bluuebunny/crossref_metadata_2025_split huggingface dataset:
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 RegistrationClinicalTrials.gov, NCT04954092, LP-007632.
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

BackgroundAntimicrobial 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.MethodsAn 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.ResultsA 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.ConclusionThis 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

IntroductionThe 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.MethodsDNA 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.ResultsThe 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.DiscussionWe 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

IntroductionPatients 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.MethodsThe 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.ResultsThere 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.DiscussionAcute 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.
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

IntroductionSpiking 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.MethodHere, 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 discussionExtensive 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

ObjectivesInitial 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).MethodsWe 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.ResultsWhen 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.ConclusionAccording 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.
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

IntroductionKombucha 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.MethodsThe 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.ResultsKombucha 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%.DiscussionAlthough 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 registrationClinicalTrials.gov, identifier NCT04107207.
Transition readiness of adolescents to adult health care
Authors: Lara-Macaraeg Beatrice Rodriguez , Cardinal Avegail , Bermejo Berith Grace 
Published: August 2023

BackgroundTransition 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.MethodsThis 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.ResultsFor 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.DiscussionThis 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

BackgroundChildhood 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.MethodsData 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.ResultsOur 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).ConclusionsIn 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.