bluuebunny/crossref_metadata_2025_split huggingface dataset:
Report of new variants in PPIL1 underlying type 14 pontocerebellar hypoplasia and their associated phenotypic manifestations in two fetuses
Authors: Zhang Yuxin , Yan Lulu , Xie Min , Xue Jiangyang , Yang Xumian , Xue Yongming , Tian Liyun , Li Haibo 
Published: May 2023

AbstractMutations in the PPIL1 gene have been linked to type 14 pontocerebellar hypoplasia (PCH14); however, prenatal clinical characteristics of PCH14 caused by mutations in the PPIL1 gene have not been reported. This study reports the first prenatal case of PCH14 diagnosed by whole‐exome sequencing (WES). Two fetuses with severe microcephaly and cerebral dysplasia, along with their parents, underwent WES. The effects of the discovered PPIL1 variants on PPIL1 protein function were investigated using bioinformatics tools. WES revealed two compound heterozygous missense mutations in PPIL1, c.376C > G (p.His126Asp) and c.392G > T (p.Arg131Leu), inherited from the mother and father, respectively. The co‐segregation of PPIL1 mutations in this family was confirmed using Sanger sequencing, identifying two PCH14‐affected fetuses. Bioinformatics analysis revealed that these mutations could disrupt the formation of hydrogen bonds, altering the structural stability of the PPIL1 protein. This study is the first to define the clinical characteristics of PCH14 during pregnancy and reports a novel heterozygous missense variant, expanding the PCH14‐related mutational spectrum of PPIL1.
The Effect of the Axle End Structure and Number of Through‐Space Bonds on the Properties of Rotaxane Crosslinked Polymers
Authors: Akae Yosuke , Sawada Jun , Nakajima Ken , Takata Toshikazu 
Published: May 2023

AbstractA rotaxane crosslinker (RC) is known to toughen the resulting rotaxane crosslinked polymer (RCP) via a stress dispersion effect that is attributed to the movable nature of the crosslinking structure. To evaluate this toughening mechanism in detail, a series of structure‐definite RCs equipped with different axle end structures or different numbers of wheel components were synthesized, and subjected to free radical polymerization with a vinyl monomer to obtain RCPs. Analyses of the obtained RCPs revealed that the size of the axle end structure should be well‐balanced to produce a strong toughening effect, and a [3]rotaxane crosslinker works more effectively than [2]rotaxane to toughen RCPs. The mobility of the crosslinking points, in terms of rotational and flipping movements, was more crucial to toughening the RCP than that of translational movement along the axle. The first observation of the above crucial findings proved the utility of the systematic molecular design used in this study.
Sulfur Poisoning and Self‐Recovery of Single‐Site Rh1/Porous Organic Polymer Catalysts for Olefin Hydroformylation
Authors: Feng Siquan , Jiang Miao , Song Xiangen , Qiao Panzhe , Yan Li , Cai Yutong , Li Bin , Li Cunyao , Ning lili , Liu Siyue , Zhang Weiqing , Wu Guorong , Yang Jiayue , Dong Wenrui , Yang Xueming , Jiang Zheng , Ding Yunjie 
Published: May 2023

AbstractSulfur poisoning and regeneration are global challenges for metal catalysts even at the ppm level. The sulfur poisoning of single‐metal‐site catalysts and their regeneration is worthy of further study. Herein, sulfur poisoning and self‐recovery are first presented on an industrialized single‐Rh‐site catalyst (Rh1/POPs). A decreased turnover frequency of Rh1/POPs from 4317 h−1 to 318 h−1 was observed in a 1000 ppm H2S co‐feed for ethylene hydroformylation, but it self‐recovered to 4527 h−1 after withdrawal of H2S, whereas the rhodium nanoparticles demonstrated poor activity and self‐recovery ability. H2S reduced the charge density of the single Rh atom and lowered its Gibbs free energy with the formation of inactive (SH)Rh(CO)(PPh3‐frame)2, which could be regenerated to active HRh(CO)(PPh3‐frame)2 after withdrawing H2S. The mechanism and the sulfur‐related structure–activity relationship were highlighted. This work provides an understanding of heterogeneous ethylene hydroformylation and sulfur‐poisoned regeneration in the science of single‐atom catalysts.
Accelerated weathering of furanoate polyesters: Effect of molecular weight, crystallinity, and time
Authors: Maaskant Evelien , Aarsen Celine V. , van Es Daan S. 
Published: May 2023

AbstractFilms of poly(ethylene furanoate) (PEF) and poly(neopentyl furanoate) (PNF) of different molecular weights were artificially weathered in a Q‐SUN test chamber for up to 500 h. The chemical and physical changes of the films have been evaluated with a wide range of techniques. All films, independent of molecular weight or crystallinity, show evidence of partial cross‐linking and the formation of new carbonyl species. Furthermore, all irradiated films show changes in thermal properties and crystallization behavior. The extent of degradation was higher for the amorphous films as compared to their semi‐crystalline counterparts, suggesting that UV degradation predominantly occurs in the amorphous phase. The apparent higher UV‐sensitivity of PNF, as compared to PEF, suggests that the nature of the diol, and the resulting polymer properties, affects the UV‐stability of the polymer. Nevertheless, comparison with poly(ethylene terephthalate) (PET) shows that the different electronic structure and properties of the furan ring are the most likely cause of the observed UV‐instability.
The behavior and mechanism of tris‐(3‐dopo‐propyl)‐triazine trione flame retardant polyethylene terephthalate
Authors: Liu Hao‐Yu , Xin Fei , Du Jia‐Ying , Chen Yu 
Published: May 2023

AbstractA 9,10‐dihydro‐9‐oxa‐10 phosphophenanthrene‐10‐oxide based derivative tris‐(3‐dopo‐propyl)‐triazine trione (TAD) is applied to polyethylene terephthalate (PET). The melting and blending process of the composite is carried out through twin screws. The flame retardancy, thermostability, and mechanical property have elevated with slight load agent. The limiting oxygen index (LOI), vertical burning test (UL 94), and cone calorimeter test are proceeded to sustain the flame retardancy of PET/TAD‐x. The 30.2% LOI value and UL 94V‐1 rating will be attained with 5 wt% load, the peak of heat release rate show 33.4% decrease, concurrently. The thermogravimetric analysis is performed to characterized the constancy of flame retardant composites during the heating process. Relevant evidence express that TAD provided appreciable assistance in improving carbon‐forming capacity and postponing initial decomposition temperature. The Raman spectra, TG‐Fourier transform infrared, Hot‐Stage FTIR are used to explain the connection about the optimization of performance and the alteration of products in pyrolyzing or after pyrolyzation. In addition, the mechanical properties are supported via tensile and impact test. This study confirms TAD has great potential competitiveness in future halogen‐free flame retardant applications as viable and environmentally friendly to polyester material.
Minimum‐energy time‐varying formation of distributed multi‐agent systems with interaction constraints
Authors: Qin Donghao , Wang Le , Li Junlong , Xi Jianxiang 
Published: May 2023

AbstractIn the current paper, minimum‐energy time‐varying formation design and analysis problems of distributed multi‐agent systems (DMASs) subjected to randomly switching topologies and aperiodic interaction pauses are investigated, which can ensure the time‐varying formation achievement with the minimum‐energy consumption in the sense of the linear matrix inequality. Firstly, a formation control protocol is designed with local information of neighboring agents, where the total energy consumption during the formation process is constructed and the impacts of interaction constraints are imposed. Then, minimum‐energy formation design and analysis criteria of DMASs are presented in terms of the linear matrix inequality tool, which can be checked by the generalized eigenvalue method. Finally, a numerical simulation is shown to verify the effectiveness of the main results.
Shared learning from a physiologically based pharmacokinetic modeling strategy for human pharmacokinetics prediction through retrospective analysis of Genentech compounds
Authors: Mao Jialin , Ma Fang , Yu Jesse , Bruyn Tom De , Ning Miaoran , Bowman Christine , Chen Yuan 
Published: May 2023

AbstractThe quantitative prediction of human pharmacokinetics (PK) including the PK profile and key PK parameters are critical for early drug development decisions, successful phase I clinical trials, and the establishment of a range of doses to enable phase II clinical dose selection. Here, we describe an approach employing physiologically based pharmacokinetic (PBPK) modeling (Simcyp) to predict human PK and to validate its performance through retrospective analysis of 18 Genentech compounds for which clinical data are available. In short, physicochemical parameters and in vitro data for preclinical species were integrated using PBPK modeling to predict the in vivo PK observed in mouse, rat, dog, and cynomolgus monkey. Through this process, the in vitro to in vivo extrapolation (IVIVE) was determined and then incorporated into PBPK modeling in order to predict human PK. Overall, the prediction obtained using this PBPK‐IVIVE approach captured the observed human PK profiles of the compounds from the dataset well. The predicted Cmax was within 2‐fold of the observed Cmax for 94% of the compounds while the predicted area under the curve (AUC) was within 2‐fold of the observed AUC for 72% of the compounds. Additionally, important IVIVE trends were revealed through this investigation, including application of scaling factors determined from preclinical IVIVE to human PK prediction for each molecule. Based upon the analysis, this PBPK‐based approach now serves as a practical strategy for human PK prediction at the candidate selection stage at Genentech.
Single‐cell atlas reveals a distinct immune profile fostered by T cell‐B cell crosstalk in triple negative breast cancer
Authors: Ding Shuning , Qiao Niu , Zhu Qingchen , Tong Yiwei , Wang Shengyue , Chen Xiaosong , Tian Qiang , Xiao Yichuan , Shen Kunwei 
Published: May 2023

AbstractBackgroundCharacterizing the unique immune microenvironment of each tumor is of great importance for better predicting prognosis and guiding cancer immunotherapy. However, the unique features of the immune microenvironment of triple negative breast cancer (TNBC) compared with other subtypes of breast cancer remain elusive. Therefore, we aimed to depict and compare the immune landscape among TNBC, human epidermal growth factor receptor 2‐positive (HER2+) breast cancer, and luminal‐like breast cancer.MethodsSingle‐cell RNA sequencing (scRNA‐seq) was performed on CD45+ immune cells isolated from human normal breast tissues and primary breast tumors of various subtypes. By analyzing the scRNA‐seq data, immune cell clusters were identified and their proportions as well as transcriptome features were compared among TNBC, human HER2+ breast cancer, and luminal‐like breast cancer. Pseudotime and cell‐cell communication analyses were also conducted to characterize the immune microenvironment.ResultsScRNA‐seq data of 117,958 immune cells were obtained and 31 immune clusters were identified. A unique immunosuppressive microenvironment in TNBC was decoded as compared to that in HER2+ or luminal‐like breast cancer, which was characterized by higher proportions of regulatory T cells (Tregs) and exhausted CD8+ T cells and accompanied by more abundant plasma cells. Tregs and exhausted CD8+T cells in TNBC exhibited increased immunosuppression signature and dysfunctional scores. Pseudotime analyses showed that B cells tended to differentiate to plasma cells in TNBC. Cell‐cell communication analyses indicated that these unique features are fostered by the diversified T cell‐B cell crosstalk in TNBC. Based on the T cell‐B cell crosstalk, a prognostic signature was established that could effectively predict the prognosis status for patients with TNBC. Additionally, it was found that TNBC had a higher proportion of cytotoxic natural killer (NK) cells, whereas HER2+ or luminal‐like breast cancer lost this feature, suggesting that HER2+ or luminal‐like breast cancer, but not TNBC, may benefit from NK‐based immunotherapy.ConclusionsThis study identified a distinct immune feature fostered by T cell‐B cell crosstalk in TNBC, which provides better prognostic information and effective therapeutic targets for breast cancer.
AEGAN: Generating imperceptible face synthesis via autoencoder‐based generative adversarial network
Authors: Che Aolin , Yang Jing‐Hua , Guo Cai , Dai Hong‐Ning , Xie Haoran , Li Ping 
Published: May 2023

AbstractFace recognition (FR) systems based on convolutional neural networks have shown excellent performance in human face inference. However, some malicious users may exploit such powerful systems to identify others' face images disclosed by victims' social network accounts, consequently obtaining private information. To address this emerging issue, synthesizing face protection images with visual and protective effects is essential. However, existing face protection methods encounter three critical problems: poor visual effect, limited protective effect, and trade‐off between visual and protective effects. To address these challenges, we propose a novel face protection approach in this article. Specifically, we design a generative adversarial network (GAN) framework with an autoencoder (AEGAN) as the generator to synthesize the protection images. It is worth noting that we introduce an interpolation upsampling module in the decoder in order to let the synthesized protection images evade recognition by powerful convolution‐based FR systems. Furthermore, we introduce an attention module with a perceptual loss in AEGAN to enhance the visual effects of synthesized images by AEGAN. Extensive experiments have shown that AEGAN not only can maintain the comfortable visual quality of synthesized images but also prevent the recognition of commercial FR systems, including Baidu and iKLYTEK.
Synthesis of New Bis(pyrazolo[1,5‐a]pyrimidines) Linked to Different Spacers as Potential MurB Inhibitors
Authors: Sanad Sherif M. H. , Abdelsalam Alshimaa A. M. , Gamal Eldin Aya A. , Abdelfattah Esraa H. , Hussein Fatma R. M. , Mohammed Nada G. , Taha Nariman A. S. , Mekky Ahmed E. M. 
Published: May 2023

AbstractAn efficient protocol was adopted to efficiently prepare three new series of bis(pyrazolo[1,5‐a]pyrimidines) linked to different spacers. The new bis(pyrazolo[1,5‐a]pyrimidines) were prepared in 80–90 % yields by reacting the respective bis(enaminones) and 4‐(4‐substituted benzyl)‐1H‐pyrazole‐3,5‐diamines in pyridine at reflux temperature for 5–7 h. The new products showed a wide spectrum of antibacterial activity against six different bacterial strains. In general, propane‐ and butane‐linked bis(pyrazolo[1,5‐a]pyrimidines), which are attached to 3‐(4‐methyl‐ or 4‐methoxybenzyl) units, had the best antibacterial activity with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values up to 2.5 and 5.1 μM, respectively. Additionally, the previous products demonstrated promising MurB inhibitory activity with IC50 values up to 7.2 μM.
Idiopathic remitting seronegative symmetrical synovitis with pitting edema syndrome with underlying history of malignancy
Authors: Kim Kain , Marvil Charles , Adhyaru Bhavin B. 
Published: May 2023

Key Clinical MessageBy reporting this case, we hope to emphasize the importance of maintaining a high index of clinical suspicion for the early recognition of RS3PE in patients presenting with atypical symptoms of PMR and underlying history of malignancy.AbstractRemitting seronegative symmetrical synovitis with pitting edema is a rare rheumatic syndrome of unknown etiology. It shares qualities with many other common rheumatological disorders such as rheumatoid arthritis and polymyalgia rheumatica, making diagnosis especially challenging. RS3PE has been speculated to be a paraneoplastic syndrome, and those cases associated with underlying malignancy have shown to respond poorly to conventional treatment. Therefore, it is advisable to routinely screen patients with malignancy and presenting with RS3PE for cancer recurrence, even if in remission.
Research on fatigue optimization simulation of polymeric heart valve based on the iterative sub‐regional thickened method
Authors: Tao Li , Jingyuan Zhou , Hongjun Zhou , Yijing Li , Yan Xiong , Yu Chen 
Published: May 2023

AbstractProsthetic polymeric heart valves (PHVs) have the potential to overcome the inherent material and design limitations of traditional valves in the treatment of valvular heart disease; however, their durability remains limited. Optimal design of the valve structure is necessary to improve their durability. This study aimed to enhance the fatigue resistance of PHVs by improving the stress distribution. Iterative subregional thickening of the leaflets was used, and the mechanical stress distribution and hemodynamics of these polymeric tri‐leaflet valves were characterized using a fluid–structure interaction approach. Subregional thickening led to a reduction in stress concentration on the leaflet, with the effective orifice area still meeting ISO 5840‐3 and the regurgitant volume achieving a similar value to those in previous studies. The maximum stress in the final iteration was reduced by 28% compared with that of the prototype. The proposed method shows potential for analyzing the stress distribution and hemodynamic performance of subregional thickened valves and can further improve the durability of PHVs.
Niche specialization and community niche space increase with species richness in filter‐feeder assemblages
Authors: Sánchez González Irene , Hopper Garrett W. , Bucholz Jamie R. , Kubala Megan E. , Lozier Jeffrey D. , Atkinson Carla L. 
Published: May 2023

AbstractEcological theory posits that higher species richness should be associated with greater exploitation of resources and niche packing resulting from either increasing species niche overlap or specialization of species' niches. Research evaluating niche theory in animals tends to focus on organisms among functional feeding guilds, while resource partitioning might be more critical within functional groups. Freshwater mussels (Family: Unionidae) are a diverse and imperiled group of animals that are ideal models to test niche occupancy due to their functional similarity as filter‐feeders and their occurrence in spatially and temporally stable multispecies aggregations. We evaluated the relationship between species richness and the trophic niche area for 25 mussel species occurring in 22 aggregations in the southeastern United States using stable isotope analysis (δ13C and δ15N) of soft tissue (n = 1057). Mean species standard ellipse area decreased with species richness, whereas ellipse overlap was not related to richness, indicating increased niche specialization may be the primary mechanism allowing coexistence in species‐rich communities. Total community isotopic area increased with richness, suggesting species‐rich communities also use a broader range of resources and may not be species‐saturated. Overall, our data support the niche‐packing hypothesis by illustrating the importance of niche partitioning within a species‐rich guild of aquatic animals.
Analytical separation of plasmid DNA isoforms using anion exchanging chromatographic monoliths with 6 µm channels
Authors: Pavlin Nejc , Černigoj Urh , Bavčar Mojca , Plesničar Tjaša , Mavri Jan , Zidar Martin , Bone Matevž , Kralj Savič Urška , Sever Tadej , Štrancar Aleš 
Published: May 2023

AbstractHigh‐performance liquid chromatography (HPLC)‐based analytical assays are used to effectively monitor purity and quantity of plasmid DNA (pDNA) throughout the purification process. However, the phenomenon of physical entrapment of open circular (OC) isoforms pDNA inside narrow channels of chromatographic support decreases its accuracy and precision and the effect increases with pDNA size. The purpose of the study was to develop a chromatographic method for accurate analytical separation between isoforms of <16 kbp pDNA using weak anion exchanging monolithic column with large (6 µm) convective channels. Purified samples of 4.7 and 15.4 kbp large pDNA with known isoform composition were prepared and their isoforms separated in ascending salt gradient. Both OC and supercoiled (SC) isoforms were baseline separated at a flow rate below 0.5 mL min−1 in a guanidinium chloride (GdnCl) gradient with a ≥95% OC pDNA elution recovery. However, these chromatographic conditions increased 2 times the peak width for linear (LIN) pDNA isoform compared to the results using monoliths with 1.4 µm channel size. If other chaotropic agents, such as urea or thiocyanate (SCN), were added to Gdn ions, the elution volume for LIN isoform decreased. Optimization of combined GdnCl/GdnSCN gradient for pDNA elution resulted in a simple and robust chromatographic method, where OC–LIN and LIN–SC pDNA (up to 15 kbp size) were separated with resolution above 1.0 and above 2.0, respectively. The accessibility and general acceptance of anion exchange chromatography for pDNA analytics give the newly developed method a great potential for in‐process control monitoring of pDNA production processes.
Influence of variants in serotonin modulating genes on the risk, aggressiveness, and prognosis of oropharynx cancer
Authors: Queiroz Gabriela Souza Rodrigues , Carron Juliana , Macedo Ligia Traldi , Lima Carmen Silvia Passos , Lourenço Gustavo Jacob 
Published: May 2023

AbstractBackgroundSerotonin (5‐HT) is involved in regulating tumor growth, as well as psychiatric disorders. It is synthesized by tryptophan hydroxylase (TPH) and acts through 5‐HT receptors (HTRs). Single‐nucleotide variations (SNVs) in TPH1 rs623580 (T>A), TPH2 rs4570625 (G>T), and HTR1D rs674386 (G>A) may affect 5‐HT levels. However, the effect of these SNVs on oropharynx carcinoma (OPC) is unknown.MethodsDNA from 251 patients with OPC and 254 controls was analyzed by RT‐PCR. Transcriptional activity of TPH1 rs623580 and HTR1D rs674386 was studied by luciferase assays. Multivariate statistical tests were utilized to evaluate group differences and survival outcomes.ResultsTPH1 TT was more frequent in patients than in controls (OR: 1.56, p = 0.03). Patients with HTR1D GG/GA showed invasive tumors (p = 0.01) and shorter survival (HR: 1.66, p = 0.04). TPH1 TT (0.79‐fold, p = 0.03) and HTR1D GG (0.64‐fold, p = 0.008) presented lower transcriptional activity.ConclusionOur data suggest that SNVs in 5‐HT modulating genes can influence OPC.
Healthcare in the Himalayan Kingdom of Bhutan: Lessons for the United States and other western healthcare systems
Authors: Meyer Rebecca C. , Meyer Shelly 
Published: May 2023

AbstractBhutan has demonstrated a trajectory of advances in healthcare, while still remaining true to its culture and traditional forms of medicine. Most recently, Bhutan gained international attention when it implemented a strategic Covid‐19 vaccination programme that protected a greater percentage of its population than observed in Western industrialised nations. This accomplishment supports the idea that there are lessons from Bhutan to be shared with the rest of the world. In this work, we delineate our observations of the Bhutanese healthcare system, based on field observations in several Bhutanese cities, and results from surveys of Bhutanese physicians. We identify a number of unique practices that influence patient compliance, health education, and access to care in the Bhutanese system, that may be of particular interest and applicability to other healthcare systems. These include housing multiple health services at one location, fully funded medical visits, using non‐physician teachers for health education and use of Gross National Happiness (GNH) measures in care.