Miracle-dz/UniFAR-FTUs huggingface dataset:
Attention Deﬁcit Hyperactivity Disorder (ADHD) and Polyphenols: A Systematic Review

: Polyphenols are natural compounds also contained in daily consumed foods that show their efﬁcacy in different clinical ﬁelds. Both pre-clinical and clinical studies demonstrated that polyphenols may manage neuroinﬂammation and oxidative stress processes tightly connected to neurodegenerative diseases and mental disorders. Thus, a neuroinﬂammatory state may inﬂuence the neurotransmitters pathways, such as the noradrenergic, glutamatergic, serotoninergic, and, in particular, dopaminergic ones, whose impairment is strongly associated with attention deﬁcit hyperactivity disorder (ADHD). Therefore, the aim of the present systematic review is to provide an overview of the clinical outcomes’ changes following ADHD treatment with polyphenols alone and in combination with the traditional drugs. This review was conducted according to PRISMA guidelines and recorded on PROSPERO with the number CRD42023438491; PubMed, Scopus, and Web of Science were used as search-engines to lead our research until June 2023. The inclusion criteria were articles written in English, including clinical, placebo-controlled, and case-control trials. We excluded reviews, metanalyses, background articles, and papers published in other languages. To avoid any bias, Rayyan software (COPYRIGHT © 2022 RAYYAN) was used to organize the work and manage the literature review. After screening, 10 studies were included, with a total of 556 patients that met the established inclusion criteria. The data obtained from these studies showed that polyphenols rebalanced oxidative stress pathways through different mechanisms, are effective for the treatment of ADHD both alone and in combination with traditional drugs, and are able to reduce symptoms as well as the side effects related to the use of conventional therapies. Finally, a positive effect of using polyphenols for ADHD prevention could be hypothesized.
Homozygous variant of MLC1 results in megalencephalic leukoencephalopathy with subcortical cysts

Abstract Background Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare, inherited disorder that causes epilepsy, intellectual disorders, and early onset macrocephaly. MLC1 has been identified as a main pathogenic gene. Methods Clinical data such as magnetic resonance imaging (MRI), routine blood tests, and physical examinations were collected from proband. Trio whole‐exome sequencing (WES) of the family was performed, and all variants with a minor allele frequency (<0.01) in the exon and canonical splicing sites were selected for further pathogenic evaluation. Candidate variants were validated using Sanger sequencing. Results Here, we report a new homozygous variant identified in two children from the same family in the MLC1 gene [NM_015166. 4: c. 838_843delinsATTTTA, (p.Ser280_Phe281delinsIleLeu)]. This variant is classified as variant of uncertain significance (VUS) according to the ACMG guidelines. Further experiments demonstrate that the newly identified variant causes a decrease of MLC1 protein levels when expressed in a heterologous expression system. Conclusion Our case expands on this genetic variation and provides new evidence for the clinical diagnosis of MLC1‐related MLC.
Bioengineered small extracellular vesicles deliver multiple SARS‐CoV‐2 antigenic fragments and drive a broad immunological response

Abstract The COVID‐19 pandemic highlighted the clear risk that zoonotic viruses pose to global health and economies. The scientific community responded by developing several efficacious vaccines which were expedited by the global need for vaccines. The emergence of SARS‐CoV‐2 breakthrough infections highlights the need for additional vaccine modalities to provide stronger, long‐lived protective immunity. Here we report the design and preclinical testing of small extracellular vesicles (sEVs) as a multi‐subunit vaccine. Cell lines were engineered to produce sEVs containing either the SARS‐CoV‐2 Spike receptor‐binding domain, or an antigenic region from SARS‐CoV‐2 Nucleocapsid, or both in combination, and we tested their ability to evoke immune responses in vitro and in vivo. B cells incubated with bioengineered sEVs were potent activators of antigen‐specific T cell clones. Mice immunised with sEVs containing both sRBD and Nucleocapsid antigens generated sRBD‐specific IgGs, nucleocapsid‐specific IgGs, which neutralised SARS‐CoV‐2 infection. sEV‐based vaccines allow multiple antigens to be delivered simultaneously resulting in potent, broad immunity, and provide a quick, cheap, and reliable method to test vaccine candidates.
Structural inheritance and magmatism during continental breakup in West Greenland and Eastern Canada

Continental extension causes rifting and thinning of the lithosphere that may result in breakup and eventually the initiation of seafloor spreading and passive continental margin development. Ambiguity exists regarding the roles of magmatism and structural inheritance during rifting and continental breakup during this process. This study focuses on the importance of these controls on the Mesozoic-Cenozoic separation between West Greenland and Eastern Canada. It is important to improve our knowledge of the processes that influenced breakup as the current understanding of these processes is limited and also to reduce hydrocarbon exploration risk in this tectonic setting. During this study passive margin processes were investigated using a variety of methodologies at a range of scales from that of conjugate margin pairs (Chapters 4 and 5), through margin and basin scale studies (Chapter 6) to the smallest scale on individual igneous intrusions (Chapter 7). At the largest scale an assessment of the magmatic and structural asymmetry between the conjugate margins of the Labrador Sea based primarily on field data and subsequent analysis near Makkovik, Labrador, but also other large-scale geophysical datasets demonstrated that early rifting was dominated by simple shear rather than pure shear. In such a scenario Labrador was have been the lower plate margin to the upper plate southwest Greenland margin. Further analysis of field observations indicated that rifting of the Labrador Sea region may have been aided by a favourably orientated basement metamorphic fabric and that observable onshore brittle deformation structures may be related to Mesozoic rifting. Further north in the Davis Strait, seismic interpretation at the margin and basin scale allowed a series of seismic surfaces, isochrons and a new offshore fault map to be produced. The results of this analysis demonstrated that the geometry of rift basins was primarily controlled by pre-existing structures, an assertion supported by observations of reactivation onshore in West Greenland. Finally, at the smallest scale, results of numerical modelling offshore Newfoundland demonstrated that even on non- volcanic passive margins, intrusive magmatism can influence thermal evolution. In addition, the presence of widespread igneous rocks on passive margins may be indicative of regional-scale thermal perturbations that should be considered in source rock maturation studies. Overall, the conclusion of this project is that both magmatism and structural inheritance have profoundly influenced the continental breakup between West Greenland and Eastern Canada, and that interplay between these two complex groups of mechanisms may have also contributed to the geological evolution of this area.
Neural Network Dynamics and Brain Oscillations Underlying Aberrant Inhibitory Control in Internet Addiction

Previous studies have reported a role of alterations in the brain’s inhibitory control mechanism in addiction. Mounting evidence from neuroimaging studies indicates that its key components can be evaluated with brain oscillations and connectivity during inhibitory control. In this study, we developed an internet-related stop-signal task with electroencephalography (EEG) signal recorded to investigate inhibitory control. Healthy controls and participants with Internet addiction were recruited to participate in the internet-related stop-signal task with 19-channel EEG signal recording, and the corresponding event-related potentials and spectral perturbations were analyzed. Brain effective connections were also evaluated using direct directed transfer function. The results showed that, relative to the healthy controls, participants with Internet addiction had increased Stop-P3 during inhibitory control, suggesting that they have an altered neural mechanism in impulsive control. Furthermore, participants with Internet addiction showed increased low-frequency synchronization and decreased alpha and beta desynchronization in the middle and right frontal regions compared to healthy controls. Aberrant brain effective connectivity was also observed, with increased occipital-parietal and intra-occipital connections, as well as decreased frontal-paracentral connection in participants with Internet addiction. These results suggest that physiological signals are essential in future implementations of cognitive assessment of Internet addiction to further investigate the underlying mechanisms and effective biomarkers.
A Minimal and Multi-Source Recording Setup for Ankle Joint Kinematics Estimation During Walking Using Only Proximal Information From Lower Limb

In this study, a minimal setup for the ankle joint kinematics estimation is proposed relying only on proximal information of the lower-limb, i.e. thigh muscles activity and joint kinematics. To this purpose, myoelectric activity of Rectus Femoris (RF), Biceps Femoris (BF), and Vastus Medialis (VM) were recorded by surface electromyography (sEMG) from six healthy subjects during unconstrained walking task. For each subject, the angular kinematics of hip and ankle joints were synchronously recorded with sEMG signal for a total of 288 gait cycles. Two feature sets were extracted from sEMG signals, i.e. time domain (TD) and wavelet (WT) and compared to have a compromise between the reliability and computational capacity, they were used for feeding three regression models, i.e. Artificial Neural Networks, Random Forest, and Least Squares - Support Vector Machine (LS-SVM). BF together with LS-SVM provided the best ankle angle estimation in both TD and WT domains (RMSE < 5.6 deg). The inclusion of Hip joint trajectory significantly enhanced the regression performances of the model (RMSE < 4.5 deg). Results showed the feasibility of estimating the ankle trajectory using only proximal and limited information from the lower limb which would maximize a potential transfemoral amputee user’s comfortability while facing the challenge of having a small amount of information thus requiring robust data-driven models. These findings represent a significant step towards the development of a minimal setup useful for the control design of ankle active prosthetics and rehabilitative solutions.
Implementasi Zigbee Transceiver Untuk Akuisisi Data Sensor Inersia Pada Wireless Body Area Network (WBAN)

Laju pertambahan jumlah penduduk yang membutuhkan layanan kesehatan di Indonesia tidak berbanding lurus dengan penambahan jumlah fasilitas kesehatan yang ada. Salah satu solusi alternatif yang dapat digunakan untuk mengatasi masalah tersebut adalah dengan mengembangkan teknologi Wireless Body Area Network (WBAN) sebagai alat bantu layanan kesehatan. WBAN adalah suatu sistem terpadu yang terdiri atas sekelompok modul sensor yang terdistribusi dan terhubung secara nirkabel pada suatu topologi jaringan tertentu dan berfungsi untuk mengekstrak dan berbagi informasi untuk diolah sesuai bidang aplikasinya. Salah satu aplikasi WBAN adalah untuk analisis gait atau metode untuk mempelajari pola berjalan manusia. Untuk melakukan proses analisis gait secara optimal dibutuhkan instrumen sensor inersia yang terpasang pada tubuh pasien yang merekam data gait dari pasien. Data dari pasien lalu dikirimkan melalui protokol komunikasi nirkabel ZigBee ke network coordinator yang berfungsi sebagai pengumpul data. Jaringan memiliki topologi dalam bentuk star dengan data rate dari sensor sebesar 50 Hz. Data dari network coordinator kemudian dibaca pada PC yang telah dilengkapi perangkat lunak pengolah data untuk diolah lebih lanjut. Sistem diuji pada ruangan koridor sejauh 4 meter dengan nilai RSSI atau kuat sinyal bernilai paling kecil sebesar -64 dBm. Dalam hal konsumsi daya, sensor node dapat digunakan secara berkelanjutan dalam jangka waktu 2 jam 25 menit
All-Hydrocarbon-Ligated Superatomic Gold/Aluminum Clusters

Key strategies in cluster synthesis include the use of modulating agents (e.g., coordinating additives). We studied the influence of various phosphines exhibiting different steric and electronic properties on the reduction of the Au(I) precursor to Au(0) clusters. We report a synthesis of the bimetallic clusters [Au6(AlCp*)6] = [Au6Al6](Cp*)6 (1) and [HAu7(AlCp*)6] = [HAu7Al6](Cp*)6 (2) (Cp* = pentamethylcyclopentadiene) using Au(I) precursors and AlCp*. The cluster [Au2(AlCp*)5] = [Au2Al5](Cp*)5 (3) was isolated and identified as an intermediate species in the reactions to 1 and 2. The processes of cluster growth and degradation were investigated by in situ 1H NMR and LIFDI-MS techniques. The structures of 1 and 2 were established by DFT geometry optimization. These octahedral clusters can both be described as closed-shell 18-electron superatoms.
Nazo, the Drosophila homolog of the NBIA-mutated protein–c19orf12, is required for triglyceride homeostasis

Lipid dyshomeostasis has been implicated in a variety of diseases ranging from obesity to neurodegenerative disorders such as Neurodegeneration with Brain Iron Accumulation (NBIA). Here, we uncover the physiological role of Nazo, the Drosophila melanogaster homolog of the NBIA-mutated protein–c19orf12, whose function has been elusive. Ablation of Drosophila c19orf12 homologs leads to dysregulation of multiple lipid metabolism genes. nazo mutants exhibit markedly reduced gut lipid droplet and whole-body triglyceride contents. Consequently, they are sensitive to starvation and oxidative stress. Nazo is required for maintaining normal levels of Perilipin-2, an inhibitor of the lipase–Brummer. Concurrent knockdown of Brummer or overexpression of Perilipin-2 rescues the nazo phenotype, suggesting that this defect, at least in part, may arise from diminished Perilipin-2 on lipid droplets leading to aberrant Brummer-mediated lipolysis. Our findings potentially provide novel insights into the role of c19orf12 as a possible link between lipid dyshomeostasis and neurodegeneration, particularly in the context of NBIA.
Hafnium-Tungsten Chronometry of Planetary Accretion and Differentiation

The formation and earliest history of many planetary bodies in the inner solar system involved heating and melting of planetary interiors, causing differentiation into silicate mantles and metal cores. A record of these earliest stages of planetary evolution is preserved in the W isotopic composition of meteorites as well as lunar and terrestrial rocks. Hafnium-tungsten chronometry reveals that the early thermal and chemical evolution of asteroids is controlled by the decay of 26 Al. This nuclide was sufficiently abundant to melt early-formed planetesimals (iron meteorite parent bodies) but could not raise the temperatures in the late-formed chondrite parent asteroids high enough to cause differentiation. Larger bodies such as the Earth grew over longer timescales and the energy required for differentiation was mainly delivered by large impacts. Formation of the Earth was largely completed by the impact of a Mars-sized body that led to the formation of the Moon between 4.53 and 4.47 billion years ago.
Association of serum YKL-40 and DPP4 with T2-high asthma in Chinese adults

This study aimed to assess the utility of serum YKL-40 and serum dipeptidyl peptidase IV (DPP4) as biomarkers for distinguishing between type 2 (T2)-high and T2-low asthma in the Chinese population. Additionally, we sought to explore the associations of serum YKL-40 and DPP4 levels with asthma characteristics and conventional markers. A real-world observational cross-sectional study was conducted, involving a total of 75 adult asthma patients. We collected general information, including demographics and medical history. Measurements included complete blood count, fractional exhaled nitric oxide (FeNO), post-bronchodilator spirometry, serum YKL-40 and serum DPP4 levels. Asthma endotypes, T2-high and T2-low, were defined through a comprehensive review of existing literature and expert group discussions. Logistic and linear regression models were employed. Our findings indicated no significant association between serum YKL-40 or serum DPP4 levels and T2-high asthma across all models. In the fully adjusted model, their odds ratios (OR) were 0.967 (95% CI: 0.920–1.017) and 0.997 (95% CI: 0.993–1.001), respectively. Notably, serum YKL-40 exhibited a positive correlation with FeNO (β = 0.382, 95% CI: 0.230–0.533) after adjusting for confounding factors. This association, however, diminished in patients under 40 years old (P = .24), males (P = .25), and those with FEV1%pred of 80% or higher (P = .25). Serum DPP4 demonstrated a negative correlation with FEV1/FVC in the fully adjusted model (β: −0.005, 95% CI: −0.009, −0.000). Among Chinese adult asthma patients, a positive correlation was observed between serum YKL-40 levels and FeNO in females aged over 40 with FEV1%pred less than 80%. Additionally, a weak negative correlation was found between serum DPP4 levels and FEV1/FVC. However, neither serum YKL-40 nor serum DPP4 levels exhibited the capability to differentiate between T2-high and T2-low asthma.
The Effects of Immersion and Visuo-Tactile Stimulation on Motor Imagery in Stroke Patients are Related to the Sense of Ownership

Visual guided motor imagery (MI) is commonly used in stroke rehabilitation, eliciting event-related desynchronization (ERD) in EEG. Previous studies found that immersion level and visuo-tactile stimulation could modulate ERD during visual guided MI, and both of two factors could also improve sense of ownership (SOO) over target limb (or body). Additionally, the relationship was also reported between the performance of MI and SOO. This study aims to investigate whether immersion and visuo-tactile stimulation affect visual guided MI through the SOO over virtual body in stroke patients. Nineteen stroke patients were recruited. The experiment included two phases (i.e., SOO induction and visual guided MI with SOO) that was manipulated across four conditions in a within-subject design: ${2}\times {2}$ , i.e., immersion (VR, 2D monitor display) $\times $ multisensory stimulation (visuo-tactile stimulation, observation without tactile stimulation). Results found peaks ERD amplitude during MI were significantly higher in stronger SOO conditions than weaker SOO conditions. Interestingly, the ERD during visual guided MI under the condition of vision only in VR and visuo-tactile stimulation in 2D monitor are similar, which indicates that SOO may be an important factor behind this phenomenon (due to the similar SOO between these two conditions). A moderate correlation was also found between SOO scores and peaks ERD amplitude during MI. This study discussed the possible factor underlying the effects of immersion and multisensory stimulation on visual guided MI in post-stroke patients, identifying the effect of SOO in this process, and could be referred in future studies for coming up with better MI paradigms for stroke rehabilitation.
Prognostic implication of novel immune-related signature in breast cancer

Checkpoint inhibitor therapy has become increasingly important and has been endorsed as a treatment regimen in breast cancer. But benefits were limited to a small proportion of patients. We aimed to develop an improved signature on the basis of immune genes for detection of potential benefit from immunotherapy. Gene expression data of patients with breast cancer initially extracted from The Cancer Genome Atlas were analyzed. Ten genes were selected from the interaction of differentially expressed genes as well as immune-related genes to develop a survival signature. We compared the high-risk and low-risk groups by gene set enrichment analysis, immune infiltration, checkpoint molecule expression and immunophenoscore. Ten genes were extracted from interactions of differentially expressed and immune-related genes. The immune risk score was determined on the basis of the Cox regression coefficient of hub genes and validated with the GSE96058 dataset. Immune cell infiltrates, including CD8 + T cells, plasma cells, follicular helper T cells, CD4 + memory T cells, M1 macrophages, regulatory T cells and resting NK cells, were more highly infiltrated in the high-risk group as compared to the low-risk group. Checkpoint molecules, including CTLA-4, PD-L1, TIM-3, VISTA, ICOS, PD-1, and PD-L2, were expressed at markedly lower levels in the high-risk group as compared to the low-risk group. Immunophenoscores, as a surrogate of response to immune checkpoint therapy, was observed significant lower in the high-risk group. The 10-gene prognostic signature could identify patients’ survival and was correlated with the biomarkers of immune checkpoint inhibitor therapy, which may guide precise therapeutic decisions in clinical practice.
The importance of considering competing treatment affecting prognosis in the evaluation of therapy in trials: the example of renal transplantation in hemodialysis trials: Clinical Epidemiology in Nephrology

Background. During the follow‐up in a randomized controlled trial (RCT), participants may receive additional (non‐randomly allocated) treatment that affects the outcome. Typically such additional treatment is not taken into account in evaluation of the results. Two pivotal trials of the effects of hemodiafiltration (HDF) versus hemodialysis (HD) on mortality in patients with end‐stage renal disease reported differing results. We set out to evaluate to what extent methods to take other treatments (i.e. renal transplantation) into account may explain the difference in findings between RCTs. This is illustrated using a clinical example of two RCTs estimating the effect of HDF versus HD on mortality. Methods. Using individual patient data from the Estudio de Supervivencia de Hemodiafiltración On‐Line (ESHOL; n = 902) and The Dutch CONvective TRAnsport STudy (CONTRAST; n = 714) trials, five methods for estimating the effect of HDF versus HD on all‐cause mortality were compared: intention‐to‐treat (ITT) analysis (i.e. not taking renal transplantation into account), per protocol exclusion (PPexcl; exclusion of patients who receive transplantation), PPcens (censoring patients at the time of transplantation), transplantation‐adjusted (TA) analysis and an extension of the TA analysis (TAext) with additional adjustment for variables related to both the risk of receiving a transplant and the risk of an outcome (transplantation‐outcome confounders). Cox proportional hazards models were applied. Results. Unadjusted ITT analysis of all‐cause mortality led to differing results between CONTRAST and ESHOL: hazard ratio (HR) 0.95 (95% CI 0.75‐1.20) and HR 0.76 (95% CI 0.59‐0.97), respectively; difference between 5 and 24% risk reductions. Similar differences between the two trials were observed for the other unadjusted analytical methods (PPcens, PPexcl, TA) The HRs of HDF versus HD treatment became more similar after adding transplantation as a time‐varying covariate and including transplantation‐outcome confounders: HR 0.89 (95% CI 0.69‐1.13) in CONTRAST and HR 0.80 (95% CI 0.62‐1.02) in ESHOL. Conclusions. The apparent differences in estimated treatment effects between two dialysis trials were to a large extent attributable to differences in applied methodology for taking renal transplantation into account in their final analyses. Our results exemplify the necessity of careful consideration of the treatment effect of interest when estimating the therapeutic effect in RCTs in which participants may receive additional treatments.