bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma proteomics analysis of Chinese HIV-1 infected individuals focusing on the immune and inflammatory factors afford insight into the viral control mechanism
Authors: Ni Wanqi , Ren Li , Liao Lingjie , Li Dan , Luo Zhenwu , Zhu Meiling , Liu Ying , Xing Hui , Wang Zheng , Shao Yiming
Published: May 2024

Background

Long-term non-progressors (LTNPs) with HIV infection can naturally control viral replication for up to a decade without antiretroviral therapy (ART), but the underlying mechanisms of this phenomenon remain elusive.

Methods

To investigate the relevant immune and inflammatory factors associated with this natural control mechanism, we collected plasma samples from 16 LTNPs, 14 untreated viral progressors (VPs), 17 successfully ART-treated patients (TPs), and 16 healthy controls (HCs). The OLINK immune response panel and inflammation panel were employed to detect critical proteins, and the plasma neutralizing activity against a global panel of pseudoviruses was assessed using TZM-bl cells.

Results

The combination of IL17C, IL18, DDX58, and NF2 contributed to discriminating LTNPs and VPs. IL18 and CCL25 were positively associated with CD4+ T cell counts but negatively correlated with viral load. Furthermore, CXCL9 and CXCL10 emerged as potential supplementary diagnostic markers for assessing the efficacy of antiretroviral therapy (ART). Finally, TNFRSF9 displayed positive correlations with neutralization breadth and Geometry Median Titer (GMT) despite the lack of significant differences between LTNPs and VPs.

Conclusion

In summary, this study identified a set of biomarkers in HIV-infected individuals at different disease stages. These markers constitute a potential network for immune balance regulation in HIV infection, which is related to the long-term control of HIV by LTNPs. It provides important clues for further exploring the immune regulatory mechanism of HIV.
Aberrant adaptive immune response underlies genetic susceptibility to tuberculosis
Authors: Tsareva Anastasiia , Shelyakin Pavel V. , Shagina Irina A. , Myshkin Mikhail Yu. , Merzlyak Ekaterina M. , Kriukova Valeriia V. , Apt Alexander S. , Linge Irina A. , Chudakov Dmitriy M. , Britanova Olga V.
Published: May 2024

Mycobacterium tuberculosis (Mtb) remains a major threat worldwide, although only a fraction of infected individuals develops tuberculosis (TB). TB susceptibility is shaped by multiple genetic factors, and we performed comparative immunological analysis of two mouse strains to uncover relevant mechanisms underlying susceptibility and resistance. C57BL/6 mice are relatively TB-resistant, whereas I/St mice are prone to develop severe TB, partly due to the MHC-II allelic variant that shapes suboptimal CD4+ T cell receptor repertoire. We investigated the repertoires of lung-infiltrating helper T cells and B cells at the progressed stage in both strains. We found that lung CD4+ T cell repertoires of infected C57BL/6 but not I/St mice contained convergent TCR clusters with functionally confirmed Mtb specificity. Transcriptomic analysis revealed a more prominent Th1 signature in C57BL/6, and expression of pro-inflammatory IL-16 in I/St lung-infiltrating helper T cells. The two strains also showed distinct Th2 signatures. Furthermore, the humoral response of I/St mice was delayed, less focused, and dominated by IgG/IgM isotypes, whereas C57BL/6 mice generated more Mtb antigen-focused IgA response. We conclude that the inability of I/St mice to produce a timely and efficient anti-Mtb adaptive immune responses arises from a suboptimal helper T cell landscape that also impacts the humoral response, leading to diffuse inflammation and severe disease.
A TLR4 ligand-based adjuvant for promoting the immunogenicity of typhoid subunit vaccines
Authors: Alugupalli Kishore R.
Published: May 2024

None of the typhoid Vi Polysaccharide (ViPS) subunit vaccines incorporate adjuvants, and the immunogenicity of ViPS vaccines (e.g. Typbar TCV® and Typhim Vi®) is in part due to associated TLR4 ligands such as endotoxin present in these vaccines. Since endotoxin content in vaccines is variable and kept very low due to inherent toxicity, it was hypothesized that incorporating a defined amount of a non-toxic TLR4-ligand such as monophosphoryl lipid A in ViPS vaccines would improve their immunogenicity. To test this hypothesis, a monophosphoryl lipid A-based adjuvant formulation named Turbo was developed. Admixing Turbo with Typbar TCV® (ViPS-conjugated to tetanus toxoid) increased the levels of anti-ViPS IgM, IgG1, IgG2b, IgG2a/c, and IgG3 in inbred and outbred mice. In infant mice, a single immunization with Turbo adjuvanted Typbar TCV® resulted in a significantly increased and durable IgG response and improved the control of bacterial burden compared to mice immunized without Turbo. Similarly, when adjuvanted with Turbo, the antibody response and control of bacteremia were also improved in mice immunized with Typhim Vi®, an unconjugated vaccine. The immunogenicity of unconjugated ViPS is inefficient in young mice and is lost in adult mice when immunostimulatory ligands in ViPS are removed. Nevertheless, when adjuvanted with Turbo, poorly immunogenic ViPS induced a robust IgG response in young and adult mice, and this was observed even under antigen-limiting conditions. These data suggest that incorporation of Turbo as an adjuvant will make typhoid vaccines more immunogenic regardless of their intrinsic immunogenicity or conjugation status and maximize the efficacy across all ages.
Follicular lymphoma regulatory T-cell origin and function
Authors: Rodriguez Stéphane , Alizadeh Mehdi , Lamaison Claire , Saintamand Alexis , Monvoisin Céline , Jean Rachel , Deleurme Laurent , Martin-Subero Jose Ignacio , Pangault Céline , Cogné Michel , Amé-Thomas Patricia , Tarte Karin
Published: May 2024

Introduction

Follicular Lymphoma (FL) results from the malignant transformation of germinal center (GC) B cells. FL B cells display recurrent and diverse genetic alterations, some of them favoring their direct interaction with their cell microenvironment, including follicular helper T cells (Tfh). Although FL-Tfh key role is well-documented, the impact of their regulatory counterpart, the follicular regulatory T cell (Tfr) compartment, is still sparse.

Methods

The aim of this study was to characterize FL-Tfr phenotype by cytometry, gene expression profile, FL-Tfr origin by transcriptomic analysis, and functionality by in vitro assays.

Results

CD4+CXCR5+CD25hiICOS+ FL-Tfr displayed a regulatory program that is close to classical regulatory T cell (Treg) program, at the transcriptomic and methylome levels. Accordingly, Tfr imprinting stigmata were found on FL-Tfh and FL-B cells, compared to their physiological counterparts. In addition, FL-Tfr co-culture with autologous FL-Tfh or cytotoxic FL-CD8+ T cells inhibited their proliferation in vitro. Finally, although FL-Tfr shared many characteristics with Treg, TCR sequencing analyses demonstrated that part of them derived from precursors shared with FL-Tfh.

Discussion

Altogether, these findings uncover the role and origin of a Tfr subset in FL niche and may be useful for lymphomagenesis knowledge and therapeutic management.
A novel humanized mouse model for HIV and tuberculosis co-infection studies
Authors: Bohórquez José Alejandro , Adduri Sitaramaraju , Ansari Danish , John Sahana , Florence Jon , Adejare Omoyeni , Singh Gaurav , Konduru Nagarjun V. , Jagannath Chinnaswamy , Yi Guohua
Published: May 2024

Background

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), continues to be a major public health problem worldwide. The human immunodeficiency virus (HIV) is another equally important life-threatening pathogen. HIV infection decreases CD4+ T cell levels markedly increasing Mtb co-infections. An appropriate animal model for HIV/Mtb co-infection that can recapitulate the diversity of the immune response in humans during co-infection would facilitate basic and translational research in HIV/Mtb infections. Herein, we describe a novel humanized mouse model.

Methods

The irradiated NSG-SGM3 mice were transplanted with human CD34+ hematopoietic stem cells, and the humanization was monitored by staining various immune cell markers for flow cytometry. They were challenged with HIV and/or Mtb, and the CD4+ T cell depletion and HIV viral load were monitored over time. Before necropsy, the live mice were subjected to pulmonary function test and CT scan, and after sacrifice, the lung and spleen homogenates were used to determine Mtb load (CFU) and cytokine/chemokine levels by multiplex assay, and lung sections were analyzed for histopathology. The mouse sera were subjected to metabolomics analysis.

Results

Our humanized NSG-SGM3 mice were able to engraft human CD34+ stem cells, which then differentiated into a full-lineage of human immune cell subsets. After co-infection with HIV and Mtb, these mice showed decrease in CD4+ T cell counts overtime and elevated HIV load in the sera, similar to the infection pattern of humans. Additionally, Mtb caused infections in both lungs and spleen, and induced granulomatous lesions in the lungs. Distinct metabolomic profiles were also observed in the tissues from different mouse groups after co-infections.

Conclusion

The humanized NSG-SGM3 mice are able to recapitulate the pathogenic effects of HIV and Mtb infections and co-infection at the pathological, immunological and metabolism levels and are therefore a reproducible small animal model for studying HIV/Mtb co-infection.
Glycan-based scaffolds and nanoparticles as drug delivery system in cancer therapy
Authors: Qin Henan , Teng Yibin , Dai Rui , Wang Aman , Liu Jiwei
Published: May 2024

Glycan-based scaffolds are unique in their high specificity, versatility, low immunogenicity, and ability to mimic natural carbohydrates, making them attractive candidates for use in cancer treatment. These scaffolds are made up of glycans, which are biopolymers with well biocompatibility in the human body that can be used for drug delivery. The versatility of glycan-based scaffolds allows for the modulation of drug activity and targeted delivery to specific cells or tissues, which increases the potency of drugs and reduces side effects. Despite their promise, there are still technical challenges in the design and production of glycan-based scaffolds, as well as limitations in their therapeutic efficacy and specificity.
Exploring the impact of colostrum supplementation on athletes: a comprehensive analysis of clinical trials and diverse properties
Authors: Yalçıntaş Yalçın Mert , Baydemir Barış , Duman Hatice , Eker Furkan , Bayraktar Biçen Ayşe , Ertürk Melih , Karav Sercan
Published: May 2024

Colostrum, an invaluable food produced by mammals during the postnatal period, contains important bioactive components. It is a valuable therapeutic substance that can be used to treat a variety of disorders, in addition to its primary function of providing passive immunity to newborns. Undoubtedly, a strong dedication to intense effort and demanding training schedules is necessary to succeed in today’s sports environment. Peak physical fitness, strategic skill development, and mental toughness are highly valued in the environments in which athletes compete. However, the inherent difficulties brought about by athletes’ intense schedules are matched with the demanding character of modern sports. The intensity of athletic activity frequently provides little time for sufficient relaxation, nutritional preparation, and overall recovery, which can contribute to mental and physical tiredness. Athletes need to develop all-encompassing strategies to overcome these obstacles. These strategies should prioritize self-care and recovery in addition to maximizing training efficiency. The bioactive components of colostrum bring forth various therapeutic effects against the challenges experienced by athletes; including diarrhea, upper respiratory tract infections, muscle injuries, intestinal disorders, etc. This review examined the different therapeutic effects of the bioactive components of colostrum on athletes, the effect of the use of colostrum as a whole on the performance of athletes, and the clinical research conducted in this field. While the majority of studies report positive effects of colostrum, further research is needed.
Efficacy and safety of lenvatinib plus durvalumab combined with hepatic arterial infusion chemotherapy for unresectable intrahepatic cholangiocarcinoma
Authors: Zhao Rongce , Zhou Jing , Miao Zhaoxia , Xiong Xinhao , Wei Wei , Li Shaohua , Guo Rongping
Published: May 2024

Background

The prognosis for unresectable intrahepatic cholangiocarcinoma (ICC) is poor and the efficacy of traditional chemotherapy remains unsatisfactory. Hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX) is effective in patients with unresectable ICC. In this study, we determined the preliminary clinical efficacy and safety of lenvatinib plus durvalumab combined with FOLFOX-HAIC in patients with untreated, unresectable ICC.

Materials and methods

Between July 2021 and July 2023, patients with unresectable ICC who initially received lenvatinib plus durvalumab combined with FOLFOX-HAIC at the Sun Yat-Sen University Cancer Center (SYSUCC) were reviewed for eligibility. Efficacy was evaluated by tumor response rate and survival, and safety was assessed by the frequency of key adverse events (AEs).

Results

A total of 28 eligible patients were enrolled. The objective response rates (ORRs) based on mRECIST and RECIST 1.1 criteria were 65.2% and 39.1%, respectively. The median OS was 17.9 months (95% CI, 5.7–30.1) and the median PFS was 11.9 months (95% CI, 6.7–17.1). Most patients (92.9%) experienced adverse events (AEs), whereas 46.5% (13/28) experienced grade 3 or 4 AEs.

Conclusion

Lenvatinib plus durvalumab combined with FOLFOX-HAIC showed promising antitumor activity and manageable AEs in patients with treatment-naive unresectable ICC. This regimen may be suitable as a novel first-line treatment option for this patient population.
Optimum eicosapentaenoic acid + docosahexaenoic acid levels for farmed Atlantic salmon: closing the gap between science and commercial practice
Authors: Carr Ian , Santigosa Ester , Chen Tony , Costantino John
Published: May 2024

The shift from fish oil to vegetable oil (VO) sources has lowered eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) levels in salmon aquafeeds. VOs are high in omega-6 and low in omega-3 essential fatty acids like EPA and DHA, crucial for fish metabolism and immunity. Algal oil (AO), with high EPA + DHA and lower omega-6 levels supports fish health and growth, but transferring lab-controlled conditions to real-world commercial farming remains a challenge. This study explored the benefits of high dietary EPA + DHA levels through a commercial farm (CF) study in Chile and a Big Data (BD) study in Norway. The CF study, involving 625,000 Atlantic salmon, compared standard feed with AO-supplemented feed. The latter resulted in improved health responses and better fillet quality. The BD study analyzed real data from 232.6 million fish, revealing that EPA + DHA levels > 8% reduce mortality variability by 21%, improve economic feed conversion ratio by 11%, and increase the likelihood of superior harvests by 27%, demonstrating productivity benefits. Both studies emphasize the advantages of feeds with EPA + DHA levels above typical industry practices, enhancing growth, health, and nutritional quality. Importantly, the BD study complements the CF study, bridging the gap between science and aquafarms, and providing evidence that diets with EPA + DHA > 8% offer biological performance benefits for farmers, regardless of farming environments.
Solid-state fermentation converts rice bran into a high-protein feed ingredient for Penaeus monodon
Authors: Huervana Fredson H. , Traifalgar Rex Ferdinand M. , Dionela Cleresa S.
Published: May 2024

Fermented rice bran (FRB) was evaluated as an alternative protein source to soybean meal (SM) in practical diets for juvenile black tiger shrimp, Penaeus monodon. This feed ingredient was tested in a feeding trial to replace soybean meal in P. monodon diets at 0% (T0), 12.5% (T12.5), 25% (T25), 37.5% (T37.5), and 50% (T50). Five iso-nitrogenous and iso-caloric experimental diets containing 44% crude protein were fed to groups of juvenile shrimp (0.47 ± 0.002 g) randomly assigned to twenty 60-l rectangular tanks equipped with a recirculating seawater system. Each dietary treatment was run in 4 replicates, and the feeding trial lasted 50 days. Results show significant improvement in weight gain, specific growth rate, and protein efficiency ratio in treatment T12.5 and T25. Treatments with higher levels of SM replacement with FRB exhibited similar growth indices to those of the control group. Polynomial regression analysis indicates that the optimum replacement of soybean meal with FRB for optimum growth is 21.08%. The apparent dry matter and protein digestibility coefficients of FRB are 83.05 ± 0.02% and 87.20 ± 0.30%, respectively. There were no significant differences in the whole-body composition (dry matter, protein, lipid, ash) among treatments of shrimp fed with FRB replacement. The data suggest that FRB replacement of dietary soybean meal is feasible at 50% without affecting the growth performance but may promote growth at 21.08% replacement of P. monodon.
Investigating the role of network former interactions on charge carrier diffusivity in glasses
Authors: Salrin Tyler C. , Bragatto Caio B. , Wilkinson Collin J.
Published: May 2024

Ionic transport is a critical property for the glass industry, since emerging applications such as sensors, batteries, and electric melting are based on the phenomenon. Short-range interactions (anion-charge carrier) have not been able to explain the total activation barrier observed experimentally, and, as such, it is critical to understand the larger role of all ions in a glass, not just the carrier and the ‘site’ ions. This research focuses on the role of network formers and their impact on diffusion in glasses, something that current models lack an explicit explanation of. Atomistic simulations with randomly generated parameters for the cation potentials and classical simulations were used to determine the diffusion coefficients and activation energies for synthetic network formers. Using this database, explainable machine learning algorithms were employed to explore network former interactions and determine which parameters are the most influential for ion diffusion. Results suggest that the bond length of the cations changes the geometry of the structure contributing the greatest to cation-modifier interactions.
Unveiling the gut-eye axis: how microbial metabolites influence ocular health and disease
Authors: Nguyen Yvonne , Rudd Zhong Manis Josephine , Ronczkowski Nicole Marie , Bui Tommy , Oxenrider Allston , Jadeja Ravirajsinh N. , Thounaojam Menaka C.
Published: May 2024

The intricate interplay between the gut microbiota and ocular health has surpassed conventional medical beliefs, fundamentally reshaping our understanding of organ interconnectivity. This review investigates into the intricate relationship between gut microbiota-derived metabolites and their consequential impact on ocular health and disease pathogenesis. By examining the role of specific metabolites, such as short-chain fatty acids (SCFAs) like butyrate and bile acids (BAs), herein we elucidate their significant contributions to ocular pathologies, thought-provoking the traditional belief of organ sterility, particularly in the field of ophthalmology. Highlighting the dynamic nature of the gut microbiota and its profound influence on ocular health, this review underlines the necessity of comprehending the complex workings of the gut-eye axis, an emerging field of science ready for further exploration and scrutiny. While acknowledging the therapeutic promise in manipulating the gut microbiome and its metabolites, the available literature advocates for a targeted, precise approach. Instead of broad interventions, it emphasizes the potential of exploiting specific microbiome-related metabolites as a focused strategy. This targeted approach compared to a precision tool rather than a broad-spectrum solution, aims to explore the therapeutic applications of microbiome-related metabolites in the context of various retinal diseases. By proposing a nuanced strategy targeted at specific microbial metabolites, this review suggests that addressing specific deficiencies or imbalances through microbiome-related metabolites might yield expedited and pronounced outcomes in systemic health, extending to the eye. This focused strategy holds the potential in bypassing the irregularity associated with manipulating microbes themselves, paving a more efficient pathway toward desired outcomes in optimizing gut health and its implications for retinal diseases.
Biodiversity of Trichoderma species of healthy and Fusarium wilt-infected banana rhizosphere soils in Tenerife (Canary Islands, Spain)
Authors: Correa-Delgado Raquel , Brito-López Patricia , Jaizme Vega María C. , Laich Federico
Published: May 2024

Banana (Musa acuminata) is the most important crop in the Canary Islands (38.9% of the total cultivated area). The main pathogen affecting this crop is the soil fungal Fusarium oxysporum f. sp. cubense subtropical race 4 (Foc-STR4), for which there is no effective control method under field conditions. Therefore, the use of native biological control agents may be an effective and sustainable alternative. This study aims to: (i) investigate the diversity and distribution of Trichoderma species in the rhizosphere of different banana agroecosystems affected by Foc-STR4 in Tenerife (the island with the greatest bioclimatic diversity and cultivated area), (ii) develop and preserve a culture collection of native Trichoderma species, and (iii) evaluate the influence of soil chemical properties on the Trichoderma community. A total of 131 Trichoderma isolates were obtained from 84 soil samples collected from 14 farms located in different agroecosystems on the northern (cooler and wetter) and southern (warmer and drier) slopes of Tenerife. Ten Trichoderma species, including T. afroharzianum, T. asperellum, T. atrobrunneum, T. gamsii, T. guizhouense, T. hamatum, T. harzianum, T. hirsutum, T. longibrachiatum, and T. virens, and two putative novel species, named T. aff. harzianum and T. aff. hortense, were identified based on the tef1-α sequences. Trichoderma virens (35.89% relative abundance) and T. aff. harzianum (27.48%) were the most abundant and dominant species on both slopes, while other species were observed only on one slope (north or south). Biodiversity indices (Margalef, Shannon, Simpson, and Pielou) showed that species diversity and evenness were highest in the healthy soils of the northern slope. The Spearman analysis showed significant correlations between Trichoderma species and soil chemistry parameters (mainly with phosphorus and soil pH). To the best of our knowledge, six species are reported for the first time in the Canary Islands (T. afroharzianum, T. asperellum, T. atrobrunneum, T. guizhouense, T. hamatum, T. hirsutum) and in the rhizosphere of banana soils (T. afroharzianum, T. atrobrunneum, T. gamsii, T. guizhouense, T. hirsutum, T. virens). This study provides essential information on the diversity/distribution of native Trichoderma species for the benefit of future applications in the control of Foc-STR4.
Intervention of computer-assisted cognitive training combined with occupational therapy in people with mild cognitive impairment: a randomized controlled trial
Authors: Wen Xin , Song Shangrong , Tian Hui , Cui Hang , Zhang Lijuan , Sun Yajie , Li Mingyue , Wang Yonghong
Published: May 2024

Objective

Investigate the impact of combined computerized cognitive training and occupational therapy on individuals with mild cognitive impairment (MCI).

Methods

We randomly assigned 118 MCI patients into two groups: a combined intervention group (n = 37) and a control group (n = 81), the latter receiving standard nursing care. The intervention group additionally underwent 12 weeks of computerized cognitive training and occupational therapy. Blind assessors evaluated cognitive performance, anxiety, depression, and daily living activities before the intervention, post-intervention, and at a 3-month follow-up.

Results

Repeated-measures analysis of variance showed that the sMoCA scores, HAMA scores, and ADL scores of the experimental group at T2 (post-intervention) and T3 (3-month follow-up) were higher than those of the control group, and the difference was statistically significant (p < 0.001, p < 0.001, p = 0.026).

Conclusion

Computerized cognitive training combined with occupational therapy can improve patients’ cognitive status, enhance their compliance with continuing care, and maintain their anxiety and self-care ability at a stable level.

Clinical trial registration

https://www.chictr.org.cn/index.html, identifier ChiCTR2200065014.
The role of syntaxins in retinal function and health
Authors: Tebbe Lars , Kakakhel Mashal , Al-Ubaidi Muayyad R. , Naash Muna I.
Published: May 2024

The soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein (SNAP) receptor (SNARE) superfamily plays a pivotal role in cellular trafficking by facilitating membrane fusion events. These SNARE proteins, including syntaxins, assemble into complexes that actively facilitate specific membrane fusion events. Syntaxins, as integral components of the SNARE complex, play a crucial role in initiating and regulating these fusion activities. While specific syntaxins have been extensively studied in various cellular processes, including neurotransmitter release, autophagy and endoplasmic reticulum (ER)-to-Golgi protein transport, their roles in the retina remain less explored. This review aims to enhance our understanding of syntaxins’ functions in the retina by shedding light on how syntaxins mediate membrane fusion events unique to the retina. Additionally, we seek to establish a connection between syntaxin mutations and retinal diseases. By exploring the intricate interplay of syntaxins in retinal function and health, we aim to contribute to the broader comprehension of cellular trafficking in the context of retinal physiology and pathology.
Evidence-based commentary on the diagnosis, management, and further research of degenerative cervical spinal cord compression in the absence of clinical symptoms of myelopathy
Authors: Horak Tomas , Horakova Magda , Kerkovsky Milos , Dostal Marek , Hlustik Petr , Valosek Jan , Svatkova Alena , Bednarik Petr , Vlckova Eva , Bednarik Josef
Published: May 2024

Degenerative cervical myelopathy (DCM) represents the final consequence of a series of degenerative changes in the cervical spine, resulting in cervical spinal canal stenosis and mechanical stress on the cervical spinal cord. This process leads to subsequent pathophysiological processes in the spinal cord tissues. The primary mechanism of injury is degenerative compression of the cervical spinal cord, detectable by magnetic resonance imaging (MRI), serving as a hallmark for diagnosing DCM. However, the relative resilience of the cervical spinal cord to mechanical compression leads to clinical-radiological discordance, i.e., some individuals may exhibit MRI findings of DCC without the clinical signs and symptoms of myelopathy. This degenerative compression of the cervical spinal cord without clinical signs of myelopathy, potentially serving as a precursor to the development of DCM, remains a somewhat controversial topic. In this review article, we elaborate on and provide commentary on the terminology, epidemiology, natural course, diagnosis, predictive value, risks, and practical management of this condition—all of which are subjects of ongoing debate.
Disrupted single-subject gray matter networks are associated with cognitive decline and cortical atrophy in Alzheimer’s disease
Authors: Xiao Yaqiong , Gao Lei , Hu Yubin ,   The Alzheimer’s Disease Neuroimaging Initiative
Published: May 2024

Background

Research has shown disrupted structural network measures related to cognitive decline and future cortical atrophy during the progression of Alzheimer’s disease (AD). However, evidence regarding the individual variability of gray matter network measures and the associations with concurrent cognitive decline and cortical atrophy related to AD is still sparse.

Objective

To investigate whether alterations in single-subject gray matter networks are related to concurrent cognitive decline and cortical gray matter atrophy during AD progression.

Methods

We analyzed structural MRI data from 185 cognitively normal (CN), 150 mild cognitive impairment (MCI), and 153 AD participants, and calculated the global network metrics of gray matter networks for each participant. We examined the alterations of single-subject gray matter networks in patients with MCI and AD, and investigated the associations of network metrics with concurrent cognitive decline and cortical gray matter atrophy.

Results

The small-world properties including gamma, lambda, and sigma had lower values in the MCI and AD groups than the CN group. AD patients had reduced degree, clustering coefficient, and path length than the CN and MCI groups. We observed significant associations of cognitive ability with degree in the CN group, with gamma and sigma in the MCI group, and with degree, connectivity density, clustering coefficient, and path length in the AD group. There were significant correlation patterns between sigma values and cortical gray matter volume in the CN, MCI, and AD groups.

Conclusion

These findings suggest the individual variability of gray matter network metrics may be valuable to track concurrent cognitive decline and cortical atrophy during AD progression. This may contribute to a better understanding of cognitive decline and brain morphological alterations related to AD.
A nomogram for predicting pathologic node negativity after neoadjuvant chemotherapy in breast cancer patients: a nationwide, multicenter retrospective cohort study (CSBrS-012)
Authors: Maimaitiaili Amina , Li Yijun , Chai Na , Liu Zhenzhen , Ling Rui , Zhao Yi , Yang Hongjian , Liu Yunjiang , Liu Ke , Zhang Jianguo , Mao Dahua , Yu Zhigang , Liu Yinhua , Fu Peifen , Wang Jiandong , Jiang Hongchuan , Zhao Zuowei , Tian Xingsong , Cao Zhongwei , Wu Kejin , Song Ailin , Jin Feng , Wu Puzhao , He Jianjun , Fan Zhimin , Zhang Huimin
Published: May 2024

Purpose

This study aimed to investigate the factors associated with pathologic node-negativity (ypN0) in patients who received neoadjuvant chemotherapy (NAC) to develop and validate an accurate prediction nomogram.

Methods

The CSBrS-012 study (2010–2020) included female patients with primary breast cancer treated with NAC followed by breast and axillary surgery in 20 hospitals across China. In the present study, 7,711 eligible patients were included, comprising 6,428 patients in the primary cohort from 15 hospitals and 1,283 patients in the external validation cohort from five hospitals. The hospitals were randomly assigned. The primary cohort was randomized at a 3:1 ratio and divided into a training set and an internal validation set. Univariate and multivariate logistic regression analyses were performed on the training set, after which a nomogram was constructed and validated both internally and externally.

Results

In total, 3,560 patients (46.2%) achieved ypN0, and 1,558 patients (20.3%) achieved pathologic complete response in the breast (bpCR). A nomogram was constructed based on the clinical nodal stage before NAC (cN), ER, PR, HER2, Ki67, NAC treatment cycle, and bpCR, which were independently associated with ypN0. The area under the receiver operating characteristic curve (AUC) for the training set was 0.80. The internal and external validation demonstrated good discrimination, with AUCs of 0.79 and 0.76, respectively.

Conclusion

We present a real-world study based on nationwide large-sample data that can be used to effectively screen for ypN0 to provide better advice for the management of residual axillary disease in breast cancer patients undergoing NAC.
From immune equilibrium to tumor ecodynamics
Authors: Chen Xiaoping
Published: May 2024

Objectives

There is no theory to quantitatively describe the complex tumor ecosystem. At the same time, cancer immunotherapy is considered a revolution in oncology, but the methods used to describe tumors and the criteria used to evaluate efficacy are not keeping pace. The purpose of this study is to establish a new theory for quantitatively describing the tumor ecosystem, innovating the methods of tumor characterization, and establishing new efficacy evaluation criteria for cancer immunotherapy.

Methods

Based on the mathematization of immune equilibrium theory and the establishment of immunodynamics in a previous study, the method of reverse immunodynamics was used, namely, the immune braking force was regarded as the tumor ecological force and the immune force was regarded as the tumor ecological braking force, and the concept of momentum in physics was applied to the tumor ecosystem to establish a series of tumor ecodynamic equations. These equations were used to solve the fundamental and applied problems of the complex tumor ecosystem.

Results

A series of tumor ecodynamic equations were established. The tumor ecological momentum equations and their component factors could be used to distinguish disease progression, pseudoprogression, and hyperprogression in cancer immunotherapy. On this basis, the adjusted tumor momentum equations were established to achieve the equivalence of tumor activity (including immunosuppressive activity and metabolic activity) and tumor volume, which could be used to calculate individual disease remission rate and establish new efficacy evaluation criteria (ieRECIST) for immunotherapy of solid tumor based on tumor ecodynamics. At the same time, the concept of moving cube-to-force square ratio and its expression were proposed to calculate the area under the curve of tumor ecological braking force of blood required to achieve an individual disease remission rate when the adjusted tumor ecological momentum was known.

Conclusions

A new theory termed tumor ecodynamics emphasizing both tumor activity and tumor volume is established to solve a series of basic and applied problems in the complex tumor ecosystem. It can be predicted that the future will be the era of cancer immune ecotherapy that targets the entire tumor ecosystem.
Mitigating jaw osteonecrosis: bioactive glass and pericardial membrane combination in a rat model
Authors: Pellicano Alexandre Antonio , Benites Bernar M. , Paschoa Amanda F. N. , Oliveira Laura C. , Campos Ana Carolina P. , Martins Daniel O. , Real Caroline C. , de Paula Faria Daniele , Fonseca Felipe P. , Martinez Raquel R. C. , Pagano Rosana L. , Fregnani Eduardo R.
Published: May 2024

Objectives

Bisphosphonates (BFs) show clinical effectiveness in managing osteoporosis and bone metastases but pose risks of bisphosphonate-related jaw osteonecrosis (BRONJ). With no established gold standard for BRONJ treatment, our focus is on symptom severity reduction. We aimed to assess the preventive effects of bioactive glass and/or pericardial membrane in a preclinical BRONJ model, evaluating their potential to prevent osteonecrosis and bone loss post-tooth extractions in zoledronic acid (ZA)-treated animals.

Methods

Rats, receiving ZA or saline biweekly for four weeks, underwent 1st and 2nd lower left molar extractions. Pericardial membrane alone or with F18 bioglass was applied post-extractions. Microarchitecture analysis and bone loss assessment utilized computerized microtomography (CT) and positron emission tomography (PET) with 18F-FDG and 18F-NaF tracers. Histological analysis evaluated bone injury.

Results

Exclusive alveolar bone loss occurred post-extraction in the continuous ZA group, inducing osteonecrosis, osteolysis, osteomyelitis, and abscess formation. Concurrent pericardial membrane with F18 bioglass application prevented these outcomes. Baseline PET/CT scans showed no discernible uptake differences, but post-extraction 18F-FDG tracer imaging revealed heightened glucose metabolism at the extraction site in the ZA-treated group with membrane, contrasting the control group.

Conclusion

These findings suggest pericardial membrane with F18 bioglass effectively prevents BRONJ in the preclinical model.
Activated interferon response from DNA damage in multiple myeloma cells contributes to the chemotherapeutic effects of anthracyclines
Authors: Li Jin , Jia Zhuxia , Wang Rongxuan , Xiao Bitao , Cai Yanan , Zhu Tianshu , Wang Weiya , Zhang Xinyue , Fan Shu , Fan Xiaolong , Han Wenmin , Lu Xuzhang
Published: May 2024

Introduction

Multiple myeloma (MM) is a malignant plasma cell disease caused by abnormal proliferation of clonal plasma cells in bone marrow. Upfront identification of tumor subgroups with specific biological markers has the potential to improve biologically-driven therapy. Previously, we established a molecular classification by stratifying multiple myeloma into two subtypes with a different prognosis based on a gene module co-expressed with MCL-1 (MCL1-M).

Methods

Gene Ontology (GO) analysis with differentially expressed genes was performed to identify signal pathway. Drug sensitivity was analyzed using the OncoPredict algorithm. Drug sensitivity of different myeloma cell lines was detected by CCK8 and flow cytometry. RNA-seq was performed on drug-sensitive cell lines before and after adriamycin treatment. RT-qPCR was used to further verify the sequencing results. The expression of γ-H2AX and dsDNA in sensitive and resistant cell lines was detected by immunofluorescence method.

Results

In our study, we demonstrated that MCL1-M low MM were more sensitive to anthracyclines. We treated different myeloma cell lines with doxorubicin in vitro and discovered the association of drug sensitivity with IFN signaling. Herein, we demonstrate that the doxorubicin-sensitive myeloma cell line showed significant DNA damage and up-regulated expression of genes related to the IFN response, which was not observed in drug-insensitive cell lines.

Discussion

Our results suggest that the active IFN signaling pathway may serve as a marker for predicting chemotherapy sensitivity in patients with myeloma. With our MCL1-M molecular classification system, we can screen patients with a potentially good response to the interferon signaling pathway and provide individualized treatment for MM. We propose IFN-a as adjuvant therapy for patients with myeloma sensitive to anthracyclines to further improve the therapeutic effect and prolong the survival of patients.
Outcomes and the effect of PGT-M in women with hormone-related hereditary tumor syndrome
Authors: Wang Dingran , Song Xueling , Zhu Xiaohui , Yan Liying , Zhi Xu , Yan Jie , Liang Huamao , Qiao Jie
Published: May 2024

Purpose

To review the outcome of PGT-M in hormone-related hereditary tumor syndrome and evaluate the effect of ovarian induction on tumor growth in those patients.

Methods

Medical records of PGT-M were retrospectively analyzed in patients with hormone-related heritage tumors in our reproductive center. A total of eleven women with hereditary breast and ovarian cancer (HBOC) (including BRCA1/2 mutation carriers), and Lynch syndrome (including MMR gene mutation carriers) were included. Thirteen IVF/PGT-M cycles were performed. Eleven for PGT-M and two for fertility preservation. The ovulation protocol, numbers of oocytes retrieved and two pronuclei (2PN) zygotes, PGT-M results, and clinical outcomes were analyzed. Tumor progression was also estimated by comparing transvaginal ultrasound (TVS), MR, CT, or colonoscopy according to the follow-up requirements of different tumors.

Results

Eleven IVF/PGT-M cycles were performed with an antagonist protocol; Two cycles were performed with a mild stimulation protocol. The total dose of gonadotropin (Gn) was 1827 IU per patient (range from 1200 to 2625 IU). The median number of oocytes retrieved was 13 (range from 4 to 30), and the median number of 2PN zygotes was 8 (range from 2 to 16). A total of 32 embryos underwent PGT-M, and 9 (28.1%) embryos were suitable for transfer. Six transfer cycles were performed, and 5 cycles got clinical pregnancy (83%) with five newborns (83%). The follow-up examinations conducted 10-18 months after PGT-M/delivery revealed no new lesions or tumor progression.

Conclusion

PGT-M results can provide important information for improving the consultation of hormone-related heritage tumor patients regarding their fertility preservation and reproductive options. Ovarian induction for women with hormone-related hereditary tumor syndrome is not associated with tumor progression.
The intricate interplay between cancer stem cells and cell-of-origin of cancer: implications for therapeutic strategies
Authors: Bamodu Oluwaseun Adebayo , Chung Chen-Chih , Pisanic Thomas R. , Wu Alexander T. H.
Published: May 2024

Background

Cancer stem cells (CSCs) have emerged as pivotal players in tumorigenesis, disease progression, and resistance to therapies.

Objective

This comprehensive review delves into the intricate relationship between CSCs and the cell-of-origin in diverse cancer types.

Design

Comprehensive review of thematically-relevant literature.

Methods

We explore the underlying molecular mechanisms that drive the conversion of normal cells into CSCs and the impact of the cell-of-origin on CSC properties, tumor initiation, and therapeutic responses. Moreover, we discuss potential therapeutic interventions targeting CSCs based on their distinct cell-of-origin characteristics.

Results

Accruing evidence suggest that the cell-of-origin, the cell type from which the tumor originates, plays a crucial role in determining the properties of CSCs and their contribution to tumor heterogeneity.

Conclusion

By providing critical insights into the complex interplay between CSCs and their cellular origins, this article aims to enhance our understanding of cancer biology and pave the way for more effective and personalized cancer treatments.
Vandetanib as a prospective anti-inflammatory and anti-contractile agent in asthma
Authors: Zeng Xiaoyue , Xue Lu , Li Wei , Zhao Ping , Chen Weiwei , Wang Wenyi , Shen Jinhua
Published: May 2024

Background: Vandetanib is a small-molecule tyrosine kinase inhibitor. It exerts its therapeutic effects primarily in a range of lung cancers by inhibiting the vascular endothelial growth factor receptor 2. However, it remains unclear whether vandetanib has therapeutic benefits in other lung diseases, particularly asthma. The present study investigated the pioneering use of vandetanib in the treatment of asthma.

Methods:In vivo experiments including establishment of an asthma model, measurement of airway resistance measurement and histological analysis were used primarily to confirm the anticontractile and anti-inflammatory effects of vandetanib, while in vitro experiments, including measurement of muscle tension and whole-cell patch-clamp recording, were used to explore the underlying molecular mechanism.

Results:In vivo experiments in an asthmatic mouse model showed that vandetanib could significantly alleviate systemic inflammation and a range of airway pathological changes including hypersensitivity, hypersecretion and remodeling. Subsequent in vitro experiments showed that vandetanib was able to relax the precontracted rings of the mouse trachea via calcium mobilization which was regulated by specific ion channels including VDLCC, NSCC, NCX and K+ channels.

Conclusions: Taken together, our study demonstrated that vandetanib has both anticontractile and anti-inflammatory properties in the treatment of asthma, which also suggests the feasibility of using vandetanib in the treatment of asthma by reducing abnormal airway contraction and systemic inflammation.
Are Turkish pharmaceutical pricing strategies an access barrier to oncology medicines for Türkiye?
Authors: Vural Elif Hilal , Kaskati Tolga , Vural İsmail Mert , Özalp Mustafa Asım , Gümüşel Bülent
Published: May 2024

Objectives: Cancer diagnosis is increasing day by day all over the world. Deaths due to cancer are among the most common causes of death. Access to cancer drugs is a priority of health policies. The aim of this study is to evaluate access to cancer drugs through drug box sales data by modeling population growth, cancer incidence, and Fixed Euro Exchange (FEE) rate parameters used in drug pricing in Türkiye.

Methods: Access to cancer drugs was evaluated by drug box sales figures obtained from IQVIA. Box sales data were classified according to diagnosis codes (ICD-10), reference, or generic status. Consumption of cancer drugs was examined over time with panel regression analysis, taking into account variables of population growth, cancer incidence, and the FEE rate in drug pricing in Türkiye.

Results: The incidence of cancer in Türkiye was 215.1 in 2010 and 223.1 (per hundred thousand) in 2017. Whereas there was a 127.02% increase in the real euro exchange rate, there was an 89.6% increase in the FEE rate. With the regression approach, there is a negative relationship between the real and fixed exchange rate difference (RFED) and reference and generic drug consumption data. Medicine access is affected depending on diagnosis codes at different levels. Colorectal cancer medicine sales had negative correlations for each variable, namely, exchange rate, population growth, and cancer incidence. On the contrary, there was a positive correlation between non-small-cell lung cancer and relevant variables. Innovative medicine groups such as monoclonal antibodies and protein kinase inhibitor consumption showed a negative correlation.

Conclusion: According to our results, pricing strategy may be an access barrier for oncology medicines in Türkiye. It should be reviewing the pricing policy that is beneficial for oncology medicine access in Türkiye.
Metabolites of traditional Chinese medicine targeting PI3K/AKT signaling pathway for hypoglycemic effect in type 2 diabetes
Authors: Feng Yuhan , Ren Yan , Zhang Xia , Yang Songqin , Jiao Qian , Li Qiuhong , Jiang Wenwen
Published: May 2024

Type 2 diabetes mellitus is a chronic metabolic disease characterized by insulin resistance, with high morbidity and mortality worldwide. Due to the tightly intertwined connection between the insulin resistance pathway and the PI3K/AKT signaling pathway, regulating the PI3K/AKT pathway and its associated targets is essential for hypoglycemia and the prevention of type 2 diabetes mellitus. In recent years, metabolites isolated from traditional Chinese medicine has received more attention and acceptance for its superior bioactivity, high safety, and fewer side effects. Meanwhile, numerous in vivo and in vitro studies have revealed that the metabolites present in traditional Chinese medicine possess better bioactivities in regulating the balance of glucose metabolism, ameliorating insulin resistance, and preventing type 2 diabetes mellitus via the PI3K/AKT signaling pathway. In this article, we reviewed the literature related to the metabolites of traditional Chinese medicine improving IR and possessing therapeutic potential for type 2 diabetes mellitus by targeting the PI3K/AKT signaling pathway, focusing on the hypoglycemic mechanism of the metabolites of traditional Chinese medicine in type 2 diabetes mellitus and elaborating on the significant role of the PI3K/AKT signaling pathway in type 2 diabetes mellitus. In order to provide reference for clinical prevention and treatment of type 2 diabetes mellitus.