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The East Asian Summer Monsoon driven by temperature and moisture gradients between the Asian continent and the Pacific Ocean, leads to approximately 50% of the annual rainfall in the region across 20-40°N. Due to its increasing scientific and social importance, there have been several previous studies on identification of moisture sources for summer monsoon rainfall over East Asia mainly using Lagrangian or Eulerian atmospheric water vapor models. The major source regions for EASM previously proposed include the North Indian Ocean, South China Sea and North western Pacific. Based on high-precision and high-frequency 6-year measurement records of hydrofluorocarbons (HFCs), here we report a direct evidence of rapid intrusion of warm and moist tropical air mass from the Southern Hemisphere (SH) reaching within a couple of days up to 33°N into East Asia. We further suggest that the combination of direct chemical tracer record and a back-trajectory model with physical meteorological variables helps pave the way to identify moisture sources for monsoon rainfall. A case study for Gosan station (33.25°N, 126.19°E) indicates that the meridional transport of precipitable water from the SH accompanying the southerly/southwesterly flow contributes most significantly to its summer rainfall.

We fabricated C-doped (1.5 wt.%) In3Sb1Te2 (CIST) thin films with amorphous phase (a-CIST) using a sputter method. Two electrical-phase-changes at 250 and 275 °C were observed in the sheet resistance measurement. In order to understand the origin of these electrical-phase-changes, all samples were characterized by XRD, TEM, and HRXPS with synchrotron radiation. In a-CIST, only weak Sb-C bonding was observed. In the first electrical-phase-change at 250 °C, strong Sb-C bonding occurred without an accompanying structural/phase change (still amorphous). On the other hand, the second electrical-phase-change at 275 °C was due to the structural/phase change from amorphous to crystalline without a chemical state change. [ABSTRACT FROM AUTHOR]

Abstract Crop plants and undomesticated resilient species employ different strategies to regulate their energy resources and growth. Most crop species are sensitive to stress and prioritise rapid growth to maximise yield or biomass production. In contrast, resilient plants grow slowly, are small, and allocate their resources for survival in challenging environments. One small group of plants, termed resurrection plants, survive desiccation of their vegetative tissue and regain full metabolic activity upon watering. However, the precise molecular mechanisms underlying this extreme tolerance remain unknown. In this study, we employed a transcriptomics and metabolomics approach, to investigate the mechanisms of desiccation tolerance in Tripogon loliiformis, a modified desiccation-tolerant plant, that survives gradual but not rapid drying. We show that T. loliiformis can survive rapid desiccation if it is gradually dried to 60% relative water content (RWC). Furthermore, the gene expression data showed that T. loliiformis is genetically predisposed for desiccation in the hydrated state, as evidenced by the accumulation of MYB, NAC, bZIP, WRKY transcription factors along with the phytohormones, abscisic acid, salicylic acid, amino acids (e.g., proline) and TCA cycle sugars during initial drying. Through network analysis of co-expressed genes, we observed differential responses to desiccation between T. loliiformis shoots and roots. Dehydrating shoots displayed global transcriptional changes across broad functional categories, although no enrichment was observed during drying. In contrast, dehydrating roots showed distinct network changes with the most significant differences occurring at 40% RWC. The cumulative effects of the early stress responses may indicate the minimum requirements of desiccation tolerance and enable T. loliiformis to survive rapid drying. These findings potentially hold promise for identifying biotechnological solutions aimed at developing drought-tolerant crops without growth and yield penalties.

Abstract In patients with left ventricular assist device (LVAD), infections and thrombotic events represent severe complications. We investigated device-specific local and systemic inflammation and its impact on cerebrovascular events (CVE) and mortality. In 118 LVAD patients referred for 18F-FDG-PET/CT, metabolic activity of LVAD components, thoracic aortic wall, lymphoid and hematopoietic organs, was quantified and correlated with clinical characteristics, laboratory findings, and outcome. Driveline infection was detected in 92/118 (78%) patients by 18F-FDG-PET/CT. Activity at the driveline entry site was associated with increased signals in aortic wall (r = 0.32, p

We fabricated C-doped (1.5 wt.%) In3Sb1Te2 (CIST) thin films with amorphous phase (a-CIST) using a sputter method. Two electrical-phase-changes at 250 and 275 °C were observed in the sheet resistance measurement. In order to understand the origin of these electrical-phase-changes, all samples were characterized by XRD, TEM, and HRXPS with synchrotron radiation. In a-CIST, only weak Sb-C bonding was observed. In the first electrical-phase-change at 250 °C, strong Sb-C bonding occurred without an accompanying structural/phase change (still amorphous). On the other hand, the second electrical-phase-change at 275 °C was due to the structural/phase change from amorphous to crystalline without a chemical state change. [ABSTRACT FROM AUTHOR]

Conserved protein-coding sequences are critical for maintaining protein function across species. Odorant receptors (ORs), a large poorly understood multigene family responsible for odor detection, lack comprehensive classification methods that reflect their functional diversity. In this study, we propose a new approach called conserved motif-based classification (CMC) for classifying ORs based on amino acid sequence similarities within conserved motifs. Specifically, we focused on three well-conserved motifs: MAYDRYVAIC in TM3, KAFSTCASH in TM6, and PMLNPFIY in TM7. Using an unsupervised clustering technique, we classified human ORs (hORs) into two main clusters with six sub-clusters. CMC partly reflects previously identified subfamilies, revealing altered residue positions among the sub-clusters. These altered positions interacted with specific residues within or adjacent to the transmembrane domain, suggesting functional implications. Furthermore, we found that the CMC correlated with both ligand responses and ectopic expression patterns, highlighting its relevance to OR function. This conserved motif-based classification will help in understanding the functions and features that are not understood by classification based solely on entire amino acid sequence similarity., (© 2024. The Author(s).)

Natural killer (NK) cells are a promising allogeneic immunotherapy option due to their natural ability to kill tumor cells, and due to their apparent safety. This study describes the development of a GMP-compliant manufacturing protocol for the local production of functionally potent NK cells tailored for high-risk acute myeloid leukemia (AML) and neuroblastoma (NBL) patients. Moreover, the quality control strategy and considerations for product batch specifications in early clinical development are described. The protocol is based on the CliniMACS Prodigy platform and Natural Killer Cell Transduction (NKCT) (Miltenyi Biotec). NK cells are isolated from leukapheresis through CD3 depletion and CD56 enrichment, followed by a 12-hour activation with IL-2 and IL-15 cytokines. Three CliniMACS Prodigy processes demonstrated the feasibility and consistency of the modified NKCT process. A three-step process without expansion, however, compromised the NK cell yield. T cells were depleted effectively, indicating excellent safety of the product. Characterization of the NK cells before and after cytokine activation revealed a notable increase in the expression of activation markers, particularly CD69, consistent with enhanced functionality. Intriguingly, the NK cells exhibited increased killing efficacy against patient-derived CD33 + AML blasts and NBL cells in vitro, suggesting a potential therapeutic benefit in AML and NBL., (© 2024. The Author(s).)

Cerebral hyperperfusion syndrome (CHS) is a serious complication after bypass surgery in Moyamoya disease (MMD), with autoregulatory dysfunction being a major pathogenesis. This study investigated the change of perioperative autoregulation and preoperative prognostic potentials in MMD with postoperative CHS. Among 26 hemispheres in 24 patients with adult MMD undergoing combined bypass, 13 hemispheres experienced postoperative CHS. Arterial blood pressure and cerebral blood flow velocity were perioperatively measured with transcranial Doppler ultrasound during resting and the Valsalva maneuver (VM). Autoregulation profiles were discovered in both the CHS and non-CHS groups using mean flow index (Mxa), VM Autoregulatory Index (VM AI ), and a new metric termed VM Overshooting Index (VM OI ). The CHS group had inferior autoregulation than the non-CHS group as indicated by VM OI on preoperative day 1 and postoperative 3rd day. Deteriorated autoregulation was observed via Mxa in the CHS group than in the non-CHS group on the postoperative 3rd and discharge days. Postoperative longitudinal autoregulation recovery in the CHS group was found in a logistic regression model with diminished group differences over the time course. This work represents a step forward in utilizing autoregulation indices derived from physiological signals, to predict the postoperative CHS in adult MMD., (© 2024. The Author(s).)

Malignant mesothelioma, a highly aggressive cancer that primarily affects the serosal membranes, has limited therapeutic options, particularly for cavitary tumors, such as peritoneal and pleural malignant mesothelioma. Intracavitary administration of a radioimmunoconjugate to locally target mesothelioma cancer cells has been proposed as a treatment. CD146, upregulated in mesothelioma but not in healthy tissues, is a promising therapeutic target. This study characterized CD146 expression and binding/internalization kinetics of the CD146-targeting antibody OI-3 coupled with 212 Pb ( 212 Pb-TCMC-OI-3) in human mesothelioma cells. Flow cytometry showed that both chimeric (chOI-3) and murine (mOI-3) antibodies rapidly bound and internalized within 1-6 h in MSTO-211H cells. 212 Pb-TCMC-chOI-3 exhibited 3.1- to 13.7-fold and 3.1- to 8.5-fold increased internalized 212 Pb and 212 Bi atoms per cell at 2 and 24 h, respectively, compared to isotype control, underscoring enhanced internalization efficiency. Intraperitoneal administration of 212 Pb-TCMC-mOI-3 to mice with intraperitoneal MSTO-211H xenografts improved median survival by a ratio of 1.3 compared to non-binding 212 Pb-TCMC-mIgG1. The ability of 212 Pb-TCMC-mOI-3 to target and inhibit the growth of intraperitoneal mesothelioma xenografts supports targeted radionuclide therapy's efficacy for metastatic peritoneal mesothelioma. This study highlights the potential of localized CD146-targeted radioimmunotherapy for malignant mesothelioma, offering a new avenue for improving patient outcomes., (© 2024. The Author(s).)

This study aimed to develop an extraction-free method for quantitative and qualitative detection of HBV DNA compared to traditional nucleic acid extraction. Paired serum and dried blood spot (DBS) samples from 67 HBsAg-positive and 67 HBsAg-negative individuals were included. Two samples with known HBV DNA titers (~ 10 9 copies/mL) were examined by extraction-free detection using three surfactants (0.2 to 1% of Sodium dodecyl sulfate:SDS, N-Lauroylsarcosine sodium salt:NL, Sodium dodecyl benzene sulfonate:SDBS), two stabilizing agents (0.1 or 0.01% 2-Mercaptoethanol:2ME and 3.5 or 7% Bovine Serum Albumin:BSA) and two Taq polymerases (Fast Advanced and Prime Direct Probe). HBV DNA in all 67 HBsAg-positive and 67 HBsAg-negative serum and DBS samples was directly quantified by Rt-PCR using 0.4% SDS or 0.4% NL with Fast Advance or Prime Direct Probe Taq. Extraction-free amplification was also performed. Detection limits were varied by different surfactants and Taq. SDS combined with Fast Advanced Taq showed lower detection limits, while SDS with Prime Direct Probe Taq outperformed NL or SDBS-based detection. Adding 2ME to SDS improved detection limit with Prime Direct Probe Taq but not significantly compared to SDS alone. BSA did not significantly enhance detection limits but provided insights into sample stability. The senitivity and specificity of 0.4% SDS and NL in combination with either Fast advanced or Prime Direct Probe Taq polymerase in serum samples were > 90% and 100% resepctively, while it was > 80% and 100% respectively in DBS samples. Extraction-free HBV DNA amplification provided 100% identity with original genomes. Our study suggests that SDS, NL or SDBS-based extraction-free HBV DNA detection strategies using Prime Direct Probe Taq have potential to simplify and accelerate HBV DNA detection with high sensitivity and specificity in both serum and DBS samples, with implications for resource-limited settings and clinical applications. Utilizing surfactants with 2ME is optional, and further research and validation are necessary to broaden its application in real-world diagnostics., (© 2024. The Author(s).)

This study aimed to develop a machine learning (ML) model for predicting pulmonary embolism (PE) in patients with gastrointestinal cancers, a group at increased risk for PE. We conducted a retrospective, multicenter study analyzing patients who underwent computed tomographic pulmonary angiography (CTPA) between 2010 and 2020. The study utilized demographic and clinical data, including the Wells score and D-dimer levels, to train a random forest ML model. The model's effectiveness was assessed using the area under the receiver operating curve (AUROC). In total, 446 patients from hospital A and 139 from hospital B were included. The training set consisted of 356 patients from hospital A, with internal validation on 90 and external validation on 139 patients from hospital B. The model achieved an AUROC of 0.736 in hospital A and 0.669 in hospital B. The ML model significantly reduced the number of patients recommended for CTPA compared to the conventional diagnostic strategy (hospital A; 100.0% vs. 91.1%, P < 0.001, hospital B; 100.0% vs. 93.5%, P = 0.003). The results indicate that an ML-based prediction model can reduce unnecessary CTPA procedures in gastrointestinal cancer patients, highlighting its potential to enhance diagnostic efficiency and reduce patient burden., (© 2024. The Author(s).)

Tandem autologous stem cell transplantation can improve the prognosis of patients with multiple myeloma. However, the precise role of tandem transplantation remains debatable. We evaluated the clinical benefits of tandem transplantation retrospectively. Of the 655 included patients, 117 underwent tandem transplantation; the remaining were assigned to the control group. After a single transplantation, the tandem group achieved a complete remission (CR) rate of 24.8%, which increased to 46.2% after a second transplantation. The tandem group had a significantly longer median PFS than the control group in patients with International Staging System (ISS) III and high-risk cytogenetics (23.1 vs. 14.7 months, p = 0.007 for ISS III; 21.7 vs. 13.2 months, p = 0.042 for high-risk cytogenetics). The tandem group exhibited significantly superior PFS to the control group (20.3 vs. 12.6 months, p = 0.003) among patients who failed to achieve CR after a single transplantation. Tandem transplantation was associated with significantly improved PFS after adjusting for maintenance therapy in patients with ISS III, those with high-risk cytogenetics, and those who did not achieve CR after a single transplantation. Following propensity score matching, the tandem group exhibited significantly longer PFS than the control group (30.3 vs. 13.5 months, p = 0.028). Tandem transplantation should be considered in high-risk patients., (© 2024. The Author(s).)

Male-male competition is a component of Darwin's theory of precopulatory intrasexual selection, where males compete for access to resources important for reproduction and successful males pass on traits that endow greater competitive ability to their offspring, thereby exaggerating the trait(s) over evolutionary time. Metals, such as lead (Pb) often occur in urban mangrove forests, where shore crabs reside, and being neurotoxic may cause sub-lethal effects on behaviour. In this study, we asked whether exposure to Pb influences the outcomes of male-male competition in the Semaphore crab, Heloecius cordiformis, thereby altering outcomes of intrasexual selection. Crabs were exposed to an environmentally relevant, and a behaviourally relevant, concentration of lead (i.e. Pb, 10 µg/L and 100 µg/L respectively) under laboratory conditions for 96 h and subsequently allowed to compete for burrow ownership in experimental arenas. Exposed crabs (100 µg/L) were less successful than control crabs in chela size-matched paired competitive interactions, spent less time in burrows and predominantly lost burrow ownership. Further, exposure to Pb contamination (both 10 µg/L and 100 µg/L) negated the chela size advantage in size-asymmetric competitive interactions. This contaminant-induced loss of size-related competitive advantage may result in relaxation in selection pressure on body size and smaller male carapace widths and especially male chela lengths in contaminated locations. Assessment of a range of locations in the wild found a consistent pattern of metal-associated size declines in more contaminated locations for males, but not for females., (© 2024. The Author(s).)

Although the prevalence of intraventricular hemorrhage (IVH) has remained high, no optimal strategy has been established to prevent it. This study included preterm newborns born at a gestational age of < 32 weeks admitted to the neonatal intensive care unit of a tertiary hospital between January 2013 and June 2022. Infants who had been observed for less than 24 h were excluded. A total of 14 features from time-series data after birth to IVH diagnosis were chosen for model development using an automated machine-learning method. The average F1 scores and area under the receiver operating characteristic curve (AUROC) were used as indicators for comparing the models. We analyzed 778 preterm newborns (79 with IVH, 10.2%; 699 with no IVH, 89.8%) with a median gestational age of 29.4 weeks and birth weight of 1180 g. Model development was performed using data from 748 infants after applying the exclusion criteria. The Extra Trees Classifier model showed the best performance with an average F1 score of 0.93 and an AUROC of 0.999. We developed a model for identifying IVH with excellent accuracy. Further research is needed to recognize high-risk infants in real time., (© 2024. The Author(s).)

Children learn about art by actively engaging with their surroundings. This makes museums potentially rich environments for learning and development. Yet, the descriptions of paintings on show are usually written for adults rather than younger visitors. This study uses mobile eye tracking to examine how painting descriptions tailored for children influence their eye movements when viewing paintings at the Rijksmuseum - the national museum of The Netherlands. Our findings underscore the importance of adapting information specifically for children, rather than simply providing them with adult-oriented museum materials. Children who received information tailored to their developmental level showed increased glance durations to areas highlighted in the descriptions. Strikingly, the behavior of children provided with painting descriptions intended for adults was no different from their behavior when they received no information at all., (© 2024. The Author(s).)

The present longitudinal study examined a large sample of individuals with PIMD/Polyhandicap to: (i) describe the evolution over time of the health status in terms of severity, (ii) identify the potential predictors of health status change. This study used the data of the French national EVAL-PLH cohort. Inclusion criteria were: individuals with PIMD/Polyhandicap; age > 3 years at the time of inclusion; age at onset of cerebral lesion younger than 3 years old. The definition of the change in health status over the 5-year period was derived from the Polyhandicap Severity Scale. Among the 875 individuals included in 2015-2016, 492 (56.2%) individuals were assessed in 2020-2021. According to the definition, 68.8% (n = 309), 64.7% (n = 310), and 80.2% (n = 368) of the individuals presented with a worsened or stable severity status based on the global score, the abilities score, and the comorbidities score, respectively. Compared with the individuals with a non-worsened health status (global score), the individuals with a stable or worsened health status were more likely to receive care in specialized rehabilitation centres, more likely to have an antenatal or progressive aetiology, and more likely to have a higher dependency level. The current study provides a robust perspective of the worsened health among persons with PIMD/Polyhandicap over time., (© 2024. The Author(s).)

We examined candidate biomarkers for efficacy outcomes in hospitalized COVID-19 patients who were treated with sirukumab, an IL-6 neutralizing antibody, in a randomized, double-blind, placebo-controlled, phase 2 trial. Between May 2020 and March 2021, 209 patients were randomized (sirukumab, n = 139; placebo, n = 70); 112 had critical COVID-19. Serum biomarkers were evaluated for the pharmacodynamic effect of sirukumab and for their potential prognostic and predictive effect on time to sustained clinical improvement up to Day 28, clinical improvement at Day 28, and mortality at Day 28. The absence of detectable IL-4 increase and smaller increases in CCL13 post-baseline were most significantly associated with better response to sirukumab (versus placebo) treatment for all clinical efficacy outcomes tested, especially in patients with critical COVID-19. These data suggest that patients with critical COVID-19 without detectable sirukumab-induced IL-4 levels are more likely to benefit from sirukumab treatment. ClinicalTrials.gov Identifier: NCT04380961., (© 2024. The Author(s).)

The control of African trypanosomiasis (AT) in Eastern and Southern Africa, including Zambia, faces huge challenges due to the involvement of wild and domestic animal reservoirs. Free-roaming dogs in wildlife-populated and tsetse-infested villages of Zambia's Mambwe district are exposed to infectious tsetse bites. Consuming fresh raw game meat and bones further exacerbates their risk of contracting AT. We focus on the reservoir role of such dogs in maintaining and transmitting diverse species of trypanosomes that are infective to humans and livestock in Zambia's Mambwe district. A cohort of 162 dogs was enrolled for follow-up at 3 different time points from June to December 2018 in selected villages of Malama, Mnkhanya, and Nsefu chiefdoms of Mambwe district, eastern Zambia. Blood and serum were screened for AT by microscopy, GM6 ELISA, PCR (ITS1 and SRA), and Sanger sequencing. Out of the 162 dogs in the cohort, 40 were lost to follow-up and only 122 remained traceable at the end of the study. GM6 ELISA detected Trypanosoma antibodies in 121 dogs (74.7%) and ITS1-PCR detected DNA involving single and mixed infections of T. congolense, T. brucei, and suspected T. simiae or T. godfreyi in 115 dogs (70.9%). The human-infective T. b. rhodesiense was detected by SRA PCR in 67 dogs (41.4%), and some sequence data that support the findings of this study have been deposited in the GenBank under accession numbers OL961811, OL961812, and OL961813. Our study demonstrates that the Trypanosoma reservoir community in Zambia is wider than was thought and includes domesticated dogs. As dogs are active carriers of human and livestock-infective trypanosomes, they pose a risk of transmitting AT in endemic villages of Mambwe district as they are neglected and left untreated. To fully bring AT under control, countries such as Zambia where the role of animal reservoirs is important, should not limit their prevention and treatment efforts to livestock (especially cattle) but also include dogs that play an integral part in most rural communities., (© 2024. The Author(s).)

Environmental health research has suggested that fine particulate matter (PM 2.5 ) exposure can lead to high blood pressures, but it is unclear whether the impacts remain the same for systolic and diastolic blood pressures (SBP and DBP). This study aimed to examine whether the effects of PM 2.5 exposure on SBP and DBP differ using data from a predominantly non-Hispanic Black cohort collected between 2013 and 2019 in the US. PM 2.5 exposure was assessed based on a satellite-derived model across exposure durations from 1 to 36 months. The average PM 2.5 exposure level was between 9.5 and 9.8 μg/m 3 from 1 through 36 months. Mixed effects models were used to estimate the association of PM 2.5 with SBP, DBP, and related hypertension types, adjusted for potential confounders. A total of 6381 participants were included. PM 2.5 exposure was positively associated with both SBP and DBP. The association magnitudes depended on exposure durations. The association with SBP was null at the 1-month duration (β = 0.05, 95% CI: - 0.23, 0.33), strengthened as duration increased, and plateaued at the 24-month duration (β = 1.14, 95% CI: 0.54, 1.73). The association with DBP started with β = 0.29 (95% CI: 0.11, 0.47) at the 1-month duration, and plateaued at the 12-month duration (β = 1.61, 95% CI: 1.23, 1.99). PM 2.5 was associated with isolated diastolic hypertension (12-month duration: odds ratio = 1.20, 95% CI: 1.07, 1.34) and systolic-diastolic hypertension (12-month duration: odds ratio = 1.18, 95% CI: 1.10, 1.26), but not with isolated systolic hypertension. The findings suggest DBP is more sensitive to PM 2.5 exposure and support differing effects of PM 2.5 exposure on SBP and DBP. As elevation of SBP and DBP differentially predict CVD outcomes, this finding is relevant for prevention and treatment., (© 2024. The Author(s).)

Sickle cell disease (SCD) is an inherited blood disorder marked by homozygosity of hemoglobin S, which is a defective hemoglobin caused by a missense mutation in the β-globin gene. However, clinical phenotypes of SCD vary among patients. To investigate genetic variants associated with various clinical phenotypes of SCD, we genotyped DNA samples from 520 SCD subjects and used a genome-wide association study (GWAS) approach to identify genetic variants associated with phenotypic features of SCD. For HbF levels, the previously reported 2p16.1 locus (BCL11A) reached genome significance (rs1427407, P = 8.58 × 10 -10 ) in our GWAS as expected. In addition, we found a new genome-wide significance locus at 15q14 (rs8182015, P = 2.07 × 10 -8 ) near gene EMC7. GWAS of acute chest syndrome (ACS) detected a locus (rs79915189, P = 3.70 × 10 -8 ) near gene IDH2 at 15q26.1. The SNP, rs79915189, is also an expression quantitative trait locus (eQTL) of IDH2 in multiple tissues. For vasoocclusive episode (VOE), GWAS detected multiple significant signals at 2p25.1 (rs62118798, P = 4.27 × 10 -8 ), 15q26.1 (rs62020555, P = 2.04 × 10 -9 ) and 15q26.3 (rs117797325, P = 4.63 × 10 -8 ). Our findings provide novel insights into the genetic mechanisms of SCD suggesting that common genetic variants play an important role in the presentation of the clinical phenotypes of patients with SCD., (© 2024. The Author(s).)

Fossils of large animals have long influenced social practices and ideologies in human societies, including the fantastic myths of giants, heroes, and gods in ancient Greece. It has been estimated that purposeful fossil collecting in Greece began in the Late Bronze Age. However, previous archaeological finds of fossils from mainland Greece were not well documented in secure contexts that dated this far back in time. Herein, we present a newly recognized fossilized astragalus bone recently found in the legacy collections of the archaeological site of Mycenae. It was originally recovered by excavations in the 1970s and recently reanalyzed at the Mycenae Museum. Our analysis explored the available evidence of the find location, the state of fossil preservation, and the species represented. The results suggest that a fossilized rhinoceros (Stephanorhinus) astragalus was collected in the past, possibly from afar. Evidence indicates it was brought to Mycenae, where it was deposited near an interesting array of artifacts in a basement storage area of the Southwest Quarter, sometime in the thirteenth century BCE. This find represents the earliest secure evidence of large animal fossil use by people in mainland Greece, dating to the Late Bronze Age., (© 2024. The Author(s).)

REBa 2 Cu 3 O 7 - x (REBCO, RE = rare earth)-coated conductor is a competitive option in terms of current-carrying capacity and high-stress durability in developing high-field magnets for nuclear magnetic resonance (NMR) research. Meanwhile, a technical challenge in utilizing a stand-alone REBCO NMR magnet is an unexpected difference in the field uniformity between the designed and measured values after being constructed and charged, i.e., harmonic errors. Bortot et al., and Li et al., reported analytic evidence of the related issue. However, sufficient research has not yet been conducted, so evidence should be supplemented further. Here we report harmonic errors due to screening current and inconsistent conductor thickness, confirmed by a 400 MHz 1 H NMR magnet development project. The magnet was first charged up to its operating current, and then multiple overcharge-discharge cycles were applied, which was an empirically optimized operation protocol. A field mapping device obtained magnetic fields at designated locations in the room-temperature bore. The result showed over 100 ppm field uniformity difference between designed and measured values. A simulation model was developed considering screening current and inconsistent conductor thickness for reproducing the field distribution. Comparison of voltages and fields between simulation and measurement validated the model. Further analysis of the overcharge-discharge effect on harmonic errors demonstrated that even and odd-order harmonics are mainly attributed to screening current and geometric inconsistency while confirming the limitation of the screening current mitigation effect. Hence, we concluded that the desirable requirement of the sub-ppm level field uniformity generation might be barely possible with the current REBCO NMR magnet design approach., (© 2024. The Author(s).)

Robotic 3D bioprinting is a rapidly advancing technology with applications in organ fabrication, tissue restoration, and pharmaceutical testing. While the stepwise generation of organs characterizes bioprinting, challenges such as non-linear material behavior, layer shifting, and trajectory tracking are common in freeform reversible embedding of suspended hydrogels (FRESH) bioprinting, leading to imperfections in complex organ construction. To overcome these limitations, we propose a computer vision-based strategy to identify discrepancies between printed filaments and the reference robot path. Employing error compensation techniques, we generate an adjusted reference path, enhancing robotic 3D bioprinting by adapting the robot path based on vision system data. Experimental assessments confirm the reliability and agility of our vision-based robotic 3D bioprinting approach, showcasing precision in fabricating human blood vessel segments through case studies. Significantly, it minimizes the printing layer width disparity to just 0.15 mm compared to the 0.6 mm in traditional methods, and it decreases the average error for curved filaments to 7.0 mm 2 from the previous 12.7 mm 2 in conventional printing. While these results underscore the significant potential of our innovation in creating precise biomimetic constructs, further investigation is necessary to tackle challenges such as accurately distinguishing closely stacked layers using a vision system, especially under varying lighting conditions. These limitations, coupled with issues of computational complexity and scalability in larger-scale bioprinting, emphasize the importance of enhancing the reliability of the vision-based approach across various conditions. Nonetheless, our innovation demonstrates substantial promise in creating precise biomimetic constructs and paves the way for future advancements in vision-guided robotic bioprinting, including the integration of multi-material printing techniques to enhance versatility., (© 2024. The Author(s).)

Oxidative stress plays an essential role in the progression of Alzheimer's disease (AD), the most common age-related neurodegenerative disorder. Streptozotocin (STZ)-induced abnormal brain insulin signaling and oxidative stress play crucial roles in the progression of Alzheimer's disease (AD)-like pathology. Peroxiredoxins (Prxs) are associated with protection from neuronal death induced by oxidative stress. However, the molecular mechanisms underlying Prxs on STZ-induced progression of AD in the hippocampal neurons are not yet fully understood. Here, we evaluated whether Peroxiredoxin 1 (Prx1) affects STZ-induced AD-like pathology and cellular toxicity. Prx1 expression was increased by STZ treatment in the hippocampus cell line, HT-22 cells. We evaluated whether Prx1 affects STZ-induced HT-22 cells using overexpression. Prx1 successfully protected the forms of STZ-induced AD-like pathology, such as neuronal apoptosis, synaptic loss, and tau phosphorylation. Moreover, Prx1 suppressed the STZ-induced increase of mitochondrial dysfunction and fragmentation by down-regulating Drp1 phosphorylation and mitochondrial location. Prx1 plays a role in an upstream signal pathway of Drp1 phosphorylation, cyclin-dependent kinase 5 (Cdk5) by inhibiting the STZ-induced conversion of p35 to p25. We found that STZ-induced of intracellular Ca 2+ accumulation was an important modulator of AD-like pathology progression by regulating Ca 2+ -mediated Calpain activation, and Prx1 down-regulated STZ-induced intracellular Ca 2+ accumulation and Ca 2+ -mediated Calpain activation. Finally, we identified that Prx1 antioxidant capacity affected Ca 2+ /Calpain/Cdk5-mediated AD-like pathology progress. Therefore, these findings demonstrated that Prx1 is a key factor in STZ-induced hippocampal neuronal death through inhibition of Ca 2+ /Calpain/Cdk5-mediated mitochondrial dysfunction by protecting against oxidative stress., (© 2024. The Author(s).)

Aging and lack of exercise are the most important etiological factors for muscle loss. We hypothesized that new factors that contribute to muscle loss could be identified from ones commonly altered in expression in aged and exercise-limited skeletal muscles. Mouse gastrocnemius muscles were subjected to mass spectrometry-based proteomic analysis. The muscle proteomes of hindlimb-unloaded and aged mice were compared to those of exercised and young mice, respectively. C1qbp expression was significantly upregulated in the muscles of both hindlimb-unloaded and aged mice. In vitro myogenic differentiation was not affected by altering intracellular C1qbp expression but was significantly suppressed upon recombinant C1qbp treatment. Additionally, recombinant C1qbp repressed the protein level but not the mRNA level of NFATc1. NFATc1 recruited the transcriptional coactivator p300, leading to the upregulation of acetylated histone H3 levels. Furthermore, NFATc1 silencing inhibited p300 recruitment, downregulated acetylated histone H3 levels, and consequently suppressed myogenic differentiation. The expression of C1qbp was inversely correlated with that of NFATc1 in the gastrocnemius muscles of exercised or hindlimb-unloaded, and young or aged mice. These findings demonstrate a novel role of extracellular C1qbp in suppressing myogenesis by inhibiting the NFATc1/p300 complex. Thus, C1qbp can serve as a novel therapeutic target for muscle loss., (© 2024. The Author(s).)

Glioblastoma (GBM) continues to exhibit a discouraging survival rate despite extensive research into new treatments. One factor contributing to its poor prognosis is the tumor's immunosuppressive microenvironment, in which the kynurenine pathway (KP) plays a significant role. This study aimed to explore how KP impacts the survival of newly diagnosed GBM patients. We examined tissue samples from 108 GBM patients to assess the expression levels of key KP markers-tryptophan 2,3-dioxygenase (TDO2), indoleamine 2,3-dioxygenase (IDO1/2), and the aryl hydrocarbon receptor (AhR). Using immunohistochemistry and QuPath software, three tumor cores were analyzed per patient to evaluate KP marker expression. Kaplan-Meier survival analysis and stepwise multivariate Cox regression were used to determine the effect of these markers on patient survival. Results showed that patients with high expression of TDO2, IDO1/2, and AhR had significantly shorter survival times. This finding held true even when controlling for other known prognostic variables, with a hazard ratio of 3.393 for IDO1, 2.775 for IDO2, 1.891 for TDO2, and 1.902 for AhR. We suggest that KP markers could serve as useful tools for patient stratification, potentially guiding future immunomodulating trials and personalized treatment approaches for GBM patients., (© 2024. The Author(s).)

Heterozygous de novo mutations in the Activity-Dependent Neuroprotective Homeobox (ADNP) gene underlie Helsmoortel-Van der Aa syndrome (HVDAS). Most of these mutations are situated in the last exon and we previously demonstrated escape from nonsense-mediated decay by detecting mutant ADNP mRNA in patient blood. In this study, wild-type and ADNP mutants are investigated at the protein level and therefore optimal detection of the protein is required. Detection of ADNP by means of western blotting has been ambiguous with reported antibodies resulting in non-specific bands without unique ADNP signal. Validation of an N-terminal ADNP antibody (Aviva Systems) using a blocking peptide competition assay allowed to differentiate between specific and non-specific signals in different sample materials, resulting in a unique band signal around 150 kDa for ADNP, above its theoretical molecular weight of 124 kDa. Detection with different C-terminal antibodies confirmed the signals at an observed molecular weight of 150 kDa. Our antibody panel was subsequently tested by immunoblotting, comparing parental and homozygous CRISPR/Cas9 endonuclease-mediated Adnp knockout cell lines and showed disappearance of the 150 kDa signal, indicative for intact ADNP. By means of both a GFPSpark and Flag-tag N-terminally fused to a human ADNP expression vector, we detected wild-type ADNP together with mutant forms after introduction of patient mutations in E. coli expression systems by site-directed mutagenesis. Furthermore, we were also able to visualize endogenous ADNP with our C-terminal antibody panel in heterozygous cell lines carrying ADNP patient mutations, while the truncated ADNP mutants could only be detected with epitope-tag-specific antibodies, suggesting that addition of an epitope-tag possibly helps stabilizing the protein. However, western blotting of patient-derived hiPSCs, immortalized lymphoblastoid cell lines and post-mortem patient brain material failed to detect a native mutant ADNP protein. In addition, an N-terminal immunoprecipitation-competent ADNP antibody enriched truncating mutants in overexpression lysates, whereas implementation of the same method failed to enrich a possible native mutant protein in immortalized patient-derived lymphoblastoid cell lines. This study aims to shape awareness for critical assessment of mutant ADNP protein analysis in Helsmoortel-Van der Aa syndrome., (© 2024. The Author(s).)

Difficulties in executive functioning (EF) can result in impulsivity, forgetfulness, and inattention. Children living in remote/regional communities are particularly at risk of impairment in these cognitive skills due to reduced educational engagement and poorer access to interventions. This vulnerability has been exacerbated by the COVID-19 pandemic and strategies are needed to mitigate long-term negative impacts on EF. Here we propose a pilot trial investigating the benefits, feasibility, and acceptability of a school-based EF intervention for primary school students (6-8 years) living in regional, developmentally vulnerable, and socio-economically disadvantaged communities. Students were randomised to a digital intervention or teaching as usual, for 7 weeks. Children completed measures of EF and parents/educators completed ratings of everyday EF and social/emotional wellbeing at pre-intervention, post-intervention, and 3-month follow-up. Change in EFs (primary outcome), everyday EF, and social/emotional wellbeing (secondary outcomes) from pre- to post-intervention and pre-intervention to 3-month follow-up were examined. Feasibility and acceptability of the intervention was assessed through educator feedback and intervention adherence.Protocol Registration: The stage 1 protocol for this Registered Report was accepted in principle on 20 April 2023. The protocol, as accepted by the journal, can be found at: https://doi.org/10.17605/OSF.IO/WT3S2 . The approved Stage 1 protocol is available here: https://osf.io/kzfwn ., (© 2024. The Author(s).)

Neurodevelopmental disorders (NDD) in offspring are associated with a complex combination of pre-and postnatal factors. This study uses machine learning and population data to evaluate the association between prepregnancy or perinatal risk factors and the NDD of offspring. Population-based retrospective cohort data were obtained from Korea National Health Insurance Service claims data for 209,424 singleton offspring and their mothers who gave birth for the first time in 2007. The dependent variables were motor development disorder (MDD), cognitive development disorder (CDD) and combined overall neurodevelopmental disorder (NDD) from offspring. Seventeen independent variables from 2002 to 2007 were included. Random forest variable importance and Shapley Additive Explanation (SHAP) values were calculated to analyze the directions of its associations with the predictors. The random forest with oversampling registered much higher areas under the receiver-operating-characteristic curves than the logistic regression of interaction and non-linearity terms, 79% versus 50% (MDD), 82% versus 52% (CDD) and 74% versus 50% (NDD). Based on random forest variable importance, low socioeconomic status and age at birth were highly ranked. In SHAP values, there was a positive association between NDD and pre- or perinatal outcomes, especially, fetal male sex with growth restriction associated the development of NDD in offspring., (© 2024. The Author(s).)

Climate change is intensifying extreme weather events, including marine heatwaves, which are prolonged periods of anomalously high sea surface temperature that pose a novel threat to aquatic animals. Tropical animals may be especially vulnerable to marine heatwaves because they are adapted to a narrow temperature range. If these animals cannot acclimate to marine heatwaves, the extreme heat could impair their behavior and fitness. Here, we investigated how marine heatwave conditions affected the performance and thermal tolerance of a tropical predatory fish, arceye hawkfish (Paracirrhites arcatus), across two seasons in Moorea, French Polynesia. We found that the fish's daily activities, including recovery from burst swimming and digestion, were more energetically costly in fish exposed to marine heatwave conditions across both seasons, while their aerobic capacity remained the same. Given their constrained energy budget, these rising costs associated with warming may impact how hawkfish prioritize activities. Additionally, hawkfish that were exposed to hotter temperatures exhibited cardiac plasticity by increasing their maximum heart rate but were still operating within a few degrees of their thermal limits. With more frequent and intense heatwaves, hawkfish, and other tropical fishes must rapidly acclimate, or they may suffer physiological consequences that alter their role in the ecosystem., (© 2024. The Author(s).)

Robotic adrenalectomy (RA) has gained significant popularity in the management of adrenal gland diseases. We report our experience at a single tertiary institution and evaluate the safety and surgical outcomes of RA. The data of 122 consecutive patients who underwent RA from October 2009 to December 2022 at Korea University Anam Hospital (Seoul, Korea) were reviewed. There were no perioperative complications. Clinicopathological features and surgical outcomes were retrospectively analyzed through complete chart reviews. Noteworthy findings include the influence of sex, tumor size, and body mass index on operation time, with the female and small tumor groups exhibiting shorter operation times (P = 0.018 and P = 0.009, respectively). Pheochromocytoma was identified as a significant independent risk factor for a longer operation time in the multivariate analysis [odds ratio (OR), 3.709; 95% confidence interval (CI), 1.127-12.205; P = 0.031]. A temporal analysis revealed a decreasing trend in mean operation times across consecutive groups, reflecting a learning curve associated with RA adoption. RA is a safe and effective operative technique alternative to laparoscopic adrenalectomy that has favorable surgical outcomes and enhances the convenience of the operation., (© 2024. The Author(s).)

This study assessed the association between arthritis, functional impairment, and nutritional risk (NR). Cross-sectional data were from the Canadian Longitudinal Study on Aging, a nationally representative sample of 45-85-year-old community-dwelling Canadians (n = 41,153). The abbreviated Seniors in the Community: Risk Evaluating for Eating and Nutrition II (SCREEN II-AB) Questionnaire determined NR scores (continuous), and high NR (score < 38); the Older American Resources and Services scale measured functional impairment. NR scores and status (low/high) were modelled using multiple linear and logistic regressions, respectively. Analyses adjusted for demographic characteristics, functional impairment, and health (body mass index, self-rated general and mental health). Additional analyses stratified the models by functional impairment. People with arthritis had poorer NR scores (B: - 0.35, CI - 0.48, - 0.22; p < 0.05) and increased risks of high NR (OR 1.11, 95% CI 1.06, 1.17). Among those with functional impairment, the likelihood of high NR was 31% higher in people with arthritis compared to those without arthritis (95% CI 1.12, 1.53). Among those with no functional impairment, the likelihood of high NR was 10% higher in people with arthritis compared to those without (95% CI 1.04, 1.16). These relationships differed based on the type of arthritis. Arthritis is associated with high NR in community-dwelling older adults, both with and without functional impairment. Findings highlight the need for further research on these relationships to inform interventions and improve clinical practices., (© 2024. The Author(s).)

Thrombus formation in extracorporeal membrane oxygenation (ECMO) remains a major concern as it can lead to fatal outcomes. To the best of our knowledge, there is no standard non-invasive method for quantitatively measuring thrombi. This study's purpose was to verify thrombus detection in an ECMO circuit using novel, non-invasive ultrasonic sensors in real-time, utilizing the fact that the ultrasonic velocity in a thrombus is known to be higher than that in the blood. Ultrasonic sensors with a customized chamber, an ultrasonic pulse-receiver, and a digital storage oscilloscope (DSO) were used to set up the measuring unit. The customized chamber was connected to an ECMO circuit primed with porcine blood. Thrombi formed from static porcine blood were placed in the circuit and ultrasonic signals were extracted from the oscilloscope at various ECMO flow rates of 1-4 L/min. The ultrasonic signal changes were successfully detected at each flow rate on the DSO. The ultrasonic pulse signal shifted leftward when a thrombus passed between the two ultrasonic sensors and was easily detected on the DSO screen. This novel real-time non-invasive thrombus detection method may enable the early detection of floating thrombi in the ECMO system and early management of ECMO thrombi., (© 2024. The Author(s).)

This retrospective study applied machine-learning models to predict treatment outcomes of women undergoing elective fertility preservation. Two-hundred-fifty women who underwent elective fertility preservation at a tertiary center, 2019-2022 were included. Primary outcome was the number of metaphase II oocytes retrieved. Outcome class was based on oocyte count (OC): Low (≤ 8), Medium (9-15) or High (≥ 16). Machine-learning models and statistical regression were used to predict outcome class, first based on pre-treatment parameters, and then using post-treatment data from ovulation-triggering day. OC was 136 Low, 80 Medium, and 34 High. Random Forest Classifier (RFC) was the most accurate model (pre-treatment receiver operating characteristic (ROC) area under the curve (AUC) was 77%, and post-treatment ROC AUC was 87%), followed by XGBoost Classifier (pre-treatment ROC AUC 74%, post-treatment ROC AUC 86%). The most important pre-treatment parameters for RFC were basal FSH (22.6%), basal LH (19.1%), AFC (18.2%), and basal estradiol (15.6%). Post-treatment parameters were estradiol levels on trigger-day (17.7%), basal FSH (11%), basal LH (9%), and AFC (8%). Machine-learning models trained with clinical data appear to predict fertility preservation treatment outcomes with relatively high accuracy., (© 2024. The Author(s).)

Recent advances in semiconductor based electronic devices can be attributed to the technological demands of ever increasing, application specific markets. These rapidly evolving markets for devices such as displays, wireless communication, photovoltaics, medical devices, etc. are demanding electronic devices that are increasingly thinner, smaller, lighter and flexible. High-quality, III-V epitaxial thin-films deposited on single-crystal substrates have yielded extremely high-performance, but are extremely expensive and rigid. Here we demonstrate heteroepitaxial deposition of GaAs thin-films on large-grained, single-crystal-like, biaxially-aligned, flexible, metallic substrates. We use molecular beam epitaxy (MBE) for the controlled growth of high quality GaAs layers on lattice matched Ge capped, flexible metal substrates. The structural, optical, interfacial and electrical characteristics and properties of the heteroepitaxial GaAs layers are analyzed and discussed. The results show that heteroepitaxial GaAs layers with good crystalline and optoelectronic properties can be realized for flexible, III-V based semiconductor devices. III-V materials integrated on large-grained, single-crystal-like, flexible, metallic substrates offer a potential route towards fabrication of large-area, high-performance electronic devices., (© 2024. The Author(s).)

Dementia is characterized by a progressive loss of cognitive abilities, and diagnosing its early stages Mild Cognitive Impairment (MCI), is difficult since it is a transitory state that is different from total cognitive collapse. Recent clinical research studies have identified that balance impairments can be a significant indicator for predicting dementia in older adults. Accordingly, the current research focuses on finding innovative postural balance-based digital biomarkers by using wearable inertial sensors and pre-screening of MCI in home settings using machine learning techniques. For this research, sixty subjects (30 cognitively normal and 30 MCI) with waist-mounted inertial sensor performed balance tasks in four different standing postures: eyes-open, eyes-closed, right-leg-lift, and left-leg-lift. The significant balance biomarkers for MCI identification are discovered by our research, demonstrating specific characteristics in each of these four states. A robust feature selection approach is ensured by the multi-step methodology that combines the strengths of Filter techniques, Wrapper methods, and SHAP (Shapley Additive exPlanations) technique. The proposed balance biomarkers have the potential to detect MCI (with 75.8% accuracy), as evidenced by the results of machine learning algorithms for classification. This work adds to the growing body of literature targeted at enhancing understanding and proactive management of cognitive loss in older populations and lays the groundwork for future research efforts aimed at refining digital biomarkers, validating findings, and exploring longitudinal perspectives., (© 2024. The Author(s).)