bluuebunny/crossref_metadata_2025 huggingface dataset:
Stakeholders' knowledge of threatened freshwater fishes and their involvement in fishery value chains in order to assist conservation in developing countries
Authors: Galib Shams M. , Naher Sheratun , Arnob Sadman S. , Khatun Mst. Tasnima , Reza Md. Selim , Parvez Md. Taskin , Sun Jingrui , Lucas Martyn C.
Published: December 2023

Introduction

Improved conservation of exploited freshwater biodiversity is an increasing priority globally, but in developing countries there is often little insight of stakeholder attitudes within the value chains through which exploited species are passed, upon which to make informed management decisions.

Methods

We determined knowledge concerning threatened freshwater fishes in Bangladesh by key stakeholder groups (fishermen, faria agents, commission agents, retailers and consumers; n = 485 respondents) and their participation level in the threatened fish value chain. We also determined factors affecting local ecological knowledge and participation in the value chain.

Results and discussion

The highest mean number of threatened fish species (4.8 ± 3.5% of species) was identified by the fishermen group, whereas consumers identified fewest (0.5 ± 1.1% of species). All respondent groups participated in the threatened fish value chain and their participation varied across respondent groups. 45.3% of the total number of threatened fish species appeared in the value chain. Participation level was highest for commission agents, involved in the trade of 21.5 ± 4.2% of threatened fish species, and lowest for consumers (7.4 ± 6.5% of threatened species). For fishermen, the principal component “experience-income-age” and the interaction between education and financial loan factors affected fishers' participation in the threatened fish value chain positively whereas, this was negatively affected by their knowledge level of threatened fishes. This study reveals the poor knowledge of stakeholder groups regarding threatened fishes, but establishes their active participation in the value chain of these species in Bangladesh. With limited resources for conservation of threatened species in many developing countries, it is very risky to implement commonly used in-situ conservation methods (e.g., habitat quality improvement) without fuller buy-in from the stakeholders.

Conclusions

We recommend specific protection laws for threatened fishes and awareness building campaigns for stakeholder groups to ensure minimum impact to threatened fish species. As overharvesting is a major cause of threatened fish species decline, such training programmes should be designed for fishers in developing regions. Education programmes on threats to ecosystems and biodiversity should be prioritized in schools and fishing communities. In addition, regular monitoring for protected species at harvesting sites and fishing markets should be ensured.
Genomic inbreeding measures applied to a population of mice divergently selected for birth weight environmental variance
Authors: Ojeda-Marín Candela , Cervantes Isabel , Formoso-Rafferty Nora , Gutiérrez Juan Pablo
Published: December 2023

This study aimed to compare different inbreeding measures estimated from pedigree and molecular data from two divergent mouse lines selected for environmental birth weight during 26 generations. Furthermore, the performance of different approaches and both molecular and pedigree data sources for estimating Ne were tested in this population. A total of 1,699 individuals were genotyped using a high-density genotyping array. Genomic relationship matrices were used to calculate molecular inbreeding: Nejati-Javaremi (FNEJ), Li and Horvitz (FL&H), Van Raden method 1 (FVR1) and method 2 (FVR2), and Yang (FYAN). Inbreeding based on runs of homozygosity (FROH) and pedigree inbreeding (FPED) were also computed. FROH, FNEJ, and FL&H were also adjusted for their average values in the first generation of selection and named FROH0, FNEJ0, and FL&H0. ∆F was calculated from pedigrees as the individual inbreeding rate between the individual and his parents (∆FPEDt) and individual increases in inbreeding (∆FPEDi). Moreover, individual ∆F was calculated from the different molecular inbreeding coefficients (∆FNEJ0, ∆FL&H, ∆FL&H0, ∆FVR1, ∆FVR2, ∆FYAN, and ∆FROH0). The Ne was obtained from different ∆F, such as NePEDt, NePEDi, NeNEJ0, NeL&H, NeL&H0, NeVR1, NeVR2, NeYAN, and NeROH0. Comparing with FPED, FROH, FNEJ and FVR2 overestimated inbreeding while FNEJ0, FL&H, FL&H0, FVR1 and FYAN underestimated inbreeding. Correlations between inbreeding coefficients and ∆F were calculated. FROH had the highest correlation with FPED (0.89); FYAN had correlations >0.95 with all the other molecular inbreeding coefficients. NePEDi was more reliable than NePEDt and presented similar behaviour to NeL&H0 and NeNEJ0. Stable trends in Ne were not observed until the 10th generation. In the 10th generation NePEDi was 42.20, NeL&H0 was 45.04 and NeNEJ0 was 45.05 and in the last generation these Ne were 35.65, 35.94 and 35.93, respectively FROH presented the highest correlation with FPED, which addresses the identity by descent probability (IBD). The evolution of NeL&H0 and NeNEJ0 was the most similar to that of NePEDi. Data from several generations was necessary to reach a stable trend for Ne, both with pedigree and molecular data. This population was useful to test different approaches to computing inbreeding coefficients and Ne using molecular and pedigree data.
Methods for quantifying rain-splash dispersal of Neonectria ditissima conidia in apple canopies
Authors: Campbell Rebecca E. , Wallis D. Roger , Walter Monika
Published: December 2023

Many microorganisms can be dispersed by rain-splash, whereby spores become suspended in water and are spread via droplets. The resulting dispersal gradient is dependent on several factors including rainfall intensity, the nature of the plant canopy and its effects on splash, deposition, redistribution (secondary splash) and filtering. Gradients of spore dispersal with distance are important for understanding epidemics, and the primary dispersal gradient can shape an epidemic for several pathogen generations. However, microorganisms are difficult to trap, identify and enumerate efficiently. This makes it difficult to study the spread and dispersal of pathogens to aid in biosecurity responses and management of epidemics. We used macroconidia of Neonectria ditissima, the causal organism of apple canker, to explore patterns of rain-splash dispersal in tree canopies. We investigated the use of a fluorescent tracer dye, PTSA (1,3,6,8-pyrenetetrasulfonic acid), as a surrogate to conidia capture during natural and artificial rain events, and lens tissue as ‘surrogate leaves’ to recapture tracer dye. Conidia and dye were released from central point sources 2.5 m above the ground and recaptured in passive rainwater traps or artificial ‘leaves’. Quantile regression and exponential models were used to explore variation and dispersal gradients derived for both conidia and dye, with and without tree canopy and with natural or artificial precipitation. Estimated dispersal gradients were steeper with a flatter tail when no tree canopy was present, whereas presence of tree canopy resulted in more variation and shallower predicted dispersal gradients, with fatter tails, predicting potential dispersal to further distances from the source. The majority of conidia and dye were recaptured at less than 1 m from the source, but small concentrations of spores were detected up to 3 m and dye more than 6 m. High variation in natural conditions requires further investigation to fully quantify natural dispersal gradients. Nevertheless, these results show the merit of tracer dye, artificial leaves, and quantile regression as tools to estimate potential dispersal patterns of N. ditissima and other rain-splash dispersed microorganisms, considering rain-splash factors in real canopies and natural situations for predicting inoculum dispersal.
Dipeptidyl peptidase 1 inhibition as a potential therapeutic approach in neutrophil-mediated inflammatory disease
Authors: Chalmers James D. , Kettritz Ralph , Korkmaz Brice
Published: December 2023

Neutrophils have a critical role in the innate immune response to infection and the control of inflammation. A key component of this process is the release of neutrophil serine proteases (NSPs), primarily neutrophil elastase, proteinase 3, cathepsin G, and NSP4, which have essential functions in immune modulation and tissue repair following injury. Normally, NSP activity is controlled and modulated by endogenous antiproteases. However, disruption of this homeostatic relationship can cause diseases in which neutrophilic inflammation is central to the pathology, such as chronic obstructive pulmonary disease (COPD), alpha-1 antitrypsin deficiency, bronchiectasis, and cystic fibrosis, as well as many non-pulmonary pathologies. Although the pathobiology of these diseases varies, evidence indicates that excessive NSP activity is common and a principal mediator of tissue damage and clinical decline. NSPs are synthesized as inactive zymogens and activated primarily by the ubiquitous enzyme dipeptidyl peptidase 1, also known as cathepsin C. Preclinical data confirm that inactivation of this protease reduces activation of NSPs. Thus, pharmacological inhibition of dipeptidyl peptidase 1 potentially reduces the contribution of aberrant NSP activity to the severity and/or progression of multiple inflammatory diseases. Initial clinical data support this view. Ongoing research continues to explore the role of NSP activation by dipeptidyl peptidase 1 in different disease states and the potential clinical benefits of dipeptidyl peptidase 1 inhibition.
Antibodies as clinical tools for tuberculosis
Authors: McIntyre Sophie , Warner Jeffrey , Rush Catherine , Vanderven Hillary A.
Published: December 2023

Tuberculosis (TB) is a leading cause of morbidity and mortality worldwide. Global research efforts to improve TB control are hindered by insufficient understanding of the role that antibodies play in protective immunity and pathogenesis. This impacts knowledge of rational and optimal vaccine design, appropriate diagnostic biomarkers, and development of therapeutics. Traditional approaches for the prevention and diagnosis of TB may be less efficacious in high prevalence, remote, and resource-poor settings. An improved understanding of the immune response to the causative agent of TB, Mycobacterium tuberculosis (Mtb), will be crucial for developing better vaccines, therapeutics, and diagnostics. While memory CD4+ T cells and cells and cytokine interferon gamma (IFN-g) have been the main identified correlates of protection in TB, mounting evidence suggests that other types of immunity may also have important roles. TB serology has identified antibodies and functional characteristics that may help diagnose Mtb infection and distinguish between different TB disease states. To date, no serological tests meet the World Health Organization (WHO) requirements for TB diagnosis, but multiplex assays show promise for improving the sensitivity and specificity of TB serodiagnosis. Monoclonal antibody (mAb) therapies and serum passive infusion studies in murine models of TB have also demonstrated some protective outcomes. However, animal models that better reflect the human immune response to Mtb are necessary to fully assess the clinical utility of antibody-based TB prophylactics and therapeutics. Candidate TB vaccines are not designed to elicit an Mtb-specific antibody response, but evidence suggests BCG and novel TB vaccines may induce protective Mtb antibodies. The potential of the humoral immune response in TB monitoring and control is being investigated and these studies provide important insight into the functional role of antibody-mediated immunity against TB. In this review, we describe the current state of development of antibody-based clinical tools for TB, with a focus on diagnostic, therapeutic, and vaccine-based applications.
Causal relationship between asthma and ulcerative colitis and the mediating role of interleukin-18: a bidirectional Mendelian study and mediation analysis
Authors: Zou Xin , Lu Rui-Ling , Liao Bin , Liu Shi-Jie , Dai Shi-Xue
Published: December 2023

Objective

Numerous observational investigations have documented a correlation between asthma and ulcerative colitis(UC). In this Mendelian Randomization (MR) study, we utilized extensive summary data from Genome-Wide Association Studies (GWAS) to further estimate the association between adult-onset asthma and the risk of UC, and to investigate the role of Interleukin-18 (IL-18) as a potential mediator.

Materials and methods

A two-step, two-sample MR study was conducted through mediation analysis. For this study, we employed a two-sample MR analysis using the inverse variance-weighted (IVW), weighted median, weighted mode, and MR-Egger regression techniques. We utilized publicly accessible summary statistics from a GWAS meta-analysis of adult-onset asthma in the UK Biobank (n=327,253; cases=26,582; controls=300,671) as the exposure factor. The outcomes were derived from GWAS data of individuals with European ancestry (n=26,405; cases=6,687; controls=19,718). GWAS data for IL-18 were obtained from individuals of European ancestry (n=9,785,222; cases=3,636; controls=9,781,586).

Results

The MR analysis indicates that adult-onset asthma is associated with an increased risk of UC, with an odds ratio (OR) of 1.019 (95% CI 1.001–1.045, P=0.006). However, there is no strong evidence to suggest that UC significantly impacts the risk of adult-onset asthma. IL-18 may act as a potential mediator in the causal relationship between adult-onset asthma and UC, with a mediation proportion of 3.9% (95% CI, 0.6%–6.9%).

Conclusion

In summary, our study established a causal relationship between asthma and UC, in which IL-18 contributes to a small extent. However, the primary factors underlying the influence of asthma on UC remain unclear. Future research should focus on identifying other potential mediators. In clinical practice, it is important to pay greater attention to intestinal lesions in patients with asthma.
Walnut peptide alleviates obesity, inflammation and dyslipidemia in mice fed a high-fat diet by modulating the intestinal flora and metabolites
Authors: Li Lei , Wang Si , Zhang Tong , Lv Bijun , Jin Yanling , Wang Yue , Chen Xiaojiao , Li Ning , Han Niping , Wu Yueying , Yuan Jiali
Published: December 2023

Introduction

Obesity is a chronic disease in which the body stores excess energy in the form of fat, and intestinal bacterial metabolism and inflammatory host phenotypes influence the development of obesity. Walnut peptide (WP) is a small molecule biopeptide, and the mechanism of action of WP against metabolic disorders has not been fully elucidated. In this study, we explored the potential intervention mechanism of WP on high-fat diet (HFD)-induced obesity through bioinformatics combined with animal experiments.

Methods

PPI networks of Amino acids and their metabolites in WP (AMWP) and “obesity” and “inflammation” diseases were searched and constructed by using the database, and their core targets were enriched and analyzed. Subsequently, Cytoscape software was used to construct the network diagram of the AMWP-core target-KEGG pathway and analyze the topological parameters. MOE2019.0102 was used to verify the molecular docking of core AMWP and core target. Subsequently, an obese Mice model induced by an HFD was established, and the effects of WP on obesity were verified by observing weight changes, glucose, and lipid metabolism levels, liver pathological changes, the size of adipocytes in groin adipose tissue, inflammatory infiltration of colon tissue, and intestinal microorganisms and their metabolites.

Results

The network pharmacology and molecular docking showed that glutathione oxide may be the main active component of AMWP, and its main targets may be EGFR, NOS3, MMP2, PLG, PTGS2, AR. Animal experiments showed that WP could reduce weight gain and improve glucose-lipid metabolism in HFD-induced obesity model mice, attenuate hepatic lesions reduce the size of adipocytes in inguinal adipose tissue, and reduce the inflammatory infiltration in colonic tissue. In addition, the abundance and diversity of intestinal flora were remodeled, reducing the phylum Firmicutes/Bacteroidetes (F/B) ratio, while the intestinal mucosal barrier was repaired, altering the content of short-chain fatty acids (SCFAs), and alleviating intestinal inflammation in HFD-fed mice. These results suggest that WP intervenes in HFD-induced obesity and dyslipidemia by repairing the intestinal microenvironment, regulating flora metabolism and anti-inflammation.

Discussion

Our findings suggest that WP intervenes in HFD-induced obesity and dyslipidemia by repairing the intestinal microenvironment, regulating flora metabolism, and exerting anti-inflammatory effects. Thus, WP may be a potential therapeutic strategy for preventing and treating metabolic diseases, and for alleviating the intestinal flora disorders induced by these diseases. This provides valuable insights for the development of WP therapies.
Comparative effects of acupuncture and metformin on insulin sensitivity in overweight/obese and lean women with polycystic ovary syndrome and insulin resistance: a post hoc analysis of a randomized trial
Authors: Cao Jie , Nie GuanHua , Dai Zhihao , Shan Dan , Wei Zhihong
Published: December 2023

Objective

This study explored the efficacy of acupuncture and metformin in enhancing insulin sensitivity among women with polycystic ovary syndrome (PCOS) and insulin resistance (IR), distinguishing between overweight/obese and lean groups.

Methods

A post-hoc analysis of a randomized trial (NCT02491333) was undertaken. Participants were women aged 18–40 with PCOS and IR. They were randomized to receive true acupuncture with a placebo, metformin with sham acupuncture, or sham acupuncture with a placebo for 4 months, with follow-up visits over 3 months. Our study, involving 339 women, assessed the differential impact of acupuncture and metformin on insulin sensitivity in overweight/obese [body mass index (BMI) ≥ 24] versus lean women (BMI < 24). Primary outcomes measured changes in the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at 4 and 7 months. Secondary outcomes assessed changes in glucose area under the curve (glucoseAUC) during the oral glucose tolerance test (OGTT) and BMI changes at 4 months.

Results

Overweight/obese participants were generally older with higher measurements in various health metrics, but lower levels in specific hormonal metrics compared to lean women (p < 0.05). Among overweight/obese women, metformin outperformed acupuncture in reducing HOMA-IR levels (p = 0.004) and showed a significant drop from the baseline after 4 months (p < 0.05). In contrast, acupuncture’s effect on HOMA-IR did not significantly differ from sham acupuncture at 4 and 7 months. For lean women, metformin and acupuncture showed comparable improvements in HOMA-IR, with notable declines at 4 and 7 months (p < 0.05). Acupuncture proved more beneficial for lean women than their overweight/obese counterparts after 4 months (p = 0.021).

Conclusion

In overweight/obese women with PCOS and IR, acupuncture was less effective than metformin in enhancing insulin sensitivity. However, in lean women, acupuncture’s efficacy was comparable to metformin. Further studies are required to validate these observations.
Comparative analysis of codon usage patterns of Plasmodium helical interspersed subtelomeric (PHIST) proteins
Authors: Yang Baoling , Cheng Ziwen , Luo Like , Cheng Kuo , Gan Shengqi , Shi Yuyi , Liu Che , Wang Dawei
Published: December 2023

Background

Plasmodium falciparum is a protozoan parasite that causes the most severe form of malaria in humans worldwide, which is predominantly found in sub-Saharan Africa, where it is responsible for the majority of malaria-related deaths. Plasmodium helical interspersed subtelomeric (PHIST) proteins are a family of proteins, with a conserved PHIST domain, which are typically located at the subtelomeric regions of the Plasmodium falciparum chromosomes and play crucial roles in the interaction between the parasite and its human host, such as cytoadherence, immune evasion, and host cell remodeling. However, the specific utilization of synonymous codons by PHIST proteins in Plasmodium falciparum is still unknown.

Methods

Codon usage bias (CUB) refers to the unequal usage of synonymous codons during translation, resulting in over- or underrepresentation of certain nucleotide patterns. This imbalance in CUB can impact various cellular processes, including protein expression levels and genetic variation. To investigate this, the CUB of 88 PHIST protein coding sequences (CDSs) from 5 subgroups were analyzed in this study.

Results

The results showed that both codon base composition and relative synonymous codon usage (RSCU) analysis identified a higher occurrence of AT-ended codons (AGA and UUA) in PHIST proteins of Plasmodium falciparum. The average effective number of codons (ENC) for these PHIST proteins was 36.69, indicating a weak codon preference among them, as it was greater than 35. Additionally, the correlation analysis among codon base composition (GC1, GC2, GC3, GCs), codon adaptation index (CAI), codon bias index (CBI), frequency of optimal codons (FOP), ENC, general average hydropathicity (GRAVY), aromaticity (AROMO), length of synonymous codons (L_sym), and length of amino acids (L_aa) revealed the influence of base composition and codon usage indices on codon usage bias, with GC1 having a significant impact in this study. Furthermore, the neutrality plot analysis, PR2-bias plot analysis, and ENC-GC3 plot analysis provided additional evidence that natural selection plays a crucial role in determining codon bias in PHIST proteins.

Conclusion

In conclusion, this study has enhanced our understanding of the characteristics of codon usage and genetic evolution in PHIST proteins, thereby providing data foundation for further research on antimalarial drugs or vaccines.
Enhanced YOLOv7 integrated with small target enhancement for rapid detection of objects on water surfaces
Authors: Yu Jie , Zheng Hao , Xie Li , Zhang Lei , Yu Mei , Han Jin
Published: December 2023

Unmanned surface vessel (USV) target detection algorithms often face challenges such as misdetection and omission of small targets due to significant variations in target scales and susceptibility to interference from complex environments. To address these issues, we propose a small target enhanced YOLOv7 (STE-YOLO) approach. Firstly, we introduce a specialized detection branch designed to identify tiny targets. This enhancement aims to improve the multi-scale target detection capabilities and address difficulties in recognizing targets of different sizes. Secondly, we present the lite visual center (LVC) module, which effectively fuses data from different levels to give more attention to small targets. Additionally, we integrate the lite efficient layer aggregation networks (L-ELAN) into the backbone network to reduce redundant computations and enhance computational efficiency. Lastly, we use Wise-IOU to optimize the loss function definition, thereby improving the model robustness by dynamically optimizing gradient contributions from samples of varying quality. We conducted experiments on the WSODD dataset and the FIOW-Img dataset. The results on the comprehensive WSODD dataset demonstrate that STE-YOLO, when compared to YOLOv7, reduces network parameters by 14% while improving AP50 and APs scores by 2.1% and 1.6%, respectively. Furthermore, when compared to five other leading target detection algorithms, STE-YOLO demonstrates superior accuracy and efficiency.
Genetic knockout of NTRK2 by CRISPR/Cas9 decreases neurogenesis and favors glial progenitors during differentiation of neural progenitor stem cells
Authors: Roussel-Gervais Audrey , Sgroi Stéphanie , Cambet Yves , Lemeille Sylvain , Seredenina Tamara , Krause Karl-Heinz , Jaquet Vincent
Published: December 2023

The tropomyosin receptor kinase B (TrkB) is encoded by the NTRK2 gene. It belongs to the family of transmembrane tyrosine kinases, which have key roles in the development and maintenance of the nervous system. Brain-derived neurotrophic factor (BDNF) and the neurotrophins NT3 and NT4/5 have high affinity for TrkB. Dysregulation of TrkB is associated to a large spectrum of diseases including neurodegeneration, psychiatric diseases and some cancers. The function of TrkB and its role in neural development have mainly been decrypted using transgenic mouse models, pharmacological modulators and human neuronal cell lines overexpressing NTRK2. In this study, we identified high expression and robust activity of TrkB in ReNcell VM, an immortalized human neural progenitor stem cell line and generated NTRK2-deficient (NTRK2–/–) ReNcell VM using the CRISPR/Cas9 gene editing technology. Global transcriptomic analysis revealed major changes in expression of specific genes responsible for neurogenesis, neuronal development and glial differentiation. In particular, key neurogenic transcription factors were massively down-regulated in NTRK2–/– cells, while early glial progenitor markers were enriched in NTRK2–/– cells compared to NTRK2+/+. This indicates a previously undescribed inhibitory role of TrkB on glial differentiation in addition to its well-described pro-neurogenesis role. Altogether, we have generated for the first time a human neural cell line with a loss-of-function mutation of NTRK2, which represents a reproducible and readily available cell culture system to study the role of TrkB during human neural differentiation, analyze the role of TrkB isoforms as well as validate TrkB antibodies and pharmacological agents targeting the TrkB pathway.
A novel cell-based immunofluorescence assay for the detection of autoantibodies to myelin-associated glycoprotein
Authors: Mariotto Sara , de Gaspari Piera , Jäger Dominik , Hahn Stefanie , Forni Cindy , Saschenbrecker Sandra , Lattwein Erik , Dinoto Alessandro , Ferrari Sergio
Published: December 2023

Peripheral neuropathy with antibodies to myelin-associated glycoprotein (MAG) is an autoimmune demyelinating disorder of the peripheral nervous system caused by pathogenic IgM recognizing the human natural killer-1 glycoepitope expressed on MAG. This study aimed to analyze the performance of a new indirect immunofluorescence cell-based assay (CBA, EUROIMMUN) for the detection of anti-MAG IgM. Antibody reactivity was determined in sera from 95 patients with clinical and neurophysiological evidence of anti-MAG-associated neuropathy and in control samples from 55 patients with other forms of peripheral neuropathy. Compared to the results of the gold standard method (ELISA, Bühlmann) and using samples at a dilution of 1:100, the CBA had a sensitivity of 98.9% and a specificity of 100% (PPV 100%, NPV 98.2%). In conclusion, the CBA allows the detection of antibodies to MAG using an easy and standardized technique, and it presents a sensitive and specific alternative to the more time-consuming ELISA. Larger studies are needed to address anti-MAG titer monitoring in parallel with clinical activity.
The burden of myasthenia gravis – highlighting the impact on family planning and the role of social support
Authors: Stein Maike , Grittner Ulrike , Stegherr Regina , Gerischer Lea , Stascheit Frauke , Hoffmann Sarah , Herdick Meret , Legg David , Marbin Derin , Meisel Andreas , Lehnerer Sophie
Published: December 2023

Background

Myasthenia gravis (MG) is a rare autoimmune disease and chronic condition that necessitates specialized care. Patients experience a significant burden of disease affecting various aspects of their lives. The aim of this study was to investigate the impact of MG on family planning, challenges associated with pregnancy, childcare responsibilities and the extent to which MG patients perceive and utilize social support.

Methods

This analysis used data from our main data of a large cross-sectional study built on a questionnaire-based survey encompassing 1,660 MG patients and members of the German Myasthenia Association (Deutsche Myasthenie Gesellschaft), and focused on sociodemographic, clinical and family planning relevant data points.

Results

Decisions regarding family planning were significantly impacted for individuals with MG when MG symptoms started either before or during their family planning (men: n = 19 and 29.7%; women: n = 156 and 58.4%). In this subgroup a substantial proportion opted against parenthood due to MG (men: n = 8 and 50.0%; women: n = 54 and 38.0% and/or another n = 12 and 8.4% of female participants encountered partner-related refusals). In the subgroup of female SP with MG starting before or during family planning who have reported ever been pregnant the self-reported miscarriage rate was 29.0% (n = 51). MG patients with medium incomes or moderate disease severity reported lower levels of perceived social support. 42.7% (n = 606) of participants needed assistance in negotiations with health insurers and 28.0% (n = 459) needed support for transportation to medical appointments.

Conclusion

This study shows a significant impact of MG on family planning decisions, affecting both women and men, and often resulting in life-altering decisions such as voluntary childlessness due to MG. The significance of social support becomes evident as a vital factor, especially when navigating through the healthcare system. Tailored healthcare approaches, organized guidance and comprehensive support is needed to enable informed decision-making and offer assistance for MG patients.

Clinical trial registration

https://clinicaltrials.gov/study/NCT03979521, Registered 7 June 2019 (retrospectively registered).
Artificial intelligence in neuro-oncology
Authors: Nakhate Vihang , Gonzalez Castro L. Nicolas
Published: December 2023

Artificial intelligence (AI) describes the application of computer algorithms to the solution of problems that have traditionally required human intelligence. Although formal work in AI has been slowly advancing for almost 70 years, developments in the last decade, and particularly in the last year, have led to an explosion of AI applications in multiple fields. Neuro-oncology has not escaped this trend. Given the expected integration of AI-based methods to neuro-oncology practice over the coming years, we set to provide an overview of existing technologies as they are applied to the neuropathology and neuroradiology of brain tumors. We highlight current benefits and limitations of these technologies and offer recommendations on how to appraise novel AI-tools as they undergo consideration for integration into clinical workflows.
Automatic epileptic seizure detection based on EEG using a moth-flame optimization of one-dimensional convolutional neural networks
Authors: Wang Baozeng , Yang Xingyi , Li Siwei , Wang Wenbo , Ouyang Yichen , Zhou Jin , Wang Changyong
Published: December 2023

Introduction

Frequent epileptic seizures can cause irreversible damage to the brains of patients. A potential therapeutic approach is to detect epileptic seizures early and provide artificial intervention to the patient. Currently, extracting electroencephalogram (EEG) features to detect epileptic seizures often requires tedious methods or the repeated adjustment of neural network hyperparameters, which can be time- consuming and demanding for researchers.

Methods

This study proposes an automatic detection model for an EEG based on moth-flame optimization (MFO) optimized one-dimensional convolutional neural networks (1D-CNN). First, according to the characteristics and need for early epileptic seizure detection, a data augmentation method for dividing an EEG into small samples is proposed. Second, the hyperparameters are tuned based on MFO and trained for an EEG. Finally, the softmax classifier is used to output EEG classification from a small-sample and single channel.

Results

The proposed model is evaluated with the Bonn EEG dataset, which verifies the feasibility of EEG classification problems that involve up to five classes, including healthy, preictal, and ictal EEG from various brain regions and individuals.

Discussion

Compared with existing advanced optimization algorithms, such as particle swarm optimization, genetic algorithm, and grey wolf optimizer, the superiority of the proposed model is further verified. The proposed model can be implemented into an automatic epileptic seizure detection system to detect seizures in clinical applications.
Toward a holographic brain paradigm: a lipid-centric model of brain functioning
Authors: Cavaglià Marco , Deriu Marco A. , Tuszynski Jack A.
Published: December 2023

Due to the stimulation of neuronal membrane dipoles by action potentials, under suitable conditions coherent dipole oscillations can be formed. We argue that these dipole oscillations satisfy the weak Bose-Einstein condensate criteria of the Froehlich model of biological coherence. They can subsequently generate electromagnetic fields (EMFs) propagating in the inter-neuronal space. When neighboring neurons fire synchronously, EMFs can create interference patterns and hence form holographic images containing analog information about the sensory inputs that trigger neuronal activity. The mirror pattern projected by EMFs inside the neuron can encode information in the neuronal cytoskeleton. We outline an experimental verification of our hypothesis and its consequences for anesthesia, neurodegenerative diseases, and psychiatric states.
Causal link between prefrontal cortex and EEG microstates: evidence from patients with prefrontal lesion
Authors: Zhao Zongya , Ran Xiangying , Lv Shiyang , Wang Junming , Qiu Mengyue , Wang Chang , Xu Yongtao , Guo Xiao , Gao Zhixian , Mu Junlin , Yu Yi
Published: December 2023

Introduction

At present, elucidating the cortical origin of EEG microstates is a research hotspot in the field of EEG. Previous studies have suggested that the prefrontal cortex is closely related to EEG microstate C and D, but whether there is a causal link between the prefrontal cortex and microstate C or D remains unclear.

Methods

In this study, pretrial EEG data were collected from ten patients with prefrontal lesions (mainly located in inferior and middle frontal gyrus) and fourteen matched healthy controls, and EEG microstate analysis was applied.

Results

Our results showed that four classical EEG microstate topographies were obtained in both groups, but microstate C topography in patient group was obviously abnormal. Compared to healthy controls, the average coverage and occurrence of microstate C significantly reduced. In addition, the transition probability from microstate A to C and from microstate B to C in patient group was significantly lower than those of healthy controls.

Discussion

The above results demonstrated that the damage of prefrontal cortex especially inferior and middle frontal gyrus could lead to abnormalities in the spatial distribution and temporal dynamics of microstate C not D, showing that there is a causal link between the inferior and middle frontal gyrus and the microstate C. The significance of our findings lies in providing new evidence for elucidating the cortical origin of microstate C.
Moderate or greater daily coffee consumption is associated with lower incidence of metabolic syndrome in Taiwanese militaries: results from the CHIEF cohort study
Authors: Tsai Kun-Zhe , Huang Wei-Chun , Sui Xuemei , Lavie Carl J. , Lin Gen-Min
Published: December 2023

Background

Daily moderate coffee intake was found with a lower risk of specific metabolic abnormalities, e.g., hypertension and hyperglycemia, while the association of coffee intake and incident metabolic syndrome (MetS) has not been clarified in prior studies, particularly in young adults.

Methods

A total of 2,890 military personnel, aged 18–39 years, free of MetS were followed for incident MetS from baseline (2014) until the end of 2020 in Taiwan. Daily coffee amount consumed was grouped to those ≥3 cups or 600 mL (moderate or more amount) and those without. Incidence of MetS was identified in annual health examinations. MetS was diagnosed on the basis of the guideline of the International Diabetes Federation. Multivariable Cox regression model with adjustments for sex, age, body mass index, physical activity and substance use status at baseline was performed to determine the association.

Results

At baseline, there were 145 subjects with daily coffee intake ≥3 cups or 600 mL (5.0%) in the overall cohort. During a mean follow-up of 6.0 years, 673 incident MetS (23.3%) were found. As compared to those consuming less coffee or none, those consuming daily coffee ≥3 cups had a lower risk of MetS [hazard ratio (HR): 0.69 (95% confidence interval: 0.48, 0.99)].

Conclusion

This study suggests that adhering to the guideline recommended moderate or greater daily coffee consumption for promoting health, may confer advantages in preventing the development of MetS among young adults.
Clinical efficacy and safety evaluation of camrelizumab plus lenvatinib in adjuvant therapy after hepatocellular carcinoma surgery
Authors: Wang Xudan , Cao Weiwei , Qiu Yan , Ji Hongchen , Yuan Juzheng , Wu Weikang , Liu Fuyuan , Feng Liangyong , Ding Rui , Li Xiao , Tao Kaishan
Published: December 2023

Objective

To assess the efficacy and safety of camrelizumab plus different targeted drugs in adjuvant therapy after hepatocellular carcinoma (HCC) surgery.

Patients and methods

This retrospective cohort study included HCC patients who, after undergoing failed postoperative adjuvant lenvatinib therapy, received intravenous camrelizumab 200 mg every 3 weeks (C group, n = 97), camrelizumab plus oral apatinib 250 mg daily (C+A group, n = 125), camrelizumab plus oral lenvatinib 12 mg daily (for bodyweight ≥60 kg)/lenvatinib 8 mg daily (for bodyweight <60 kg) (C+L group, n = 120), or camrelizumab plus oral sorafenib 400 mg bi-daily (C+S group, n = 114) between October 2020 and October 2021. The outcomes including the objective response rate (ORR) and disease control rate (DCR) were evaluated by RECIST 1.1 and iRECIST. The median progression-free survival (mPFS), median overall survival (mOS), 6-month OS rate, 12-month OS rate, and adverse events were evaluated.

Results

As of 31 May 2022 with last follow-up time, the ORR was 17.2% for the C group, 44.6% for the C+A group, 47.9% for the C+L group, and 36.3% for the C+S group. The DCR was 72.0% for the C group, 81.8% for the C+A group, 85.5% for the C+L group, and 77.9% for the C+S group. The mPFS was 11.0 months (10.1–12.8) for the C group, 14.0 months (12.7–16.5) for the C+A group, 18.0 months (16.9–20.1) for the C+L group, and 12.0 months (9.7–14.4) for the C+S group. The mOS was 13.0 months (11.6–15.3) for the C group, 17.0 months (15.8–19.4) for the C+A group, 19.0 months (17.7–20.2) for the C+L group, and 15.0 months (14.1–17.3) for the C+S group. Grade 3 or 4 treatment-related adverse events occurred in 14 patients (14.4%) for the C group, 10 patients (8.0%) for the C+A group, 5 patients (4.2%) for the C+L group, and 11 patients (9.6%) for the C+S group. The most common adverse events were fatigue and transaminitis.

Conclusion

Camrelizumab combined with lenvatinib as adjuvant therapy showed promising efficacy and manageable safety in HCC patients. It might be a potential adjuvant therapy or second-line treatment for these patients.
Efficacy and safety of chlorpromazine as an adjuvant therapy for glioblastoma in patients with unmethylated MGMT gene promoter: RACTAC, a phase II multicenter trial
Authors: Pace Andrea , Lombardi Giuseppe , Villani Veronica , Benincasa Dario , Abbruzzese Claudia , Cestonaro Ilaria , Corrà Martina , Padovan Marta , Cerretti Giulia , Caccese Mario , Silvani Antonio , Gaviani Paola , Giannarelli Diana , Ciliberto Gennaro , Paggi Marco G.
Published: December 2023

Introduction

Drug repurposing is a promising strategy to develop new treatments for glioblastoma. In this phase II clinical trial, we evaluated the addition of chlorpromazine to temozolomide in the adjuvant phase of the standard first-line therapeutic protocol in patients with unmethylated MGMT gene promoter.

Methods

This was a multicenter phase II single-arm clinical trial. The experimental procedure involved the combination of CPZ with standard treatment with TMZ in the adjuvant phase of the Stupp protocol in newly-diagnosed GBM patients carrying an unmethylated MGMT gene promoter. Progression-free survival was the primary endpoint. Secondary endpoints were overall survival and toxicity.

Results

Forty-one patients were evaluated. Twenty patients (48.7%) completed 6 cycles of treatment with TMZ+CPZ. At 6 months, 27 patients (65.8%) were without progression, achieving the primary endpoint. Median PFS was 8.0 months (95% CI: 7.0-9.0). Median OS was 15.0 months (95% CI: 13.1-16.9). Adverse events led to reduction or interruption of CPZ dosage in 4 patients (9.7%).

Discussion

The addition of CPZ to standard TMZ in the first-line treatment of GBM patients with unmethylated MGMT gene promoter was safe and led to a longer PFS than expected in this population of patients. These findings provide proof-of-concept for the potential of adding CPZ to standard TMZ treatment in GBM patients with unmethylated MGMT gene promoter.

Clinical trial registration

https://clinicaltrials.gov/study/NCT04224441, identifier NCT04224441.
Hidden family rules: perspective on a dysfunctional paternalistic system and the persistence of pain
Authors: Hudson Matt , Johnson Mark I.
Published: December 2023

This article explores how paternalistic control and power reside within the family system and how this may influence pain and its persistence. Drawing upon clinical case studies and existing literature, this exploration emphasises the role of paternal dysfunction in creating emotional memory images and delves into how this may influence the chronification and treatment resistance of pain (i.e., making pain “sticky”). We argue that a dysfunctional paternalistic family system, often characterised by authoritarian dynamics, emotional neglect, and abuse, results in adverse experiences and emotional memory images that create a fertile ground for the entrenchment and propagation of psychosomatic symptoms, including pain. Further, the paper emphasizes the potential intergenerational effects of such a scenario, where inherited “Family Rules” drive maladaptive coping mechanisms, which contribute to the persistence of psychological and physiological distress across generations. Understanding these complexities offers new perspectives on treating psychological disorders and their physiological ramifications. It also highlights the urgency of addressing dysfunctional familial dynamics in psychotherapeutic interventions for both immediate and long-term psychophysiological health outcomes.
Moderate selenium mitigates hand grip strength impairment associated with elevated blood cadmium and lead levels in middle-aged and elderly individuals: insights from NHANES 2011–2014
Authors: Liang Yafeng , Wang Junqi , Wang Tianyi , Li Hangyu , Yin Chaohui , Liu Jialin , Wei Yulong , Fan Junxing , Feng Shixing , Zhai Shuangqing
Published: December 2023

Background: Selenium (Se) has been reported to have an antagonistic effect on heavy metals in animals. Nevertheless, there is a lack of epidemiological research examining whether Se can mitigate the adverse effects of cadmium (Cd) and lead (Pb) on hand grip strength (HGS) in middle-aged and elderly individuals.

Methods: This study used data from the 2011–2014 National Health and Nutrition Examination Survey (NHANES). HGS measurements were conducted by trained examiners with a dynamometer. Concentrations of Se, Cd, and Pb in blood were determined via inductively coupled plasma mass spectrometry. We employed linear regression, restricted cubic splines, and quantile g-computation (qgcomp) to assess individual and combined associations between heavy metals and HGS. The study also explored the potential influence of Se on these associations.

Results: In both individual metal and multi-metal models adjusted for confounders, general linear regression showed Se’s positive association with HGS, while Cd and Pb inversely related to it. At varying Se-Cd and Se-Pb concentrations, high Se relative to low Se can attenuate Cd and Pb’s HGS impact. An inverted U-shaped correlation exists between Se and both maximum and combined HGS, with Se’s benefit plateauing beyond approximately 200 μg/L. Stratified analysis by Se quartiles reveals Cd and Pb’s adverse HGS effects diminishing as Se levels increase. Qgcomp regression analysis detected Se alleviating HGS damage from combined Cd and Pb exposure. Subsequent subgroup analyses identified the sensitivity of women, the elderly, and those at risk of diabetes to HGS impairment caused by heavy metals, with moderate Se supplementation beneficial in mitigating this effect. In the population at risk for diabetes, the protective role of Se against heavy metal toxicity-induced HGS reduction is inhibited, suggesting that diabetic individuals should particularly avoid heavy metal-induced handgrip impairment.

Conclusion: Blood Cd and Pb levels are negatively correlated with HGS. Se can mitigate this negative impact, but its effectiveness plateaus beyond 200 μg/L. Women, the elderly, and those at risk of diabetes are more vulnerable to HGS damage from heavy metals. While Se supplementation can help, its protective effect is limited in high diabetes risk groups.
Rheological characterization of human follicular fluid under shear and extensional stress conditions
Authors: Muto Masakazu , Kikuchi Keigo , Yoshino Tatsuya , Muraoka Ayako , Iwata Shuichi , Nakamura Masanori , Osuka Satoko , Tamano Shinji
Published: December 2023

The rheology of human follicular fluid has been empirically evinced to be related to the reproductive health status of individuals, which supports its use as an indicator for improving the success rates of in vitro fertilization. However, there is a dearth of studies investigating the viscoelastic properties of human follicular fluid. Moreover, a comprehensive elucidation of the rheological properties of complex fluids necessitates the assessment of data regarding both shear and extensional viscosities. Nonetheless, to the best of our knowledge, the extant literature does not include reports on the behavior of follicular fluid under extensional conditions. Consequently, this study aimed to analyze the shear and extensional viscosities of human follicular fluid. Primarily, the impact of oocytes on the rheology of follicular fluid was evaluated by measuring the shear viscosity of this fluid using a high-resolution coaxial cylinder viscometer. The shear viscosity of follicular fluid exhibited marked differences depending on the presence or absence of oocytes. Subsequently, a measurement system that enables the handling of minute quantities of body fluid was developed to determine the extensional viscosity of follicular fluid, which contains albumin. A comparison of the acquired follicular fluid data with that of the protein solution containing albumin demonstrated that the follicular fluid alone displayed extensional behavior, whereas the protein solution did not. Therefore, it can be inferred that the protein solution is not its sole determinant, as other constituents of the fluid, such as peptides and cumulus cells, may determine its rheological properties. This observation was not attained through the conventional technique consisting in shear viscosity measurements.