bluuebunny/crossref_metadata_2025_split huggingface dataset:
π‐Electron Fluctuation‐Induced P+/C− Ambiphilic Interaction for Intramolecular CAr−H Bond Activation
Authors: Chen Jianzhou , Wang Junjian , Wang Xinghua , Wei Donghui , Duan Zheng 
Published: November 2023

AbstractHerein, we describe how computational mechanistic understanding has led directly to the discovery of new 2H‐phosphindole for C−CAr bond activation and dearomatization reaction. We uncover an unexpected intramolecular C−H bond activation with a 2H‐phosphindole derivative. This new intriguing experimental observation and further theoretical studies led to an extension of the reaction mechanism with 2H‐phosphindole. Through DFT calculations, we confirm that within a five‐membered ring, the polarizable PC3 unit orchestrates the formation of an electrophilic phosphorus atom (P+) and a nucleophilic carbon atom (C−). This kinetically accessible ambiphilic phosphorus/carbon couple is spatially separated by geometric constraints, and their reactivity is modulated through structural resonance.
Research on promoting the asymmetric reaction of phenylacetylene with aldehydes by chloramphenicol base ligands
Authors: Lu Baozhao , Zhang Ruifeng , Chen Congdi , Jin Liming , Xu Jiaqi , Yang Hongjun 
Published: November 2023

AbstractA series of chiral ligands were synthesized using chloramphenicol base as starting materials. These ligands were applied to the asymmetric catalytic reactions of terminal alkynes with aldehydes to obtain a propargyl alcohol product in high yield (80–94%) with excellent enantioselectivities (82–96%).
Investigating the role of genetic variation in vgll3 and six6 in the domestication of gilthead seabream (Sparus aurata Linnaeus) and European seabass (Dicentrarchus labrax Linnaeus)
Authors: Moulistanos Aristotelis , Nikolaou Theopisti , Sismanoglou Smaragda , Gkagkavouzis Konstantinos , Karaiskou Nikoleta , Antonopoulou Efthimia , Triantafyllidis Alexandros , Papakostas Spiros 
Published: November 2023

AbstractGene function conservation is crucial in molecular ecology, especially for key traits like growth and maturation in teleost fish. The vgll3 and six6 genes are known to influence age‐at‐maturity in Atlantic salmon, but their impact on other fish species is poorly understood. Here, we investigated the association of vgll3 and six6 in the domestication of gilthead seabream and European seabass, both undergoing selective breeding for growth‐related traits in the Mediterranean. We analysed two different sets of samples using two different genotyping approaches. The first dataset comprised farmed and wild populations from Greece, genotyped for SNPs within the two genes (‘gene‐level genotyping’). The second dataset examined 300–600 k SNPs located in the chromosomes of the two genes, derived from a meta‐analysis of a Pool‐Seq experiment involving farmed and wild populations distributed widely across the Mediterranean (‘chromosome‐level genotyping’). The gene‐level analysis revealed a statistically significant allele frequency differences between farmed and wild populations on both genes in each species. This finding was partially supported by the chromosome‐level analysis, identifying highly differentiated regions may be involved in the domestication process at varying distances from the candidate genes. Noteworthy genomic features were found, such as a CpG island in gilthead seabream and novel candidate genes in European seabass, warranting further investigation. These findings support a putative role of vgll3 and six6 in the maturation and growth of gilthead seabream and European seabass, emphasizing the need for further research on their conserved function.
Cheaters among pollinators: Nectar robbing and thieving vary spatiotemporally with floral traits in Afrotropical forests
Authors: Sakhalkar Sailee P. , Janeček Štěpán , Klomberg Yannick , Mertens Jan E. J. , Hodeček Jiří , Tropek Robert 
Published: November 2023

AbstractNectar robbers and thieves are common antagonists in plant–pollinator communities, where they deplete nectar without pollinating flowers, substantially affecting plant reproduction. Nevertheless, little is known about the relative abundance of such nectar exploiters in communities, even though spatiotemporal changes in the frequencies of antagonists and mutualists can exert opposing selection pressures on the traits of the interacting species. Although these effects are highly dependent on the community context, interspecific interactions have almost exclusively been studied in interacting species pairs or single‐plant studies. We hypothesized that flowers might experience a trade‐off between filtering out robbers and thieves. We used an extensive dataset of video‐recorded flower–visitor interactions along a complete elevational gradient in wet and dry seasons on Mount Cameroon to assess spatiotemporal changes in robbing and thieving associated with several floral traits. Of the 14,391 recorded visits, ~4.3% were from robbers (mostly bees and birds) and ~2.1% were from thieves (mostly flies, bees, and moths). Only 29 and 39 of the 194 studied plants were robbed and thieved, respectively. We found that specialized floral traits that prevented thieving (such as long floral tubes or spurs) made flowers susceptible to robbing, and vice versa. Cheating behavior was most frequent at mid‐elevations, with more frequent robbing during the wet season and thieving during the dry season. These trends were linked to the local floral trait composition and the associations of cheating groups with specific floral traits. Our results suggest that the roles of antagonists and mutualists in shaping partner traits may vary across communities and that they deserve more attention in future studies of interspecific interactions.
A novel endoscopic nasopharyngectomy by low‐temperature plasma radiofrequency ablation in localized recurrent nasopharyngeal carcinoma
Authors: Zou Xiong , Feng Zheng‐Kai , Hua Yi‐Jun , Liu You‐Ping , Xie Yu‐Long , Ouyang Yan‐Feng , Liu Yong‐Long , Wang Zhi‐Qiang , You Rui , Ding Xi , Yang Qi , Yu Zi‐Kun , Huang Pei‐Yu , Wang Shun‐Lan , Chen Ming‐Yuan 
Published: November 2023

AbstractObjectiveEndoscopic nasopharyngectomy (ENPG) with en bloc resection has been well accepted in resectable localized recurrent nasopharyngeal carcinoma (rNPC), but it is a difficult technique to master for most otorhinolaryngology head and neck surgeons. Ablation surgery is a new and simplified method to remove tumors. We designed a novel method using low‐temperature plasma radiofrequency ablation (LPRA) and evaluated the survival benefit.MethodsA total of 56 localized rNPC patients were explained in detail and retrospectively analyzed. The surgery method was ablated from the resection margin to the center of the tumor. The postmetastatic overall survival (OS), local relapse‐free survival (LRFS) rate, progression‐free survival (PFS) and distant metastasis‐free survival (DMFS) were analyzed using the Kaplan–Meier method and compared by the log‐rank test.ResultsAll surgeries were successfully performed without any severe postoperative complications or deaths. The median operation time of ablation and harvested NSFF respectively were 29 min (range, 15–100 min) and 101 min (range, 30–180 min). The average number of hospital days postoperation was 3 days (range, 2–5 days). All cases (100.0%) had radical ablation with negative resection margins. The nasopharyngeal defects were completely re‐epithelialized in 54 (96.4%) patients. As of the data cutoff (September 3, 2023), the median follow‐up time was 44.3 months (range, 17.1–52.7 months, 95% CI: 40.4–48.2). The 3‐year OS, LRFS, PFS and DMFS of the entire cohort were 92.9% (95% CI: 0.862–0.996), 89.3% (95% CI: 0.813–0.973), 87.5% (95% CI: 0.789–0.961), and 92.9% (95% CI: 0.862–0.996), respectively. Cycles of radiotherapy were independent risk factors for OS (p = 0.003; HR, 32.041; 95% CI: 3.365–305.064), LRFS (p = 0.002; HR, 10.762; 95% CI: 2.440–47.459), PFS (p = 0.004; HR, 7.457; 95% CI: 1.925–28.877), and DMFS (p = 0.002; HR, 34.776; 95% CI: 3.806–317.799).ConclusionRadical endoscopic nasopharyngectomy by using low‐temperature plasma radiofrequency ablation is a novel, safe and simplified method to master and disseminate for treating resectable rNPC. However, further data and longer follow‐up time are needed to prove its efficacy.
Scalable Preparation of 1‐Aminoethyl Oxindoles From Simple Benzaldehydes
Authors: Bürki Cédric , Diethelm Stefan , D'Aiuto Fabio , Künzli Marco , Mathieu Gaëlle , Schmitt Christine 
Published: November 2023

AbstractOxindoles are prevalent structures in natural products and pharmaceutically active molecules. To support structure–activity‐relationship (SAR) studies in a medicinal chemistry program, we developed a straightforward and scalable synthesis route to 1‐aminoethyl oxindole building blocks harboring various types of substituents. Our strategy relies on an intramolecular Buchwald–Hartwig amidation of a 2‐bromophenylacetic amide precursor. The cyclization substrates can be prepared from readily available benzaldehydes by ortho‐selective C(sp2)−H bromination followed by homologation to the corresponding phenylacetic acid derivatives. The process was optimized to allow for preparation of 246 g of one representative example.
Systems archetypes to investigate the unintended consequences of telehealth in rural Australia: A systems thinking approach to telehealth evaluation and policymaking
Authors: Osman Sagda , Churruca Kate , Ellis Louise A. , Braithwaite Jeffrey 
Published: November 2023

AbstractAs an alternative model of delivery to standard care, telehealth offers a promising solution to health access issues faced by rural and remote communities in Australia and worldwide. However, research typically focuses on its expected benefits and pitfalls, with little to no consideration of its unintended consequences and factors influencing its better utilisation. Drawing on systems thinking and informed by complexity science, we propose using systems archetypes—systems thinking tools ‐ as a magnifying lens to investigate potential telehealth unintended consequences or outcomes. We conceptualise telehealth implementation in rural and remote Australia as a sociotechnical system whereby the interactions between its various agents shape telehealth implementation and, in turn, are shaped by it. When introducing new policies or interventions to any system, these interactions often lead to outcomes other than those initially planned or intended. Although systems archetypes cannot necessarily predict these outcomes, they are valuable for helping anticipate unintended, unforeseen outcomes and facilitating discussions about them to mitigate their negative impact and maximise their benefits. Outcomes are not necessarily adverse; they can also be positive. So, investigating such outcomes will minimise their negative impact and maximise their benefit. Our method was to review existing research and a selection of complexity and systems informed frameworks. Then, we assessed systems archetypes. And how they can be utilised to investigate unintended consequences. A worked example of what an unintended consequence in the implementation of telehealth in rural and remote Australia is presented.
Improved GAN for image resolution enhancement using ViT for breast cancer detection
Authors: Rautela Kamakshi , Kumar Dinesh , Kumar Vijay 
Published: November 2023

AbstractBreast cancer has a significant mortality rate and is widespread among women. Detecting it early is crucial for effective treatment. While mammograms provide detailed anatomical visuals, their accuracy is hindered by low sensitivity and high background noise, especially in dense breast tissue. This study introduces a new network architecture integrating generative adversarial networks (GANs) and vision transformers to improve reference‐based super‐resolution. The proposed model combines image generation and classification in a unified framework, eliminating the need for a separate classifier during training. To enhance GAN robustness, a unique two‐channel approach is employed, and transformer and residual learning techniques improve overall efficiency. The study introduces a novel synthetic image‐based model to improve feature detection for breast cancer classification. The proposed model shows the ability to understand information variability across different representations, enhancing accuracy and reducing computational time. Using the INbreast dataset, the results indicate the model's capability to generate high‐quality images with sensitivity and accuracy values of 0.932 and 0.988, respectively.
Deleted in Azoospermia Associated Protein 1 Shuttles Between Nucleus and Cytoplasm During Normal Germ Cell Maturation
Authors: VERA YANIRA , DAI TIANE , HIKIM AMIYA P. SINHA , LUE YANHE , SALIDO EDUARDO C. , SWERDLOFF RONALD S. , YEN PAULINE H. 
Published: November 2023

ABSTRACTDAZAP1 (Deleted in Azoospermia Associated Protein 1) was originally identified through its interaction with a putative male azoospermia factor, DAZ (Deleted in Azoospermia). It contains 2 RNA‐binding domains (RBDs) and a proline‐rich C‐terminal portion and is expressed most abundantly in testes. We used RNA in situ hybridization and immunocytochemistry to study the expression of Dazap1 in mouse testes. Dazap1 messenger RNA (mRNA) was present predominantly in immature germ cells, between the intermediate spermatogonia and preleptotene spermatocyte stages. The DAZAP1 protein was more abundant in germ cells of later stages of development and showed a dynamic subcellular distribution. High expression of DAZAP1 was first detected in midpachytene spermatocytes in stage VII tubules. In these cells, DAZAP1 was present in both the cytoplasm and the nuclei and was clearly excluded from the sex vesicles. In round spermatids, DAZAP1 was localized mainly in the nuclei, whereas in elongated spermatids, it redistributed to the cytoplasm. The subcellular distribution of DAZAP1 suggests that it shuttles between the nucleus and the cytoplasm and may play a role in mRNA transport and/or localization.
Transitory Activation and Improved Transition from Erosion to Formation within Intracortical Bone Remodeling in Hypoparathyroid Patients Treated with rhPTH(1–84)
Authors: van Dijk Christiansen Pernille , Sikjær Tanja , Andreasen Christina Møller , Thomsen Jesper Skovhus , Brüel Annemarie , Hauge Ellen Margrethe , Delaisse Jean‐Marie , Rejnmark Lars , Andersen Thomas Levin 
Published: November 2023

ABSTRACTIn hypoparathyroidism, lack of parathyroid hormone (PTH) leads to low calcium levels and decreased bone remodeling. Treatment with recombinant human PTH (rhPTH) may normalize bone turnover. This study aimed to investigate whether rhPTH(1–84) continued to activate intracortical bone remodeling after 30 months and promoted the transition from erosion to formation and whether this effect was transitory when rhPTH(1–84) was discontinued. Cortical histomorphometry was performed on 60 bone biopsies from patients (aged 31 to 78 years) with chronic hypoparathyroidism randomized to either 100 μg rhPTH(1–84) a day (n = 21) (PTH) or similar placebo (n = 21) (PLB) for 6 months as add‐on to conventional therapy. This was followed by an open‐label extension, where patients extended their rhPTH(1–84) (PTH) (n = 5), continued conventional treatment (CON) (n = 5), or withdrew from rhPTH(1–84) and resumed conventional therapy (PTHw) for an additional 24 months (n = 8). Bone biopsies were collected at months 6 (n = 42) and 30 (n = 18). After 6 and 30 months, the overall cortical microarchitecture (cortical porosity, thickness, pore density, and mean pore diameter) in the PTH group did not differ from that of the PLB/CON and PTHw groups. Still, the PTH group had a significantly and persistently higher percentage of pores undergoing remodeling than the PLB/CON groups. A significantly higher percentage of these pores was undergoing bone formation in the PTH compared with the PLB/CON groups, whereas the percentage of pores with erosion only was not different. This resulted in a shift in the ratio between formative and eroded pores, reflecting a faster transition from erosion to formation in the PTH‐treated patients. In the rhPTH(1–84) withdrawal group PTHw, the latter effects of PTH were completely reversed in comparison to those of the PLB/CON groups. In conclusion, rhPTH(1–84) replacement therapy in hypoparathyroidism patients promotes intracortical remodeling and its transition from erosion to formation without affecting the overall cortical microstructure. The effect persists for at least 30 months and is reversible when treatment is withdrawn. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Utility and Limitations of TALLYHO/JngJ as a Model for Type 2 Diabetes–Induced Bone Disease
Authors: Emini Lejla , Salbach‐Hirsch Juliane , Krug Johannes , Jähn‐Rickert Katharina , Busse Björn , Rauner Martina , Hofbauer Lorenz C. 
Published: November 2023

ABSTRACTType 2 diabetes mellitus (T2DM) increases risk of fractures due to bone microstructural and material deficits, though the mechanisms remain unclear. Preclinical models mimicking diabetic bone disease are required to further understand its pathogenesis. The TALLYHO/JngJ (TH) mouse is a polygenic model recapitulating adolescent‐onset T2DM in humans. Due to incomplete penetrance of the phenotype ~25% of male TH mice never develop hyperglycemia, providing a strain‐matched nondiabetic control. We performed a comprehensive characterization of the metabolic and skeletal phenotype of diabetic TH mice and compared them to either their nondiabetic TH controls or the recommended SWR/J controls to evaluate their suitability to study diabetic bone disease in humans. Compared to both controls, male TH mice with T2DM exhibited higher blood glucose levels, weight along with impaired glucose tolerance and insulin sensitivity. TH mice with/without T2DM displayed higher cortical bone parameters and lower trabecular bone parameters in the femurs and vertebrae compared to SWR/J. The mechanical properties remained unchanged for all three groups except for a low‐energy failure in TH mice with T2DM only compared to SWR/J. Histomorphometry analyses only revealed higher number of osteoclasts and osteocytes for SWR/J compared to both groups of TH. Bone turnover markers procollagen type 1 N‐terminal propeptide (P1NP) and tartrate‐resistant acid phosphatase (TRAP) were low for both groups of TH mice compared to SWR/J. Silver nitrate staining of the femurs revealed low number of osteocyte lacunar and dendrites in TH mice with T2DM. Three‐dimensional assessment showed reduced lacunar parameters in trabecular and cortical bone. Notably, osteocyte morphology changed in TH mice with T2DM compared to SWR/J. In summary, our study highlights the utility of the TH mouse to study T2DM, but not necessarily T2DM‐induced bone disease, as there were no differences in bone strength and bone cell parameters between diabetic and non‐diabetic TH mice. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Future Frontiers: Exploration of practices, challenges, and educational needs of genetic counselors in emerging subspecialties
Authors: Ahimaz Priyanka , Ross Meredith , Foltz Jennah , Sebastin Monisha , Naik Ketki , Kramer Tamar , Bogyo Kelsie , Primiano Michelle 
Published: November 2023

AbstractThe augmented use of genomic testing across different medical subspecialties has led to increased involvement of genetic counselors (GCs) in specialized areas of medicine. However, the lack of educational infrastructure required for changing scholastic needs of GCs entering new subspecialties lends to the burden of self‐directed learning and inconsistent knowledge. We conducted a cross‐sectional study surveying GCs with experience in the emerging genetic subspecialties of Immunology, Dermatology, Endocrinology, and Pulmonology (abbreviated as “IDEP”) on current practices, clinical challenges, and educational strategies undertaken while working in these settings. We compared knowledge and confidence in skills related to IDEP patient care between GCs who do (experienced cohort) and do not (control cohort) practice in these settings to assess their comfort with working in subspecialties. Participants were recruited from the National Society of Genetic Counselors membership. A total of 304 GCs (178 experienced and 126 control) completed the survey. Most GCs in the experienced cohort saw IDEP patients by themselves (n = 104; 58.4%) or with a geneticist (n = 97; 54.4%) and almost all (n = 176; 99%) cited GeneReviews as a primary informational source for IDEP genetics but half (n = 91; 51.1%) agreed that a dedicated online course would be the best way to learn about a specific subspecialty. The experienced cohort scored higher on confidence in all skills (p < 0.001, z = 7.32) and knowledge (p < 0.001, z = 5.68) related to IDEP genetics than the control cohort. Previous exposure to IDEP through graduate school coursework and rotations positively correlated with better self‐confidence in skills (p = 0.02, z = −2.19; p < 0.001, z = −5.25) and genetic knowledge (p = 0.03, z = −2.09; p < 0.001, z = −2.81) related to IDEP patient care. Years of experience working as a GC did not correlate with better confidence in skills (p = 0.53) or better IDEP genetic knowledge (p = 0.15). Our findings show that provision of opportunities for increased exposure to subspecialties could help maximize GCs' ability to work in emerging niche fields.
Role of dysregulated macrophage subpopulation ratios and functional changes in the development of coronary atherosclerosis
Authors: Xiao Yingjie , Huang Xin , Xia Yijun , Ding Minjun , Li Anqi , Yang Bo , She Qian 
Published: November 2023

AbstractCoronary heart disease is one of the most significant risk factors affecting human health worldwide. Its pathogenesis is intricate, with atherosclerosis being widely regarded as the leading cause. Aberrant lipid metabolism in macrophages is recognized as one of the triggering factors in atherosclerosis development. To investigate the role of macrophages in the formation of coronary artery atherosclerosis, we utilized single‐cell data from wild‐type mice obtained from the aortic roots and ascending aortas after long‐term high‐fat diet feeding, as deposited in GSE131776. Seurat software was employed to refine the single‐cell data in terms of scale and cell types, facilitating the identification of differentially expressed genes. Through the application of differential expression genes, we conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional enrichment analyses at 0, 8 and 16 weeks, aiming to uncover pathways with the most pronounced functional alterations as the high‐fat diet progressed. The AddModuleScore function was employed to score the expression of these pathways across different cell types. Subsequently, macrophages were isolated and further subdivided into subtypes, followed by an investigation into intercellular communication within these subtypes. Subsequent to this, we induced THP‐1 cells to generate foam cells, validating critical genes identified in prior studies. The results revealed that macrophages underwent the most substantial functional changes as the high‐fat diet progressed. Furthermore, two clusters were identified as potentially playing pivotal roles in macrophage functional regulation during high‐fat diet progression. Additionally, macrophage subtypes displayed intricate functionalities, with mutual functional counterbalances observed among these subtypes. The proportions of macrophage subtypes and the modulation of anti‐inflammatory and pro‐inflammatory functions played significant roles in the development of coronary artery atherosclerosis.