bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanisms of alkaliptosis
Authors: Chen Fangquan , Kang Rui , Liu Jiao , Tang Daolin
Published: August 2023

Malignant tumors represent a major threat to global health and the search for effective treatments is imperative. While various treatments exist, including surgery, radiotherapy, chemotherapy, immunotherapy and combination therapies, there remains a need to develop therapies that target regulated cell death pathways to eliminate cancer cells while preserving normal cells. Alkaliptosis, a pH-dependent cell death process triggered by the small molecular compound JTC801, has been identified as a novel approach for malignant tumor treatment, particularly in pancreatic cancer. Two major signaling pathways, the NF-κB-CA9 pathway and the ATP6V0D1-STAT3 pathway, contribute to the induction of alkaliptosis. This review summarizes recent developments in our understanding of alkaliptosis signals, mechanisms, and modulation, and explores its context-dependent effects on drug resistance, inflammation, and immunity. By providing a deeper understanding of the heterogeneity and plasticity of cell death mechanisms, this information holds promise for informing the design of more effective anti-tumor therapies.
NMJ-related diseases beyond the congenital myasthenic syndromes
Authors: Navarro-Martínez Alejandra , Vicente-García Cristina , Carvajal Jaime J.
Published: August 2023

Neuromuscular junctions (NMJs) are a special type of chemical synapse that transmits electrical stimuli from motor neurons (MNs) to their innervating skeletal muscle to induce a motor response. They are an ideal model for the study of synapses, given their manageable size and easy accessibility. Alterations in their morphology or function lead to neuromuscular disorders, such as the congenital myasthenic syndromes, which are caused by mutations in proteins located in the NMJ. In this review, we highlight novel potential candidate genes that may cause or modify NMJs-related pathologies in humans by exploring the phenotypes of hundreds of mouse models available in the literature. We also underscore the fact that NMJs may differ between species, muscles or even sexes. Hence the importance of choosing a good model organism for the study of NMJ-related diseases: only taking into account the specific features of the mammalian NMJ, experimental results would be efficiently translated to the clinic.
Regulation of insulin secretion by the post-translational modifications
Authors: Yang Chunhua , Wei Mengna , Zhao Yanpu , Yang Zhanyi , Song Mengyao , Mi Jia , Yang Xiaoyong , Tian Geng
Published: August 2023

Post-translational modification (PTM) has a significant impact on cellular signaling and function regulation. In pancreatic β cells, PTMs are involved in insulin secretion, cell development, and viability. The dysregulation of PTM in β cells is clinically associated with the development of diabetes mellitus. Here, we summarized current findings on major PTMs occurring in β cells and their roles in insulin secretion. Our work provides comprehensive insight into understanding the mechanisms of insulin secretion and potential therapeutic targets for diabetes from the perspective of protein PTMs.
The role of epigenetic changes in the pathology and treatment of inherited retinal diseases
Authors: Miller Annie L. , James Rebekah E. , Harvey Alan R. , Trifunović Dragana , Carvalho Livia S.
Published: August 2023

Elucidation of the cellular changes that occur in degenerating photoreceptors of people with inherited retinal diseases (IRDs) has been a focus for many research teams, leading to numerous theories on how these changes affect the cell death process. What is clearly emerging from these studies is that there are common denominators across multiple models of IRD, regardless of the underlying genetic mutation. These common markers could open avenues for broad neuroprotective therapeutics to prevent photoreceptor loss and preserve functional vision. In recent years, the role of epigenetic modifications contributing to the pathology of IRDs has been a particular point of interest, due to many studies noting changes in these epigenetic modifications, which coincide with photoreceptor cell death. This review will discuss the two broad categories of epigenetic changes, DNA methylation and histone modifications, that have received particular attention in IRD models. We will review the altered epigenetic regulatory events that are believed to contribute to cell death in IRDs and discuss the therapeutic potential of targeting these alterations.
The significance of ERK5 catalytic-independent functions in disease pathways
Authors: Le Nhat-Tu
Published: August 2023

Extracellular signal-regulated kinase 5 (ERK5), also known as BMK1 or MAPK7, represents a recent addition to the classical mitogen-activated protein kinase (MAPK) family. This family includes well-known members such as ERK1/2, c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38 MAPK), as well as atypical MAPKs such as ERK3, ERK4, ERK7 (ERK8), and Nemo-like kinase (NLK). Comprehensive reviews available elsewhere provide detailed insights into ERK5, which interested readers can refer to for in-depth knowledge (Nithianandarajah-Jones et al., 2012; Monti et al., Cancers (Basel), 2022, 14). The primary aim of this review is to emphasize the essential characteristics of ERK5 and shed light on the intricate nature of its activation, with particular attention to the catalytic-independent functions in disease pathways.
Mode of action studies confirm on-target engagement of lysyl-tRNA synthetase inhibitor and lead to new selection marker for Cryptosporidium
Authors: Hanna Jack C. , Corpas-Lopez Victor , Seizova Simona , Colon Beatrice L. , Bacchetti Ross , Hall Grant M. J. , Sands Emma M. , Robinson Lee , Baragaña Beatriz , Wyllie Susan , Pawlowic Mattie C.
Published: August 2023

Introduction

Cryptosporidiosis is a leading cause of diarrheal-associated morbidity and mortality, predominantly affecting children under 5 years old in low-and-middle-income countries. There is no effective treatment and no vaccine. New therapeutics are emerging from drug discovery efforts. It is critical that mode of action studies are performed alongside drug discovery to ensure the best clinical outcomes. Unfortunately, technology to identify and validate drug targets for Cryptosporidium is severely lacking.

Methods

We used C. parvum lysyl-tRNA synthetase (CpKRS) and DDD01510706 as a target-compound pair to develop both chemical and genetic tools for mode of action studies for Cryptosporidium. We adapted thermal proteome profiling (TPP) for Cryptosporidium, an unbiased approach for target identification.

Results

Using TPP we identified the molecular target of DDD01510706 and confirm that it is CpKRS. Genetic tools confirm that CpKRS is expressed throughout the life cycle and that this target is essential for parasite survival. Parasites genetically modified to over-express CpKRS or parasites with a mutation at the compound-binding site are resistant to treatment with DDD01510706. We leveraged these mutations to generate a second drug selection marker for genetic modification of Cryptosporidium, KRSR. This second selection marker is interchangeable with the original selection marker, NeoR, and expands the range of reverse genetic approaches available to study parasite biology. Due to the sexual nature of the Cryptosporidium life cycle, parental strains containing different drug selection markers can be crossed in vivo.

Discussion

Selection with both drug markers produces highly efficient genetic crosses (>99% hybrid progeny), paving the way for forward genetics approaches in Cryptosporidium.
Compelled and constrained migration: restrictions to migration agency in the Marshall Islands
Authors: Roland Hugh B.
Published: August 2023

Migration as adaptation implies agency, yet environmental and non-environmental factors and their interactions may limit the availability of adaptation options, including migration. This study investigates migration agency in the Marshall Islands, particularly the role of geographic isolation and climate change. Interviews with internal migrants living in Majuro and members of government and civil society reveal how social, economic, cultural, and environmental factors shape migration contexts. Results suggest that geographic isolation-related factors may increase likelihoods of simultaneously more compelled and more constrained moves, particularly as climate change impacts increase. Climate change-related impacts on resource-dependent livelihoods may compel migration in search of new economic opportunities. However, worsening environmental conditions may also exacerbate cost-related migration constraints by reducing the resources available to support migration.
Cardiovascular mortality by cancer risk stratification in patients with localized prostate cancer: a SEER-based study
Authors: Luo Zehao , Chi Kaiyi , Zhao Hongjun , Liu Linglong , Yang Wenting , Luo Zhijuan , Liang Yinglan , Zeng Liangjia , Zhou Ruoyun , Feng Manting , Li Yemin , Hua Guangyao , Rao Huying , Lin Xiaozhen , Yi Min
Published: August 2023

Purpose

The risk of cardiovascular disease (CVD) mortality in patients with localized prostate cancer (PCa) by risk stratification remains unclear. The aim of this study was to determine the risk of CVD death in patients with localized PCa by risk stratification.

Patients and methods

Population-based study of 340,806 cases in the Surveillance, Epidemiology, and End Results (SEER) database diagnosed with localized PCa between 2004 and 2016. The proportion of deaths identifies the primary cause of death, the competing risk model identifies the interaction between CVD and PCa, and the standardized mortality rate (SMR) quantifies the risk of CVD death in patients with PCa.

Results

CVD-related death was the leading cause of death in patients with localized PCa, and cumulative CVD-related death also surpassed PCa almost as soon as PCa was diagnosed in the low- and intermediate-risk groups. However, in the high-risk group, CVD surpassed PCa approximately 90 months later. Patients with localized PCa have a higher risk of CVD-related death compared to the general population and the risk increases steadily with survival (SMR = 4.8, 95% CI 4.6–5.1 to SMR = 13.6, 95% CI 12.8–14.5).

Conclusions

CVD-related death is a major competing risk in patients with localized PCa, and cumulative CVD mortality increases steadily with survival time and exceeds PCa in all three stratifications (low, intermediate, and high risk). Patients with localized PCa have a higher CVD-related death than the general population. Management of patients with localized PCa requires attention to both the primary cancer and CVD.
On the correlations between the largest foreshocks and mainshocks of earthquake sequences in Taiwan
Authors: Chen Kou-Cheng , Kim Kwang-Hee , Wang Jeen-Hwa
Published: August 2023

We collected a data set of mainshocks and their respective largest foreshocks of 38 earthquake sequences in Taiwan. The plot of local magnitude, ML, of a mainshock (denoted by MLm) versus ML of its largest foreshock (denoted by MLf) shows an increase in MLm with MLf. This indicates that for Taiwan’s earthquakes the bigger the largest foreshock is, the larger the mainshock is. The plot of the epicentral distance, Δ (in km), from the largest foreshock to the mainshock versus ML of the mainshock exhibits a weak increase in Δ with MLm as Δ<10 km. The plot of the focal depth of the largest foreshock and that of the mainshock shows a linear increase in the former along with the latter for most event-pairs. Let T be the interval between the occurrence time of the largest foreshock and the mainshock. The plot of T versus MLm exhibits that the mainshock will occur within 5 days, with the highest probability of 1 day, after the occurrence of the largest foreshock. Let H be the hypocentral distance between the largest foreshock and the mainshock. The plot of T versus H reveals a slight increase in T with H when T>1 day.
An app by students for students – the DPaCK-model for a digital collaborative teamwork project to identify butterflies
Authors: Baumann Birgit , Groß Jorge , Michelsen Malte
Published: August 2023

Acquiring digital literacy has become one of the most important tasks in school. But also acquiring species knowledge is an important task and essential to understand the value of biodiversity. In order to achieve this, a toolbox was developed to enable students to create an identification key on any group of living species. This can be either a species group of animals or plants or living creatures of the school ground. It is based on the interactive identification tool “ID-Logics” which was changed into an easy-to-use learning platform for the students. The students (n = 26, age 11–13, Gymnasium) were interviewed using the method of Retrospective Inquiry into Learning Process to capture changes in imagination. The results were analyzed and discussed using the DPaCK-Model. Based on the data, we can demonstrate the utility of the DPaCK-Model and discuss the implications for (biology) teaching. The DPaCK-Model proves to be a useful tool for analyzing this student project from the subject didactic perspective. Compared to the TPaCK-Model, digitality brings up new aspects, which we discuss in terms of the implications for (biology) teaching. In summary, the focus of the ID-Nature project is on: Collaboration, cooperation, and participation combined with publication, sharpening the eye for characteristic items for identification. And this is the new challenge of digitality. The orientation framework for the acquisition of digital competences developed for teacher education should also be seen as an enrichment for students. In accordance with these results, guidelines were set up for teaching digital literacy. The project is furthermore seen as an example for Education for sustainable Development (ESD).
Histone modifications in embryo implantation and placentation: insights from mouse models
Authors: Bi Shilei , Tu Zhaowei , Chen Dunjin , Zhang Shuang
Published: August 2023

Embryo implantation and placentation play pivotal roles in pregnancy by facilitating crucial maternal-fetal interactions. These dynamic processes involve significant alterations in gene expression profiles within the endometrium and trophoblast lineages. Epigenetics regulatory mechanisms, such as DNA methylation, histone modification, chromatin remodeling, and microRNA expression, act as regulatory switches to modulate gene activity, and have been implicated in establishing a successful pregnancy. Exploring the alterations in these epigenetic modifications can provide valuable insights for the development of therapeutic strategies targeting complications related to pregnancy. However, our current understanding of these mechanisms during key gestational stages remains incomplete. This review focuses on recent advancements in the study of histone modifications during embryo implantation and placentation, while also highlighting future research directions in this field.
Lesion-based indicators predict long-term outcomes of pheochromocytoma and paraganglioma– SIZEPASS
Authors: Hanschell Helena , Diaz-Cano Salvador , Blanes Alfredo , Talat Nadia , Galatá Gabriele , Aylwin Simon , Schulte Klaus Martin
Published: August 2023

Aim

We seek a simple and reliable tool to predict malignant behavior of pheochromocytoma and paraganglioma (PPGL).

Methods

This single-center prospective cohort study assessed size of primary PPGLs on preoperative cross-sectional imaging and prospectively scored specimens using the Pheochromocytoma of the Adrenal Gland Scaled Score (PASS). Multiplication of PASS points with maximum lesion diameter (in mm) yielded the SIZEPASS criterion. Local recurrence, metastasis or death from disease were surrogates defining malignancy.

Results

76 consecutive PPGL patients, whereof 58 with pheochromocytoma and 51 female, were diagnosed at a mean age of 52.0 ± 15.2 years. 11 lesions (14.5%) exhibited malignant features at a median follow-up (FU) of 49 months (range 4-172 mo). Median FU of the remaining cohort was 139 months (range 120-226 mo). SIZEPASS classified malignancy with an area under the curve (AUC) of 0.97 (95%CI 0.93-1.01; p<0.0001). Across PPGL, SIZEPASS >1000 outperformed all known predictors of malignancy, with sensitivity 91%, specificity 94%, and accuracy 93%, and an odds ratio of 72 fold (95%CI 9-571; P<0.001). It retained an accuracy >90% in cohorts defined by location (adrenal, extra-adrenal) or mutation status.

Conclusions

The SIZEPASS>1000 criterion is a lesion-based, clinically available, simple and effective tool to predict malignant behavior of PPGLs independently of age, sex, location or mutation status.
Monitoring and control of water-ecological space in the Dongting Lake region
Authors: Zeng Zhiwei , Yang Hua , Zhou Hui , Lai Nan , Song Qidi , Ji Qianfu , Ning Qimeng
Published: August 2023

The territorial spatial planning in the new era strengthens the control of different functional spaces and emphasizes integrated and coordinated development of each functional space. Therefore, it is important to monitor the “structure-function” characteristics of water-ecological space based on the context of territorial spatial planning and develop a management and control framework. Based on land use and social statistics, and with the help of ArcGIS analysis, this paper examined the structure and function of the water-ecological space in the Dongting Lake study for 2010, 2015, and 2020, generating a control framework and proposing key initiatives. The main results are as follows: 1) The overall scale of the water ecological space in the Dongting Lake study is over 7,300 km2. Water bodies had the largest share, followed by coastal terrestrial areas, while the land-water ecotone was the smallest. There was a small decrease in the water ecological space during the study period. Yueyang had the largest overall scale of water ecological space, while Linli had the smallest. 2) The comprehensive function of water ecological space in the Dongting Lake study was about 0.4000, increasing somewhat during the study period. Among the units, the comprehensive function value was highest in Yuanjiang City, while Jincheng City had the lowest. 3) From the structural elements of water ecological space, scientific planning of functional zoning of water ecological space should be carried out and combined with the delineation of “three zones and three lines.” Key initiatives such as multi-scale and multi-level planning and control, use control and access restrictions, determination of water ecological space ownership, pollution control and accountability, and comprehensive water ecological treatment and restoration should be promoted.
Assessments of TP53 and CTNNB1 gene hotspot mutations in circulating tumour DNA of hepatitis B virus-induced hepatocellular carcinoma
Authors: Kumar Sonu , Nadda Neeti , Quadri Afnan , Kumar Rahul , Paul Shashi , Tanwar Pranay , Gamanagatti Shivanand , Dash Nihar Ranjan , Saraya Anoop , Shalimar  , Nayak Baibaswata
Published: August 2023

Graphical Abstract

Created with BioRender.com.
Virus-specific and shared gene expression signatures in immune cells after vaccination in response to influenza and vaccinia stimulation
Authors: Quach Huy Quang , Goergen Krista M. , Grill Diane E. , Haralambieva Iana H. , Ovsyannikova Inna G. , Poland Gregory A. , Kennedy Richard B.
Published: August 2023

Background

In the vaccine era, individuals receive multiple vaccines in their lifetime. Host gene expression in response to antigenic stimulation is usually virus-specific; however, identifying shared pathways of host response across a wide spectrum of vaccine pathogens can shed light on the molecular mechanisms/components which can be targeted for the development of broad/universal therapeutics and vaccines.

Method

We isolated PBMCs, monocytes, B cells, and CD8+ T cells from the peripheral blood of healthy donors, who received both seasonal influenza vaccine (within <1 year) and smallpox vaccine (within 1 - 4 years). Each of the purified cell populations was stimulated with either influenza virus or vaccinia virus. Differentially expressed genes (DEGs) relative to unstimulated controls were identified for each in vitro viral infection, as well as for both viral infections (shared DEGs). Pathway enrichment analysis was performed to associate identified DEGs with KEGG/biological pathways.

Results

We identified 2,906, 3,888, 681, and 446 DEGs in PBMCs, monocytes, B cells, and CD8+ T cells, respectively, in response to influenza stimulation. Meanwhile, 97, 120, 20, and 10 DEGs were identified as gene signatures in PBMCs, monocytes, B cells, and CD8+ T cells, respectively, upon vaccinia stimulation. The majority of DEGs identified in PBMCs were also found in monocytes after either viral stimulation. Of the virus-specific DEGs, 55, 63, and 9 DEGs occurred in common in PBMCs, monocytes, and B cells, respectively, while no DEGs were shared in infected CD8+ T cells after influenza and vaccinia. Gene set enrichment analysis demonstrated that these shared DEGs were over-represented in innate signaling pathways, including cytokine-cytokine receptor interaction, viral protein interaction with cytokine and cytokine receptor, Toll-like receptor signaling, RIG-I-like receptor signaling pathways, cytosolic DNA-sensing pathways, and natural killer cell mediated cytotoxicity.

Conclusion

Our results provide insights into virus-host interactions in different immune cells, as well as host defense mechanisms against viral stimulation. Our data also highlights the role of monocytes as a major cell population driving gene expression in ex vivo PBMCs in response to viral stimulation. The immune response signaling pathways identified in this study may provide specific targets for the development of novel virus-specific therapeutics and improved vaccines for vaccinia and influenza. Although influenza and vaccinia viruses have been selected in this study as pathogen models, this approach could be applicable to other pathogens.
Outlook for CRISPR-based tuberculosis assays now in their infancy
Authors: Huang Zhen , Zhang Guoliang , Lyon Christopher J. , Hu Tony Y. , Lu Shuihua
Published: August 2023

Tuberculosis (TB) remains a major underdiagnosed public health threat worldwide, being responsible for more than 10 million cases and one million deaths annually. TB diagnosis has become more rapid with the development and adoption of molecular tests, but remains challenging with traditional TB diagnosis, but there has not been a critical review of this area. Here, we systematically review these approaches to assess their diagnostic potential and issues with the development and clinical evaluation of proposed CRISPR-based TB assays. Based on these observations, we propose constructive suggestions to improve sample pretreatment, method development, clinical validation, and accessibility of these assays to streamline future assay development and validation studies.
Machine learning-based on cytotoxic T lymphocyte evasion gene develops a novel signature to predict prognosis and immunotherapy responses for kidney renal clear cell carcinoma patients
Authors: Chen Mei , Nie Zhenyu , Huang Denggao , Gao Yuanhui , Cao Hui , Zheng Linlin , Zhang Shufang
Published: August 2023

Background

Immunotherapy resistance has become a difficult point in treating kidney renal clear cell carcinoma (KIRC) patients, mainly because of immune evasion. Currently, there is no effective signature to predict immunotherapy. Therefore, we use machine learning algorithms to construct a signature based on cytotoxic T lymphocyte evasion genes (CTLEGs) to predict the immunotherapy responses of patients, so as to screen patients effective for immunotherapy.

Methods

In public data sets and our in-house cohort, we used 10 machine learning algorithms to screen the optimal model with 89 combinations under the cross-validation framework, and 101 published signatures were collected. The relationship between the CTLEG signature (CTLEGS) and clinical variables was analyzed. We analyzed the role of CTLES in other types of cancer by pan-cancer analysis. The immune cell infiltration and biological characteristics were evaluated. Moreover, the response to immunotherapy and drug sensitivity of different risk groups were investigated. The key gene closely related to the signature was identified by WGCNA. We also conducted cell functional experiments and clinical tissue validation of key gene.

Results

In public data sets and our in-house cohort, the CTLEGS shows good prediction performance. The CTLEGS can be regard as an independent risk factor for KIRC. Compared with 101 published models, our signature shows considerable superiority. The high-risk group has abundant infiltration of immunosuppressive cells and high expression of T cell depletion markers, which are characterized by immunosuppressive phenotype, minimal benefit from immunotherapy, and resistance to sunitinib and sorafenib. The CTLEGS was also strongly correlated with immunity in pan-cancer. Immunohistochemistry verified that T cell depletion marker LAG3 is highly expressed in high-risk groups in the clinical in-house cohort. The key CTLEG STAT2 can promote the proliferation, migration and invasion of KIRC cell.

Conclusions

CTLEGS can accurately predict the prognosis of patients and their response to immunotherapy. It can provide guidance for the precise treatment of KIRC and help clinicians identify patients who may benefit from immunotherapy.
The effect of sequential perioperative intravenous tranexamic acid in reducing postoperative blood loss and hidden blood loss after posterior lumbar interbody fusion: a randomized controlled trial
Authors: Dong Wei , Liang Yi , Li Dongxu , Ma Zhaoxin , Cheng Minghuang , Zhang Xiaojun , Shen Jieliang , Zhou Nian , Hao Jie , Jiang Wei , Hu Zhenming
Published: August 2023

Background

Tranexamic acid (TXA) has previously been shown to be effective in reducing intraoperative blood loss (IBL) and transfusion requirements in spine surgery. A conventional TXA regimen is a simple preoperative or intraoperative administration. However, the hyperfibrinolysis caused by surgical trauma lasts at least 24 h, and a single dose of TXA cannot cover the whole process of hyperfibrinolysis. Moreover, its ability to control postoperative blood loss (PBL) may be insufficient. Therefore, this study aimed to explore the effects and safety of sequential perioperative intravenous TXA for reducing bleeding after posterior lumbar interbody fusion (PLIF).

Methods

Patients requiring PLIF were randomly divided into two groups. All patients were intravenously injected with 1 g of TXA 15 min before skin resection. Every day after the surgery, 200 ml saline was intravenously injected for 1–3 days in Group A, while Group B received 1 g of TXA instead of saline. The total blood loss (TBL), IBL, PBL, HCT, Hb, blood transfusion volume, inflammation-related indicators, and complications were recorded.

Results

TBL, PBL, and hidden blood loss (HBL) in Group B were significantly lower than those in Group A (P < 0.05). The maximum decreases in HCT and Hb in Group B were also significantly lower than those in Group A (P < 0.05), and the drainage removal time (DRT) was sooner in Group B than in Group A (P = 0.003). On the 3rd and 5th days after surgery, the level of CRP in Group B was significantly lower than that in Group A (P < 0.05). Similarly, IL-6 levels were significantly lower in Group B for the first 5 days postoperatively (P < 0.001). Sex, operation time, level of decompression, length of incision, and change in HCT were significant predictors of both TBL and HBL. TBL was also significantly associated with BMI and preoperative fibrinogen, while postoperative TXA was a significant predictor of HBL only.

Conclusion

Intravenous injection of 1 g of TXA 15 min before skin resection combined with continuous intravenous injection of 1 g of TXA 1 to 3 days after PLIF can reduce postoperative bleeding and shorten the time to drainage tube removal. In addition, it can also inhibit the postoperative inflammatory response.

Clinical trial registration

ChiCTR2200056210.
A posteriori diagnosis of DRESS syndrome induced by diazoxide in a patient with an insulinoma: a case report and review of the literature
Authors: Lassoued Najoua , Alaya Wafa , Arfa Sondos , Korbi Mouna , Lassoued Ines , Amor Soumaya Ben , Zaouali Fatma , Farhat Zayneb , Chelly Jihen , Habib Sfar Mohamed
Published: August 2023

The Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome can be potentially life-threatening. The diagnosis is sometimes difficult since the clinical manifestations may be incomplete or non-specific. Insulinoma is a rare functioning neuroendocrine tumor (NET) of the pancreas. Medical therapy may be needed when surgery is contraindicated, delayed or refused. Diazoxide is widely used to control hypoglycemia in patients with insulinoma. We report a clinical case of an insulinoma in a 85-year-old patient treated with diazoxide with a fatal outcome due to a delayed diagnosis of a DRESS syndrome. This is the first case of DRESS syndrome reported after using diazoxide for insulinoma treatment in our knowledge.
Multi-virulence of Campylobacter jejuni carried by chicken meat in Brazil
Authors: Peres Phelipe Augusto Borba Martins , de Melo Roberta Torres , Armendaris Paulo Marcel , Barreto Fabiano , Perin Tiago Follmann , Grazziotin Ana Laura , Monteiro Guilherme Paz , Buiatte Ana Beatriz Garcez , Mendonça Eliane Pereira , Lourenzatto Eduarda Cristina Alves , Bicalho Artur Slompo Muniz , Filho Marcelo de Vito , Rossi Daise Aparecida
Published: August 2023

Campylobacter jejuni is the most frequent cause of bacterial gastroenteritis; therefore, the characteristics of its epidemiology must be continuously investigated to support possible mitigating measures. This is particularly important when evaluating representative strains from the world's leading chicken meat exporter, Brazil. We evaluated a panel of 14 virulence genes in 359 strains of C. jejuni isolated from chilled broiler carcasses in Brazil. The genes were classified into five virulence categories (B: biofilm/motility; SS: secretion/cytotoxicity system; CI: invasion/colonization; GB: Guillain-Barré; and AE: adaptation to stress). The percentage of strains with stress adaptation genes (86.07%) indicates the ability to survive in unfavorable environments; in addition, the strains showed a risk of causing infections in humans due to the frequency of the hcp gene (97.77%). Genes related to Guillain-Barre syndrome (GBS) in 77.44% of strains are an additional concern, which must be monitored. The gene panel showed the presence of 124 virulence profiles. Individual analyses by carcass, slaughter establishment, and municipalities in which they were located showed high index variabilities (I.Var.) of 0.82, 0.87, and 0.78, respectively. Georeferencing indicated the state of Paraná as a hotspot for virulent strains. Higher levels of isolation and multi-virulence were identified in the summer, which is hot and humid in Brazil. Together, our results showed that the studied strains are a potential danger to public health and that there is an urgent need for their surveillance and the adoption of control measures, especially in the state of Paraná.
Deciphering growth abilities of fusarium oxysporum f. sp. pisi under variable temperature, pH and nitrogen
Authors: Chakrapani Kota , Chanu W. Tampakleima , Sinha Bireswar , Thangjam Bijeeta , Hasan Wajid , Devi Konjengbam Sarda , Chakma Tusi , Phurailatpam Sumitra , Mishra Lokesh Kumar , Singh Gopi Mohan , Khoyumthem Pramesh , Saini Rahul
Published: August 2023

Fusarium wilt caused by Fusarium oxysporum f. sp. pisi (Fop) is an important disease and major obstacle to pea production, causing huge losses to growers. The focus of this study was on isolation followed by morphological, molecular characterization and analyzing the growth of the casual agent under variable temperature, pH and Nitrogen levels. The morphological features of radial growth, sporulation, pigmentation and mycelial characterization were examined and the variability of all isolates was presented. Molecular characterization of the fungus by ITS rDNA sequencing revealed that all 13 isolates belong to Fusarium oxysporum species. Six isolates were tested for temperature, pH and nitrogen dosage optimization studies. Seven different temperatures, viz., 21, 23, 25, 27, 29, 31, 33°C and pH values, having 3, 4, 5, 6, 7, 8, and 9 pH, as well as nitrogen dosage levels of 0 g, 3 g, 5 g, 7 g, 9 g, 11 g, and 13 g were tested against all six isolates, respectively. The results showed that all isolates exhibited the highest growth at a temperature of 25°C and the optimal temperature range for growth of Fusarium oxysporum was 23–27°C. All isolates showed the highest growth at pH5. Change in the nitrogen doses of the base ended in formation of thick, dense, fluffy mycelium of the casual agent. Six isolates were used for combination studies with seven different levels of temperatures, pH levels and nitrogen dosages. The density plots revealed the variations in the growth of the isolates with changes in temperature, pH and nitrogen levels, which can lead to mutations or genetic changes in the pathogens that could potentially introduce new threats to pea cultivation.
Associations among multidomain lifestyles, chronic diseases, and dementia in older adults: a cross-sectional analysis of a cohort study
Authors: Zhang Jing-jing , Wu Zhao-xia , Tan Wei , Liu Dan , Cheng Gui-rong , Xu Lang , Hu Fei-fei , Zeng Yan
Published: August 2023

Background

Unhealthy lifestyles and chronic diseases are commonly seen and treatable factors in older adults and are both associated with dementia. However, the synergistic effect of the interaction of lifestyles and chronic diseases on dementia is unknown.

Methods

We determined independent associations of multidomain lifestyles and chronic diseases (cerebrovascular disease, diabetes, and hypertension) with dementia and examined their synergistic impact on dementia among older adults. The data were drawn from the Hubei Memory and Aging Cohort Study. We created a summary score of six factors for multidomain lifestyles. Dementia was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders IV. Logistic regression and multiple correspondence analyses were used to explore the relationships among multidomain lifestyles, chronic diseases, and dementia. A sensitivity analysis was performed to minimize the interference of reverse causality and potential confounders.

Results

Independent associations with dementia were found in unhealthy (OR = 1.90, 95% CI: 1.38–2.61) and intermediate healthy lifestyles (OR, 3.29, 2.32–4.68), hypertension (OR, 1.21, 1.01–1.46), diabetes (OR, 1.30, 1.04–1.63), and cerebrovascular disease (OR, 1.39, 1.12–1.72). Interactions of diabetes (p = 0.004), hypertension (p = 0.004), and lifestyles were significant, suggesting a combined impact on dementia. Sensitivity analysis supported the strong association among multidomain lifestyles, chronic diseases, and dementia prevalence.

Conclusion

An unhealthy lifestyle was associated with a higher prevalence of dementia, regardless of whether the participants had chronic diseases; however, this association was stronger in individuals with chronic diseases. Multidomain lifestyles and chronic diseases may have an enhanced impact on dementia.
Cognitive function and cardiovascular health in the elderly: network analysis based on hypertension, diabetes, cerebrovascular disease, and coronary heart disease
Authors: Wang Yucheng , Zhang Huanrui , Liu Linzi , Li Zijia , Zhou Yang , Wei Jiayan , Xu Yixiao , Zhou Yifang , Tang Yanqing
Published: August 2023

Introduction

Cognitive decline in the elderly population is a growing concern, and vascular factors, such as hypertension, diabetes, cerebrovascular disease, and coronary heart disease, have been associated with cognitive impairments. This study aims to provide deeper insights into the structure of cognitive function networks under these different vascular factors and explore their potential associations with specific cognitive domains.

Methods

Cognitive function was assessed using a modified Chinese version of the mini-mental state examination (MMSE) scale, and intensity centrality and side weights were estimated by network modeling. The network structure of cognitive function was compared across subgroups by including vascular factors as subgroup variables while controlling for comorbidities and confounders.

Results

The results revealed that cerebrovascular disease and coronary heart disease had a more significant impact on cognitive function. Cerebrovascular disease was associated with weaker centrality in memory and spatial orientation, and a sparser cognitive network structure. Coronary heart disease was associated with weaker centrality in memory, repetition, executive function, recall, attention, and calculation, as well as a sparser cognitive network structure. The NCT analyses further highlighted significant differences between the cerebrovascular disease and coronary heart disease groups compared to controls in terms of overall network structure and connection strength.

Conclusion

Our findings suggest that specific cognitive domains may be more vulnerable to impairments in patients with cerebrovascular disease and coronary heart disease. These insights could be used to improve the accuracy and sensitivity of cognitive screening in these patient populations, inform personalized cognitive intervention strategies, and provide a better understanding of the potential mechanisms underlying cognitive decline in patients with vascular diseases.
Exercise therapy to prevent and treat Alzheimer’s disease
Authors: Pahlavani Hamed Alizadeh
Published: August 2023

Alzheimer’s disease (AD) is a progressive neurodegenerative disease in the elderly with dementia, memory loss, and severe cognitive impairment that imposes high medical costs on individuals. The causes of AD include increased deposition of amyloid beta (Aβ) and phosphorylated tau, age, mitochondrial defects, increased neuroinflammation, decreased synaptic connections, and decreased nerve growth factors (NGF). While in animals moderate-intensity exercise restores hippocampal and amygdala memory through increased levels of p-AKT, p-TrkB, and p-PKC and decreased levels of Aβ, tau phosphorylation, and amyloid precursor proteins (APP) in AD. Aerobic exercise (with an intensity of 50–75% of VO2 max) prevents hippocampal volume reduction, spatial memory reduction, and learning reduction through increasing synaptic flexibility. Exercise training induces the binding of brain-derived neurotrophic factor (BDNF) to TrkB and the binding of NGF to TrkA to induce cell survival and neuronal plasticity. After aerobic training and high-intensity interval training, the increase of VEGF, angiopoietin 1 and 2, NO, tPA, and HCAR1 in cerebral vessels causes increased blood flow and angiogenesis in the cerebellum, motor cortex, striatum, and hippocampus. In the hippocampus, exercise training decreases mitochondrial fragmentation, DRP1, and FIS1, improving OPA1, MFN1, MFN2, and mitochondrial morphology. In humans, acute exercise as an anti-inflammatory condition causes an acute increase in IL-6 and an increase in anti-inflammatory factors such as IL-1RA and IL-10. Moderate-intensity exercise also inhibits inflammatory markers such as IFN-γ, IL-1β, IL-6, CRP, TNF-α, sTNFR1, COX-2, and NF-κB. Aerobic exercise significantly increases plasma levels of BDNF, nerve growth factor, synaptic plasticity, motor activity, spatial memory, and exploratory behavior in AD subjects. Irisin is a myokine released from skeletal muscle during exercise and protects the hippocampus by suppressing Aβ accumulation and promoting hippocampal proliferation through STAT3 signaling. Therefore, combined exercise training such as aerobic training, strength training, balance and coordination training, and cognitive and social activities seems to provide important benefits for people with AD.
Case report: Ruptured internal carotid artery fusiform aneurysm mimicking pituitary apoplexy after stereotactic radiosurgery
Authors: Wang Peng Wei , Chung Ming Hsuan , Feng Shao Wei , Liao Hsiang Chih , Wu Yi Chieh , Hueng Dueng Yuan , Yang Yun Ju , Ju Da Tong
Published: August 2023

Pituitary adenomas are benign tumors of the anterior pituitary gland for which surgery or pharmacological treatment is the primary treatment. When initial treatment fails, radiation therapy should be considered. There are several case reports demonstrating radiation-induced vascular injury. We report an adult patient who presented with headache and diplopia for 6 months and a sellar tumor with optic chiasm compression. The patient received transnasal surgery, and the tumor was partially removed, which demonstrated adenoma. Stereotactic radiosurgery (SRS) was arranged. However, owing to progressive tumor growth, the patient received further transnasal surgery and stereotactic radiosurgery (SRS). After 14 years, the patient reported the sudden onset of headache and diplopia, and a ruptured fusiform aneurysm from the left internal carotid artery with pituitary apoplexy was diagnosed. The patient received transarterial embolization of the aneurysm. There were no complications after embolization, and this patient was ambulatory on discharge with blindness in the left eye and cranial nerve palsies. Aneurysm formation may be a complication of SRS, and it may occur after several years. Further research is needed to investigate the pathogenesis of radiosurgery and the development of cerebral aneurysms.
Psychopathic traits and altered resting-state functional connectivity in incarcerated adolescent girls
Authors: Allen Corey H. , Maurer J. Michael , Gullapalli Aparna R. , Edwards Bethany G. , Aharoni Eyal , Harenski Carla L. , Anderson Nathaniel E. , Harenski Keith A. , Calhoun Vince D. , Kiehl Kent A.
Published: August 2023

Previous work in incarcerated boys and adult men and women suggest that individuals scoring high on psychopathic traits show altered resting-state limbic/paralimbic, and default mode functional network properties. However, it is unclear whether similar results extend to high-risk adolescent girls with elevated psychopathic traits. This study examined whether psychopathic traits [assessed via the Hare Psychopathy Checklist: Youth Version (PCL:YV)] were associated with altered inter-network connectivity, intra-network connectivity (i.e., functional coherence within a network), and amplitude of low-frequency fluctuations (ALFFs) across resting-state networks among high-risk incarcerated adolescent girls (n = 40). Resting-state networks were identified by applying group independent component analysis (ICA) to resting-state fMRI scans, and a priori regions of interest included limbic, paralimbic, and default mode network components. We tested the association of psychopathic traits (PCL:YV Factor 1 measuring affective/interpersonal traits and PCL:YV Factor 2 assessing antisocial/lifestyle traits) to these three resting-state measures. PCL:YV Factor 1 scores were associated with increased low-frequency and decreased high-frequency fluctuations in components corresponding to the default mode network, as well as increased intra-network FNC in components corresponding to cognitive control networks. PCL:YV Factor 2 scores were associated with increased low-frequency fluctuations in sensorimotor networks and decreased high-frequency fluctuations in default mode, sensorimotor, and visual networks. Consistent with previous analyses in incarcerated adult women, our results suggest that psychopathic traits among incarcerated adolescent girls are associated with altered intra-network ALFFs—primarily that of increased low-frequency and decreased high-frequency fluctuations—and connectivity across multiple networks including paralimbic regions. These results suggest stable neurobiological correlates of psychopathic traits among women across development.
Validity and reproducibility of a food frequency questionnaire assessing food group intake in the PERSIAN Cohort Study
Authors: Eghtesad Sareh , Hekmatdoost Azita , Faramarzi Elnaz , Homayounfar Reza , Sharafkhah Maryam , Hakimi Hamid , Dehghani Ali , Moosazadeh Mahmood , Mortazavi Zinat , Pasdar Yahya , Poustchi Hossein , Willett Walter C. , Malekzadeh Reza
Published: August 2023

Purpose

A semi-quantitative food frequency questionnaire (FFQ) was developed for use in the Prospective Epidemiological Research Studies in IrAN (PERSIAN Cohort), investigating non-communicable disease risk factors. This study aimed to assess the validity and reproducibility of this FFQ, through food group intake.

Methods

Participants, recruited from seven PERSIAN cohort centers, completed the FFQ at the beginning of the study (FFQ1) and at the end (FFQ2), with a 12-month interval in between, during which two 24-h dietary recalls (24 h) were completed each month. Correlation coefficients of the median intake of food groups recorded by the FFQs were compared to those of the 24 h to assess validity, and the two FFQs were compared to assess reproducibility of findings.

Results

Overall, data from 978 participants were included in this validation analysis. Of the 26 food groups assessed, Tea, Sugars, Whole/Refined Grains, and Solid Fats/Oils, had the strongest correlations (0.6–0.79), while Red Meat, Chicken and Eggs showed moderate correlations (0.42–0.59). The weakest correlations observed belonged to Fresh fruit Juice and Other Meats (0.23–0.32). Reproducibility was assessed among those who completed both FFQ1 and FFQ2 (n = 848), revealing moderate to strong correlations in all food groups, ranging from 0.42 in Legumes to 0.72 in both Sugar and Sweetened Drinks.

Conclusion

The PERSIAN Cohort FFQ is appropriate to rank individuals based on food group intake.
AAV-mediated gene transfer to colon-innervating primary afferent neurons
Authors: Gore Reshma , Esmail Tina , Pflepsen Kelsey , Marron Fernandez de Velasco Ezequiel , Kitto Kelley F. , Riedl Maureen S. , Karlen Andrea , McIvor R. Scott , Honda Christopher N. , Fairbanks Carolyn A. , Vulchanova Lucy
Published: August 2023

Investigation of neural circuits underlying visceral pain is hampered by the difficulty in achieving selective manipulations of individual circuit components. In this study, we adapted a dual AAV approach, used for projection-specific transgene expression in the CNS, to explore the potential for targeted delivery of transgenes to primary afferent neurons innervating visceral organs. Focusing on the extrinsic sensory innervation of the mouse colon, we first characterized the extent of dual transduction following intrathecal delivery of one AAV9 vector and intracolonic delivery of a second AAV9 vector. We found that if the two AAV9 vectors were delivered one week apart, dorsal root ganglion (DRG) neuron transduction by the second vector was greatly diminished. Following delivery of the two viruses on the same day, we observed colocalization of the transgenes in DRG neurons, indicating dual transduction. Next, we delivered intrathecally an AAV9 vector encoding the inhibitory chemogenetic actuator hM4D(Gi) in a Cre-recombinase dependent manner, and on the same day injected an AAV9 vector carrying Cre-recombinase in the colon. DRG expression of hM4D(Gi) was demonstrated at the mRNA and protein level. However, we were unable to demonstrate selective inhibition of visceral nociception following hM4D(Gi) activation. Taken together, these results establish a foundation for development of strategies for targeted transduction of primary afferent neurons for neuromodulation of peripheral neural circuits.