bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adipokine-Enriched Adipose Extract Restores Skin Barrier and Ameliorates Inflammatory Dysregulation in Atopic Dermatitis Mice
Authors: Guan Jingyan , Feng Jingwei , Xu Mimi , Liu Meiqi , He Yunfan , Lu Feng 
Published: October 2023

Background:
Atopic dermatitis (AD) is a chronic dermatosis with high incidence worldwide characterized by skin barrier abnormalities and immune dysregulation. Conventional therapies are usually limited by side effects and high cost. Given the antiinflammatory and repairing properties, adipokines are increasingly considered as promising therapeutic agents for dermatoses. Adipose collagen fragments (ACF), a novel adipokine-enriched product, may alleviate AD through modulating immune microenvironment and restoring skin barrier.

Methods:
ACF was extracted from adipose tissue by means of high-speed homogenization (10,000 rpm/min for 1 minute) and centrifugation (3000 g for 3 minutes). Ovalbumin-induced AD female BALB/c mice (6-week-old) were intradermally injected with 0.2 mL of ACF or phosphate-buffered saline (negative control), with normal mice being set as normal control (n = 6). Dermatitis severity, inflammatory metrics (epidermal thickness, infiltrated mast cells, T helper cell [Th]–type cytokine expression), and skin barrier–related metrics (transepidermal water loss, skin barrier–related proteins expression) were evaluated after the AD induction period (day 50). ACF-derived bioactive components were also evaluated using proteomic analysis.

Results:
ACF-derived adipokines contained antiinflammatory, skin barrier– and lipid biosynthesis–related components. ACF treatment decreased dermatitis severity (6.2 ± 1.8 [P < 0.0001]), epidermal thickness (25.7 ± 12.8 μm [P = 0.0045]), infiltrated mast cells (31.3 ± 12.4 cells/field [P = 0.0475]), and expression of Th-type cytokines (interferon-γ, tumor necrosis factor-α, interleukin [IL]-4, IL-4R, IL-13, and IL-17A [P < 0.05]) in AD skins. Transepidermal water loss (29.8 ± 13.8 g/m2 per hour [P = 0.0306]) and skin barrier–related protein expression (filaggrin, 14,258 ± 4375 [P = 0.0162]; loricrin, 6037 ± 1728 [P = 0.0010]; claudin-1, 20,043 ± 6406 [P = 0.0420]; and zonula occludens-1, 4494 ± 1114 [P = 0.0134]) were also improved.

Conclusions:
ACF improved AD in a murine model by ameliorating inflammatory dysregulation and skin barrier defects. Further validation is needed in more advanced animal models.

Clinical Relevance Statement:
ACF is an injectable, adipose-derived collagen scaffold prepared from autologous harvested fat using fast and simple mechanical methods. ACF may reduce the limitations associated with health care regulatory issues and serve as a promising autologous therapeutic agent for skin disorders in clinics.
Menopause in Plastic Surgery Patients: An Underrecognized and Undertreated Comorbidity
Authors: Malphrus Elizabeth L. , Perelmuter Sara , Rubin Rachel , Percec Ivona 
Published: October 2023

Summary:
Nearly half of all patients undergoing plastic surgery are middle-aged cisgender women, all of whom will experience menopause. Plastic surgeons do not treat menopause directly, but it can be a concern—and even a motivating factor—for patients seeking plastic surgery. In addition, the changes associated with menopause underlie problems that many plastic surgeons seek to address, including with face lifts, breast surgery, and vaginal rejuvenation. Hormone replacement therapy has the potential to improve quality of life by treating bothersome symptoms and delaying the physical changes brought on by loss of estrogen. However, recent reports in the media highlight that women face significant barriers to accessing menopause care due to a lack of trained providers willing to manage hormone replacement therapy, as well as historical concerns regarding increased cancer risk, which recent evidence suggests were overestimated. Plastic surgeons may be the first, or only, providers with whom women discuss how their bodies change with age. As a result, plastic surgeons should consider menopause as an underlying risk factor or comorbidity for any woman presenting with aging-related complaints, and to ensure that these patients have access to appropriate menopause care in their communities. This is especially important for surgeons offering vaginal rejuvenation therapies, given that locally acting topical estrogen is a safe and highly effective treatment. The authors present guidance and recommendations for how plastic surgeons should take menopause into account when evaluating and advising patients. In addition, the authors present a treatment algorithm for safe prescribing of locally acting hormone replacement therapy for vaginal rejuvenation.
HIF-1 inactivation empowers HIF-2 to drive hypoxia adaptation in aggressive forms of medulloblastoma
Authors: Contenti J. , Guo Y. , Larcher M. , Mirabal-Ortega L. , Rouleau M. , Irondelle M. , Tiroille V. , Mazzu A. , Duranton-Tanneur V. , Pedeutour F. , Ben-Sahra I. , Lago C. , Leva G. , Tiberi L. , Robert G. , Pouponnot C. , Bost F. , Mazure N.M. 
Published: October 2023

AbstractMedulloblastoma (MB) is the most prevalent brain cancer in children. Four subgroups of MB have been identified; of these, Group 3 is the most metastatic. Its genetics and biology remain less clear than the other groups, and it has a poor prognosis and few effective treatments available. Tumor hypoxia and the resulting metabolism are known to be important in the growth and survival of tumors but, to date, have been only minimally explored in MB. Here we show that Group 3 MB tumors do not depend on the canonical transcription factor hypoxia-inducible factor-1α (HIF-1α) to mount an adaptive response to hypoxia. We discovered that HIF-1α is rendered inactive either through post-translational methylation, preventing its nuclear localization specifically in Group 3 MB, or by a low expression that prevents modulation of HIF-target genes. Strikingly, we found that HIF-2 takes over the role of HIF-1 in the nucleus and promotes the activation of hypoxia-dependent anabolic pathways. The exclusion of HIF-1 from the nucleus in Group 3 MB cells enhances the reliance on HIF-2’s transcriptional role, making it a viable target for potential anticancer strategies. By combining pharmacological inhibition of HIF-2α with the use of metformin, a mitochondrial complex I inhibitor to block respiration, we effectively induced Group 3 MB cell death, surpassing the effectiveness observed in Non-Group 3 MB cells. Overall, the unique dependence of MB cells, but not normal cells, on HIF-2-mediated anabolic metabolism presents an appealing therapeutic opportunity for treating Group 3 MB patients with minimal toxicity.
Open-top Bessel beam two-photon light sheet microscopy for three-dimensional pathology
Authors: Park Won Yeong , Yun Jieun , Shin Jinho , Oh Byung Ho , Yoon Gilsuk , Hong Seung-Mo , Kim Ki Hean 
Published: October 2023

AbstractNondestructive pathology based on three-dimensional (3D) optical microscopy holds promise as a complement to traditional destructive hematoxylin and eosin (H&E) stained slide-based pathology by providing cellular information in high throughput manner. However, conventional techniques provided superficial information only due to shallow imaging depths. Herein, we developed open-top two-photon light sheet microscopy (OT-TP-LSM) for intraoperative 3D pathology. An extended depth of field two-photon excitation light sheet was generated by scanning a nondiffractive Bessel beam, and selective planar imaging was conducted with cameras at 400 frames/s max during the lateral translation of tissue specimens. Intrinsic second harmonic generation was collected for additional extracellular matrix (ECM) visualization. OT-TP-LSM was tested in various human cancer specimens including skin, pancreas, and prostate. High imaging depths were achieved owing to long excitation wavelengths and long wavelength fluorophores. 3D visualization of both cells and ECM enhanced the ability of cancer detection. Furthermore, an unsupervised deep learning network was employed for the style transfer of OT-TP-LSM images to virtual H&E images. The virtual H&E images exhibited comparable histological characteristics to real ones. OT-TP-LSM may have the potential for histopathological examination in surgical and biopsy applications by rapidly providing 3D information.
Patient-derived tumor organoids from resected non-small cell lung cancers for high-throughput response testing with approved and repurposed drugs
Authors: Suvilesh Kanve N. , Manjunath Yariswamy , Nussbaum Yulia I. , Gadelkarim Mohamed , Srivastava Akhil , Li Guangfu , Warren Wesley C. , Shyu Chi-Ren , Gao Feng , Ciorba Matthew A. , Mitchem Jonathan B. , Rachagani Satyanarayana , Kaifi Jussuf T. 
Published: October 2023

ABSTRACTBackgroundThe five-year survival for non-metastatic non-small cell lung cancer (NSCLC) patients undergoing curative surgery remains poor at ∼50% that is due to locoregional and/or distant metastatic recurrences. Patient-derived tumor organoids (PDTOs) have high potential as clinically relevant high-throughput drug testing platforms to personalize and improve treatment of NSCLC patients. We aimed to develop PDTOs from non-metastatic NSCLC patients to assess their suitability to study tumor heterogeneities and personalized drug responses.MethodsTen non-metastatic (stage I-IIIA) NSCLC patients undergoing curative surgical resection were prospectively enrolled. PDTOs were established from resected lung tumor tissues and were compared with matched primary tumors by histopathology, immunohistochemistry, whole exome and whole transcriptome sequencing analysis. PDTO responses to standard of care carboplatin/paclitaxel chemotherapy were determined by measuring organoid growth using bright-field 3D imaging. Transcriptomic differential gene expression analysis identified molecular targets for drug repurposing to overcome chemoresistance.ResultsNSCLC PDTOs were successfully generated from all 10 (100%) primary tumors with a median time of 12 days (range 4-16 days). All 10 PDTOs could be grown from cryopreserved tumor tissues or reconstituted from frozen PDTOs (living biobank). PDTOs retained histopathological, immunohistochemical protein expression and mutational landscape of the matched primary tumors. Microenvironment cell population analysis revealed epithelial cell signatures of the PDTOs that matched the patients’ lung tumor tissues. Treatment responses of PDTOs to carboplatin/paclitaxel were determined by growth differences versus vehicle control group. 5/10 (50%) PDTOs were chemo-sensitive, whereas 5/10 (50%) were chemo-resistant. Upregulation of aldo-keto reductases (AKR1B10/15) was observed in chemoresistant PDTOs by differential gene expression analysis and confirmed by real-time PCR and immunohistochemistry in PDTOs and tumor tissues. Epalrestat, an anti-diabetic AKR1B10 inhibitory drug, was repurposed to effectively sensitize PDTOs to carboplatin/paclitaxel.ConclusionsPDTOs can be established from resected NSCLC primary tumor tissues with high success rates and conserve cellular, molecular and genomic characteristics of the matched NSCLC tumors. PDTOs can serve as clinically applicable and relevant personalized drug screening platforms to evaluate the therapeutic efficacy of drugs, including repurposed drugs, to overcome chemoresistance.
Towards a species-level phylogeny for Neotropical Myrtaceae: notes on topology and resources for future studies
Authors:   The Neotropical Myrtaceae Working Group, Staggemeier Vanessa G. , Amorim Bruno , Bünger Mariana , Costa Itayguara R. , Quintino de Faria Jair Eustáquio , Flickinger Jonathan , Giaretta de Oliveira Augusto , Kubo Marcelo T. , Lima Duane Fernandes , Lima dos Santos Leidiana , Lourenço Ana Raquel , Lucas Eve , Mazine Fiorella Fernanda , Murillo-A José , Ibrahim Uehbe de Oliveira Marla , Parra-O Carlos , E. B. Proença Carolyn , Reginato Marcelo , Rosa Priscila , Santos Matheus Fortes , Stadnik Aline , Tuler Amélia Carlos , Valdemarin Karinne Sampaio , Vasconcelos Thais 
Published: October 2023

ABSTRACTPremise of the studyIncreasingly complete phylogenies underpin studies in systematics, ecology, and evolution. Myrteae (Myrtaceae), with c. 2,500 species, is a key component of the exceptionally diverse Neotropical flora, but given its complicated taxonomy, automated assembling of molecular supermatrices from public databases often lead to unreliable topologies due to poor species identification.MethodsHere, we build a taxonomically verified molecular supermatrix of Neotropical Myrteae by assembling 3,954 published and 959 unpublished sequences from two nuclear and seven plastidial molecular markers. We infer a time calibrated phylogenetic tree that covers 712 species of Myrteae (c. 28% of the total diversity in the clade) and evaluate geographic and taxonomic gaps in sampling.Key resultsThe tree inferred from the fully concatenated matrix mostly reflects the topology of the plastid dataset and there is a moderate to strong incongruence between trees inferred from nuclear and plastid partitions. Large, species-rich genera are still the poorest sampled within the group. Eastern South America is the best-represented area in proportion to its species diversity, while Western Amazon, Mesoamerica, and the Caribbean are the least represented.ConclusionsWe provide a time-calibrated tree that can be more reliably used to address finer-scale eco-evolutionary questions that involve this group in the Neotropics. Gaps to be filled by future studies include improving representation of taxa and areas that remain poorly sampled, investigating causes of conflict between nuclear and plastidial partitions and the role of hybridization and incomplete lineage sorting in relationships that are poorly supported.
Sex differences in aggression and its neural substrate in a cichlid fish
Authors: Jackson Lillian R. , Dumitrascu Mariam , Alward Beau A. 
Published: October 2023

AbstractAggression is ubiquitous among social species and functions to maintains social dominance hierarchies. The African cichlid fishAstatotilapia burtoniis an ideal study species for studying aggression due to their unique and flexible dominance hierarchy. However, female aggression in this species and the neural mechanisms of aggression in both sexes is not well understood. To further understand the potential sex differences in aggression in this species, we characterized aggression in male and femaleA. burtoniin a mirror assay. We then quantified neural activation patterns in brain regions of the social behavior network (SBN) to investigate if differences in behavior are reflected in the brain with immunohistochemistry by detecting the phosphorylated ribosome marker phospho-S6 ribosomal protein (pS6), a marker for neural activation. We found thatA. burtoniperform both identical and sex-specific aggressive behaviors in response to a mirror assay. We observed sex differences in pS6 immunoreactivity in the Vv, a homolog of the lateral septum in mammals. Males but not females had higher ps6 immunoreactivity in the ATn after the aggression assay. The ATn is a homolog of the ventromedial hypothalamus in mammals, which is strongly implicated in the regulation of aggression in males. Several regions also have higher pS6 immunoreactivity in negative controls than fish exposed to a mirror, implicating a role for inhibitory neurons in suppressing aggression until a relevant stimulus is present. Male and femaleA. burtonidisplay both similar and sexually dimorphic behavioral patterns in aggression in response to a mirror assay. There are also sex differences in the corresponding neural activation patterns in the SBN. In mirror males but not females, the ATn clusters with the POA, revealing a functional connectivity of these regions that is triggered in an aggressive context in males. These findings suggest that distinct neural circuitry underlie aggressive behavior in male and femaleA. burtoni, serving as a foundation for future work investigating the molecular and neural underpinnings of sexually dimorphic behaviors in this species to reveal fundamental insights into understanding aggression.
Differential effects of follicle-stimulating hormone glycoforms on the transcriptome profile of cultured rat granulosa cells as disclosed by RNA-seq
Authors: Zariñán Teresa , Espinal-Enriquez Jesús , De Anda-Jáuregui Guillermo , Lira-Albarrán Saúl , Hernández-Montes Georgina , Gutiérrez-Sagal Rubén , Rebollar-Vega Rosa G. , Bousfield George R. , Butnev Viktor Y. , Hernández-Lemus Enrique , Ulloa-Aguirre Alfredo 
Published: October 2023

ABSTRACTIt has been documented that variations in glycosylation on glycoprotein hormones, confer distinctly different biological features to the corresponding glycoforms when multiplein vitrobiochemical readings are analyzed. We here applied next generation RNA sequencing to explore changes in the transcriptome of rat granulosa cells exposed for 0, 6, and 12 h to 100 ng/ml of four highly purified follicle-stimulating hormone (FSH) glycoforms, each exhibiting different glycosylation patterns: human pituitary FSH18/21and equine FSH (eqFSH) (hypo-glycosylated), and human FSH24and chinese-hamster ovary cell-derived human recombinant FSH (recFSH) (fully-glycosylated). Total RNA from triplicate incubations was prepared from FSH glycoform-exposed cultured granulosa cells obtained from DES-pretreated immature female rats, and RNA libraries were sequenced in a HighSeq 2500 sequencer (2 x 125 bp paired-end format, 10-15 x 106reads/sample). The computational workflow focused on investigating differences among the four FSH glycoforms at three levels: gene expression, enriched biological processes, and perturbed pathways. Among the top 200 differentially expressed genes, only 4 (0.6%) were shared by all 4 glycoforms at 6 h, whereas 118 genes (40%) were shared at 12 h. Follicle-stimulating hormone glycocoforms stimulated different patterns of exclusive and associated up regulated biological processes in a glycoform and time-dependent fashion with more shared biological processes after 12 h of exposure and fewer treatment-specific ones, except forrecFSH, which exhibited stronger responses with more specifically associated processes at this time. Similar results were found for down-regulated processes, with a greater number of processes at 6 h or 12 h, depending on the particular glycoform. In general, there were fewer downregulated than upregulated processes at both 6 h and 12 h, with FSH18/21exhibiting the largest number of down-regulated associated processes at 6 h whileeqFSH exhibited the greatest number at 12 h. Signaling cascades, largely linked to cAMP-PKA, MAPK, and PI3/AKT pathways were detected as differentially activated by the glycoforms, with each glycoform exhibiting its own molecular signature. These data extend previous observations demonstrating glycosylation-dependent differential regulation of gene expression and intracellular signaling pathways triggered by FSH in granulosa cells. The results also suggest the importance of individual FSH glycoform glycosylation for the conformation of the ligand-receptor complex and induced signalling pathways.
Characterizing the Cellulose Binding Interactions of Type-A Carbohydrate-Binding Modules using Acoustic Force Spectroscopy
Authors: Ganesan Gokulnath , Hackl Markus , Chundawat Shishir P.S. 
Published: October 2023

AbstractA critical understanding of carbohydrate binding modules (CBMs) is vital for the manipulation of a variety of biological functions they support, including biomass deconstruction, polysaccharide biosynthesis, pathogen defence, and plant development. The unbinding characteristics of CBMs from a polysaccharide substrate surface can be studied using rupture force measurements since it enables a quantitative inference of binding properties through the application of dynamic force spectroscopy (DFS) theory. With the increase in usage of CBMs for diverse applications, it is important to engineer and characterize CBMs that have desired sets of interactions with various carbohydrate substrates. However, though the effect of mutations in the binding motif residues is known to influence CBM binding affinity, its effect on the rupture forces is still not well quantified. This is primarily due to the low experimental throughput of most single-molecule DFS techniques available to characterize the force-induced dissociation of protein-ligand interactions. Here, we have determined the rupture forces of microscopic beads functionalized with various wild-type and mutant CBMs using a highly multiplexed DFS technique called Acoustic Force Spectroscopy (AFS). We have characterized the acoustic force-induced dissociation of specifically two type A CBMs (i.e., CBM3a and CBM64) and relevant seven binding motif targeting CBM mutants unbinding from a nanocellulose surface, over a broad range of DFS loading rates (i.e., 0.1 pN/s to 100 pN/s). Our analysis of the rupture force DFS data yields apparent CBM-cellulose bond interaction parameters, which enables a quantitative comparison of the effect of corresponding mutations on cellulose-CBM binding interactions that compares favorably with results from classical bulk ensemble based binding assays. In summary, detailed insights into the rupturing mechanism of multi-CBM fused domains provides motivation for usage of specific constructs for industrial biotechnological applications.
Correlation of coalescence times in a diploid Wright-Fisher model with recombination and selfing
Authors: Kogan David , Diamantidis Dimitrios , Wakeley John , Fan Wai-Tong (Louis) 
Published: October 2023

AbstractThe correlation among the gene genealogies at different loci is crucial in biology, yet challenging to understand because such correlation depends on many factors including genetic linkage, recombination, natural selection and population structure. Based on a diploid Wright-Fisher model with a single mating type and partial selfing for a constant large population with sizeN, we quantify the combined effect of genetic drift and two competing factors, recombination and selfing, on the correlation of coalescence times at two linked loci for samples of size two. Recombination decouples the genealogies at different loci and decreases the correlation while selfing increases the correlation. We obtain explicit asymptotic formulas for the correlation for four scaling scenarios that depend on whether the selfing probability and the recombination probability are of orderO(1/N) orO(1) asNtends to infinity. Our analytical results confirm that the asymptotic lower bound in [King, Wakeley, Carmi (TPB 2018)] is sharp when the loci are unlinked and when there is no selfing, and provide a number of new formulas for other scaling scenarios that have not been considered before. We present asymptotic results for the variance of Tajima’s estimator of the population mutation rate for infinitely many loci asNtends to infinity. When the selfing probability is of orderO(1) and is equal to a positive constantsfor allNand if the samples at both loci are in the same individual, then the variance of the Tajima’s estimator tends tos/2 (hence remains positive) even when the recombination rate, the number of loci and the population size all tend to infinity.