bluuebunny/crossref_metadata_2025 huggingface dataset:
Cryptogenic chronic hepatitis: looking for an ideal diagnostic algorithm
Authors: Cançado Guilherme Grossi Lopes , Candolo Aline Coelho Rocha , Nardelli Mateus Jorge , Zitelli Patricia Momoyo , Mazo Daniel Ferraz de Campos , Oliveira Claudia Pinto , Cunha-Silva Marlone , Greca Raquel Dias , Araújo Roberta Chaves , Alustau Amanda Sacha Paulino Tolentino , Couto Cláudia Alves , Roque Gabriel Rezende de Lima , Farias Alberto Queiroz , Carrilho Flair José , Pessôa Mário Guimarães
Published: August 2023

Introduction

Cryptogenic chronic hepatitis is a growing cause of liver transplants, affecting 5%–15% of patients with chronic liver diseases. This study aimed to identify underlying causes of cryptogenic liver disease in a Brazilian cohort and propose a new diagnostic algorithm, including investigation for metabolic-dysfunction-associated fatty liver disease (MAFLD) and lysosomal acid lipase deficiency (LAL-D).

Methods

A retrospective analysis was conducted on 326 patients with presumed cryptogenic hepatitis.

Results

Using Czaja’s algorithm, non-alcoholic fatty liver disease was diagnosed in 21.3% of patients, while alpha-1 antitrypsin deficiency, alcoholic liver disease, autoimmune hepatitis, hemochromatosis, biliary-related hepatitis, viral hepatitis, Budd–Chiari syndrome, glycogenosis, drug-induced liver injury, and Wilson’s disease were diagnosed in smaller proportions (< 3.5% each). LAL-D was found in 1% of patients, and 53.6% of patients remained with cryptogenic hepatitis. The etiology of the liver disease in a subset of patients undergoing liver transplantation was updated post hoc based on explant histology, and non-alcoholic steatohepatitis was found in 52.5% of patients. By incorporating the concept of MAFLD, the new algorithm could diagnose 49.1% of patients, reducing the number of individuals without an etiological diagnosis by 11.4%.

Conclusion

One-third of patients with initially presumed cryptogenic liver disease were diagnosed with MAFLD. LAL-D should be considered in patients with chronic liver disease of unknown etiology. The updated diagnostic algorithm proposed in this study could improve diagnostic accuracy and aid in the management of patients with cryptogenic hepatitis.
NO–IL-6/10–IL-1β axis: a new pathway in steatotic and non-steatotic liver grafts from brain-dead donor rats
Authors: Casillas-Ramírez Araní , Micó-Carnero Marc , Sánchez-González Alfredo , Maroto-Serrat Cristina , Trostchansky Andrés , Peralta Carmen
Published: August 2023

Introduction

Brain death (BD) and steatosis are both risk factors for organ dysfunction or failure in liver transplantation (LT)

Material and methods

Here, we examine the role of interleukin 6 (IL- 6) and IL-10 in LT of both non-steatotic and steatotic liver recovered from donors after brain death (DBDs), as well as the molecular signaling pathways underlying the effects of such cytokines.

Results

BD reduced IL-6 levels only in nonsteatotic grafts, and diminished IL-10 levels only in steatotic ones. In both graft types, BD increased IL-1β, which was associated with hepatic inflammation and damage. IL-6 administration reduced IL-1β only in non-steatotic grafts and protected them against damage and inflammation. Concordantly, IL-1β inhibition via treatment with an IL-1 receptor antagonist caused the same benefits in non-steatotic grafts. Treatment with IL-10 decreased IL-1β only in steatotic grafts and reduced injury and inflammation specifically in this graft type. Blockading the IL-1β effects also reduced damage and inflammation in steatotic grafts. Also, blockade of IL-1β action diminished hepatic cAMP in both types of livers, and this was associated with a reduction in liver injury and inflammation, then pointing to IL-1β regulating cAMP generation under LT and BD conditions. Additionally, the involvement of nitric oxide (NO) in the effects of interleukins was evaluated. Pharmacological inhibition of NO in LT from DBDs prompted even more evident reductions of IL-6 or IL-10 in non-steatotic and steatotic grafts, respectively. This exacerbated the already high levels of IL-1β seen in LT from DBDs, causing worse damage and inflammation in both graft types. The administration of NO donors to non-steatotic grafts potentiated the beneficial effects of endogenous NO, since it increased IL-6 levels, and reduced IL-1β, inflammation, and damage. However, treatment with NO donors in steatotic grafts did not modify IL-10 or IL-1β levels, but induced more injurious effects tan the induction of BD alone, characterized by increased nitrotyrosine, lipid peroxidation, inflammation, and hepatic damage.

Conclusion

Our study thus highlights the specificity of new signaling pathways in LT from DBDs: NO–IL-6–IL-1β in non-steatotic livers and NO–IL-10–IL-1β in steatotic ones. This opens up new therapeutic targets that could be useful in clinical LT.
Hypomethylated interferon regulatory factor 8 recruits activating protein-2α to attenuate porcine epidemic diarrhea virus infection in porcine jejunum
Authors: Zong Qiufang , Qu Huan , Zheng Xianrui , Wang Haifei , Wu Shenglong , Yin Zongjun , Bao Wenbin
Published: August 2023

Interferon regulatory factor 8 (IRF8) is a key regulator of innate immune receptor signaling that resists pathogen invasion by regulating cell growth and differentiation. Porcine epidemic diarrhea virus (PEDV) targets the intestine and damages the mucosal barrier. However, whether IRF8 regulates PEDV replication remains unclear. We revealed that PEDV infection activated IRF8 expression. Moreover, IRF8 deletion drastically promoted PEDV replication and invasion, increasing the virus copies and titers. Hypomethylation enrichment of activating protein (AP)-2α was significantly negatively correlated with high IRF8 expression, and AP-2α directly targeted the IRF8 promoter to regulate PEDV replication. Furthermore, IRF8 overexpression decreased the cellular reactive oxygen species levels and mitochondrial membrane potential and increased the antioxidant enzyme activities to alleviate PEDV-induced oxidative damage. IRF8 overexpression suppressed apoptotic gene expression, thereby inhibiting apoptosis in response to PEDV stimulation. Taken together, this study demonstrates that AP-2α is involved in PEDV-induced epigenetic modification of IRF8 to reduce cell apoptosis and oxidative stress and facilitate host resistance to PEDV in the intestinal epithelium.
Regulatory T cells targeting a pathogenic MHC class II: Insulin peptide epitope postpone spontaneous autoimmune diabetes
Authors: Obarorakpor Nyerhovwo , Patel Deep , Boyarov Reni , Amarsaikhan Nansalmaa , Cepeda Joseph Ray , Eastes Doreen , Robertson Sylvia , Johnson Travis , Yang Kai , Tang Qizhi , Zhang Li
Published: August 2023

Introduction

In spontaneous type 1 diabetes (T1D) non-obese diabetic (NOD) mice, the insulin B chain peptide 9-23 (B:9-23) can bind to the MHC class II molecule (IAg7) in register 3 (R3), creating a bimolecular IAg7/InsulinB:9-23 register 3 conformational epitope (InsB:R3). Previously, we showed that the InsB:R3-specific chimeric antigen receptor (CAR), constructed using an InsB:R3-monoclonal antibody, could guide CAR-expressing CD8 T cells to migrate to the islets and pancreatic lymph nodes. Regulatory T cells (Tregs) specific for an islet antigen can broadly suppress various pathogenic immune cells in the islets and effectively halt the progression of islet destruction. Therefore, we hypothesized that InsB:R3 specific Tregs would suppress autoimmune reactivity in islets and efficiently protect against T1D.

Methods

To test our hypothesis, we produced InsB:R3-Tregs and tested their disease-protective effects in spontaneous T1D NOD.CD28-/- mice.

Results

InsB:R3-CAR expressing Tregs secrete IL-10 dominated cytokines upon engagement with InsB:R3 antigens. A single infusion of InsB:R3 Tregs delayed the onset of T1D in 95% of treated mice, with 35% maintaining euglycemia for two healthy lifespans, readily home to the relevant target whereas control Tregs did not. Our data demonstrate that Tregs specific for MHC class II: Insulin peptide epitope (MHCII/Insulin) protect mice against T1D more efficiently than polyclonal Tregs lacking islet antigen specificity, suggesting that the MHC II/insulin-specific Treg approach is a promising immune therapy for safely preventing T1D.
Impact of mAb-induced A475V substitution on viral fitness and antibody neutralization of SARS-CoV-2 omicron variants in the presence of monoclonal antibodies and human convalescent sera
Authors: Viriyakitkosol Ratchanont , Wanitchang Asawin , Srisutthisamphan Kanjana , Saenboonreung Janya , Boonkrai Chatikorn , Pisitkun Trairak , Jongkaewwattana Anan
Published: August 2023

The emergence and rapid evolution of SARS-CoV-2 variants have posed a major challenge to the global efforts to control the COVID -19 pandemic. In this study, we investigated the potential of two SARS-CoV-2 variants, BA.2 and BA.5, to evade neutralization by a human monoclonal antibody targeting the virus’s spike RBD (mAb 1D1). By subjecting the viruses to serial propagation in the presence of the antibody, we found that BA.2 exhibited poor growth, whereas BA.5 regained robust growth with significantly higher kinetics than the parental virus. Genetic analysis identified a single mutation, A475V, in the spike protein of BA.5 that substantially reduced the neutralizing activities of monoclonal antibodies and convalescent sera. In addition, the A475V mutation alone in BA.2 moderately reduced the neutralizing activity but completely abolished the neutralizing effect of mAb 1D1 when F486V or L452R were also present. Our results shed light on the possible evolutionary development of SARS-CoV-2 variants under selection pressure by monoclonal antibodies and have implications for the development of effective antibody therapies and vaccines against the virus.
Safety and immunogenicity of rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine against SARS-CoV-2 in healthy adolescents: an open-label, non-randomized, multicenter, phase 1/2, dose-escalation study
Authors: Tukhvatulin Amir I. , Dolzhikova Inna V. , Dzharullaeva Alina S. , Grousova Daria M. , Kovyrshina Anna V. , Zubkova Olga V. , Zorkov Ilya D. , Iliukhina Anna A. , Shelkov Artem Y. , Erokhova Alina S. , Popova Olga , Ozharovskaia Tatiana A. , Zrelkin Denis I. , Izhaeva Fatima M. , Shcheblyakov Dmitry V. , Esmagambetov Ilias B. , Tokarskaya Elisaveta A. , Nikitenko Natalia A. , Lubenets Nadezhda L. , Khadorich Elizaveta A. , Gushchin Vladimir A. , Borzakova Svetlana N. , Vlasova Anna V. , Osmanov Ismail M. , Gorev Valerii V. , Naroditsky Boris S. , Logunov Denis Y. , Gintsburg Alexander L.
Published: August 2023

To protect young individuals against SARS-CoV-2 infection, we conducted an open-label, prospective, non-randomised dose-escalation Phase 1/2 clinical trial to evaluate the immunogenicity and safety of the prime-boost “Sputnik V” vaccine administered at 1/10 and 1/5 doses to adolescents aged 12–17 years. The study began with the vaccination of the older cohort (15-to-17-year-old participants) with the lower (1/10) dose of vaccine and then expanded to the whole group (12-to-17-year-old participants). Next, 1/5 dose was used according to the same scheme. Both doses were well tolerated by all age groups. No serious or severe adverse events were detected. Most of the solicited adverse reactions were mild. No significant differences in total frequencies of adverse events were registered between low and high doses in age-pooled groups (69.6% versus 66.7%). In contrast, the 1/5 dose induced significantly higher humoral and T cell-mediated immune responses than the 1/10 dose. The 1/5 vaccine dose elicited higher antigen-binding (both S and RBD-specific) as well as virus-neutralising antibody titres at the maximum of response (day 42), also resulting in a statistically significant difference at a distanced timepoint (day 180) compared to the 1/10 vaccine dose. Higher dose resulted in increased cross-neutralization of Delta and Omicron variants.;

Clinical Trial Registration

ClinicalTrials.gov, NCT04954092, LP-007632.
Towards a global Fishing Vessel Ocean Observing Network (FVON): state of the art and future directions
Authors: Van Vranken Cooper , Jakoboski Julie , Carroll John W. , Cusack Christopher , Gorringe Patrick , Hirose Naoki , Manning James , Martinelli Michela , Penna Pierluigi , Pickering Mathew , Piecho-Santos A. Miguel , Roughan Moninya , de Souza João , Moustahfid Hassan
Published: August 2023

Ocean observations are the foundation of our understanding of ocean processes. Improving these observations has critical implications for our ability to sustainably derive food from the ocean, predict extreme weather events that take a toll on human life, and produce the goods and services that are needed to meet the needs of a vast and growing population. While there have been great leaps forward in sustained operational monitoring of our oceans there are still key data gaps which result in sub-optimal ocean management and policy decisions. The global fishing industry represents a vast opportunity to create a paradigm shift in how ocean data are collected: the spatio-temporal extent of ocean data gaps overlaps significantly with fishers’ activities; fishing vessels are suitable platforms of opportunity to host communications and sensor equipment; and many fishing vessels effectively conduct a depth-profile through the water column in the course of normal fishing activities, representing a powerful subsurface data collection opportunity. Fishing vessel-collected ocean data can complement existing ocean observing networks by enabling the cost-effective collection of vast amounts of subsurface ocean information in data-sparse regions. There is an emerging global network of fishing vessels participating in collaborative efforts to collect oceanographic data accelerated by innovations in enabling technologies. While there are clear opportunities that arise from partnering with fishing vessels, there are also challenges ranging from geographic and cultural differences in fleets, fishing methods and practices, data processing and management for heterogeneous data, as well as long term engagement of the fishers. To advance fishing vessel-based ocean observation on a global scale, the Fishing Vessel Ocean Observing Network (FVON) aims to maximize data value, establish best practices around data collection and management, and facilitate observation uptake. FVON’s ultimate goals are to foster collaborative fishing vessel-based observations, democratize ocean observation, improve ocean predictions and forecasts, promote sustainable fishing, and power a data-driven blue economy.
The assembly, biogeography and co-occurrence of abundant and rare microbial communities in a karst river
Authors: Wu Yongjie , Zhang Yang , Fang Huaiyang , Wang Cheng , Wang Zengrui , Zhang Wucai , Mai Bixian , He Zhili , Wu Renren , Li Kaiming
Published: August 2023

Karst rivers are highly susceptible to environmental disturbance due to their robust hydraulic connectivity. However, current knowledge of the mechanisms that regulate the assembly of bacterial and protistan subcommunities in river ecosystems, particularly in karst regions, is limited. By employing 16S and 18S rRNA gene amplicon sequencing, we explored how the diversities and assembly of abundant and rare bacterial and protistan subcommunities adapt to the local environmental variables in a karst river. Both bacterial and protistan rare subcommunities in karst river environments showed a similar biogeography to their abundant subcommunities. Also, a significant distance-decay pattern was observed in all components of the bacterial and protistan subcommunities along the Chishui River, with the rare subcommunities showing a more pronounced distance-decay pattern compared to the abundant subcommunities. Except protist rare subcommunity, the abundant and rare bacterial and abundant protistan subcommunities were strongly structured by the dispersal limitation processes rather than heterogeneous selection. Either bacteria or temperature, elevation and conductivity were the primary drivers for both abundant and rare subcommunities. Additionally, our results suggested that the rare subcommunities contribute significantly to the persistence and stability of microbial networks in the Chishui River, as they exhibited a higher number of keystones compared to the abundant subcommunities. Overall, our study revealed that in the karst river ecosystem, abundant bacterial subcommunities had a higher potential for environmental adaptation than rare bacterial and protistan subcommunities and identified the factors that moderate their assembly processes.
Development, roll-out and implementation of an antimicrobial resistance training curriculum harmonizes delivery of in-service training to healthcare workers in Kenya
Authors: Njeru Josiah , Odero Joshua , Chebore Sheilla , Ndung’u Mungai , Tanui Emmanuel , Wesangula Evelyn , Ndanyi Romona , Githii Susan , Gunturu Revathi , Mwangi Willy , Mutonga David , Dahourou Anicet , Thaiyah Andrew
Published: August 2023

Background

Antimicrobial resistance (AMR) is an increasingly severe threat to global public health that requires action across different sectors. Selection of appropriate antimicrobials is an urgent challenge due to the emergence of drug resistance. In 2017, Kenya developed an AMR policy and National Action Plan to drive prevention and containment of AMR. A priority activity under AMR surveillance strategic objective was to develop a national AMR training curriculum for in-service healthcare workers. In this paper we discuss the development process, gains achieved through implementation across the country and lessons learned.

Methods

An initial stakeholders’ forum was convened to brainstorm on the process for developing the curriculum and some issues deliberated upon include the design approach, development roadmap, curriculum outline and scope, delivery, and evaluation methodologies. A dedicated team of subject matter experts (SMEs), drawn from the project and government ministries, compiled the initial draft of the curriculum and later the training materials. A series of other stakeholders’ meetings were convened to review these materials. The National Antimicrobial Stewardship Interagency Committee (NASIC) of the MOH in Kenya identified a team of experts from academia, research, and government to work with the SMEs in reviewing and providing valuable inputs to the curriculum. Additionally, principles of adult learning and a One Health approach for development were considered as AMR has drivers and impacts across sectors. A validation workshop was held to finalize the documents with a formal launch conducted during the World Antibiotics Awareness Week of 2020.

Results

A multisectoral AMR surveillance training curriculum and facilitator and trainee manuals were developed and endorsed by MOH and Ministry of Agriculture, Livestock, Fisheries and Cooperatives within one year. Over 500 healthcare workers in 19 counties were trained, with overwhelming adoption by other stakeholders in Kenya and beyond.

Conclusion

This curriculum was developed to standardize training for AMR detection and surveillance. The central role played by the MOH ensured expeditious development and roll-out of this curriculum. The in-service curriculum, now available on an e-learning platform, provides a ready opportunity to build capacity of healthcare professionals. Additional resources are needed to standardize and scale these efforts to reach all healthcare workers.
Application of feature-based molecular networking and MassQL for the MS/MS fragmentation study of depsipeptides
Authors: Selegato Denise M. , Zanatta Ana C. , Pilon Alan C. , Veloso Juvenal H. , Castro-Gamboa Ian
Published: August 2023

The Feature-based Molecular Networking (FBMN) is a well-known approach for mapping and identifying structures and analogues. However, in the absence of prior knowledge about the molecular class, assessing specific fragments and clusters requires time-consuming manual validation. This study demonstrates that combining FBMN and Mass Spec Query Language (MassQL) is an effective strategy for accelerating the decoding mass fragmentation pathways and identifying molecules with comparable fragmentation patterns, such as beauvericin and its analogues. To accomplish this objective, a spectral similarity network was built from ESI-MS/MS experiments of Fusarium oxysporum at various collision energies (CIDs) and paired with a MassQL search query for conserved beauvericin ions. FBMN analysis revealed that sodiated and protonated ions clustered differently, with sodiated adducts needing more collision energy and exhibiting a distinct fragmentation pattern. Based on this distinction, two sets of particular fragments were discovered for the identification of these hexadepsipeptides: ([M + H]+) m/z 134, 244, 262, and 362 and ([M + Na]+) m/z 266, 284 and 384. By using these fragments, MassQL accurately found other analogues of the same molecular class and annotated beauvericins that were not classified by FBMN alone. Furthermore, FBMN analysis of sodiated beauvericins at 70 eV revealed subclasses with distinct amino acid residues, allowing distinction between beauvericins (beauvericin and beauvericin D) and two previously unknown structural isomers with an unusual methionine sulfoxide residue. In summary, our integrated method revealed correlations between adduct types and fragmentation patterns, facilitated the detection of beauvericin clusters, including known and novel analogues, and allowed for the differentiation between structural isomers.
Longitudinal study of epigenetic aging and its relationship with brain aging and cognitive skills in young adulthood
Authors: Mareckova Klara , Pacinkova Anna , Marecek Radek , Sebejova Ludmila , Izakovicova Holla Lydie , Klanova Jana , Brazdil Milan , Nikolova Yuliya S.
Published: August 2023

Introduction

The proportion of older adults within society is sharply increasing and a better understanding of how we age starts to be critical. However, given the paucity of longitudinal studies with both neuroimaging and epigenetic data, it remains largely unknown whether the speed of the epigenetic clock changes over the life course and whether any such changes are proportional to changes in brain aging and cognitive skills. To fill these knowledge gaps, we conducted a longitudinal study of a prenatal birth cohort, studied epigenetic aging across adolescence and young adulthood, and evaluated its relationship with brain aging and cognitive outcomes.

Methods

DNA methylation was assessed using the Illumina EPIC Platform in adolescence, early and late 20 s, DNA methylation age was estimated using Horvath’s epigenetic clock, and epigenetic age gap (EpiAGE) was calculated as DNA methylation age residualized for batch, chronological age and the proportion of epithelial cells. Structural magnetic resonance imaging (MRI) was acquired in both the early 20 s and late 20 s using the same 3T Prisma MRI scanner and brain age was calculated using the Neuroanatomical Age Prediction using R (NAPR) platform. Cognitive skills were assessed using the Wechsler Adult Intelligence Scale (WAIS) in the late 20 s.

Results

The EpiAGE in adolescence, the early 20 s, and the late 20 s were positively correlated (r = 0.34–0.47), suggesting that EpiAGE is a relatively stable characteristic of an individual. Further, a faster pace of aging between the measurements was positively correlated with EpiAGE at the end of the period (r = 0.48–0.77) but negatively correlated with EpiAGE at the earlier time point (r = −0.42 to −0.55), suggesting a compensatory mechanism where late matures might be catching up with the early matures. Finally, higher positive EpiAGE showed small (Adj R2 = 0.03) but significant relationships with a higher positive brain age gap in all participants and lower full-scale IQ in young adult women in the late 20 s.

Discussion

We conclude that the EpiAGE is a relatively stable characteristic of an individual across adolescence and early adulthood, but that it shows only a small relationship with accelerated brain aging and a women-specific relationship with worse performance IQ.
Loss of normal Alzheimer's disease-associated Presenilin 2 function alters antiseizure medicine potency and tolerability in the 6-Hz focal seizure model
Authors: Lehmann Leanne M. , Barker-Haliski Melissa
Published: August 2023

Introduction

Patients with early-onset Alzheimer's disease (EOAD) experience seizures and subclinical epileptiform activity, which may accelerate cognitive and functional decline. Antiseizure medicines (ASMs) may be a tractable disease-modifying strategy; numerous ASMs are marketed with well-established safety. However, little information is available to guide ASM selection as few studies have rigorously quantified ASM potency and tolerability in traditional seizure models in rodents with EOAD-associated risk factors. Presenilin 2 (PSEN2) variants evoke EOAD, and these patients experience seizures. This study thus established the anticonvulsant profile of mechanistically distinct ASMs in the frontline 6-Hz limbic seizure test evoked in PSEN2-knockout (KO) mice to better inform seizure management in EOAD.

Methods

The median effective dose (ED50) of prototype ASMs was quantified in the 6-Hz test in male and female PSEN2-KO and wild-type (WT) C57BL/6J mice (3–4 months old). Minimal motor impairment (MMI) was assessed to estimate a protective index (PI). Immunohistological detection of cFos established the extent to which 6-Hz stimulation activates discrete brain regions in KO vs. WT mice.

Results

There were significant genotype-related differences in the potency and tolerability of several ASMs. Valproic acid and levetiracetam were significantly more potent in male KO than in WT mice. Additionally, high doses of valproic acid significantly worsened MMI in KO mice. Conversely, carbamazepine was significantly less potent in female KO vs. WT mice. In both male and female KO mice vs. WTs, perampanel and lamotrigine were equally potent. However, there were marked genotype-related shifts in PI of both carbamazepine and perampanel, with KO mice exhibiting less MMI at the highest doses tested. Gabapentin was ineffective against 6-Hz seizures in KO mice vs. WTs without MMI changes. Neuronal activation 90 min following 6-Hz stimulation was significantly increased in the posterior parietal association cortex overlying CA1 and in the piriform cortex of WT mice, while stimulation-induced increases in cFos immunoreactivity were absent in KO mice.

Discussion

Acute ASM potency and tolerability in the high-throughput 6-Hz test may be significantly altered with loss of normal PSEN2 function. Seizures in discrete EOAD populations may benefit from precisely selected medicines optimized for primary ASM pharmacological mechanisms.
The neurophysiological Behavioral Perspective Model of consumer choice and its contribution to the intentional behaviorist research programme
Authors: Foxall Gordon R.
Published: August 2023

Cognitive explanations raise epistemological problems not faced by accounts confined to observable variables. Many explanatory components of cognitive models are unobservable: beliefs, attitudes, and intentions, for instance, must be made empirically available to the researcher in the form of measures of observable behavior from which the latent variables are inferred. The explanatory variables are abstract and theoretical and rely, if they are to enter investigations and explanations, on reasoned agreement on how they can be captured by proxy variables derived from what people say and how they behave. Psychometrics must be founded upon a firm, intersubjective agreement among researchers and users of research on the relationship of behavioral measures to the intentional constructs to which they point and the latent variables they seek to operationalize. Only if these considerations are adequately addressed can we arrive at consistent interpretations of the data. This problem provides the substance of the intentional behaviorist research programme which seeks to provide a rationale for the cognitive explanation. Within this programme, two versions of the Behavioral Perspective Model (BPM), an extensional portrayal of socioeconomic behavior and a corresponding intentional approach, address the task of identifying where intentional explanation becomes necessary and the form it should take. This study explores a third version, based on neurophysiological substrates of consumer choice as a contributor to this task. The nature of “value” is closely related to the rationale for a neurophysiological model of consumer choice. The variables involved are operationally specified and measured with high intersubjective agreement. The intentional model (BPM-I), depicting consumer action in terms of mental processes such as perception, deliberation, and choice, extends the purview of the BPM to new situations and areas of explanation.
Incorporating structural plasticity into self-organization recurrent networks for sequence learning
Authors: Yuan Ye , Zhu Yongtong , Wang Jiaqi , Li Ruoshi , Xu Xin , Fang Tao , Huo Hong , Wan Lihong , Li Qingdu , Liu Na , Yang Shiyan
Published: August 2023

Introduction

Spiking neural networks (SNNs), inspired by biological neural networks, have received a surge of interest due to its temporal encoding. Biological neural networks are driven by multiple plasticities, including spike timing-dependent plasticity (STDP), structural plasticity, and homeostatic plasticity, making network connection patterns and weights to change continuously during the lifecycle. However, it is unclear how these plasticities interact to shape neural networks and affect neural signal processing.

Method

Here, we propose a reward-modulated self-organization recurrent network with structural plasticity (RSRN-SP) to investigate this issue. Specifically, RSRN-SP uses spikes to encode information, and incorporate multiple plasticities including reward-modulated spike timing-dependent plasticity (R-STDP), homeostatic plasticity, and structural plasticity. On the one hand, combined with homeostatic plasticity, R-STDP is presented to guide the updating of synaptic weights. On the other hand, structural plasticity is utilized to simulate the growth and pruning of synaptic connections.

Results and discussion

Extensive experiments for sequential learning tasks are conducted to demonstrate the representational ability of the RSRN-SP, including counting task, motion prediction, and motion generation. Furthermore, the simulations also indicate that the characteristics arose from the RSRN-SP are consistent with biological observations.
Alterations in static and dynamic regional homogeneity in mesial temporal lobe epilepsy with and without initial precipitating injury
Authors: Mao Xinyue , Zhang Xiaonan , Song Chengru , Ma Keran , Wang Kefan , Wang Xin , Lian Yajun , Zhang Yong , Han Shaoqiang , Cheng Jingliang , Zhang Yan
Published: August 2023

Objectives

Initial precipitating injury (IPI) such as febrile convulsion and intracranial infection will increase the susceptibility to epilepsy. It is still unknown if the functional deficits differ between mesial temporal lobe epilepsy with IPI (mTLE-IPI) and without IPI (mTLE-NO).

Methods

We recruited 25 mTLE-IPI patients, 35 mTLE-NO patients and 33 healthy controls (HC). Static regional homogeneity (sReHo) and dynamic regional homogeneity (dReHo) were then adopted to estimate the alterations of local neuronal activity. One-way analysis of variance was used to analyze the differences between the three groups in sReHo and dReHo. Then the results were utilized as masks for further between-group comparisons. Besides, correlation analyses were carried out to detect the potential relationships between abnormal regional homogeneity indicators and clinical characteristics.

Results

When compared with HC, the bilateral thalamus and the visual cortex in mTLE-IPI patients showed an increase in both sReHo and variability of dReHo. Besides, mTLE-IPI patients exhibited decreased sReHo in the right cerebellum crus1/crus2, inferior parietal lobule and temporal neocortex. mTLE-NO patients showed decreased sReHo and variability of dReHo in the bilateral temporal neocortex compared with HC. Increased sReHo and variability of dReHo were found in the bilateral visual cortex when mTLE-IPI patients was compared with mTLE-NO patients, as well as increased variability of dReHo in the left thalamus and decreased sReHo in the right dorsolateral prefrontal cortex. Additionally, we discovered a negative correlation between the national hospital seizure severity scale testing score and sReHo in the right cerebellum crus1 in mTLE-IPI patients.

Conclusion

According to the aforementioned findings, both mTLE-IPI and mTLE-NO patients had significant anomalies in local neuronal activity, although the functional deficits were much severer in mTLE-IPI patients. The use of sReHo and dReHo may provide a novel insight into the impact of the presence of IPI on the development of mTLE.
Palmitoylethanolamide counteracts high-fat diet-induced gut dysfunction by reprogramming microbiota composition and affecting tryptophan metabolism
Authors: Pirozzi Claudio , Coretti Lorena , Opallo Nicola , Bove Maria , Annunziata Chiara , Comella Federica , Turco Luigia , Lama Adriano , Trabace Luigia , Meli Rosaria , Lembo Francesca , Mattace Raso Giuseppina
Published: August 2023

Obesity is associated with gastrointestinal (GI) tract and central nervous system (CNS) disorders. High-fat diet (HFD) feeding-induced obesity in mice induces dysbiosis, causing a shift toward bacteria-derived metabolites with detrimental effects on metabolism and inflammation: events often contributing to the onset and progression of both GI and CNS disorders. Palmitoylethanolamide (PEA) is an endogenous lipid mediator with beneficial effects in mouse models of GI and CNS disorders. However, the mechanisms underlining its enteroprotective and neuroprotective effects still need to be fully understood. Here, we aimed to study the effects of PEA on intestinal inflammation and microbiota alterations resulting from lipid overnutrition. Ultramicronized PEA (30 mg/kg/die per os) was administered to HFD-fed mice for 7 weeks starting at the 12th week of HFD regimen. At the termination of the study, the effects of PEA on inflammatory factors and cells, gut microbial features and tryptophan (TRP)-kynurenine metabolism were evaluated. PEA regulates the crosstalk between the host immune system and gut microbiota via rebalancing colonic TRP metabolites. PEA treatment reduced intestinal immune cell recruitment, inflammatory response triggered by HFD feeding, and corticotropin-releasing hormone levels. In particular, PEA modulated HFD-altered TRP metabolism in the colon, rebalancing serotonin (5-HT) turnover and reducing kynurenine levels. These effects were associated with a reshaping of gut microbiota composition through increased butyrate-promoting/producing bacteria, such as Bifidobacterium, Oscillospiraceae and Turicibacter sanguinis, with the latter also described as 5-HT sensor. These data indicate that the rebuilding of gut microbiota following PEA supplementation promotes host 5-HT biosynthesis, which is crucial in regulating intestinal function.
Kombucha tea as an anti-hyperglycemic agent in humans with diabetes – a randomized controlled pilot investigation
Authors: Mendelson Chagai , Sparkes Sabrina , Merenstein Daniel J. , Christensen Chloe , Sharma Varun , Desale Sameer , Auchtung Jennifer M. , Kok Car Reen , Hallen-Adams Heather E. , Hutkins Robert
Published: August 2023

Introduction

Kombucha is a popular fermented tea that has attracted considerable attention due, in part, to its suggested health benefits. Previous results from animal models led us to hypothesize kombucha may reduce blood sugar levels in humans with diabetes. The objective of this pilot clinical study was to evaluate kombucha for its anti-hyperglycemic activities in adults with diabetes mellitus type II.

Methods

The study was organized as a prospective randomized double-blinded crossover study at a single-center urban hospital system. Participants (n = 12) were instructed to consume either a kombucha product or a placebo control (each 240 mL) for 4 weeks. After an 8-week washout period, participants consumed the alternate product. Fasting blood glucose levels were self-determined at baseline and at 1 and 4 weeks during each treatment period. Secondary health outcomes, including overall health, insulin requirement, gut health, skin health, mental health, and vulvovaginal health were measured by questionnaire at the same time points. The kombucha microbiota was assessed by selective culturing and 16S rRNA gene (bacteria) and ITS (fungi) sequencing. Fermentation end products were assessed by HPLC. Statistical significance of changes in fasting blood glucose was determined using paired, two-tailed student’st-tests.

Results

Kombucha lowered average fasting blood glucose levels at 4 weeks compared to baseline (164 vs. 116 mg/dL,p = 0.035), whereas the placebo did not (162 vs. 141 mg/dL,p = 0.078). The kombucha microbiota, as assessed by cultural enumeration, was mainly comprised of lactic acid bacteria, acetic acid bacteria, and yeast, with each group present at about 106colony forming units (CFU)/mL. Likewise, 16S rRNA gene sequencing confirmed that lactic acid and acetic acid bacteria were the most abundant bacteria, and ITS sequencing showed Dekkera was the most abundant yeast. The primary fermentation end products were lactic and acetic acids, both less than 1%. Ethanol was present at 1.5%.

Discussion

Although this pilot study was limited by a small sample size, kombucha was associated with reduced blood glucose levels in humans with diabetes. Larger follow-up studies are warranted.

Clinical trial registration

ClinicalTrials.gov, identifier NCT04107207.
A review on recent advances in mass spectrometry analysis of harmful contaminants in food
Authors: Sun Qiannan , Dong Yide , Wen Xin , Zhang Xu , Hou Shijiao , Zhao Wuduo , Yin Dan
Published: August 2023

Food safety is a widespread global concern with the emergence of foodborne diseases. Thus, establishing accurate and sensitive detection methods of harmful contaminants in different food matrices is essential to address and prevent the associated health risks. Among various analytical tools, mass spectrometry (MS) can quantify multiple impurities simultaneously due to high resolution and accuracy and can achieve non-target profiling of unknown pollutants in food. Therefore, MS has been widely used for determination of hazardous contaminants [e.g., mycotoxin, pesticide and veterinary drug residues, polychlorinated biphenyls (PCBs), dioxins, acrylamide, perfluorinated compounds (PFCs) and p-Phenylenediamine compounds (PPDs) in food samples]. This work summarizes MS applications in detecting harmful contaminants in food matrices, discusses advantages of MS for food safety study, and provides a perspective on future directions of MS development in food research. With the persistent occurrence of novel contaminants, MS will play a more and more critical role in food analysis.
Transition readiness of adolescents to adult health care
Authors: Lara-Macaraeg Beatrice Rodriguez , Cardinal Avegail , Bermejo Berith Grace
Published: August 2023

Background

Transition in health care is a process wherein adolescents gradually prepare for and shift towards care in the adult system. An initial assessment of the readiness of these adolescents is fundamental in providing appropriate health services for them. This paper aims to determine the readiness of adolescent patients towards transitioning to adult care.

Methods

This is a prospective cross-sectional study utilizing an interviewer-guided modified Transition Readiness Assessment Questionnaire (TRAQ). Sixty-three adolescents ages 15 to 18 years seen in the Pediatric Outpatient Department (OPD) of a tertiary hospital in Baguio City from July 1 to October 31, 2020 were enrolled. Frequency and percentages were used to describe the demographic data; while mean score and standard deviation determined readiness based on a Likert scale. One-way ANOVA was utilized to determine association between factors and readiness to transition.

Results

For all domains of TRAQ, the mean score was 3.64, implying that they are not yet ready to transition. 49.2% belong to General Pediatrics. 44.4% belong to the Igorot ethnic groups. Most are still in High school, and majority of their parents finished High School level. Furthermore, the P-values were more than 0.05 for all variables suggesting no association between readiness to transition and the identified factors in this study.

Discussion

This study showed that adolescents who had both acute and chronic illnesses, were not yet ready to transition. Provision of a platform for assisting the adolescents in their assumption of bigger roles/responsibilities for their own health care is necessary to ensure proper transitioning to adult health care.
Mendelian randomization analyses support causal relationship between gut microbiota and childhood obesity
Authors: Li Qi , Gao Jiawei , Luo Jiashun , Lin Dihui , Wu Xinrui
Published: August 2023

Background

Childhood obesity (CO) is an increasing public health issue. Mounting evidence has shown that gut microbiota (GM) is closely related to CO. However, the causal association needs to be treated with caution due to confounding factors and reverse causation.

Methods

Data were obtained from the Microbiome Genome Consortium for GM as well as the Early Growth Genetics Consortium for childhood obesity and childhood body mass index (CBMI). Inverse variance weighted, maximum likelihood, weighted median, and MR.RAPS methods were applied to examine the causal association. Then replication dataset was used to validate the results and reverse Mendelian randomization analysis was performed to confirm the causal direction. Additionally, sensitivity analyses including Cochran's Q statistics, MR-Egger intercept, MR-PRESSO global test, and the leave-one-out analysis were conducted to detect the potential heterogeneity and horizontal pleiotropy.

Results

Our study found suggestive causal relationships between eight bacterial genera and the risk of childhood obesity (five for CO and four for CBMI). After validating the results in the replication dataset, we finally identified three childhood obesity-related GM including the genera Akkermansia, Intestinibacter, and Butyricimonas. Amongst these, the genus Akkermansia was both negatively associated with the risk of CO (OR = 0.574; 95% CI: 0.417, 0.789) and CBMI (β = −0.172; 95% CI: −0.306, −0.039).

Conclusions

In this study, we employed the MR approach to investigate the causal relationship between GM and CO, and discovered that the genus Akkermansia has a protective effect on both childhood obesity and BMI. Our findings may provide a potential strategy for preventing and intervening in CO, while also offering novel insights into the pathogenesis of CO from the perspective of GM.
Study of the antioxidant and anti-pancreatic cancer activities of Anchusa strigosa aqueous extracts obtained by maceration and ultrasonic extraction techniques
Authors: Chebaro Ziad , Abdallah Rola , Badran Adnan , Hamade Kamar , Hijazi Akram , Maresca Marc , Mesmar Joelle Edward , Baydoun Elias
Published: August 2023

Pancreatic cancer is a highly aggressive malignancy and a leading cause of cancer-related deaths worldwide. Moreover, the incidence and mortality rates for pancreatic cancer are projected to keep increasing. A major challenge in the treatment of pancreatic cancer is the lack of effective screening approaches, which contributes to its poor prognosis, indicating the need for new treatment regimens and alternative therapies, such as herbal medicine. The medicinal plantA. strigosa, which is widely distributed in the Eastern Mediterranean region, is a short prickly plant from the Boraginaceae family that has been widely used in traditional medicine for treating various diseases. Nevertheless, its effect on human pancreatic cancer remains poorly investigated. In the present study, we screened the phytochemical content ofAnchusa strigosaaqueous extracts obtained by maceration and ultrasound-assisted methods (ASM and ASU, respectively) and evaluated their antioxidant effects. We also investigated their anticancer effects and possible underlying mechanisms. The results show that both extracts were rich in bioactive molecules, with slight differences in their composition. Both extracts exhibited remarkable antioxidant potential and potent radical-scavenging activityin vitro. Additionally, non-cytotoxic concentrations of both extracts attenuated cell proliferation in a time- and concentration-dependent manner, which was associated with a decrease in the proliferation marker Ki67 and an induction of the intrinsic apoptotic pathway. Furthermore, the extracts increased the aggregation of pancreatic cancer cells and reduced their migratory potential, with a concomitant downregulation of integrin β1. Finally, we showed that the ASM extract caused a significant decrease in the levels of COX-2, an enzyme that has been linked to inflammation, carcinogenesis, tumor progression, and metastasis. Taken together, our findings provide evidence thatA. strigosaextracts, particularly the extract obtained using the maceration method, have a potential anticancer effect and may represent a new resource for the design of novel drugs against pancreatic cancer.
The applications of functional materials-based nano-formulations in the prevention, diagnosis and treatment of chronic inflammation-related diseases
Authors: Wang Jingjing , Ni Rui , Jiang Tingting , Peng Dan , Ming Yue , Cui Hongjuan , Liu Yao
Published: August 2023

Chronic inflammation, in general, refers to systemic immune abnormalities most often caused by the environment or lifestyle, which is the basis for various skin diseases, autoimmune diseases, cardiovascular diseases, liver diseases, digestive diseases, cancer, and so on. Therapeutic strategies have focused on immunosuppression and anti-inflammation, but conventional approaches have been poor in enhancing the substantive therapeutic effect of drugs. Nanomaterials continue to attract attention for their high flexibility, durability and simplicity of preparation, as well as high profitability. Nanotechnology is used in various areas of clinical medicine, such as medical diagnosis, monitoring and treatment. However, some related problems cannot be ignored, including various cytotoxic and worsening inflammation caused by the nanomaterials themselves. This paper provides an overview of functional nanomaterial formulations for the prevention, diagnosis and treatment of chronic inflammation-related diseases, with the intention of providing some reference for the enhancement and optimization of existing therapeutic approaches.
Oxaliplatin-induced peripheral neurotoxicity in colorectal cancer patients: mechanisms, pharmacokinetics and strategies
Authors: Cheng Fang , Zhang Ruoqi , Sun Chen , Ran Qian , Zhang Cuihan , Shen Changhong , Yao Ziqing , Wang Miao , Song Lin , Peng Cheng
Published: August 2023

Oxaliplatin-based chemotherapy is a standard treatment approach for colorectal cancer (CRC). However, oxaliplatin-induced peripheral neurotoxicity (OIPN) is a severe dose-limiting clinical problem that might lead to treatment interruption. This neuropathy may be reversible after treatment discontinuation. Its complicated mechanisms are related to DNA damage, dysfunction of voltage-gated ion channels, neuroinflammation, transporters, oxidative stress, and mitochondrial dysfunction, etc. Several strategies have been proposed to diminish OIPN without compromising the efficacy of adjuvant therapy, namely, combination with chemoprotectants (such as glutathione, Ca/Mg, ibudilast, duloxetine, etc.), chronomodulated infusion, dose reduction, reintroduction of oxaliplatin and topical administration [hepatic arterial infusion chemotherapy (HAIC), pressurized intraperitoneal aerosol chemotherapy (PIPAC), and hyperthermic intraperitoneal chemotherapy (HIPEC)]. This article provides recent updates related to the potential mechanisms, therapeutic strategies in treatment of OIPN, and pharmacokinetics of several methods of oxaliplatin administration in clinical trials.