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Yttria-stabilized zirconia (Y-TZP) ceramics with a drastically reduced yttria content have been introduced by different manufacturers, aiming at improving the damage tolerance of ceramic components. In this study, an alumina-doped 1.5Y-TZP was axially pressed, pressureless sintered in air at 1250–1400 °C for 2 h and characterized with respect to mechanical properties, microstructure, and phase composition. The material exhibits a combination of a high strength of 1000 MPa and a high toughness of 8.5–10 MPa√m. The measured fracture toughness is, however, extremely dependent on the measurement protocol. Direct crack length measurements overestimate toughness due to trapping effects. The initially purely tetragonal material has a high transformability of >80%, the transformation behavior is predominantly dilational, and the measured R-curve-related toughness increments are in good agreement with the transformation toughness increments derived from XRD data.

Abstract The capability to excite, probe, and manipulate vibrational modes is essential for understanding and controlling chemical reactions at the molecular level. Recent advancements in tip-enhanced Raman spectroscopies have enabled the probing of vibrational fingerprints in a single molecule with Ångström-scale spatial resolution. However, achieving controllable excitation of specific vibrational modes in individual molecules remains challenging. Here, we demonstrate the selective excitation and probing of vibrational modes in single deprotonated phthalocyanine molecules utilizing resonance Raman spectroscopy in a scanning tunneling microscope. Selective excitation is achieved by finely tuning the excitation wavelength of the laser to be resonant with the vibronic transitions between the molecular ground electronic state and the vibrational levels in the excited electronic state, resulting in the state-selective enhancement of the resonance Raman signal. Our approach contributes to setting the stage for steering chemical transformations in molecules on surfaces by selective excitation of molecular vibrations.

Abstract Oscillatory activity within the beta frequency range (13–30 Hz) serves as a Parkinson’s disease biomarker for tailoring deep brain stimulation (DBS) treatments. Currently, identifying clinically relevant beta signals, specifically frequencies of peak amplitudes within the beta spectral band, is a subjective process. To inform potential strategies for objective clinical decision making, we assessed algorithms for identifying beta peaks and devised a standardized approach for both research and clinical applications. Employing a novel monopolar referencing strategy, we utilized a brain sensing device to measure beta peak power across distinct contacts along each DBS electrode implanted in the subthalamic nucleus. We then evaluated the accuracy of ten beta peak detection algorithms against a benchmark established by expert consensus. The most accurate algorithms, all sharing similar underlying algebraic dynamic peak amplitude thresholding approaches, matched the expert consensus in performance and reliably predicted the clinical stimulation parameters during follow-up visits. These findings highlight the potential of algorithmic solutions to overcome the subjective bias in beta peak identification, presenting viable options for standardizing this process. Such advancements could lead to significant improvements in the efficiency and accuracy of patient-specific DBS therapy parameterization.

Abstract Backgrounds Cognitive problems are common symptoms among individuals with stress-related exhaustion. It is still unknown whether these individuals are at a higher risk of developing dementia later. This study aims to examine the relationship between midlife stress-related exhaustion and dementia incidence. Methods A population sample of 777 women (aged 38, 46, 50 and 54 years) without dementia at baseline was followed over 50 years, from 1968 to 2019. Stress-related exhaustion was based on information from the psychiatric examination in 1968/69. Information on dementia incidence between 1968 and 2019 was obtained from neuropsychiatric examinations, key-informant interviews, and hospital registry. Dementia was diagnosed according to the DSM-III-R criteria. A subgroup of non-demented women (n = 284) was examined for cognitive functions by the Gottfries-Bråne-Steen scale 24 years after baseline. Results Stress-related exhaustion in midlife was associated with higher risk for development of dementia before age 75 (Hazard ratio and 95% confidence interval: 2.95 and 1.35–6.44). The association remained after adjustment for age, major depression, and anxiety disorder. Mean age of dementia onset was younger for women with stress-related exhaustion than women without stress (mean ± SD, 76 ± 9 vs. 82 ± 8 . p = 0.009). Women with stress-related exhaustion in midlife still showed more cognitive impairments 24 years later compared with women without stress (Odds ratio and 95% confidence interval: 2.64 and 1.15–6.06). Conclusions We found that women with stress-related exhaustion in midlife were at a higher risk to develop dementia at relatively younger age. These women showed persistently lower cognitive functions over years even without dementia. Present study results need to be interpreted with caution due to small sample size and should be confirmed in future studies with larger sample size. Our study findings may imply the importance of long-term follow-up regarding cognitive function among individuals with stress-related exhaustion.

Introduction: The time elapsed from diagnosis to hematopoietic stem cell transplantation (HSCT) is influenced by numerous factors. In Brazil, patients using the public health system are also dependent on the availability of HSCT-specific beds in the hematology ward. Objective and Methods: We conducted a cohort study of listed patients who underwent allogeneic HSCT at a Brazilian public hospital to investigate the impact of the waitlist time on post-HSCT survival. Results: The median time from diagnosis to HSCT was 19 months (IQR, 10 - 43), of which 6 months (IQR, 3 - 9) were spent on the waitlist. The time on the waitlist for HSCT appeared to influence mainly the survival of adult patients (≥ 18 years), with an increasing risk according to this time (RR, 3.53 and 95%CI, 1.81 - 6.88 for > 3 and ≤ 6 months; RR 5.86 and 95%CI, 3.26 - 10.53 for > 6 and ≤ 12 months, and; RR 4.24 and 95%CI, 2.32 - 7.75 for > 12 months). Conclusion: Patients who remained on the waitlist for less than 3 months had the highest survival (median survival, 856 days; IQR, 131 - 1607). The risk of reduced survival was about 6-fold higher (95%CI, 2.8 - 11.5) in patients with malignancies.

Yttria stabilized zirconia materials are frequently used in mechanical engineering and biomedical applications. Demanding loading conditions require materials combining a high level of strength and fracture toughness. A ready-to-press alumina doped 2 mol% yttria-stabilized zirconia powder was shaped by axial pressing and sintering in air at 1250–1500 °C for 2 h. At 1350 °C the best combination of strength (1450 MPa) and toughness (7.8 MPa√m) was achieved. Materials sintered in the middle of the chosen temperature range combine full density, high transformability and small grain size. Toughness measurements by direct crack length measurements delivered unrealistically high fracture toughness values.

Abstract The microbial communities of the oral cavity are important elements of oral and systemic health. With emerging evidence highlighting the heritability of oral bacterial microbiota, this study aimed to identify host genome variants that influence oral microbial traits. Using data from 16S rRNA gene amplicon sequencing, we performed genome-wide association studies with univariate and multivariate traits of the salivary microbiota from 610 unrelated adults from the Danish ADDITION-PRO cohort. We identified six single nucleotide polymorphisms (SNPs) in human genomes that showed associations with abundance of bacterial taxa at different taxonomical tiers (P

Abstract Atomic-scale molecular modeling and simulation are powerful tools for computational biology. However, constructing models with large, densely packed molecules, non-water solvents, or with combinations of multiple biomembranes, polymers, and nanomaterials remains challenging and requires significant time and expertise. Furthermore, existing tools do not support such assemblies under the periodic boundary conditions (PBC) necessary for molecular simulation. Here, we describe Multicomponent Assembler in CHARMM-GUI that automates complex molecular assembly and simulation input preparation under the PBC. In this work, we demonstrate its versatility by preparing 6 challenging systems with varying density of large components: (1) solvated proteins, (2) solvated proteins with a pre-equilibrated membrane, (3) solvated proteins with a sheet-like nanomaterial, (4) solvated proteins with a sheet-like polymer, (5) a mixed membrane-nanomaterial system, and (6) a sheet-like polymer with gaseous solvent. Multicomponent Assembler is expected to be a unique cyberinfrastructure to study complex interactions between small molecules, biomacromolecules, polymers, and nanomaterials.

Abstract Background Teratomas are germ cell tumors composed of somatic tissues from up to three germ layers. Primary retroperitoneal teratomas usually develop during childhood and are uncommon in adults and in the retroperitoneal space. While there are only a few cases of retroperitoneal thyroid tissue, we report a unique case of a retroperitoneal papillary thyroid carcinoma. Case presentation A 41-year-old woman presented in our institution due to intermitted unspecific abdominal pain. Magnetic resonance imaging detected a multi-cystic solid retroperitoneal mass ventral to the psoas muscle and the left iliac artery. After surgical removal of the retroperitoneal mass, histology sections of the specimen indicated evidence of papillary thyroid carcinoma cells. A staging computed tomography scan of the body showed no further manifestations. To reduce the risk of recurrence, total thyroidectomy was performed followed by radioiodine therapy with lifelong hormone substitution. Conclusions Primary retroperitoneal teratoma with evidence of papillary thyroid carcinoma is a rare condition. Preoperative diagnosis is difficult due to its non-specific clinical manifestation and lack of specific radiologic findings. Histopathology analysis is necessary for diagnosis. Although surgery is considered the first line treatment, there is still discussion about the extent of resection and the need for total thyroidectomy with adjuvant radioiodine therapy.

Students with emotional and behavioral problems have poor academic and behavioral outcomes, both short- and long-term. Psychotropic medications are commonly used as an intervention with this population and their use has increased significantly. This study investigated adolescent and family variables associated with medication use among high school students with elevated emotional and behavioral problems, including those with a label of emotional and behavioral disorders. Participants included 548 adolescents from a larger randomized controlled trial, 184 (33.6%) of whom were receiving medication. Hierarchical linear modeling revealed that special education status, externalizing and internalizing behavior symptoms and participant race were significant student predictors of medication use. Parenting stress, family structure, positive parenting, and poor monitoring were significant family predictors of participants' medication use. These findings have implications for current practices in schools pertaining to screening and access to interventions as well as future research focused on the parent and student decision making process for choice of interventions.

Non-alcoholic fatty liver disease (NAFLD) is a liver manifestation of metabolic syndrome, and is estimated to affect one billion individuals worldwide. An increased intake of a high-fat diet (HFD) and sugar-sweetened beverages are risk-factors for NAFLD development, but how their combined intake promotes progression to a more severe form of liver injury is unknown. Here we show that fructose metabolism via ketohexokinase (KHK) C isoform leads to unresolved endoplasmic reticulum (ER) stress when coupled with a HFD intake. Conversely, a liver-specific knockdown of KHK in mice consuming fructose on a HFD is adequate to improve the NAFLD activity score and exert a profound effect on the hepatic transcriptome. Overexpression of KHK-C in cultured hepatocytes is sufficient to induce ER stress in fructose free media. Upregulation of KHK-C is also observed in mice with genetically induced obesity or metabolic dysfunction, whereas KHK knockdown in these mice improves metabolic function. Additionally, in over 100 inbred strains of male or female mice hepatic KHK expression correlates positively with adiposity, insulin resistance, and liver triglycerides. Similarly, in 241 human subjects and their controls, hepatic Khk expression is upregulated in early, but not late stages of NAFLD. In summary, we describe a novel role of KHK-C in triggering ER stress, which offers a mechanistic understanding of how the combined intake of fructose and a HFD propagates the development of metabolic complications.

X-ray crystallography and X-ray spectroscopy using X-ray free electron lasers plays an important role in understanding the interplay of structural changes in the protein and the chemical changes at the metal active site of metalloenzymes through their catalytic cycles. As a part of such an effort, we report here our recent development of methods for X-ray absorption spectroscopy (XAS) at XFELs to study dilute biological samples, available in limited volumes. Our prime target is Photosystem II (PS II), a multi subunit membrane protein complex, that catalyzes the light-driven water oxidation reaction at the Mn4CaO5 cluster. This is an ideal system to investigate how to control multi-electron/proton chemistry, using the flexibility of metal redox states, in coordination with the protein and the water network. We describe the method that we have developed to collect XAS data using PS II samples with a Mn concentration of