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Abstract Alzheimer's disease is a devastating neurodegenerative disease eventually leading to dementia. An effective treatment does not yet exist. Here we show that oral application of the compound anle138b restores hippocampal synaptic and transcriptional plasticity as well as spatial memory in a mouse model for Alzheimer's disease, when given orally before or after the onset of pathology. At the mechanistic level, we provide evidence that anle138b blocks the activity of conducting Aβ pores without changing the membrane embedded Aβ‐oligomer structure. In conclusion, our data suggest that anle138b is a novel and promising compound to treat AD‐related pathology that should be investigated further.

Abstract Although misfolded and aggregated α‐synuclein (α‐syn) is recognized in the disease progression of synucleinopathies, its role in the impairment of cortical circuitries and synaptic plasticity remains incompletely understood. We investigated how α‐synuclein accumulation affects synaptic plasticity in the mouse somatosensory cortex using two distinct approaches. Long‐term in vivo imaging of apical dendrites was performed in mice overexpressing wild‐type human α‐synuclein. Additionally, intracranial injection of preformed α‐synuclein fibrils was performed to induce cortical α‐syn pathology. We find that α‐synuclein overexpressing mice show decreased spine density and abnormalities in spine dynamics in an age‐dependent manner. We also provide evidence for the detrimental effects of seeded α‐synuclein aggregates on dendritic architecture. We observed spine loss as well as dystrophic deformation of dendritic shafts in layer V pyramidal neurons. Our results provide a link to the pathophysiology underlying dementia associated with synucleinopathies and may enable the evaluation of potential drug candidates on dendritic spine pathology in vivo.

Abstract As stated by the prevailing amyloid cascade hypothesis, Alzheimer's disease (AD) is caused by the aggregation and cerebral deposition of long amyloid‐β peptide (Aβ) species, which are released from a C‐terminal amyloid precursor protein fragment by γ‐secretase. Mutations in its catalytic subunit presenilin‐1 (PS1) increase the Aβ42 to Aβ40 ratio and are the major cause of familial AD (FAD). An opposing hypothesis states that loss of essential presenilin functions underlies the disease. A major argument for this hypothesis is the observation that the nearly inactive PS1 L435F mutant, paradoxically, causes FAD. We now show that the very little Aβ generated by PS1 L435F consists primarily of Aβ43, a highly amyloidogenic species which was overlooked in previous studies of this mutant. We further demonstrate that the generation of Aβ43 is not due to a trans‐dominant effect of this mutant on WT presenilin. Furthermore, we found Aβ43‐containing plaques in brains of patients with this mutation. The aberrant generation of Aβ43 by this particular mutant provides a direct objection against the presenilin hypothesis.

Abstract Deregulated expression of MYC is a driver of colorectal carcinogenesis, necessitating novel strategies to inhibit MYC function. The ubiquitin ligase HUWE1 (HECTH9, ARF‐BP1, MULE) associates with both MYC and the MYC‐associated protein MIZ1. We show here that HUWE1 is required for growth of colorectal cancer cells in culture and in orthotopic xenograft models. Using high‐throughput screening, we identify small molecule inhibitors of HUWE1, which inhibit MYC‐dependent transactivation in colorectal cancer cells, but not in stem and normal colon epithelial cells. Inhibition of HUWE1 stabilizes MIZ1. MIZ1 globally accumulates on MYC target genes and contributes to repression of MYC‐activated target genes upon HUWE1 inhibition. Our data show that transcriptional activation by MYC in colon cancer cells requires the continuous degradation of MIZ1 and identify a novel principle that allows for inhibition of MYC function in tumor cells.

Numerous dynamic mass balances in the literature that describe the adsorption of gases in a column are written in terms of actual or absolute adsorption, while unwittingly and incorrectly utilizing excess adsorption isotherms. Perhaps this is because the actual and absolute adsorption isotherms cannot be experimentally measured nor predicted without making uncertain assumptions. The objective here was to derive unambiguous relationships between actual, absolute, excess, net and column amounts adsorbed that provide a straightforward understanding of the subtle differences between these quantities and that provide a simple means for incorporating them into dynamic mass balances. For this purpose, the actual, absolute, excess, net and column amounts adsorbed (loadings) were clearly defined, along with various volumes, porosities and densities that exist inside and outside an adsorbent contained in a column with a gaseous adsorbate. These adsorption definitions and quantities were used to derive four interconversion relationships for each type of adsorption in terms of the actual loading. The resulting expressions, based on intensive properties, can be used to relate any adsorption definition to any other adsorption definition. These relationships were also used to derive five dynamic mass balances, one for each type of adsorption. The similarities and differences in the terms between each of these five dynamic mass balances were discussed, along with their applicability to real world problems. In some cases at low pressure where the isotherms do not differ appreciably, it may be approximately correct to use excess or net adsorption isotherms in a dynamic mass balance written in terms of actual or absolute adsorption. However, the extent of the incorrectness is unknown due to mass transfer effects. So, it is recommended to use the dynamic mass balance with its specific type of adsorption, most likely excess adsorption. Then, when certain assumptions are made about the adsorbing and non-adsorbing void fractions, these expressions can be readily used in adsorption process simulation. [ABSTRACT FROM AUTHOR]

In this article, two accurate nonlinear methods are proposed to calculate non-symmetrical locking ranges of the Injected Cross-Coupled Oscillator (ICCO) with the parallel RLC tank and series RL with a parallel C tank for both weak and strong injection levels. By writing governing differential equations of circuit elements of the ICCO, graphical presenting of current vectors, and using the averaging method for solving nonlinear equations, equations of the ICCO are simplified. Then, exact non-symmetrical locking ranges are calculated using the iterative method. Moreover, the describing function of the oscillator's nonlinear part, an inverse tangent function, is applied to the model. The inverse tangent function generates complicated governing differential equations of circuit elements that are accurate. Then, it is solved to ICCO for the first time and has novel results for calculating non-symmetrical locking ranges. There is a good agreement between theoretical and simulation results. The proposed non-symmetrical locking ranges are accurate in both weak and strong injections. The absolute percent of errors for various levels of the injection signal is less than 20%. In the bargain, proposed locking ranges are the most accurate compared to previously published results. [ABSTRACT FROM AUTHOR]

In this study, the annual, seasonal and monthly trends of total cloud cover (TCC) and associated climatic variables are investigated for a period of 63 (1959–2022) years in Iran based on ERA5 reanalysis data extracted from ECMWF. To analyze temporal trends, the Mann–Kendall test is used. The geographical location within Iran, especially distance from moisture sources and different atmospheric systems, influences cloudiness such that TCC decreases from north to south and from west to east. With respect to seasons, the highest and lowest average TCC is observed in winter and summer, respectively. The annual trend analysis reveals a decreasing trend in TCC (i.e., Mann–Kendall's tau is negative: −0.40 per decade). On the monthly scale, a statistically significant decrease in TCC occurs during January, February, March, June, August, November, and December. There is a significant decreasing trend in all seasons, among which the maximum decreasing trend is observed in the summer season with a value of −0.31 per decade. Examining the trends of climatic variables shows that on all three temporal scales (annual, seasonal, and monthly) the number of rainy days (NRD) decreases and temperature (T) increases. Spatial analysis of trends (seasonal, annual) suggests the highest decrease in TCC in the west, northwest, east, and southeast, whereas the lowest decrease is in the center of Iran. Spatially, the T trend (annually and spring, summer, and winter seasons) indicates a consistent increase in temperature in the central and eastern parts of Iran. The spatial trend (annual and seasonal) of NRD in the limited parts of northwestern Iran exhibits the highest increasing trend. The results of investigating the anomalies in TCC relative to the long-term average amount of cloud cover on annual and seasonal scales show zero anomalies in most of the years (67% on an annual scale and 73% in summer and 71% in winter). [ABSTRACT FROM AUTHOR]

Objective: To establish an image acquisition and post-processing workflow for the determination of the proton density fat fraction (PDFF) in calf muscle tissue at 7 T. Materials and methods: Echo times (TEs) of the applied vendor-provided multi-echo gradient echo sequence were optimized based on simulations of the effective number of signal averages (NSA*). The resulting parameters were validated by measurements in phantom and in healthy calf muscle tissue (n = 12). Additionally, methods to reduce phase errors arising at 7 T were evaluated. Finally, PDFF values measured at 7 T in calf muscle tissue of healthy subjects (n = 9) and patients with fatty replacement of muscle tissue (n = 3) were compared to 3 T results. Results: Simulations, phantom and in vivo measurements showed the importance of using optimized TEs for the fat–water separation at 7 T. Fat–water swaps could be mitigated using a phase demodulation with an additional B0 map, or by shifting the TEs to longer values. Muscular PDFF values measured at 7 T were comparable to measurements at 3 T in both healthy subjects and patients with increased fatty replacement. Conclusion: PDFF determination in calf muscle tissue is feasible at 7 T using a chemical shift-based approach with optimized acquisition and post-processing parameters. [ABSTRACT FROM AUTHOR]

Women with intellectual and developmental disabilities (I/DD) are less likely to receive cervical cancer screening (CCS) relative to women without disabilities. Primary care providers (PCPs) play key roles in recommending CCS. The purpose of this study was to identify factors PCPs consider when recommending and performing CCS for women with I/DD. Using a qualitative approach, in-depth semi-structured interviews (N = 13) were conducted with majority family medicine-trained PCPs. Through inductive data analysis, it was found that most PCPs reported recommending CCS; however, follow-through for performing CCS varied. PCPs attempted to align their CCS recommendations with national guidelines and provided counseling and education to families and patients about CCS while taking an individualized risk–benefit approach. Despite most PCPs reporting a lack of knowledge or training related to providing I/DD-specific care, PCPs attempted to draw upon experiences with similar populations to recommend and perform CCS. There is an opportunity to improve knowledge of PCPs related to performing CCS for women with I/DD. [ABSTRACT FROM AUTHOR]

Background: Mandibular advancement devices (MAD) are a well-established treatment option for obstructive sleep apnea (OSA). MAD are considered preferably for patients with mild to moderate OSA presenting with a elevated night-to-night variability (NNV). This study aimed to determine the treatment effect of MAD on NNV considering different protrusion distances and patient related outcome (PRO). Methods: We conducted a prospective cohort analysis of patients before MAD with 60% and 80% of the maximum protrusion. OSA severity was assessed using a home-sleep test for two consecutive nights. PRO contained the Epworth Sleepiness Scale (ESS) and sleep related quality of life (FOSQ). Results: Twenty patients with a median overweight body-mass-index of 27.1 (interquartile range (IQR) 16.3 kg/m²), with a mainly mild to moderate OSA with an apnea -hypopnea index (AHI) of 18.3 / h (IQR 17.7) and elevated ESS of 12.5 (IQR 8.0) were included. As opposed to 80%, 60% protrusion significantly but not 80% relevantly reduced AHI (60%%: 11.2 (IQR 5.5)/h, p = 0.01; 80%: 12.9 (IQR18,0)/h, p = 0.32) and improved the ESS (60%: 8.0 (IQR 10,0); 80%: 10 (IQR 9.0)), with therapy settings. No correlation could be detected between NNV and ESS, and FOSQ changes. Higher baseline NNV was associated with severe OSA (p = 0.02) but not with gender, overweight, or status post-tonsillectomy. Conclusions: OSA improvement is associated with lower NNV; both OSA and NNV are connected to the degree of protrusion. Therefore, higher NNV does not justify the exclusion of candidates for MAD treatment. PRO changes are not visibly affected by NNV but by general OSA changes. These findings may help to define and optimize future study designs for the primary outcome decision between objective OSA parameters and PRO. [ABSTRACT FROM AUTHOR]

This paper evaluates the performance of electrostatic-doped silicene nanoribbon field-effect transistors (ED SiNR-FET) and graphene nanoribbon field-effect transistors (ED GNR-FET) through quantum-based electron transport simulations. It assesses the impact of ribbon widths and device geometry, revealing that ED SiNR-FET generally outperforms ED GNR-FET, particularly in terms of resistance to impurities and short-channel effects. The study identifies optimal ribbon widths for superior performance and introduces the extended channel ED (ECED) structure, which significantly enhances the ION/IOFF ratio to 3.8 × 105 in SiNR-FET compared to 3.9 × 103 in GNR-FET for 15 nm devices. Additionally, analyses of ECED SiNR-FETs and ECED GNR-FET across various channel and gate lengths suggest that ECED devices are suitable for low-power and high-performance applications, with the ECED SiNR-FET displaying excellent subthreshold swing (SS) of 64 mV/dec and high transconductance (gm) of 63 µS. This research confirms the advanced performance of SiNR-FETs over GNR-FETs and the potential of ECED SiNR-FETs in diverse applications. [ABSTRACT FROM AUTHOR]

Purpose: To describe policy and system-level interventions with potential to improve cancer care at six sites. Methods: In 2016, six institutions received foundation support to develop unique multi-component interventions aimed at improving cancer care for underserved populations. These organizations, located across the United States, participated in a cross-site evaluation to assess the overall initiative impact and to identify potentially promising policy and system-level solutions for dissemination and broader implementation. A health system and policy tracking tool was developed to collect data from each site and included a description of their efforts, strategies employed, and changes achieved (e.g., new policies, clinical protocols). Tracking tool data were analyzed using rapid qualitative analyses and a matrix approach. Semi-structured interviews were conducted with site leaders (N = 65) and were analyzed by thematic analysis. Results: Sites reported 20 system and policy efforts, which resulted in improvements to electronic health records and telehealth strategies, changes to hospital/health system policies, and standardized clinical protocols/guidelines, among others. Efforts were aimed at: (1) coordinating care across multiple providers, supported by patient navigators; (2) expanding psychosocial and supportive care; (3) improving patient-provider communication; and (4) addressing barriers to accessing care. Interview analyses provided insights into successful strategies, challenges, and implications of the COVID-19 pandemic on cancer care. Conclusions and implications for cancer survivors: Despite advances in diagnosis and treatment, cancer care remains inequitable. System-level improvements aimed at eliminating common barriers faced by underserved populations offer opportunities to improve the delivery of equitable, effective, and efficient care. [ABSTRACT FROM AUTHOR]

Triticale is a man-made crop produced by crossing wheat (Triticum aestivum) and rye (Secal cereal) with the aim of increasing the adaptability and potential production of its parental line (wheat) under environmental stresses and harsh conditions. Accordingly, the objectives of this study are as follow, a: compare different stability measurement methods regarding their suitability, b: identify most stable genotypes for cultivar release, and c: provide a freely available package in R programming language (named 'Stbidx') capable of exploiting all stability methods for similar studies. Accordingly, 30 triticale genotypes were evaluated for their stability and adaptability to changing environments during four consecutive years from 2016 to 2020 in different locations in Iran (one year in Zarghan, two years in Ghorveh, one year in Sanandaj) and under two different irrigation regimes (normal irrigation and water deficit stress conditions). All 30 triticale genotypes were cultivated in a randomized complete block design (RCBD) with three replications in each environment (12 environments: 6 trials in 2 conditions). Grain yield of triticale genotypes was measured and it applied to calculate all known stability indices (univariate methods) along with the meta-analysis models were evaluated in this study. Additionally, two novel techniques (Stability ID: SID and AMMI PC Value: APCV) were introduced and successfully tested for screening stable genotypes. These methods were introduced to improve and resolve the limitation of the previous stability methods. Meanwhile, heatmap analysis, as a proper data-mining technique, has been successfully applied for the first time to find stable genotypes in different environments in this study. The results clearly indicated a higher suitability of our introduced methods over previous multi-trials screening methods. Based on our methods and considering all environments, triticale genotypes ELTTCL21 (SID = 8.00; APCV = 28.12), ELTTCL25‌ (SID = 8.14; APCV = 30.02), ELTTCL30 (SID = 8.43; APCV = 17.00), ET-90-8 (SID = 14.00; APCV = 42.05), and Sanabad (SID = 10.57; APCV = 12.44) were among stable genotypes and they can be nominated as new cultivars. Additionally, for stress condition genotypes ELTTCL30 (stress: 380.6 g/m2) and ELTTCL18 (stress: 360.79 g/m2) and for normal condition genotypes ET-90-4 (normal: 849.4 g/m2) and ELTTCL20 (normal:845 g/m2) were respectively the most proper genotypes with the highest production to be considered for each condition separately. [ABSTRACT FROM AUTHOR]

From the start of life on Earth, several immune defense mechanisms have evolved to guarantee cellular integrity, homeostasis, and host survival. All these sophisticated balances as shaped by and towards the environmental needs have occurred over hundreds of millions of years. Human spaceflight involves various health hazards, such as higher levels of radiation, altered gravity, isolation and confinement, living in tight quarters, and stress associated with being away from home. A growing body of evidence points towards immunological changes in astronauts, including heightened pro-inflammatory responses, reactivation of latent viruses, and cell-mediated alterations, reflecting a dysbalanced state in astronauts. Simultaneously, enhanced pathogenicity, virulence, and drug resistance properties of microorganisms tip the scale out of favor for prolonged stay in space. As we have learned from the past, we see potential for the human immune system, forged and maintained throughout evolutionary history, to adapt to the space exposome. It is unlikely that this will happen in the short time frames set for current space exploration missions. Instead, major risks to astronaut health need to be addressed first, before humans can safely evolve into the space environment. [ABSTRACT FROM AUTHOR]

The activation of the Ca2+-channel Orai1 via the physiological activator stromal interaction molecule 1 (STIM1) requires structural rearrangements within the entire channel complex involving a series of gating checkpoints. Focusing on the gating mechanism operating along the peripheral transmembrane domain (TM) 3/TM4-interface, we report here that some charged substitutions close to the center of TM3 or TM4 lead to constitutively active Orai1 variants triggering nuclear factor of activated T-cell (NFAT) translocation into the nucleus. Molecular dynamics simulations unveil that this gain-of-function correlates with enhanced hydration at peripheral TM-interfaces, leading to increased local structural flexibility of the channel periphery and global conformational changes permitting pore opening. Our findings indicate that efficient dehydration of the peripheral TM-interfaces driven by the hydrophobic effect is critical for maintaining the closed state of Orai1. We conclude that a charge close to the center of TM3 or TM4 facilitates concomitant hydration and widening of peripheral TM interfaces to trigger constitutive Orai1 pore opening to a level comparable to or exceeding that of native activated Orai1. The Ca2+ ion channel Orai1 plays an important role in T-cell activation. A charged amino acid side chain close to the center of Orai1-transmembrane domain (TM)3 or -TM4 triggers robust constitutive activity due to enhanced hydration and widening of peripheral TM-interfaces. [ABSTRACT FROM AUTHOR]

Computerized numerical controls (CNCs) have been invented for the automation of industrial processes. They are used, when the process to be automated is required to be exact and fast with repeatable quality. Originally, the use of CNCs was primarily focused on milling and drilling processes. Today, CNCs are utilized in a wide range of industrial processes due to the growing importance of automation. However, the integration of process information or adaptation to the needs of these processes to achieve advanced manufacturing with CNCs is difficult: Industrial CNCs are rather closed real-time machining systems. Today, process integration is possible, when the interaction between the process and the machine is decoupled in view of the bandwidth of machine dynamics and process dynamics. There are interfaces that allow for process-motivated control loops that are realized on top of the machine control loop (e.g. chatter control). Then, machine-integrated real-time control is not the focus. Besides, it is often possible to change desired values inside the control loop (position, velocity, acceleration) on an axes basis. In this case, adaptation to the process can be realized in each computation cycle. However, process dynamics and machine axes dynamics are generally treated separately. The same holds for extra actuators (e.g., in the spindle) for position control. This paper has two goals. First, it wants to create an understanding for different levels of process-machine coupling. Second, the problem of direct coupling of process dynamics and machine dynamics is focused. Machining systems design propositions as well as some examples for the coupling of process and machine dynamics in the CNC are given. [ABSTRACT FROM AUTHOR]

We present an exploration of the effect of electron-phonon coupling and broken inversion symmetry on the electronic and thermal properties of the semimetal LaRhGe3. Our transport measurements reveal evidence for electron-hole compensation at low temperatures, resulting in a large magnetoresistance of 3000% at 1.8 K and 14 T. The carrier concentration is on the order of 1021/cm3 with high carrier mobilities of 2000 cm2/Vs. When coupled to our theoretical demonstration of symmetry-protected almost movable Weyl nodal lines, we conclude that LaRhGe3 supports a Weyl semimetallic state. We discover superconductivity in this compound with a Tc of 0.39(1) K and Bc(0) of 2.2(1) mT, with evidence from specific heat and transverse-field muon spin relaxation. We find an exponential dependence in the normal state electrical resistivity below ~50 K, while Seebeck coefficient and thermal conductivity measurements each reveal a prominent peak at low temperatures, indicative of strong electron-phonon interactions. To this end, we examine the temperature-dependent Raman spectra of LaRhGe3 and find that the lifetime of the lowest energy A1 phonon is dominated by phonon-electron scattering instead of anharmonic decay. We conclude that LaRhGe3 has strong electron-phonon coupling in the normal state, while the superconductivity emerges from weak electron-phonon coupling. These results open up the investigation of electron-phonon interactions in the normal state of superconducting non-centrosymmetric Weyl semimetals. [ABSTRACT FROM AUTHOR]

The Vertex Morphing method is a node-based shape parameterization that uses an explicit filtering approach to regularize the optimization problem and generate smooth shapes. It has been successfully applied to shape optimization problems of industrial size in recent years. This work investigates in detail how irregular discretizations, design surface boundaries, and complex geometries can influence the progress of a gradient-based optimization using the standard Vertex Morphing formulation. A sensitivity weighting approach based on the available shape morphing functions is presented, which eliminates all of the aforementioned influences. Subsequently, a design variable scaling strategy is developed that transforms the optimization problem into an alternative design space and allows the use of arbitrary, even highly irregular surface discretizations in combination with black-box optimization algorithms for shape optimization with the Vertex Morphing method. Illustrative academic examples and an application case of an additively manufactured part are presented to support the work. [ABSTRACT FROM AUTHOR]

This paper deals with the local bifurcation analysis of a nanotube with a nanostring passing through it. Eringen's two-phase local/nonlocal model and Eringen's differential model are employed as constitutive equations. The governing equations are derived as two nonlinear first-order systems of ordinary differential equations. Nonlinear analysis is performed by using the Lyapunov–Schmidt method. The influence of the small length scale parameter and the phase parameter on critical buckling load, type of bifurcation and post-buckling shape of the nanotube is examined for both types of constitutive equations. Depending on the values of the small length scale parameter and the phase parameter, the critical buckling load corresponding to Eringen's two-phase local/nonlocal model can be greater or less than that corresponding to Eringen's differential model. It is shown that for both models supercritical pitchfork bifurcation occurs. The post-buckling shapes of nanotube, obtained by numerical integration, exhibit a qualitative difference between the two models. [ABSTRACT FROM AUTHOR]

Introduction: The combination of anterior large glenoid rim fractures (GRF) and proximal humerus fractures (PHF) is rare, with limited data available on specific treatments for these glenohumeral combination fractures (GCF). This study aimed to evaluate the treatment approaches for GCF, analyze patient outcomes, and outline surgical management strategies for different fracture types. Materials and methods: This retrospective study included patients with GCF, excluding those with fossa glenoidalis fractures, isolated greater tuberosity fractures, or small glenoid rim fractures (< 5 mm). Preoperative radiographs, CT scans, and follow-up radiographs were reviewed. Clinical outcomes were assessed using the Constant-Murley Score (CMS), Western Ontario Shoulder Instability Index (WOSI), Rowe Score (RS), and Oxford Shoulder Score (OSS). Results: Sixteen patients with 17 GCFs (mean age 62 years) were followed for an average of 39 months. PHFs were categorized into three-part (76%), four-part (12%), and two-part fractures (12%). The average medial displacement of GRF was 5 mm, with an average dehiscence of 4 mm in the sagittal plane. Fourteen patients (88%) underwent surgical treatment; 35% had only the PHF surgically addressed, while 53% had both lesions surgically treated. Two patients (12%) received non-operative treatment. Complications were observed in 29% of cases, primarily involving the humeral side. The average CMS was 68 points, WOSI was 75%, RS was 77 points, and OSS was 41 points. Conclusion: Treating GCF is complex and routinely necessitates surgical intervention, with or without GRF refixation. CT imaging is crucial for precise assessment of fracture morphology. The involvement of the minor tuberosity is critical in selecting the optimal surgical approach and managing the subscapularis muscle. [ABSTRACT FROM AUTHOR]

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Background: The European Society of Gastroenterology and Endoscopy recommends a primarily flexible endoscopic approach for the treatment of Zenker's diverticulum. Due to the rarity of the disorder, evidence for its effectiveness and safety comes mainly from small, retrospective, single-center studies. Methods: In this retrospective, observational, multicenter cohort study, data from six German tertiary referral centers were analyzed. The primary outcome parameters were technical and clinical success; among the secondary outcomes, the rates of adverse events (AE) and re-admission with symptomatic recurrence and mortality were the most relevant. Results: Between 2003 and 2024, 384 treatments were performed in 327 patients (61.8% male, mean age 74.70 (± 10.60)). Incision methods/techniques were 250 needle knives, 44 ESD knives, 64 stag beetle knives, 24 staplers, one APC-probe, and one Z-POEM. The Zenker's diverticulum overtube was used in 65.1%, prophylactic clipping in 30.2%, and antibiotic therapy in 25.3% of treatments. The rates of technical and clinical success were 99.2% and 97.4%, and the rates of AE and re-admission with symptomatic recurrence were 11.2% and 16.7%, respectively. Mortality was 0.3%. Comparative subgroup analyses of 312 diverticula without prior treatment versus 72 symptomatic recurrences and incision methods/techniques showed no significant differences in outcome parameters. The use of additional devices and prophylactic measures (clipping, antibiotic therapy) were not independent predictors of technical/clinical success or AE in uni-/multivariable regression analysis. Conclusions: Flexible endoscopic Zenker's diverticulotomy is a safe and effective minimally invasive treatment. Recurrences can be treated by flexible endoscopy with comparable results. None of the cutting methods, ancillary devices, or prophylactic measures showed superiority in effectiveness or safety. [ABSTRACT FROM AUTHOR]

The aim of this paper is to establish the existence of infinitely many solutions for a class of anisotropic p → -Laplacian problems with Dirichlet boundary conditions, depending on two real parameters. These problems have a variational structure and some critical point theorems are applied. We also give an example to illustrate the obtained results. [ABSTRACT FROM AUTHOR]

Objective: To compare image quality and diagnostic performance of 3T and 7T magnetic resonance imaging (MRI) for direct depiction of finger flexor pulleys A2, A3 and A4 before and after artificial pulley rupture in an ex-vivo model using anatomic preparation as reference. Materials and Methods: 30 fingers from 10 human cadavers were examined at 3T and 7T before and after being subjected to iatrogenic pulley rupture. MRI protocols were comparable in duration, both lasting less than 22 min. Two experienced radiologists evaluated the MRIs. Image quality was graded according to a 4-point Likert scale. Anatomic preparation was used as gold standard. Results: In comparison, 7T versus 3T had a sensitivity and specificity for the detection of A2, A3 and A4 pulley lesions with 100% vs. 95%, respectively 98% vs. 100%. In the assessment of A3 pulley lesions sensitivity of 7T was superior to 3T MRI (100% vs. 83%), whereas specificity was lower (95% vs. 100%). Image quality assessed before and after iatrogenic rupture was comparable with 2.74 for 7T and 2.61 for 3T. Visualization of the A3 finger flexor pulley before rupture creation was significantly better for 7 T (p < 0.001). Interobserver variability showed substantial agreement at 3T (κ = 0.80) and almost perfect agreement at 7T (κ = 0.90). Conclusion: MRI at 3T allows a comparable diagnostic performance to 7T for direct visualization and characterization of finger flexor pulleys before and after rupture, with superiority of 7T MRI in the visualization of the normal A3 pulley. [ABSTRACT FROM AUTHOR]

We provide updated results (median follow-up duration: 20.4 months) of a retrospective study on the effectiveness of trastuzumab deruxtecan (T-DXd) in patients with human epidermal growth factor receptor 2-positive (HER2+) breast cancer with brain metastases (BM) and/or leptomeningeal disease (ROSET-BM). Median progression-free survival (PFS) was 14.6 months. Median overall survival (OS) was not reached (NR); 24-month OS rate was 56.0%. Subgroup analysis showed that median PFS was 13.2 months in patients with analytical active BM, 17.5 months in patients with leptomeningeal carcinomatosis (LMC), and NR in patients with analytical stable BM (24-month PFS rates in patients with analytical active BM, LMC, and analytical stable BM were 32.7%, 25.1%, and 60.8%, respectively). Median OS was 27.0 months in patients with analytical active BM and NR in patients with LMC or analytical stable BM (24-month OS rates in patients with analytical active BM, LMC, and analytical stable BM were 52.0%, 61.6%, and 71.6%, respectively). The most common adverse event leading to discontinuation of T-DXd was interstitial lung disease (ILD; 23.1%); median ILD onset time among patients who discontinued T-DXd treatment due to ILD was 5.3 months. T-DXd has promising effectiveness in heavily pre-treated HER2+ metastatic breast cancer patients with BM and LMC. The incidence and median onset time of ILD were similar to those of Japanese subgroups in previous studies. [ABSTRACT FROM AUTHOR]

The (re-)construction of past and future personal experiences, termed mental time travel (MTT), is highly adaptive and contributes to self-related beliefs and attitudes. Mounting evidence suggests that self-efficacy (SE), the belief that one can overcome obstacles on their own account, is functionally related to MTT. In the present study, we used novel methods for the analysis of MTT narratives based on natural language processing (NLP) to investigate the relation between SE and MTT. We demonstrated that self-efficacious participants remembered and imagined experiences which were semantically less similar and contained a wider variety of contents. Additionally, increased SE was related to a positive reappraisal of personal episodes and reports of a more active role within mental scenarios. In conclusion, NLP appears to be a valuable method to quantify changes to the (re-)construction of personal experience that might support cognitive and emotional functioning. [ABSTRACT FROM AUTHOR]

Shock is a life-threatening condition. This study evaluated if sublingual microcirculatory perfusion on admission is associated with 30-day mortality in older intensive care unit (ICU) shock patients. This trial prospectively recruited ICU patients (≥ 80 years old) with arterial lactate above 2 mmol/L, requiring vasopressors despite adequate fluid resuscitation, regardless of shock cause. All patients received sequential sublingual measurements on ICU admission (± 4 h) and 24 (± 4) hours later. The primary endpoint was 30-day mortality. From September 4th, 2022, to May 30th, 2023, 271 patients were screened, and 44 included. Patients were categorized based on the median percentage of perfused small vessels (sPPV) into those with impaired and sustained microcirculation. 71% of videos were of good or acceptable quality without safety issues. Patients with impaired microcirculation had significantly shorter ICU and hospital stays (p = 0.015 and p = 0.019) and higher 30-day mortality (90.0% vs. 62.5%, p = 0.036). Cox regression confirmed the independent association of impaired microcirculation with 30-day mortality (adjusted hazard ratio 3.245 (95% CI 1.178 to 8.943, p = 0.023). Measuring sublingual microcirculation in critically ill older patients with shock on ICU admission is safe, feasible, and provides independent prognostic information about outcomes. Trial registration NCT04169204. [ABSTRACT FROM AUTHOR]

Decision to explore new options with uncertain outcomes or exploit familiar options with known outcomes is a fundamental challenge that the brain faces in almost all real-life decisions. Previous studies have shown that humans use two main explorative strategies to negotiate this explore-exploit tradeoff. Exploring for the sake of information is called directed exploration, and exploration driven by behavioral variability is known as random exploration. While previous neuroimaging studies have shown different neural correlates for these explorative strategies, including right frontopolar cortex (FPC), right dorsolateral prefrontal cortex (DLPFC), and dorsal anterior cingulate cortex (dACC), there is still a lack of causal evidence for most of these brain regions. Here, we focused on the right DLPFC, which was previously supported to be involved in exploration. Using the continuous theta burst stimulation (cTBS) and Horizon task on twenty-five healthy right-handed adult participants, we showed that inhibiting rDLPFC did not change directed exploration but selectively reduced random exploration, by increasing reward sensitivity over the average reward of each option. This suggests a causal role for rDLPFC in random exploration, and further supports dissociable neural implementations for these two explorative strategies. [ABSTRACT FROM AUTHOR]

Objective: To investigate the prognostic value of baseline health-related quality of life (HRQOL) for patients with intermediate-risk localized prostate cancer (IR-PCa) undergoing radical prostatectomy (RP). Methods: 4780 patients with IR-PCa according to NCCN risk stratification were identified from a prospectively maintained database. All patients were treated with RP and had prospectively assessed baseline HRQOL. Main outcomes were oncologic endpoints metastasis-free survival (MFS); biochemical recurrence free survival (BRFS) and overall survival (OS). Multivariable Cox regression models assessed prognostic significance of baseline global health status (GHS) on survival outcomes. Harrell's discrimination C-index was applied to calculate the predictive accuracy of the model. Decision curve analysis (DCA) tested the clinical net benefit associated with adding the GHS domain to our multivariable model (p < 0.05). Results: Median follow-up was 51 months. Multivariable analysis confirmed baseline GHS as an independent predictor for increased MFS (HR 0.976, 95%CI 0.96–0.99; p < 0.001), increased BRFS (HR 0.993, 95%CI 0.99–1.00; p = 0.027) and increased OS (HR 0.969, 95%CI 0.95–0.99; p = 0.002), indicating a relative risk reduction of 2.4% for MFS, 0.7% for BRFS and 3.1% for OS per 1-point increase of baseline GHS. Baseline HRQOL improved discrimination in predicting MFS, BRFS and OS. DCA revealed a net benefit over all threshold probabilities. Conclusions: We found baseline HRQOL to substantially improve risk stratification for the heterogeneous cohort of IR-PCa. Baseline HRQOL accurately predicts increased MFS, BRFS and OS. Our findings therefore support the role of preoperative HRQOL as an adjunct to established prognosticators for IR-PCa, potentially facilitating guidance of therapy. [ABSTRACT FROM AUTHOR]

In mean-variance portfolio optimization, multi-index models often accelerate computation, reduce input requirements, facilitate understanding, and allow easy adjustment to changing conditions more effectively than full covariance matrix estimation in many situations. In this paper, we develop a multi-index model-based portfolio optimization approach that takes into account aspects of the environment, social responsibility and corporate governance (ESG). Investments in assets related to ESG have recently grown, attracting interest from both academic research and investment fund practice. Various literature strands in this area address the theoretical and empirical relation among return, risk and ESG. Our portfolio optimization approach is flexible enough to take these literature strands into account and does not require large-scale covariance matrix estimation. An extension of our approach even allows investors to empirically discriminate among the literature strands. A case study demonstrates the application of our portfolio optimization approach. [ABSTRACT FROM AUTHOR]

Prior studies have shown strong genetic effects on cortical thickness (CT), structural covariance, and neurodevelopmental trajectories in childhood and adolescence. However, the importance of genetic factors on the induction of spatiotemporal variation during neurodevelopment remains poorly understood. Here, we explore the genetics of maturational coupling by examining 308 MRI-derived regional CT measures in a longitudinal sample of 677 twins and family members. We find dynamic inter-regional genetic covariation in youth, with the emergence of regional subnetworks in late childhood and early adolescence. Three critical neurodevelopmental epochs in genetically-mediated maturational coupling were identified, with dramatic network strengthening near eleven years of age. These changes are associated with statistically-significant (empirical p-value <0.0001) increases in network strength as measured by average clustering coefficient and assortativity. We then identify genes from the Allen Human Brain Atlas with similar co-expression patterns to genetically-mediated structural covariation in children. This set was enriched for genes involved in potassium transport and dendrite formation. Genetically-mediated CT-CT covariance was also strongly correlated with expression patterns for genes located in cells of neuronal origin.Schmitt et al. studied the genetics of maturational coupling via longitudinal models of cortical thickness in N=677. Genetic correlations were dynamic. Patterns resembled expression of genes associated with potassium channels and dendrite formation. [ABSTRACT FROM AUTHOR]

Introduction: Evidence from Asian studies suggests that minimally-invasive gastrectomy achieves equivalent oncological but improved perioperative outcomes compared to open surgery. Oncological gastric resections are less frequent in European countries. Index procedures may play a role for the learning curve of minimally-invasive gastrectomy. The aim of our study was to evaluate if skills acquired in bariatric surgery allow a safe and oncologically adequate implementation of minimally-invasive gastrectomy in a cohort of european patients. Methods: In this single-center retrospective study, all patients who received primary bariatric surgery between January 2015 and December 2018 and minimally-invasive surgery for gastric cancer treated from June 2019 to January 2023 were evaluated. Primary endpoints were operation time, lymph node yield and lymph node fractions. Secondary endpoints included postoperative complications and oncological outcomes. Results: Learning curves for two surgeons with 350 bariatric procedures and 44 minimally-invasive gastrectomies were analyzed. For bariatric surgery, the mean operation time decreased from initially 82 ± 27 to 45 ± 21 min and 118 ± 28 to 81 ± 36 min for sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB), while the complication rate remained within the international benchmark. For laparoscopic gastrectomy (n = 30), operation times decreased but then remained stable over time. Operation times for the robotic platform were longer (302 ± 60 vs. 390 ± 48 min; p < 0.001) with the learning curve remaining incomplete after 14 procedures. R0 status was achieved in 95.5% of patients; the mean number of lymph nodes retrieved was 37 ± 14 with no differences between the groups. Complete mesogastric excision was more frequently achieved during the later laparoscopic cases whereas it occurred earlier for the robotic group (p = 0.004). Perioperative morbidity was comparable to the European benchmark. Textbook outcome was achieved in 54.4% of the cases. Conclusion: In summary, we could demonstrate a successful skill transfer from bariatric surgery to minimally-invasive laparoscopic oncological gastric surgery enabling safe and oncologically adequate minimally-invasive D2 gastrectomy in a central European patient collective. [ABSTRACT FROM AUTHOR]

Quantum computing is a rapidly evolving computational means that offers significant speedups for a variety of scientific applications, including machine learning, unsorted database queries, cryptography, and number factorization. Quantum computing holds a significant advantage in its capacity to run quantum algorithms that surpass current classical computer algorithms. However, practical realization of quantum computers remains in its nascent stages, necessitating reliance on classical computation platforms for simulating quantum circuit behavior and developing quantum algorithms. Simulating quantum algorithms presents a formidable challenge due to exponential memory and computation resource demands. In this study, we introduce a novel approach to optimize computational workload distribution during simulation by leveraging Dynamic Load Partitioning (DLP) between host CPUs and GPUs, with the primary aim of reducing resource and computation time requirements. Our method employs a hybrid CPU-GPU platform that divides quantum circuit simulation into two sections, utilizing parallel vector and recursive methods. We conducted our experiments on a cluster of nodes with multiple GPUs to scale qubit simulation and achieve significant speedup over existing simulators. Specifically, our approach demonstrates a remarkable 96X speedup over recursive path-summing on a single GPU and 12.98X speedup over the latest implementation on a multi-node cluster system. Furthermore, our method exhibits energy efficiency, surpassing the state-of-the-art technique by a 55X improvement. These results underscore the effectiveness of the proposed method, especially in leveraging low-cost systems for simulating and processing quantum circuits. [ABSTRACT FROM AUTHOR]

Autoimmune cerebellar ataxia (ACA) is a condition characterized by progressive ataxia resulting from an immune-mediated attack on cerebellar structures. The presence of anti-Tr/DNER antibodies, strongly associated with Hodgkin lymphoma, has been identified in ACA. However, cases with no underlying malignancy are rare. We report the case of a 49-year-old woman presenting with progressive ataxia, slurred speech, and dizziness over three months. The patient exhibited significant cerebellar symptoms, including dysarthria and limb ataxia, without signs of other systemic illnesses. Comprehensive investigations, including imaging, lumbar puncture, and autoantibody testing, were performed. The cerebrospinal fluid (CSF) sample revealed positivity for Tr/DNER antibodies, leading to a diagnosis of autoimmune cerebellar ataxia. The patient underwent nine sessions of plasmapheresis, followed by six doses of intravenous immunoglobulin (IVIG), resulting in significant clinical improvement. Despite extensive cancer screening, no underlying malignancy was detected, suggesting a non-tumor origin of anti-Tr/DNER antibodies. The patient's gait improved, ataxia resolved, and cerebellar tests normalized following treatment. The patient was further managed with rituximab treatment every six months. This case represents a presentation of anti-Tr/DNER-associated autoimmune cerebellar ataxia without malignancy. The successful treatment with plasmapheresis and IVIG suggests that these interventions may be effective in managing autoimmune cerebellar ataxia associated with anti-Tr/DNER antibodies. Further research is needed to understand the underlying mechanisms of this condition and to determine the optimal treatment strategies. [ABSTRACT FROM AUTHOR]

The potential of tasks to foster mathematical learning and understanding is an important aspect of instruction and their implementation in teaching is thus often viewed to be positively related to the quality of instruction. Both the selection of tasks as well as their implementation in the classroom depend on many factors, with teachers' knowledge and skills as one of the most important ones. The present study aims to analyze the relations between different aspects of task potential, the quality of instruction, and teachers' competence in order to investigate whether task potential can be seen as an indicator for teaching quality, for teacher competence, or as an independent construct in models of educational effectiveness. To this end, we draw on data from the TEDS-Validate study, namely tests of mathematics teachers' competence (n = 31) observations in their classrooms (n = 60), and an in-depth analysis of all tasks used in the respective lessons (n = 2490). Multiple regression analysis suggests that while some facets of task potential are related to either teaching quality or teacher competence, the potential of tasks emerges as an independent construct with some characteristics predicting the teaching quality of the respective lessons. Implications of these results for the role of tasks in educational effectiveness research are discussed. [ABSTRACT FROM AUTHOR]

In educational research, teaching quality is extensively studied because of its role of a mediator between teacher characteristics and student learning. However, empirical evidence on differences between video and live scoring of teaching quality is rare. In the present study, thirty lessons from 15 secondary mathematics classrooms in a German metropolitan area were observed. Lessons were scored both live in the classroom and using video recordings. Live and video scoring was conducted by (different) trained observers. Ratings were obtained with a "hybrid" observational instrument that covers generic and subject-specific characteristics of teaching quality in mathematics classrooms. Generalizability analysis and paired t tests were performed to investigate mode effects. The findings showed that in live scoring, classroom management was rated lower, and cognitive activation was rated higher. Rankings of lessons or classrooms were very similar across modes, and reliabilities did not differ to a meaningful extent either, except for classroom management reaching better results for live ratings. This suggests that based on the present findings, classroom observation performed with our hybrid framework of teaching quality generalizes across observation mode only under certain circumstances. Further research is necessary to better understand the relation between observation mode and teaching quality ratings, as well as the impact of the scoring procedures. We discuss the implications of our findings for educational research and practice. [ABSTRACT FROM AUTHOR]

Background: Do different genetic disorders impart different psychiatric risk profiles? This question has major implications for biological and translational aspects of psychiatry, but has been difficult to tackle given limited access to shared batteries of fine-grained clinical data across genetic disorders. Methods: Using a new suite of generalizable analytic approaches, we examine gold-standard diagnostic ratings, scores on 66 dimensional measures of psychopathology, and measures of cognition and functioning in two different sex chromosome aneuploidies (SCAs)—Klinefelter (XXY/KS) and XYY syndrome (n = 102 and 64 vs. n = 74 and 60 matched XY controls, total n = 300). We focus on SCAs for their high collective prevalence, informativeness regarding differential X- vs. Y-chromosome effects, and potential relevance for normative sex differences. Results: We show that XXY/KS elevates rates for most psychiatric diagnoses as previously reported for XYY, but disproportionately so for anxiety disorders. Fine-mapping across all 66 traits provides a detailed profile of psychopathology in XXY/KS which is strongly correlated with that of XYY (r =.75 across traits) and robust to ascertainment biases, but reveals: (i) a greater penetrance of XYY than KS/XXY for most traits except mood/anxiety problems, and (ii) a disproportionate impact of XYY vs. XXY/KS on social problems. XXY/KS and XYY showed a similar coupling of psychopathology with adaptive function and caregiver strain, but not IQ. Conclusions: This work provides new tools for deep-phenotypic comparisons of genetic disorders in psychiatry and uses these to detail unique and shared effects of the X- and Y-chromosome on human behavior. [ABSTRACT FROM AUTHOR]

Background: Post-operative atrial fibrillation (POAF) is associated with adverse long-term cardiovascular events. Objectives: This study investigated the effects of a high-dose vitamin D administered preoperatively on the postoperative atrial fibrillation (POAF) incidence in patients with vitamin D deficiency following coronary artery bypass grafting (CABG) surgery. Methods: This randomized controlled clinical trial was conducted on 246 CABG patients with vitamin D deficiency. All patients were randomly divided into intervention and control groups including 123 cases for each group. In the intervention group, from 3 days before surgery, they received a daily dose of 150,000 units of vitamin D orally (50,000 units of Vit D tablet three times a day) and the patients in the control group received placebo tablets before surgery. All patients in the intervention group were assessed continuously for the occurrence of POAF during the recovery period. Results: In terms of gender, age, and BMI there were no significant differences between intervention and control groups. Our findings showed that the use of vitamin D supplements did not cause a significant change in the duration of intubation and hospitalization. The ratio of POAF following CABG surgery in the control and treatment groups was 26% and 11.4%, respectively (odds ratio = 0.36; 95% CI = 0.18–0.72; P = 0.003). Conclusions: Our findings revealed that high-dose vitamin D supplementation before CABG surgery significantly reduced the incidence of POAF. Further multicenter randomized trials with larger sample sizes are certainly warranted to confirm our results. [ABSTRACT FROM AUTHOR]

Nanomedicine holds promise for potentiating drug combination therapies. Increasing (pre)clinical evidence is available exemplifying the value of co-formulating and co-delivering different drugs in modular nanocarriers. Taxanes like paclitaxel (PTX) are widely used anticancer agents, and commonly combined with corticosteroids like dexamethasone (DEX), which besides for suppressing inflammation and infusion reactions, are increasingly explored for modulating the tumor microenvironment towards enhanced nano-chemotherapy delivery and efficacy. We here set out to develop a size- and release rate-tunable polymeric micelle platform for co-delivery of taxanes and corticosteroids. We synthesized amphiphilic mPEG-b-p(HPMAm-Bz) block copolymers of various molecular weights and used them to prepare PTX and DEX single- and double-loaded micelles of different sizes. Both drugs could be efficiently co-encapsulated, and systematic comparison between single- and co-loaded formulations demonstrated comparable physicochemical properties, encapsulation efficiencies, and release profiles. Larger micelles showed slower drug release, and DEX release was always faster than PTX. The versatility of the platform was exemplified by co-encapsulating two additional taxane-corticosteroid combinations, demonstrating that drug hydrophobicity and molecular weight are key properties that strongly contribute to drug retention in micelles. Altogether, our work shows that mPEG-b-p(HPMAm-Bz) polymeric micelles serve as a tunable and versatile nanoparticle platform for controlled co-delivery of taxanes and corticosteroids, thereby paving the way for using these micelles as a modular carrier for multidrug nanomedicine. [ABSTRACT FROM AUTHOR]

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Introduction: Urethral strictures and fistulas arising after gender-affirming surgery in transmen require meticulous management strategies. This study evaluates the safety and efficacy of urethral reconstruction and patient satisfaction post-surgery. Methods: A retrospective analysis examined peri- and postoperative data from transmen undergoing urethral reconstruction for urethral fistula and/or strictures at the distal urethral anastomosis between December 2017 and April 2023. Follow-up involved clinical examinations, uroflowmetry, and voiding cystourethrography. Patient satisfaction and quality of life were assessed using USS PROM and ICIQ-S questionnaires. Results: Among 25 patients, 88% (n = 23) had urethral fistulas, and 48% (n = 12) had urethral strictures. 41% of fistula patients also had strictures, while 75% of stricture patients had concurrent fistulas. Previous surgeries for fistula or stricture repair were noted in 26% of cases. Techniques for stricture included modified flap (50%), buccal oral mucosal grafting (33%), and primary anastomosis (17%). Post-operative urethrogram revealed urethral strictures in 15% (n = 3) and urinary extravasation in an equal number. Postoperative uroflow parameters showed improvement (Qmax 18 ml/s, Qave 7.9 ml, time 37 s, volume 332 ml). Perioperative complications were low (n = 6, 24%), all grade one (Clavien-Dindo). Follow-up revealed that 33% required another surgical intervention. The mean six-item LUTS score was 6.7 (SD 3.9). Mean ICIQ-S overall satisfaction score was 8.6 (SD 1.6) and outcome score was 20 (SD 2.8). Discussion: Our study found a significant recurrence rate of urethral strictures and fistulas post-surgery. Despite this, patient satisfaction remains high and complications are generally low-grade, highlighting the importance of expert surgical intervention. [ABSTRACT FROM AUTHOR]

Humin-sulfuric acid (Humin-SO3H) as a novel efficient biobased sulfonic acid was easily prepared by adding chlorosulfuric acid (ClSO3H) to Humin and characterized by potentiometric titration and FT-IR spectrum. Humin-SO3H is an eco-friendly, heterogeneous biobased, and efficient catalyst for Paal-Knorr and Clauson-Kaas pyrrole synthesis. The catalyst is easily recovered by simple filtration and has excellent turnover efficiency even after 4 cycles. Besides, due to the clearance of the biocatalyst away from the reaction media, the desired highly pure products can be achieved in high to excellent yields. Due to high water dispersibility, Humin-SO3H can be utilized as a highly efficient green catalyst for pyrrole synthesis. [ABSTRACT FROM AUTHOR]

Visual working memory depends on both material-specific brain areas in the ventral visual stream (VVS) that support the maintenance of stimulus representations and on regions in the prefrontal cortex (PFC) that control these representations. How executive control prioritizes working memory contents and whether this affects their representational formats remains an open question, however. Here, we analyzed intracranial EEG (iEEG) recordings in epilepsy patients with electrodes in VVS and PFC who performed a multi-item working memory task involving a retro-cue. We employed Representational Similarity Analysis (RSA) with various Deep Neural Network (DNN) architectures to investigate the representational format of prioritized VWM content. While recurrent DNN representations matched PFC representations in the beta band (15–29 Hz) following the retro-cue, they corresponded to VVS representations in a lower frequency range (3–14 Hz) towards the end of the maintenance period. Our findings highlight the distinct coding schemes and representational formats of prioritized content in VVS and PFC. How prioritization affects the format of visual working memory representations is currently not understood. Analyzing iEEG recordings in epilepsy patients, the authors demonstrate the critical role of recurrent computations and beta frequency oscillations during the selective attention to particular visual working memory content in the PFC. [ABSTRACT FROM AUTHOR]

Large biobanks have dramatically advanced our understanding of genetic influences on human brain anatomy. However, most studies have combined rather than compared male and female participants. Here we screen for sex differences in the common genetic architecture of over 1000 neuroanatomical phenotypes in the UK Biobank and establish a general concordance between male and female participants in heritability estimates, genetic correlations, and variant-level effects. Notable exceptions include higher mean heritability in the female group for regional volume and surface area phenotypes; between-sex genetic correlations that are significantly below 1 in the insula and parietal cortex; and a common variant with stronger effect in male participants mapping to RBFOX1 - a gene linked to multiple neuropsychiatric disorders more common in men. This work suggests that common variant influences on human brain anatomy are largely consistent between males and females, with a few exceptions that will guide future research in growing datasets. Here, the authors screen for sex differences in the common genetic architecture of over 1000 neuroanatomical phenotypes, showing overall concordance between female and male individuals. [ABSTRACT FROM AUTHOR]

Borna disease virus 1 (BoDV-1) is the causative agent of Borna disease, a fatal neurologic disorder of domestic mammals and humans, resulting from spill-over infection from its natural reservoir host, the bicolored white-toothed shrew (Crocidura leucodon). The known BoDV-1-endemic area is remarkably restricted to parts of Germany, Austria, Switzerland and Liechtenstein. To gain comprehensive data on its occurrence, we analysed diagnostic material from suspected BoDV-1-induced encephalitis cases based on clinical and/or histopathological diagnosis. BoDV-1 infection was confirmed by RT-qPCR in 207 domestic mammals, 28 humans and seven wild shrews. Thereby, this study markedly raises the number of published laboratory-confirmed human BoDV-1 infections and provides a first comprehensive summary. Generation of 136 new BoDV-1 genome sequences from animals and humans facilitated an in-depth phylogeographic analysis, allowing for the definition of risk areas for zoonotic BoDV-1 transmission and facilitating the assessment of geographical infection sources. Consistent with the low mobility of its reservoir host, BoDV-1 sequences showed a remarkable geographic association, with individual phylogenetic clades occupying distinct areas. The closest genetic relatives of most human-derived BoDV-1 sequences were located at distances of less than 40 km, indicating that spill-over transmission from the natural reservoir usually occurs in the patient´s home region. Borna disease virus 1 (BoDV-1) is a zoonotic pathogen endemic in bicoloured white-toothed shrews in Central Europe that can cause fatal encephalitis in humans and other mammals. Here, the authors investigate the molecular epidemiology and phylogeography of BoDV-1 using newly collected and archived samples. [ABSTRACT FROM AUTHOR]