bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics of macrophage-like cells in acute nonarteritic anterior ischemic optic neuropathy and the normal fellow eyes on en face optical coherence tomography
Authors: Wang Wenyu , Chen Changzheng , Yi Zuohuizi , Wang Xiaoling , Luo Huijuan
Published: December 2022

Purpose

To quantitatively analyze macrophage-like cells (MLCs) at the vitreoretinal interface (VRI) in acute nonarteritic anterior ischemic optic neuropathy (NAION) using en face swept-source optical coherence tomography (OCT).

Methods

Twenty-five acute NAION eyes and 25 normal fellow eyes from 25 patients were included in the study. MLCs were visualized in a 3 μm 6 mm×6 mm en face OCT slab above the VRI centered on the optic nerve head (ONH). After semiautomatic binarization and quantification, we evaluated the MLC density between the two groups. We also investigated the relationship between MLC density and other OCT parameters, including the increase in peripapillary retinal nerve fiber layer (RNFL) thickness and loss of vessel density (VD) in radical peripapillary capillary (RPC).

Results

The MLC density in the affected eye of the ONH was highly correlated with that in the fellow eye (r=0.612, p=0.001). The MLC density significantly increased in acute NAION eyes (NAION vs. normal, 11.97 ± 6.66 vs. 9.31 ± 6.10 cell/mm2, p=0.028). In sectorial analysis, the increase in MLCs was mainly in the superior regions (4.13 ± 7.49 vs. 0.94 ± 5.21 cell/mm2, p=0.001). The VD of RPC decreased significantly in the affected eyes (NAION vs. normal, 37.54 ± 5.25 vs. 40.56 ± 4.25, p=0.016), and the loss of RPC was predominantly in the superior sectors and the temporal sectors when compared to the inferior sectors and the nasal sectors, respectively (superior vs. inferior, -3.54 ± 6.71 vs. -0.37 ± 8.07, p=0.004; temporal vs. nasal, -2.69 ± 8.72 vs. -1.22 ± 6.06, p=0.005). The loss of RPC and the increase in MLC density were greater in affected sector corresponding to the visual field (VF) defect.

Conclision

MLCs located above the VRI increased significantly in acute NAION eyes, especially in subregions corresponding to VF defect, which provides clinical evidence supporting that the inflammatory response participates in the pathological process of NAION. The magnitude of the increase in MLCs corresponds to the RPC loss in the quadrant analysis.
Characterization and genomic Analysis of a novel Pseudomonas phage vB_PsaP_M1, representing a new viral family, Psaeviridae
Authors: Ren Linyi , Liu Yundan , Liang Yantao , Liu Baohong , McMinn Andrew , Zheng Kaiyang , Wang Ziyue , Wang Hongmin , Shao Hongbing , Sung Yeong Yik , Mok Wen Jye , Wong Li Lian , Wang Min
Published: December 2022

Pseudomonas is a ubiquitous and ambiguous opportunistic pathogen, and plays an important ecological role in the ocean. Here, a new species, Pseudomonas phage vB_PsaP_M1, is described, which was isolated from the surface coastal waters of Qingdao, China. vB_PsaP_M1 contains a linear, double-stranded 89,387-bp genome with a GC content of 41.04% and encoding 184 putative open reading frames (ORFs). There were 50 conservative domains were predicted with BLASTp, including two auxiliary metabolic genes (Phosphate-inducible gene phoH and signal peptide peptidase A, sppA). Phylogenetic analysis of whole genome amino acid sequence and comparative genomic analysis showed that vB_PsaP_M1 has a distant evolutionary relationship with previously isolated viruses and can be grouped into a family-level novel viral cluster (VC_61) with eleven uncultured, assembled viral genomes, named as Psaeviridae. Psaeviridae contains two ORFs (ORFs 117 and 127), which were not detected in the genomes of other viral families, confirming the proposal for a new family. Combined with its ability to infect Pseudomonas and its representation of an unstudied viral family, vB_PsaP_M1 may be an important and novel model system for the study of interactions between viruses and host cells in marine ecosystems.
High-throughput prediction and characterization of antimicrobial peptides from multi-omics datasets of Chinese tubular cone snail (Conus betulinus)
Authors: Li Ruihan , Huang Yu , Peng Chao , Gao Zijian , Liu Jie , Yin Xiaoting , Gao Bingmiao , Ovchinnikova Tatiana V. , Qiu Limei , Bian Chao , Shi Qiong
Published: December 2022

Individual cone snail (Conus sp.) contains thousands of bioactive peptides, but there are limited studies on its antimicrobial peptides (AMPs). Here, we investigated AMPs along with AMP-derived genes in the representative Chinese tubular cone snail (C. betulinus) by integration of our previously published multi-omics (genomics, transcriptomics, and peptidomics) data. We identified a total of 466 putative AMP-derived genes from the genome, and most of them were annotated as histones. While at the mRNA level, only 77 AMP-derived genes were confirmed with transcriptomic evidence, among them Ubiquicidin, cgUbiquitin, Ap, and VK10 were the most abundant transcripts in the venom gland. In addition, 30 AMPs were further validated by peptidomics data. After in silico analysis including 3D modeling, 11 putative AMPs were chemically synthesized for an in vitro assessment, and eight peptides were proved with good antifungal activity. In summary, this work systematically characterized the AMP repertoire in C. betulinus. This valuable genetic resource provides a solid foundation for in-depth therapeutic applications and drug development.
Scoping an integrated ecosystem assessment for South Africa
Authors: Skein Lisa , Sink Kerry J. , Majiedt Prideel A. , van der Bank Megan G. , Smit Kaylee P. , Shannon Lynne J.
Published: December 2022

The need to move toward marine ecosystem-based management is globally recognized. Few countries effectively account for multiple interacting pressures in their marine assessments, planning and management. Many socio-economic sectors currently operate in South African waters and in most cases, their associated pressures are managed on a sector-by-sector basis and interacting pressures are seldom accounted for in assessments or decision-making. For ecosystem-based management to be effective, a science-based approach to prioritize sectors and pressures needing most urgent action, and to identify affected ecological components is needed. Integrated Ecosystem Assessment (IEA) has hence been put forward as a tool that can organize relevant information and provide context for cross-sectoral management decisions. Consisting of five main stages that form an iterative cycle, the first IEA stage involves scoping of top management priorities in a given area and can be done by way of risk assessment. Through the ODEMM (Options for Delivering Ecosystem-based Marine Management) approach, linkage chains (interactions) among sectors, pressures and affected ecological components for the entirety of the South African marine territory were identified. Subsequently, impact risk scores of each linkage chain were calculated based on the exposure and severity of impacts faced by ecological components from pressures that are associated with each sector. Fishing was the sector with the greatest connectivity (11.65% proportional connectance) in the framework and ranked highest in terms of impact risk (summed), followed by Shipping and Coastal infrastructure. Pressures with the most serious impacts on ecological components, as identified through summed impact risk scores, included Bycatch, Species extraction, and Incidental loss and the ecological components most affected were those primarily associated with Fishing and its associated pressures. These findings align with those of the recent South African National Biodiversity Assessment and corroborate views of local stakeholders. This study also identified key local knowledge gaps, including impacts of underwater noise, invasive species, and climate change, that must be better understood to improve assessment accuracy and guide management prioritization of pressures exerted by most impactful sectors.
Mo modified Co3O4 nanosheets array by a rapid quenching strategy for efficient oxygen evolution electrocatalysis
Authors: Yang Jiangping , Zhang Zhe , Sun Siyuan , Wang Cheng
Published: December 2022

The development of transition metal oxides (TMOs) as electrocatalysts for oxygen evolution reaction (OER) has the potential to surpass the performance of noble-metal-based catalysts. In this work, a quenching rapidly strategy was used to synthesize Mo-modified Co3O4 nanosheet arrays as advanced catalysts. The resulting Mo-Co3O4 electrodes showed superior activity and reaction kinetics, with an overpotential of only 341 mV to drive a current density of 100 mA cm−2 and a Tafel slope of 69.0 mV dec−1. This improved performance is thought to be due to the formation of high-valence Co sites, which creates a synergistic effect. The ability to regulate the synthesis without causing obvious agglomeration and nucleation growth during annealing makes this method a promising approach for the design of other advanced functional materials.
Distribution of bacteria in different regions of the small intestine with Zanthoxylum bungeanum essential oil supplement in small-tailed Han sheep
Authors: Zhang Hailong , Lang Xia , Zhang Yanshu , Wang Cailian
Published: December 2022

Zanthoxylum bungeanum essential oil (EOZB) as an extract of Zanthoxylum bungeanum has a range of pharmacological effects such as antibacterial, anti-inflammatory, and antioxidant. However, there were no relevant studies on the regulation of gut microbes by EOZB in ruminants. In this study, the effects of different doses of EOZB on the structure and distribution of microorganisms in the small intestine of small-tailed Han sheep (STH) were investigated by 16s rRNA gene sequencing technique. We found that with the intervention of EOZB. The differential bacteria of duodenal at the phylum level were Firmicutes, Bacteroidetes, Tenericutes and Proteobacteria, and genus level differential bacteria were Prevotella 1, Ruminococcus 2 and Eubacterium coprostanoligenes group. The differential bacteria of jejunal at the phylum level were Firmicutes, Bacteroidetes, Tenericutes and Proteobacteria, and genus level differential bacteria were Prevotella 1, Rikenellaceae RC9 gut group, Christensenellaceae R-7 group, Ruminococcaceae UCG-014, Saccharofermentans, Ruminococcaceae NK4A214 group and Prevotellaceae UCG-001. The differential bacteria of ileal at the phylum level were Firmicutes, Bacteroidetes and Tenericutes, and genus level differential bacteria were Prevotella 1, Christensenellaceae R-7 group, Romboutsia and Ruminococcaceae UCG-014. In addition, at the same dose of EOZB, the five most abundant genera of bacteria varied in different regions of the small intestine. Among them, the abundance of Prevotella 1, Christensenellacea R-7 group and Ruminococcus 2 in ALW group was the highest in jejunum, duodenum and ileum, respectively. The abundance of Prevotella 1, Christensenellacea R-7 group and Rikenellacea RC9 gut group in BLW group was the highest in duodenum, jejunum and ileum, respectively. The abundance of Prevotella 1, Christensenellacea R-7 group and Ruminococcaeae NK4A214 group in CLW group was the highest in jejunum, duodenum and ileum, respectively. The abundance of Prevotella 1, Ruminococcus 2 and Ruminococcus NK4A214 groups in DLW group was the highest in jejunum, duodenum and ileum, respectively. Differential bacteria formed under the regulation of EOZB are associated with the digestion and absorption of nutrients and the state of intestinal health in the host. This study is the first to investigate the effect of EOZB on the distribution and structure of bacteria in the small intestine of STH. The results of the study enriched the structure and distribution of bacteria in the small intestine of ruminants and provided new insights into the future application of herbal medicine in ruminant production. Additionally, it provides a theoretical basis for the selection of probiotic bacteria for ruminants and the development and application of microecological preparations.
In vivo investigation of Lcr35® anti-candidiasis properties in Caenorhabditis elegans reveals the involvement of highly conserved immune pathways
Authors: Poupet Cyril , Rifa Étienne , Theil Sébastien , Bonnet Muriel , Veisseire Philippe , Cardin Guillaume , Guéret Élise , Rialle Stéphanie , Chassard Christophe , Nivoliez Adrien , Bornes Stéphanie
Published: December 2022

Lactic acid bacteria, including the microorganisms formerly designated as Lactobacillus, are the major representatives of Live Biotherapeutic Microorganisms (LBM) when used for therapeutic purposes. However, in most cases, the mechanisms of action remain unknown. The antifungal potential of LBM has already been demonstrated using preclinical models (cell cultures, laboratory animals). Understanding their mechanisms of action is strategic for the development of new therapeutics for humans. Here, Caenorhabditis elegans was used as an in vivo model to analyze pro-longevity, anti-aging and anti-candidiasis effects of the LBM Lacticaseibacillus rhamnosus (formerly Lactobacillus rhamnosus) Lcr35®. A high-throughput transcriptomic analysis revealed a specific response of C. elegans depending on whether it is in the presence of the LBM L. rhamnosus Lcr35® (structural response), the yeast Candida albicans (metabolic response) or both (structural and metabolic responses) in a preventive and a curative conditions. Studies on C. elegans mutants demonstrated that the p38 MAPK (sek-1, skn-1) and the insulin-like (daf-2, daf-16) signaling pathways were involved in the extended lifespan provided by L. rhamnosus Lcr35® strain whereas the JNK pathway was not involved (jnk-1). In addition, the anti C. albicans effect of the bacterium requires the daf-16 and sek-1 genes while it is independent of daf-2 and skn-1. Moreover, the anti-aging effect of Lcr35®, linked to the extension of longevity, is not due to protection against oxidative stress (H2O2). Taken together, these results formally show the involvement of the p38 MAP kinase and insulin-like signaling pathways for the longevity extension and anti-Candida albicans properties of Lcr35® with, however, differences in the genes involved. Overall, these findings provide new insight for understanding the mechanisms of action of a probiotic strain with antimicrobial potential.
Recent development in the preservation effect of lactic acid bacteria and essential oils on chicken and seafood products
Authors: Sharma Heena , Fidan Hafize , Özogul Fatih , Rocha João Miguel
Published: December 2022

Chicken and seafood are highly perishable owing to the higher moisture and unsaturated fatty acids content which make them more prone to oxidation and microbial growth. In order to preserve the nutritional quality and extend the shelf-life of such products, consumers now prefer chemical-free alternatives, such as lactic acid bacteria (LAB) and essential oils (EOs), which exert a bio-preservative effect as antimicrobial and antioxidant compounds. This review will provide in-depth information about the properties and main mechanisms of oxidation and microbial spoilage in chicken and seafood. Furthermore, the basic chemistry and mode of action of LAB and EOs will be discussed to shed light on their successful application in chicken and seafood products. Metabolites of LAB and EOs, either alone or in combination, inhibit or retard lipid oxidation and microbial growth by virtue of their principal constituents and bioactive compounds including phenolic compounds and organic acids (lactic acid, propionic acid, and acetic acid) and others. Therefore, the application of LAB and EOs is widely recognized to extend the shelf-life of chicken and seafood products naturally without altering their functional and physicochemical properties. However, the incorporation of any of these agents requires the optimization steps necessary to avoid undesirable sensory changes. In addition, toxicity risks associated with EOs also demand the regularization of an optimum dose for their inclusion in the products.
Pathological functional impairment: Neuropsychological correlates of the shared variance between everyday functioning and brain volumetrics
Authors: Fellows Robert P. , Bangen Katherine J. , Graves Lisa V. , Delano-Wood Lisa , Bondi Mark W.
Published: December 2022

Objective

Given that several non-cognitive factors can contribute to difficulties with everyday functioning, examining the extent to which cognition is associated with brain-related changes in everyday functioning is critical to accurate characterization of cognitive disorders. In this study, we examined neuropsychological correlates of the shared variance between everyday functioning and pathological indicators of cognitive aging using MRI brain volumetrics.

Participants and methods

Participants were 600 adults aged 55 and older without dementia [432 cognitively normal; 168 mild cognitive impairment (MCI)] from the National Alzheimer’s Coordinating Center cohort who underwent neuropsychological testing, informant-rated everyday functioning, and brain MRI scanning at baseline. The shared variance between everyday functioning and brain volumetrics (i.e., hippocampal volume, white matter hyperintensity volume) was extracted using the predicted value from multiple regression. The shared variance was used as an indicator of pathological everyday functional impairment. The residual variance from the regression analysis was used to examine functional reserve.

Results

Larger white matter hyperintensity volumes (p = 0.002) and smaller hippocampal volumes (p < 0.001) were significantly correlated with worse informant-rated everyday functioning. Among individuals with MCI, worse performances on delayed recall (p = 0.013) and category fluency (p = 0.012) were significantly correlated with pathological functional impairment in multiple regression analysis. In the cognitively normal group, only worse auditory working memory (i.e., digit span backward; p = 0.025) significantly correlated with pathological functioning. Functional reserve was inversely related to anxiety (p < 0.001) in the MCI group and was associated with depressive symptoms (p = 0.003) and apathy (p < 0.001) in the cognitively normal group.

Conclusion

Subtle brain-related everyday functioning difficulties are evident in MCI and track with expected preclinical Alzheimer’s disease cognitive phenotypes in this largely amnestic sample. Our findings indicate that functional changes occur early in the disease process and that interventions to target neuropsychiatric symptoms may help to bolster functional reserve in those at risk.
Impact of specific serotonin receptor modulation on restricted repetitive behaviors
Authors: Alvarez Bryan D. , Cavazos Cassandra , Morales Cheyenne A. , M. Lopez Shannon , Amodeo Dionisio A.
Published: December 2022

Restricted, repetitive behaviors (RRBs) are commonly divided into two behavioral categories, lower-order and higher-order RRBs. Individuals displaying lower-order motoric RRBs may express repetitive hand flapping behaviors, body rocking back and forth movements, and continuous body spinning. Higher-order RRBs most commonly cover the behavior inflexibility and cognitive rigidity commonly found in disorders such as autism spectrum disorder and obsessive-compulsive disorder. Various neuropsychiatric disorders are plagued by RRBs yet no FDA-approved treatments have been identified. In rodents, lower-order RRBs are commonly measured through various tasks, such as repetitive self-grooming, marble burying, and stereotypic motor behaviors. This review focuses on the effects that modulation of specific serotonin receptors have on lower-order RRBs. Although there is research examining how changes in 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT3, 5-HT6, and 5-HT7 receptor modulation, more research has focused on the 5-HT1A, 5-HT2A, and 5-HT2C receptors. The accumulating data suggest that increasing 5-HT1A activation decreases RRBs while blocking 5-HT1A activation has no effect on RRBs. While there are mixed findings regarding the impact of 5-HT2A modulation on RRBs, the general trend shows mixed effects of 5-HT2A receptor activation RRB expression, whereas blockade generally decreases RRBs. 5-HT2C receptor activation can modulate RRBs in either direction depending on the 5-HT2C drug used, blocking 5-HT2C activation only seems to show therapeutic properties when 5-HT2C activation is already elevated. The other 5-HT receptors have been explored far less but show promise as potential targets for regulating RRBs. Although it is less clear due to the involvement of 5-HT1D, 5-HT1A activation increases RRBs, and blocking 5-HT1A tends to decrease RRBs. 5-HT2B activation could reduce RRBs, while inhibiting 5-HT2B does not impact RRBs. Increasing 5-HT3 has not been shown to affect RRBs. Yet, increases in RRBs have been observed in Htr3a KO mice. 5-HT6 receptor activation can increase RRBs, while blocking 5-HT6 activity tends to decrease RRBs. Lastly, neither increasing or blocking 5-HT7 activity can reduce RRBs. In sum, there is no uniform pattern in whether all specific 5-HT receptors affect RRBs in either direction, instead, there is evidence suggesting that different 5-HT receptors can modulate RRBs in different directions. Further researching the less explored receptors and aiming to understand why these receptors can differently modulate RRBs, may play a key role in developing therapeutics that treat RRBs.
N6-methyladenosine modulation classes and immune microenvironment regulation in ischemic stroke
Authors: Tao Hongmiao , Dong Lihua , Li Lin
Published: December 2022

N6-methyladenosine (m6A) modifications play an important role in the differentiation and regulation of immune cells. However, research on m6A in ischemic stroke (IS) is still in its infancy, and their role of the immune microenvironment remains unknown. In this study, we systematically assessed the modification classes of m6A regulators in IS based on the GEO database (GSE16561 and GSE22255). We found that in IS patients, IGF2BP2, IGF2BP1, and YTHDF2 expression was significantly upregulated, and ELAVL1, LRPPRC, METTL3, ALKBH5, CBLL1, and METTL14 expression was significantly downregulated. Seven IS-related genes (ELAVL1, IGF2BP2, LRPPRC, YTHDF2, ALKBH5, METTL14, and YTHDC1) were finally screened by logistic and least absolute shrinkage and selection operator (LASSO) regressions, and the AUC of the riskScore was 0.942, which was a good classification. For immune infiltration, there were highly significant differences in memory B cells, CD8 T cells, monocytes, activated dendritic cells, and mast cells between IS and normal samples. The IS samples were grouped into three classes by consistent clustering, and 15 m6A genes were differentially expressed in the different classes. Multiple infiltrating immune cells, immune-associated genes, and HLA-associated genes differed significantly across m6A modification classes, indicating the diversity and complexity of m6A modifications in the immune microenvironment of IS. Finally, 487 genes associated with the m6A modification class were identified, and 227 potential drugs were found. Our findings demonstrated that m6A modification plays a crucial role in the immune regulation of IS.
The function of VAMP2 in mediating membrane fusion: An overview
Authors: Yan Chong , Jiang Jie , Yang Yuan , Geng Xiaoqi , Dong Wei
Published: December 2022

Vesicle-associated membrane protein 2 (VAMP2, also known as synaptobrevin-2), encoded by VAMP2 in humans, is a key component of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex. VAMP2 combined with syntaxin-1A (SYX-1A) and synaptosome-associated protein 25 (SNAP-25) produces a force that induces the formation of fusion pores, thereby mediating the fusion of synaptic vesicles and the release of neurotransmitters. VAMP2 is largely unstructured in the absence of interaction partners. Upon interaction with other SNAREs, the structure of VAMP2 stabilizes, resulting in the formation of four structural domains. In this review, we highlight the current knowledge of the roles of the VAMP2 domains and the interaction between VAMP2 and various fusion-related proteins in the presynaptic cytoplasm during the fusion process. Our summary will contribute to a better understanding of the roles of the VAMP2 protein in membrane fusion.
Time-restricted feeding ameliorates dextran sulfate sodium-induced colitis via reducing intestinal inflammation
Authors: Song Shuo , Chen Lingling , Bai Meijuan , Wang Shuo , Ye Xiaoyi , Lin Yijun , Luo Xuemei , Li Zixuan , Zhang Lingling , Zhu Xinyu , Wang Zinan , Chen Yan
Published: December 2022

Time-restricted feeding (TRF) is an emerging dietary intervention that improves metabolic disorders such as obesity, insulin resistance and dyslipidemia. Inflammatory bowel disease (IBD) is a chronic inflammatory disorder affecting the gastrointestinal tract, where nutrition plays an important role in its pathogenesis. Although numerous strategies of nutritional intervention have been reported, whether TRF can improve IBD has been elusive. In this study, we investigated the effect of two cycles of 7-day TRF intervention in a dextran sulfate sodium-induced IBD mouse model. We found that TRF was able to reduce the disease activity index and ameliorate the IBD-associated symptoms, as well as increase the number of colonic crypts and decrease the histological score in the colon. Furthermore, TRF lowered the percentage of CD4+ T cells in the peripheral blood and mesenteric lymph node, and increased the number of CD4+CD25+ T cells in the mesenteric lymph nodes. Additionally, TRF reduced the infiltration of leukocytes and macrophages around the crypt base in the colon. However, unlike the intermittent caloric restriction with fasting-mimicking diet, TRF was not able to increase the markers of progenitor and cell proliferation in the colon. Collectively, these results demonstrated that TRF is able to improve IBD in mice via reduction in intestinal inflammation.
Paternal dietary ratio of n-6: n-3 polyunsaturated fatty acids programs offspring leptin expression and gene imprinting in mice
Authors: Shi Qiaoyu , Liu Xuanyi , Fan Xiuqin , Wang Rui , Qi Kemin
Published: December 2022

Background

This study determined the effects of the paternal dietary ratio of n-6: n-3 polyunsaturated fatty acids (PUFAs) on leptin expression in the offspring and associated gene imprinting in a mouse model.

Methods

Three- to four-week-old male C57BL/6J mice (F0) were fed an n-3 PUFA-deficient (n-3 D) diet, a diet with normal n-3 PUFA content (n-3 N; n-6: n-3 = 4.3:1), or a diet with a high n-3 PUFA content (n-3 H; n-6: n-3 = 1.5:1) for 8 weeks. Two subsequent generations were generated by mating F0 and F1 male mice with 10-week-old virgin female C57 BL/6J mice, to produce F1 and F2 offspring.

Results

Compared to the paternal n-3 D diet, paternal n-3 N and n-3 H diets reduced adipose mRNA expression of leptin (Lep) and its plasma concentrations in juvenile F1 male and female offspring, and adult F1 male and F2 female offspring, with upregulated Lep receptor mRNA expression in the hypothalamus. Meanwhile, paternal n-3 N and n-3 H diets altered the expression of the imprinted genes H19, Igf2, Igf2r, Plagl1, Cdkn1c, Kcnq1ot1, Peg3, and Grb10 in the adipose tissue of juvenile and adult F1 males, with almost no effects on F1 females, while more effects were observed in the adult F2 females than F2 males. Principal component analysis verified that Plagl1, Cdkn1c, and Kcnq1ot1 contributed the most to variation in adipose tissue expression in all offspring. Some of these genes (Plagl1, Cdkn1c, Kcnq1ot1, Peg3, and Grb10) were altered by the paternal n-3 N and n-3 H diets in the F1 and F2 generation testes as well. Furthermore, adipose Lep expression was positively correlated with expressions of H19, Igf2r, Plagl1, and Kcnq1ot1 in juvenile F1 males and females, negatively correlated with the Kcnq1ot1 expression in adult F1 males, and positively correlated with the Plagl1 expression in adult F2 females.

Conclusion

These data imply that paternal Plagl1, Cdkn1c, and Kcnq1ot1 might be part of the pathways involved in offspring leptin programming. Therefore, a lower ratio of n-6: n-3 PUFAs, with higher intake of n-3 PUFAs in paternal pre-conception, may help maintain the offspring’s optimal leptin pattern in a sex-specific manner through multiple generations, and thereby, be beneficial for the offspring’s long-term health.
Association of baseline self-reported fatigue with overall survival after stereotactic body radiation therapy for localized prostate cancer
Authors: Simhal Rishabh K. , Sholklapper Tamir N. , Simhal Anish K. , Zwart Alan L. , Danner Malika T. , Kumar Deepak , Aghdam Nima , Suy Simeng , Hankins Ryan A. , Kowalczyk Keith J. , Collins Sean P.
Published: December 2022

Introduction

Stereotactic Body Radiation Therapy (SBRT) has emerged as a definitive therapy for localized prostate cancer (PCa). However, more data is needed to predict patient prognosis to help guide which patients will benefit most from treatment. The FACIT-Fatigue (FACIT-F) is a well validated, widely used survey for assessing fatigue. However, the role of fatigue in predicting PCa survival has yet to be studied. Herein, we investigate the role of FACIT-F as a baseline predictor for overall survival (OS) in patients undergoing SBRT for localized PCa.

Methods

A retrospective review was conducted of 1358 patients who received SBRT monotherapy between January 2008 to April 2021 at an academic, tertiary referral center. FACIT-F scores (range 0 to 52) were summed for patients who answered all 13-items on the survey. FACIT-F total scores of ≥35 represented severe fatigue. Patients receiving androgen deprivation therapy were excluded. Differences in fatigue groups were evaluated using chi-squared tests. OS rates were determined using the Kaplan-Meier method and predictors of OS were evaluated using Cox proportional hazard method.

Results

Baseline full FACIT-F scores and survival data was available for 891 patients. 5-year OS was 87.6% and 95.2%, respectively, for the severely fatigued and non-fatigued groups. Chi-squared analysis of fatigue groups showed no significant difference in the following categories: D’Amico risk group, age, ethnicity, grade group, T-stage, or PSA density. Severe fatigue was associated with a significant decrease in OS (hazard ratio 2.76; 95%CI 1.55 - 4.89). The Cox proportional hazard model revealed that age and FACIT-F were both statistically significant (p <0.05).

Conclusion

Baseline FACIT-F scores are significantly associated with OS. Higher FACIT-F scores, representing less fatigued patients, are associated with an overall survival benefit. These results indicate that the FACIT-F survey could serve as an additional metric for clinicians in determining prognostic factors for patients undergoing SBRT.
What is the future of treatment de-escalation for HPV-positive oropharyngeal cancer? A review of ongoing clinical trials
Authors: Mensour Emma A. , Alam Shintha , Mawani Seliya , Bahig Houda , Lang Pencilla , Nichols Anthony , Palma David A. , Jasper Katie
Published: December 2022

Background

Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) has increased in incidence in recent decades. With higher cure rates in younger populations, long-term survivors may live with acute- and long-term toxicity, leading to increased interest in de-escalation treatment strategies for HPV-related OPSCC. Herein, we have examined the current landscape of clinical trials in this context.

Methods

A review of active clinical trials related to de-escalation of HPV-associated OPSCC treatment was performed using the clinicaltrials.gov database from inception to January 2022. A search using the key words “oropharyngeal cancer” and “HPV” was completed. Three investigators independently reviewed each trial, with any discrepancies settled by a fourth. Data collected from each study included study phase, study design, primary, and secondary endpoints, and de-escalation treatment strategies. A final 24 articles were selected for full text review.

Results

Many trials (n=19, 79%) were non-randomized, and most studies employed a phase II design (n=14, 58%). Only 13% (n=3) were randomized trials, and 8% (n=2) included a phase III component. The most frequent primary endpoint was progression-free survival (PFS) (n=9, 37.5%). With regards to the identified de-escalation strategies, all the studies (n=24) had at least one component assessing changes in RT dose/fractionation and/or a reduction in RT volumes. A smaller percentage of trials assessed surgical interventions (n=9, 37.5%) and/or changes in systemic therapy (n=8, 33.3%).

Conclusion

A small number of randomized trials are underway, and a transition to more randomized phase III trials in the future will be important to change clinical practice.
Comprehensive analysis of the significance of METTL7A gene in the prognosis of lung adenocarcinoma
Authors: Pan Ya-Qiang , Xiao Ying , Li Zhenhua , Tao Long , Chen Ge , Zhu Jing-Feng , Lv Lu , Liu Jian-Chao , Qi Jun-Qing , Shao AiZhong
Published: December 2022

Background

The most common subtype of lung cancer, called lung adenocarcinoma (LUAD), is also the largest cause of cancer death in the world. The aim of this study was to determine the importance of the METTL7A gene in the prognosis of patients with LUAD.

Methods

This particular study used a total of four different LUAD datasets, namely TCGA-LUAD, GSE32863, GSE31210 and GSE13213. Using RT-qPCR, we were able to determine METTL7A expression levels in clinical samples. Univariate and multivariate Cox regression analyses were used to identify factors with independent effects on prognosis in patients with LUAD, and nomograms were designed to predict survival in these patients. Using gene set variation analysis (GSVA), we investigated differences in enriched pathways between METTL7A high and low expression groups. Microenvironmental cell population counter (MCP-counter) and single-sample gene set enrichment analysis (ssGSEA) methods were used to study immune infiltration in LUAD samples. Using the ESTIMATE technique, we were able to determine the immune score, stromal score, and estimated score for each LUAD patient. A competing endogenous RNA network, also known as ceRNA, was established with the help of the Cytoscape program.

Results

We detected that METTL7A was down-regulated in pan-cancer, including LUAD. The survival study indicates that METTL7A was a protective factor in the prognosis of LUAD. The univariate and multivariate Cox regression analyses revealed that METTL7A was a robust independent prognostic indicator in survival prediction. Through the use of GSVA, several immune-related pathways were shown to be enriched in both the high-expression and low-expression groups of METTL7A. Analysis of the tumor microenvironment revealed that the immune microenvironment of the group with low expression was suppressed, which may be connected to the poor prognosis. To explore the ceRNA regulatory mechanism of METTL7A, we finally constructed a regulatory network containing 1 mRNA, 2 miRNAs, and 5 long non-coding RNAs (lncRNAs).

Conclusion

In conclusion, we presented METTL7A as a potential and promising prognostic indicator of LUAD. This biomarker has the potential to offer us with a comprehensive perspective of the prediction of prognosis and treatment for LUAD patients.
Case report: 18F-FES PET/CT predicted treatment responses of second-line and third-line CDK4/6 inhibitors after disease progression on first-line CDK4/6 inhibitor in a HR+/HER2- metastatic breast cancer patient
Authors: Pan Bo , Hao Zhixin , Xu Ying , Wang Zhe , Yao Ru , Wang Xuefei , Ren Chao , Zhou Yidong , Sun Qiang , Huo Li
Published: December 2022

Background

Cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) has become the commonest first-line treatment of hormonal receptor positive and human epidermal growth factor receptor 2 negative (HR+/HER2-) metastatic breast cancer (MBC). However, therapy is quite individualized after progression of disease (PD) when CDK4/6i fails. Estrogen receptor (ER) status of metastatic lesions of bone, lung or liver might be different from the primary tumor and biopsy of metastatic lesions was invasive and not always available. Prediction of treatment response after PD of CDK4/6i remains unsolved. 18F-fluoroestradiol (FES) PET/CT could non-invasively reveal ER expression both in primary and metastatic breast cancer and recognize heterogeneity of ER status.

Case presentation

A 70-year-old woman with Parkinson’s disease, osteoporosis and cardiovascular co-morbidity was diagnosed with HR+/HER2- breast cancer (pT2N2M0, stage IIIa). Three years later, she developed metastases in right lung and pleura with pleural effusion and received palbociclib + letrozole. After 8 months the disease progressed, and 18F-FES PET/CT revealed multiple ER-positive pleural lesions and ER-negative pulmonary nodules after PD and the progression-free survival (PFS) of first-line CDK4/6i was 8 months. Since most of the metastatic lesions were ER-positive, abemaciclib + fulvestrant were chosen as the second-line CDK4/6i treatment and the PFS was 15 months. Another 18F-FES PET/CT showed a new ER-positive pleural mass with multiple ER-negative pulmonary nodules. Since 18F-FES PET/CT revealed that the dominant lesions were still ER-positive, dalpiciclib + exemestane + fulvestrant were prescribed as the third-line CDK4/6i treatment. Currently the patient’s disease had been stable for 2 months.

Conclusion

This case demonstrated that 18F-FES PET/CT could show ER heterogeneity non-invasively and reveal the treatment responses a predictive imaging tool of serial second- and third-line of CDK4/6i treatments when first-line CDK4/6i failed in HR+/HER2- MBC. So long as the dominant or newly-developed metastatic lesion was ER-positive on 18F-FES PET after first-line CDK4/6i, the patient might show certain therapeutic response towards endocrine-based treatment including second- and third-line of CDK4/6i, and thus increased the time to chemotherapy (TTC).
Spondyloarthritides: Theories and beyond
Authors: Kocatürk Begüm , Balık Zeynep , Pişiren Gaye , Kalyoncu Umut , Özmen Füsun , Özen Seza
Published: December 2022

Spondyloarthritides (SpA) are a family of interrelated rheumatic disorders with a typical disease onset ranging from childhood to middle age. If left untreated, they lead to a severe decrease in patients' quality of life. A succesfull treatment strategy starts with an accurate diagnosis which is achieved through careful analysis of medical symptoms. Classification criterias are used to this process and are updated on a regular basis. Although there is a lack of definite knowledge on the disease etiology of SpA, several studies have paved the way for understanding plausible risk factors and developing treatment strategies. The significant increase of HLA-B27 positivity in SpA patients makes it a strong candidate as a predisposing factor and several theories have been proposed to explain HLA-B27 driven disease progression. However, the presence of HLA-B27 negative patients underlines the presence of additional risk factors. The current treatment options for SpAs are Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), TNF inhibitors (TNFis), Disease-Modifying Anti-Rheumatic Drugs (DMARDs) and physiotherapy yet there are ongoing clinical trials. Anti IL17 drugs and targeted synthetic DMARDs such as JAK inhibitors are also emerging as treatment alternatives. This review discusses the current diagnosis criteria, treatment options and gives an overview of the previous findings and theories to clarify the possible contributors to SpA pathogenesis with a focus on Ankylosing Spondylitis (AS) and enthesitis-related arthritis (ERA).
Volume-guarantee vs. pressure-limited ventilation in evolving bronchopulmonary dysplasia
Authors: Cuevas Guaman Milenka , Hagan Joseph , Sabic Dajana , Tillman Davlyn M. , Fernandes Caraciolo J.
Published: December 2022

Introduction

Extremely premature infants are at high risk for developing bronchopulmonary dysplasia (BPD). While noninvasive support is preferred, they may require ventilator support. Although volume-targeted ventilation (VTV) has been shown to be beneficial in preventing BPD, no data exists to guide ventilator management of infants with evolving BPD. Thus, clinicians employ a host of ventilator strategies, traditionally time-cycled pressure-limited ventilation (PLV) and more recently volume-guarantee ventilation (VGV) (a form of VTV). In this study, we sought to test the hypothesis that use of VGV in evolving BPD is associated with improved clinical and pulmonary outcomes when compared with PLV.

Design

Single-center, retrospective cohort review of premature infants born less than 28 weeks inborn to a Level 4 NICU from January 2015 to December 2020. Data abstracted included demographics, maternal and birth data, and ventilator data until death or discharge. Exposure to either VGV or PLV was also examined, including ventilator “dose” (number of time points from DOL 14, 21 and 28 the patient was on that particular ventilator) during the period of evolving BPD.

Results

Of a total of 471 patients with ventilation data available on DOL 14, 268 were not ventilated and 203 were ventilated. PLV at DOL 21 and 28 was associated with significantly higher risk of BPD and the composite outcome of BPD or death before 36 weeks compared to VGV. Both increasing VGV and PLV doses were significantly associated with higher odds of BPD and the composite outcome. For each additional time point of VGV and PLV exposure, the predicted length of stay (LOS) increased by 15.3 days (p < 0.001) and 28.8 days (p < 0.001), respectively.

Discussion

Our study demonstrates the association of use of VGV at DOL 21 and 28 with decreased risk of BPD compared to use of PLV. Prospective trials are needed to further delineate the most effective ventilatory modality for this population with “evolving” BPD.
Elucidating the role of keratin 75 in enamel using Krt75tm1Der knock-in mouse model
Authors: Deshmukh Rutuja , Vasquez Brent , Bhogadi Lasya , Gabe Claire M. , Lukashova Lyudmila , Verdelis Kostas , Morasso Maria I. , Beniash Elia
Published: December 2022

Keratin 75 (K75) was recently discovered in ameloblasts and enamel organic matrix. Carriers of A161T substitution in K75 present with the skin condition Pseudofollicullitis barbae. This mutation is also associated with high prevalence of caries and compromised structural and mechanical properties of enamel. Krt75tm1Der knock-in mouse (KI) with deletion of Asn159, located two amino acids away from KRT75A161T, can be a potential model for studying the role of K75 in enamel and the causes of the higher caries susceptibility associated with KRT75A161T mutation. To test the hypotheses that KI enamel is more susceptible to a simulated acid attack (SAA), and has altered structural and mechanical properties, we conducted in vitro SAA experiments, microCT, and microhardness analyses on 1st molars of one-month-old WT and KI mice. KI and WT hemimandibles were subjected to SAA and contralateral hemimandibles were used as controls. Changes in enamel porosity were assessed by immersion of the hemimandibles in rhodamine, followed by fluorescent microscopy analysis. Fluorescence intensity of KI enamel after SSA was significantly higher than in WT, indicating that KI enamel is more susceptible to acid attack. MicroCT analysis of 1st molars revealed that while enamel volumes were not significantly different, enamel mineral density was significantly lower in KI, suggesting a potential defect of enamel maturation. Microhardness tests revealed that in KI enamel is softer than in WT, and potentially less resilient to damages. These results suggest that the KI enamel can be used as a model to study the role of K75 in enamel.
Integrated multi-omics reveals the molecular mechanisms underlying efficient phosphorus use under phosphate deficiency in elephant grass (Pennisetum purpureum)
Authors: Luo Jiajia , Cai Zeping , Huang Rui , Wu Yuanhang , Liu Chun , Huang Chunqiong , Liu Pandao , Liu Guodao , Dong Rongshu
Published: December 2022

Phosphorus (P) is an essential macronutrient element for plant growth, and deficiency of inorganic phosphate (Pi) limits plant growth and yield. Elephant grass (Pennisetum purpureum) is an important fodder crop cultivated widely in tropical and subtropical areas throughout the world. However, the mechanisms underlying efficient P use in elephant grass under Pi deficiency remain poorly understood. In this study, the physiological and molecular responses of elephant grass leaves and roots to Pi deficiency were investigated. The results showed that dry weight, total P concentration, and P content decreased in Pi-deprived plants, but that acid phosphatase activity and P utilization efficiency (PUE) were higher than in Pi-sufficient plants. Regarding Pi starvation-responsive (PSR) genes, transcriptomics showed that 59 unigenes involved in Pi acquisition and transport (especially 18 purple acid phosphatase and 27 phosphate transporter 1 unigenes) and 51 phospholipase unigenes involved in phospholipids degradation or Pi-free lipids biosynthesis, as well as 47 core unigenes involved in the synthesis of phenylpropanoids and flavonoids, were significantly up-regulated by Pi deprivation in leaves or roots. Furthermore, 43 unigenes related to Pi-independent- or inorganic pyrophosphate (PPi)-dependent bypass reactions were markedly up-regulated in Pi-deficient leaves, especially five UDP-glucose pyrophosphorylase and 15 phosphoenolpyruvate carboxylase unigenes. Consistent with PSR unigene expression changes, metabolomics revealed that Pi deficiency significantly increased metabolites of Pi-free lipids, phenylpropanoids, and flavonoids in leaves and roots, but decreased phospholipid metabolites. This study reveals the mechanisms underlying the responses to Pi starvation in elephant grass leaves and roots, which provides candidate unigenes involved in efficient P use and theoretical references for the development of P-efficient elephant grass varieties.
Wheat yield estimation using remote sensing data based on machine learning approaches
Authors: Cheng Enhui , Zhang Bing , Peng Dailiang , Zhong Liheng , Yu Le , Liu Yao , Xiao Chenchao , Li Cunjun , Li Xiaoyi , Chen Yue , Ye Huichun , Wang Hongye , Yu Ruyi , Hu Jinkang , Yang Songlin
Published: December 2022

Accurate predictions of wheat yields are essential to farmers’production plans and to the international trade in wheat. However, only poor approximations of the productivity of wheat crops in China can be obtained using traditional linear regression models based on vegetation indices and observations of the yield. In this study, Sentinel-2 (multispectral data) and ZY-1 02D (hyperspectral data) were used together with 15709 gridded yield data (with a resolution of 5 m × 5 m) to predict the winter wheat yield. These estimates were based on four mainstream data-driven approaches: Long Short-Term Memory (LSTM), Random Forest (RF), Gradient Boosting Decision Tree (GBDT), and Support Vector Regression (SVR). The method that gave the best estimate of the winter wheat yield was determined, and the accuracy of the estimates based on multispectral and hyperspectral data were compared. The results showed that the LSTM model, for which the RMSE of the estimates was 0.201 t/ha, performed better than the RF (RMSE = 0.260 t/ha), GBDT (RMSE = 0.306 t/ha), and SVR (RMSE = 0.489 t/ha) methods. The estimates based on the ZY-1 02D hyperspectral data were more accurate than those based on the 30-m Sentinel-2 data: RMSE = 0.237 t/ha for the ZY-1 02D data, which is about a 5% improvement on the RSME of 0.307 t/ha for the 30-m Sentinel-2 data. However, the 10-m Sentinel-2 data performed even better, giving an RMSE of 0.219 t/ha. In addition, it was found that the greenness vegetation index SR (simple ratio index) outperformed the traditional vegetation indices. The results highlight the potential of the shortwave infrared bands to replace the visible and near-infrared bands for predicting crop yields Our study demonstrates the advantages of the deep learning method LSTM over machine learning methods in terms of its ability to make accurate estimates of the winter wheat yield.