stimulation (rTMS). However, the clinical decision on which treatment method to use remains generally informed and the individual clinical response is difficult to predict. Most likely, a combination of neural variability and heterogeneity in MDD still impedes a full understanding of the disorder, as well as influences treatment success in many cases. With the help of neuroimaging methods like functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI), the brain can be understood as a modular set of functional and structural networks. In recent years, many studies have investigated baseline connectivity biomarkers of treatment response and the connectivity changes after successful treatment. Here, we systematically review the literature and summarize findings from longitudinal interventional studies investigating the functional and structural connectivity in MDD. By compiling and discussing these findings, we recommend the scientific and clinical community to deepen the systematization of findings to pave the way for future systems neuroscience roadmaps that include brain connectivity parameters as a possible precision component of the clinical evaluation and therapeutic decision.
CircRNAs in colorectal cancer: potential biomarkers and therapeutic targets
Authors: Zhang Yuying , Luo Jingyan , Yang Weikang , Ye Wen-Chu 
Published: June 2023

AbstractGlobally, colorectal cancer (CRC) is the third most prevalent cancer and the second leading cause of cancer-related deaths. Circular RNAs (circRNAs) are single-stranded RNA with covalently closed-loop structures and are highly stable, conserved, and abundantly expressed in various organs and tissues. Recent research found abnormal circRNA expression in CRC patients’ blood/serum, cells, CRC tissues, and exosomes. Furthermore, mounting data demonstrated that circRNAs are crucial to the development of CRC. CircRNAs have been shown to exert biological functions by acting as microRNA sponges, RNA-binding protein sponges, regulators of gene splicing and transcription, and protein/peptide translators. These characteristics make circRNAs potential markers for CRC diagnosis and prognosis, potential therapeutic targets, and circRNA-based therapies. However, further studies are still necessary to improve the understanding of the roles and biological mechanisms of circRNAs in the development of CRC. In this review, up-to-date research on the role of circRNAs in CRC was examined, focusing on their potential application in CRC diagnosis and targeted therapy, which would advance the knowledge of the functions of circRNAs in the development and progression of CRC.
Histone H2A Lys130 acetylation epigenetically regulates androgen production in prostate cancer
Authors: Nguyen Thanh , Sridaran Dhivya , Chouhan Surbhi , Weimholt Cody , Wilson Audrey , Luo Jingqin , Li Tiandao , Koomen John , Fang Bin , Putluri Nagireddy , Sreekumar Arun , Feng Felix Y. , Mahajan Kiran , Mahajan Nupam P. 
Published: June 2023

AbstractThe testicular androgen biosynthesis is well understood, however, how cancer cells gauge dwindling androgen to dexterously initiate its de novo synthesis remained elusive. We uncover dual-phosphorylated form of sterol regulatory element-binding protein 1 (SREBF1), pY673/951-SREBF1 that acts as an androgen sensor, and dissociates from androgen receptor (AR) in androgen deficient environment, followed by nuclear translocation. SREBF1 recruits KAT2A/GCN5 to deposit epigenetic marks, histone H2A Lys130-acetylation (H2A-K130ac) in SREBF1, reigniting de novo lipogenesis & steroidogenesis. Androgen prevents SREBF1 nuclear translocation, promoting T cell exhaustion. Nuclear SREBF1 and H2A-K130ac levels are significantly increased and directly correlated with late-stage prostate cancer, reversal of which sensitizes castration-resistant prostate cancer (CRPC) to androgen synthesis inhibitor, Abiraterone. Further, we identify a distinct CRPC lipid signature resembling lipid profile of prostate cancer in African American (AA) men. Overall, pY-SREBF1/H2A-K130ac signaling explains cancer sex bias and reveal synchronous inhibition of KAT2A and Tyr-kinases as an effective therapeutic strategy.
Substrate binding-induced conformational transitions in the omega-3 fatty acid transporter MFSD2A
Authors: Bergman Shana , Cater Rosemary J. , Plante Ambrose , Mancia Filippo , Khelashvili George 
Published: June 2023

AbstractMajor Facilitator Superfamily Domain containing 2 A (MFSD2A) is a transporter that is highly enriched at the blood-brain and blood-retinal barriers, where it mediates Na+-dependent uptake of ω−3 fatty acids in the form of lysolipids into the brain and eyes, respectively. Despite recent structural insights, it remains unclear how this process is initiated, and driven by Na+. Here, we perform Molecular Dynamics simulations which demonstrate that substrates enter outward facing MFSD2A from the outer leaflet of the membrane via lateral openings between transmembrane helices 5/8 and 2/11. The substrate headgroup enters first and engages in Na+ -bridged interactions with a conserved glutamic acid, while the tail is surrounded by hydrophobic residues. This binding mode is consistent with a “trap-and-flip” mechanism and triggers transition to an occluded conformation. Furthermore, using machine learning analysis, we identify key elements that enable these transitions. These results advance our molecular understanding of the MFSD2A transport cycle.
Inflationary theory of branching morphogenesis in the mouse salivary gland
Authors: Bordeu Ignacio , Chatzeli Lemonia , Simons Benjamin D. 
Published: June 2023

AbstractThe mechanisms that regulate the patterning of branched epithelia remain a subject of long-standing debate. Recently, it has been proposed that the statistical organization of multiple ductal tissues can be explained through a local self-organizing principle based on the branching-annihilating random walk (BARW) in which proliferating tips drive a process of ductal elongation and stochastic bifurcation that terminates when tips encounter maturing ducts. Here, applied to mouse salivary gland, we show the BARW model struggles to explain the large-scale organization of tissue. Instead, we propose that the gland develops as a tip-driven branching-delayed random walk (BDRW). In this framework, a generalization of the BARW, tips inhibited through steric interaction with proximate ducts may continue their branching program as constraints become alleviated through the persistent expansion of the surrounding tissue. This inflationary BDRW model presents a general paradigm for branching morphogenesis when the ductal epithelium grows cooperatively with the domain into which it expands.
Directed natural evolution generates a next-generation oncolytic virus with a high potency and safety profile
Authors: Guo Li , Hu Cheng , Liu Yang , Chen Xiaoyu , Song Deli , Shen Runling , Liu Zhanzhen , Jia Xudong , Zhang Qinfen , Gao Yuanzhu , Deng Zhezhi , Zuo Tao , Hu Jun , Zhu Wenbo , Cai Jing , Yan Guangmei , Liang Jiankai , Lin Yuan 
Published: June 2023

AbstractOncolytic viruses (OVs) represent a type of encouraging multi-mechanistic drug for the treatment of cancer. However, attenuation of virulence, which is generally required for the development of OVs based on pathogenic viral backbones, is frequently accompanied by a compromised killing effect on tumor cells. By exploiting the property of viruses to evolve and adapt in cancer cells, we perform directed natural evolution on refractory colorectal cancer cell HCT-116 and generate a next-generation oncolytic virus M1 (NGOVM) with an increase in the oncolytic effect of up to 9690-fold. The NGOVM has a broader antitumor spectrum and a more robust oncolytic effect in a range of solid tumors. Mechanistically, two critical mutations are identified in the E2 and nsP3 genes, which accelerate the entry of M1 virus by increasing its binding to the Mxra8 receptor and antagonize antiviral responses by inhibiting the activation of PKR and STAT1 in tumor cells, respectively. Importantly, the NGOVM is well tolerated in both rodents and nonhuman primates. This study implies that directed natural evolution is a generalizable approach for developing next-generation OVs with an expanded scope of application and high safety.
Cryo-EM structures of ClC-2 chloride channel reveal the blocking mechanism of its specific inhibitor AK-42
Authors: Ma Tao , Wang Lei , Chai Anping , Liu Chao , Cui Wenqiang , Yuan Shuguang , Wing Ngor Au Shannon , Sun Liang , Zhang Xiaokang , Zhang Zhenzhen , Lu Jianping , Gao Yuanzhu , Wang Peiyi , Li Zhifang , Liang Yujie , Vogel Horst , Wang Yu Tian , Wang Daping , Yan Kaige , Zhang Huawei 
Published: June 2023

AbstractClC-2 transports chloride ions across plasma membranes and plays critical roles in cellular homeostasis. Its dysfunction is involved in diseases including leukodystrophy and primary aldosteronism. AK-42 was recently reported as a specific inhibitor of ClC-2. However, experimental structures are still missing to decipher its inhibition mechanism. Here, we present cryo-EM structures of apo ClC-2 and its complex with AK-42, both at 3.5 Å resolution. Residues S162, E205 and Y553 are involved in chloride binding and contribute to the ion selectivity. The side-chain of the gating glutamate E205 occupies the putative central chloride-binding site, indicating that our structure represents a closed state. Structural analysis, molecular dynamics and electrophysiological recordings identify key residues to interact with AK-42. Several AK-42 interacting residues are present in ClC-2 but not in other ClCs, providing a possible explanation for AK-42 specificity. Taken together, our results experimentally reveal the potential inhibition mechanism of ClC-2 inhibitor AK-42.
Predicting the storage time of green tea by myricetin based on surface-enhanced Raman spectroscopy
Authors: Xiao Mengxuan , Chen Yingqi , Zheng Fangling , An Qi , Xiao Mingji , Wang Huiqiang , Li Luqing , Dai Qianying 
Published: June 2023

AbstractThe quality of green tea changes rapidly due to the oxidation and degradation of polyphenols during storage. Herein, a simple and fast Surface-enhanced Raman spectroscopy (SERS) strategy was established to predict changes in green tea during storage. Raman spectra of green tea with different storage times (2020–2015) were acquired by SERS with silver nanoparticles. The PCA-SVM model was established based on SERS to quickly predict the storage time of green tea, and the accuracy of the prediction set was 97.22%. The Raman peak at 730 cm−1 caused by myricetin was identified as a characteristic peak, which increased with prolonged storage time and exhibited a linear positive correlation with myricetin concentration. Therefore, SERS provides a convenient method for identifying the concentration of myricetin in green tea, and myricetin can function as an indicator to predict the storage time of green tea.
A genotype-to-phenotype approach suggests under-reporting of single nucleotide variants in nephrocystin-1 (NPHP1) related disease (UK 100,000 Genomes Project)
Authors: Leggatt Gary , Cheng Guo , Narain Sumit , Briseño-Roa Luis , Annereau Jean-Philippe ,   The Genomics England Research Consortium, Ambrose J. C. , Arumugam P. , Bevers R. , Bleda M. , Boardman-Pretty F. , Boustred C. R. , Brittain H. , Brown M. A. , Caulfield M. J. , Chan G. C. , Giess A. , Griffin J. N. , Hamblin A. , Henderson S. , Hubbard T. J. P. , Jackson R. , Jones L. J. , Kasperaviciute D. , Kayikci M. , Kousathanas A. , Lahnstein L. , Lakey A. , Leigh S. E. A. , Leong I. U. S. , Lopez F. J. , Maleady-Crowe F. , McEntagart M. , Minneci F. , Mitchell J. , Moutsianas L. , Mueller M. , Murugaesu N. , Need A. C. , O‘Donovan P. , Odhams C. A. , Patch C. , Perez-Gil D. , Pereira M. B. , Pullinger J. , Rahim T. , Rendon A. , Rogers T. , Savage K. , Sawant K. , Scott R. H. , Siddiq A. , Sieghart A. , Smith S. C. , Sosinsky A. , Stuckey A. , Tanguy M. , Tavares A. L. Taylor , Thomas E. R. A. , Thompson S. R. , Tucci A. , Welland M. J. , Williams E. , Witkowska K. , Wood S. M. , Zarowiecki M. , Gast Christine , Gilbert Rodney D. , Ennis Sarah 
Published: June 2023

AbstractAutosomal recessive whole gene deletions of nephrocystin-1 (NPHP1) result in abnormal structure and function of the primary cilia. These deletions can result in a tubulointerstitial kidney disease known as nephronophthisis and retinal (Senior–Løken syndrome) and neurological (Joubert syndrome) diseases. Nephronophthisis is a common cause of end-stage kidney disease (ESKD) in children and up to 1% of adult onset ESKD. Single nucleotide variants (SNVs) and small insertions and deletions (Indels) have been less well characterised. We used a gene pathogenicity scoring system (GenePy) and a genotype-to-phenotype approach on individuals recruited to the UK Genomics England (GEL) 100,000 Genomes Project (100kGP) (n = 78,050). This approach identified all participants with NPHP1-related diseases reported by NHS Genomics Medical Centres and an additional eight participants. Extreme NPHP1 gene scores, often underpinned by clear recessive inheritance, were observed in patients from diverse recruitment categories, including cancer, suggesting the possibility of a more widespread disease than previously appreciated. In total, ten participants had homozygous CNV deletions with eight homozygous or compound heterozygous with SNVs. Our data also reveals strong in-silico evidence that approximately 44% of NPHP1 related disease may be due to SNVs with AlphaFold structural modelling evidence for a significant impact on protein structure. This study suggests historical under-reporting of SNVS in NPHP1 related diseases compared with CNVs.
Lifelong nnU-Net: a framework for standardized medical continual learning
Authors: González Camila , Ranem Amin , Pinto dos Santos Daniel , Othman Ahmed , Mukhopadhyay Anirban 
Published: June 2023

AbstractAs the enthusiasm surrounding Deep Learning grows, both medical practitioners and regulatory bodies are exploring ways to safely introduce image segmentation in clinical practice. One frontier to overcome when translating promising research into the clinical open world is the shift from static to continual learning. Continual learning, the practice of training models throughout their lifecycle, is seeing growing interest but is still in its infancy in healthcare. We present Lifelong nnU-Net, a standardized framework that places continual segmentation at the hands of researchers and clinicians. Built on top of the nnU-Net—widely regarded as the best-performing segmenter for multiple medical applications—and equipped with all necessary modules for training and testing models sequentially, we ensure broad applicability and lower the barrier to evaluating new methods in a continual fashion. Our benchmark results across three medical segmentation use cases and five continual learning methods give a comprehensive outlook on the current state of the field and signify a first reproducible benchmark.
MATLAB simulation based study on poliovirus sensing through one-dimensional photonic crystal with defect
Authors: Aly Arafa H. , Mohamed B. A. , Awasthi S. K. , Abdallah Suhad Ali Osman , Amin A. F. 
Published: June 2023

AbstractThe present work, theoretically examined the poliovirus sensor model composed of one-dimensional photonic crystal with defect. The transfer matrix method with the help of MATLAB software has been used to detect poliovirus present in the water sample. The main objective of the present work is to design an efficient sensor by identifying the minute variation in the refractive index of water sample due to change in the poliovirus concentration present in the sample. The alternate layers of aluminum nitride and gallium nitride has been taken to realize Bragg reflector having defect layer of air at center of the Bragg reflector. The effect of change in thickness of defect layer region, period number and incident angle corresponding to transverse electric wave has been examined to optimize the structure which correspond maximum performance of the proposed poliovirus sensing structure. The maximum performance of the structure has been obtained with optimum value of defect layer thickness 1200 nm, period number 10 and incident angle 40°. Under optimum condition maximum sensitivity of 1189.65517 nm/RIU has been obtained when the structure is loaded with waters sample of poliovirus concentration C = 0.005 g/ml whereas figure of merit, quality factor, signal to noise ratio, dynamic range, limit of detection and resolution values become 2618.28446 per RIU, 3102.06475, 2.27791, 2090.99500, 1.91E−05 and 0.24656 respectively.
Real time monitoring of COVID-19 intervention effectiveness through contact tracing data
Authors: Gibson Graham C. , Woody Spencer , James Emily , Weldon Minda , Fox Spencer J. , Meyers Lauren Ancel , Bhavnani Darlene 
Published: June 2023

AbstractCommunities worldwide have used vaccines and facemasks to mitigate the COVID-19 pandemic. When an individual opts to vaccinate or wear a mask, they may lower their own risk of becoming infected as well as the risk that they pose to others while infected. The first benefit–reducing susceptibility–has been established across multiple studies, while the second–reducing infectivity–is less well understood. Using a new statistical method, we estimate the efficacy of vaccines and facemasks at reducing both types of risks from contact tracing data collected in an urban setting. We find that vaccination reduced the risk of onward transmission by 40.7% [95% CI 25.8–53.2%] during the Delta wave and 31.0% [95% CI 19.4–40.9%] during the Omicron wave and that mask wearing reduced the risk of infection by 64.2% [95% CI 5.8–77.3%] during the Omicron wave. By harnessing commonly-collected contact tracing data, the approach can broadly provide timely and actionable estimates of intervention efficacy against a rapidly evolving pathogen.
Improve the performance of CT-based pneumonia classification via source data reweighting
Authors: Xie Pengtao , Zhao Xingchen , He Xuehai 
Published: June 2023

AbstractPneumonia is a life-threatening disease. Computer tomography (CT) imaging is broadly used for diagnosing pneumonia. To assist radiologists in accurately and efficiently detecting pneumonia from CT scans, many deep learning methods have been developed. These methods require large amounts of annotated CT scans, which are difficult to obtain due to privacy concerns and high annotation costs. To address this problem, we develop a three-level optimization based method which leverages CT data from a source domain to mitigate the lack of labeled CT scans in a target domain. Our method automatically identifies and downweights low-quality source CT data examples which are noisy or have large domain discrepancy with target data, by minimizing the validation loss of a target model trained on reweighted source data. On a target dataset with 2218 CT scans and a source dataset with 349 CT images, our method achieves an F1 score of 91.8% in detecting pneumonia and an F1 score of 92.4% in detecting other types of pneumonia, which are significantly better than those achieved by state-of-the-art baseline methods.
A randomized controlled trial for comparing efficacy and safety between intraarticular polynucleotide and hyaluronic acid for knee osteoarthritis treatment
Authors: Kim Tae Woo , Chang Moon Jong , Shin Chung Yeop , Chang Chong Bum , Kang Seung-Baik 
Published: June 2023

AbstractAlthough the use of intra-articular polynucleotide (IA PN) injection as a viscosupplement for knee osteoarthritis (OA) treatment has been proposed, its efficacy and safety compared to high molecular weight hyaluronic acid (HMWHA) injection has not yet been established. The present double-blind, multicenter, randomized controlled trial aimed to investigate the efficacy and safety of IA PN injection compared to IA HMWHA injection. A total of 60 patients (15 men, 45 women, 64.5 ± 7.5 years) with knee OA (Kellgren–Lawrence grade 1–4) were randomly allocated to each group. All patients were given three IA injections of PN (n = 30) or HMWHA (n = 30) at intervals of 1 week. The primary endpoint was the change rate in weight-bearing pain (WBP) 16 weeks from the baseline. The secondary endpoint included multiple measurements: the change rate in WBP rate at 8 weeks; the change rate in pain level at rest and during walking at 8 and 16 weeks; the Korean-Western Ontario and McMaster University Osteoarthritis index; the Euro-Quality of Life-5 Dimension; Clinical Global Impression, Patient Global Impression at 8 and16 weeks, and total consumption of rescue medicine. The mean change rate in the WBP at 16 weeks from the baseline was − 54.0 ± 38.1% in the IA PN group and − 42.8 (± 35.8%) in the IA HMWHA group, and there was no significant difference between the two groups (p = 0.296). All secondary endpoints related with pain and functional outcome also showed no significant difference between the two groups. Pain at the injection site and swelling were reported as adverse events, and the incidence was similar between the two groups. IA PN showed comparable efficacy and safety to IA HMWHA at 3 times injection with an interval of 1 week. IA PN can be useful alternative to IA HMWHA for the treatment of knee OA.