bluuebunny/crossref_metadata_2025_split huggingface dataset:
CRISPR/Cas9 correction of a dominant cis-double-variant in COL1A1 isolated from a patient with osteogenesis imperfecta increases the osteogenic capacity of induced pluripotent stem cells
Authors: Cao Yixuan , Li Lulu , Ren Xiuzhi , Mao Bin , Yang Yujiao , Mi Huan , Guan Yun , Li Shan , Zhou Siji , Guan Xin , Yang Tao , Zhao Xiuli 
Published: February 2023

ABSTRACT
Osteogenesis imperfecta (OI) is a hereditary skeletal disorder that is mainly caused by variants in COL1A1/2. So far, no specific treatment has been developed to correct its underlying etiology. We aimed to gain a better understanding of the pathological mechanisms of OI and develop gene therapies to correct OI-causing variants. A de novel cis-double-variant c.[175C&gt;T; 187T&gt;A] in COL1A1 was identified from a 5-year-old OI patient by whole-exome sequencing (WES). Three peptide nucleic acids (PNAs) were designed and then transfected patient-derived fibroblasts. PNA2 affected the translational strand and induced an optimal interfering effect at 0.25μM concentration, proved by Sanger sequencing, qPCR, Western blot, and immunostaining. Additionally, induced pluripotent stem cells (iPSCs) were cultured from patient-derived fibroblasts. Clones of iPSCs with c.187T&gt;A variant and those with both variants largely restored their osteogenic capacities after CRISPR/Cas9 gene editing, which corrected the variants. Importantly, correcting c.187T&gt;A variant alone in CRISPR-edited iPSCs was sufficient to alleviate OI phenotypes, as indicated by increased levels of COL1A1, COL1A2, ALP mRNAs, and COL1A1 protein. Our findings suggest that c.187T&gt;A is the dominant variant of cis-double-variant in COL1A1 that led to OI, and PNA interference and CRISPR/Cas9 gene editing may be new therapeutic tools for OI treatment. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Enhanced conformational exploration of protein loops using a global parameterization of the backbone geometry
Authors: O'Donnell Timothée , Cazals Frédéric 
Published: February 2023

AbstractFlexible loops are paramount to protein functions, with action modes ranging from localized dynamics contributing to the free energy of the system, to large amplitude conformational changes accounting for the repositioning whole secondary structure elements or protein domains. However, generating diverse and low energy loops remains a difficult problem. This work introduces a novel paradigm to sample loop conformations, in the spirit of the hit‐and‐run (HAR) Markov chain Monte Carlo technique. The algorithm uses a decomposition of the loop into tripeptides, and a novel characterization of necessary conditions for Tripeptide Loop Closure to admit solutions. Denoting m the number of tripeptides, the algorithm works in an angular space of dimension 12 m. In this space, the hyper‐surfaces associated with the aforementioned necessary conditions are used to run a HAR‐like sampling technique. On classical loop cases up to 15 amino acids, our parameter free method compares favorably to previous work, generating more diverse conformational ensembles. We also report experiments on a 30 amino acids long loop, a size not processed in any previous work.
Unraveling multilayered extracellular vesicles: Speculation on cause
Authors: Broad Kelly , Walker Sierra A. , Davidovich Irina , Witwer Kenneth , Talmon Yeshayahu , Wolfram Joy 
Published: February 2023

AbstractExtracellular vesicles (EVs) are cell‐released, heterogenous nanoparticles that play important roles in (patho)physiological processes through intercellular communication. EVs are often depicted as having a single lipid bilayer, but many studies have demonstrated the existence of multilayered EVs. There has been minimal inquiry into differences between unilamellar and multilamellar EVs in terms of biogenesis mechanisms and functional effects. This commentary speculates on potential causes and roles of multilamellar EVs and serves as a call to action for the research community to unravel the complex layers of EVs.
Features of T1 pancreatic cancer and validation of the eighth edition AJCC staging system definition using a Korean–Japanese joint cohort and the SEER database
Authors: Kwon Wooil , Heo Jin Seok , Han In Woong , Kang Chang Moo , Hwang Ho Kyoung , Kim Song Cheol , Park Sang‐Jae , Yoon Yoo‐Seok , Kim Yong Hoon , Lim Chang‐Sup , Lee Seung Yeoun , Park Taesung , Takami Hideki , Watanabe Nobuyuki , Shimizu Yasuhiro , Okuno Masataka , Yamaue Hiroki , Kawai Manabu , Seiko Hirono , Nagakawa Yuichi , Osakabe Hiroaki , Sugiura Teiichi , Toyama Hirochika , Ohtsuka Masayuki , Unno Michiaki , Endo Itaru , Kitago Minoru , Jang Jin‐Young 
Published: February 2023

AbstractBackground/PurposeLittle is known about the features of T1 pancreatic ductal adenocarcinoma (PDAC) and its definition in the eighth edition of the American Joint Committee on Cancer (AJCC) staging system needs validation. The aims were to analyze the clinicopathologic features of T1 PDAC and investigate the validity of its definition.MethodData from 1506 patients with confirmed T1 PDAC between 2000 and 2019 were collected and analyzed. The results were validated using 3092 T1 PDAC patients from the Surveillance, Epidemiology, and End Results (SEER) database.ResultsThe median survival duration of patients was 50 months, and the 5‐year survival rate was 45.1%. R0 resection was unachievable in 10.0% of patients, the nodal metastasis rate was 40.0%, and recurrence occurred in 55.2%. The current T1 subcategorization was not feasible for PDAC, tumors with extrapancreatic extension (72.8%) had worse outcomes than those without extrapancreatic extension (median survival 107 vs. 39 months, p < .001). Extrapancreatic extension was an independent prognostic factor whereas the current T1 subcategorization was not. The results of this study were reproducible with data from the SEER database.ConclusionDespite its small size, T1 PDAC displayed aggressive behavior warranting active local and systemic treatment. The subcategorization by the eighth edition of the AJCC staging system was not adequate for PDAC, and better subcategorization methods need to be explored. In addition, the role of extrapancreatic extension in the staging system should be reconsidered.
High C‐reactive protein to lymphocyte ratio predicts mortality outcomes of patients with severe fever with thrombocytopenia syndrome: A multicenter study in China
Authors: Qian Fang , Zhou Wei , Liu Yuanni , Ge Ziruo , Lai Jianming , Zhao Zhenghua , Feng Yang , Lin Ling , Shen Yi , Zhang Zhonglu , Zhang Wei , Fan Tianli , Zhao Yongxiang , Chen Zhihai 
Published: February 2023

AbstractSevere fever with thrombocytopenia syndrome (SFTS) is a life‐threatening infectious disease caused by the SFTS virus (SFTSV). This study aimed to evaluate the predictive power of C‐reactive protein to lymphocyte ratio (CLR) and establish an early‐warning model for SFTS mortality. We retrospectively analyzed hospitalized SFTS patients in six clinical centers from May 2011 to 2022. The efficacy of CLR prediction was evaluated by the receiver operating characteristic (ROC) analysis. A nomogram was established and validated. Eight hundred and eighty‐two SFTS patients (median age 64 years, 48.5% male) were enrolled in this study, with a mortality rate of 17.8%. The area under the ROC curve (AUC) of CLR was 0.878 (95% confidence interval [CI]: 0.850−0.903, p < 0.001), which demonstrates high predictive strength. The least absolute shrinkage and selection operator regression selected seven potential predictors. Multivariate logistic regression analysis determined three independent risk factors, including CLR, to construct the nomogram. The performance of the nomogram displayed excellent discrimination and calibration, with significant net benefits in clinical uses. CLR is a brand‐new predictor for SFTS mortality. The nomogram based on CLR can serve as a convenient tool for physicians to identify critical SFTS cases in clinical practice.
Investigating the effect of ribavirin treatment on genetic mutations in Crimean–Congo haemorrhagic fever virus (CCHFV) through next‐generation sequencing
Authors: D'Addiego Jake , Elaldi Nazif , Wand Nadina , Osman Karen , Bagci Binnur Koksal , Kennedy Emma , Pektas Ayse Nur , Hart Eilish , Slack Gillian , Hewson Roger 
Published: February 2023

AbstractCrimean–Congo haemorrhagic fever (CCHF) is the most widespread tick‐borne viral haemorrhagic fever affecting humans, and yet a licensed drug against the virus (CCHFV) is still not available. While several studies have suggested the efficacy of ribavirin against CCHFV, current literature remains inconclusive. In this study, we have utilised next‐generation sequencing to investigate the mutagenic effect of ribavirin on the CCHFV genome during clinical disease. Samples collected from CCHF patients receiving ribavirin treatment or supportive care only at Sivas Cumhuriyet University Hospital, Turkey, were analysed. By comparing the frequency of mutations in each group, we found little evidence of an overall mutagenic effect. This suggests that ribavirin, administered at the acute stages of CCHFV infection (at the World Health Organization‐recommended dose) is unable to induce lethal mutagenesis that would cause an extinction event in the CCHFV population and reduce viremia.
When time is running out: A growth curve analysis of older workers' retirement intentions
Authors: Cregan Christina , Kulik Carol T. , Perera Sanjeewa , Sardeshmukh Shruti 
Published: February 2023

SummaryUsing dynamic theory and methods, we investigate the phenomenon of older workers who withdraw from paid work while still healthy. We focus on intention to retire as the penultimate stage in the retirement process. We extend socio‐emotional selectivity theory to explain the growth of intention to retire. Older workers have a rising perception of time running out but good health allows for an ongoing choice between remaining in work or active retirement. While, in general, older people in poor health have a greater intention to retire than those in good health, we hypothesize that the passage of time motivates the healthy to increase their intention to retire, especially when manager support is low. We examine longitudinal data consisting of three waves of survey responses (2011, 2012, and 2013) from 495 workers in their 50th year and older. We employ growth curve analysis (random coefficient modeling). The findings show that over a 2‐year period, in contrast to other older workers whose retirement intention remains stable, individuals in consistently good health but with low manager support demonstrate a growth in intention to retire. That is, we identify the “queue jumpers”: those workers who speeded up their retirement process relative to other older workers.
Conditional survival in patients treated for gastric cancer with a curative intent
Authors: Ayloor Seshadri Ramakrishnan , Soman Arya C. , Aggrawal Ajit , Karnawat Anand , Patidar Shailesh , Swaminathan Rajaraman 
Published: February 2023

AbstractBackground and ObjectivesConditional survival (CS) provides the probability that a patient who has already survived a certain number of years after treatment will survive an additional number of years. We aim to study the CS of patients with gastric cancer.MethodsPatients who underwent curative intent treatment for gastric cancer in a single institution between 2007 and 2018 were included in the analysis. The probability (CS) that a patient who has already survived x years will survive an additional y year, was calculated as CS (y/x) = S(x + y)/S(x).ResultsThe probability of surviving an additional 3 years if a patient had already survived 1, 2, 3, 4, and 5 years after treatment were 64.2%, 74.5%, 81.6%, 83.2%, and 88.2%, respectively whereas the 4‐, 5‐, 6‐, 7‐, and 8‐year actuarial OS were only 47.2%, 43.2%, 41%, 39.4%, and 38.2%, respectively. The independent prognostic factors associated with poor survival were age >60 years, T stage ≥T3, N stage ≥N2, proximal tumor location, and lymph node ratio > 0.18. Patients with these high‐risk features showed the greatest increase in CS3 over time.ConclusionCS estimates provided a more dynamic prognostic information over time for patients treated for gastric cancer with curative intent.
Coherent Random Lasing in Subwavelength Quasi‐2D Perovskites
Authors: Fruhling Colton , Wang Kang , Chowdhury Sarah , Xu Xiaohui , Simon Jeffrey , Kildishev Alexander , Dou Letian , Meng Xiangeng , Boltasseva Alexandra , Shalaev Vladimir M. 
Published: February 2023

AbstractQuasi‐2D lead halide perovskites have garnered increasing interest as lasing gain media. Relatively simple fabrication, high refractive index, and unique quantum well structure encourage their use in traditional cavity lasers and cavity‐free systems called random lasers (RLs). Despite tremendous advances reported thus far, coherent random lasing in quasi‐2D perovskite subwavelength films has not been reported. Consequently, coherent optical feedback mechanisms in quasi‐2D perovskite systems are still unexplored. Here, this work reports the observation of coherent random lasing in subwavelength quasi‐2D perovskite films. Statistical analysis of spectral measurements reveals Lévy‐like intensity fluctuations, replica symmetry breaking confirms random lasing, and the coherent modes are studied with spectral and spatial correlation techniques. The observed coherent lasing modes are found to be extended states that arise from the random crystal grain structure during fabrication and span the entire pump volume. These modes out‐compete diffusive lasing due to their coherence.
Image‐based scatter correction for cone‐beam CT using flip swin transformer U‐shape network
Authors: Zhang Xueren , Jiang Yangkang , Luo Chen , Li Dengwang , Niu Tianye , Yu Gang 
Published: February 2023

AbstractBackgroundCone beam computed tomography (CBCT) plays an increasingly important role in image‐guided radiation therapy. However, the image quality of CBCT is severely degraded by excessive scatter contamination, especially in the abdominal region, hindering its further applications in radiation therapy.PurposeTo restore low‐quality CBCT images contaminated by scatter signals, a scatter correction algorithm combining the advantages of convolutional neural networks (CNN) and Swin Transformer is proposed.MethodsIn this paper a scatter correction model for CBCT image, the Flip Swin Transformer U‐shape network (FSTUNet) model, is proposed. In this model, the advantages of CNN in texture detail and Swin Transformer in global correlation are used to accurately extract shallow and deep features, respectively. Instead of using the original Swin Transformer tandem structure, we build the Flip Swin Transformer Block to achieve a more powerful inter‐window association extraction. The validity and clinical relevance of the method is demonstrated through extensive experiments on a Monte Carlo (MC) simulation dataset and frequency split dataset generated by a validated method, respectively.ResultExperimental results on the MC simulated dataset show that the root mean square error of images corrected by the method is reduced from over 100 HU to about 7 HU. Both the structural similarity index measure (SSIM) and the universal quality index (UQI) are close to 1. Experimental results on the frequency split dataset demonstrate that the method not only corrects shading artifacts but also exhibits a high degree of structural consistency. In addition, comparison experiments show that FSTUNet outperforms UNet, Deep Residual Convolutional Neural Network (DRCNN), DSENet, Pix2pixGAN, and 3DUnet methods in both qualitative and quantitative metrics.ConclusionsAccurately capturing the features at different levels is greatly beneficial for reconstructing high‐quality scatter‐free images. The proposed FSTUNet method is an effective solution to CBCT scatter correction and has the potential to improve the accuracy of CBCT image‐guided radiation therapy.
Composite nerve conduction scores and signs for diagnosis and somatic staging of diabetic polyneuropathy: Mid North American ethnic cohort survey
Authors: Davies Jenny L. , Lodermeier Karen A. , Klein Diane M. , Carter Rickey E. , Dyck P. James B. , Litchy William J. , Dyck Peter J. 
Published: February 2023

AbstractIntroduction/AimsIn the Diabetes Control and Complications Trial (DCCT), the minimal nerve conduction (NC) criterion for diabetic sensorimotor polyneuropathy (DSPN) was abnormality of NC in more than one peripheral nerve without specifying the attributes of NCs to be evaluated. In the present study, we assess individual and composite scores of NCs meeting the DCCT criterion and signs for improved diagnosis and assessment of DSPN severity.MethodsEvaluated were 13 attributes and 6 composite NC scores and signs and symptoms in 395 healthy subjects (HS) and 388 persons with diabetes (DM).ResultsPercent abnormality between subjects with DM and HS was remarkably different among individual attributes and the six composite NC scores. For diagnosis of DSPN using the DCCT criterion, assessment of conduction velocities (CVs) and distal latencies (DLs) provided sensitive diagnoses of DSPN. NC amplitudes provided stronger measures of severity. In studied cohorts, DSPN was staged: N0, no NC abnormality using NC score 2 (CVs and DLs), 60.0%; N1, NC abnormality only, 18.4%; N2, NC abnormality and signs of feet or legs, 16.3%; and N3, NC abnormality and signs of thighs, 5.3%.DiscussionFor sensitive and standard diagnosis of DSPN using the DCCT NC criterion, specifically defined composite scores of CVs and DLs, e.g., score 2, is recommended. A composite score of amplitudes, e.g., score 4, provides a stronger measure of neuropathy severity. Also, provided are HS reference values of evaluated attributes of NCs and estimates of staged severity of DSPN of mid North American DM cohorts.
A kind of linear‐quadratic Pareto cooperative differential game with partial information
Authors: Nie Panpan , Wang Guangchen , Wang Yu 
Published: February 2023

SummaryThis article is concerned with a linear‐quadratic (LQ) Pareto cooperative differential game of stochastic differential equation (SDE) with partial information, where the control system is nonhomogeneous. First, we give the existence and uniqueness of solution to a new class of conditional mean‐field forward‐backward stochastic differential equations (CMF‐FBSDEs). Next, we obtain Pareto efficient strategies with a method of weighted sum optimization. It should be noted that the results depend on weight here. Feedback Pareto efficient strategies are obtained under some special information structure, and Pareto solutions are derived through six equations. Meanwhile, we give a characterization of optimal weight under stochastic case. Finally, the theoretical results are used to solve a kind of national income problem, and numerical simulations are given.
Incorporation of graphene oxide to metal‐free phthalocyanine through hydrogen bonding for optoelectronic applications: An experimental and computational study
Authors: Yabaş Ebru , Şenadım‐Tüzemen Ebru , Kaya Savaş , Maslov Michael M. , Erden Fuat 
Published: February 2023

AbstractThis paper focuses on incorporation of graphene oxide (GO) to metal‐free phthalocyanine (MPc) through only hydrogen bonding and π‐π stacking. Briefly, Pc‐GO composites at various concentrations were prepared by self‐assembly method. The processing time was kept below 10 min to avoid covalent attachment and we aimed at answering the research question of what will happen if the conjugation is realized only through hydrogen bonding under extremely limited processing times. The as‐prepared MPc‐GO composites were characterized by Fourier transform infrared (FT‐IR), UV‐Vis, scanning electron microscope (SEM), and fluorescence analysis. We report that the interaction between MPc and GO could immediately be initiated upon mixing of corresponding solutions. Also, complete conjugation by hydrogen bonding and π‐π stacking could be reached even only in 5 min of sonication time. In addition, it was also determined that the prepared MPc‐GO composites are stable at room conditions and during dilution. Finally, the optoelectronic properties of MPc and MPc‐GO composites were also investigated experimentally and theoretically. Both experimental and theoretical results suggest that MPc‐GO composites exhibit improved optoelectronic properties as compared to MPc, even though the conjugation of GO to MPc was only via hydrogen bonding without covalent attachment.
Inhibition of heat‐induced protein aggregation by zirconium phthalocyanines
Authors: Chernii Svitlana , Losytskyy Mykhaylo , Tretyakova Iryna , Kharchuk Maksym , Vakarov Serhii , Kovalskyy Dmytro , Gerasymchyk Yuriy , Pekhnyo Vasyl , Chernii Viktor , Kovalska Vladyslava 
Published: February 2023

AbstractSpecific proteins found in food sources tend to aggregate into fibrils under heat treatment; studying these aggregation processes and developing tools to control protein heat‐induced aggregation is an active area of research. Phthalocyanine complexes are known to exhibit antiprionic and anti‐fibrillogenic activity. Thus, the anti‐fibrillogenic effect of a series of Zr phthalocyanines with different out‐of‐plane coordinated ligands, namely positively charged (PcZrLys2), negatively charged (PcZrCitr2), and group able to form disulfide bridges (PcZrS2), on the heat‐induced aggregation of such proteins as BLG, insulin, and lysozyme was studied. The inhibition of reaction activity up to about 90% was observed in the presence of these compounds for all proteins. The effective concentration of the inhibitor was calculated for the compound with the highest activity (PcZrS2) to be 10.6 ± 3.6 and 7.3 ± 1.2 μM/L, respectively. Fluorescence spectroscopy studies demonstrated similar binding constants of three phthalocyanines binding with BLG globule. This is consistent with the results of molecular dynamics simulation, which imply the interaction of the globule with the tetrapyrrole macrocycle of phthalocyanine, leading to the globule stabilization. At the same time, TEM shows that in the presence of phthalocyanine PcZrS2, thinner and longer fibrils were formed compared to control in all three proteins (BLG, insulin, and lysozyme). Thus, we can conclude that phthalocyanine PcZrS2 affects the amyloid aggregation's general mechanism, which is typical for proteins of different structures. Therefore, the phthalocyanine PcZrS2 is proposed as an anti‐amyloidogenic agent suppressing heat‐induced aggregation of proteins of different structures, making it potentially suitable for application in the food industry.