bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolutionary conservation of Trichomonas-mycoplasma symbiosis across the host species barrier
Authors: Bailey Nicholas P. , Shao Yuxin , Du Shaodua , Foster Peter G. , Fettweis Jennifer , Hall Neil , Wang Zheng , Hirt Robert P.
Published: September 2023

Introduction

The protozoan parasite Trichomonas vaginalis is the most common cellular sexually transmitted disease in humans, and the closely related species Trichomonas gallinae is an avian parasite of ecological and economic importance. Phylogenetic evidence suggests T. vaginalis arose during bird to human transmission of a T. gallinae-like ancestor. Trichomonas vaginalis shares a strong clinical association with the independent sexually transmitted pathogen Metamycoplasma (formerly Mycoplasma) hominis, and the uncultured bacterium “Candidatus Malacoplasma (formerly Mycoplasma) girerdii,” with the latter association being an order of magnitude stronger. Both bacterial species have been shown to profoundly influence T. vaginalis growth, energy production and virulence-associated mechanisms.

Methods

Evidence for a novel Malacoplasma sp. was discovered by in vivo Illumina metatranscriptomics sequencing of the T. gallinae-infected pigeon mouth. We leveraged published 16S rDNA profiling data from digestive tract of 12 healthy and 24 T. gallinae-infected pigeons to investigate association between the novel Malacoplasma sp. and T. gallinae. We utilised Illumina metagenomics sequencing targeted to pigeon oral and crop samples infected with the novel Malacoplasma sp. to generate its full-length genome sequence. Sequence similarity network analysis was used to compare annotated proteins from the novel Malacoplasma sp. with a range of other related species.

Results

Here we present evidence for a novel Malacoplasma species, related to “Ca. M. girerdii,” that is strongly associated with T. gallinae in the upper digestive tract of domestic pigeons. Analysis of the genome sequence revealed gene features apparently specific to a Trichomonas-symbiotic Malacoplasma lineage.

Discussion

These data support a model of long-term association between Trichomonas and Malacoplasma spp. that has been conserved across diversification of the Trichomonas lineage and the host species barrier from birds to human.
The transcriptome landscape of 3D-cultured placental trophoblasts reveals activation of TLR2 and TLR3/7 in response to low Trypanosoma cruzi parasite exposure
Authors: Silberstein Erica , Chung Charles C. , Debrabant Alain
Published: September 2023

Vertical transmission of Trypanosoma cruzi (T. cruzi) become a globalized health problem accounting for 22% of new cases of Chagas disease (CD). Congenital infection is now considered the main route of CD spread in non-endemic countries where no routine disease testing of pregnant women is implemented. The main mechanisms that lead to fetal infection by T. cruzi remain poorly understood. Mother-to-child transmission may occur when bloodstream trypomastigotes interact with the syncytiotrophoblasts (SYNs) that cover the placenta chorionic villi. These highly specialized cells function as a physical barrier and modulate immune responses against pathogen infections. To model the human placenta environment, we have previously used a three-dimensional (3D) cell culture system of SYNs that exhibits differentiation characteristics comparable to placental trophoblasts. Further, we have shown that 3D-grown SYNs are highly resistant to T. cruzi infection. In this work, we used RNA sequencing and whole transcriptome analysis to explore the immunological signatures that drive SYNs’ infection control. We found that the largest category of differentially expressed genes (DEGs) are associated with inflammation and innate immunity functions. Quantitative RT-PCR evaluation of selected DEGs, together with detection of cytokines and chemokines in SYNs culture supernatants, confirmed the transcriptome data. Several genes implicated in the Toll-like receptors signaling pathways were upregulated in 3D-grown SYNs. In fact, TLR2 blockade and TLR3/7 knockdown stimulated T. cruzi growth, suggesting that these molecules play a significant role in the host cell response to infection. Ingenuity Pathway Analysis of DEGs predicted the activation of canonical pathways such as S100 protein family, pathogen induced cytokine storm, wound healing, HIF1α signaling and phagosome formation after T. cruzi exposure. Our findings indicate that SYNs resist infection by eliciting a constitutive pro-inflammatory response and modulating multiple defense mechanisms that interfere with the parasite’s intracellular life cycle, contributing to parasite killing and infection control.
Bacterial community assembly driven by temporal succession rather than spatial heterogeneity in Lake Bosten: a large lake suffering from eutrophication and salinization
Authors: Liu Hao , Dai Jiangyu , Fan Ziwu , Yang Bei , Wang Hang , Hu Yang , Shao Keqiang , Gao Guang , Tang Xiangming
Published: September 2023

Oligosaline lakes in arid and semi-arid regions play a crucial role in providing essential water resources for local populations. However, limited research exists on the impact of the environment on bacterial community structure in these lakes, co-occurrence patterns and the mechanisms governing bacterial community assembly. This study aims to address this knowledge gap by examining samples collected from five areas of Lake Bosten over four seasons. Using the 16S rRNA gene sequencing method, we identified a total of 510 to 1,005 operational taxonomic units (OTUs) belonging to 37 phyla and 359 genera in Lake Bosten. The major bacterial phyla were Proteobacteria (46.5%), Actinobacteria (25.9%), Bacteroidetes (13.2%), and Cyanobacteria (5.7%), while the major genera were hgcI_clade (12.9%), Limnohabitans (6.2%), and Polynucleobacter (4.7%). Water temperature emerged as the primary driver of these community structure variations on global level. However, when considering only seasonal variations, pH and nitrate were identified as key factors influencing bacterial community structures. Summer differed from other seasons in aspects of seasonal symbiotic patterns of bacterial communities, community assembly and function are different from other seasons. There were notable variations in bacterial community structures between winter and summer. Deterministic processes dominated community assembly, but there was an increase in the proportion of stochastic processes during summer. In summer, the functions related to photosynthesis, nitrogen fixation, and decomposition of organic matter showed higher abundance. Our findings shed light on the response of bacterial communities to environmental changes and the underlying mechanisms of community assembly in oligosaline lakes in arid regions.
Unveiling the dual role of heterotrophic ammonia-oxidizing bacteria: enhancing plant regrowth through modulating cytokinin delivery
Authors: Wang Xiao-Ling , Si Zhen-Qiang , Yu Hao , Qi Lin , Liu Wei , Shi Jiang , Song Peng
Published: September 2023

This study aims to investigate the dual impacts of heterotrophic ammonia-oxidizing bacteria (HAOB) strains on the regrowth of Italian ryegrass by studying cytokinin delivery from roots to leaves. The dual impacts encompass both the “soil-inside-role” and “soil-outside-role,” which refer to the HAOB operating inside and outside the rhizosphere soil within the rhizosphere microenvironment. The experimental design consisted of two sets of experiments, Exp-1 and Exp-2, involving different treatments. In Exp-1, various concentrations of NO3− were added to the roots to observe the soil-inside-role on cytokinin delivery from roots to leaves. In Exp-2, NO3− addition was combined with HAOB inoculation to observe the combined effects of the root-outside-role and root-inside-role on cytokinin synthesis and transport. The results indicated that NO3− concentrations ranging from 30 to 40 mmol L−1 had the most optimal effect on increasing leaf cytokinin content and delivery from roots to leaves, consequently promoting greater leaf regrowth biomass. When inoculated, the HAOB strain significantly increased rhizosphere soil nitrification rates under the soil-inside-role, leading to increased NO3− release from the soil and a subsequent boost in cytokinin delivery from roots to leaves. Additionally, the HAOB strain independently enhanced cytokinin delivery from roots to leaves outside the rhizosphere soil within the rhizosphere microenvironment, demonstrating its soil-outside-role. The combined effects of the soil-inside-role and soil-outside-role substantially increased leaf cytokinin content, playing a crucial role in promoting Italian ryegrass regrowth. The study’s findings shed light on the mechanisms through which HAOB can enhance plant growth by performing dual roles in the rhizosphere, offering potential applications in agriculture. Understanding the interaction between HAOB, cytokinins, and plant growth could lead to more effective strategies for improving crop productivity and promoting sustainable agriculture.
Impaired cAMP processivity by phosphodiesterase-protein kinase A complexes in acrodysostosis
Authors: Venkatakrishnan Varun , Ghode Abhijeet , Tulsian Nikhil K. , Anand Ganesh S.
Published: September 2023

Acrodysostosis represents a group of rare genetic disorders characterized by defective skeletal development and is often accompanied by intellectual disabilities. Mutations in the 3′5′cyclic AMP (cAMP)-dependent protein kinase (PKA) type I regulatory subunit isoform α (RIα) and phosphodiesterase (PDE) PDE4D have both been implicated in impaired PKA regulation in acrodysostosis. How mutations on PDEs and RIα interfere with the regulation of cAMP-PKA signaling is not understood. cAMP-PKA signaling can be described in two phases. In the activation phase, cAMP binding to RIα dissociates the free C-subunit (Catalytic subunit). PDEs hydrolyze cAMP bound to RIα, priming the cAMP-free RIα for reassociation with the C-subunit, thereby completing one PKA activation cycle. Signal termination is thus critical for resetting PKA to its basal state and promoting adaptation to hormonal hyperstimulation. This proceeds through formation of a transient signal termination RIα: PDE complex that facilitates cAMP channeling from the cAMP-binding domain of RIα to the catalytic site of PDE. Signal termination of cAMP-PKA proceeds in three steps: Step 1) Channeling: translocation of cAMP from the CNB of RIα to the PDE catalytic site for hydrolysis. Step 2) Processivity: binding of free cAMP from the cytosol at both CNBs of RIα. Step 3) Product (5′AMP) release from the PDE hydrolysis site through competitive displacement by a new molecule of cAMP that triggers subsequent activation cycles of PKA. We have identified the molecular basis for two acrodysostosis mutants, PDE (PDE8 T690P) and RIα (T207A), that both allosterically impair cAMP-PKA signal termination. A combination of amide hydrogen/deuterium exchange mass spectrometry (HDXMS) and fluorescence polarization (FP) reveals that PDE8 T690P and RIα T207A both blocked processive hydrolysis of cAMP by interfering with competitive displacement of product 5′AMP release from the nucleotide channel at the end of each round of cAMP hydrolysis. While T690P blocked product 5′AMP release from the PDE, T207A greatly slowed the release of the substrate from RIα. These results highlight the role of processivity in cAMP hydrolysis by RIα: PDE termination complexes for adaptation to cAMP from GPCR hyperstimulation. Impairment of the signal termination process provides an alternate molecular basis for acrodysostosis.
Unleashing Nature’s potential: a computational approach to discovering novel VEGFR-2 inhibitors from African natural compound using virtual screening, ADMET analysis, molecular dynamics, and MMPBSA calculations
Authors: Baammi Soukayna , El Allali Achraf , Daoud Rachid
Published: September 2023

One of the characteristic features of cancer is angiogenesis, the process by which new, aberrant blood vessels are formed from pre-existing blood vessels. The process of angiogenesis begins when VEGF binds to its receptor, the VEGF receptor (VEGFR). The formation of new blood vessels provides nutrients that can promote the growth of cancer cells. When it comes to new blood vessel formation, VEGFR2 is a critical player. Therefore, inhibiting VEGFR2 is an effective way to target angiogenesis in cancer treatment. The aim of our research was to find new VEGFR-2 inhibitors by performing a virtual screening of 13313 from African natural compounds using different in silico techniques. Using molecular docking calculations and ADMET properties, we identified four compounds that exhibited a binding affinity ranging from −11.0 kcal/mol to −11.5 Kcal/mol when bound to VEGFR-2. These four compounds were further analyzed with 100 ns simulations to determine their stability and binding energy using the MM-PBSA method. After comparing the compounds with Regorafenib, a drug approved for anti-angiogenesis treatment, it was found that all the candidates (EANPDB 252, NANPDB 4577, and NANPDB 4580), with the exception of EANPDB 76, could target VEGFR-2 similarly effectively to Regorafenib. Therefore, we recommend three of these agents for anti-angiogenesis treatment because they are likely to deactivate VEGFR-2 and thus inhibit angiogenesis. However, it should be noted that the safety and suitability of these agents for clinical use needs further investigation, as the computer-assisted study did not include in vitro or in vivo experiments.
Uncovering the Achilles heel of genetic heterogeneity: machine learning-based classification and immunological properties of necroptosis clusters in Alzheimer’s disease
Authors: Wei Huangwei , Wu Chunle , Yuan Yulin , Lai Lichuan
Published: September 2023

Background

Alzheimer’s disease (AD) is an age-associated neurodegenerative disease, and the currently available diagnostic modalities and therapeutic agents are unsatisfactory due to its high clinical heterogeneity. Necroptosis is a common type of programmed cell death that has been shown to be activated in AD.

Methods

In this study, we first investigated the expression profiles of necroptosis-related genes (NRGs) and the immune landscape of AD based on GSE33000 dataset. Next, the AD samples in the GSE33000 dataset were extracted and subjected to consensus clustering based upon the differentially expressed NRGs. Key genes associated with necroptosis clusters were identified using Weighted Gene Co-Expression Network Analysis (WGCNA) algorithm, and then intersected with the key gene related to AD. Finally, we developed a diagnostic model for AD by comparing four different machine learning approaches. The discrimination performance and clinical relevance of the diagnostic model were assessed using various evaluation metrics, including the nomogram, calibration plot, decision curve analysis (DCA), and independent validation datasets.

Results

Aberrant expression patterns of NRGs and specific immune landscape were identified in the AD samples. Consensus clustering revealed that patients in the GSE33000 dataset could be classified into two necroptosis clusters, each with distinct immune landscapes and enriched pathways. The Extreme Gradient Boosting (XGB) was found to be the most optimal diagnostic model for the AD based on the predictive ability and reliability of the models constructed by four machine learning approaches. The five most important variables, including ACAA2, BHLHB4, CACNA2D3, NRN1, and TAC1, were used to construct a five-gene diagnostic model. The constructed nomogram, calibration plot, DCA, and external independent validation datasets exhibited outstanding diagnostic performance for AD and were closely related with the pathologic hallmarks of AD.

Conclusion

This work presents a novel diagnostic model that may serve as a framework to study disease heterogeneity and provide a plausible mechanism underlying neuronal loss in AD.
Case report: Use of granulocyte-colony stimulating factor as an immunomodulatory therapy in a patient with neuromyelitis optica spectrum disorder and comorbid immunodeficiency
Authors: Perez Giraldo Gina S. , Graham Edith L. , VanHaerents Stephen , Balabanov Roumen
Published: September 2023

Background

Autoimmune diseases can coexist with immunodeficiency. We describe a treatment approach in which granulocyte-colony stimulating factor (G-CSF) is used to restore immune competence without worsening autoimmunity. G-CSF is a polyfunctional cytokine that influences survival, proliferation, and differentiation of hematopoietic stem cells, and has immunomodulatory effects on the innate and adaptive immune systems.

Objective

To report a case of neuromyelitis optica spectrum disorder (NMOSD) with comorbid immunodeficiency and frequent infections.

Methods

Case report and review of literature.

Results

A 23 years-old man presented with a focal onset seizure with impaired awareness at age 12. At age 18, he developed headaches, recurrent multifocal seizures, and non-convulsive status epilepticus. Brain magnetic resonance imaging (MRI) showed extensive T2 hyperintense and gadolinium-enhancing periventricular and corpus callosum lesions. Serum aquaporin 4 antibody was positive 1:10,000 (normal value <1.5 titer), hence he was diagnosed with NMOSD. As a complication, patient developed mucormycotic pneumonia with cavitation, requiring thoracotomy precluding use of immunosuppressants. Gene testing demonstrated a mutation in MT-ND4 gene encoding for NADH dehydrogenase 4 in mitochondrial complex 1. Eventually, he began a treatment with filgrastim, a G-CSF analog, in addition to intravenous immunoglobulins and prednisone. Patient’s NMOSD has been in remission without relapses, or coexistent infections ever since.

Conclusion

G-CSF is a polyfunctional cytokine with important immunomodulatory effects, which makes it an interesting therapeutic option when autoimmunity coexists with immunodeficiency and was used successfully in this case.
Spinal muscular atrophy type I associated with a novel SMN1 splicing variant that disrupts the expression of the functional transcript
Authors: Votsi Christina , Koutsou Pantelitsa , Ververis Antonis , Georghiou Anthi , Nicolaou Paschalis , Tanteles George , Christodoulou Kyproula
Published: September 2023

Introduction

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by pathogenic variants in the SMN1 gene. The majority of SMA patients harbor a homozygous deletion of SMN1 exon 7 (95%). Heterozygosity for a conventional variant and a deletion is rare (5%) and not easily detected, due to the highly homologous SMN2 gene interference. SMN2 mainly produces a truncated non-functional protein (SMN-d7) instead of the full-length functional (SMN-FL). We hereby report a novel SMN1 splicing variant in an infant with severe SMA.

Methods

MLPA was used for SMN1/2 exon dosage determination. Sanger sequencing approaches and long-range PCR were employed to search for an SMN1 variant. Conventional and improved Real-time PCR assays were developed for the qualitative and quantitative SMN1/2 RNA analysis.

Results

The novel SMN1 splice-site variant c.835-8_835-5delinsG, was identified in compound heterozygosity with SMN1 exons 7/8 deletion. RNA studies revealed complete absence of SMN1 exon 7, thus confirming a disruptive effect of the variant on SMN1 splicing. No expression of the functional SMN1-FL transcript, remarkable expression of the SMN1-d7 and increased levels of the SMN2-FL/SMN2-d7 transcripts were observed.

Discussion

We verified the occurrence of a non-deletion SMN1 variant and supported its pathogenicity, thus expanding the SMN1 variants spectrum. We discuss the updated SMA genetic findings in the Cypriot population, highlighting an increased percentage of intragenic variants compared to other populations.
A nomogram predicts early neurological deterioration after mechanical thrombectomy in patients with ischemic stroke
Authors: Wu Kongyuan , Yuan Zhengzhou , Chen Wenhuo , Yi Tingyu , Chen Xiwen , Ma Mengmeng , Guo Jian , Zhou Muke , Chen Ning , He Li
Published: September 2023

Introduction

Early neurological deterioration (END) is common in acute ischemic stroke and is directly associated with poor outcome after stroke. Our aim is to develop and validate a nomogram to predict the risk of END after mechanical thrombectomy (MT) in acute ischemic stroke patients with anterior circulation large-vessel occlusion.

Methods

We conducted a real-world, multi-center study in patients with stroke treated with mechanical thrombectomy. END was defined as a worsening by 2 or more NIHSS points within 72-hour after stroke onset compared to admission. Multivariable logistic regression was used to determine the independent predictors of END, and the discrimination of the scale was assessed using the C-index. Calibration curves were constructed to evaluate the calibration of the nomogram, and decision curves were used to describe the benefits of using the nomogram.

Results

A total of 1007 patients were included in our study. Multivariate logistic regression analysis found age, admission systolic blood pressure, initial NIHSS scores, history of hyperlipemia, and location of occlusion were independent predictors of END. We developed a nomogram that included these 6 factors, and it revealed a prognostic accuracy with a C-index of 0.678 in the derivation group and 0.650 in the validation group. The calibration curves showed that the nomogram provided a good fit to the data, and the decision curves demonstrated a large net benefit.

Discussion

Our study established and validated a nomogram to stratify the risk of END before mechanical embolectomy and identify high-risk patients, who should be more cautious when making clinical decisions.
Visual-auditory perception of prosodic focus in Japanese by native and non-native speakers
Authors: Zhang Yixin , Chen Xi , Chen Si , Meng Yuzhe , Lee Albert
Published: September 2023

Introduction

Speech communication is multi-sensory in nature. Seeing a speaker’s head and face movements may significantly influence the listeners’ speech processing, especially when the auditory information is not clear enough. However, research on the visual-auditory integration speech processing has left prosodic perception less well investigated than segmental perception. Furthermore, while native Japanese speakers tend to use less visual cues in segmental perception than in other western languages, to what extent the visual cues are used in Japanese focus perception by the native and non-native listeners remains unknown. To fill in these gaps, we test focus perception in Japanese among native Japanese speakers and Cantonese speakers who learn Japanese, using auditory-only and auditory-visual sentences as stimuli.

Methodology

Thirty native Tokyo Japanese speakers and thirty Cantonese-speaking Japanese learners who had passed the Japanese-Language Proficiency Test with level N2 or N3 were asked to judge the naturalness of 28 question-answer pairs made up of broad focus eliciting questions and three-word answers carrying broad focus, or contrastive or non-contrastive narrow focus on the middle object words. Question-answer pairs were presented in two sensory modalities, auditory-only and visual-auditory modalities in two separate experimental sessions.

Results

Both the Japanese and Cantonese groups showed weak integration of visual cues in the judgement of naturalness. Visual-auditory modality only significantly influenced Japanese participants’ perception when the questions and answers were mismatched, but when the answers carried non-contrastive narrow focus, the visual cues impeded rather than facilitated their judgement. Also, the influences of specific visual cues like the displacement of eyebrows or head movements of both Japanese and Cantonese participants’ responses were only significant when the questions and answers were mismatched. While Japanese participants consistently relied on the left eyebrow for focus perception, the Cantonese participants referred to head movements more often.

Discussion

The lack of visual-auditory integration in Japanese speaking population found in segmental perception also exist in prosodic perception of focus. Not much foreign language effects has been found among the Cantonese-speaking learners either, suggesting a limited use of facial expressions in focus marking by native and non-native Japanese speakers. Overall, the present findings indicate that the integration of visual cues in perception of focus may be specific to languages rather than universal, adding to our understanding of multisensory speech perception.
APPlications of amyloid-β precursor protein metabolites in macrocephaly and autism spectrum disorder
Authors: Sokol Deborah K. , Lahiri Debomoy K.
Published: September 2023

Metabolites of the Amyloid-β precursor protein (APP) proteolysis may underlie brain overgrowth in Autism Spectrum Disorder (ASD). We have found elevated APP metabolites (total APP, secreted (s) APPα, and α-secretase adamalysins in the plasma and brain tissue of children with ASD). In this review, we highlight several lines of evidence supporting APP metabolites’ potential contribution to macrocephaly in ASD. First, APP appears early in corticogenesis, placing APP in a prime position to accelerate growth in neurons and glia. APP metabolites are upregulated in neuroinflammation, another potential contributor to excessive brain growth in ASD. APP metabolites appear to directly affect translational signaling pathways, which have been linked to single gene forms of syndromic ASD (Fragile X Syndrome, PTEN, Tuberous Sclerosis Complex). Finally, APP metabolites, and microRNA, which regulates APP expression, may contribute to ASD brain overgrowth, particularly increased white matter, through ERK receptor activation on the PI3K/Akt/mTOR/Rho GTPase pathway, favoring myelination.
Molecular pathways and nutrigenomic review of insulin resistance development in gestational diabetes mellitus
Authors: Guevara-Ramírez Patricia , Paz-Cruz Elius , Cadena-Ullauri Santiago , Ruiz-Pozo Viviana A. , Tamayo-Trujillo Rafael , Felix Maria L. , Simancas-Racines Daniel , Zambrano Ana Karina
Published: September 2023

Gestational diabetes mellitus is a condition marked by raised blood sugar levels and insulin resistance that usually occurs during the second or third trimester of pregnancy. According to the World Health Organization, hyperglycemia affects 16.9% of pregnancies worldwide. Dietary changes are the primarily alternative treatment for gestational diabetes mellitus. This paper aims to perform an exhaustive overview of the interaction between diet, gene expression, and the metabolic pathways related to insulin resistance. The intake of foods rich in carbohydrates can influence the gene expression of glycolysis, as well as foods rich in fat, can disrupt the beta-oxidation and ketogenesis pathways. Furthermore, vitamins and minerals are related to inflammatory processes regulated by the TLR4/NF-κB and one carbon metabolic pathways. We indicate that diet regulated gene expression of PPARα, NOS, CREB3L3, IRS, and CPT I, altering cellular physiological mechanisms and thus increasing or decreasing the risk of gestational diabetes. The alteration of gene expression can cause inflammation, inhibition of fatty acid transport, or on the contrary help in the modulation of ketogenesis, improve insulin sensitivity, attenuate the effects of glucotoxicity, and others. Therefore, it is critical to comprehend the metabolic changes of pregnant women with gestational diabetes mellitus, to determine nutrients that help in the prevention and treatment of insulin resistance and its long-term consequences.
Association between dietary zinc intake and Helicobacter pylori seropositivity in US adults: National Health and Nutrition Examination Survey
Authors: Zhang Kai , Han Yu , Gu Fangming , Gu Zhaoxuan , Zhao JiaYu , Chen Jianguo , Chen Bowen , Gao Min , Hou Zhengyan , Yu Xiaoqi , Cai Tianyi , Gao Yafang , Hu Rui , Xie Jinyu , Liu Tianzhou
Published: September 2023

Purpose

Helicobacter pylori infection is a well-established etiological factor for gastric inflammation and a significant risk factor for the development of gastric cancer. However, the precise relationship between dietary zinc intake and seropositivity for Helicobacter pylori remains uncertain.

Methods

This cross-sectional observational study utilized data from the United States National Health and Nutrition Examination Survey conducted between 1999 and 2000. The study cohort comprised 2,884 adults aged 20 years or older who provided comprehensive 24-h dietary recall data. The presence of Helicobacter pylori infection was confirmed using serum analysis and lgG protein enzyme-linked immunosorbent assay (ELISA). Multivariable logistic regression models and generalized additive model (GAM) were employed to explore the potential association between dietary zinc intake and Helicobacter pylori seropositivity.

Results

Additionally, subgroup analysis was performed to evaluate the robustness of the primary findings. Of the 1,281 participants, 47.8% were male and the average age was 49.5 years. In the fully adjusted model, a statistically significant inverse association between dietary zinc intake and Helicobacter pylori seropositivity was observed [quartile variable, Q4 vs. Q1, odds ratio (OR): 0.72, 95% confidence interval (CI): 0.57–0.91, p = 0.007]. Furthermore, the relationship between dietary zinc intake and Helicobacter pylori seropositivity exhibited an L-shaped pattern, indicating a saturation effect. The results of sensitivity analysis remained consistent and reliable.

Conclusion

Therefore, this study suggests that higher dietary zinc intake may be associated with a lower prevalence of Helicobacter pylori seropositivity. Notably, this association follows an L-shaped pattern, with a threshold point estimated at 24.925 mg/day.
The effectiveness of exercise on the symptoms in breast cancer patients undergoing adjuvant treatment: an umbrella review of systematic reviews and meta-analyses
Authors: Zhao Yuan , Tang Leiwen , Shao Jing , Chen Dandan , Jiang Yueying , Tang Panpan , Wang Xueqing
Published: September 2023

Background

Exercise has the potential to reduce symptoms for breast cancer patients during adjuvant treatment, and high-quality systematic reviews are essential for guiding clinical practice. The objective of this umbrella review is to examine current research evidence concerning the effectiveness of exercise on symptom management in breast cancer patients undergoing adjuvant treatment.

Methods

An umbrella review was conducted. We searched for eligible systematic reviews through 11 databases until August 13rd, 2023. Two authors independently screened titles and abstracts, assessing the full-text studies based on inclusion criteria. We used AMSTAR-2 to appraise the quality of the meta-analyses. The results would be presented with narrative summaries if the replication rate of the original study for a symptom was higher than 5% (calculated via the Corrected Covered Area, CCA). The protocol was documented in the PROSPERO registry (CRD42023403990).

Results

Of the 807 systematic reviews identified, 15 met the inclusion criteria, and 7 symptoms were the main focus. The main form of exercise mentioned was aerobic combined resistance exercise. The results of the quality assessment were mostly critically low (10/15). The repetition rate calculated by CCA showed moderate to very high repetition rates (10% to 18.6%). The findings of the included reviews indicated that the effects of exercise on relieving symptoms during breast cancer adjuvant treatment were mixed.

Conclusions

Research is still needed to confirm the majority of studies’ recommendations for exercise during adjuvant treatment for breast cancer patients, as it is crucial for managing symptoms in the rehabilitation process. To increase the efficiency of exercise in symptom management, future studies may focus more on the application of bridge symptoms, symptom networks, and ecological instantaneous assessment.
The presence of autoantibodies is associated with improved overall survival in lung cancer patients
Authors: Jing Keying , Zhao Huijuan , Cai Jun , Chen Lianlian , Zheng Peiming , Ouyang Libo , Li Gang , Wang Rong
Published: September 2023

Objective

Autoantibodies have been reported to be associated with cancers. As a biomarker, autoantibodies have been widely used in the early screening of lung cancer. However, the correlation between autoantibodies and the prognosis of lung cancer patients is poorly understood, especially in the Asian population. This retrospective study investigated the association between the presence of autoantibodies and outcomes in patients with lung cancer.

Methods

A total of 264 patients diagnosed with lung cancer were tested for autoantibodies in Henan Provincial People’s Hospital from January 2017 to June 2022. The general clinical data of these patients were collected, and after screening out those who met the exclusion criteria, 151 patients were finally included in the study. The Cox proportional hazards model was used to analyze the effect of autoantibodies on the outcomes of patients with lung cancer. The Kaplan-Meier curve was used to analyze the relationship between autoantibodies and the overall survival of patients with lung cancer.

Results

Compared to lung cancer patients without autoantibodies, those with autoantibodies had an associated reduced risk of death (HRs: 0.45, 95% CIs 0.27~0.77), independent of gender, age, smoking history, pathological type, and pathological stage of lung cancer. Additionally, the association was found to be more significant by subgroup analysis in male patients, younger patients, and patients with small cell lung cancer. Furthermore, lung cancer patients with autoantibodies had significantly longer survival time than those without autoantibodies.

Conclusion

The presence of autoantibodies is an independent indicator of good prognosis in patients with lung cancer, providing a new biomarker for prognostic evaluation in patients with lung cancer.
Potential role of vacuum-assisted procedures in resecting breast cancers and highlighting selection criteria to support future trials
Authors: Valadares C. N. , Couto H. L. , Soares A. N. , Toppa P. H. , Ricardo B. P. , McIntosh S. A. , Sharma N. , Resende V.
Published: September 2023

Purpose

The purpose of this study was to evaluate the role of vacuum-assisted biopsy (VAB) in resecting breast cancers.

Methods

Retrospective database analysis of 116 cancers [both invasive breast cancers (IC) and ductal carcinoma in situ (DCIS)] diagnosed by VAB submitted to standard surgical treatment with complete histological data from VAB and surgery. Excision following VAB was defined as complete resection (CR) if there was no residual tumor in the surgical specimen, minimal residual disease (MRD) if residual tumor ≤ 3 mm, gross residual disease (GRD) if residual tumor > 3 mm, and upgrade from DCIS on VAB to IC. CR and MRD were combined as potentially resected percutaneously (PRP). GRD and those with upgrade to IC were determined not eligible for percutaneous resection (NPR). Factors predictive of PRP were evaluated.

Results

Mean age was 55.6 years (20–91; SD: 12,27). CR was seen in 29 of 116 cases (25%), MRD in 18 of 116 cases (15.5%), GRD in 64 of 116 cases (55.2%), and five of 116 cases (4.3%) were upgraded from DCIS to IC, and those groups combined represented 47 cases of PRP (40.5%) and 69 (59,5%) of NPR. For 77 tumors ≤ 10 mm, 45 (58.5%) were PRP. Multivariate analysis reveals significance for enlarged VAB (EVAB) (p = 0.008, OR: 4.4, 95% CI), low/intermediate nuclear grade (p < 0.001, OR: 12.5, 95% CI) and final tumor size (T) ≤ 10 mm (p = 0.001, OR: 50.1, 95% CI) for PRP.

Conclusions

This study showed that lesions completely excised with VAB that were cancer could have been treated with VAB rather than surgery but tumor selection in terms of subtype and size is important.
Malignant lung PEComa (clear cell tumor): rare case report and literature review
Authors: Campos Marcos Adriano Garcia , Vasques Lucas Fernandes , Medeiros Rafael Goulart de , Monteiro Cutrim Érico Murilo , Favarin Ana Júlia , Silva Sarah Rebecca Machado , Silva Gyl Eanes Barros , Moraes Marcelo Padovani de Toledo , Zanatta Mariana Lopes , Queiróz Diego Aparecido Rios
Published: September 2023

Clear cell tumors of the lung (CCTL), or “sugar tumors” of lung, are very uncommon lesions and are mostly benign perivascular epithelioid cell (PEC) tumors with no specific morphologic features. Fewer than 100 cases have been reported; the aggressive nature demonstrated in sporadic reports has rarely been described in the literature. Although the course is generally described as benign, eight reported cases showed malignant behavior. We report a case of a PEC with a malignant presentation in a young man, correlating the main characteristics of the tumor with other cases reported in the literature to better elucidate this rare presentation. We also performed a literature review of reports on benign and malignant CCTL cases, with a focus on clinical, imaging, and immunohistochemical differentiation. CCTLs are rare tumors that require histopathological and immunohistochemical confirmation; to date, criteria that can predict malignant evolution are lacking.
Diagnostic challenges and prognostic implications of extranodal extension in head and neck cancer: a state of the art review and gap analysis
Authors: Henson Christina E. , Abou-Foul Ahmad K. , Morton Daniel J. , McDowell Lachlan , Baliga Sujith , Bates James , Lee Anna , Bonomo Pierluigi , Szturz Petr , Nankivell Paul , Huang Shao Hui , Lydiatt William M. , O’Sullivan Brian , Mehanna Hisham
Published: September 2023

Extranodal extension (ENE) is a pattern of cancer growth from within the lymph node (LN) outward into perinodal tissues, critically defined by disruption and penetration of the tumor through the entire thickness of the LN capsule. The presence of ENE is often associated with an aggressive cancer phenotype in various malignancies including head and neck squamous cell carcinoma (HNSCC). In HNSCC, ENE is associated with increased risk of distant metastasis and lower rates of locoregional control. ENE detected on histopathology (pathologic ENE; pENE) is now incorporated as a risk-stratification factor in human papillomavirus (HPV)-negative HNSCC in the eighth edition of the American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC) TNM classification. Although ENE was first described almost a century ago, several issues remain unresolved, including lack of consensus on definitions, terminology, and widely accepted assessment criteria and grading systems for both pENE and ENE detected on radiological imaging (imaging-detected ENE; iENE). Moreover, there is conflicting data on the prognostic significance of iENE and pENE, particularly in the context of HPV-associated HNSCC. Herein, we review the existing literature on ENE in HNSCC, highlighting areas of controversy and identifying critical gaps requiring concerted research efforts.
The prognostic significance of circulating plasma cells in newly diagnosed multiple myeloma patients
Authors: Yao Weiqin , Yang Haifei , You Hongying , Shang Jingjing , Zhai Yingying , Yan Zhi , Yan Shuang , Shi Xiaolan , Yao Ying , Wang Jing , Wang Panfeng , Xu Yun , Jin Song , Yan Lingzhi , Wu Depei , Fu Chengcheng
Published: September 2023

Objective

Multiple myeloma (MM) is a highly characteristic tumor that is influenced by numerous factors that determine its prognosis. Studies indicate that the presence of circulating plasma cells (cPCs) is a detrimental factor that significantly impacts the prognosis of patients with MM.

Methods

This study retrospectively analyzed the prognostic value of cPCs quantified by 10-color flow cytometry in 145 newly diagnosed MM (NDMM) cases in the First Affiliated Hospital of Soochow University from November 2018 to February 2021. The study was approved by the Ethics Committee of the hospital (2021 No. 93).

Results

Of the 145 patients, 99 (68.2%) were detected cPCs. Through receiver operating characteristics (ROC) analysis, an optimal threshold of 0.165% was identified as a predictor for overall survival (OS). The median progression-free survival (PFS) was 33 months in patients with cPCs ≥0.165%, whereas those with cPCs <0.165% had a PFS of <33 months (p=0.001). The median OS was not reached for two groups; the 3-year OS for patients with cPCs ≥0.165% was 71% compared with 87% for those with cPCs <0.165% (p=0.003). In transplant patients, cPCs ≥0.165% also predicted worse prognosis. Similarly, when considering cytogenetic risk factors in conjunction with cPC levels, comparable results were obtained. To evaluate whether the Revised International Staging System (R-ISS) groups could be further stratified based on different prognostic factors related to cPCs, our study revealed similar median PFS and OS rates in R-ISS II stage patients with cPCs ≥0.165% compared to those in the III stage (p=0.659 and 0.249, respectively).

Conclusion

This study demonstrates that a high ratio of cPCs serves as a reliable indicator for predicting a poorer prognosis in MM cases. Furthermore, incorporating the R-ISS system and cytogenetic risk factors alongside the level of cPCs enhances the accuracy of prognostic predictions for patients with MM.
Comparison of the efficacy and safety of third-line treatments for metastatic colorectal cancer: a systematic review and network meta-analysis
Authors: Gao Loulu , Tang Lin , Hu Zixuan , Peng Jieqiong , Li Xiaoqian , Liu Bo
Published: September 2023

Background

The objective of this study is to evaluate the efficacy and safety of different third-line treatment regimens for metastatic colorectal cancer (mCRC) through a comprehensive analysis and network meta-analysis (NMA). Additionally, the study aims to provide guidance on selecting appropriate third-line systemic treatment regimens for patients with mCRC.

Methods

We conducted a search of the PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials databases from January 1, 2005, to May 20, 2023, to include phase II/III randomized clinical trials (RCTs) of third-line treatments for mCRC. The primary outcome assessed in the NMA was median overall survival (mOS), and other outcomes included median progression-free survival (mPFS), disease control rate (DCR), and grade 3 or higher adverse events (≥3AEs).

Results

Ultimately, nine phase II/III RCTs involving five treatment regimens were included in this study. Trifluridine/tipiracil (TAS-102) plus bevacizumab (hazard ratio [HR] 0.41, 95% credible interval [CrI] 0.32-0.52) was found to be the most effective treatment for mOS compared to best supportive care (BSC). TAS-102 plus bevacizumab also significantly improved mPFS compared to BSC (HR 0.20, 95% CrI 0.16-0.25). In terms of adverse events (AEs), TAS-102 (RR 0.52, 95% CrI 0.35-0.74) had a lower incidence of ≥3AEs compared to fruquintinib, but fruquintinib (RR 1.79, 95% CrI 1.10-3.11) showed better improvement in DCR than TAS-102. Subgroup analysis using the Bayesian surface under the cumulative ranking curve (SUCRA) ranked the regimens based on the OS benefit. The results indicated that TAS-102 plus bevacizumab ranked first across age, gender, Eastern Cooperative Oncology Group performance status (ECOG PS), and time from initial diagnosis of metastatic disease to randomization.

Conclusion

TAS-102, fruquintinib, TAS-102 plus bevacizumab, the regorafenib standard dose regimen (regorafenib), and the regorafenib dose-escalation regimen (regorafenib 80+) all demonstrated improved OS and PFS compared to BSC in mCRC patients. However, TAS-102 plus bevacizumab may be the optimal choice for third-line treatment in mCRC patients.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php, CRD42023434929.
Clinical features and risk factors analysis for poor outcomes of severe community-acquired pneumonia in children: a nomogram prediction model
Authors: Xu Changjing , Tao Xuemei , Zhu Junlong , Hou Chao , Liu Yujie , Fu Liya , Zhu Wanlong , Yang Xuping , Huang Yilan
Published: September 2023

Background

Pneumonia remains the leading cause of death among children aged 1–59 months. The early prediction of poor outcomes (PO) is of critical concern. This study aimed to explore the risk factors relating to PO in severe community-acquired pneumonia (SCAP) and build a PO-predictive nomogram model for children with SCAP.

Methods

We retrospectively identified 300 Chinese pediatric patients diagnosed with SCAP who were hospitalized in the Affiliated Hospital of Southwest Medical University from August 1, 2018, to October 31, 2021. Children were divided into the PO and the non-PO groups. The occurrence of PO was designated as the dependent variable. Univariate and multivariate logistic regression analyses were used to identify the risk factors of PO. A nomogram model was constructed from the multivariate logistic regression analysis and internally validated for model discrimination and calibration. The performance of the nomogram was estimated using the concordance index (C-index).

Results

According to the efficacy evaluation criteria, 56 of 300 children demonstrated PO. The multivariate logistic regression analysis resulted in the following independent risk factors for PO: co-morbidity (OR: 8.032, 95% CI: 3.556–18.140, P < 0.0001), requiring invasive mechanical ventilation (IMV) (OR: 7.081, 95% CI: 2.250–22.282, P = 0.001), and ALB < 35 g/L (OR: 3.203, 95% CI: 1.151–8.912, P = 0.026). Results of the internal validation confirmed that the model provided good discrimination (concordance index [C-index], 0.876 [95% CI: 0.828–0.925]). The calibration plots in the nomogram model were of high quality.

Conclusion

The nomogram facilitated accurate prediction of PO in children diagnosed with SCAP and could be helpful for clinical decision-making.
Preterm infant retinal OCT markers of perinatal health and retinopathy of prematurity
Authors: Mangalesh Shwetha , Toth Cynthia A.
Published: September 2023

The increasing survival of preterm infants has led to the importance of improving long-term outcomes associated with preterm birth. Antenatal and perinatal insults not only impact mortality, but also long-term disability. While in the intensive care nursery, preterm infants are also exposed to various stressors that lead to long-term cognitive deficits. It is therefore critical to identify early, low-stress, non-invasive biomarkers for preterm infant health. Optical coherence tomography (OCT) is a powerful imaging modality that has recently been adapted to the infant population and provides noninvasive, high-resolution, cross-sectional imaging of the infant eye at the bedside with low stress relative to conventional examination. In this review we delve into discussing the associations between preterm systemic health factors and OCT-based retinal findings and their potential contribution to the development of non-invasive biomarkers for infant health and for retinopathy of prematurity (ROP).
The capacity of exosomes derived from adipose-derived stem cells to enhance wound healing in diabetes
Authors: Cai Feiyu , Chen Wenjiao , Zhao Ruomei , Liu Yi
Published: September 2023

The slow healing and nonhealing of diabetic wounds have long posed challenges for clinical practitioners. In the presence of elevated glucose levels, the body’s regulatory mechanisms undergo alterations that impede normal wound healing processes, including cell proliferation, cytokine release, and growth factor activity. Consequently, the advancement of stem cell technology has sparked growing interest in utilizing stem cells and their derivatives as potential therapeutic agents to enhance diabetic wound healing. This paper aims to provide an academic review of the therapeutic effects of adipose-derived stem cell-EXOs (ADSC-EXOs) in diabetic wound healing. As a cell-free therapy, exosomes (EXOs) possess a multitude of proteins and growth factors that have been shown to be advantageous in promoting wound healing and mitigating the potential risks associated with stem cell therapy. By examining the current knowledge on ADSC-EXOs, this review seeks to offer insights and guidance for the potential application of EXOs in the treatment of diabetic wounds.