bluuebunny/crossref_metadata_2025 huggingface dataset:
Endoscopic thyroidectomy via areola approach for stage T1 papillary thyroid carcinoma: feasibility, safety, and oncologic outcomes
Authors: Huo Jinlong , Xu Yaxuan , Yu Jie , Guo Youming , Hu Xiaochi , Ou Dong , Qu Rui , Zhao Lijin
Published: November 2023

Purpose

To evaluate the feasibility, safety, and oncologic outcomes associated with endoscopic thyroidectomy via the areolar approach (ETAA), compared with conventional open thyroidectomy (COT) for the treatment of stage T1 papillary thyroid carcinoma (PTC).

Methods

Between January 2021 and June 2022, a total of 1204 patients diagnosed with PTC underwent screening, out of which 138 patients were selected for inclusion in the study population after propensity score matching (92 patients in the ETAA group and 46 patients in the COT group). The study included the collection and analysis of clinicopathologic characteristics, intraoperative outcomes, postoperative outcomes, complications, and follow-up data using R software.

Results

The operative time for the ETAA group was longer than that for the COT group (160.42 ± 32.21 min vs. 121.93 ± 29.78 min, p < 0.0001). However, there were no significant differences between the two groups in terms of intraoperative blood loss, the extent of surgical resection, the number of dissected lymph nodes, the number of metastatic lymph nodes, and the rate of parathyroid autotransplantation. Postoperative drainage and C-reactive protein levels were higher in the ETAA group than in the COT group, but there were no significant differences in 24-hour visual analogue scale scores, white blood cell counts, drainage duration, or postoperative hospital stay. Complication rates were similar between the two groups, and no permanent recurrent laryngeal nerve palsy or hypoparathyroidism was observed. Patients who underwent ETAA reported greater cosmetic satisfaction and quality of life than those who underwent COT. During the follow-up phase, only one patient in the COT group developed lateral cervical lymph node involvement requiring reoperation.

Conclusion

ETAA is a safe and feasible surgical method for patients with stage T1 PTC, providing results similar to COT in terms of oncologic completeness, while avoiding neck scars, with excellent cosmetic effects.

Clinical trial registration

Chinese Clinical Trial Registry center, identifier ChiCTR2300077109
Case Report: Whole-exome sequencing identified two novel COMP variants causing pseudoachondroplasia
Authors: Zhou Lin , Chen Jing , Liu Qian , Yang Shuting , Xie Wanqin , Peng Ying
Published: November 2023

Pseudoachondroplasia (PSACH) is a rare, dominant genetic disorder affecting bone and cartilage development, characterized by short-limb short stature, brachydactyly, loose joints, joint stiffness, and pain. The disorder is caused by mutations in the COMP gene, which encodes a protein that plays a role in the formation of collagen fibers. In this study, we present the clinical and genetic characteristics of PSACH in two Chinese families. Whole-exome sequencing (WES) analysis revealed two novel missense variants in the COMP gene: NM_000095.3: c.1319G>T (p.G440V, maternal) and NM_000095.3: c.1304A>T (p.D435V, paternal-mosaic). Strikingly, both the G440V and D435V mutations were located in the same T3 repeat motif and exhibited the potential to form hydrogen bonds with each other. Upon further analysis using Missense3D and PyMOL, we ascertained that these mutations showed the propensity to disrupt the protein structure of COMP, thus hampering its functioning. Our findings expand the existing knowledge of the genetic etiology underlying PSACH. The identification of new variants in the COMP gene can broaden the range of mutations linked with the condition. This information can contribute to the diagnosis and genetic counseling of patients with PSACH.
Pancreas and islet morphology in cystic fibrosis: clues to the etiology of cystic fibrosis-related diabetes
Authors: Malik Sarah S. , Padmanabhan Diksha , Hull-Meichle Rebecca L.
Published: November 2023

Cystic fibrosis (CF) is a multi-organ disease caused by loss-of-function mutations in CFTR (which encodes the CF transmembrane conductance regulator ion channel). Cystic fibrosis related diabetes (CFRD) occurs in 40-50% of adults with CF and is associated with significantly increased morbidity and mortality. CFRD arises from insufficient insulin release from β cells in the pancreatic islet, but the mechanisms underlying the loss of β cell function remain understudied. Widespread pathological changes in the CF pancreas provide clues to these mechanisms. The exocrine pancreas is the epicenter of pancreas pathology in CF, with ductal pathology being the initiating event. Loss of CFTR function results in ductal plugging and subsequent obliteration. This in turn leads to destruction of acinar cells, fibrosis and fatty replacement. Despite this adverse environment, islets remain relatively well preserved. However, islet composition and arrangement are abnormal, including a modest decrease in β cells and an increase in α, δ and γ cell abundance. The small amount of available data suggest that substantial loss of pancreatic/islet microvasculature, autonomic nerve fibers and intra-islet macrophages occur. Conversely, T-cell infiltration is increased and, in CFRD, islet amyloid deposition is a frequent occurrence. Together, these pathological changes clearly demonstrate that CF is a disease of the pancreas/islet microenvironment. Any or all of these changes are likely to have a dramatic effect on the β cell, which relies on positive signals from all of these neighboring cell types for its normal function and survival. A thorough characterization of the CF pancreas microenvironment is needed to develop better therapies to treat, and ultimately prevent CFRD.
Diagnostic efficacy of the triglyceride–glucose index in the prediction of contrast-induced nephropathy following percutaneous coronary intervention
Authors: Chang Wei−Ting , Liu Chien-Cheng , Huang Yen-Ta , Wu Jheng-Yan , Tsai Wen-Wen , Hung Kuo−Chuan , Chen I−Wen , Feng Ping-Hsun
Published: November 2023

Introduction

Contrast-induced nephropathy (CIN) is a common complication of percutaneous coronary intervention (PCI). Identifying patients at high CIN risk remains challenging. The triglyceride-glucose (TyG) index may help predict CIN but evidence is limited. We conducted a meta-analysis to evaluate the diagnostic value of TyG index for CIN after PCI.

Methods

A systematic literature search was performed in MEDLINE, Cochrane, and EMBASE until August 2023 (PROSPERO registration: CRD42023452257). Observational studies examining TyG index for predicting CIN risk in PCI patients were included. This diagnostic meta-analysis aimed to evaluate the accuracy of the TyG index in predicting the likelihood of CIN. Secondary outcomes aimed to assess the pooled incidence of CIN and the association between an elevated TyG index and the risk of CIN.

Results

Five studies (Turkey, n=2; China, n=3) with 3518 patients (age range: 57.6 to 68.22 years) were included. The pooled incidence of CIN was 15.3% [95% confidence interval (CI) 11-20.8%]. A high TyG index associated with increased CIN risk (odds ratio: 2.25, 95% CI 1.82-2.77). Pooled sensitivity and specificity were 0.77 (95% CI 0.59-0.88) and 0.55 (95% CI 0.43-0.68) respectively. Analysis of the summary receiver operating characteristic (sROC) curve revealed an area under the curve of 0.69 (95% CI 0.65-0.73). There was a low risk of publication bias (p = 0.81).

Conclusion

The TyG index displayed a noteworthy correlation with the risk of CIN subsequent to PCI. However, its overall diagnostic accuracy was found to be moderate in nature. While promising, the TyG index should not be used in isolation for CIN screening given the heterogeneity between studies. In addition, the findings cannot be considered conclusive given the scarcity of data. Further large-scale studies are warranted to validate TyG cutoffs and determine how to optimally incorporate it into current risk prediction models.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023452257, identifier CRD42023452257.
PFOS-elicited metabolic perturbation in liver and fatty acid metabolites in testis of adult mice
Authors: Lee Wang Ka , Lam Thomas Ka Yam , Tang Hiu Ching , Ho Tsz Chun , Wan Hin Ting , Wong Chris Kong Chu
Published: November 2023

Introduction

Multiple factors can contribute to sub-fecundity, including genetics, lifestyle, and environmental contaminants. PFASs are characterized as “forever chemicals” due to their ubiquitous contamination and their persistence in the environment, wildlife, and humans. Numerous studies have demonstrated that PFAS exposure adversely affects multiple bodily functions, including liver metabolism and gonadal function. It is unclear, however, how the disruption of hepatic fatty acid metabolism affects testicular function.

Methods

In this study, male mice were administered 0.3 and 3 μg/g body weight of PFOS for 21 days.

Results

Our data showed that PFOS exposure caused hepatic steatosis, as evidenced by significant increases in triglyceride levels, expression of ATP-citrate lyase, and fatty acid synthase, as well as fasting insulin levels. PFOS perturbed the expression levels of hepatokines, of which fibroblast growth factor-21 (Fgf-21), leukocyte cell-derived chemotaxin-2 (Lect-2), and retinol-binding protein-4 (Rbp-4) were significantly reduced, whereas angiopoietin-like 4 (Angptl4) was noticeably increased. While Rbp-4 and Fgf-21 are known to contribute to spermatogenesis and testosterone synthesis. In PFOS-exposed groups, testicular ATP, and testosterone decreased significantly with a significant increase in the expression of peroxisome proliferator-activated receptor-coactivator 1α. Mass spectrophotometry imaging revealed the localization of PFOS in testes, along with significant increases in fatty acid metabolites. These included arachidonic acid, dihomo-α-linolenic acid, dihomo-γ-linolenic acid, oxidized ceramide, diacylglycerol, phosphatidylcholine, and phosphatidylethanolamine, which are associated with inflammation and post-testicular causes of infertility.

Discussion

This study revealed potential links between PFOS-elicited changes in hepatic metabolism and their impacts on testicular biology. This study provides insights into alternative targets elicited by PFOS that can be used to develop diagnostic and therapeutic strategies for improving testicular dysfunction.
Optimal scheduling of integrated energy systems with exergy and demand responsiveness
Authors: Zhang Baorui , Wang Ruiqi , Wang Ming , Wang Mingyuan , Li Ke , Yan Yi , Gao He
Published: November 2023

To fairly use demand response to regulate customer load , support the economic and environmental protection, and assess the quantity and quality of the synergistic growth of the integrated energy system, a multi-objective optimum scheduling model and a solution method considering exergy efficiency and demand response are presented. To begin with, a mathematical model of each energy gadget is created. The electricity–gas load demand response model is then built using the price elasticity matrix, while the cooling load demand response model is built taking into account the user’s comfort temperature. On this basis, a multi-objective optimal dispatching model is developed with the optimization goals of minimizing system operation costs, reducing carbon emissions, and increasing exergy efficiency. Finally, the model is solved using NSGA-II to produce the Pareto optimal frontier solution set in various situations, and the VIKOR decision procedure is utilized to identify the complete best dispatching solution. The simulation results suggest that the proposed model can match the system’s scheduling needs in terms of numerous objectives such as economy, environmental protection, and exergy efficiency while also assuring user’s comfort.
Effects of environmental factors on vertical distribution of the eukaryotic plankton community in early summer in Danjiangkou Reservoir, China
Authors: Mai Sijie , He Yuxiao , Li Weiguo , Zhao Tongqian
Published: November 2023

Introduction

Eukaryotic plankton plays crucial roles in ecosystem processes, impacting aquatic ecosystem stability. This study focuses on Danjiangkou Reservoir, a canyon lake in central China, that acts as the water source of the Mid-route of the South-to-North Water Diversion Project.

Methods

In this study, high-throughput 18S rDNA gene sequencing was employed to investigate eukaryotic plankton community at four water depths (0.5 m, 5 m, 10 m, and 20 m). The environmental factors including pH, water temperature (WT), nitrate nitrogen (NO3−-N), ammonia nitrogen (NH4+-N), total nitrogen (TN), conductivity (Cond), and dissolved oxygen (DO) in reservoir areas were measured, and their correlations with abundance and diversity of eukaryotic plankton were analyzed.

Results

The results showed the presence of 122 genera of eukaryotic plankton from 38 phyla. Eukaryotic plankton communities were mainly composed of Eurytemora, Thermocyclops, Sinocalanus, Mesocyclops, and Cryptomonas. In particular, significant differences in the diversity of eukaryotic plankton communities were found in vertical distribution. The diversity and abundance of eukaryotic plankton communities in 7 sampling sites decreased with the increase of depth from 0.5 to 10 m, while the diversity and abundance of plankton communities increased at 20 m. RDA analysis indicated that pH, depth, WT, NH4+-N, DO, Cond, and NO3−-N could influence the vertical distribution of the eukaryotic plankton community in the Danjiangkou Reservoir. Among these eukaryotic plankton, Eurytemora, Thermocyclops, and Volvox were negatively correlated with pH and WT and positively correlated with depth.

Discussion

This study revealed a novel perspective on the distribution of the eukaryotic plankton community in Danjiangkou Reservoir, particularly in terms of vertical variation, which will be helpful to comprehensively understand ecological processes and to further ensure the water quality safety in this canyon-style reservoir.
A genome-wide association study reveals novel SNP markers associated with resilience traits in two Mediterranean dairy sheep breeds
Authors: Argyriadou Angeliki , Michailidou Sofia , Vouraki Sotiria , Tsartsianidou Valentina , Triantafyllidis Alexandros , Gelasakis Athanasios , Banos Georgios , Arsenos Georgios
Published: November 2023

Genetic selection for higher productivity increased dairy sheep susceptibility to diseases and environmental stressors, challenging their health and welfare status and production efficiency. Improving resilience to such stressors can enhance their ability to face these challenges without compromising productivity. Our objective was to estimate genomic heritability and perform genome-wide association studies (GWAS) to detect SNPs and candidate genes associated with three proxy traits for resilience (milk somatic cell count—SCC, lactation persistency—LP, body condition score—BCS) of Chios and Frizarta dairy ewes. We used genome-wide genotypes of 317 Chios and 346 Frizarta ewes. Individual records of milk yield and BCS, and milk samples were collected monthly for two consecutive milking periods; samples were analyzed to determine SCC. The LP was calculated as the regression coefficient of daily milk yield on days from lambing. Within breed, variance components analyses and GWAS were performed using genomic relatedness matrices in single-trait animal linear mixed models. Genomic-based heritability estimates were relatively high (BCS: h2 = 0.54 and 0.55, SCC: h2 = 0.25 and 0.38, LP: h2 = 0.43 and 0.45, for Chios and Frizarta ewes, respectively), compared to previous pedigree-based studies. The GWAS revealed 7 novel SNPs associated with the studied traits; one genome-wide and two suggestive significant SNPs for SCC (Frizarta: rs403061409, rs424064526 and rs428540973, on chromosomes 9, 1 and 12, respectively), one suggestive significant SNP for BCS (Chios: rs424834097 on chromosome 4) and three suggestive significant SNPs for LP (Frizarta: rs193632931 and rs412648955 on chromosomes 1 and 6, Chios: rs428128299 on chromosome 3). Nineteen candidate genes were detected: two for BCS (Chios: POT1, TMEM229A), thirteen for SCC (Frizarta: NTAQ1, ZHX1, ZHX2, LOC101109545, HAS2, DERL1, FAM83A, ATAD2, RBP7, FSTL1, CD80, HCLS1, GSK3B) and four for LP (Frizarta: GRID2, FAIM, CEP70—Chios: GRIP1). Present results show that resilience in the studied dairy sheep breeds is heritable and advance existing knowledge on the genomic background of SCC, LP, and BCS. Future research will quantify effects of different alleles of significant SNPs on the studied traits and search for possible correlations among traits to facilitate their effective incorporation in breeding programs aiming to improve resilience.
The Rac-GEF Tiam1 controls integrin-dependent neutrophil responses
Authors: Hornigold Kirsti , Baker Martin J. , Machin Polly A. , Chetwynd Stephen A. , Johnsson Anna-Karin , Pantarelli Chiara , Islam Priota , Stammers Melanie , Crossland Laraine , Oxley David , Okkenhaug Hanneke , Walker Simon , Walker Rachael , Segonds-Pichon Anne , Fukui Yoshinori , Malliri Angeliki , Welch Heidi C. E.
Published: November 2023

Rac GTPases are required for neutrophil adhesion and migration, and for the neutrophil effector responses that kill pathogens. These Rac-dependent functions are impaired when neutrophils lack the activators of Rac, Rac-GEFs from the Prex, Vav, and Dock families. In this study, we demonstrate that Tiam1 is also expressed in neutrophils, governing focal complexes, actin cytoskeletal dynamics, polarisation, and migration, in a manner depending on the integrin ligand to which the cells adhere. Tiam1 is dispensable for the generation of reactive oxygen species but mediates degranulation and NETs release in adherent neutrophils, as well as the killing of bacteria. In vivo, Tiam1 is required for neutrophil recruitment during aseptic peritonitis and for the clearance of Streptococcus pneumoniae during pulmonary infection. However, Tiam1 functions differently to other Rac-GEFs. Instead of promoting neutrophil adhesion to ICAM1 and stimulating β2 integrin activity as could be expected, Tiam1 restricts these processes. In accordance with these paradoxical inhibitory roles, Tiam1 limits the fMLP-stimulated activation of Rac1 and Rac2 in adherent neutrophils, rather than activating Rac as expected. Tiam1 promotes the expression of several regulators of small GTPases and cytoskeletal dynamics, including αPix, Psd4, Rasa3, and Tiam2. It also controls the association of Rasa3, and potentially αPix, Git2, Psd4, and 14-3-3ζ/δ, with Rac. We propose these latter roles of Tiam1 underlie its effects on Rac and β2 integrin activity and on cell responses. Hence, Tiam1 is a novel regulator of Rac-dependent neutrophil responses that functions differently to other known neutrophil Rac-GEFs.
Validation of elevated levels of interleukin-8 in the cerebrospinal fluid, and discovery of new biomarkers in patients with GBS and CIDP using a proximity extension assay
Authors: Kmezic Ivan , Gustafsson Rasmus , Fink Katharina , Svenningsson Anders , Samuelsson Kristin , Ingre Caroline , Olsson Tomas , Hansson Magnus , Kockum Ingrid , Adzemovic Milena Z. , Press Rayomand
Published: November 2023

Background

Biomarkers for diagnosis of inflammatory neuropathies, assessment of prognosis, and treatment response are lacking.

Methods

CSF and EDTA plasma from patients with Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), healthy controls (HC) and disease controls were analyzed with Olink multiplex proximity extension assay (PEA) from two independent cohorts. Levels of interleukin-8 (IL8) were further analyzed with ELISA in patients with GBS, CIDP, paraproteinemia-related demyelinating polyneuropathy (PDN), multifocal motor neuropathy (MMN), HC and disease controls. ROC analysis was performed. Outcome was measured with the GBS-disability score (GBS-ds) or Inflammatory Neuropathy Cause and Treatment (INCAT) score.

Results

In CSF, multiplex PEA analysis revealed up-regulation of IL8 in GBS compared to CIDP and HC respectively, and CIDP compared to HC. In addition, levels of IL2RA were upregulated in GBS compared to both HC and CIDP, SELE in GBS compared to HC, and ITGAM, IL6, and NRP1 in GBS compared to CIDP. In plasma, levels of MMP3, THBD and ITGAM were upregulated in CIDP compared to HC. Validation of multiplex IL8 results using ELISA, revealed increased levels of IL8 in CSF in patients with GBS and CIDP versus HC and non-inflammatory polyneuropathies (NIP) respectively, as well as in PDN versus NIP and HC. Levels of IL8 in CSF correlated with impairment in the acute phase of GBS as well as outcome at 6-months follow up.

Conclusion

IL8 in CSF is validated as a diagnostic biomarker in GBS and CIDP, and a prognostic biomarker in GBS. Multiplex PEA hereby identifies several potential biomarkers in GBS and CIDP.
Case Report: HAVCR2 mutation-associated Hemophagocytic lymphohistiocytosis
Authors: Song Deli , Wang Jingshi , Zhang Jia , Hu Junxia , Wu Chaofan , Wang Zhao
Published: November 2023

Germline HAVCR2 mutation has been reported to be associated with subcutaneous panniculitis-like T-cell lymphoma (SPTCL) leading to Hemophagocytic lymphohistiocytosis (HLH). Several studies have indicated that HAVCR2 mutation can cause HLH even in the absence of lymphoma, though the exact mechanism remains unclear. In this article, we reported five cases of HAVCR2 mutation-associated HLH. Our analysis revealed an elevated level of IL-1RA in the serum of these patients. Furthermore, we investigated the potential mechanisms underlying HLH associated with HAVCR2 mutation based on changes in cytokine levels. Our findings suggest that HAVCR2 mutation may represent a distinct genetic defect underlying HLH, differing from traditional primary HLH.
Limitations of PLX3397 as a microglial investigational tool: peripheral and off-target effects dictate the response to inflammation
Authors: Claeys Wouter , Verhaege Daan , Van Imschoot Griet , Van Wonterghem Elien , Van Acker Lore , Amelinck Laura , De Ponti Federico F. , Scott Charlotte , Geerts Anja , Van Steenkiste Christophe , Van Hoecke Lien , Vandenbroucke Roosmarijn E.
Published: November 2023

Microglia, the resident macrophages of the central nervous system (CNS), play a critical role in CNS homeostasis and neuroinflammation. Pexidartinib (PLX3397), a colony-stimulating factor 1 (CSF1) receptor inhibitor, is widely used to deplete microglia, offering flexible options for both long-term depletion and highly versatile depletion-repopulation cycles. However, the potential impact of PLX3397 on peripheral (immune) cells remains controversial. Until now, the microglia-specificity of this type of compounds has not been thoroughly evaluated, particularly in the context of peripherally derived neuroinflammation. Our study addresses this gap by examining the effects of PLX3397 on immune cells in the brain, liver, circulation and bone marrow, both in homeostasis and systemic inflammation models. Intriguingly, we demonstrate that PLX3397 treatment not only influences the levels of tissue-resident macrophages, but also affects circulating and bone marrow immune cells beyond the mononuclear phagocyte system (MPS). These alterations in peripheral immune cells disrupt the response to systemic inflammation, consequently impacting the phenotype irrespective of microglial depletion. Furthermore, we observed that a lower dose of PLX3397, which does not deplete microglia, demonstrates similar (non-)MPS effects, both in the periphery and the brain, but fails to fully replicate the peripheral alterations seen in the higher doses, questioning lower doses as a ‘peripheral control’ strategy. Overall, our data highlight the need for caution when interpreting studies employing this compound, as it may not be suitable for specific investigation of microglial function in the presence of systemic inflammation.
An integrated study of glutamine alleviates enteritis induced by glycinin in hybrid groupers using transcriptomics, proteomics and microRNA analyses
Authors: He Yuanfa , Dong Xiaohui , Yang Qihui , Liu Hongyu , Zhang Shuang , Xie Shiwei , Chi Shuyan , Tan Beiping
Published: November 2023

Glutamine has been used to improve intestinal development and immunity in fish. We previously found that dietary glutamine enhances growth and alleviates enteritis in juvenile hybrid groupers (Epinephelus fuscoguttatus♀ × Epinephelus lanceolatus♂). This study aimed to further reveal the protective role of glutamine on glycinin-induced enteritis by integrating transcriptome, proteome, and microRNA analyses. Three isonitrogenous and isolipidic trial diets were formulated: a diet containing 10% glycinin (11S group), 10% glycinin diet supplemented with 2% alanine-glutamine (Gln group), and a diet containing neither glycinin nor alanine-glutamine (fishmeal, FM group). Each experimental diet was fed to triplicate hybrid grouper groups for 8 weeks. The analysis of intestinal transcriptomic and proteomics revealed a total of 570 differentially expressed genes (DEGs) and 169 differentially expressed proteins (DEPs) in the 11S and FM comparison group. Similarly, a total of 626 DEGs and 165 DEPs were identified in the Gln and 11S comparison group. Integration of transcriptome and proteome showed that 117 DEGs showed consistent expression patterns at both the transcriptional and translational levels in the Gln and 11S comparison group. These DEGs showed significant enrichment in pathways associated with intestinal epithelial barrier function, such as extracellular matrix (ECM)-receptor interaction, tight junction, and cell adhesion molecules (P < 0.05). Further, the expression levels of genes (myosin-11, cortactin, tenascin, major histocompatibility complex class I and II) related to these pathways above were significantly upregulated at both the transcriptional and translational levels (P < 0.05). The microRNA results showed that the expression levels of miR-212 (target genes colla1 and colla2) and miR-18a-5p (target gene colla1) in fish fed Gln group were significantly lower compared to the 11S group fish (P < 0.05). In conclusion, ECM-receptor interaction, tight junction, and cell adhesion molecules pathways play a key role in glutamine alleviation of hybrid grouper enteritis induced by high-dose glycinin, in which miRNAs and target mRNAs/proteins participated cooperatively. Our findings provide valuable insights into the RNAs and protein profiles, contributing to a deeper understanding of the underlying mechanism for fish enteritis.
Molecular mechanisms of pruritus in prurigo nodularis
Authors: Shao Yixin , Wang Duoqin , Zhu Yiqi , Xiao Zijing , Jin Taiyu , Peng Lisi , Shen Yanyun , Tang Hui
Published: November 2023

Pruritus is the most common symptom of dermatological disorders, and prurigo nodularis (PN) is notorious for intractable and severe itching. Conventional treatments often yield disappointing outcomes, significantly affecting patients’ quality of life and psychological well-being. The pathogenesis of PN is associated with a self-sustained “itch-scratch” vicious cycle. Recent investigations of PN-related itch have partially revealed the intricate interactions within the cutaneous neuroimmune network; however, the underlying mechanism remains undetermined. Itch mediators play a key role in pruritus amplification in PN and understanding their action mechanism will undoubtedly lead to the development of novel targeted antipruritic agents. In this review, we describe a series of pruritogens and receptors involved in mediating itching in PN, including cytokines, neuropeptides, extracellular matrix proteins, vasculogenic substances, ion channels, and intracellular signaling pathways. Moreover, we provide a prospective outlook on potential therapies based on existing findings.
Liquid biopsy biomarkers to guide immunotherapy in breast cancer
Authors: Yang Jinghan , Qiu Liang , Wang Xi , Chen Xi , Cao Pingdong , Yang Zhe , Wen Qiang
Published: November 2023

Immune checkpoint inhibitors (ICIs) therapy has emerged as a promising treatment strategy for breast cancer (BC). However, current reliance on immunohistochemical (IHC) detection of PD-L1 expression alone has limited predictive capability, resulting in suboptimal efficacy of ICIs for some BC patients. Hence, developing novel predictive biomarkers is indispensable to enhance patient selection for immunotherapy. In this context, utilizing liquid biopsy (LB) can provide supplementary or alternative value to PD-L1 IHC testing for identifying patients most likely to benefit from immunotherapy and exhibit favorable responses. This review discusses the predictive and prognostic value of LB in breast cancer immunotherapy, as well as its limitations and future directions. We aim to promote the individualization and precision of immunotherapy in BC by elucidating the role of LB in clinical practice.
Enhancement of mucosal innate and adaptive immunity following intranasal immunization of mice with a bovine adenoviral vector
Authors: Sayedahmed Ekramy E. , Elshafie Nelly O. , Zhang GuangJun , Mohammed Sulma I. , Sambhara Suryaprakash , Mittal Suresh K.
Published: November 2023

Introduction

Nonhuman adenoviral (AdV) gene delivery platforms have significant value due to their ability to elude preexisting AdV vector immunity in most individuals. Previously, we have demonstrated that intranasal (IN) immunization of mice with BAd-H5HA, a bovine AdV type 3 (BAdV3) vector expressing H5N1 influenza virus hemagglutinin (HA), resulted in enhanced humoral and cell-mediated immune responses. The BAd-H5HA IN immunization resulted in complete protection following the challenge with an antigenically distinct H5N1 virus compared to the mouse group similarly immunized with HAd-H5HA, a human AdV type 5 (HAdV5) vector expressing HA.

Methods

Here, we attempted to determine the activation of innate immune responses in the lungs of mice inoculated intranasally with BAd-H5HA compared to the HAd-H5HA-inoculated group.

Results

RNA-Seq analyses of the lung tissues revealed differential expression (DE) of genes involved in innate and adaptive immunity in animals immunized with BAd-H5HA. The top ten enhanced genes were verified by RT-PCR. Consistently, there were transient increases in the levels of cytokines (IL-1α, IL-1β, IL-5, TNF- α, LIF, IL-17, G-CSF, MIP-1β, MCP-1, MIP-2, and GM-CSF) and toll-like receptors in the lungs of the group inoculated with BAdV vectors compared to that of the HAdV vector group.

Conclusion

These results demonstrate that the BAdV vectors induce enhanced innate and adaptive immunity-related factors compared to HAdV vectors in mice. Thus, the BAdV vector platform could be an excellent gene delivery system for recombinant vaccines and cancer immunotherapy.
Mind the gap: comparing exploration effort with global biodiversity patterns and climate projections to determine ocean areas with greatest exploration needs
Authors: Kennedy Brian R. C. , Rotjan Randi D.
Published: November 2023

The oceans contain 1,335 million km3 of water covering 361.9 million km2 of seafloor across 71% of the planet. In the past few decades, there has been substantial effort put into mapping and exploring the ocean fueled by the advent of new technologies that more easily enable deepwater access. However, we are still far from achieving our shared goals of a well characterized and documented ocean. In 2010, Webb et al. documented the paucity of deep-sea data in general, with a specific focus on the lack of pelagic records in the Ocean Biogeographic Information System OBIS, which is the largest of the ocean biodiversity archives. While significant exploration progress has been made, the rate of change in the ocean is outstripping the rate of characterization and research. Given the limited resources available, future work needs to be prioritized to focus on areas of greatest need. Here, we investigated several lines of inquiry to determine priority areas for future exploration. We accumulated the largest database of global deep submergence dive records ever compiled and used it, plus OBIS biodiversity records, to assess the level of exploration in different ocean regions. Then, we compared these measures of exploration effort with different biogeographic province schemas and estimates of climate change velocity projections to identify the largest remaining gaps in exploration and research sampling. Given that marine science has only explored between 5 and 20% of the ocean (depending on estimates) in the last hundred and fifty years, future exploration needs to be more targeted to attempt to keep pace with the rate and impact of environmental and biodiversity change in the ocean.
Standardizing gross descriptions of skin lesions in common bottlenose dolphins (Tursiops truncatus) stranded in Southwest Florida, 2015–2019
Authors: Ewing Ruth Y. , Sutton Meghan N. , Herring Hada M. , Schubert Molly R. , Boyd Denise M. , Richardson Jill L. , Rotstein David S.
Published: November 2023

As the first line of defense, the integumentary system is critical in comprehensively evaluating dolphin morbidity during stranding response. Most published studies on skin lesions in bottlenose dolphins (Tursiops truncatus) lack standardized gross descriptions and methodologies for evaluating lesions. The primary objective of this study was to evaluate the effectiveness of an assessment matrix designed to consistently describe skin lesions based on a set of standardized gross description characteristics. The matrix was implemented by reviewing necropsy reports, histopathology reports, and photographs collected from bottlenose dolphins stranded in Southwest Florida from 2015 through 2019. Of the 32 dolphins that met the inclusion criteria, 19 presented with skin lesions and five reviewers described each of the 46 lesions according to a novel, standardized assessment matrix. The most common descriptor selected, in each of the respective matrix categories, were, by anatomic location, head; distribution, multifocal to coalescing; quantity, moderate (10–30); size, <2 cm; shape, punctate; margin, rounded; color modifier, hyperpigmentation; texture, smooth; and texture modifier, flat. These prevalent descriptors coincided with the frequent occurrence of histologically described hydropic degeneration (n=7, 15.2%) and were confirmed poxviral lesions in 6.52% (n=3). Identifying lesion patterns using standardized descriptors capitalizes on the unique pathogen tissue tropism and the implementation of certain disease mechanisms in the integumentary system. Therefore, it can facilitate differential disease diagnoses and guide ancillary diagnostics testing. The use of standardized descriptors will aid in etiologic identification and monitoring of skin lesions and associated diseases, advancing our understanding of dolphin morbidity and mortality.
Post-consolidation process for modifying microscale and mesoscale parameters of 3D printed composite materials
Authors: Yudhanto Arief , Aldhirgham Alwaleed , Feron Eric , Lubineau Gilles
Published: November 2023

Advancements in additive manufacturing technology (3D printing) have enabled us to fabricate reasonably good parts using continuous fiber-reinforced matrix composites. Unfortunately, most of these 3D-printed composite parts inherently possess a large number of voids originating from the trapped air within and between molten composite beads during the deposition stage. Removing the voids has thus become a key challenge in attempts to apply 3D printed composite parts for fabricating stiff/strong load-bearing structures. Here, we employed a classical process, viz. compression molding, to post-consolidate 3D-printed continuous carbon fiber-reinforced polyamide (CFPA), and to investigate the implications in terms of microscale parameters (void content) and mesoscale parameters (mechanical properties, plasticity, damage) using matrix-dominated lay-up of [±45]2s. We found that the proposed post-consolidation process could reduce the void of 3D-printed CFPA from 12.2% to 1.8%, enhancing the shear modulus and shear strength by 135% and 116%, respectively. The mesoscale analysis shows that, albeit with less ductility, the post-consolidated CFPA laminate was more resistant to damage than the 3D-printed CFPA. Classical compression molding is thus a promising technique for improving the physical and mechanical performances of 3D-printed composites by reducing inherent void built-ups.
Alternative biomarkers of tuberculosis infection in patients with immune-mediated inflammatory diseases
Authors: Petruccioli Elisa , Petrone Linda , Najafi-Fard Saeid , Navarra Assunta , Vanini Valentina , Cuzzi Gilda , Cantini Fabrizio , Gualano Gina , Palmieri Fabrizio , Goletti Delia
Published: November 2023

Introduction

IFN-γ release assays (IGRAs) are one of the referral tests for diagnosing tuberculosis infection (TBI). To improve IGRAs accuracy, several markers have been investigated. Patients with immune-mediated inflammatory diseases (IMID), taking biological drugs, have a higher risk to progress to TB-disease compared to the general population. In several guidelines, annual TBI screening is recommended for patients undergoing biological therapy. Aim of this study was to investigate, within the QuantiFERON-TB-Plus (QFT-Plus) platform, if beside IFN-γ, alternative biomarkers help to diagnose TBI-IMID patients.

Methods

We enrolled 146 subjects: 46 with TB disease, 20 HD, 35 with TBI and 45 with TBI and IMID. Thirteen IMID subjects with a QFT-Plus negative result were diagnosed as TBI based on radiological evidence of TBI. We evaluated the IP-10 level in response to TB1 and TB2 peptides of QFT-Plus assay and we compared these results with the standardized assay based on IFN-γ. Multiplex immune assay was performed on plasma from TB1 and TB2 tubes and results were analyzed by a gradient boosting machine (GBM) as learning technique.

Results

TBI-IMID showed a significant decreased IP-10 level in response to TB1 and TB2 stimulation compared to TBI-NO IMID (p < 0.0001 and p = 0.0002). The TBI-IMID showed a moderate agreement between the IP-10-based assay and QFT-Plus scores. In TBI-IMID, QFT-Plus showed 70% sensitivity for TBI detection whereas the IP-10-based assay reached 61%. Tests combination increased the sensitivity for TBI diagnosis up to 77%. By a GBM, we explored alternative biomarkers for diagnosing TBI in IMID population reaching 89% sensitivity. In particular, the signature based on IL-2, IP-10, and IL-9 detection was associated with TB status (infection/disease). However, by applying the cut-off identified by ROC analysis, comparing TB and TBI with the HD group, within the IMID population, we did not improve the accuracy for TBI-diagnosis. Similarly, this signature did not improve TBI diagnosis in IMID with radiological evidence of TBI but negative QFT-Plus score.

Discussion

To develop alternative strategies for TBI immune-diagnosis, future studies are needed to evaluate the memory response of TBI defined by radiological tools. These results may help in tuberculosis management of patients taking lifelong immune-suppressive drugs.
A critical systematic review assessing undergraduate neurology pipeline programs
Authors: Minen Mia T. , Aymon Ramisha , Yusaf Ishah , Oza Khushalee , Ekhtman Jane , Katara Aarti , Lebowitz Naomi , Plovnick Caitlin
Published: November 2023

Background

Although current programs exist to encourage undergraduate interest in neuroscience and neurology, few students go on to pursue a career in neurology. Thus, there is a need for more neurologists in the US. To assess undergraduate pipeline programs and their goals of garnering interest and knowledge of neurology, we systematically reviewed available literature on existing undergraduate neurology pipeline programs.

Methods

A medical librarian conducted an electronic database search of PubMed, EMBASE, PsycINFO, Education Source, and ERIC based on a search strategy developed with a team of undergraduates and a neurologist. Of the 2,852 articles screened, 33 met the systematic review criteria and were evaluated based on the type and goal of the pipeline program, its delivery, and efficacy.

Results

The 33 programs were classified into subtypes of pipeline programs, with focuses ranging from student-led projects to early clinical research opportunities. All programs were found to be successful in attracting student interest in neurology, providing exposure to relevant opportunities, and classroom enrichment.

Discussion

The existing literature shows that neurology pipeline programs successfully inspire interest in a career in neurology among undergraduate students. These programs are valuable supplements to undergraduate neuroscience curricula and instrumental in introducing students to various fields.
Gut microbiota from essential tremor patients aggravates tremors in mice
Authors: Zhang Ruo-Xin , Xu Jia-Ting , Zhong Hao-Jie , Cai Ying-Li , Zhuang Yu-Pei , Xie Ya-Ting , He Xing-Xiang
Published: November 2023

Background and objective

Essential tremor (ET) lacks effective treatments because its underlying mechanism is largely unknown, but may involve gut microbiota via the microbiome-gut-brain axis. We explored the effects of gut microbiota on ET in mice.

Methods

Specific pathogen-free C57BL/6J mice were gavaged with stools from ET patients or matched healthy individuals. After 3 weeks of gavaging, behavioral tests were performed on all mice. Next, each mouse was injected with harmaline to induce tremors. The tremor duration was recorded; the tremor score was estimated every 30 min. Behavioral tests were repeated after modeling. Intestinal tissues and fecal samples of the mice were examined using histology and 16Sr DNA sequencing, respectively.

Results

Compared with mice receiving microbiota from healthy controls, mice receiving fecal suspensions from ET patients showed worse performance in the pre-modeling behavioral tests. After modeling, ET-group mice showed significantly greater tremor scores, longer tremor duration, and worse motor performance. They also had significantly lower body weight and lower fecal pellet count. Pathological scoring revealed more severe intestinal lesions in ET-group mice. The 16S rDNA sequencing data revealed significant differences in microbiota indices, and a correlation between these indices and tremors in mice. Functional predictions indicated that the abundance of GABA-related enzymes was altered in ET-group mice.

Conclusion

Mice transplanted with gut microbiota from ET patients showed worse performance in behavioral tests. After modeling, ET-group mice presented longer tremor duration, higher tremor score, and worse motor performance. This study provides evidence for gut microbiota dysbiosis that may affect the pathogenesis of ET.
Effect of sugar transporter on galactose utilization in Streptococcus thermophilus
Authors: Zhao Jiancun , Liang Yan , Zhang Susu , Xu Zhenshang
Published: November 2023

Introduction

Streptococcus thermophilus is a traditional starter for dairy products. The lactose rich in milk is the main carbon source for the growth of S. thermophilus. However, the utilization of galactose by S. thermophilus is strain-specific, and many genetic factors can affect the sugar utilization phenotype of S. thermophilus strains.

Methods

In this study, S. thermophilus A25, which is capable of utilizing lactose and galactose, was used as the starting strain to construct lactose permease-deficient mutant S. thermophilus ΔlacS. Subsequently, the complement vectors expressing complete lactose permease of S. thermophilus and its N-terminal 1–486 amino acid residues were constructed and transformed into S. thermophilus ΔlacS, respectively. Meanwhile, complement vectors expressing lactose permease and galactose/proton symporter of Escherichia coli were also constructed.

Results and Discussion

Results showed that S. thermophilus ΔlacS lost the ability to utilize lactose and galactose. By measuring the growth of the recombinant strains, it was found that the strain expressing complete lactose permease of S. thermophilus recovered the growth ability in lactose and galactose medium, while the strain expressing N-terminal of lactose permease recovered the growth ability only in lactose medium. Furthermore, the transformation of S. thermophilus ΔlacS was not successful with the complement vector expressing E. coli lactose permease, while the strain expressing E. coli galactose/proton symporter could recover its growth ability in the galactose medium. These results suggest that the properties of sugar transporters play an important role in galactose utilization by S. thermophilus.
Occurrence and characterization of NDM-5-producing Escherichia coli from retail eggs
Authors: Liu Yi-Yun , Li Tong , Yue Huiying , Yue Chao , Lu Litao , Chen Junqiang , Deng Haotian , Gao Xun , Liu Jian-Hua
Published: November 2023

The New Delhi Metallo-β-lactamase (NDM) producing Enterobacterales has been detected from diverse sources but has rarely been reported in retail eggs. In this study, 144 eggshell and 96 egg content samples were collected in 2022 from Guangdong province and were screened for NDM-producing strains. Four Escherichia coli strains (ST3014, ST10, ST1485, and ST14747) recovered from two (1.39%, 2 of 144) eggshells and two (2.08%, 2 of 96) egg content samples were identified as blaNDM−5-positive strains. Oxford Nanopore MinION sequencing and conjugation assays revealed that the blaNDM−5 gene was carried by IncX3 (n = 1), IncI1 (n = 1), and IncHI2 (n = 2). The IncI1-plasmid-carrying blaNDM−5 displayed high homology with one plasmid pEC6563-NDM5 from the human clinic, while the IncHI2 plasmid harboring blaNDM−5 shared highly similar structures with plasmids of animal origin. To the best of our knowledge, this is the first report on the identification of blaNDM−5-positive bacteria in retail eggs. NDM-producing E. coli could be transmitted to humans by the consumption of eggs or direct contact, which could pose a potential threat to human health.
Identification of novel small RNAs in extracellular vesicles produced by Actinobacillus pleuropneumoniae
Authors: da Silva Giarlã Cunha , Rosa Jéssica Nogueira , Fontes Patrícia Pereira , de Castro Alex Gazolla , Barbosa Éverton De Almeida Alves , Clarindo Wellington Ronildo , Mantovani Hilário Cuquetto , Li Yanwen , Bossé Janine Thérèse , Langford Paul Richard , Bazzolli Denise Mara Soares
Published: November 2023

Extracellular vesicle (EV) production by bacteria is an important mechanism for microbial communication and host-pathogen interaction. EVs of some bacterial species have been reported to contain nucleic acids. However, the role of small RNAs (sRNAs) packaged in EVs is poorly understood. Here, we report on the RNA cargo of EVs produced by the pig pathogen Actinobacillus pleuropneumoniae, the causal agent of porcine pleuropneumonia, a disease which causes substantial economic losses to the swine industry worldwide. The EVs produced by aerobically and anaerobically grown bacteria were only slightly different in size and distribution. Total cell and outer membrane protein profiles and lipid composition of A. pleuropneumoniae whole cell extracts and EVs were similar, although EVs contained rough lipopolysaccharide compared to the smooth form in whole cells. Approximately 50% of Galleria mellonella larvae died after the injection of EVs. RNAseq, RT-PCR, protection from nuclease degradation, and database searching identified previously described and 13 novel A. pleuropneumoniae sRNAs in EVs, some of which were enriched compared to whole cell content. We conclude that A. pleuropneumoniae EVs contain sRNAs, including those known to be involved in virulence, and some with homologs in other Pasteurellaceae and/or non-Pasteurellaceae. Further work will establish whether the novel sRNAs in A. pleuropneumoniae EVs play any role in pathogenesis.