Miracle-dz/UniFAR-FTUs huggingface dataset:
Efficacy of the low dose apatinib plus deep hyperthermia as third-line or later treatment in HER-2 negative advanced gastric cancer

Aim: To observe the efficacy of the low dose apatinib plus deep hyperthermia as third-line or later treatment for patients with human epidermal growth factor receptor 2 (HER-2) negative advanced gastric cancer. Methods: 80 eligible patients with HER-2 negative advanced gastric cancer admitted to Jingjiang People’s Hospital Affiliated with Yangzhou University-from March 2021 to March 2022 were selected, and they were divided into the control group (n = 40, apatinib) and experimental group (n = 40, apatinib plus deep hyperthermia) on the basis of random number table method. The levels of serum carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), and vascular endothelial growth factor (VEGF) were monitored, and the efficacy of the two groups was analyzed by referring to Karnofsky performance status (KPS), overall survival (OS) and disease control rate (DCR) before and after treatment. Results: The levels of CEA, CA199, and VEGF in both groups were lower after treatment than before (p < 0.05), and lower (CEA: 8.85 ± 1.36 vs. 12.87 ± 1.23, CA199: 34.19 ± 4.68 vs. 50.11 ± 5.73, VEGF: 124.8 ± 18.03 vs. 205.9 ± 19.91) in the experimental group than in the control group (p < 0.05). The DCR and KPS of the patients in the experimental group were significantly higher (DCR: 62.50% vs. 40.00%; KPS: 83.25 ± 1.15 vs. 76.25 ± 1.17) than in the control group (p < 0.05). In survival analysis, patients with control group had shorter OS than the experimental group. (median 5.65 vs. 6.50 months; hazard ratio [HR], 1.63 [95% confidence interval (CI) 1.02–2.60], p = 0.0396). Conclusion: The application of low-dose apatinib plus deep hyperthermia for patients with HER-2 negative gastric cancer who failed second-line treatment should be a promising option.
Ascites-derived CDCP1+ extracellular vesicles subcluster as a novel biomarker and therapeutic target for ovarian cancer

Introduction Ovarian cancer (OVCA) is one of the most prevalent malignant tumors of the female reproductive system, and its diagnosis is typically accompanied by the production of ascites. Although liquid biopsy has been widely implemented recently, the diagnosis or prognosis of OVCA based on liquid biopsy remains the primary emphasis. Methods In this study, using proximity barcoding assay, a technique for analyzing the surface proteins on single extracellular vesicles (EVs). For validation, serum and ascites samples from patients with epithelial ovarian cancer (EOC) were collected, and their levels of CDCP1 was determined by enzyme-linked immunosorbent assay. Tissue chips were prepared to analyze the relationship between different expression levels of CDCP1 and the prognosis of ovarian cancer patients. Results We discovered that the CUB domain-containing protein 1+ (CDCP1+) EVs subcluster was higher in the ascites of OVCA patients compared to benign ascites. At the same time, the level of CDCP1 was considerably elevated in the ascites of OVCA patients. The overall survival and disease-free survival of the group with high CDCP1 expression in EOC were significantly lower than those of the group with low expression. In addition, the receiver operating characteristic curve demonstrates that EVs-derived CDCP1 was a biomarker of early response in OVCA ascites. Discussion Our findings identified a CDCP1+ EVs subcluster in the ascites of OVCA patients as a possible biomarker for EOC prevention.
Brodalumab for the treatment of plaque psoriasis in a real-life setting: a 3 years multicenter retrospective study—IL PSO (Italian landscape psoriasis)

Introduction Brodalumab is a monoclonal antibody that targets the subunit A of the interleukin-17A receptor (IL17RA), inhibiting the signaling of various isoforms of the IL-17 family. It has been approved for the treatment of moderate-to-severe plaque psoriasis after being evaluated in three Phase-3 trials. However, long-term data on brodalumab in a real-life setting are still limited. Methods The aim of this study was to evaluate the long-term effectiveness and safety of brodalumab in psoriasis. We also assessed the drug survival of brodalumab in a 3 years timespan. We conducted a retrospective multicenter study on 606 patients followed up at 14 Italian dermatology units, all treated with brodalumab according to Italian guidelines. Patients’ demographics and disease characteristics were retrieved from electronic databases. At baseline and weeks 12, 24, 52, 104 and 156, we evaluated the psoriasis area and severity index (PASI) score and investigated for adverse events. The proportions of patients reaching 75, 90 and 100% (PASI 75, PASI 90 and PASI 100, respectively) improvement in PASI, compared with baseline, were also recorded. Results At week 12, 63.53% of the patients reached PASI 90 and 49.17% PASI 100. After 3 years of treatment, 65.22% of patients maintained a complete skin clearance, and 91.30% had an absolute PASI of 2 or less. Patients naïve to biological therapies had better clinical responses at weeks 12, 24 and 52. However, after 2 years of treatment, no significant differences were observed. Body mass index did not interfere with the effectiveness of brodalumab throughout the study. No new safety findings were recorded. After 36 months, 85.64% of our patients were still on treatment with brodalumab. Conclusion Our data confirm the effectiveness and the safety of brodalumab in the largest real-life cohort to date, up to 156 weeks.
Impairments to the multisensory integration brain regions during migraine chronification: correlation with the vestibular dysfunction

Objectives Migraine is often combined with vestibular dysfunction, particularly in patients with chronic migraine (CM). However, the pathogenesis of migraine chronification leading to vestibular dysfunction is not fully understood. The current study investigated whether structural or functional impairments to the brain during migraine chronification could be associated with vestibular dysfunction development. Methods The eligible participants underwent clinical assessment and magnetic resonance imaging (MRI) scans. Voxel-based morphometry (VBM) determined structural impairment by evaluating alterations in gray matter volume (GMV). Functional impairment was assessed by the mean amplitude of low-frequency fluctuation (mALFF). Furthermore, the resting-state functional connectivity (rsFC) of regions possessing impairment was examined with a seed-based approach. We also analyzed the correlations between altered neuroimaging features with clinical variables and performed multiple linear regression. Results Eighteen CM patients, 18 episodic migraine (EM) patients, and 18 healthy controls (HCs) were included in this study. A one-way ANOVA indicated the group differences in mALFF. These were located within right supramarginal gyrus (SMG), left angular gyrus (AG), middle frontal gyrus (MFG), left middle occipital gyrus (MOG), right rolandic operculum (Rol) and left superior parietal gyrus (SPG). During rsFC analysis, the CM group had more enhanced rsFC of left SPG with left MOG than the EM and HC groups. The EM group revealed enhanced rsFC of left SPG with left AG than the CM and HC groups. In multiple linear regression, after controlling for age, body mass index (BMI) and disease duration, the rsFC of left SPG with left MOG (β = 48.896, p = 0.021) was found to predict the total Dizziness Handicap Inventory (DHI) score with an explained variance of 25.1%. Moreover, the rsFC of left SPG with left MOG (β = 1.253, p = 0.003) and right SMG (β = −1.571, p = 0.049) were significant predictors of migraine frequency, accounting for a total explained variance of 73.8%. Conclusion The functional impairments due to migraine chronification are primarily concentrated in the multisensory integration-related brain regions. Additionally, the rsFC of SPG with MOG can predict the frequency of migraine and the degree of vestibular dysfunction. Therefore, these neuroimaging features could be potential mechanisms and therapeutic targets for developing vestibular dysfunction in migraine.
Population structure of Pacific green turtles: a new perspective from microsatellite DNA variation

This study builds upon the current understanding of green turtle population genetic structure in the Pacific that has largely been based on mitochondrial DNA (mtDNA), by examining nuclear DNA (nDNA) diversity, regional connectivity, and male-mediated gene flow. A total of 1,111 nesting green turtle samples were analyzed with 10 microsatellite markers from 20 Pacific rookeries. Population differentiation (FST) was significant (p <0.05) in all but 8 of 190 pairwise rookery comparisons. Pairwise F ST values and discriminant analysis of principal components (DAPC) revealed a defined East-West split consistent with mtDNA studies. Additionally, isolation-by-distance was evaluated with estimated effective migration surfaces (EEMS). The data indicated structure throughout the Pacific rookeries largely in agreement with stock structure defined by mtDNA studies, except for some areas on the Central American and Australian continental shelves, providing evidence of possible male-mediated gene flow. The series of analyses performed did indicate that male-mediated gene flow has likely occurred where breeding migration corridors of separate populations overlap with courtship areas. This may occur primarily along the margins of continents, including along Mexico and Central America in the East Pacific. Our study provides an ocean-wide baseline nDNA dataset for green turtle rookeries in the Pacific and reexamines the current thinking regarding the role of male turtles in the population dynamics of management units (MU) and to what extent nuclear gene flow occurs among designated MUs.
Feedback on audit and action planning for dental caries control: a qualitative study to investigate the acceptability among interdisciplinary pediatric dental care teams

Introduction American Indian and Alaska Native children suffer from the poorest oral health of all populational groups in the United States. Evidence-based practices (EBP) for caries control are well established, but systematically implementing such practices have proven difficult. Audit and feedback with goal setting, and action planning to implement these EBPs have not been tested or adapted for Alaska Native healthcare settings. The aim of this study was to investigate acceptability and perceived feasibility of an audit and feedback intervention for pediatric dental caries control among dental providers and patient stakeholders. Methods The pilot program was implemented in two dental clinics from a tribal healthcare consortium in Alaska. Key-informant interviews were conducted to investigate the contextual, organizational, and behavioral facilitators and barriers to the implementation and expansion of the program. Interview transcripts were analyzed by two researchers using thematic analysis. Results Eight key informants were interviewed twice (during and after the intervention period), and one once, for a total of 17 interviews. Patient stakeholders were not interviewed due to COVID-19 pandemic clinic closures and social isolation mandates. Three principal themes emerged: a positive organizational climate and culture fostered the acceptability of the program, the positive impacts of the program observed in the pediatric dental teams and the organization, and the challenges to implement the program including understanding the data reports, trusting the accuracy of the data, and competing priorities. Conclusions The intervention of audit and feedback with goal setting and action planning was well accepted and perceived as feasible by the study participants given the financial and human resources provided by the research project. This qualitative study can inform the design and evaluation of process-oriented implementation strategies geared towards decreasing health inequities and improving health outcomes, such as dental caries in American Indian and Alaska Native children and adolescents.
Genome wide association and haplotype analyses for the crease depth trait in bread wheat (Triticum aestivum L.)

Wheat grain has a complex structure that includes a crease on one side, and tissues within the crease region play an important role in nutrient transportation during wheat grain development. However, the genetic architecture of the crease region is still unclear. In this study, 413 global wheat accessions were resequenced and a method was developed for evaluating the phenotypic data of crease depth (CD). The CD values exhibited continuous and considerable large variation in the population, and the broad-sense heritability was 84.09%. CD was found to be positively correlated with grain-related traits and negatively with quality-related traits. Analysis of differentiation of traits between landraces and cultivars revealed that grain-related traits and CD were simultaneously improved during breeding improvement. Moreover, 2,150.8-Mb genetic segments were identified to fall within the selective sweeps between the landraces and cultivars; they contained some known functional genes for quality- and grain-related traits. Genome-wide association study (GWAS) was performed using around 10 million SNPs generated by genome resequencing and 551 significant SNPs and 18 QTLs were detected significantly associated with CD. Combined with cluster analysis of gene expression, haplotype analysis, and annotated information of candidate genes, two promising genes TraesCS3D02G197700 and TraesCS5A02G292900 were identified to potentially regulate CD. To the best of our knowledge, this is the first study to provide the genetic basis of CD, and the genetic loci identified in this study may ultimately assist in wheat breeding programs.
The effect of cannabidiol on seizure features and quality of life in drug-resistant frontal lobe epilepsy patients: a triple-blind controlled trial

Background Treatment-resistant epileptic seizures are associated with reduced quality of life (QoL). As polypharmacy with routine antiseizure medications has many side effects, novel add-on treatments are necessary. Recent research showed the efficacy of add-on therapy by cannabidiol (CBD) on refractory epilepsy. We attempted to extend data on the efficacy and safety profile of CBD in patients with frontal lobe treatment-resistant epilepsy. Methods A total of 27 patients were recruited into two CBD (n = 12) and placebo (n = 15) groups. The CBD group received a highly purified liposomal preparation of the drug in addition to routine antiseizure medications. The placebo group only received antiseizure medications. This experiment followed a triple-blinding protocol. Outcome measures were seizure frequency, the Chalfont seizure severity scale (CSSS), and the quality of life questionnaire score (QOLIE-31) assessed at baseline, 4 weeks, and 8 weeks. Results At 4 weeks, results indicated that a higher fraction of patients in the CBD group (66.67%) showed improvement in seizure, compared to the placebo group (20.00%). Before–after comparison revealed that CBD, unlike routine ADEs, was effective in reducing the occurrence of seizures at the study's final timepoint [mean difference 45.58, 95% CI (8.987 to 82.18), p = 0.009]. Seizure severity was not affected by study groups or time intervals (repeated-measures ANOVA p > 0.05). Post-hoc tests found that the QoLI-31 score was improved at 8 weeks compared to baseline [mean diff. −5.031, 95% CI (−9.729 to −0.3328), p = 0.032]. The difference in cases who experienced enhanced QoL was meaningful between the CBD and placebo groups at 8 weeks [RR: 2.160, 95% CI (1.148 to 4.741), p = 0.018] but not at 4 weeks (p = 0.653). A positive finding for QoL improvement was associated with a positive finding for seizure frequency reduction [r = 0.638, 95% CI (0.296 to 0.835), p = 0.001]. Interestingly, limiting the correlation analysis to cases receiving CBD indicated that QoL improvement was not linked with seizure parameters such as severity and frequency (p > 0.05). Conclusion The present study suggests the benefit of a purified and highly efficient preparation of CBD for seizure frequency reduction and improvement of QoL in refractory frontal lobe epilepsy. Further study with longer follow-ups and larger sample size is advised. Clinical trial registration https://www.irct. ir/trial/56790, identifier: IRCT20210608051515N1.
Allometric equations for estimating peak uprooting force of riparian vegetation

Uprooting caused by flood events is a significant disturbance factor that affects the establishment, growth, and mortality of riparian vegetation. If the hydraulic drag force acting on riparian plants exceeds the peak uprooting force originate from their below-ground portion, it may result in the uprooting of these plants. Despite previous studies have documented and investigated the uprooting processes and factors influencing the peak uprooting force of plants, most of these studies have focused on how the root morphological traits of tree and shrub seedlings affect peak uprooting force or mainly collected data in indoor experiments, which may limit the extrapolation of the results to natural environments. To address these limitations, we assume that the peak uprooting force can be estimated by the morphological traits of the above-ground portion of the vegetation. In this study, we conducted in-situ vertical uprooting tests on three locally dominant species: Conyza canadensis, Daucus carota, and Leonurus sibiricus, in a typical riverine environment. The three species were found to have the highest abundance based on the outcomes of the quadrat method. We measured the peak uprooting force, plant height, stem basal diameter, shoot and root wet biomass, and shoot and root dry biomass of each plant and compared them between species. Furthermore, we quantified the influence of morphology on peak uprooting force. Our results showed significant differences in morphological traits and peak uprooting force among the three species. We found a significant positive correlation between peak uprooting force and the morphological traits of the three species. The peak uprooting force increases with plant size following a power law function which is analogous to allometric equations. The allometric equation provided a convenient and non-destructive method to estimate the peak uprooting force based on the above-ground morphological traits of the plants, which may help to overcome the limitations of measuring root morphological traits.
Distance education project of English idioms learning from watching YouTube

Idioms have been recognized to be commonly adopted by academic practitioners in their speech and writing. However, despite their common occurrence in English communication, idioms pose great challenges for non-native English speakers, as they are often ignored in English classrooms. Particularly in Vietnam, a minimal number of idioms appear in English textbooks published by the Ministry of Education, and teachers appeared to under-emphasize English idioms’ usefulness in conversation. To fill the gap, the present study adopted YouTube for Vietnamese students to undertake supplementary learning of English idiom knowledge. The study recruited 34 students and randomly assigned them to a control group and an experimental group. Both groups were required to take notes during their watching. Yet, only the experimental group would take extra exercises at the end of their watching. Immediate post-tests, delayed post-tests, and a survey were conducted. The findings demonstrate that the students in the two groups retained idiom knowledge similarly well. They were also positive towards learning English idioms through YouTube. Pedagogical implications and research suggestions are provided to conclude the study.
Functional and structural lesion network mapping in neurological and psychiatric disorders: a systematic review

Background The traditional approach to studying the neurobiological mechanisms of brain disorders and localizing brain function involves identifying brain abnormalities and comparing them to matched controls. This method has been instrumental in clinical neurology, providing insight into the functional roles of different brain regions. However, it becomes challenging when lesions in diverse regions produce similar symptoms. To address this, researchers have begun mapping brain lesions to functional or structural networks, a process known as lesion network mapping (LNM). This approach seeks to identify common brain circuits associated with lesions in various areas. In this review, we focus on recent studies that have utilized LNM to map neurological and psychiatric symptoms, shedding light on how this method enhances our understanding of brain network functions. Methods We conducted a systematic search of four databases: PubMed, Scopus, and Web of Science, using the term “Lesion network mapping. ” Our focus was on observational studies that applied lesion network mapping in the context of neurological and psychiatric disorders. Results Following our screening process, we included 52 studies, comprising a total of 6,814 subjects, in our systematic review. These studies, which utilized functional connectivity, revealed several regions and network overlaps across various movement and psychiatric disorders. For instance, the cerebellum was found to be part of a common network for conditions such as essential tremor relief, parkinsonism, Holmes tremor, freezing of gait, cervical dystonia, infantile spasms, and tics. Additionally, the thalamus was identified as part of a common network for essential tremor relief, Holmes tremor, and executive function deficits. The dorsal attention network was significantly associated with fall risk in elderly individuals and parkinsonism. Conclusion LNM has proven to be a powerful tool in localizing a broad range of neuropsychiatric, behavioral, and movement disorders. It holds promise in identifying new treatment targets through symptom mapping. Nonetheless, the validity of these approaches should be confirmed by more comprehensive prospective studies.
Transferrin receptor-targeting property of pabinafusp alfa facilitates its uptake by various types of human brain-derived cells in vitro

Pabinafusp alfa, which is an anti-mucopolysaccharidosis II drug, consists of iduronate-2-sulfatase (IDS) genetically fused with an anti-transferrin receptor (TfR) antibody. While IDS is known to enter cells via mannose-6-phosphate receptor (M6PR)-mediated endocytosis, the anti-TfR antibody moiety of pabinafusp alfa is supposed to trigger the TfR-mediated transcytosis involved in its blood-brain barrier (BBB) penetration to deliver IDS into the brain, which thus makes it effective for treatment of brain symptoms of the disease. However, since these uptake processes remain unexamined in vitro, this study aims at elucidating how human brain cells manipulate these receptors to facilitate pabinafusp alfa uptake. The results of pabinafusp alfa uptake assays showed that the TfR played an primary role in its uptake by brain microvascular endothelial cells. The TfR contribution was also found in neuronal cells at levels comparable to M6PR. Interestingly, the predominant roles of TfR over M6PR in pabinafusp alfa uptake were also observed in astrocytes and pericytes. To summarize, our results support the TfR-targeting strategy of pabinafusp alfa for facilitating its BBB penetration while simultaneously identifying previously unnoticed TfR roles in its uptake into human neuronal and non-neuronal brain cells. These findings are certain to provide important insights into the mechanisms behind clinical actions of pabinafusp alfa.