bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term green-Mediterranean diet may favor fasting morning cortisol stress hormone; the DIRECT-PLUS clinical trial
Authors: Alufer Liav , Tsaban Gal , Rinott Ehud , Kaplan Alon , Meir Anat Yaskolka , Zelicha Hila , Ceglarek Uta , Isermann Berend , Blüher Matthias , Stumvoll Michael , Stampfer Meir J. , Shai Iris
Published: November 2023

Background

Fasting morning cortisol (FMC) stress hormone levels, are suggested to reflect increased cardiometabolic risk. Acute response to weight loss diet could elevate FMC. Richer Polyphenols and lower carbohydrates diets could favor FMC levels. We aimed to explore the effect of long-term high polyphenol Mediterranean diet (green-MED) on FMC and its relation to metabolic health.

Methods

We randomized 294 participants into one of three dietary interventions for 18-months: healthy dietary guidelines (HDG), Mediterranean (MED) diet, and Green-MED diet. Both MED diets were similarly hypocaloric and lower in carbohydrates and included walnuts (28 g/day). The high-polyphenols/low-meat Green-MED group further included green tea (3-4 cups/day) and a Wolffia-globosa Mankai plant 1-cup green shakeFMC was obtained between 07:00-07:30AM at baseline, six, and eighteen-months.

Results

Participants (age=51.1years, 88% men) had a mean BMI of 31.3kg/m2, FMC=304.07nmol\L, and glycated-hemoglobin-A1c (HbA1c)=5.5%; 11% had type 2 diabetes and 38% were prediabetes. Baseline FMC was higher among men (308.6 ± 90.05nmol\L) than women (269.6± 83.9nmol\L;p=0.02). Higher baseline FMC was directly associated with age, dysglycemia, MRI-assessed visceral adiposity, fasting plasma glucose (FPG), high-sensitivity C-reactive-protein (hsCRP), testosterone, Progesterone and TSH levels (p ≤ 0.05 for all). The 18-month retention was 89%. After 6 months, there were no significant changes in FMC among all intervention groups. However, after 18-months, both MED groups significantly reduced FMC (MED=-1.6%[-21.45 nmol/L]; Green-MED=-1.8%[-26.67 nmol/L]; p<0.05 vs. baseline), as opposed to HDG dieters (+4%[-12 nmol/L], p=0.28 vs. baseline), whereas Green-MED diet FMC change was significant as compared to HDG diet group (p=0.048 multivariable models). Overall, 18-month decrease in FMC levels was associated with favorable changes in FPG, HbA1c, hsCRP, TSH, testosterone and MRI-assessed hepatosteatosis, and with unfavorable changes of HDLc (p<0.05 for all, weight loss adjusted, multivariable models).

Conclusion

Long-term adherence to MED diets, and mainly green-MED/high polyphenols diet, may lower FMC, stress hormone, levels,. Lifestyle-induced FMC decrease may have potential benefits related to cardiometabolic health, irrespective of weight loss.

Clinical trial registration

ClinicalTrials.gov, identifier NCT03020186.
The predictive significance of lipid accumulation products for future diabetes in a non-diabetic population from a gender perspective: an analysis using time-dependent receiver operating characteristics
Authors: Qiu Jiajun , Kuang Maobin , Zou Yang , Yang Ruijuan , Shangguan Qing , Liu Dingyang , Sheng Guotai , Wang Wei
Published: November 2023

Objective

The increasing prevalence of diabetes is strongly associated with visceral adipose tissue (VAT), and gender differences in VAT remarkably affect the risk of developing diabetes. This study aimed to assess the predictive significance of lipid accumulation products (LAP) for the future onset of diabetes from a gender perspective.

Methods

A total of 8,430 male and 7,034 female non-diabetic participants in the NAGALA (NAfld in the Gifu Area, Longitudinal Analysis) program were included. The ability of LAP to assess the risk of future new-onset diabetes in both genders was analyzed using multivariate Cox regression. Subgroup analysis was conducted to explore the impact of potential modifiers on the association between LAP and diabetes. Additionally, time-dependent receiver operator characteristics (ROC) curves were used to assess the predictive power of LAP in both genders for new-onset diabetes over the next 2-12 years.

Results

Over an average follow-up of 6.13 years (maximum 13.14 years), 373 participants developed diabetes. Multivariate Cox regression analysis showed a significant gender difference in the association between LAP and future diabetes risk (P-interaction<0.05): the risk of diabetes associated with LAP was greater in females than males [hazard ratios (HRs) per standard deviation (SD) increase: male 1.20 (1.10, 1.30) vs female 1.35 (1.11, 1.64)]. Subgroup analysis revealed no significant modifying effect of factors such as age, body mass index (BMI), smoking history, drinking history, exercise habits, and fatty liver on the risk of diabetes associated with LAP (All P-interaction <0.05). Time-dependent ROC analysis showed that LAP had greater accuracy in predicting diabetes events occurring within the next 2-12 years in females than males with more consistent predictive thresholds in females.

Conclusions

This study highlighted a significant gender difference in the association between LAP and future diabetes risk. The risk of diabetes associated with LAP was greater in females than in males. Furthermore, LAP showed superior predictive ability for diabetes at different time points in the future in females and had more consistent and stable predictive thresholds in females, particularly in the medium and long term.
Dietary flexibility of western red colobus in two protected areas with contrasting anthropogenic pressure
Authors: Aleixo-Pais Isa , Borges Filipa , Sesay Nazie , Songe Mustapha , Cassama Mamadu , Camara Iaia T. , Ramos Catarina , Barca Benjamin , Turay Brima S. , Swaray Mohamed , de Barros Aissa Regalla , Quecuta Queba , Ferreira da Silva Maria Joana , Frazão-Moreira Amélia , Bruford Michael William , Minhós Tânia
Published: November 2023

Food distribution and abundance can affect intra- and inter-dietary variation in non-human primates, influencing feeding ecology and altering behaviour. Natural and/or human-induced actions can influence the dynamics between primates and the environment, with associated impacts on socio-ecology and demography. This relationship in anthropogenic landscapes, however, is poorly understood. Here, we use DNA metabarcoding to obtain high resolution dietary diversity data, and multivariate generalised linear models to investigate variation in the diet of this threatened primate. We characterise the diet of the western red colobus (Piliocolobus badius) in both the better preserved Gola Rainforest National Park (GRNP, Sierra Leone), and in the fragmented forests of Cantanhez National Park (CNP, Guinea-Bissau), and evaluate biological, ecological and temporal differences. Dietary plant species richness was high in both protected areas, and the type of plants consumed varied significantly across seasons, space, and time. Although we identify dependence on a few key plants, red colobus in CNP consumed a higher average number of plant taxa than in GRNP, and 11% of the diet consisted of cultivated foods (e.g. mango). This is the first time a molecular approach has been used to investigate red colobus diet, and reveal dietary flexibility in degraded forests. Predicting the consequences of dietary change on long-term population persistence, however, remains a significant knowledge gap. Nevertheless, our results provide critical information to inform targeted regional conservation planning and implementation.
Case Report: I feel like a mother to other babies: experiences and perspectives on bereavement and breastmilk donation from Vietnam
Authors: Tran Hoang Thi , Nguyen Tuan Thanh , Nguyen Oanh Thi Xuan , Mathisen Roger , Cassidy Tanya M.
Published: November 2023

There is a growing recognition globally that care regarding lactation following a perinatal death needs to potentially offer the opportunity for maternal donation. This article discusses this experience and perspectives from a human milk bank (HMB) in Vietnam. This is a descriptive exploratory case study that has a long tradition in both the social and health sciences. Triangulated data collection involved a review of video data, interview data with the donor, and data review for the Da Nang HMB, a Center for Excellence in Breastfeeding. We found that although it is common for mothers in Vietnam to donate breastmilk to HMBs, it is less common for this to occur following perinatal loss. We offer a descriptive case study of the maternal loss of twins and a subsequent choice to donate for approximately 1 month to the Da Nang HMB, the first HMB in Vietnam. We discuss four reasons derived from this case regarding donation following perinatal loss. (1) A strong motivation to donate breastmilk when aware of the service, (2) donating breastmilk helped her deal with grief, (3) family members supported her through this tough time and supported her decision, and (4) health staff supported her decision. While human milk sharing (e.g., wet nursing) has been practiced in Vietnam, breastmilk donation from bereaved mothers has neither been discussed nor well-researched. Because maternal grief is complex and individual, deciding to donate breastmilk is a personal decision that needs to be supported, without creating guilt for those who do not wish to donate.
Activation of the aryl hydrocarbon receptor inhibits neuropilin-1 upregulation on IL-2-responding CD4+ T cells
Authors: Sandoval Simone , Malany Keegan , Thongphanh Krista , Martinez Clarisa A. , Goodson Michael L. , Souza Felipe Da Costa , Lin Lo-Wei , Sweeney Nicolle , Pennington Jamie , Lein Pamela J. , Kerkvliet Nancy I. , Ehrlich Allison K.
Published: November 2023

Neuropilin-1 (Nrp1), a transmembrane protein expressed on CD4+ T cells, is mostly studied in the context of regulatory T cell (Treg) function. More recently, there is increasing evidence that Nrp1 is also highly expressed on activated effector T cells and that increases in these Nrp1-expressing CD4+ T cells correspond with immunopathology across several T cell-dependent disease models. Thus, Nrp1 may be implicated in the identification and function of immunopathologic T cells. Nrp1 downregulation in CD4+ T cells is one of the strongest transcriptional changes in response to immunoregulatory compounds that act though the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor. To better understand the link between AhR and Nrp1 expression on CD4+ T cells, Nrp1 expression was assessed in vivo and in vitro following AhR ligand treatment. In the current study, we identified that the percentage of Nrp1 expressing CD4+ T cells increases over the course of activation and proliferation in vivo. The actively dividing Nrp1+Foxp3- cells express the classic effector phenotype of CD44hiCD45RBlo, and the increase in Nrp1+Foxp3- cells is prevented by AhR activation. In contrast, Nrp1 expression is not modulated by AhR activation in non-proliferating CD4+ T cells. The downregulation of Nrp1 on CD4+ T cells was recapitulated in vitro in cells isolated from C57BL/6 and NOD (non-obese diabetic) mice. CD4+Foxp3- cells expressing CD25, stimulated with IL-2, or differentiated into Th1 cells, were particularly sensitive to AhR-mediated inhibition of Nrp1 upregulation. IL-2 was necessary for AhR-dependent downregulation of Nrp1 expression both in vitro and in vivo. Collectively, the data demonstrate that Nrp1 is a CD4+ T cell activation marker and that regulation of Nrp1 could be a previously undescribed mechanism by which AhR ligands modulate effector CD4+ T cell responses.
Paraneoplastic isolated adrenocorticotropic hormone deficiency revealed after immune checkpoint inhibitors therapy: new insights into anti-corticotroph antibody
Authors: Urai Shin , Watanabe Miki , Bando Hironori , Motomura Yuma , Yamamoto Masaaki , Tachihara Motoko , Kanzawa Maki , Fukuoka Hidenori , Iguchi Genzo , Ogawa Wataru
Published: November 2023

Introduction

A recently discovered facet of paraneoplastic adrenocorticotropic hormone (ACTH) deficiency exists in two forms: a paraneoplastic spontaneous isolated ACTH deficiency (IAD) and an immune checkpoint inhibitor (ICI)-related hypophysitis. Autoantibodies against corticotrophs, such as circulating anti-proopiomelanocortin (POMC) antibodies are considered disease markers. However, the number of identified cases was limited, implying that the characteristics of these autoantibodies are not fully understood.

Methods

We investigate circulating autoimmune autoantibodies in detail through a novel case of IAD that developed as a paraneoplastic autoimmune ACTH deficiency.

Results

The patient developed IAD after 25 weeks of ICI therapy for metastasis of large-cell neuroendocrine carcinoma at 69 years of age. Ectopic ACTH expression and infiltration of CD3+, CD4+, CD8+, and CD20+ lymphocytes were observed in the tumor tissues and circulating anti-POMC antibodies were detected specifically in the patient’s serum. Moreover, detailed analyses of immunofluorescence staining using patient serum revealed that the recognition site of the autoantibody was ACTH25-39, which had not been identified in previous cases of paraneoplastic autoimmune ACTH deficiency.

Conclusion

This case involved a combination of paraneoplastic spontaneously acquired IAD and ICI-related hypophysitis occupying the middle ground. Moreover, our study reveals new aspects of anti-POMC antibodies in patients with paraneoplastic ACTH deficiency. This report expands our understanding of the immunological landscape and provides new insights for the identification of antibodies associated with paraneoplastic autoimmune ACTH deficiency.
Scale-dependent influence of multiple environmental drivers on estuarine macrobenthic crustaceans
Authors: Lam-Gordillo Orlando , Lohrer Andrew M. , Douglas Emily , Hailes Sarah , Carter Kelly , Greenfield Barry
Published: November 2023

Estuarine ecosystems are transitional environments, where land, freshwater, and marine ecosystems converge. Estuaries are also hotspots of ecological functioning and considered highly economically and culturally valuable for the ecosystem services they provide to humankind. However, multiple stressors (e.g., nutrient and sediment loading, pollution, climate change) are threatening the survival of estuarine organisms and therefore affecting the functions and services estuarine ecosystems provide. In this study, we investigated the influence of multiple environmental variables on long-term estuarine crustacean data across several estuaries in New Zealand. We focused on responses of specific crustacean groups and total crustacean abundance and richness to freshwater, ocean, and climate variables as drivers of change at large, medium, and fine spatial scales. Our analyses revealed that the abundance and richness of crustaceans, as well as the abundance of specific crustacean groups (i.e., Amphipoda, Decapoda, Cumacea, Tanaidacea), were influenced by unique combinations of environmental variables, resulting in scale dependent interactions. We also identified negative relationships between estuarine crustaceans and drivers, with decreased abundance and richness of crustaceans as the magnitude of drivers increased. Sea Surface Temperature (SST) and climate-related drivers (Southern Oscillation Index, SOI) were the dominant drivers affecting estuarine crustaceans, yet sediment muddiness negatively affected crustacean communities at all spatial scales assessed. Our research suggests that the combined effects of multiple environmental drivers such as increased muddiness, ocean warming, and climate change are likely to act in a concerted way to affect the health and functioning of estuarine ecosystems. The observed interactions between macrobenthic crustaceans and climatic and oceanic drivers have important implications for understanding climate change impacts on marine ecosystems and assist management and conservation efforts.
What did we learn about tocilizumab use against COVID-19? A single-center observational study from an intensive care unit in Serbia
Authors: Adzic-Vukicevic Tatjana , Markovic Dejan , Reljic Aleksandar , Brkovic Voin
Published: November 2023

Background

Selection of effective and safe therapy for management of patients with coronavirus disease is challenging. Tocilizumab (TZB) has emerged as a potential treatment option for COVID-19. Several aspects regarding Tocilizumab treatment remain uncertain, such as the optimal timing for its administration and the safety profile, including the potential risk of infections. The aim of the study is to present the clinical characteristics of patients with COVID-19 following the application of Tocilizumab.

Methods

This is a retrospective analysis of 121 patients with severe forms of COVID-19 previously treated with Tocilizumab was conducted. All patients were admitted to intensive care units (ICUs).

Results

Of 121 patients, the majority were men 72 (59.5%) with a median age at presentation of 65 ± 13 years. Only 9 (7.43%) patients were without comorbidities, while the other 112 (92.55%) had two or more comorbidities. Almost all of the 120 patients (99.2%) needed oxygen therapy, such as nasal cannulas in 110 (90.9%) patients, high flow nasal catheter (HFNC) in 4 (3.3%) patients, and continuous positive airway pressure (CPAP) in 5 (4.1%) patients while 1 patient was intubated at the time of hospital admission. The average time from Tocilizumab application to admission to the ICU was 3 days. During clinical deterioration, almost half 57 (47.1%) of the patients were intubated, and 52 (82.5%) of these intubated patients (p < 0.001) had lethal outcomes. The most significant predictors for a lethal outcome according to multivariate analysis were diabetes mellitus (p < 0.001) followed by a subsequent elevation in C-reactive protein levels (CRP; p < 0.002) and ferritin (p < 0.013) after Tocilizumab application. Bloodstream infections were found in 20 (16.5%) patients, most frequently with Gram-negative pathogens like Acinetobacter spp. as in 12 (18.6%) patients, Klebsiella spp. in 6 (8%) patients, and Pseudomonas spp. in 2 (3.2%) patients. Urine culture isolates were found in 9 (7.43%) patients, with Candida spp. being most frequently isolated in 7 (5.8%) patients, followed by Klebsiella spp. and Pseudomonas spp. in 1 patient each (0.8%). Significantly lower survival was seen in patients with proven infection.

Conclusion

The benefit of tocilizumab was not found in our study. The high mortality rate among intubated patients after Tocilizumab use suggests appropriate patient selection and monitoring and emphasizes the risk of superinfections. Diabetes mellitus, increased levels of CRP, and ferritin were identified as the most significant predictors of poor outcomes in contrast to increased levels of IL-6.
Endothelial activation and damage as a common pathological substrate in different pathologies and cell therapy complications
Authors: Palomo Marta , Moreno-Castaño Ana Belén , Salas María Queralt , Escribano-Serrat Silvia , Rovira Montserrat , Guillen-Olmos Elena , Fernandez Sara , Ventosa-Capell Helena , Youssef Lina , Crispi Fatima , Nomdedeu Meritxell , Martinez-Sanchez Julia , De Moner Blanca , Diaz-Ricart Maribel
Published: November 2023

The endothelium is a biologically active interface with multiple functions, some of them common throughout the vascular tree, and others that depend on its anatomical location. Endothelial cells are continually exposed to cellular and humoral factors, and to all those elements (biological, chemical, or hemodynamic) that circulate in blood at a certain time. It can adapt to different stimuli but this capability may be lost if the stimuli are strong enough and/or persistent in time. If the endothelium loses its adaptability it may become dysfunctional, becoming a potential real danger to the host. Endothelial dysfunction is present in multiple clinical conditions, such as chronic kidney disease, obesity, major depression, pregnancy-related complications, septic syndromes, COVID-19, and thrombotic microangiopathies, among other pathologies, but also in association with cell therapies, such as hematopoietic stem cell transplantation and treatment with chimeric antigen receptor T cells. In these diverse conditions, evidence suggests that the presence and severity of endothelial dysfunction correlate with the severity of the associated disease. More importantly, endothelial dysfunction has a strong diagnostic and prognostic value for the development of critical complications that, although may differ according to the underlying disease, have a vascular background in common. Our multidisciplinary team of women has devoted many years to exploring the role of the endothelium in association with the mentioned diseases and conditions. Our research group has characterized some of the mechanisms and also proposed biomarkers of endothelial damage. A better knowledge would provide therapeutic strategies either to prevent or to treat endothelial dysfunction.
Endocytosis inhibitors block SARS-CoV-2 pseudoparticle infection of mink lung epithelium
Authors: Song Ann , Phandthong Rattapol , Talbot Prue
Published: November 2023

Introduction

Both spill over and spill back of SARS-CoV-2 virus have been reported on mink farms in Europe and the United States. Zoonosis is a public health concern as dangerous mutated forms of the virus could be introduced into the human population through spillback.

Methods

The purpose of our study was to determine the SARS-CoV-2 entry mechanism using the mink lung epithelial cell line (Mv1Lu) and to block entry with drug inhibitors.

Results

Mv1Lu cells were susceptible to SARS-CoV-2 viral pseudoparticle infection, validating them as a suitable disease model for COVID-19. Inhibitors of TMPRSS2 and of endocytosis, two pathways of viral entry, were tested to identify those that blocked infection. TMPRSS2 inhibitors had minimal impact, which can be explained by the apparent lack of activity of this enzyme in the mink and its localization within the cell, not on the cell surface.

Discussion

Dyngo4a, a small molecule endocytosis inhibitor, significantly reduced infection, supporting the conclusion that the entry of the SARS-CoV-2 virus into Mv1Lu cells occurs primarily through endocytosis. The small molecule inhibitors that were effective in this study could potentially be used therapeutically to prevent SARS-CoV-2 infection in mink populations. This study will facilitate the development of therapeutics to prevent zoonotic transmission of SARS-CoV-2 variants to other animals, including humans.
Cortical gyrification pattern of depression in Parkinson’s disease: a neuroimaging marker for disease severity?
Authors: Shen Qin , Liao Haiyan , Cai Sainan , Liu Qinru , Wang Min , Song Chendie , Zhou Fan , Liu Yujing , Yuan Jiaying , Tang Yuqing , Li Xu , Liu Jun , Tan Changlian
Published: November 2023

Background

Although the study of the neuroanatomical correlates of depression in Parkinson’s Disease (PD) is gaining increasing interest, up to now the cortical gyrification pattern of PD-related depression has not been reported. This study was conducted to investigate the local gyrification index (LGI) in PD patients with depression, and its associations with the severity of depression.

Methods

LGI values, as measured using FreeSurfer software, were compared between 59 depressed PD (dPD), 27 non-depressed PD (ndPD) patients and 43 healthy controls. The values were also compared between ndPD and mild-depressed PD (mi-dPD), moderate-depressed PD (mo-dPD) and severe-depressed PD (se-dPD) patients as sub-group analyses. Furthermore, we evaluated the correlation between LGI values and depressive symptom scores within dPD group.

Results

Compared to ndPD, the dPD patients exhibited decreased LGI in the left parietal, the right superior-frontal, posterior cingulate and paracentral regions, and the LGI values within these areas negatively correlated with the severity of depression. Specially, reduced gyrification was observed in mo-dPD and involving a larger region in se-dPD, but not in mi-dPD group.

Conclusion

The present study demonstrated that cortical gyrification is decreased within specific brain regions among PD patients with versus without depression, and those changes were associated with the severity of depression. Our findings suggested that cortical gyrification might be a potential neuroimaging marker for the severity of depression in patients with PD.
Blood-brain barrier dysfunction and Alzheimer’s disease: associations, pathogenic mechanisms, and therapeutic potential
Authors: Chen Yanting , He Yanfang , Han Jinling , Wei Wenyan , Chen Feng
Published: November 2023

Alzheimer’s disease (AD) is a common neurodegenerative disorder characterized by the accumulation of amyloid-beta (Aβ), hyperphosphorylation of tau, and neuroinflammation in the brain. The blood–brain barrier (BBB) limits solutes from circulating blood from entering the brain, which is essential for neuronal functioning. Focusing on BBB function is important for the early detection of AD and in-depth study of AD pathogenic mechanisms. However, the mechanism of BBB alteration in AD is still unclear, which hinders further research on therapeutics that target the BBB to delay the progression of AD. The exact timing of the vascular abnormalities in AD and the complex cause-and-effect relationships remain uncertain. Thus, it is necessary to summarize and emphasize this process. First, in this review, the current evidence for BBB dysfunction in AD is summarized. Then, the interrelationships and pathogenic mechanisms between BBB dysfunction and the risk factors for AD, such as Aβ, tau, neuroinflammation, apolipoprotein E (ApoE) genotype and aging, were analyzed. Finally, we discuss the current status and future directions of therapeutic AD strategies targeting the BBB. We hope that these summaries or reviews will allow readers to better understand the relationship between the BBB and AD.
Treatment of Parkinson’s disease with biologics that penetrate the blood–brain barrier via receptor-mediated transport
Authors: Pardridge William M.
Published: November 2023

Parkinson’s disease (PD) is characterized by neurodegeneration of nigral-striatal neurons in parallel with the formation of intra-neuronal α-synuclein aggregates, and these processes are exacerbated by neuro-inflammation. All 3 components of PD pathology are potentially treatable with biologics. Neurotrophins, such as glial derived neurotrophic factor or erythropoietin, can promote neural repair. Therapeutic antibodies can lead to disaggregation of α-synuclein neuronal inclusions. Decoy receptors can block the activity of pro-inflammatory cytokines in brain. However, these biologic drugs do not cross the blood–brain barrier (BBB). Biologics can be made transportable through the BBB following the re-engineering of the biologic as an IgG fusion protein, where the IgG domain targets an endogenous receptor-mediated transcytosis (RMT) system within the BBB, such as the insulin receptor or transferrin receptor. The receptor-specific antibody domain of the fusion protein acts as a molecular Trojan horse to ferry the biologic into brain via the BBB RMT pathway. This review describes the re-engineering of all 3 classes of biologics (neurotrophins, decoy receptor, therapeutic antibodies) for BBB delivery and treatment of PD. Targeting the RMT pathway at the BBB also enables non-viral gene therapy of PD using lipid nanoparticles (LNP) encapsulated with plasmid DNA encoding therapeutic genes. The surface of the lipid nanoparticle is conjugated with a receptor-specific IgG that triggers RMT of the LNP across the BBB in vivo.
Research progress of ferroptosis in Parkinson’s disease: a bibliometric and visual analysis
Authors: Lu Yangguang , Chen Yiqun , Jiang Zihan , Ge Yaoying , Yao Ruotong , Geng Shangze , Zhang Jinxiu , Chen Feng , Wang Yukai , Chen Guangyong , Yang Dehao
Published: November 2023

Background

In recent years, the role of ferroptosis in Parkinson’s disease (PD) has become a research hotspot based on evidence of abnormal iron deposition and lipid peroxidation damage in the brains of PD patients. This study aims to examine the relevant research on ferroptosis and PD from a bibliometric perspective.

Methods

Original research and review articles related to ferroptosis and PD were retrieved from the Web of Science Core Collection (WOSCC) database. Statistical analysis and visualization of information including countries, institutions, authors, journals, and keywords of the included studies were conducted using the R software package “bibliometrix.”

Results

A total of 414 articles met the inclusion criteria, averaging 37.86 citations per article. From 2012 to 2022, the average annual growth rate of research in this area was 63.44%. The corresponding authors of published articles were mainly affiliated with institutions in China, the United States, and Australia. Shanghai Jiao Tong University in China and the University of Melbourne in Australia emerged as the most active and influential institutions. The journal with the highest H-index and publication output was Free Radical Biology and Medicine. “Ferroptosis,” “immunotherapy,” “prognosis” and “microenvironment” were identified as high-frequency keywords, indicating current and future research directions in this field.

Conclusion

This bibliometric study provides insights into current research hotspots and emerging trends in the growing field of ferroptosis research related to PD. The high-frequency keywords identified highlight active areas of investigation involving methods, mechanisms, and populations of interest.
A predictive model for the recurrence of intracranial aneurysms following coil embolization
Authors: He Tao , Chen Kun , Chen Ru-Dong
Published: November 2023

Objective

This study aimed to identify risk factors for intracranial aneurysms (IAs) recurrence and establish a predictive model to aid evaluation.

Methods

A total of 302 patients with 312 IAs undergoing coil embolization between September 2017 and October 2022 were divided into two groups based on digital subtraction angiography follow-up. Clinical characteristics, operation-related factors, and morphologies were measured. Cox proportional hazard regression was used to identify the risk factors. Hazard ratios (HRs) were used to score points, and a predictive model was established. The test cohorts consisted of 51 IAs. Receiver operating characteristic curves were generated to determine the cutoff values and area under the curves (AUCs). A Delong test was performed to compare the AUCs.

Results

Diameter maximum (D max) (p < 0.001, HR = 1.221), Raymond-Roy occlusion classification (RROC) II or III (p = 0.004, HR = 2.852), and ruptured status (p < 0.001, HR = 7.782) were independent risk factors for the recurrence of IAs. A predictive model was established: D max + 2 * RROC (II or III; yes = 1, no = 0) + 6 * ruptured status (yes = 1; no = 0). The AUC of the predictive model (0.818) was significantly higher than those of D max (0.704), RROC (II or III) (0.645), and rupture status (0.683), respectively (Delong test, p < 0.05). The cutoff values of the predictive model and D max were 9.75 points and 6.65 mm, respectively.

Conclusion

The D max, RROC (II or III), and ruptured status could independently predict the recurrence of IAs after coil embolization. Our model could aid in practical evaluations.
Relapsing polychondritis-associated meningoencephalitis initially presenting as seizure: a case report and literature review
Authors: Zhang Dan , Shi Jiamin , Zhang Xinhua , Wang Jin , Shao Yuquan
Published: November 2023

Background and purpose

Relapsing polychondritis (RP) is a rare rheumatologic disorder that may affect the neurological system with various presentations. In this study, we present a case and summarize the clinical characteristics of RP-associated meningoencephalitis.

Case presentation

A 48-year-old man presented with first-ever seizures that were well controlled by valproate. Physical examination results were unremarkable, except for binaural deformation. The initial brain magnetic resonance imaging (MRI) without contrast and electroencephalogram (EEG) findings were normal. However, the patient subsequently developed recurrent fever, scleritis, headache, lethargy, and left arm paresis. Repeated brain MRI with contrast demonstrated increased enhancement of the pia mater and abnormal diffusion-weighted imaging (DWI) signals in the bilateral auricles. The cerebrospinal fluid (CSF) analysis showed 2 leukocytes/μL, 736.5 mg/L of protein, and no evidence of infectious disease or autoimmune encephalitis. Meningoencephalitis secondary to RP was considered. The patient's condition improved significantly and quickly with the administration of dexamethasone (10 mg per day). Oral methylprednisolone was continued, and the patient remained well without relapse during the 9-month follow-up period.

Conclusion

RP-associated meningoencephalitis is rare but fatal. Although symptoms vary, red or deformed ears remain the most common and suggestive features. Non-specific parenchymal changes and/or meningeal enhancement can be observed on brain MRI scans. CSF lymphocytic pleocytosis with mild protein elevation was observed in most patients.
The contribution of being physically active to successful aging
Authors: Piccardi Laura , Pecchinenda Anna , Palmiero Massimiliano , Giancola Marco , Boccia Maddalena , Giannini Anna Maria , Guariglia Cecilia
Published: November 2023

Growing old involves changes in physical, psychological, and cognitive functions. Promoting physical and mental health has become one of the priorities for an aging population. Studies have demonstrated the benefits of engaging in regular physical activity. Here, we aimed to understand the relationships between physical activity and working memory complaints in attention, memory storage, and executive functions. We hypothesized that physical activity was negatively associated with complaints in working memory domains after controlling for socio-demographics and distress factors, such as anxiety, stress, and depression. Two hundred and twenty-three individuals aged between 65 and 100 years (74.84; SD = 7.74; 133 males) without self-reported neurological and/or psychiatric disorders completed a questionnaire on socio-demographic, with questions on physical activity and the Italian version of the working memory questionnaire (WMQ) and the DASS-21 measuring anxiety, stress, and depression. Results from three linear regression models showed that low physical activity was associated with complaints in attention (R2 = 0.35) and executive functions (R2 = 0.37) but not in memory storage (R2 = 0.28). Notably, age, gender, and total emotional distress (DASS score) were significant in all regression models. Our results suggested regular physical activity, even just walking, is crucial for maintaining efficient cognitive function. Theoretical and practical implications for engaging in physical activity programs and social aggregation during exercise are considered. Limitations are also presented.
Altered neural encoding of vowels in noise does not affect behavioral vowel discrimination in gerbils with age-related hearing loss
Authors: Heeringa Amarins N. , Jüchter Carolin , Beutelmann Rainer , Klump Georg M. , Köppl Christine
Published: November 2023

Introduction

Understanding speech in a noisy environment, as opposed to speech in quiet, becomes increasingly more difficult with increasing age. Using the quiet-aged gerbil, we studied the effects of aging on speech-in-noise processing. Specifically, behavioral vowel discrimination and the encoding of these vowels by single auditory-nerve fibers were compared, to elucidate some of the underlying mechanisms of age-related speech-in-noise perception deficits.

Methods

Young-adult and quiet-aged Mongolian gerbils, of either sex, were trained to discriminate a deviant naturally-spoken vowel in a sequence of vowel standards against a speech-like background noise. In addition, we recorded responses from single auditory-nerve fibers of young-adult and quiet-aged gerbils while presenting the same speech stimuli.

Results

Behavioral vowel discrimination was not significantly affected by aging. For both young-adult and quiet-aged gerbils, the behavioral discrimination between /eː/ and /iː/ was more difficult to make than /eː/ vs. /aː/ or /iː/ vs. /aː/, as evidenced by longer response times and lower d’ values. In young-adults, spike timing-based vowel discrimination agreed with the behavioral vowel discrimination, while in quiet-aged gerbils it did not. Paradoxically, discrimination between vowels based on temporal responses was enhanced in aged gerbils for all vowel comparisons. Representation schemes, based on the spectrum of the inter-spike interval histogram, revealed stronger encoding of both the fundamental and the lower formant frequencies in fibers of quiet-aged gerbils, but no qualitative changes in vowel encoding. Elevated thresholds in combination with a fixed stimulus level, i.e., lower sensation levels of the stimuli for old individuals, can explain the enhanced temporal coding of the vowels in noise.

Discussion

These results suggest that the altered auditory-nerve discrimination metrics in old gerbils may mask age-related deterioration in the central (auditory) system to the extent that behavioral vowel discrimination matches that of the young adults.
Homeostatic NREM sleep and salience network function in adult mice exposed to ethanol during development
Authors: Shah Prachi , Kaneria Aayush , Fleming Gloria , Williams Colin R. O. , Sullivan Regina M. , Lemon Christian H. , Smiley John , Saito Mariko , Wilson Donald A.
Published: November 2023

Developmental exposure to ethanol is a leading cause of cognitive, emotional and behavioral problems, with fetal alcohol spectrum disorder (FASD) affecting more than 1:100 children. Recently, comorbid sleep deficits have been highlighted in these disorders, with sleep repair a potential therapeutic target. Animal models of FASD have shown non-REM (NREM) sleep fragmentation and slow-wave oscillation impairments that predict cognitive performance. Here we use a mouse model of perinatal ethanol exposure to explore whether reduced sleep pressure may contribute to impaired NREM sleep, and compare the function of a brain network reported to be impacted by insomnia–the Salience network–in developmental ethanol-exposed mice with sleep-deprived, saline controls. Mice were exposed to ethanol or saline on postnatal day 7 (P7) and allowed to mature to adulthood for testing. At P90, telemetered cortical recordings were made for assessment of NREM sleep in home cage before and after 4 h of sleep deprivation to assess basal NREM sleep and homeostatic NREM sleep response. To assess Salience network functional connectivity, mice were exposed to the 4 h sleep deprivation period or left alone, then immediately sacrificed for immunohistochemical analysis of c-Fos expression. The results show that developmental ethanol severely impairs both normal rebound NREM sleep and sleep deprivation induced increases in slow-wave activity, consistent with reduced sleep pressure. Furthermore, the Salience network connectome in rested, ethanol-exposed mice was most similar to that of sleep-deprived, saline control mice, suggesting a sleep deprivation-like state of Salience network function after developmental ethanol even without sleep deprivation.
The cross-talk between macrophages and tumor cells as a target for cancer treatment
Authors: Aizaz Muhammad , Khan Aakif , Khan Faisal , Khan Maria , Musad Saleh Ebraheem Abdu , Nisar Maryum , Baran Natalia
Published: November 2023

Macrophages represent an important component of the innate immune system. Under physiological conditions, macrophages, which are essential phagocytes, maintain a proinflammatory response and repair damaged tissue. However, these processes are often impaired upon tumorigenesis, in which tumor-associated macrophages (TAMs) protect and support the growth, proliferation, and invasion of tumor cells and promote suppression of antitumor immunity. TAM abundance is closely associated with poor outcome of cancer, with impediment of chemotherapy effectiveness and ultimately a dismal therapy response and inferior overall survival. Thus, cross-talk between cancer cells and TAMs is an important target for immune checkpoint therapies and metabolic interventions, spurring interest in it as a therapeutic vulnerability for both hematological cancers and solid tumors. Furthermore, targeting of this cross-talk has emerged as a promising strategy for cancer treatment with the antibody against CD47 protein, a critical macrophage checkpoint recognized as the “don’t eat me” signal, as well as other metabolism-focused strategies. Therapies targeting CD47 constitute an important milestone in the advancement of anticancer research and have had promising effects on not only phagocytosis activation but also innate and adaptive immune system activation, effectively counteracting tumor cells’ evasion of therapy as shown in the context of myeloid cancers. Targeting of CD47 signaling is only one of several possibilities to reverse the immunosuppressive and tumor-protective tumor environment with the aim of enhancing the antitumor response. Several preclinical studies identified signaling pathways that regulate the recruitment, polarization, or metabolism of TAMs. In this review, we summarize the current understanding of the role of macrophages in cancer progression and the mechanisms by which they communicate with tumor cells. Additionally, we dissect various therapeutic strategies developed to target macrophage–tumor cell cross-talk, including modulation of macrophage polarization, blockade of signaling pathways, and disruption of physical interactions between leukemia cells and macrophages. Finally, we highlight the challenges associated with tumor hypoxia and acidosis as barriers to effective cancer therapy and discuss opportunities for future research in this field.
Structural modeling of hERG channel–drug interactions using Rosetta
Authors: Emigh Cortez Aiyana M. , DeMarco Kevin R. , Furutani Kazuharu , Bekker Slava , Sack Jon T. , Wulff Heike , Clancy Colleen E. , Vorobyov Igor , Yarov-Yarovoy Vladimir
Published: November 2023

The human ether-a-go-go-related gene (hERG) not only encodes a potassium-selective voltage-gated ion channel essential for normal electrical activity in the heart but is also a major drug anti-target. Genetic hERG mutations and blockage of the channel pore by drugs can cause long QT syndrome, which predisposes individuals to potentially deadly arrhythmias. However, not all hERG-blocking drugs are proarrhythmic, and their differential affinities to discrete channel conformational states have been suggested to contribute to arrhythmogenicity. We used Rosetta electron density refinement and homology modeling to build structural models of open-state hERG channel wild-type and mutant variants (Y652A, F656A, and Y652A/F656 A) and a closed-state wild-type channel based on cryo-electron microscopy structures of hERG and EAG1 channels. These models were used as protein targets for molecular docking of charged and neutral forms of amiodarone, nifekalant, dofetilide, d/l-sotalol, flecainide, and moxifloxacin. We selected these drugs based on their different arrhythmogenic potentials and abilities to facilitate hERG current. Our docking studies and clustering provided atomistic structural insights into state-dependent drug–channel interactions that play a key role in differentiating safe and harmful hERG blockers and can explain hERG channel facilitation through drug interactions with its open-state hydrophobic pockets.
Short-chain fatty acids are potential goalkeepers of atherosclerosis
Authors: Feng Yu , Xu Danyan
Published: November 2023

Short-chain fatty acids (SCFAs) are metabolites produced by gut bacteria and play a crucial role in various inflammatory diseases. Increasing evidence suggests that SCFAs can improve the occurrence and progression of atherosclerosis. However, the molecular mechanisms through which SCFAs regulate the development of atherosclerosis have not been fully elucidated. This review provides an overview of the research progress on SCFAs regarding their impact on the risk factors and pathogenesis associated with atherosclerosis, with a specific focus on their interactions with the endothelium and immune cells. These interactions encompass the inflammation and oxidative stress of endothelial cells, the migration of monocytes/macrophages, the lipid metabolism of macrophages, the proliferation and migration of smooth muscle cells, and the proliferation and differentiation of Treg cells. Nevertheless, the current body of research is insufficient to comprehensively understand the full spectrum of SCFAs’ mechanisms of action. Therefore, further in-depth investigations are imperative to establish a solid theoretical foundation for the development of clinical therapeutics in this context.
Parasitic infections related to anti-type 2 immunity monoclonal antibodies: a disproportionality analysis in the food and drug administration’s adverse event reporting system (FAERS)
Authors: Pera Victor , Brusselle Guy G. , Riemann Sebastian , Kors Jan A. , Van Mulligen Erik M. , Parry Rowan , de Wilde Marcel , Rijnbeek Peter R. , Verhamme Katia M. C.
Published: November 2023

Introduction: Monoclonal antibodies (mAbs) targeting immunoglobulin E (IgE) [omalizumab], type 2 (T2) cytokine interleukin (IL) 5 [mepolizumab, reslizumab], IL-4 Receptor (R) α [dupilumab], and IL-5R [benralizumab]), improve quality of life in patients with T2-driven inflammatory diseases. However, there is a concern for an increased risk of helminth infections. The aim was to explore safety signals of parasitic infections for omalizumab, mepolizumab, reslizumab, dupilumab, and benralizumab.

Methods: Spontaneous reports were used from the Food and Drug Administration’s Adverse Event Reporting System (FAERS) database from 2004 to 2021. Parasitic infections were defined as any type of parasitic infection term obtained from the Standardised Medical Dictionary for Regulatory Activities® (MedDRA®). Safety signal strength was assessed by the Reporting Odds Ratio (ROR).

Results: 15,502,908 reports were eligible for analysis. Amongst 175,888 reports for omalizumab, mepolizumab, reslizumab, dupilumab, and benralizumab, there were 79 reports on parasitic infections. Median age was 55 years (interquartile range 24–63 years) and 59.5% were female. Indications were known in 26 (32.9%) reports; 14 (53.8%) biologicals were reportedly prescribed for asthma, 8 (30.7%) for various types of dermatitis, and 2 (7.6%) for urticaria. A safety signal was observed for each biological, except for reslizumab (due to lack of power), with the strongest signal attributed to benralizumab (ROR = 15.7, 95% Confidence Interval: 8.4–29.3).

Conclusion: Parasitic infections were disproportionately reported for mAbs targeting IgE, T2 cytokines, or T2 cytokine receptors. While the number of adverse event reports on parasitic infections in the database was relatively low, resulting safety signals were disproportionate and warrant further investigation.