Miracle-dz/UniFAR-FTUs huggingface dataset:
Mediators and Moderators of Active Music Engagement to Reduce Traumatic Stress Symptoms and Improve Well-being in Parents of Young Children With Cancer

Objective: This trial examined the effects of proximal/distal mediators and moderators of an Active Music Engagement (AME) intervention on young child/parent distress, quality of life, and family function outcomes. Methods: Child/parent dyads (n = 125) were randomized to AME or Audio-storybooks attention control condition. Each group received 3 sessions with a credentialed music therapist for 3 consecutive days with data collection at baseline, post-intervention (T2), and 30-days later (T3). Potential proximal mediators included within session child and parent engagement. Potential distal mediators included changes in perceived family normalcy, parent self-efficacy, and independent use of play materials. Potential moderators included parent/child distress with prior hospitalizations, parent traumatic stress screener (PCL-6), and child age. Outcomes included child emotional distress and quality of life; parent emotion, traumatic stress symptoms (IES-R), well-being; and family function. Mediation effects were estimated using ANCOVA, with indirect effects estimated using the percentile bootstrap approach. Moderation effects were tested by including appropriate interaction terms in models. Results: No significant mediation effects were observed. Child distress with prior hospitalizations moderated AME effects for IES-R intrusion subscale scores at T2 (P = .01) and avoidance subscale scores at T3 (P = .007). Traumatic stress screener scores (PCL-6) moderated intervention effects for IES-R hyperarousal subscale scores at T2 (P = .01). There were no moderation effects for child age. Conclusions: AME is a promising intervention for mitigating traumatic stress symptoms and supporting well-being in parents of children with cancer, particularly for parents who screen high for traumatic stress and whose children are more highly distressed with hospitalization.
Molecular characteristics of early‐onset pancreatic ductal adenocarcinoma

The median age of patients with pancreatic ductal adenocarcinoma (PDAC) at diagnosis is 71 years; however, around 10% present with early‐onset pancreatic cancer (EOPC), i.e., before age 50. The molecular mechanisms underlying such an early onset are unknown. We assessed the role of common PDAC drivers (KRAS, TP53, CDKN2A and SMAD4) and determined their mutational status and protein expression in 90 formalin‐fixed, paraffin‐embedded tissues, including multiple primary and matched metastases, from 37 EOPC patients. KRAS was mutated in 88% of patients; p53 was altered in 94%, and p16 and SMAD4 were lost in 86% and 71% of patients, respectively. Meta‐synthesis showed a higher rate of p53 alterations in EOPC than in late‐onset PDAC (94% vs. 69%, P = 0.0009) and significantly higher loss of SMAD4 (71% vs. 44%, P = 0.0025). The majority of EOPC patients accumulated aberrations in all four drivers; in addition, high tumour heterogeneity was observed across all tissues. The cumulative effect of an exceptionally high rate of alterations in all common PDAC driver genes combined with high tumour heterogeneity suggests an important mechanism underlying the early onset of PDAC.
Effects of healthy aging and mnemonic strategies on verbal memory performance across the adult lifespan: Mediating role of posterior hippocampus.

In this study, we aimed to understand the contributions of hippocampal anteroposterior subregions (head, body, tail) and subfields (cornu ammonis 1-3 [CA1-3], dentate gyrus [DG], and subiculum [Sub]) and encoding strategies to the age-related verbal memory decline. Healthy participants were administered the California Verbal Learning Test-II to evaluate verbal memory performance and encoding strategies and underwent 4.7 T magnetic resonance imaging brain scan with subsequent hippocampal subregions and subfields manual segmentation. While total hippocampal volume was not associated with verbal memory performance, we found the volumes of the posterior hippocampus (body) and Sub showed significant effects on verbal memory performance. Additionally, the age-related volume decline in hippocampal body volume contributed to lower use of semantic clustering, resulting in lower verbal memory performance. The effect of Sub on verbal memory was statistically independent of encoding strategies. While total CA1-3 and DG volumes did not show direct or indirect effects on verbal memory, exploratory analyses with DG and CA1-3 volumes within the hippocampal body subregion suggested an indirect effect of age-related volumetric reduction on verbal memory performance through semantic clustering. As semantic clustering is sensitive to age-related hippocampal volumetric decline but not to the direct effect of age, further investigation of mechanisms supporting semantic clustering can have implications for early detection of cognitive impairments and decline.
New bis-isoxazole with monoterpenic skeleton: regioselective synthesis, spectroscopic investigation, electrochemical, and density functional theory (DFT) studies

A novel bis-isoxazole was synthesized from (R)-Carvone and p-methylbenzaldoxime, via two successive [3+2] cycloaddition reactions (32CA). The newly obtained bis-isoxazole has been fully characterized by HRMS and NMR spectroscopy. The HMBC experiment was performed to determine the stereo and the regioselectivity of the reaction. The electrochemical behavior of the studied compound, in oxidation and reduction processes, was examined using the cyclic voltammetry technique. In addition, the regioselectivity of the [3+2] cycloaddition reaction and the molecular structure of the title compound was performed by density functional theory (DFT). The HOMO and LUMO orbitals were investigated to determine the electronic properties of the synthesized compound. Besides, the global reactivity indexes were used to explain the regioselectivity for the formation of the bis-isoxazole, the theoretical results are in good agreement with experimental findings.
Multiomics analysis reveals metabolic subtypes and identifies diacylglycerol kinase α (DGKA) as a potential therapeutic target for intrahepatic cholangiocarcinoma

Abstract Background Intrahepatic cholangiocarcinoma (iCCA) is a highly heterogeneous and lethal hepatobiliary tumor with few therapeutic strategies. The metabolic reprogramming of tumor cells plays an essential role in the development of tumors, while the metabolic molecular classification of iCCA is largely unknown. Here, we performed an integrated multiomics analysis and metabolic classification to depict differences in metabolic characteristics of iCCA patients, hoping to provide a novel perspective to understand and treat iCCA. Methods We performed integrated multiomics analysis in 116 iCCA samples, including whole‐exome sequencing, bulk RNA‐sequencing and proteome analysis. Based on the non‐negative matrix factorization method and the protein abundance of metabolic genes in human genome‐scale metabolic models, the metabolic subtype of iCCA was determined. Survival and prognostic gene analyses were used to compare overall survival (OS) differences between metabolic subtypes. Cell proliferation analysis, 5‐ethynyl‐2'‐deoxyuridine (EdU) assay, colony formation assay, RNA‐sequencing and Western blotting were performed to investigate the molecular mechanisms of diacylglycerol kinase α (DGKA) in iCCA cells. Results Three metabolic subtypes (S1‐S3) with subtype‐specific biomarkers of iCCA were identified. These metabolic subtypes presented with distinct prognoses, metabolic features, immune microenvironments, and genetic alterations. The S2 subtype with the worst survival showed the activation of some special metabolic processes, immune‐suppressed microenvironment and Kirsten rat sarcoma viral oncogene homolog (KRAS)/AT‐rich interactive domain 1A (ARID1A) mutations. Among the S2 subtype‐specific upregulated proteins, DGKA was further identified as a potential drug target for iCCA, which promoted cell proliferation by enhancing phosphatidic acid (PA) metabolism and activating mitogen‐activated protein kinase (MAPK) signaling. Conclusion Via multiomics analyses, we identified three metabolic subtypes of iCCA, revealing that the S2 subtype exhibited the poorest survival outcomes. We further identified DGKA as a potential target for the S2 subtype.
Assessment and prediction of the first‐flowering dates for the major fruit trees in Korea using a multi‐RCM ensemble

An impact of global warming on the first‐flowering date (FFD) of cherry, peach and pear in north‐eastern Asia are investigated using the Korean national scenario. For the study, we used the dynamically downscaled daily temperature with 12.5 km horizontal resolution derived from five regional climate models (RCMs) under the same lateral forcing from HadGEM2‐AO on the basis of Historical (1981–2010) and four Representative Concentration Pathway (RCP) (2021–2100) scenarios. According to our analysis of the Historical simulations, the five RCMs and phenological model have good capability in simulating temperature and FFD with uncertainties of about 2.4–3.4 °C and 8.4–13.9 days, respectively, while well reflecting the topographical effect. On the basis of the highest emission scenario (RCP8.5), the temperature increments of 4.8 °C induce an acceleration in blooming rate, thereby advancing the FFDs of cherry, peach and pear by the end of the 21st century by about 14.5, 15.8 and 14.5 days, respectively, compared with the current reference simulation (Historical). We found high availability of the Korean national scenarios with moderate reliability. We believe that the next generation of the Korean national downscaling project considering diverse lateral forcing will offer better performance and more useful projections to end users.
Circulating-tumor DNA Assessment in Diffuse Large B-cell Lymphoma to Determine Up-front Stem Cell Transplantation: A Pilot Study

Background/Aim: This study evaluated the possibility of clinical use of circulating-tumor DNA (ctDNA) as a biomarker to determine up-front autologous stem cell transplantation (auto-SCT) for patients with high-risk diffuse large B-cell lymphoma (DLBCL) in practice. Patients and Methods: To explore the dynamics of ctDNA in DLBCL, blood samples were collected sequentially before and after treatment from patients with newly diagnosed DLBCL who received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy. To conduct ctDNA genotyping and ctDNA monitoring simultaneously, targeted sequencing by cancer personalized profiling using deep sequencing was used. Results: Ten patients between the ages of 50 and 60 years were enrolled. Based on the international prognostic index (IPI), seven patients were classified as high-IPI-risk group, and three patients were classified as low-IPI-risk group. The IPI risk group correlated with total metabolic tumor volume. All patients completed six cycles of R-CHOP chemotherapy, and seven patients achieved complete response. Changes in ctDNA mutation numbers did not correlate with changes in PET scan images and treatment response. In most high-risk patients, new mutations appeared in ctDNA after completion of chemotherapy that conceivably marked resistant clones. Notably, disease relapse did not occur in high-risk patients with poor prognostic mutations who underwent autologous SCT. Conclusion: ctDNA monitoring was meaningful in high-risk patients. Moreover, ctDNA and well-known prognostic factors should be considered in the decision making for auto-SCT. If a new genetic mutation in ctDNA with a negative prognosis would emerge during treatment, high-risk patients should consider auto-SCT.
The Long-term Lung and Respiratory Outcomes of Acid Sphingomyelinase Deficiency: A 10- and 20-year Follow-up Study

Background/Aim: Acid sphingomyelinase deficiency (ASMD) is a rare lysosomal storage disorder characterized by sphingomyelin accumulation causing progressive lung disease, respiratory failure, and death. Patients and Methods: This retrospective observational study used the TriNetX database of electronic health records for 15,108 patients with ASMD from 2000-2020. After exclusions, 8,980 individuals were followed for 10 or 20 years. Outcomes included incidence and prevalence of respiratory disorders. Associations of age, sex and race were assessed. Results: Nearly all respiratory outcomes increased significantly over 20 versus 10 years. Other respiratory disorders, specified respiratory disorders and secondary pulmonary hypertension exhibited the greatest increases, reflecting progressive lung damage in ASMD. While outcomes were poor overall, older age, male sex, and racial minority status associated with greater risks, indicating differences in disease progression or care. Conclusion: This study confirms the progressive nature of ASMD and need for close monitoring and treatment of pulmonary complications to reduce long-term morbidity and mortality. Genetic testing enabling diagnosis even for milder, adult-onset forms is critical to optimize outcomes.
Assessment of the impacts of ergonomic risk factors on shopping centre employees

Abstract Employees of shopping malls face various physiological and psychological health problems due to their specific working conditions. The purpose of this descriptive study was to evaluate the ergonomic risk factors for employees (N=222) from three shopping centres in the city of Erzurum, Turkey. We wanted to learn more about the attitudes of the shopping mall employees regarding their current working conditions, which we hoped would help us propose measures for the elimination or reduction of the most prominent ergonomic risk factors. Data were collected between May 1 and July 1, 2022 using our own questionnaire, which consisted of questions regarding personal characteristics (gender, age, education level, marital status, working year, unit, working position, nature of the job, presence of chronic disease, etc.) and the Workplace Ergonomics Scale, which consists of 32 items divided into 6 sub-dimensions (Occupational Health and Safety, Environmental Conditions, Psychological Elements, Employee Safety, Workplace Social Environment, and Working Environment). The obtained results indicated that the majority of employees were young, healthy, high school graduates mainly working as sales consultants. Their average income was low, their working hours were long, and they found their rest periods shorter than needed. The study found that, although shopping centre employees rated their work environment as low risk in terms of ergonomics, their scores on the workplace ergonomics scale were above average. The results of this study could contribute to a better understanding and identification of ergonomic risks in the trade sector and serve for planning future prevention strategies.
Frequency of thrombophilia-associated mutations and polymorphisms in pregnant women with a history of thrombosis or pregnancy complications

Abstract Objectives To assess the frequency of multiple thrombophilia-associated mutations and polymorphisms in a selected population of high-risk pregnancies. Methods Thrombophilia screening was performed for 1,500 pregnant women with prior pregnancy complications or thrombotic events. Nine thrombophilia-associated mutations or polymorphisms were screened: factor V Leiden, factor V H1299R, prothrombin G20210A, MTHFR C677T, MTHFR A1298C, factor XIII V34L, PAI-1 4G/5G polymorphisms, EPCR G4600A, EPCR C4678G. Results Out of the 1,500 patients, 1,291 fulfilled the criteria for data interpretation. All patients had low-risk thrombophilia-associated genetic variants. Only 1.24 % of cases presented high-risk abnormalities (homozygous factor V Leiden/prothrombin G20210A, or both mutations in heterozygous form). Heterozygous factor V Leiden occurred in 10.38 % of cases, while only 5.81 % carried heterozygous prothrombin G20210A mutation. The frequency of prothrombin G20210A mutation was higher (10.37 %) in the subgroup associating factor V Leiden, than in the subgroup lacking it (5.36 %). Low-risk genetic variants occurred with a higher frequency: 23.78 % factor V H1299R, 57.32 % MTHFR C677T, 55.54 % MTHFR A1298C, 44.07 % factor XIII V34L, 73.20 % PAI-1 4G/5G polymorphisms, 69.64 % EPCR G4600A, and 69.63 % EPCR C4678G. Conclusions All patients had at least one prothrombotic genetic mutation or variant. Our data highlight the need for thrombophilia screening, including low-risk genetic variants, in a high-risk population of pregnant women with a history of pregnancy complications or thrombotic events.
Characterization of Meloidogyne enterolobii intercepted from baobab (Adansonia digitata L.) seedlings from Thailand during Japanese import plant quarantine inspection

Summary In April 2019, baobab (Adansonia digitata L.) seedlings from Thailand, exhibiting galls on the roots, were intercepted during an import plant quarantine inspection at Chubu Centrair International Airport, Japan. Root-knot nematodes (RKNs) were extracted from the galled roots of baobab seedlings and identified by morphological, morphometrical and molecular methods as the guava root-knot nematode, Meloidogyne enterolobii Yang & Eisenback. The morphology and morphometrics of the intercepted population were similar to those of the original and subsequent descriptions of M. enterolobii. The sequences of D2–D3 of 28S rRNA, mtDNA intergenic COII-16S rRNA and COI genes obtained in this study matched well (99–100% similarity) with each of the gene sequences of M. enterolobii deposited in GenBank. Phylogenetic analysis of these genes revealed that the intercepted population clustered with M. enterolobii and clearly differed from other RKN species. To the best of our knowledge, this is the first report of M. enterolobii from baobab.
A secure regenerating code‐based cloud storage with efficient integrity verification

Cloud storage is gaining popularity as it relieves the data owners from the burden of data storage and maintenance cost. However, outsourcing data to third‐party cloud servers raise several concerns such as data availability, confidentiality, and integrity. Recently, regenerating codes have gained popularity because of their low repair bandwidth while ensuring data availability. In this paper, we propose a secure regenerating code‐based cloud storage (SRCCS) scheme, which utilizes the verifiable computation property of homomorphic encryption scheme to check the integrity of outsourced data. In this work, an error‐correcting code (ECC)–based homomorphic encryption scheme (HES) is employed to simultaneously provide data privacy as well as error correction while supporting efficient integrity verification. In SRCCS, server regeneration process is initiated on detection of data corruption events in order to ensure data availability. The ECC‐based HES significantly reduces the probability of server regeneration and minimizes the repair cost. Extensive theoretical analysis and simulation results validate the security, efficiency, and practicability of the proposed scheme.
Allosteric Modulation of Fluorescence Revealed by Hydrogen Bond Dynamics in a Genetically Encoded Maltose Biosensor

Genetically encoded fluorescent biosensors (GEFBs) proved to be reliable tracers for many metabolites and cellular processes. In the simplest case, a fluorescent protein (FP) is genetically fused to a sensing protein which undergoes a conformational change upon ligand binding. This drives a rearrangement in the chromophore environment and changes the spectral properties of the FP. Structural determinants of successful biosensors are revealed only in hindsight when the crystal structures of both ligand-bound and ligand-free forms are available. This makes the development of new biosensors for desired analytes a long trial-and-error process. In the current study, we conducted µs-long all atom molecular dynamics (MD) simulations of a maltose biosensor in both the apo (dark) and holo (bright) forms. We performed detailed hydrogen bond occupancy analyses to shed light on the mechanism of ligand induced conformational change in the sensor protein and its allosteric effect on the chromophore environment. We find that two strong indicators for distinguishing bright and dark states of biosensors are due to substantial changes in hydrogen bond dynamics in the system and solvent accessibility of the chromophore.
Association between electrophysiological phenotypes and Kv2.1 potassium channel expression explained by geometrical analysis

Excitable cells exhibit different electrophysiological profiles while responding to current stimulation in current-clamp experiments. In theory, the differences could be explained by changes in the expression of proteins mediating transmembrane ion transport. Experimental verification by performing systematic, controlled variations in the expression of proteins of the same type (e.g. voltage-dependent, noninactivating Kv2.1 channels) is difficult to achieve in the absence of other changes. However, biophysical models enable this possibility and allows us to assess and characterise the electrophysiological phenotypes associated to different levels of expression of non-inactivating voltage-dependent K-channels of type Kv2.1. To do so, we use a 2-dimensional biophysical model of neuronal membrane potential and study the phase plane geometry and bifurcation structures associated with different levels of Kv2.1 expression with the input current as bifurcation parameter. We find that increasing the expression of Kv2.1 channels reduces the size of the region of the phase plane from which action potentials can be initiated. The changes in expression can also be related to different transitions between rest and repetitive firing in current clamp experiments. For instance, increasing the number of Kv2.1 channels shifts the rheobase current to higher levels, but also expands the dynamic range in which excitatory external current produces repetitive spiking. Our analysis shows that changes in the responses to increasing input currents can be associated to different sequences of fixed point bifurcations. In general, the fixed points are attracting, then repulsive, and later become attracting again as the input current increases, but the bifurcation sequences also include changes in fixed point type, and change qualitatively with the expression of Kv2.1 channels. In the non-repetitive spiking regime with low current stimulation, low expression of Kv2.1 channels yields bifurcation sequences that include transitions between 3 and 1 fixed points, and repetitive firing starts with delays that decrease with increasing current (aggregation). For higher expression of Kv2.1 channels there is only one fixed point that changes in type and attractivity as the input current increases, convergence to rest tends to be oscillatory (resonance), and repetitive spiking starts without noticeable delays. Our models explain how the same neuron is theoretically be capable of including both aggregating and resonant modes of integration for synaptic input, as shown in current clamp experiments.