bluuebunny/crossref_metadata_2025 huggingface dataset:
Pulmonary hypertension and insulin resistance: a mechanistic overview
Authors: Zanotto Tamires M. , Gonçalves Any Elisa de Souza Schmidt , Saad Mario J. A.
Published: January 2024

Pulmonary arterial hypertension (PAH) is a vascular remodeling disease, characterized by increased blood pressure levels in pulmonary circulation, leading to a restriction in the circulation flow and heart failure. Although the emergence of new PAH therapies has increased survival rates, this disease still has a high mortality and patients that receive diagnosis die within a few years. The pathogenesis of PAH involves multiple pathways, with a complex interaction of local and distant cytokines, hormones, growth factors, and transcription factors, leading to an inflammation that changes the vascular anatomy in PAH patients. These abnormalities involve more than just the lungs, but also other organs, and between these affected organs there are different metabolic dysfunctions implied. Recently, several publications demonstrated in PAH patients a disturbance in glucose metabolism, demonstrated by higher levels of glucose, insulin, and lipids in those patients. It is possible that a common molecular mechanism can have a significant role in this connection. In this regard, this narrative review intends to focus on the recent papers that mainly discuss the molecular determinants between insulin resistance (IR) associated PAH, which included obesity subclinical inflammation induced IR, PPAR gamma and Adiponectin, BMPR2, mitochondrial dysfunction and endoplasmic reticulum stress. Therefore, the following review will summarize some of the existing data for IR associated PAH, focusing on the better understanding of PAH molecular mechanisms, for the development of new translational therapies.
Prospective application of a prediction model for lateral lymph node metastasis in papillary thyroid cancer patients with central lymph node metastasis
Authors: Ma Yunhan , Li Yi , Zheng Luming , He Qingqing
Published: January 2024

Objective

This study aimed to develop and apply a prediction model to estimate the probability of lateral lymph node metastasis (LLNM) in patients with cN0 unilateral papillary thyroid carcinoma (PTC) with central lymph node metastasis (CLNM).

Setting

All study data were collected from a single tertiary hospital.

Methods

Univariable and multivariable logistic regression analyses were used to explore independent predictors of LLNM in the derivation and internal validation cohorts, which were used to construct and validate a nomogram. Another 96 patients were included prospectively to evaluate the efficacy of this nomogram.

Results

Maximum tumor diameter greater than 1.0 cm (OR, 2.712; 95% CI, 1.412–5.210), multifocality (OR, 2.758; 95% CI, 1.120–6.789), the number of CLNM ≥3 (OR, 2.579; 95% CI, 1.315–5.789), CLNM ratio ≥0.297 (OR, 2.905; 95% CI, 1.396–6.043), and tumors located in the upper portion (OR 2.846, 95% CI 1.151–7.039) were independent predictors associated with LLNM. The prediction model showed excellent discrimination with an AUC of 0.731 (95% CI, 0.635–0.827). Novel risk stratification for LLNM was constructed based on this nomogram. In the prospective cohort, we stratified these patients into three risk subgroups: low-, moderate-, and high-risk subgroups and we found that the probability of LLNM was positively correlated with the total points from the nomogram.

Conclusion

This nomogram was applied in prospective clinical practice and distinguished PTC patients with a genuinely high risk of LLNM. Surgeons can use our nomogram to tailor the surgical plan and to credibly determine further postoperative therapy.
Exploiting in silico structural analysis to introduce emerging genotype–phenotype correlations in DHCR24-related sterol biosynthesis disorder: a case study
Authors: Cocciadiferro Dario , Mazza Tommaso , Vecchio Davide , Biagini Tommaso , Petrizzelli Francesco , Agolini Emanuele , Villani Andrea , Minervino Daniele , Martinelli Diego , Rizzo Cristiano , Boenzi Sara , Panfili Filippo Maria , Buonuomo Paola Sabrina , Macchiaiolo Marina , Bartuli Andrea , Novelli Antonio
Published: January 2024

Desmosterolosis is a rare sterol biosynthesis disorder characterized by multiple congenital anomalies, failure to thrive, severe developmental delay, progressive epileptic encephalopathy, and elevated levels of desmosterol caused by biallelic mutations of DHCR24 encoding 3-β-hydroxysterol Δ-24-reductase. DHCR24 is regarded as the key enzyme of cholesterol synthesis in the metabolism of brain cholesterol as it catalyzes the reduction of the Δ-24 double bond of sterol intermediates during cholesterol biosynthesis. To date, 15 DHCR24 variants, detected in 2 related and 14 unrelated patients, have been associated with the desmosterolosis disorder. Here, we describe a proband harboring the never-described DHCR24 homozygous missense variant NM_014762.4:c.506T>C, NP_055577.1:p.M169T, whose functional validation was confirmed through biochemical assay. By using molecular dynamics simulation techniques, we investigated the impact of this variant on the protein stability and interaction network with the flavin adenine dinucleotide cofactor, thereby providing a preliminary assessment of its mechanistic role in comparison to all known pathogenic variants, the wild-type protein, and a known benign DHCR24 variant. This report expands the clinical and molecular spectra of the DHCR24-related disorder, reports on a novel DHCR24 deleterious variant associated with desmosterolosis, and gives new insights into genotype–phenotype correlations.
Limosilactobacillus reuteri DSM 17938 and ATCC PTA 6475 for the treatment of moderate to severe irritable bowel syndrome in adults: a randomized controlled trial
Authors: Cruchet Silvia , Hirsch Sandra , Villa-López Diana , Moreno-Portillo Mucio , Palomo Juan C. , Abreu-Abreu Ana T. , Abdo-Francis Juan M. , Jiménez-Gutiérrez Carlos , Rojano Martin , López-Velázquez Gabriel , Gutiérrez-Castrellón Pedro
Published: January 2024

Background

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder in adults. Systematic reviews with meta-analyses have demonstrated the efficacy and safety of probiotics in improving symptoms of IBS.

Aim

The aim of the study was to demonstrate the efficacy and safety of Limosilactobacillus reuteri (L. reuteri) DSM 17938 combined with L. reuteri ATCC PTA 6475 regarding improving the symptoms associated with IBS in adults.

Methods

A randomized, double-blind, placebo-controlled clinical trial was conducted in 140 adults aged 18 years to 65 years with a diagnosis of IBS (based on the Rome IV criteria). After 2 weeks of washout, subjects were randomized to receive either 2 × 108 colony-forming units (CFUs) of L. reuteri DSM 17938 combined with L. reuteri ATCC PTA 6475 plus standard of care or placebo plus standard of care for 14 weeks, followed by a post-intervention period of 2 additional weeks. Changes in gastrointestinal symptoms (as measured with the GSRS-IBS), stool pattern (as measured with the Bristol scale), quality of life, depression and anxiety, frequency of adverse events, and fecal calprotectin concentrations were evaluated.

Results

In total, 70 subjects were allocated to receive L. reuteri and 70 were allocated to receive placebo. During the pre-randomization phase, no differences were observed between the groups in terms of IBS-associated symptoms and stool consistency. Starting at week 6 of the intervention, subjects in group L. reuteri showed a significant improvement in IBS-associated symptoms (p < 0.01). A significant improvement was also observed in fecal calprotectin concentration in the L. reuteri group at the end of interventions (30.2 ± 11.8 mg/g of stool in the L. reuteri group and 41.6 mg/g ± 10.7 mg/g in the placebo group; p = 0.019). The frequency of adverse events was similar between groups.

Conclusions

A twice-a-day intervention for 14 weeks is safe and effective, reduces the symptoms associated with IBS in adults aged 18 years to 65 years, improves stool consistency, and reduces symptoms associated with anxiety after 6 weeks.
Humoral and cellular immune responses after COVID-19 vaccination of lung transplant recipients and patients on the waiting list: a 6-month follow-up
Authors: Hoek Rogier A. S. , Liu Siqi , GeurtsvanKessel Corine H. , Verschuuren Erik A. M. , Vonk Judith M. , Hellemons Merel E. , Kool Mirjam , Wijbenga Nynke , Bogers Susanne , Scherbeijn Sandra , Rugebregt Sharona , van Gemert Johanna P. , Steenhuis Willie N. , Niesters Hubert G. M. , van Baarle Debbie , de Vries Rory D. , Van Leer Buter Coretta
Published: January 2024

Background

Data on cellular response and the decay of antibodies and T cells in time are scarce in lung transplant recipients (LTRs). Additionally, the development and durability of humoral and cellular immune responses have not been investigated in patients on the waitlist for lung transplantation (WLs). Here, we report our 6-month follow-up of humoral and cellular immune responses of LTRs and WLs, compared with controls.

Methods

Humoral responses to two doses of the mRNA-1273 vaccination were assessed by determining spike (S)-specific IgG antibodies and neutralizing antibodies. Cellular responses were investigated by interferon gamma (IFN-γ) release assay (IGRA) and IFN-γ ELISpot assay at 28 days and 6 months after the second vaccination.

Results

In LTRs, the level of antibodies and T-cell responses was significantly lower at 28 days after the second vaccination. Also, WLs had lower antibody titers and lower T-cell responses compared with controls. Six months after the second vaccination, all groups showed a decrease in antibody titers and T-cell responses. In WLs, the rate of decline of neutralizing antibodies and T-cell responses was significantly higher than in controls.

Conclusion

Our results show that humoral and cellular responses in LTRs, if they develop, decrease at rates comparable with controls. In contrast, the inferior cellular responses and the rapid decay of both humoral and cellular responses in the WL groups imply that WLs may not be protected adequately by two vaccinations and repeat boostering may be necessary to induce protection that lasts beyond the months immediately post-transplantation.
Exploring the causal role of gut microbiota in giant cell arteritis: a Mendelian randomization analysis with mediator insights
Authors: Wu Menglin , Liao Zhixiong , Zeng Kaidong , Jiang Qiaohui
Published: January 2024

Background

Giant Cell Arteritis (GCA) is a complex autoimmune condition. With growing interest in the role of gut microbiota in autoimmune diseases, this research aimed to explore the potential causal relationship between gut microbiota and GCA, and the mediating effects of specific intermediaries.

Methods

Using a bidirectional two-sample Mendelian randomization (MR) design, we investigated associations between 191 microbial taxa and GCA. A two-step MR technique discerned the significant mediators on this relationship, followed by Multivariable MR analyses to quantify the direct influence of gut microbiota on GCA and mediation effect proportion, adjusting for these mediators.

Results

Nine taxa displayed significant associations with GCA. Among them, families like Bacteroidales and Clostridiaceae1 had Odds Ratios (OR) of 1.48 (p=0.043) and 0.52 (p=5.51e-3), respectively. Genera like Clostridium sensu stricto1 and Desulfovibrio showed ORs of 0.48 (p=5.39e-4) and 1.48 (p=0.037), respectively. Mediation analyses identified 25 hydroxyvitamin D level (mediation effect of 19.95%), CD14+ CD16- monocyte counts (mediation effect of 27.40%), and CD4+ T cell counts (mediation effect of 28.51%) as significant intermediaries.

Conclusion

Our findings provide invaluable insights into the complex interplay between specific gut microbiota taxa and GCA. By highlighting the central role of gut microbiota in influencing GCA risk and long-term recurrence, and their interactions with vital immune mediators, this research paves the way for potential therapeutic interventions in GCA management.
Management of the refractory vitiligo patient: current therapeutic strategies and future options
Authors: Wang Xinju , Wu Wei , Chen Jianru , Li Chunying , Li Shuli
Published: January 2024

Vitiligo is an autoimmune disease that leads to disfiguring depigmented lesions of skin and mucosa. Although effective treatments are available for vitiligo, there are still some patients with poor responses to conventional treatment. Refractory vitiligo lesions are mostly located on exposed sites such as acral sites and lips, leading to significant life stress. Understanding the causes of refractory vitiligo and developing targeted treatments are essential to enhance vitiligo outcomes. In this review, we summarized recent treatment approaches and some potential methods for refractory vitiligo. Janus kinase inhibitors have shown efficacy in refractory vitiligo. A variety of surgical interventions and fractional carbon dioxide laser have been widely applied to combination therapies. Furthermore, melanocyte regeneration and activation therapies are potentially effective strategies. Patients with refractory vitiligo should be referred to psychological monitoring and interventions to reduce the potential pathogenic effects of chronic stress. Finally, methods for depigmentation and camouflage may be beneficial in achieving uniform skin color and improved quality of life. Our ultimate focus is to provide alternative options for refractory vitiligo and to bring inspiration to future research.
Electroacupuncture for acute gouty arthritis: a systematic review and meta-analysis of randomized controlled trials
Authors: Ni Zhichao , Xiao Qinwen , Xia Zihao , Kuang Kunlin , Yin Bingzun , Peng Dezhong
Published: January 2024

Acute gouty arthritis (AGA) is a metabolic disorder in which recurrent pain episodes can severely affect the quality of life of gout sufferers. Electroacupuncture (EA) is a non-pharmacologic therapy. This systematic review aimed to assess the efficacy and safety of electroacupuncture in treating acute gouty arthritis. We searched eight Chinese and English databases from inception to July 30, 2023, and 242 studies were retrieved. Finally, 15 randomized controlled trials (n=1076) were included in a meta-analysis using Review Manager V.5.4.1. meta-analysis results included efficacy rate, visual rating scale (VAS) for pain, serum uric acid level (SUA), immediate analgesic effect, and incidence of adverse events. Electroacupuncture (or combined non-pharmacologic) treatment of AGA was significantly different from treatment with conventional medications (RR = 1.14, 95% confidence interval CI = 1.10 to 1.19, P < 0.00001). The analgesic effect of the electroacupuncture group was superior to that of conventional Western drug treatment (MD = -2.26, 95% CI = -2.71 to -1.81, P < 0.00001). The electroacupuncture group was better at lowering serum uric acid than the conventional western drug group (MD =-31.60, CI -44.24 to -18.96], P < 0.00001). In addition, electroacupuncture combined with Western drugs had better immediate analgesic effects than conventional Western drug treatment (MD = -1.85, CI -2.65 to -1.05, P < 0.00001). Five studies reported adverse events in the electroacupuncture group versus the drug group, including 19 cases of gastrointestinal symptoms and 6 cases of neurological symptoms (RR = 0.20, 95% CI = 0.04 to 0.88, P = 0.03).

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=450037, identifier CRD42023450037.
Role of MCP-1 as an inflammatory biomarker in nephropathy
Authors: Liu Yanlong , Xu Ke , Xiang Yuhua , Ma Boyan , Li Hailong , Li Yuan , Shi Yue , Li Shuju , Bai Yan
Published: January 2024

The Monocyte chemoattractant protein-1 (MCP-1), also referred to as chemokine ligand 2 (CCL2), belongs to the extensive chemokine family and serves as a crucial mediator of innate immunity and tissue inflammation. It has a notable impact on inflammatory conditions affecting the kidneys. Upon binding to its receptor, MCP-1 can induce lymphocytes and NK cells’ homing, migration, activation, differentiation, and development while promoting monocytes’ and macrophages’ infiltration, thereby facilitating kidney disease-related inflammation. As a biomarker for kidney disease, MCP-1 has made notable advancements in primary kidney diseases such as crescentic glomerulonephritis, chronic glomerulonephritis, primary glomerulopathy, idiopathic proteinuria glomerulopathy, acute kidney injury; secondary kidney diseases like diabetic nephropathy and lupus nephritis; hereditary kidney diseases including autosomal dominant polycystic kidney disease and sickle cell kidney disease. MCP-1 not only predicts the occurrence, progression, prognosis of the disease but is also closely associated with the severity and stage of nephropathy. When renal tissue is stimulated or experiences significant damage, the expression of MCP-1 increases, demonstrating a direct correlation with the severity of renal injury.
Immune cells in the epithelial immune microenvironment of psoriasis: emerging therapeutic targets
Authors: Li Lisha , Lu Jiaye , Liu Jun , Wu Junchao , Zhang Xinyue , Meng Yu , Wu Xiying , Tai Zongguang , Zhu Quangang , Chen Zhongjian
Published: January 2024

Psoriasis is a chronic autoimmune inflammatory disease characterized by erroneous metabolism of keratinocytes. The development of psoriasis is closely related to abnormal activation and disorders of the immune system. Dysregulated skin protective mechanisms can activate inflammatory pathways within the epithelial immune microenvironment (EIME), leading to the development of autoimmune-related and inflammatory skin diseases. In this review, we initially emphasized the pathogenesis of psoriasis, paying particular attention to the interactions between the abnormal activation of immune cells and the production of cytokines in psoriasis. Subsequently, we delved into the significance of the interactions between EIME and immune cells in the emergence of psoriasis. A thorough understanding of these immune processes is crucial to the development of targeted therapies for psoriasis. Finally, we discussed the potential novel targeted therapies aimed at modulating the EIME in psoriasis. This comprehensive examination sheds light on the intricate underlying immune mechanisms and provides insights into potential therapeutic avenues of immune-mediated inflammatory diseases.
Understanding the oceanographic dynamics of the Isla Chañaral baleen whale feeding ground, (Humboldt Archipelago, Northern Chile) to extend habitat protection
Authors: Buchan Susannah J. , Ramos Marcel , Oyanadel Jorge , Santos-Carvallo Macarena , Bedriñana-Romano Luis , Valladares María , Maldonado Marinella , Astudillo Orlando , Sepúlveda Maritza , Pearce Steve , Olavarría Carlos
Published: January 2024

Off Northern Chile, baleen whales use the area around Isla Chañaral as a feeding ground where they forage on euphausiids. Isla Chañaral is part of the highly productive Humboldt Archipelago (∼ 28°S-29°S) within the Humboldt Current System (HCS). In this study, we seek to understand the sub-mesoscale spatial distribution of fin and blue whales and their prey around Isla Chañaral using systematic and opportunistic visual sighting data of whales and systematic acoustic backscatter data of zooplankton from an Acoustic Zooplankton and Fish Profiler (AZFP); and to examine the oceanographic dynamics of the wider Humboldt Archipelago area with remote-sensing oceanographic data. We completed a total of 512.6 km of survey effort over 20 days in 2018 and 318.3 km over 16 days in 2019 collecting systematic whale sighting and backscatter data. A total of 42 fin whales, 0 blue whales and 66 unidentified whales were sighted in 2018, and 7 fin whales, 3 blue whales and 12 unidentified whales were sighted in 2019. Observed spatial distribution of backscatter and whales was strongly associated with a bathymetric feature, i.e., the submarine canyon that curves around Isla Chañaral. Generalized Additive Models showed that fin whale presence was associated with high levels of backscatter and shallow depths similar to those of the canyon. We found that long-term average geostrophic currents form a recirculation system between 28°S and 31°S that can transport nutrient-rich upwelled surface waters back towards the Humboldt Archipelago and contribute to high biological productivity in this area. However, in summer 2019 geostrophic flow occurred away from the coast and a warm low-productivity spring explained low backscatter and whale sightings around Isla Chañaral. The unique oceanographic features of Isla Chañaral and the Humboldt Archipelago that contribute to high concentrations of Endangered baleen whales and their prey justify the extension of the Isla Chañaral Marine Reserve to include the canyon between the mainland and the island, and the implementation of a Multiple Use Marine Protected Area for the entire Humboldt Archipelago area that explicitly protects this critical feature.
Cyclic resistance evaluation of marine clay based on CPTu data: a case study of Shaba Wind Farm
Authors: Wu Qi , Zhu En-ci , Xiao Xing , Li Yuan-xi , Chen Guo-xing
Published: January 2024

The offshore wind farm industry has recently experienced significant global growth. This study presents a thorough site investigation and analysis of the cyclic resistance of marine clay for offshore foundation design, using the Shaba wind farm in southern China as a case study. In-situ cone penetrometer (CPTu) tests and borehole sampling are conducted to explore the geotechnical characteristics of the soils. However, the soil conditions are characterized by multiple layers and complex sedimentary components. The classification and mechanical properties, such as water content and cyclic resistances, are compared through CPTu interpretation and laboratory tests. The findings indicated that a single physical indicator cannot determine cyclic resistance. In addition, the well-established method in existing literature proved unsuitable for marine clay. Consequently, multiple regression analysis shows that a linear relationship exist between cyclic resistance and depth-corrected CPTu index [EXP(qE/fs)0.3/H], hence a new evaluation method is developed to predict the cyclic resistance of marine clay based on CPTu data. This research aims to provide more reliable guidance for geotechnical investigations, supporting the rapid expansion of offshore wind farms.
Study of the damage characteristics and corrosion mechanism of tunnel lining in a sulfate environment
Authors: Liu Xinrong , Zhuang Yang , Zhou Xiaohan , Liang Ninghui , Mao Jinwang , Chen Hai
Published: January 2024

Sulfate corrosion is one of the main causes of tunnel lining deterioration. An accurate understanding of the damage characteristics and corrosion mechanism of sulfate-corroded tunnels is the basis for the anti-corrosion design and damage control of the tunnel lining. Based on a project concerning a sulfate-corroded tunnel in the mountainous area of Southwest China, this study conducted a field investigation and laboratory tests and, combined with existing research data, summarized the damage characteristics and corrosion mechanism of this type of tunnel and proposed the characteristic corrosion state of tunnel lining in a sulfate environment. The results show that 1) sulfate corrosion led to leakage, surface spalling crystallization, and strength loss, and the corrosion typically occurred at the arch waist and arch foot. 2) Physical and chemical corrosion occurred in the tunnel lining, and the corrosion products included sodium sulfate, calcium carbonate, gypsum, ettringite, and thaumasite. 3) In China, this type of tunnel is mainly located in the Southwest and Northwest, and its lining is in a special state of “one-sided accelerated corrosion.”
Overexpression of regulatory T cells in patients with unexplained recurrent pregnancy loss: friend or foe?
Authors: Liu Peng-cheng , Li Jian-bin , Huang Yi-ping , Zhang Min , Yu Shu-jiao , Wu Rui
Published: January 2024

Background

This study aimed to investigate the role of regulatory T cells in patients with unexplained recurrent pregnancy loss (URPL).

Methods

We retrospectively analyzed 136 women who had experienced two or more miscarriages before 24 weeks of gestation for no obvious reason from May 2018 to October 2021. The basic clinical data of the patients and expression of lymphocyte subsets such as regulatory T cells (Tregs) and natural killer cells (NKs) by flow cytometry were collected to explore the risk factors of pregnancy outcome in URPL patients.

Results

A total of 136 URPL patients were enrolled in this study. Eventually, 50 patients attained clinical pregnancy. The median age was 31.8 ± 4.6 years in patients with clinical pregnancy. The univariate and multivariate logistic regression analyses indicated that Tregs was associated with the pregnancy outcomes of patients with URPL (odds ratio 0.63, 95% confidence interval 0.50–0.80). More importantly, a U-shaped association was found between Tregs and pregnancy outcome (p < 0.001), with either higher or lower Tregs levels adversely affecting pregnancy outcome.

Conclusion

Tregs levels that are either too high or too low can harm pregnancy outcomes. It was expected to be a very promising quantitative biomarker for predicting pregnancy outcomes in URPL patients.
Population health interventions for cardiometabolic diseases in primary care: a scoping review and RE-AIM evaluation of current practices
Authors: Rakers Margot , van Hattem Nicoline , Plag Sabine , Chavannes Niels , van Os Hendrikus J. A. , Vos Rimke C.
Published: January 2024

Introduction

Cardiometabolic diseases (CMD) are the leading cause of death in high-income countries and are largely attributable to modifiable risk factors. Population health management (PHM) can effectively identify patient subgroups at high risk of CMD and address missed opportunities for preventive disease management. Guided by the Reach, Efficacy, Adoption, Implementation and Maintenance (RE-AIM) framework, this scoping review of PHM interventions targeting patients in primary care at increased risk of CMD aims to describe the reported aspects for successful implementation.

Methods

A comprehensive search was conducted across 14 databases to identify papers published between 2000 and 2023, using Arksey and O’Malley’s framework for conducting scoping reviews. The RE-AIM framework was used to assess the implementation, documentation, and the population health impact score of the PHM interventions.

Results

A total of 26 out of 1,100 studies were included, representing 21 unique PHM interventions. This review found insufficient reporting of most RE-AIM components. The RE-AIM evaluation showed that the included interventions could potentially reach a large audience and achieve their intended goals, but information on adoption and maintenance was often lacking. A population health impact score was calculated for six interventions ranging from 28 to 62%.

Discussion

This review showed the promise of PHM interventions that could reaching a substantial number of participants and reducing CMD risk factors. However, to better assess the generalizability and scalability of these interventions there is a need for an improved assessment of adoption, implementation processes, and sustainability.
A hybrid neural network approach for classifying diabetic retinopathy subtypes
Authors: Xu Huanqing , Shao Xian , Fang Dandan , Huang Fangliang
Published: January 2024

Objective

Diabetic retinopathy is a prevalent complication among diabetic patients that, if not predicted and treated promptly, can lead to blindness. This paper proposes a method for accurately and swiftly predicting the degree of diabetic retinopathy using a hybrid neural network model. Timely prediction of diabetic retinopathy is crucial in preventing blindness associated with this condition.

Methods

This study aims to enhance the prediction accuracy of diabetic retinopathy by utilizing the hybrid neural network model EfficientNet and Swin Transformer. The specific methodology includes: (1) combining local and global features to accurately capture lesion characteristics by leveraging the strengths of both Swin Transformer and EfficientNet models; (2) improving prediction accuracy through a comprehensive analysis of the model’s training details and applying data augmentation techniques such as Gaussian blur to enhance the hybrid model’s performance; (3) validating the effectiveness and utility of the proposed hybrid model for diabetic retinopathy detection through extensive experimental evaluations and comparisons with other deep learning models.

Results

The hybrid model was trained and tested on the large-scale real-world diabetic retinopathy detection dataset APTOS 2019 Blindness Detection. The experimental results show that the hybrid model in this paper achieves the best results in all metrics, including sensitivity of 0.95, specificity of 0.98, accuracy of 0.97, and AUC of 0.97. The performance of the model is significantly improved compared to the mainstream methods currently employed. In addition, the model provides interpretable neural network details through class activation maps, which enables the visualization of diabetic retinopathy. This feature helps physicians to make more accurate diagnosis and treatment decisions. The model proposed in this paper shows higher accuracy in detecting and diagnosing diabetic retinopathy, which is crucial for the treatment and rehabilitation of diabetic patients.

Conclusion

The hybrid neural network model based on EfficientNet and Swin Transformer significantly contributes to the prediction of diabetic retinopathy. By combining local and global features, the model achieves improved prediction accuracy. The validity and utility of the model are verified through experimental evaluations. This research provides robust support for the early diagnosis and treatment of diabetic patients.
Prevalence and antibiotic resistance of Salmonella in organic and non-organic chickens on the Eastern Shore of Maryland, USA
Authors: Punchihewage-Don Anuradha Jeewantha , Schwarz Jurgen , Diria Abdirahman , Bowers John , Parveen Salina
Published: January 2024

Introduction

Salmonella infections have been intensely increasing and becoming a universal public health crisis. This study investigated the prevalence of Salmonella in organic and non-organic chickens and the antimicrobial resistance profiles and virulence genes (invA, pagC, and spvC) in recovered Salmonella isolates.

Methods

Whole chicken carcasses [organic (n = 240) and non-organic (n = 240)] were obtained monthly for 1 year (n = 480) from a retail store on the Eastern Shore of Maryland. Salmonella isolation and identification were conducted by following the whole carcass enrichment method recommended by USDA-FSIS. Confirmed Salmonella isolates (organic n = 76; non-organic n = 137) were serotyped and tested for antibiotic susceptibility and virulence genes using standard methods.

Results

Forty-nine percent (237/480) of the carcasses were positive for Salmonella. Organic and non-organic positivity rates were 37.1 and 61.8%, respectively. A significantly higher Salmonella contamination was observed in non-organic chickens (p < 0.05). The most common serovars were Salmonella Kentucky (47%), S. Infantis (35%), S. Enteritidis (6%), S. Typhimurium (5%), and S. Blockley (4%). Isolates were frequently resistant to at least one antibiotic (91.24%) or multidrug resistant (45.54%). Resistance was observed to tetracycline (82.8%), minocycline (42.3%), nitrofurantoin (40.3%), cefazolin (38.3%), ampicillin (32.1%), and ceftriaxone (26%). All isolates were susceptible to fluoroquinolone, carbapenem, and glycylcycline. The majority of isolates (99.1%) possessed at least one of three virulence genes of concern and 4.2% tested positive for all three. Ninety-five, 89, and 6.6% of isolates contained invA, pagC, and spvC genes, respectively. The spvC gene was not detected in serovars recovered from organic chickens though 92% and 82% of isolates were positive for invA and pagC. The frequency of Salmonella recovered from non-organic chickens possessing invA, pagC, and spvC genes were 97.1, 89.8, and 10.2%, respectively. Detection of invA and pagC genes showed no significant difference (p > 0.05) between organic and non-organic chickens but a significantly higher spvC gene (p < 0.05) was detected in non-organic chickens due to the majority of S. Enteritidis (92.3%) exclusively recovered from non-organic chicken carried spvC gene.

Discussion

This study reveals a high prevalence of Salmonella in both organic and non-organic chickens, which exhibit resistance to vital antibiotics and carry virulence genes, thereby creating a potential risk of salmonellosis.
Characteristics of a lipase ArEstA with lytic activity against drug-resistant pathogen from a novel myxobacterium, Archangium lipolyticum sp. nov.
Authors: Zhou Yang , Chen Haixin , Jiang Hongxia , Yao Qing , Zhu Honghui
Published: January 2024

Bacteriolytic myxobacteria are versatile micropredators and are proposed as potential biocontrol agents against diverse bacterial and fungal pathogens. Isolation of new myxobacteria species and exploration of effective predatory products are necessary for successful biocontrol of pathogens. In this study, a myxobacterium strain CY-1 was isolated from a soil sample of a pig farm using the Escherichia coli baiting method. Based on the morphological observation, physiological test, 16S rRNA gene sequence, and genomic data, strain CY-1 was identified as a novel species of the myxobacterial genus Archangium, for which the name Archangium lipolyticum sp. nov. was proposed. Subsequent predation tests indicated that the strain efficiently lysed drug-resistant pathogens, with a higher predatory activity against E. coli 64 than Staphylococcus aureus GDMCC 1.771 (MRSA). The lysis of extracellular proteins against ester-bond-containing substrates (tributyrin, tween 80, egg-yolk, and autoclaved drug-resistant pathogens) inspired the mining of secreted predatory products with lipolytic activity. Furthermore, a lipase ArEstA was identified from the genome of CY-1, and the heterologously expressed and purified enzyme showed bacteriolytic activity against Gram-negative bacteria E. coli 64 but not against Gram-positive MRSA, possibly due to different accessibility of enzyme to lipid substrates in different preys. Our research not only provided a novel myxobacterium species and a candidate enzyme for the development of new biocontrol agents but also reported an experimental basis for further study on different mechanisms of secreted predatory products in myxobacterial killing and degrading of Gram-negative and Gram-positive preys.
Epidemiology and molecular analyses of respiratory syncytial virus in the 2021–2022 season in northern Italy
Authors: Lai Alessia , Bergna Annalisa , Fabiano Valentina , Ventura Carla della , Fumagalli Giulia , Mari Alessandra , Loiodice Martina , Zuccotti Gian Vincenzo , Zehender Gianguglielmo
Published: January 2024

Background

Human respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infection among infants and young children worldwide, with seasonal peaks in January and February. This study aimed to characterize the RSV samples from a pediatric cohort in the 2021–2022 season in Italy.

Methods

In total, 104 samples were collected from pediatric patients attending the “Vittore Buzzi” Children’s Hospital in Milan, Italy in the 2021–2022 season. RT-PCR and next-generation sequencing were used to discriminate subgroups and obtain whole genomes. Maximum likelihood and Bayesian phylogenetic methods were used to analyze Italian sequences in the European contest and date Italian clusters.

Results

The median age was 78 days, and 76.9% of subjects required hospitalization, with a higher proportion of patients under 3 months of age. An equal proportion of subgroups A (GA2.3.5) and B (GB5.0.5a) was found, with significant differences in length of hospitalization, days of supplemental oxygen treatment, and intravenous hydration duration. Phylogeny highlighted 26 and 37 clusters containing quite the total of Italian sequences for RSV-A and -B, respectively. Clusters presented a tMRCA between December 2011–February 2017 and May 2014–December 2016 for A and B subgroups, respectively. Compared to European sequences, specific mutations were observed in Italian strains.

Conclusion

These data confirmed a more severe clinical course of RSV-A, particularly in young children. This study permitted the characterization of recent Italian RSV whole genomes, highlighting the peculiar pattern of mutations that needs to be investigated further and monitored.
Tomato seed bio-priming with Pseudomonas aeruginosa strain PAR: a study on plant growth parameters under sodium fluoride stress
Authors: Singh Anamika , Patani Anil , Patel Margi , Vyas Suhas , Verma Rakesh Kumar , Amari Abdelfattah , Osman Haitham , Rathod Lokendra , Elboughdiri Noureddine , Yadav Virendra Kumar , Sahoo Dipak Kumar , Chundawat Rajendra Singh , Patel Ashish
Published: January 2024

The primary goal of this experiment is to examine the effectiveness of Pseudomonas aeruginosa strain PAR as a rhizobacterium that promotes plant growth in mitigating the negative effects of fluoride-induced stress in tomato (Lycopersicon esculentum Mill.) plants. A total of 16 rhizobacterial strains were tested for plant growth-promoting (PGP) attributes, with isolates S1, S2, and S3 exhibiting different characteristics. Furthermore, growth kinetics studies revealed that these isolates were resilient to fluoride stress (10, 20, 40, and 80 ppm), with isolate S2 exhibiting notable resilience compared to the other two strains. Phylogenetic analysis revealed isolate S2 as P. aeruginosa strain PAR. Physiological analyses demonstrated that P. aeruginosa strain PAR had a beneficial impact on plant properties under fluoride stress, comprising seed germination, root length, shoot height, relative water content, and leaf area, the strain also impacted the buildup of glycine betaine, soluble sugar, and proline, demonstrating its significance in enhancing plant stress tolerance. In P. aeruginosa strain PAR-treated plants, chlorophyll content increased while malondialdehyde (MDA) levels decreased, indicating enhanced photosynthetic efficiency and less oxidative stress. The strain modified antioxidant enzyme action (catalase, ascorbate, glutathione reductase, peroxidase, and superoxide dismutase), which contributed to improved stress resilience. Mineral analysis revealed a decrease in sodium and fluoride concentrations while increasing magnesium, potassium, phosphorus, and iron levels, emphasizing the strain’s significance in nutrient management. Correlation and principal component analysis revealed extensive correlations between physiological and biochemical parameters, underscoring P. aeruginosa strain PAR’s multifaceted impact on plant growth and stress response. This study offers valuable information on effectively utilizing PGPR, particularly P. aeruginosa strain PAR, in fluoride-contaminated soils for sustainable agriculture. It presents a promising biological strategy to enhance crop resilience and productivity.
Construction and evaluation of endometriosis diagnostic prediction model and immune infiltration based on efferocytosis-related genes
Authors: Pei Fang-Li , Jia Jin-Jin , Lin Shu-Hong , Chen Xiao-Xin , Wu Li-Zheng , Lin Zeng-Xian , Sun Bo-Wen , Zeng Cheng
Published: January 2024

Background: Endometriosis (EM) is a long-lasting inflammatory disease that is difficult to treat and prevent. Existing research indicates the significance of immune infiltration in the progression of EM. Efferocytosis has an important immunomodulatory function. However, research on the identification and clinical significance of efferocytosis-related genes (EFRGs) in EM is sparse.

Methods: The EFRDEGs (differentially expressed efferocytosis-related genes) linked to datasets associated with endometriosis were thoroughly examined utilizing the Gene Expression Omnibus (GEO) and GeneCards databases. The construction of the protein-protein interaction (PPI) and transcription factor (TF) regulatory network of EFRDEGs ensued. Subsequently, machine learning techniques including Univariate logistic regression, LASSO, and SVM classification were applied to filter and pinpoint diagnostic biomarkers. To establish and assess the diagnostic model, ROC analysis, multivariate regression analysis, nomogram, and calibration curve were employed. The CIBERSORT algorithm and single-cell RNA sequencing (scRNA-seq) were employed to explore immune cell infiltration, while the Comparative Toxicogenomics Database (CTD) was utilized for the identification of potential therapeutic drugs for endometriosis. Finally, immunohistochemistry (IHC) and reverse transcription quantitative polymerase chain reaction (RT-qPCR) were utilized to quantify the expression levels of biomarkers in clinical samples of endometriosis.

Results: Our findings revealed 13 EFRDEGs associated with EM, and the LASSO and SVM regression model identified six hub genes (ARG2, GAS6, C3, PROS1, CLU, and FGL2). Among these, ARG2, GAS6, and C3 were confirmed as diagnostic biomarkers through multivariate logistic regression analysis. The ROC curve analysis of GSE37837 (AUC = 0.627) and GSE6374 (AUC = 0.635), along with calibration and DCA curve assessments, demonstrated that the nomogram built on these three biomarkers exhibited a commendable predictive capacity for the disease. Notably, the ratio of nine immune cell types exhibited significant differences between eutopic and ectopic endometrial samples, with scRNA-seq highlighting M0 Macrophages, Fibroblasts, and CD8 Tex cells as the cell populations undergoing the most substantial changes in the three biomarkers. Additionally, our study predicted seven potential medications for EM. Finally, the expression levels of the three biomarkers in clinical samples were validated through RT-qPCR and IHC, consistently aligning with the results obtained from the public database.

Conclusion: we identified three biomarkers and constructed a diagnostic model for EM in this study, these findings provide valuable insights for subsequent mechanistic research and clinical applications in the field of endometriosis.
Ontogenetic changes in the tyrosine hydroxylase immunoreactive preoptic area in the small-spotted catshark Scyliorhinus canicula (L., 1758) females: catecholaminergic involvement in sexual maturation
Authors: Porceddu Riccardo , Porcu Cristina , Mulas Giovanna , Spiga Saturnino , Follesa Maria Cristina
Published: January 2024

Introduction

The catecholaminergic component of the brain-pituitary-gonadal axis, which mediates the influence of external and internal stimuli on the central nervous system and gonad development in vertebrates, is largely unexplored in Chondrichthyes. We considered Scyliorhinus canicula (L., 1758) females as a model for this vertebrate's class, to assess the involvement of the catecholaminergic system of the brain in its reproduction. Along the S. canicula reproductive cycle, we characterized and evaluated differences in somata morphometry and the number of putative catecholaminergic neurons in two brain nuclei: the periventricular preoptic nucleus, hypothesized to be a positive control for ovarian development, and the suprachiasmatic nucleus, examined as a negative control.

Materials and methods

16 S. canicula wild females were sampled and grouped in maturity stages (immature, maturing, mature, and mature egg-laying). The ovary was histologically processed for the qualitative description of maturity stages. Anti-tyrosine hydroxylase immunofluorescence was performed on the diencephalic brain sections. The immunoreactive somata were investigated for morphometry and counted using the optical fractionator method, throughout the confocal microscopy.

Results and discussions

Qualitative and quantitative research confirmed two separate populations of immunoreactive neurons. The modifications detected in the preoptic nucleus revealed that somata were more numerous, significantly smaller in size, and more excitable during the maturing phase but decreased, becoming slightly bigger and less excitable in the egg-laying stage. This may indicate that the catecholaminergic preoptic nucleus is involved in the control of reproduction, regulating both the onset of puberty and the imminent spawning. In contrast, somata in the suprachiasmatic nucleus grew in size and underwent turnover in morphometry, increasing the total number from the immature-virgin to maturing stage, with similar values in the more advanced maturity stages. These changes were not linked to a reproductive role. These findings provide new valuable information on Chondrichthyes, suggesting the existence of an additional brain system implicated in the integration of internal and environmental cues for reproduction.
Safety and efficacy analysis of the off-label use of pipeline embolization devices for intracranial aneurysms: a propensity score matching study
Authors: Ma Yajing , Deng Xin , Chen Zhen , Yuan Yongjie , Guan Sheng , Guo Xinbin
Published: January 2024

Background and objective

The safety and efficacy of on-label use of pipeline embolization devices (PEDs) are well established; however, there is much controversy over their off-label use. This study aimed to investigate the safety and efficacy of the off-label use of PEDs for treating intracranial aneurysms.

Methods

This single-center study retrospectively included patients with digital subtraction angiography, computed tomographic angiography, or magnetic resonance angiography confirmed intracranial aneurysms treated with PEDs who were admitted to our institution between 1 January 2018 and 1 July 2022. Patients were divided into on- and off-label groups according to the Food and Drug Administration criteria published in 2021. Propensity score matching (PSM) was used to balance disparities in baseline information between the two groups. Safety outcomes included postoperative mortality and complication rates, whereas effectiveness outcomes included aneurysm occlusion rate (O’Kelly-Marotta grading system C + D grades), retreatment rate within 12 months, and postoperative functional score [modified Rankin scale (mRS) score]. The study was approved by the Ethics Committee of Scientific Research and Clinical Trial of the First Affiliated Hospital of Zhengzhou University (Ethics number: KY 2018–098-02). All patients provided informed consent.

Results

A total of 242 patients with 261 aneurysms (160 on-label and 101 off-label aneurysms) were included in this study. PSM yielded 81 pairs of patients matched for baseline information. Postoperative hemorrhagic, ischemic, and procedure-related complication rates did not reach statistical significance. In addition, no statistically significant differences in the aneurysm occlusion rate, retreatment rate within 12 months, postoperative functional score (mRS score), or mRS score deterioration rate were observed between the two groups. A higher incidence of in-stent stenosis was observed in the off-label (4.9% vs. 21%, p = 0.002) group than in the on-label group; however, all patients were asymptomatic.

Conclusion

Compared with on-label use, off-label use of PEDs for treating intracranial aneurysms did not increase the risk of complications, and the occlusion rates were comparable. Therefore, decisions regarding clinical management should not rely solely on on- or off-label indications.