bluuebunny/crossref_metadata_2025 huggingface dataset:
Cyanoacrylate glue for iatrogenic retinal breaks during vitrectomy in stage 5 familial exudative vitreoretinopathy
Authors: Zou Yihua , Peng Jie , Zhao Peiquan
Published: June 2024

Purpose

To describe the role of cyanoacrylate glue in sealing iatrogenic retinal breaks (IRBs) during vitrectomy in stage 5 familial exudative vitreoretinopathy (FEVR) with funneled retinal detachment (RD).

Methods

Nine eyes of nine patients diagnosed as stage 5 FEVR were treated with cyanoacrylate glue for IRBs during vitrectomy from July 2020 to January 2022. The clinical records, including patient information, surgical process, and follow-up examinations, were collected retrospectively. Anatomical outcomes and visual outcomes were summarized.

Results

The average age at surgery was 19.6 months (range: 3.8–41.1 months). The mean post-operative follow-up period was 12.5 months (range: 9.8–18.8 months). Before surgery, five eyes had an open-funnel RD and four eyes had a closed-funnel RD. All the preretinal fibroplasia membranes were removed as thoroughly as possible in the nine eyes. IRBs formed at the posterior pole in two eyes and peripheral retina in seven eyes. All the IRBs were sealed successfully by the cyanoacrylate glue when they appeared. At the final post-operative visit, eight eyes had partial retinal reattachment without progression of fibroplasia tissues, while one eye had total retinal redetachment. The rate for stable anatomical outcome was 88.9% (8/9) in this study. The visual testing available for seven eyes demonstrated light perception in five eyes and no light perception in two eyes. No severe perioperative glue-related complications were noted during the follow-ups.

Conclusion

The application of cyanoacrylate glue may be an alternative therapy for IRBs in stage 5 FEVR surgeries, while the long-term efficacy and safety still need further investigation.
Evaluation of large language models as a diagnostic aid for complex medical cases
Authors: Ríos-Hoyo Alejandro , Shan Naing Lin , Li Anran , Pearson Alexander T. , Pusztai Lajos , Howard Frederick M.
Published: June 2024

Background

The use of large language models (LLM) has recently gained popularity in diverse areas, including answering questions posted by patients as well as medical professionals.

Objective

To evaluate the performance and limitations of LLMs in providing the correct diagnosis for a complex clinical case.

Design

Seventy-five consecutive clinical cases were selected from the Massachusetts General Hospital Case Records, and differential diagnoses were generated by OpenAI’s GPT3.5 and 4 models.

Results

The mean number of diagnoses provided by the Massachusetts General Hospital case discussants was 16.77, by GPT3.5 30 and by GPT4 15.45 (p < 0.0001). GPT4 was more frequently able to list the correct diagnosis as first (22% versus 20% with GPT3.5, p = 0.86), provide the correct diagnosis among the top three generated diagnoses (42% versus 24%, p = 0.075). GPT4 was better at providing the correct diagnosis, when the different diagnoses were classified into groups according to the medical specialty and include the correct diagnosis at any point in the differential list (68% versus 48%, p = 0.0063). GPT4 provided a differential list that was more similar to the list provided by the case discussants than GPT3.5 (Jaccard Similarity Index 0.22 versus 0.12, p = 0.001). Inclusion of the correct diagnosis in the generated differential was correlated with PubMed articles matching the diagnosis (OR 1.40, 95% CI 1.25–1.56 for GPT3.5, OR 1.25, 95% CI 1.13–1.40 for GPT4), but not with disease incidence.

Conclusions and relevance

The GPT4 model was able to generate a differential diagnosis list with the correct diagnosis in approximately two thirds of cases, but the most likely diagnosis was often incorrect for both models. In its current state, this tool can at most be used as an aid to expand on potential diagnostic considerations for a case, and future LLMs should be trained which account for the discrepancy between disease incidence and availability in the literature.
Morphology of human sinoatrial node and its surrounding right atrial muscle in the global obesity pandemic—does fat matter?
Authors: Chen Weixuan , Rams Daniel , Zając Maciej , Albalawi Raghad , Atkinson Andrew J. , Aminu Abimbola J. , Mazur Malgorzata , Hołda Mateusz K. , Walocha Jerzy , Gil Krzysztof , Kuniewicz Marcin , Dobrzynski Halina
Published: June 2024

Introduction

The sinus node (SN) is the main pacemaker site of the heart, located in the upper right atrium at the junction of the superior vena cava and right atrium. The precise morphology of the SN in the human heart remains relatively unclear especially the SN microscopical anatomy in the hearts of aged and obese individuals. In this study, the histology of the SN with surrounding right atrial (RA) muscle was analyzed from young non-obese, aged non-obese, aged obese and young obese individuals. The impacts of aging and obesity on fibrosis, apoptosis and cellular hypertrophy were investigated in the SN and RA. Moreover, the impact of obesity on P wave morphology in ECG was also analyzed to determine the speed and conduction of the impulse generated by the SN.

Methods

Human SN/RA specimens were dissected from 23 post-mortem hearts (preserved in 4% formaldehyde solution), under Polish local ethical rules. The SN/RA tissue blocks were embedded in paraffin and histologically stained with Masson’s Trichrome. High and low-magnification images were taken, and analysis was done for appropriate statistical tests on Prism (GraphPad, USA). 12-lead ECGs from 14 patients under Polish local ethical rules were obtained. The P wave morphologies from lead II, lead III and lead aVF were analyzed.

Results

Compared to the surrounding RA, the SN in all four groups has significantly more connective tissue (P ≤ 0.05) (young non-obese individuals, aged non-obese individuals, aged obese individuals and young obese individuals) and significantly smaller nodal cells (P ≤ 0.05) (young non-obese individuals, aged non-obese individuals, aged obese individuals, young obese individuals). In aging, overall, there was a significant increase in fibrosis, apoptosis, and cellular hypertrophy in the SN (P ≤ 0.05) and RA (P ≤ 0.05). Obesity did not further exacerbate fibrosis but caused a further increase in cellular hypertrophy (SN P ≤ 0.05, RA P ≤ 0.05), especially in young obese individuals. However, there was more infiltrating fat within the SN and RA bundles in obesity. Compared to the young non-obese individuals, the young obese individuals showed decreased P wave amplitude and P wave slope in aVF lead.

Discussion

Aging and obesity are two risk factors for extensive fibrosis and cellular hypertrophy in SN and RA. Obesity exacerbates the morphological alterations, especially hypertrophy of nodal and atrial myocytes. These morphological alterations might lead to functional alterations and eventually cause cardiovascular diseases, such as SN dysfunction, atrial fibrillation, bradycardia, and heart failure.
Intelligent diagnosis system based on artificial intelligence models for predicting freezing of gait in Parkinson’s disease
Authors: Al-Nefaie Abdullah H. , Aldhyani Theyazn H. H. , Farhah Nesren , Koundal Deepika
Published: June 2024

Introduction

Freezing of gait (FoG) is a significant issue for those with Parkinson’s disease (PD) since it is a primary contributor to falls and is linked to a poor superiority of life. The underlying apparatus is still not understood; however, it is postulated that it is associated with cognitive disorders, namely impairments in executive and visuospatial functions. During episodes of FoG, patients may experience the risk of falling, which significantly effects their quality of life.

Methods

This research aims to systematically evaluate the effectiveness of machine learning approaches in accurately predicting a FoG event before it occurs. The system was tested using a dataset collected from the Kaggle repository and comprises 3D accelerometer data collected from the lower backs of people who suffer from episodes of FoG, a severe indication frequently realized in persons with Parkinson’s disease. Data were acquired by measuring acceleration from 65 patients and 20 healthy senior adults while they engaged in simulated daily life tasks. Of the total participants, 45 exhibited indications of FoG. This research utilizes seven machine learning methods, namely the decision tree, random forest, Knearest neighbors algorithm, LightGBM, and CatBoost models. The Gated Recurrent Unit (GRU)-Transformers and Longterm Recurrent Convolutional Networks (LRCN) models were applied to predict FoG. The construction and model parameters were planned to enhance performance by mitigating computational difficulty and evaluation duration.

Results

The decision tree exhibited exceptional performance, achieving sensitivity rates of 91% in terms of accuracy, precision, recall, and F1- score metrics for the FoG, transition, and normal activity classes, respectively. It has been noted that the system has the capacity to anticipate FoG objectively and precisely. This system will be instrumental in advancing consideration in furthering the comprehension and handling of FoG.
68Ga-PSMA-11 PET and mpMRI in the diagnosis of initial lymph node staging of prostate cancer: a head-to-head comparative meta-analysis
Authors: Wang Yuanrong , Jing Ren , Wang Haiyan , Zhao Qiuyan
Published: June 2024

Purpose

This meta-analysis evaluates the comparative diagnostic efficacy of 68Ga-prostate-specific membrane antigen-11 PET (68Ga-PSMA-11 PET) and multiparametric MRI (mpMRI) for the initial lymph node staging of prostate cancer.

Methods

We searched PubMed and Embase databases through October 2023 for studies that provide a head-to-head comparison of 68Ga-PSMA-11 PET and mpMRI, using pelvic lymph node dissection as the gold standard. We assessed sensitivity and specificity using the DerSimonian and Laird method, with variance stabilization via the Freeman-Tukey double inverse sine transformation. The quality of included studies was evaluated using the Quality Assessment of Diagnostic Performance Studies (QUADAS-2) tool.

Results

The meta-analysis incorporated 13 articles, involving a total of 1,527 patients. 68Ga-PSMA-11 PET demonstrated an overall sensitivity of 0.73 (95% CI: 0.51–0.91) and a specificity of 0.94 (95% CI: 0.88–0.99). In comparison, mpMRI showed a sensitivity of 0.49 (95% CI: 0.30–0.68) and a specificity of 0.94 (95% CI: 0.88–0.99). Although 68Ga-PSMA-11 PET appeared to be more sensitive than mpMRI, the differences in sensitivity (p = 0.11) and specificity (p = 0.47) were not statistically significant.

Conclusion

Our findings indicated that 68Ga-PSMA-11 PET and mpMRI exhibit similar sensitivity and specificity in the diagnosis of initial lymph node staging of prostate cancer. However, given that most included studies were retrospective, further prospective studies with larger sample sizes are essential to validate these results.

Systematic Review Registration

PROSPERO code is CRD42023495266.
Identification of the Ilex macrocarpa anthracnose pathogen and the antifungal potential of the cell-free supernatant of Bacillus velezensis against Colletotrichum fioriniae
Authors: Fu Chun , Wan Shushan , Yang Peng , Zhao Xizhu , Yan Yueyao , Jiang Shijiao , Ali Habib
Published: June 2024

Introduction

Anthracnose is a significant fungal disease that affects tree growth and development, with Colletotrichum spp. exhibiting host non-specificity and targeting various organs, making disease control challenging.

Methods

This study aimed to identify the pathogenic species causing anthracnose in Ilex macrocarpa in Nanchong, Sichuan Province, and screen effective fungicides, particularly biological ones. The pathogen was identified as Colletotrichum fioriniae through morphological observation, pathogenicity assays, and molecular biological methods. Three biological and five chemical fungicides were evaluated for their effects on the mycelial growth and spore germination rate of the pathogen.

Results

The results indicated that prochloraz was the most effective chemical fungicide, while the cell-free supernatant (CFS) of Bacillus velezensis had the most significant inhibitory effect among the biological fungicides. Transcriptome analysis revealed that the CFS of B. velezensis significantly reduced the expression of genes associated with ribosomes, genetic information processing, membrane lipid metabolism, and sphingolipid biosynthesis in C. fioriniae. Additionally, the glutathione pathway’s expression of various genes, including key genes such as GST, GFA, Grx, TRR, and POD, was induced. Furthermore, the expression of 17 MFS transporters and 9 ABC transporters was increased. Autophagy-related ATGs were also affected by the B. velezensis CFS.

Discussion

These findings suggest that the B. velezensis CFS may inhibit C. fioriniae through interference with ribosomes, genetic information processing, cell membrane metabolism, and energy metabolism. These results provide potential target genes for the B. velezensis CFS and insights into the antifungal mechanism by which B. velezensis inhibits C. fioriniae.
Physiological evaluation of PVP-coated AgNP in the rat small intestine: an ex vivo approach
Authors: Chávez-Hernández Jorge Antonio , España-Sánchez Beatriz Liliana , Aguirre-Bañuelos Patricia , Granados-López Lucero , Velarde-Salcedo Aída Jimena , Luna-Bárcenas Gabriel , Gonzalez Carmen
Published: June 2024

Silver nanoparticles (AgNP) are widely used globally due to their numerous properties, mainly because of their antimicrobial activity. However, the need for further regulations and legislation regarding their presence in products has led to concerns about their biosecurity, necessitating relevant biological studies at different levels. The present work aimed to evaluate the effect of the polyvinylpyrrolidone (PVP)-coated AgNP on the small intestine contraction and other mediators involved and the mediators involved (nitric oxide and serotonin) in an ex vivo model. Intestinal segments (duodenum, jejunum, and ileum) were treated in the presence and absence of five cumulative, increasing concentrations of AgNP (0.01, 0.1, 1, 10, and 100 μg/mL) and three individual concentrations of PVP-coated AgNP (0.01, 1, and 100 μg/mL), showing a transient decrease in the contractile effect in the small intestine segments treated with cumulative, increasing concentrations. This effect did not allow the isolated small intestine rings to return to their contractile basal level, and it was associated with an increase in nitric oxide (NO) production and variations in the amount of serotonin. A similar effect was observed at individual AgNP administrations but with a lesser influence on NO production. These results show that AgNP, in the function of the administration (cumulative or individual) and the segment type, can modify the contraction of the small intestine, mediated in part by NO and exerting a differential pattern in the amount of serotonin. Histological analysis revealed that specific morphological alterations induced by AgNP, such as necrosis and villi detachment, were more evident in the ileum segment. Furthermore, the accumulation of silver was observed in the small intestine villi, which could determine the physiological effects exerted upon the intestinal contraction associated with the release of a specific mediator like NO production and the presence of serotonin. These findings suggest that the small intestine is an essential target of the actions induced by AgNP, which could be ingested and reach this conduit because of the consumption of products containing these materials, modifying the intestinal motility that influences the efficiency of nutrient absorption—aspects that need to be explored and investigated in the short, medium, and long terms.
Translational symmetry in convolutions with localized kernels causes an implicit bias toward high frequency adversarial examples
Authors: Caro Josue O. , Ju Yilong , Pyle Ryan , Dey Sourav , Brendel Wieland , Anselmi Fabio , Patel Ankit B.
Published: June 2024

Adversarial attacks are still a significant challenge for neural networks. Recent efforts have shown that adversarial perturbations typically contain high-frequency features, but the root cause of this phenomenon remains unknown. Inspired by theoretical work on linear convolutional models, we hypothesize that translational symmetry in convolutional operations together with localized kernels implicitly bias the learning of high-frequency features, and that this is one of the main causes of high frequency adversarial examples. To test this hypothesis, we analyzed the impact of different choices of linear and non-linear architectures on the implicit bias of the learned features and adversarial perturbations, in spatial and frequency domains. We find that, independently of the training dataset, convolutional operations have higher frequency adversarial attacks compared to other architectural parameterizations, and that this phenomenon is exacerbated with stronger locality of the kernel (kernel size) end depth of the model. The explanation for the kernel size dependence involves the Fourier Uncertainty Principle: a spatially-limited filter (local kernel in the space domain) cannot also be frequency-limited (local in the frequency domain). Using larger convolution kernel sizes or avoiding convolutions (e.g., by using Vision Transformers or MLP-style architectures) significantly reduces this high-frequency bias. Looking forward, our work strongly suggests that understanding and controlling the implicit bias of architectures will be essential for achieving adversarial robustness.
Diving deep: zebrafish models in motor neuron degeneration research
Authors: Garg Vranda , Geurten Bart R. H.
Published: June 2024

In the dynamic landscape of biomedical science, the pursuit of effective treatments for motor neuron disorders like hereditary spastic paraplegia (HSP), amyotrophic lateral sclerosis (ALS), and spinal muscular atrophy (SMA) remains a key priority. Central to this endeavor is the development of robust animal models, with the zebrafish emerging as a prime candidate. Exhibiting embryonic transparency, a swift life cycle, and significant genetic and neuroanatomical congruencies with humans, zebrafish offer substantial potential for research. Despite the difference in locomotion—zebrafish undulate while humans use limbs, the zebrafish presents relevant phenotypic parallels to human motor control disorders, providing valuable insights into neurodegenerative diseases. This review explores the zebrafish's inherent traits and how they facilitate profound insights into the complex behavioral and cellular phenotypes associated with these disorders. Furthermore, we examine recent advancements in high-throughput drug screening using the zebrafish model, a promising avenue for identifying therapeutically potent compounds.
CNS cell-derived exosome signatures as blood-based biomarkers of neurodegenerative diseases
Authors: Park Calvin , Weerakkody Jonathan S. , Schneider Raphael , Miao Sheng , Pitt David
Published: June 2024

Molecular biomarkers require the reproducible capture of disease-associated changes and are ideally sensitive, specific and accessible with minimal invasiveness to patients. Exosomes are a subtype of extracellular vesicles that have gained attention as potential biomarkers. They are released by all cell types and carry molecular cargo that reflects the functional state of the cells of origin. These characteristics make them an attractive means of measuring disease-related processes within the central nervous system (CNS), as they cross the blood–brain barrier (BBB) and can be captured in peripheral blood. In this review, we discuss recent progress made toward identifying blood-based protein and RNA biomarkers of several neurodegenerative diseases from circulating, CNS cell-derived exosomes. Given the lack of standardized methodology for exosome isolation and characterization, we discuss the challenges of capturing and quantifying the molecular content of exosome populations from blood for translation to clinical use.
Surgery induces neurocognitive disorder via neuroinflammation and glymphatic dysfunction in middle-aged mice with brain lymphatic drainage impairment
Authors: Zhu Xiaoqiu , Lin Jingrun , Yang Pengfeng , Wu Shaotao , Lin Huijun , He Wen , Lin Daowei , Cao Minghui
Published: June 2024

Background

Brain lymphatic drainage impairment is a prevalent characteristic in both aging and neurodegeneration. Surgery is more likely to induce excessive neuroinflammation and postoperative neurocognitive disorder (PND) among patients with aging and neurodegeneration. We hypothesized that surgical trauma may aggravate PND through preexisting cerebral lymphatic drainage impairment. However, there remains limited understanding about the role of surgery in changes of neurocognitive function in the populations with preoperative brain lymphatic drainage impairment. This study aims to expand our insight into surgery-induced glymphatic dysfunction, neuroinflammation and PND in middle-aged mice with preoperative brain lymphatic drainage impairment.

Materials and methods

Deep cervical lymph nodes ligation (LdcLNs) was performed on middle-aged mice to establish preoperative brain lymphatic drainage impairment. A month later, laparotomy was performed on these mice with or without LdcLNs followed by analysis of brain neuroinflammation, glymphatic function, neuronal damage, and behavioral test.

Results

LdcLNs disrupted meningeal lymphatic drainage. In middle-aged mice with LdcLNs, surgery exacerbated more serious glymphatic dysfunction accompanied by aggravation of A1 astrocytes activation and AQP4 depolarization. Furthermore, surgery caused neuronal damage via reducing expression of neuronal nuclei (NeuN), post-synaptic density protein 95 (PSD95) and synaptophysin (SYP), as well as impairment in exploratory behavior and spatial working memory in middle-aged mice with LdcLNs. Additionally, surgery induced neuroinflammation with elevated microglia activation and increased the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6, as well as activated more expression of HMGB1/TLR-4/NF-κB pathway in middle-aged mice with LdcLNs.

Conclusion

Surgery exacerbates neuroinflammation and glymphatic dysfunction, ultimately resulting in neuronal damage and neurocognitive disorder in middle-aged mice with preoperative brain lymphatic drainage impairment. These results suggest that brain lymphatic drainage impairment may be a deteriorating factor in the progression of PND, and restoring its function may serve as a potential strategy against PND.
Frontier and hot topics in home enteral nutrition based on CiteSpace bibliometric analysis
Authors: Qin Shuwen , Chen Qin , Huang Jingjing , Xu Dandan , Hu Kangkang , Suo Yaxi , Hu Qin , Peng Yangyao
Published: June 2024

Background

The benefits of home enteral nutrition (HEN) are increasingly recognized, with more scholars focusing on this field. This study aimed to comprehensively identify collaborative networks, analyze, and track research trends, focus on current hotspots, and accurately predict the forefront and focus of home enteral nutrition.

Methods

A computer search of the Web of Science Core Collection (WoSCC) was conducted for studies related to home enteral nutrition published from January 1, 2004, to December 31, 2023, and select them in compliance with the PRISMA guidelines. The CiteSpace software was used for bibliometric visualization and comparative analysis of countries, institutions, journals, references, and keywords.

Results

A total of 1,113 documents were included, showing a steady annual increase in publication volume. The United States and the Mayo Clinic were the top publishing country and institution, with 302 and 41 papers, respectively. “CLIN NUTR” had the highest number of publications, totaling 221, while “ESPEN guideline on home enteral nutrition” was the most cited reference, with 43 citations. The most prolific author was Manpreet S with 29 papers.

Conclusion

The management of HEN is a current research hotspot. The safety of HEN and how to improve patient compliance are critical areas for researchers to consider. Future research could focus on these aspects. The blurring of boundaries between hospital and home care and how to utilize telemedicine technologies to serve more patients deserve in-depth exploration. Researchers worldwide should combine their unique characteristics and advantages to strengthen international cooperation.
Protein and amino acid digestibility: definitions and conventional oro-ileal determination in humans
Authors: Hodgkinson Suzanne M.
Published: June 2024

When assessing protein quality, a correction needs to be made to take into consideration the availability of the amino acids. This correction is based on the digestibility of the amino acids. It is recommended to use ileal (end of small intestine) digestibility as opposed to faecal digestibility. A correction needs to be made for endogenous (gut sourced as opposed to diet sourced) amino acids to give true digestibility as opposed to apparent digestibility. Also, this correction should be made by correcting the amino acid composition for individual amino acid digestibilities as opposed to correcting all amino acids for nitrogen digestibility. Determination of true ileal amino acid digestibility requires the collection of ileal digesta. In the human there are two methods that can be used; naso-ileal intubation and using the ileostomy model. Both are discussed in detail and it is concluded that both are appropriate methods to collect ileal digesta.
Values of a novel comprehensive prognostic nutritional index (FIDA) in the prognosis of non-small cell lung cancer
Authors: Qiao Han , Feng Yan , Han Xiaolei , Tang Huaping
Published: June 2024

Background

This study focuses on determining the prognostic and predictive value of the comprehensive prognostic nutrition index (FIDA) in individuals undergoing treatment for Non-Small-Cell Lung Carcinoma (NSCLC).

Methods

This retrospective analysis encompassed 474 of NSCLC patients treated from January 2010 through December 2019. Employing the Lasso-COX regression approach, eight blood parameters were identified as significant prognostic indicators. These parameters contributed to the formulation of the comprehensive prognostic nutrition index FIDA. Utilizing X-tile software, the patient cohort was categorized into either a high or low FIDA group based on an established optimal threshold. The cohort was then randomly segmented into a training set and a validation set using SPSS software. Subsequent steps involved conducting univariate and multivariate regression analyze to develop a prognostic nomogram. The effectiveness of this nomogram was evaluated by calculating the AUC.

Results

Analysis of survival curves for both the training and validation sets revealed a poorer prognosis in the high FIDA group compared to the low FIDA group. This trend persisted across various subgroups, including gender, age, and smoking history, with a statistical significance (p<0.05). Time-dependent ROC and diagnostic ROC analyses affirmed that FIDA serves as an effective diagnostic and prognostic marker in NSCLC. Moreover, Cox regression multivariate analysis established FIDA as an independent prognostic factor for NSCLC. The prognostic nomogram, integrating FIDA and clinical data, demonstrated substantial prognostic utility and outperformed the traditional TNM staging systemin predicting overall survival (OS).

Conclusion

FIDA emerges as a dependable predictor of outcomes for patients with NSCLC. It offers a practical, cost-effective tool for prognostication in regular clinical applications.
Myelofibrosis and allogeneic transplantation: critical points and challenges
Authors: Ranalli Paola , Natale Annalisa , Guardalupi Francesco , Santarone Stella , Cantò Chiara , La Barba Gaetano , Di Ianni Mauro
Published: June 2024

New available drugs allow better control of systemic symptoms associated with myelofibrosis (MF) and splenomegaly but they do not modify the natural history of progressive and poor prognosis disease. Thus, hematopoietic stem cell transplantation (HSCT) is still considered the only available curative treatment for patients with MF. Despite the increasing number of procedures worldwide in recent years, HSCT for MF patients remains challenging. An increasingly complex network of the patient, disease, and transplant-related factors should be considered to understand the need for and the benefits of the procedure. Unfortunately, prospective trials are often lacking in this setting, making an evidence-based decision process particularly arduous. In the present review, we will analyze the main controversial points of allogeneic transplantation in MF, that is, the development of more sophisticated models for the identification of eligible patients; the need for tools offering a more precise definition of expected outcomes combining comorbidity assessment and factors related to the procedure; the decision-making process about the best transplantation time; the evaluation of the most appropriate platform for curative treatment; the impact of splenomegaly; and splenectomy on outcomes.
Water decoction of Pericarpium citri reticulatae and Amomi fructus ameliorates alcohol-induced liver disease involved in the modulation of gut microbiota and TLR4/NF-κB pathway
Authors: Zhang Xing-Min , Huang Yue-Chang , Chen Bai-Zhong , Li Qian , Wu Pan-Pan , Chen Wen-Hua , Wu Ri-Hui , Li Chen
Published: June 2024

Introduction

Alcohol consumption alters the diversity and metabolic activities of gut microbiota, leading to intestinal barrier dysfunction and contributing to the development of alcoholic liver disease (ALD), which is the most prevalent cause of advanced liver diseases. In this study, we investigated the protective effects and action mechanism of an aqueous extraction of Pericarpium citri reticulatae and Amomi fructus (PFE) on alcoholic liver injury.

Methods

C57BL/6 mice were used to establish the mouse model of alcoholic liver injury and orally administered 500 and 1,000 mg/kg/d of PFE for 2 weeks. Histopathology, immunohistochemistry, immunofluorescence, Western blotting, qRT-PCR, and 16S rDNA amplicon sequencing were used to analyze the mechanism of action of PFE in the treatment of alcohol-induced liver injury.

Results

Treatment with PFE significantly improved alcohol-induced liver injury, as illustrated by the normalization of serum alanine aminotransferase, aspartate aminotransferase, total triglyceride, and cholesterol levels in ALD mice in a dose-dependent manner. Administration of PFE not only maintained the intestinal barrier integrity prominently by upregulating mucous production and tight junction protein expressions but also sensibly reversed the dysregulation of intestinal microecology in alcohol-treated mice. Furthermore, PFE treatment significantly reduced hepatic lipopolysaccharide (LPS) and attenuated oxidative stress as well as inflammation related to the TLR4/NF-κB signaling pathway. The PFE supplementation also significantly promoted the production of short-chain fatty acids (SCFAs) in the ALD mice.

Conclusion

Administration of PFE effectively prevents alcohol-induced liver injury and may also regulate the LPS-involved gut–liver axis; this could provide valuable insights for the development of drugs to prevent and treat ALD.
Suppression by central adenosine A3 receptors of the cholinergic defense against cardiovascular aberrations of sepsis: role of PI3K/MAPKs/NFκB signaling
Authors: El-Naggar Amany E. , Helmy Mai M. , El-Gowilly Sahar M. , El-Mas Mahmoud M.
Published: June 2024

Introduction: Despite the established role of peripheral adenosine receptors in sepsis-induced organ dysfunction, little or no data is available on the interaction of central adenosine receptors with sepsis. The current study tested the hypothesis that central adenosine A3 receptors (A3ARs) modulate the cardiovascular aberrations and neuroinflammation triggered by sepsis and their counteraction by the cholinergic antiinflammatory pathway.

Methods: Sepsis was induced by cecal ligation and puncture (CLP) in rats pre-instrumented with femoral and intracisternal (i.c.) catheters for hemodynamic monitoring and central drug administration, respectively.

Results: The CLP-induced hypotension, reduction in overall heart rate variability (HRV) and sympathovagal imbalance towards parasympathetic predominance were abolished by i.v. nicotine (100 μg/kg) or i.c. VUF5574 (A3AR antagonist, 2 µg/rat). In addition, the selective A3AR agonist, 3-iodobenzyl-5′-N-methylcarboxamidoadenosine IB-MECA, 4 µg/rat, i.c.) exaggerated the hypotension and cardiac autonomic dysfunction induced by sepsis and opposed the favorable nicotine actions against these septic manifestations. Immunohistochemically, IB-MECA abolished the nicotine-mediated downregulation of NFκB and NOX2 expression in rostral ventrolateral medullary areas (RVLM) of brainstem of septic rats. The inhibitory actions of IB-MECA on nicotine responses disappeared after i.c. administration of PD98059 (MAPK-ERK inhibitor), SP600125 (MAPK-JNK inhibitor) or wortmannin (PI3K inhibitor). Moreover, infliximab (TNFα inhibitor) eliminated the IB-MECA-induced rises in RVLM-NFκB expression and falls in HRV, but not blood pressure.

Conclusion: Central PI3K/MAPKs pathway mediates the A3AR counteraction of cholinergic defenses against cardiovascular and neuroinflammatory aberrations in sepsis.
Assessment of the effect of 21-day head-down bed rest on the cardiovascular system by blood protein composition
Authors: Kashirina Daria N. , Pastushkova Ludmila Kh. , Goncharova Anna G. , Larina Irina M.
Published: June 2024

Head-down bed rest (HDBR) is one of the models of the physiological effects of weightlessness used, among other things, to assess the effect of hypokinesia on the physiological systems of the human body and, first of all, on the cardiovascular system. The aim of the work was to study the effect of 21 days of HDBR factors on the cardiovascular system based on blood proteomic profile data. It was revealed that HDBR conditions led to an increase in the levels of proteins of the complement and the coagulation cascade systems, platelet degranulation, fibrinolysis, acute phase proteins, post-translational modification of proteins, retinol-binding protein 4 (RBP4), apolipoprotein B, which are associated with cardiovascular diseases, and other proteins that affect the functions of endothelial cells. Blood levels of proteins involved in cytoskeletal remodelling, oxygen transport, heme catabolism, etc. have been shown to decrease during HDBR.
Introgression of an adult-plant powdery mildew resistance gene Pm4VL from Dasypyrum villosum chromosome 4V into bread wheat
Authors: Wei Yi , Zhang Ting , Jin Yinyu , Li Wen , Kong Lingna , Liu Xiaoxue , Xing Liping , Cao Aizhong , Zhang Ruiqi
Published: June 2024

Powdery mildew caused by Blumeria graminis f. sp. tritici (Bgt) seriously threatens wheat production worldwide. It is imperative to identify novel resistance genes from wheat and its wild relatives to control this disease by host resistance. Dasypyrum villosum (2n = 2x = 14, VV) is a relative of wheat and harbors novel genes for resistance against multi-fungal diseases. In the present study, we developed a complete set of new wheat-D. villosum disomic introgression lines through genomic in situ hybridization (GISH), fluorescence in situ hybridization (FISH) and molecular markers analysis, including four disomic substitution lines (2n=42) containing respectively chromosomes 1V#6, 2V#6, 3V#6, and 6V#6, and four disomic addition lines (2n=44) containing respectively chromosomes 4V#6, 5V#6, 6V#6 and 7V#6. These lines were subsequently evaluated for their responses to a mixture Bgt isolates at both seedling and adult-plant stages. Results showed that introgression lines containing chromosomes 3V#6, 5V#6, and 6V#6 exhibited resistance at both seedling and adult-plant stages, whereas the chromosome 4V#6 disomic addition line NAU4V#6-1 exhibited a high level of adult plant resistance to powdery mildew. Moreover, two translocation lines were further developed from the progenies of NAU4V#6-1 and the Ph1b mutation line NAU0686-ph1b. They were T4DL·4V#6S whole-arm translocation line NAU4V#6-2 and T7DL·7DS-4V#6L small-fragment translocation line NAU4V#6-3. Powdery mildew tests of the two lines confirmed the presence of an adult-plant powdery mildew resistance gene, Pm4VL, located on the terminal segment of chromosome arm 4V#6L (FL 0.6-1.00). In comparison with the recurrent parent NAU0686 plants, the T7DL·7DS-4V#6L translocation line NAU4V#6-3 showed no obvious negative effect on yield-related traits, providing a new germplasm in breeding for resistance.
Transcriptome- and genome-wide systematic identification of expansin gene family and their expression in tuberous root development and stress responses in sweetpotato (Ipomoea batatas)
Authors: Zhang Jianling , Dong Tingting , Zhu Mingku , Du Dan , Liu Ranran , Yu Qianqian , Sun Yueying , Zhang Zhihuan
Published: June 2024

Introduction

Expansins (EXPs) are essential components of the plant cell wall that function as relaxation factors to directly promote turgor-driven expansion of the cell wall, thereby controlling plant growth and development and diverse environmental stress responses. EXPs genes have been identified and characterized in numerous plant species, but not in sweetpotato.

Results and methods

In the present study, a total of 59 EXP genes unevenly distributed across 14 of 15 chromosomes were identified in the sweetpotato genome, and segmental and tandem duplications were found to make a dominant contribution to the diversity of functions of the IbEXP family. Phylogenetic analysis showed that IbEXP members could be clustered into four subfamilies based on the EXPs from Arabidopsis and rice, and the regularity of protein motif, domain, and gene structures was consistent with this subfamily classification. Collinearity analysis between IbEXP genes and related homologous sequences in nine plants provided further phylogenetic insights into the EXP gene family. Cis-element analysis further revealed the potential roles of IbEXP genes in sweetpotato development and stress responses. RNA-seq and qRT-PCR analysis of eight selected IbEXPs genes provided evidence of their specificity in different tissues and showed that their transcripts were variously induced or suppressed under different hormone treatments (abscisic acid, salicylic acid, jasmonic acid, and 1-aminocyclopropane-1-carboxylic acid) and abiotic stresses (low and high temperature).

Discussion

These results provide a foundation for further comprehensive investigation of the functions of IbEXP genes and indicate that several members of this family have potential applications as regulators to control plant development and enhance stress resistance in plants.
Cognitive simulation along with neural adaptation explain effects of suggestions: a novel theoretical framework
Authors: Zahedi Anoushiravan , Lynn Steven Jay , Sommer Werner
Published: June 2024

Hypnosis is an effective intervention with proven efficacy that is employed in clinical settings and for investigating various cognitive processes. Despite their practical success, no consensus exists regarding the mechanisms underlying well-established hypnotic phenomena. Here, we suggest a new framework called the Simulation-Adaptation Theory of Hypnosis (SATH). SATH expands the predictive coding framework by focusing on (a) redundancy elimination in generative models using intrinsically generated prediction errors, (b) adaptation due to amplified or prolonged neural activity, and (c) using internally generated predictions as a venue for learning new associations. The core of our treatise is that simulating proprioceptive, interoceptive, and exteroceptive signals, along with the top-down attenuation of the precision of sensory prediction errors due to neural adaptation, can explain objective and subjective hypnotic phenomena. Based on these postulations, we offer mechanistic explanations for critical categories of direct verbal suggestions, including (1) direct-ideomotor, (2) challenge-ideomotor, (3) perceptual, and (4) cognitive suggestions. Notably, we argue that besides explaining objective responses, SATH accounts for the subjective effects of suggestions, i.e., the change in the sense of agency and reality. Finally, we discuss individual differences in hypnotizability and how SATH accommodates them. We believe that SATH is exhaustive and parsimonious in its scope, can explain a wide range of hypnotic phenomena without contradiction, and provides a host of testable predictions for future research.
High-income ZIP codes in New York City demonstrate higher case rates during off-peak COVID-19 waves
Authors: Tung Steven T. L. , Perveen Mosammat M. , Wohlars Kirsten N. , Promisloff Robert A. , Lee-Wong Mary F. , Szema Anthony M.
Published: June 2024

Introduction

Our study explores how New York City (NYC) communities of various socioeconomic strata were uniquely impacted by the COVID-19 pandemic.

Methods

New York City ZIP codes were stratified into three bins by median income: high-income, middle-income, and low-income. Case, hospitalization, and death rates obtained from NYCHealth were compared for the period between March 2020 and April 2022.

Results

COVID-19 transmission rates among high-income populations during off-peak waves were higher than transmission rates among low-income populations. Hospitalization rates among low-income populations were higher during off-peak waves despite a lower transmission rate. Death rates during both off-peak and peak waves were higher for low-income ZIP codes.

Discussion

This study presents evidence that while high-income areas had higher transmission rates during off-peak periods, low-income areas suffered greater adverse outcomes in terms of hospitalization and death rates. The importance of this study is that it focuses on the social inequalities that were amplified by the pandemic.
Impact of mobile Internet use on health-seeking behaviors: evidence from China
Authors: Lin ChenLei , Lin Hong
Published: June 2024

Introduction

Although health-seeking behaviors are crucial to China’s healthcare delivery system, the influence of mobile Internet use in this context remains under-explored. This study aimed to comprehensively explore the influence of mobile Internet use on health-seeking behaviors, and meticulously examined the heterogeneity in health outcomes associated with the intersection between mobile Internet use and health-seeking behaviors.

Methods

We used nationally representative data derived from the China Family Panel Studies. Given that individuals typically make the decision to use mobile Internet autonomously, an instrumental variable regression methodology was adopted to mitigate potential selection biases.

Results

Our findings revealed that mobile Internet use significantly promoted self-medication and adversely affected the use of primary care facilities among Chinese adults. Furthermore, our findings highlighted the heterogeneous effects of mobile Internet use across diverse health demographic groups.

Conclusion

These findings underscore the importance of strategic planning and utilizing mobile Internet resources to steer individuals toward more appropriate healthcare-seeking behaviors.
Effects of dietary selenium deficiency and supplementation on liver in grazing sheep: insights from transcriptomic and metabolomic analysis
Authors: Jin Xiwei , Meng Lingbo , Qi Zhi , Mi Lan
Published: June 2024

Background

Mineral elements play a crucial role in supporting the life activities and physiological functions of animals. However, numerous studies have revealed that in some geographical areas and certain grazing situations, grazing livestock frequently suffers from mineral element deficiencies due to the loss of mineral elements from grassland forages, such as selenium (Se). To shed fresh light on this issue, this study aims to investigate the impact of dietary Se deficiency and supplementation on the liver of grazing sheep in these challenging conditions.

Method

This study involved 28 grazing Mongolian Wu Ranke sheep with an average body weight of about 32.20 ± 0.37 kg, which were divided into the Se treatment group and the control group. The Se treatment group was fed with the low-Se diet for 60 days and then continued to be fed with the high-Se diet for 41 days. The liver concentration of minerals, transcriptomic analysis, and untargeted metabolomic analysis were conducted to assess the impact of Se deficiency and supplementation on the liver of grazing sheep.

Results

Dietary Se deficiency and supplementation significantly reduced and elevated liver concentration of Se, respectively (p < 0.05). Gene functional enrichment analysis suggested that dietary Se deficiency might impair protein synthesis efficiency, while Se supplementation was found to enhance liver protein synthesis in grazing sheep. AGAP1, ERN1, MAL2, NFIC, and RERG were identified as critical genes through the weighted gene correlation network analysis, the quantitative real-time polymerase chain reaction, and the receiver operating characteristic curve validation that could potentially serve as biomarkers. Metabolomics analysis revealed that dietary Se deficiency significantly reduced the abundance of metabolites such as 5-hydroxytryptamine, while dietary Se supplementation significantly elevated the abundance of metabolites such as 5-hydroxytryptophan (p < 0.05).

Conclusion

Integrative analysis of the transcriptome and metabolome revealed that dietary Se deficiency led to reduced hepatic antioxidant and anti-inflammatory capacity, whereas Se supplementation increased the hepatic antioxidant and anti-inflammatory capacity in grazing Wu Ranke sheep. These findings provide new insights into the effects of dietary Se deficiency and supplementation on the liver of grazing sheep, potentially leading to improved overall health and well-being of grazing livestock.
Prognostic value of lung immune prognostic index in non-small cell lung cancer patients receiving immune checkpoint inhibitors: a meta-analysis
Authors: Wang Yi , Lei Yu , Zheng Delai , Yang Yanhui , Luo Lei , Li Ji , Xie Xiaoyang
Published: June 2024

Background and Purpose

Until now, it has been difficult to accurately predict the efficacy of immunotherapy in patients with non-small cell lung cancer (NSCLC). A novel indicator, the lung immune prognostic index (LIPI), has shown relatively high prognostic value in patients with solid cancer. Therefore, this study aimed to further identify the association between LIPI and the survival of patients with NSCLC who receive immune checkpoint inhibitors (ICIs).

Methods

Several electronic databases were searched for available publications up to April 23, 2023. Immunotherapy outcomes included overall survival (OS), progression-free survival (PFS), and hazard ratios (HRs) with 95% confidence intervals (CIs). Subgroup analysis based on the study design and comparison of the LIPI was conducted.

Results

In this meta-analysis, 21 studies with 9,010 patients were included in this meta-analysis. The pooled results demonstrated that elevated LIPI was significantly associated with poor OS (HR = 2.50, 95% CI:2.09–2.99, p < 0.001) and PFS (HR = 1.77, 95% CI:1.64–1.91, p < 0.001). Subgroup analyses stratified by study design (retrospective vs. prospective) and comparison of LIPI (1 vs. 0, 2 vs. 0, 1–2 vs. 0, 2 vs. 1 vs. 0, 2 vs. 0–1 and 2 vs. 1) showed similar results.

Conclusion

LIPI could serve as a novel and reliable prognostic factor in NSCLC treated with ICIs, and elevated LIPI predicts worse prognosis.