bluuebunny/crossref_metadata_2025 huggingface dataset:
Explainability agreement between dermatologists and five visual explanations techniques in deep neural networks for melanoma AI classification
Authors: Giavina-Bianchi Mara , Vitor William Gois , Fornasiero de Paiva Victor , Okita Aline Lissa , Sousa Raquel Machado , Machado Birajara
Published: August 2023

Introduction

The use of deep convolutional neural networks for analyzing skin lesion images has shown promising results. The identification of skin cancer by faster and less expensive means can lead to an early diagnosis, saving lives and avoiding treatment costs. However, to implement this technology in a clinical context, it is important for specialists to understand why a certain model makes a prediction; it must be explainable. Explainability techniques can be used to highlight the patterns of interest for a prediction.

Methods

Our goal was to test five different techniques: Grad-CAM, Grad-CAM++, Score-CAM, Eigen-CAM, and LIME, to analyze the agreement rate between features highlighted by the visual explanation maps to 3 important clinical criteria for melanoma classification: asymmetry, border irregularity, and color heterogeneity (ABC rule) in 100 melanoma images. Two dermatologists scored the visual maps and the clinical images using a semi-quantitative scale, and the results were compared. They also ranked their preferable techniques.

Results

We found that the techniques had different agreement rates and acceptance. In the overall analysis, Grad-CAM showed the best total+partial agreement rate (93.6%), followed by LIME (89.8%), Grad-CAM++ (88.0%), Eigen-CAM (86.4%), and Score-CAM (84.6%). Dermatologists ranked their favorite options: Grad-CAM and Grad-CAM++, followed by Score-CAM, LIME, and Eigen-CAM.

Discussion

Saliency maps are one of the few methods that can be used for visual explanations. The evaluation of explainability with humans is ideal to assess the understanding and applicability of these methods. Our results demonstrated that there is a significant agreement between clinical features used by dermatologists to diagnose melanomas and visual explanation techniques, especially Grad-Cam.
Prophylactic feeding of neomycin to Holstein calves alters gut microbiota, bile acid metabolism, and expression of genes involved in immunometabolic regulation
Authors: Cangiano Lautaro R. , Ipharraguerre Ignacio R. , Guan Le Luo , Buss Lauralise N. , Amorin-Hegedus Rocio , Chirivi Miguel , Contreras G. Andres , Steele Michael A.
Published: August 2023

The objective of this study was to evaluate the effects of prophylactic neomycin administration on Holstein bull calves’ intestinal microbiota, bile acid (BA) metabolism, and transcript abundance of genes related to BA metabolism. A total of 36 calves were blocked by body weight and assigned to either non-medicated milk replacer (CTL), or neomycin for 14 days (ST) or 28 days (LT) in their milk replacer. At the end of the study, calves were euthanized to collect tissue and digesta samples from the gastrointestinal tract, liver, and adipose tissue for analysis of intestinal microbial diversity, bile acid concentration and profile in various body tissues, and gene expression related to bile acid, lipid, carbohydrate metabolism, and inflammation. Calves that received prophylactic administration of neomycin for 28 d (LT) had reduced species richness (chao1 index), and tended to have reduced phylogenetic diversity in the ileum tissue. The relative abundance of Lactobacillus, and Bifidobacterium in ileum and colon digesta were decreased in LT compared with CTL. Concentrations of primary, secondary, and total BA were increased by ST in ileal tissue. In plasma, ST and LT treatments had lower concentrations of secondary BA. Gene expression of the BA receptor FXR was increased in ileum and liver by LT compared to CTL. The expression of FXR and TGR5 in the liver was increased in the ST group compared with CTL, and in adipose tissue, 5 genes related to triglyceride, gluconeogenesis, and immune activation were differentially expressed between CTL and ST. In conclusion, we provide evidence that prophylactic administration of neomycin leads to aberrant changes in BA concentration and profile in different compartments of the enterohepatic system through a process that possibly entails antimicrobial disruption of key bacterial groups, which persists even after cessation of neomycin administration. Additionally, we uncovered an apparent link between dysregulated BA metabolism and changes in lipid metabolism and immune activation in adipose tissue and liver.
Microbial succession and its correlation with the dynamics of flavor compounds involved in the fermentation of Longxi bacon
Authors: Qu Yuling , Yun Jianmin , Li Yanhu , Ai Duiyuan , Zhang Wenwei
Published: August 2023

Introduction

Longxi bacon is a traditional fermented meat from Gansu province, China. The ripening process of the bacon is crucial for quality and flavor. The aim of this study was to gain deeper knowledges on the bacterial and fungal community diversity and the changes of chemical components including fatty acids and volatile compounds at different time points during the ripening of the bacon and to understand the relationship between microbial profiles and the chemical components related the bacon flavor.

Methods

Bacon samples were collected from days 0, 15, 30, 60 and 90. The bacterial and fungal compositions were analyzed with next generation sequencing targeting the 16S rDNA loci for bacteria and ITS loci for fungi. The fatty acids and the volatile components were analyzed by headspace solid phase micro extraction followed by gas chromatography/mass spectrometry (HS-SPME-GC/MS).

Results

We found that the abundance of bacteria in bacon was higher than that of fungi, and Psychrobacter, Brochothrix, Phoma and Trichoderma was the dominant bacon’s population. The largest contributors of volatiles were aldehydes, ketones and esters, and the main fatty acids were palmitic, oleic and linoleic acids. Pearson correlation analysis between microbial succession and key flavor substances showed that the production of Longxi bacon flavor is the result of a combination of bacteria and fungi. Ten bacteria genera and six fungi genera were determined as functional core microbiota for the flavor production based their dominance and functionality in microbial community. In addition, bacteria and fungi are involved in the oxidation and hydrolysis of fatty acids during the ripening of bacon, which also contributes to the formation of bacon flavor.

Discussion

This study provides a comprehensive analysis of the key microbiota involved in shaping bacon’s distinctive flavor. Here, the results presented should provide insight into the influence of the microenvironment on the microbial community in bacon and lay a foundation for further investigations into the food ecology of bacon.
Stronger effects of simultaneous warming and precipitation increase than the individual factor on soil bacterial community composition and assembly processes in an alpine grassland
Authors: Wei Xiaoting , Han Bing , Wu Bo , Shao Xinqing , Qian Yongqiang
Published: August 2023

Composition and traits of soil microbial communities that closely related to their ecological functions received extensive attention in the context of climate changes. We investigated the responses of soil bacterial community structure, traits, and functional genes to the individual warming, precipitation increases, and the combination of warming and precipitation increases in an alpine grassland in the Qinghai-Tibet Plateau that is experiencing warming and wetting climate change. Soil properties, plant diversity and biomass were measured, and the ecological processes and environmental factors driving bacterial community changes were further explored. Results indicated that the Shannon diversity of soil bacterial communities decreased significantly only under the combination treatment, which might due to the decreased plant diversity. Soil bacterial community composition was significantly correlated with soil pH, and was affected obviously by the combination treatment. At the taxonomic classification, the relative abundance of Xanthobacteraceae and Beijerinckiaceae increased 127.67 and 107.62%, while the relative abundance of Rubrobacteriaceae and Micromonosporaceae decreased 78.29 and 54.72% under the combination treatment. Functional genes related to nitrogen and phosphorus transformation were enhanced in the combination treatment. Furthermore, weighted mean ribosomal operon copy numbers that positively correlated with plant aboveground biomass increased remarkably in the combination treatment, indicating a trend of life-history strategies shift from oligotrophic to copiotrophic. Stochastic processes dominated soil bacterial community, and the proportion of stochasticity increased under the combination treatment. Our study highlights the significant effects of simultaneous warming and precipitation increase on soil bacterial community.
Thermophilic methane oxidation is widespread in Aotearoa-New Zealand geothermal fields
Authors: Houghton Karen M. , Carere Carlo R. , Stott Matthew B. , McDonald Ian R.
Published: August 2023

Geothermal areas represent substantial point sources for greenhouse gas emissions such as methane. While it is known that methanotrophic microorganisms act as a biofilter, decreasing the efflux of methane in most soils to the atmosphere, the diversity and the extent to which methane is consumed by thermophilic microorganisms in geothermal ecosystems has not been widely explored. To determine the extent of biologically mediated methane oxidation at elevated temperatures, we set up 57 microcosms using soils from 14 Aotearoa-New Zealand geothermal fields and show that moderately thermophilic (>40°C) and thermophilic (>60°C) methane oxidation is common across the region. Methane oxidation was detected in 54% (n = 31) of the geothermal soil microcosms tested at temperatures up to 75°C (pH 1.5–8.1), with oxidation rates ranging from 0.5 to 17.4 μmol g−1 d−1 wet weight. The abundance of known aerobic methanotrophs (up to 60.7% Methylacidiphilum and 11.2% Methylothermus) and putative anaerobic methanotrophs (up to 76.7% Bathyarchaeota) provides some explanation for the rapid rates of methane oxidation observed in microcosms. However, not all methane oxidation was attributable to known taxa; in some methane-consuming microcosms we detected methanotroph taxa in conditions outside of their known temperature range for growth, and in other examples, we observed methane oxidation in the absence of known methanotrophs through 16S rRNA gene sequencing. Both of these observations suggest unidentified methane oxidizing microorganisms or undescribed methanotrophic syntrophic associations may also be present. Subsequent enrichment cultures from microcosms yielded communities not predicted by the original diversity studies and showed rates inconsistent with microcosms (≤24.5 μmol d−1), highlighting difficulties in culturing representative thermophilic methanotrophs. Finally, to determine the active methane oxidation processes, we attempted to elucidate metabolic pathways from two enrichment cultures actively oxidizing methane using metatranscriptomics. The most highly expressed genes in both enrichments (methane monooxygenases, methanol dehydrogenases and PqqA precursor peptides) were related to methanotrophs from Methylococcaceae, Methylocystaceae and Methylothermaceae. This is the first example of using metatranscriptomics to investigate methanotrophs from geothermal environments and gives insight into the metabolic pathways involved in thermophilic methanotrophy.
The relation of ApoE and COMT gene–gene interactions to cognitive and motor function in community-dwelling older adults: a pilot study
Authors: Pizzonia Kendra L. , Suhr Julie A. , Clark Leatha A. , Clark Brian C.
Published: August 2023

Introduction

Certain genes increase the risk of age-related neurological dysfunction and/or disease. For instance, ApoE is a well-known gene carrying risk for Alzheimer’s disease, while COMT has been associated with age-related reductions in motor function. There is growing interest in the interrelationship between age-related changes in cognitive and motor function, and examining gene–gene interactions in this context. In this pilot study we examined the relations of the ApoE and COMT genes and their interaction to both cognitive and motor performance in community-dwelling older adults.

Methods

We leveraged an archived dataset from a prior study on age-related muscle weakness in community-dwelling older adults. Sample size was between 72 and 82 individuals based on missing data. We examined the relationship of ApoE (Ɛ4 presence/absence), rs4680 SNP on the COMT gene (Val/Met, Val/Val, Met/Met), and sex on (1) overall cognitive functioning and specific cognitive domains known to decline in aging (processing speed, immediate and delayed memory, semantic and phonemic fluency, and executive functioning), and (2) indices of motor function (four square step test, short physical performance battery, grip strength/forearm lean mass, and purdue pegboard test).

Results

Homozygous COMT genotypes were associated with worse global cognitive performance, immediate memory, and semantic fluency, but only for older adults with at least one ApoE Ɛ4 allele. There were main effects for COMT for delayed memory and a main effect for both COMT and ApoE for coding and phonemic fluency. Women scored higher than men in overall cognition, immediate and delayed memory, and semantic fluency. There were no main effects or gene interactions for a measure of executive functioning (trial making test part B) or any of the measures of motor function.

Discussion

COMT, ApoE, and their interaction influence cognitive performance, but not motor functioning, in community dwelling older adults. Our work supports prior literature concluding that a heterozygous COMT genotype may be beneficial to sustain healthy cognitive functioning with advancing age for those who have a higher ApoE genetic risk status (at least one Ɛ4 allele). Future research should investigate interactions between COMT and ApoE in larger samples with comprehensive assessment of cognition and motor functioning.
Ring attractor bio-inspired neural network for social robot navigation
Authors: Rivero-Ortega Jesús D. , Mosquera-Maturana Juan S. , Pardo-Cabrera Josh , Hurtado-López Julián , Hernández Juan D. , Romero-Cano Victor , Ramírez-Moreno David F.
Published: August 2023

Introduction

We introduce a bio-inspired navigation system for a robot to guide a social agent to a target location while avoiding static and dynamic obstacles. Robot navigation can be accomplished through a model of ring attractor neural networks. This connectivity pattern between neurons enables the generation of stable activity patterns that can represent continuous variables such as heading direction or position. The integration of sensory representation, decision-making, and motor control through ring attractor networks offers a biologically-inspired approach to navigation in complex environments.

Methods

The navigation system is divided into perception, planning, and control stages. Our approach is compared to the widely-used Social Force Model and Rapidly Exploring Random Tree Star methods using the Social Individual Index and Relative Motion Index as metrics in simulated experiments. We created a virtual scenario of a pedestrian area with various obstacles and dynamic agents.

Results

The results obtained in our experiments demonstrate the effectiveness of this architecture in guiding a social agent while avoiding obstacles, and the metrics used for evaluating the system indicate that our proposal outperforms the widely used Social Force Model.

Discussion

Our approach points to improving safety and comfort specifically for human-robot interactions. By integrating the Social Individual Index and Relative Motion Index, this approach considers both social comfort and collision avoidance features, resulting in better human-robot interactions in a crowded environment.
Emotional state as a modulator of autonomic and somatic nervous system activity in postural control: a review
Authors: Hall Karlee J. , Van Ooteghem Karen , McIlroy William E.
Published: August 2023

Advances in our understanding of postural control have highlighted the need to examine the influence of higher brain centers in the modulation of this complex function. There is strong evidence of a link between emotional state, autonomic nervous system (ANS) activity and somatic nervous system (somatic NS) activity in postural control. For example, relationships have been demonstrated between postural threat, anxiety, fear of falling, balance confidence, and physiological arousal. Behaviorally, increased arousal has been associated with changes in velocity and amplitude of postural sway during quiet standing. The potential links between ANS and somatic NS, observed in control of posture, are associated with shared neuroanatomical connections within the central nervous system (CNS). The influence of emotional state on postural control likely reflects the important influence the limbic system has on these ANS/somatic NS control networks. This narrative review will highlight several examples of behaviors which routinely require coordination between the ANS and somatic NS, highlighting the importance of the neurofunctional link between these systems. Furthermore, we will extend beyond the more historical focus on threat models and examine how disordered/altered emotional state and ANS processing may influence postural control and assessment. Finally, this paper will discuss studies that have been important in uncovering the modulatory effect of emotional state on postural control including links that may inform our understanding of disordered control, such as that observed in individuals living with Parkinson’s disease and discuss methodological tools that have the potential to advance understanding of this complex relationship.
Efficacy and safety of perampanel as early add-on therapy in Chinese patients with focal-onset seizures: a multicenter, open-label, single-arm study
Authors: Gao Lehong , Lu Qiang , Wang Zan , Yue Wei , Wang Guoping , Shao Xiaoqiu , Guo Yi , Yi Yonghong , Hong Zhen , Jiang Yuwu , Xiao Bo , Cui Guiyun , Gao Feng , Hu Jiasheng , Liang Jianmin , Zhang Meiyun , Wang Yuping
Published: August 2023

Background

No interventional study has been conducted in China to assess efficacy and safety of perampanel in treating Chinese patients with epilepsy, nor has there been any study on perampanel early add-on therapy in China. This interventional study aimed to assess efficacy and safety of perampanel as an early add-on treatment of focal-onset seizures (FOS) with or without focal-to-bilateral tonic–clonic seizures (FBTCS) in Chinese patients.

Methods

In this multicenter, open-label, single-arm, phase 4 interventional study, Chinese patients ≥ 12 years old with FOS with or without FBTCS who failed anti-seizure medication (ASM) monotherapy from 15 hospitals in China were enrolled and treated with perampanel add-on therapy (8-week titration followed by 24-week maintenance). The primary endpoint was 50% responder rate. Secondary endpoints included seizure-freedom rate and changes in seizure frequency from baseline. Treatment-emergent adverse events (TEAEs) and drug-related TEAEs were recorded.

Results

The full analysis set included 150 patients. The mean maintenance perampanel dose was 5.9 ± 1.5 mg/day and the 8-month retention rate was 72%. The 50% responder rate and seizure-freedom rate for all patients during maintenance were 67.9 and 30.5%, respectively. Patients with FBTCS had higher 50% responder rate (96.0%) and seizure-freedom rate (76.0%) during maintenance. Patients on concomitant sodium valproate had a significantly higher seizure-freedom rate than those on concomitant oxcarbazepine. Eight-six (55.1%) patients experienced treatment-related TEAEs, and the most common TEAEs were dizziness (36.5%), hypersomnia (11.5%), headache (3.9%), somnolence (3.2%), and irritability (3.2%). Withdrawal due to TEAEs occurred to 14.7% of the patients.

Conclusion

Perampanel early add-on was effective and safe in treating Chinese patients≥12 years old with FOS with or without FBTCS.

Clinical trial registrationwww.chictr.org.cn, Identifier ChiCTR2000039510.
Acupuncture for Parkinson's disease-related constipation: current evidence and perspectives
Authors: Zhang Jiale , Ge Xiaolei , Zhang Kaiqi , Qi Yun , Ren Shuo , Zhai Xu
Published: August 2023

Parkinson's disease-related constipation (PDC) is commonly associated with impaired dopamine transmission and gastrointestinal dysfunction. Current pharmacological treatments have limited efficacy and potential side effects. Acupuncture has shown promise as an alternative or adjunct therapy by modulating the brain–gut axis, gastrointestinal hormones, and autonomic function. Preliminary randomized trials have shown that acupuncture significantly improves constipation symptoms, bowel movements, and comfort compared to sham or drug treatments and is well-tolerated. The mechanisms of action may involve regulating the gut microbiota and mucosal immunity to improve dysbiosis and gastrointestinal motility. However, more rigorous studies are required to optimize acupuncture protocols and determine long-term efficacy and safety. In summary, acupuncture shows promise as an adjunct therapy for PDC, but further research is needed to confirm its efficacy and safety.
EEG-based clinical decision support system for Alzheimer's disorders diagnosis using EMD and deep learning techniques
Authors: AlSharabi Khalil , Salamah Yasser Bin , Aljalal Majid , Abdurraqeeb Akram M. , Alturki Fahd A.
Published: August 2023

Introduction

Despite the existence of numerous clinical techniques for identifying neurological brain disorders in their early stages, Electroencephalogram (EEG) data shows great promise as a means of detecting Alzheimer's disease (AD) at an early stage. The main goal of this research is to create a reliable and accurate clinical decision support system leveraging EEG signal processing to detect AD in its initial phases.

Methods

The research utilized a dataset consisting of 35 neurotypical individuals, 31 patients with mild AD, and 22 patients with moderate AD. Data were collected while participants were at rest. To extract features from the EEG signals, a band-pass filter was applied to the dataset and the Empirical Mode Decomposition (EMD) technique was employed to decompose the filtered signals. The EMD technique was then leveraged to generate feature vectors by combining multiple signal features, thereby enhancing diagnostic performance. Various artificial intelligence approaches were also explored and compared to identify features of the extracted EEG signals distinguishing mild AD, moderate AD, and neurotypical cases. The performance of the classifiers was evaluated using k-fold cross-validation and leave-one-subject-out (LOSO) cross-validation methods.

Results

The results of this study provided valuable insights into potential avenues for the early diagnosis of AD. The performance of the various offered methodologies has been compared and evaluated by computing the overall diagnosis precision, recall, and accuracy. The proposed methodologies achieved a maximum classification accuracy of 99.9 and 94.8% for k-fold and LOSO cross-validation techniques, respectively.

Conclusion

The study aims to assess and compare different proposed methodologies and determine the most effective combination approach for the early detection of AD. Our research findings strongly suggest that the proposed diagnostic support technique is a highly promising supplementary tool for discovering prospective diagnostic biomarkers that can greatly aid in the early clinical diagnosis of AD.
Cogs in the autophagic machine—equipped to combat dementia-prone neurodegenerative diseases
Authors: de Wet Sholto , Theart Rensu , Loos Ben
Published: August 2023

Neurodegenerative diseases are often characterized by hydrophobic inclusion bodies, and it may be the case that the aggregate-prone proteins that comprise these inclusion bodies are in fact the cause of neurotoxicity. Indeed, the appearance of protein aggregates leads to a proteostatic imbalance that causes various interruptions in physiological cellular processes, including lysosomal and mitochondrial dysfunction, as well as break down in calcium homeostasis. Oftentimes the approach to counteract proteotoxicity is taken to merely upregulate autophagy, measured by an increase in autophagosomes, without a deeper assessment of contributors toward effective turnover through autophagy. There are various ways in which autophagy is regulated ranging from the mammalian target of rapamycin (mTOR) to acetylation status of proteins. Healthy mitochondria and the intracellular energetic charge they preserve are key for the acidification status of lysosomes and thus ensuring effective clearance of components through the autophagy pathway. Both mitochondria and lysosomes have been shown to bear functional protein complexes that aid in the regulation of autophagy. Indeed, it may be the case that minimizing the proteins associated with the respective neurodegenerative pathology may be of greater importance than addressing molecularly their resulting inclusion bodies. It is in this context that this review will dissect the autophagy signaling pathway, its control and the manner in which it is molecularly and functionally connected with the mitochondrial and lysosomal system, as well as provide a summary of the role of autophagy dysfunction in driving neurodegenerative disease as a means to better position the potential of rapamycin-mediated bioactivities to control autophagy favorably.
Beyond rhythm – a framework for understanding the frequency spectrum of neural activity
Authors: Perrenoud Quentin , Cardin Jessica A.
Published: August 2023

Cognitive and behavioral processes are often accompanied by changes within well-defined frequency bands of the local field potential (LFP i.e., the voltage induced by neuronal activity). These changes are detectable in the frequency domain using the Fourier transform and are often interpreted as neuronal oscillations. However, aside some well-known exceptions, the processes underlying such changes are difficult to track in time, making their oscillatory nature hard to verify. In addition, many non-periodic neural processes can also have spectra that emphasize specific frequencies. Thus, the notion that spectral changes reflect oscillations is likely too restrictive. In this study, we use a simple yet versatile framework to understand the frequency spectra of neural recordings. Using simulations, we derive the Fourier spectra of periodic, quasi-periodic and non-periodic neural processes having diverse waveforms, illustrating how these attributes shape their spectral signatures. We then show how neural processes sum their energy in the local field potential in simulated and real-world recording scenarios. We find that the spectral power of neural processes is essentially determined by two aspects: (1) the distribution of neural events in time and (2) the waveform of the voltage induced by single neural events. Taken together, this work guides the interpretation of the Fourier spectrum of neural recordings and indicates that power increases in specific frequency bands do not necessarily reflect periodic neural activity.
Association of dietary inflammatory index with sarcopenia in asthmatic patients: a cross-sectional study
Authors: Lin Shuqiong , Su Xia , Chen Liqun , Cai Zhiming
Published: August 2023

Background

Sarcopenia is a complication of asthma, and asthmatics with sarcopenia are at an increased risk of poor prognosis. Anti-inflammatory intervention promising as an effective measure to prevent sarcopenia among patients with asthma. Diet is an important way to regulate inflammation throughout the body. The dietary inflammatory index (DII) is an index that assesses an individual’s overall dietary inflammatory potential. The relationship between DII and sarcopenia among patients with asthma is not clear.

Objective

To examine the correlation between DII and the sarcopenia among individuals with asthma.

Methods

The National Health and Nutrition Examination Survey (NHANES) was the data source utilized in this study, spanning two time periods from 1999 to 2006 and 2011 to 2018. The study encompassed 3,389 participants in total. DII was calculated using the results of the participants’ 24-h dietary recall interviews. Patients were categorized into three groups based on the DII tertile: T1 group (n = 1,130), T2 group (n = 1,129), and T3 group (n = 1,130). Logistic regression analysis, taking into account the NHANES recommended weights, was performed to assess the relationship between DII and sarcopenia.

Results

After full adjustment, there was a significant positive correlation between DII levels and the risk of sarcopenia in asthmatic patients (OR: 1.27, 95% CI: 1.13–1.42, p < 0.001). Compared with T1 group, T3 group had higher risk of sarcopenia (T2: OR: 1.39, 95%CI: 0.88–2.18, p = 0.157; T3: OR: 2.37, 95%CI: 1.47–3.83, p < 0.001).

Conclusion

There was a significant positive correlation between DII and the risk of sarcopenia.
A randomized controlled trial to examine the impact of a multi-strain probiotic on self-reported indicators of depression, anxiety, mood, and associated biomarkers
Authors: Walden Kylie E. , Moon Jessica M. , Hagele Anthony M. , Allen Leah E. , Gaige Connor J. , Krieger Joesi M. , Jäger Ralf , Mumford Petey W. , Pane Marco , Kerksick Chad M.
Published: August 2023

Objective

To examine the efficacy of supplementing with a multi-strain probiotic (MSP) on changes associated with mood, anxiety, and neurotransmitter levels.

Method

In a randomized, double-blind, placebo-controlled fashion, 70 healthy men and women (31.0 ± 9.5 years, 173.0 ± 10.4 cm, 73.9 ± 13.8 kg, 24.6 ± 3.5 kg/m2) supplemented with a single capsule of MSP (a total daily dose of 4 × 109 live cells comprised of a 1 × 109 live cells dose from each of the following strains: Limosilactobacillus fermentum LF16, Lacticaseibacillus rhamnosus LR06, Lactiplantibacillus plantarum LP01, and Bifidobacterium longum 04, Probiotical S.p.A., Novara, Italy) or a maltodextrin placebo (PLA). After 0, 2, 4, and 6 weeks of supplementation and 3 weeks after ceasing supplementation, study participants completed the Beck Depression Inventory (BDI-II), State-Trait Anxiety Inventory (STAI), and Leiden Index of Depression Sensitivity (LEIDS-R) questionnaires and had plasma concentrations of cortisol, dopamine, serotonin, and C-reactive protein determined.

Results

BDI, STAI, and total LEIDS-R scores were reduced from baseline (p < 0.05) with MSP supplementation after 4 and 6 weeks of supplementation and 3 weeks after supplementation while no changes (p > 0.05) were reported in PLA. When compared to PLA, MSP scores for state anxiety, trait anxiety, and LEIDS-R (hopeless, aggression, rumination, and total score) were significantly lower (p < 0.05) after supplementation. Plasma serotonin concentrations in MSP were increased from baseline after 6 weeks of supplementation and 3 weeks after ceasing supplementation. No changes (p > 0.05) in plasma dopamine, C-reactive protein, or cortisol concentrations were observed between groups.

Conclusion

MSP supplementation resulted in widespread improvements in several questionnaires evaluating mood, anxiety, and depression in young, healthy men and women. MSP supplementation increased serotonin increased after 6 weeks of MSP supplementation with no change in dopamine, C-reactive protein, or cortisol.

Clinical trial registration

https://classic.clinicaltrials.gov/ct2/show/NCT05343533, NCT05343533.
Evidence or no evidence for essential fatty acids in the treatment of autism spectrum disorders?
Authors: Pancheva Rouzha Zlatanova , Nikolova Silviya , Serbezova Asena , Zaykova Krassimira , Zhelyazkova Desislava , Dimitrov Lubomir
Published: August 2023

Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders that affect social communication, behavior, and sensory processing, in which PUFAs are considered important. This mini-review article aims to investigate the current evidence regarding the use of essential fatty acids (EFAs) in the treatment of autism spectrum disorders (ASDs). The study examines various research studies, related to EFAs, their benefits, and their role in ASD treatment. The article focuses on exploring the potential mechanisms underlying the effects of EFAs on ASDs, including their anti-inflammatory, antioxidant, and neuroprotective properties. Furthermore, the study discusses limitations and challenges associated with the use of EFAs in ASD treatment, including variability in dosage and duration of treatment. The results of this review indicate that while some studies suggest a positive effect of EFAs on ASD symptoms, there is currently insufficient evidence to support their routine use as a stand-alone treatment for ASD. The need for further research to better understand the potential benefits and limitations of EFAs in ASD treatment is highlighted.
Transarterial infusion chemotherapy for advanced esophageal cancer with airway stenosis
Authors: Zhou Gang , Yin Meipan , He Wei , Ma Yaozhen , Li Chunxia , Li Zhen , Li Xiaobing , Wang Shuai , Wu Gang
Published: August 2023

Purpose

This study aimed to investigate the safety and efficacy of transarterial infusion chemotherapy for the treatment of esophageal cancer with airway stenosis.

Methods

Data of patients with advanced esophageal cancer complicated with airway stenosis treated with transarterial infusion chemotherapy were retrospectively analyzed. Dyspnea, clinical efficacy and adverse reactions were evaluated.

Results

Of these patients, 27 had grade II preoperative dyspnea, and 31 had grade III preoperative dyspnea, 26 had grade I postoperative dyspnea, 25 had grade II postoperative dyspnea, and 7 had grade III postoperative dyspnea. Among 3 patients with left main bronchial stenosis and atelectasis, 2 had complete remission after transarterial infusion chemotherapy, and 1 demonstrated partial remission. After treatment, complete response, partial response, and stable disease were observed in 7, 34, and 17 cases, respectively. Total objective effective rate and disease control rate were 70.6% (41/58) and 100.0%, respectively. During follow up, 24 patients died of organ failure, and 17 patients died of tumor-related respiratory failure. Seven patients died of gastrointestinal bleeding, 1 patient died of myocardial infarction, and 9 patients survived.

Conclusions

Transarterial infusion chemotherapy is safe and effective for the treatment of advanced esophageal cancer with airway stenosis.
Intracavitary cardiac metastasis of cervical squamous cell carcinoma with immune thrombocytopenia: a rare case report
Authors: Liu Ning , Lv Deguan , Schneider Raydonna Rachel , Yang Hongyan , Zhang Mingyan , Liu Yanan , Sun Meili
Published: August 2023

Cervical cancer is a prevalent gynecological malignancy; however, intracavitary cardiac metastasis of cervical squamous cell carcinoma is exceptionally rare. In addition, the co-occurrence of cervical cancer and right ventricular cancer thrombus with autoimmune diseases is extremely uncommon. Furthermore, the role of immune checkpoint inhibitors in the treatment process of such cases remains controversial. Given the scarcity of reported cases, it is imperative to document and highlight this unique presentation, providing novel insights into diagnosis and management strategies. We present the case of an adult patient diagnosed with cervical cancer and concurrent right ventricular cancer thrombus, accompanied by immune thrombocytopenia (ITP). The patient exhibited resistance to conventional ITP drugs, with suboptimal platelet response. However, upon achieving initial control of the tumor, the patient’s platelet counts returned to normal. Notably, the addition of immune checkpoint inhibitors targeting PD-L1 resulted in effective tumor control, accompanied by sustained high platelet levels. Unfortunately, during subsequent anti-tumor therapy, the patient experienced a prolonged platelet rise time, rendering continuous effective anti-tumor therapy and anticoagulant therapy unattainable. This led to a gradual increase in intraventricular thrombosis, ultimately resulting in the patient’s demise due to circulatory failure. This rare case sheds light on the potential alleviation of ITP in patients with tumor complications through effective antitumor therapy. The successful control of ITP after tumor management highlights the importance of integrated treatment approaches. Furthermore, the inclusion of immune checkpoint inhibitors demonstrated their potential role in achieving tumor control and maintaining platelet levels. However, the prolonged platelet rise time observed during subsequent therapy underscores the challenges in maintaining both effective anti-tumor therapy and anticoagulant therapy, necessitating careful management strategies. This case report emphasizes the need for a comprehensive evaluation and tailored therapeutic interventions in similar complex scenarios. In summary, this case report offers valuable clinical insights into the management of intracavitary cardiac metastasis of cervical squamous cell carcinoma, the coexistence of immune thrombocytopenia, and the potential implications of immune checkpoint inhibitors in such cases. Understanding these rare occurrences and their clinical impact can contribute to improved diagnostic approaches, therapeutic decision-making, and patient outcomes.
Comparison of the effectiveness and safety of perampanel and oxcarbazepine as monotherapy in children and adolescents with newly diagnosed focal epilepsy
Authors: Yi Jia-Qin , Huang Sheng , Wu Miao-Juan , Ma Jie-Hui , Huang Li-Juan , Liang Song , Sun Dan
Published: August 2023

Objective: This study aims to compare the effectiveness and safety of perampanel and oxcarbazepine as monotherapy in children with focal epilepsy (FE).

Methods: This is an ambispective, single-center, non-inferiority study comparing the effectiveness and safety of perampanel (PER) monotherapy and oxcarbazepine (OXC) monotherapy in children with newly diagnosed FE. The primary endpoint was a six-month seizure freedom rate. The secondary endpoints included retention, responder, and seizure freedom rates at 3, 6, and 12 months, respectively. Adverse events (AEs) were also recorded for both groups.

Results: One hundred and thirty children and adolescents aged from 4 to 18years newly diagnosed with FE between May 2020 and November 2022 in Wuhan Children’s Hospital were included. There were 71 patients in the PER group and 59 patients in the OXC group. In the per protocol set (PPS), 50 (78.1%) in the PER group and 43 (78.2%) in the OXC group completed six months of treatment without seizures. The lower 95% CI (66.0%–87.5%) limit of PER was higher than the non-inferiority margin of 62.4% (80% of the 6-month seizure freedom rate in the OXC group); PER was non-inferior to OXC. The 3-month and 12-month seizure freedom rates were 77.1% and 82.9% for the PER group, respectively, while they were 80.4% and 75.8% for the OXC group. There were no serious adverse events in both groups.

Conclusion: PER showed comparable effectiveness and safety compared with OXC in children with newly diagnosed focal epilepsy, which might be an effective and safe treatment for children and adolescents with newly diagnosed FE.

Clinical Trial Registration: Identifier ChiCTR2300074696
An ethnobotanical study on the medicinal herb practices of the gelao ethnic minority in North Guizhou, China: an exploration of traditional knowledge
Authors: Liu Fusong , Peng Jie , Feng Yi , Ma Yuhan , Ren Yan , Sun Pei , Zhao Yongxia , Liu Sha , Wu Faming , Xie Jian
Published: August 2023

Introduction: The Gelao ethnic minority of northern Guizhou, China have long possessed extensive traditional knowledge of medicinal herbs. This ethnobotanical study aimed to document and evaluate wild plants used medicinally by the Gelao people, providing insights into their traditional medicine and knowledge systems.

Methods: Field research was conducted in Gelao communities of Daozhen, Wuchuan and Zheng’an counties using interviews, surveys and participatory rural appraisal.

Results: Quantitative ethnobotanical indices were utilized to assess the cultural significance of 187 herbs identified. The herbs belonged to 84 families, primarily Compositae, and were mostly roots, rhizomes and whole plants. They were used to treat digestive, respiratory and inflammatory disorders, gynecological diseases, bites and other conditions, mainly through decoctions. 25 highly significant herbs (national plant cultural significance index > 1000) were known to protect health. Some function as food and are considered safe. However, the study revealed issues including a declining number of knowledgeable elders and inadequate hygiene controls.

Conclusion: Our findings demonstrate the Gelao’s extensive medicinal plant knowledge and highlight the need for further ethnobotanical research to document and preserve this culturally important tradition. The identified herbs also represent an alternative medicinal resource with potential modern applications pending further investigation of their pharmacology and sustainable use. Overall, this study provides valuable insights into Gelao ethnobotanical knowledge and the potential of indigenous medicine for modern healthcare.
Hepatoprotective agents in the management of intrahepatic cholestasis of pregnancy: current knowledge and prospects
Authors: Shan Dan , Dai Siyu , Chen Qian , Xie Yupei , Hu Yayi
Published: August 2023

Intrahepatic cholestasis of pregnancy (ICP) is characterized by unexplained distressing pruritus in the mother and poses significant risk to the fetus of perinatal mortality. Occurring in the second and third trimester, the serum bile acid and aminotransferase are usually elevated in ICP patients. Ursodeoxycholic acid (UDCA) is the first line drug for ICP but the effectiveness for hepatoprotection is to a certain extent. In ICP patients with severe liver damage, combination use of hepatoprotective agents with UDCA is not uncommon. Herein, we reviewed the current clinical evidence on application of hepatoprotective agents in ICP patients. The underlying physiological mechanisms and their therapeutic effect in clinical practice are summarized. The basic pharmacologic functions of these hepatoprotective medications include detoxification, anti-inflammation, antioxidation and hepatocyte membrane protection. These hepatoprotective agents have versatile therapeutic effects including anti-inflammation, antioxidative stress, elimination of free radicals, anti-steatohepatitis, anti-fibrosis and anti-cirrhosis. They are widely used in hepatitis, non-alcoholic fatty liver disease, drug induced liver injury and cholestasis. Evidence from limited clinical data in ICP patients demonstrate reliable effectiveness and safety of these medications. Currently there is still no consensus on the application of hepatoprotective agents in ICP pregnancies. Dynamic monitoring of liver biochemical parameters and fetal condition is still the key recommendation in the management of ICP pregnancies.
Community pharmacists’ skills and practice regarding dispensing fiscalized substances: a cross-sectional survey
Authors: El-Dahiyat Faris , Jairoun Ammar Abdulrahman , Al-Hemyari Sabaa Saleh , Shahwan Moyad , Jairoun Maimona , Zyoud Sa’ed H. , Jaber Ammar Ali Saleh , Faisal Alkhanani Mustfa , Alhasani Reem Hasaballah , Ashour Ahmed M. , Alshehri Fahad S , Alorfi Nasser M.
Published: August 2023

Background: The use of drugs containing fiscalized substances is essential in different medical areas, including pain management, obstetric emergencies, and the treatment of mental disorders. However, due to their potential for abuse and negative health effects, the dispensing of these substances demands pharmacists with the requisite skills and practice.

Objective: This study assesses the skills and practices of pharmacy personnel in the United Arab Emirates (UAE) regarding the dispensing of tramadol, a medication containing fiscalized substances, in community pharmacies.

Methodology: A cross-sectional study was conducted. Community Pharmacies were chosen via random sampling, and seven well-trained final year pharmacy students visited them and conducted face-to-face interviews. The survey tool covered items highlighting the demographic data of the subjects, and items on the practice and skills regarding dispensing the fiscalized substances. The content validity ratio values of all tool questions were more than 0.78, suggesting acceptable validity and the Cronbach’s α of 0.75 showed as acceptable internal reliability. The primary outcome measures of interest were the skills and practice regarding dispensing Fiscalized substances.

Results: A total of 612 pharmacists were recruited in the study. The average practice score was 80%. There was a statistically significant association (p < 0.05) between practices about dispensing fiscalized substances and gender, age group, pharmacy type, work experience, university of graduation, and receiving training on epilepsy and antiepileptic drugs.

Conclusion: The results implied that competency and experience are vital factors for the dispensing of tramadol. Contextually, the majority of the pharmacists evidently have the requisite competencies to provide high-quality and proper medical care, with regards to dispensing tramadol, which will minimize drug abuse and medication errors, and assist outpatients to manage their drugs containing fiscalized substances.
Metallodrugs in the battle against non-small cell lung cancer: unlocking the potential for improved therapeutic outcomes
Authors: Xu Xianzhi , Dai Feng , Mao Yiting , Zhang Kai , Qin Ying , Zheng Jiwei
Published: August 2023

Non-small cell lung cancer (NSCLC) remains a leading cause of cancer mortality worldwide. Platinum-based chemotherapy is standard-of-care but has limitations including toxicity and resistance. Metal complexes of gold, ruthenium, and other metals have emerged as promising alternatives. This review provides a comprehensive analysis of metallodrugs for NSCLC. Bibliometric analysis reveals growing interest in elucidating mechanisms, developing targeted therapies, and synergistic combinations. Classification of metallodrugs highlights platinum, gold, and ruthenium compounds, as well as emerging metals. Diverse mechanisms include DNA damage, redox modulation, and immunomodulation. Preclinical studies demonstrate cytotoxicity and antitumor effects in vitro and in vivo, providing proof-of-concept. Clinical trials indicate platinums have utility but resistance remains problematic. Non-platinum metallodrugs exhibit favorable safety but modest single agent efficacy to date. Drug delivery approaches like nanoparticles show potential to enhance therapeutic index. Future directions include optimization of metal-based complexes, elucidation of resistance mechanisms, biomarker development, and combination therapies to fully realize the promise of metallodrugs for NSCLC.