bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacokinetic Profile of Aripiprazole 2-Month Ready-to-Use 960 mg in Adult Patients With Schizophrenia or Bipolar I Disorder
Authors: Harlin Matthew , Yildirim Murat , Such Pedro , Madera-McDonough Jessica , Larsen Frank
Published: April 2023

Introduction

Aripiprazole 2-month ready-to-use 960 mg (Ari 2MRTU 960) is a new long-acting injectable (LAI) antipsychotic formulation for gluteal administration every 2 months, intended for the treatment of schizophrenia and maintenance monotherapy treatment of bipolar I disorder (BP-I). This 32-week trial evaluated the safety, tolerability, and pharmacokinetic profile of multiple-dose administration of Ari 2MRTU 960 in clinically stable adult patients with a diagnosis of schizophrenia or BP-I, versus that of aripiprazole once-monthly 400 mg (AOM 400; an LAI indicated for the treatment of schizophrenia and maintenance monotherapy treatment of BP-I).

Methods

This was an open-label, multiple-dose, randomized, parallel-arm trial conducted at 16 sites in the US. Patients were randomized to receive Ari 2MRTU 960 every 56±2 days (n=132) or AOM 400 every 28±2 days (n=134). The primary objective was to establish the similarity of aripiprazole concentrations on the last day of the dosing interval, as well as exposure during the dosing interval (area under the concentration-time curve [AUC]), between Ari 2MRTU 960 and AOM 400 following multiple doses. It was pre-specified that the lower bound of the 90% confidence interval (CI) of the geometric means ratio (GMR) for these parameters must be >0.8.

Results

In the Ari 2MRTU 960 group, 102 patients (77.3%) completed the study; in the AOM 400 group, 92 patients (68.7%) completed the study. The GMR of C56 for Ari 2MRTU 960 to C28 for AOM 400 was 1.011 (90% CI: 0.893, 1.145). The GMR (90% CI) of AUC0–56 for Ari 2MRTU 960 to AUC0–28 for AOM 400 was 1.006 (90% CI: 0.851, 1.190). Mean (standard deviation) maximum aripiprazole plasma concentration was 342 (157) ng/ml after the fourth Ari 2MRTU 960 dose and 344 (212) ng/ml after the eighth AOM 400 dose.

Conclusion

Pharmacokinetic parameters were similar between Ari 2MRTU 960 and AOM 400.

Funding

Otsuka Pharmaceutical Development & Commercialization, Inc. (Princeton, NJ, USA) and H. Lundbeck A/S (Valby, Denmark).
The Bitter Touch: Acquired Tactile-Gustatory Synesthesia
Authors: Sadana Sabina , Ratra Raunaq Singh , Kainth Harman , Nijhar Pukhraj Singh , Sahni Manmeet Singh , Hirsch Alan
Published: April 2023

Introduction

Gustatory sensation in response to tactile stimulation has been reported to occur in only 0.6% of synesthetes and has rarely been formally described.

Methods

Case Study: A 29-year-old female with schizoaffective disorder – depressed subtype, two months prior to presentation, began noticing that when she touched objects, she would experience an abnormal taste in her mouth. When she would touch specific items with her fingertips, for instance wood, bedsheets, tables, cups, plates, silverware, metal, trash cans, and toothpaste would induce a bitter taste. Touching wood caused the most intense bitter taste. Touching glass did not precipitate a taste.

Results

Mental Status Examination: Disheveled and guarded with minimal eye contact. Anxious and agitated. She believes people are stalking her and that cell phones, radios, and computers emit radiation which makes her head burn as if it is on fire. She perceived that inanimate objects, such as furniture, were staring at her. Other: CT scan of brain with and without contrast: normal.

Discussion

This could be due to neural overactivation between brain regions due to a neighborhood effect, with cross-firing of connecting fibers. The cortical taste area of the brain lies within the Brodmann area 43 of the parietal lobe which includes the pre- as well as post-central gyri extending into the parietal operculum. Brodmann areas 3, 1, and 2 in the postcentral gyrus is where the primary sensation for touch is mediated. The stimulation in adjacent and overlapping anatomical structures may be explained by ephaptic transmission with firing of one causing discharge of the second, yclept the adjacency principle.This co-localization hypothesis is further supported by the occurrence of pathological state of seizures which manifest both tactile and gustatory sensation. Such a hypothesis would be supported by Anderson’s 1886 observation discussing a peculiar sensation in the right arm and hand elicited concurrently with a bitter sensation in the mouth. Through an overflow phenomenon, touch may induce a diffuse serotonergic discharge to more remote regions of the brain that may mediate their functions through serotonin, such as taste. Possibly, other pathology may be invoked to explain this synesthesia. A deprived sensory system may be hyper-receptive to stray or overflow of sensations which are then interpreted within the sensorily deprived sensory system, as in Charles Bonnet syndrome. In the chemosensory sphere, sensory deprivation is associated with chemosensory hallucinations. If the patient manifests gustatory deficit, it may have predisposed her to sensitivity to such stray or overflowing sensory stimulus from touch manifesting as gustation. In those who present with synesthesia, investigation of pathology in the sensory system of the receiving concurrent sensation is warranted.

Funding

No Funding
Impact of AXS-05 (DEXTROMETHORPHAN-BUPROPION), an Oral NMDA Receptor Antagonist, on Anhedonic Symptoms in Major Depressive Disorder
Authors: Jones Amanda , McIntyre Roger S. , Jacobsen Mark , Streicher Caroline , Thomas Zachariah , Tabuteau Herriot
Published: April 2023

Background

Treatments for MDD that can improve both overall depressive and anhedonic symptoms are urgently needed.

AXS-05 (dextromethorphan-bupropion) is a novel, oral, investigational NMDA receptor antagonist with multimodal activity being developed for MDD. The dextromethorphan component of AXS-05 is an NMDA receptor antagonist and a sigma-1 receptor agonist. The bupropion component of AXS-05 serves primarily to increase the bioavailability of dextromethorphan.

Objective

To evaluate the effect of AXS-05 in improving anhedonic symptoms in MDD.

Methods

GEMINI (N=327) was a randomized, double-blind, placebo-controlled, 6-week study, which randomized adults with MDD to AXS-05 (dextromethorphan HBr 45 mg- bupropion HCl 105 mg) or placebo, twice daily. The primary endpoint was change from baseline in the MADRS total score at Week 6. A post-hoc analysis was conducted to determine the impact of AXS-05 versus placebo on the 5-item MADRS anhedonia subscale (MAS).

Results

Baseline MAS scores were 19.8 and 19.6 in the AXS-05 and placebo group, respectively. At Week 1, AXS-05 treatment resulted in a significant mean reduction from baseline in the MAS score of 4.44 versus 2.69 points for placebo (p< 0.001). At Week 6, the mean reduction from baseline in the MAS was 9.70 for AXS-05 compared to 7.22 for placebo (p=0.001). Response rates (≥ 50% MAS improvement) were significantly greater for AXS-05 compared to placebo at Week 1 (p< 0.001) and at every time point thereafter.

Treatment with AXS-05 was generally safe and well tolerated. The most common adverse events being dizziness, nausea, headache, diarrhea, somnolence, and dry mouth.

Conclusions

Treatment with AXS-05 rapidly and significantly reduced anhedonic symptoms as well as overall depressive symptoms.

Funding

Axsome Therapeutics
Candidates, voters, and voting advice applications
Authors: Tromborg Mathias Wessel , Albertsen Andreas
Published: April 2023

Voters often face a complex information environment with many options when they vote in elections. Research on democratic representation has traditionally been skeptical about voters’ ability to navigate this complexity. However, voting advice applications (VAAs) offer voters a shortcut to compare their own preferences across numerous issues with those of a large number of political candidates. As VAAs become more prevalent, it is critical to understand whether and how voters use them when they vote. We analyze how VAA users process and use VAA information about their district candidates with original survey data from the 2019 Danish parliamentary election in collaboration with the administrators of one of the most widely used Danish VAAs. The results demonstrate that VAAs have substantively large effects on their users’ choices between parties and between candidates within parties.
Modulation of Energetic Electron Precipitation Driven by Three Types of Whistler Mode Waves
Authors: Shen Xiao‐Chen , Li Wen , Capannolo Luisa , Ma Qianli , Qin Murong , Artemyev Anton V. , Angelopoulos Vassilis , Zhang Xiao‐Jia , Huang Sheng
Published: April 2023

Precipitation into the Earth's atmosphere due to pitch angle scattering by plasma waves has been recognized as one of the major loss mechanisms for energetic electrons. In this study, we quantitatively evaluate their roles in precipitating electrons during a conjunction event with modulated electron precipitation observed at low altitudes by Electron Loss and Fields INvestigation and three types of whistler mode waves (hiss, plume hiss, and chorus) measured near the equator by Time History of Events and Macroscale Interactions during Substorms. Electron precipitation was observed from ∼50 keV to <1 MeV with a spatial modulation, suggested by a good correlation between L shell‐sorted precipitation fluxes and wave intensities. A quasi‐linear analysis supports the observed energy range of precipitation and the ratio of precipitating‐to‐trapped flux. Our findings reveal that the modulated energetic electron precipitation is driven by hiss, plume hiss, and chorus waves.
The Seasonal Cycle of the Eastern Boundary Currents of the North Atlantic Subtropical Gyre
Authors: Pérez‐Hernández M. D. , Hernández‐Guerra A. , Cana‐Cascallar L. , Arumí‐Planas C. , Caínzos V. , González‐Santana A. J. , Gutiérrez‐Guerra M. Á. , Martínez‐Marrero A. , Mosquera Giménez Á. , Presas Navarro C. , Santana‐Toscano D. , Vélez‐Belchí P.
Published: April 2023

For the first time, four dedicated hydrographic cruises—one in each season—took place in 2015 around the Canary Islands to determine the seasonality of the flows at the eastern boundary of the North Atlantic Subtropical Gyre. The Canary Current (CC) is the eastern boundary current of the North Atlantic Subtropical Gyre and links the Azores Current with the North Equatorial Current. The 2015 estimations show that the CC has a seasonal behavior in its path and strength, flowing on its easternmost position in winter (3.4 ± 0.3 Sv), through the Canary Islands in spring (2.1 ± 0.7 Sv) and summer (2.0 ± 0.6 Sv) and on its westernmost position in fall (3.2 ± 0.4 Sv). At the Lanzarote Passage (LP), the dominant flow is southward except in fall, where a northward transport is observed at the surface (1.1 ± 0.3 Sv) and intermediate (1.3 ± 0.2 Sv) layers. Combining all the available transport estimations, a historical composite observational seasonal cycle is constructed which fits the 2015 seasonal cycle. Hence, a solid seasonal cycle is constructed supported by all the available observations in the area. The LP seasonal cycle and its seasonal amplitude match the seasonal cycle and amplitude of the Atlantic Meridional Overturning Circulation (AMOC) measured by the RAPID‐MOCHA data array. These results indicate that the seasonal cycle of the AMOC of the RAPID‐MOCHA data array is driven by the dynamics of the eastern boundary current system.
Water Age Dynamics in Plant Transpiration: The Effects of Climate Patterns and Rooting Depth
Authors: Luo Zidong , Nie Yunpeng , Chen Hongsong , Guan Huade , Zhang Xinping , Wang Kelin
Published: April 2023

Water ages in plant transpiration reveal important processes of water dynamics in soil‐plant‐atmosphere continuum, which is regulated by water variability and availability in both precipitation inputs and root zone. However, the impacts of climate patterns and rooting depth on water age dynamics in transpiration are inadequately investigated. In this study, variations in root‐zone water replenishment are estimated based on stable isotope compositions of precipitation and plant xylem water, and a piecewise linear mixing water age model is employed to quantify water ages in plant transpiration under five different climates. The results show that water ages in transpiration are very dynamic in all climates with a range between 1 and 229 days. Water replenishments in the root‐zone reveal whether and how much precipitation enters the root zone. Climate patterns control median (mean) water age in plant transpiration but modified by rooting depth. In wet climates, plants mainly rely on water source that originates from precipitation in the current month (accounting for about 60% on average of their water sources), while plants in dry climates largely rely on water source that originates from precipitation fallen on previous months/seasons. These indicate that climate has profound impacts on plant water source by regulating precipitation inputs, root zone water storage and residence time, and evapotranspiration. Despite the limitations of this study, our study provides an alternative way to reveal the precipitation partitioning in root‐zone and seasonal changes in plant water use of precipitation, which highlights different vegetation responses to water variability between climate types.
Urban Surface Thermal Runoff Generation Mechanism and Scenario Simulation
Authors: Luo Yi , Zhang Yang , Yang Kun , Zhou Xiaolu , Peng Zongqi
Published: April 2023

When precipitation happens in summer, the thermal runoff from impervious surfaces flow into urban lakes, causing the rise of the surface water temperature. Such a process eventually leads to the short‐term effects of cyanobacteria blooms in eutrophic lakes and the long‐term effects of changes in the structure and quantity of lake species. It is of great scientific significance to understand the heat exchange process between surface air, underlying surface, and surface runoff and reveal the thermal runoff formation mechanism. In this study, the heat transfer models between land, surface‐air, and surface‐water were implemented, aiming to quantify the heating process of surface runoff caused by surface heat load under real conditions. The results show that the two established models can accurately simulate the heat exchange process. Based on our model simulations and field measurements, we analyzed the impact of weather conditions, hydrological conditions, and underlying surface types on runoff temperature. The study finds that the initial surface temperature, wind speed, rainfall intensity, thermal conductivity, and the underlying surface's water permeability can explain 95.4% and 91.9% of the observed differences in surface runoff heating and temperature increase rate, respectively. The initial surface temperature is the most critical factor in the heat exchange process. The reduction of urban ventilation will aggravate the heat effect of surface runoff. Compared with the underlying permeable surface, the impervious surface is the main driving force for the formation of surface thermal runoff pollution.
How can general dental practitioners help in the management of sleep apnoea?
Authors: Parmenter David , Millar Brian J.
Published: April 2023

This article discusses the aetiology, prevalence and treatment of obstructive sleep apnoea (OSA) and highlights the important role general dental practitioners can perform in improving the quality of life of patients suffering from OSA. Clinical and laboratory stages of making a mandibular advancement appliance are also highlighted.

Members of the dental team have a duty of care to our patients. The earlier undiagnosed cases of OSA are referred for treatment, the less morbidity and potential mortality endured by patients.

After reading this article, the reader should have a greater understanding of OSA, how to identify symptoms of the condition in patients and be confident in referring patients to appropriate healthcare professionals.
Homogenous TP53mut-associated tumor biology across mutation and cancer types revealed by transcriptome analysis
Authors: Romanovsky Eva , Kluck Klaus , Ourailidis Iordanis , Menzel Michael , Beck Susanne , Ball Markus , Kazdal Daniel , Christopoulos Petros , Schirmacher Peter , Stiewe Thorsten , Stenzinger Albrecht , Budczies Jan
Published: April 2023

TP53 is the most frequently mutated gene in human cancer. While no TP53-targeting drugs have been approved in the USA or Europe so far, preclinical and clinical studies are underway to investigate targeting of specific or all TP53 mutations, for example, by restoration of the functionality of mutated TP53 (TP53mut) or protecting wildtype TP53 (TP53wt) from negative regulation. We performed a comprehensive mRNA expression analysis in 24 cancer types of TCGA to extract (i) a consensus expression signature shared across TP53 mutation types and cancer types, (ii) differential gene expression patterns between tumors harboring different TP53 mutation types such as loss of function, gain of function or dominant-negative mutations, and (iii) cancer-type-specific patterns of gene expression and immune infiltration. Analysis of mutational hotspots revealed both similarities across cancer types and cancer type-specific hotspots. Underlying ubiquitous and cancer type-specific mutational processes with the associated mutational signatures contributed to explaining this observation. Virtually no genes were differentially expressed between tumors harboring different TP53 mutation types, while hundreds of genes were over- and underexpressed in TP53mut compared to TP53wt tumors. A consensus list included 178 genes that were overexpressed and 32 genes that were underexpressed in the TP53mut tumors of at least 16 of the investigated 24 cancer types. In an association analysis of immune infiltration with TP53 mutations in 32 cancer subtypes, decreased immune infiltration was observed in six subtypes, increased infiltration in two subtypes, a mixed pattern of decreased and increased immune cell populations in four subtypes, while immune infiltration was not associated with TP53 status in 20 subtypes. The analysis of a large cohort of human tumors complements results from experimental studies and supports the view that TP53 mutations should be further evaluated as predictive markers for immunotherapy and targeted therapies.
Bi-terminal fusion of intrinsically-disordered mussel foot protein fragments boosts mechanical strength for protein fibers
Authors: Li Jingyao , Jiang Bojing , Chang Xinyuan , Yu Han , Han Yichao , Zhang Fuzhong
Published: April 2023

Microbially-synthesized protein-based materials are attractive replacements for petroleum-derived synthetic polymers. However, the high molecular weight, high repetitiveness, and highly-biased amino acid composition of high-performance protein-based materials have restricted their production and widespread use. Here we present a general strategy for enhancing both strength and toughness of low-molecular-weight protein-based materials by fusing intrinsically-disordered mussel foot protein fragments to their termini, thereby promoting end-to-end protein-protein interactions. We demonstrate that fibers of a ~60 kDa bi-terminally fused amyloid-silk protein exhibit ultimate tensile strength up to 481 ± 31 MPa and toughness of 179 ± 39 MJ*m−3, while achieving a high titer of 8.0 ± 0.70 g/L by bioreactor production. We show that bi-terminal fusion of Mfp5 fragments significantly enhances the alignment of β-nanocrystals, and intermolecular interactions are promoted by cation-π and π-π interactions between terminal fragments. Our approach highlights the advantage of self-interacting intrinsically-disordered proteins in enhancing material mechanical properties and can be applied to a wide range of protein-based materials.
Centennial scale sequences of environmental deterioration preceded the end-Permian mass extinction
Authors: Saito Ryosuke , Wörmer Lars , Taubner Heidi , Kaiho Kunio , Takahashi Satoshi , Tian Li , Ikeda Masayuki , Summons Roger E. , Hinrichs Kai-Uwe
Published: April 2023

The exact drivers for the end-Permian mass extinction (EPME) remain controversial. Here we focus on a ~10,000 yr record from the marine type section at Meishan, China, preceding and covering the onset of the EPME. Analyses of polyaromatic hydrocarbons at sampling intervals representing 1.5–6.3 yr reveal recurrent pulses of wildfires in the terrestrial realm. Massive input pulses of soil-derived organic matter and clastic materials into the oceans are indicated by patterns of C2-dibenzofuran, C30 hopane and aluminum. Importantly, in the ~2,000 years preceding the main phase of the EPME, we observe a clearly defined sequence of wildfires, soil weathering, and euxinia provoked by the fertilization of the marine environment with soil-derived nutrients. Euxinia is indicated by sulfur and iron concentrations. Our study suggests that, in South China, centennial scale processes led to a collapse of the terrestrial ecosystem ~300 yr (120–480 yr; ± 2 s.d.) before the onset of the EPME and that this collapse induced euxinic conditions in the ocean, ultimately resulting in the demise of marine ecosystems.
SynDLP is a dynamin-like protein of Synechocystis sp. PCC 6803 with eukaryotic features
Authors: Gewehr Lucas , Junglas Benedikt , Jilly Ruven , Franz Johannes , Zhu Wenyu Eva , Weidner Tobias , Bonn Mischa , Sachse Carsten , Schneider Dirk
Published: April 2023

Dynamin-like proteins are membrane remodeling GTPases with well-understood functions in eukaryotic cells. However, bacterial dynamin-like proteins are still poorly investigated. SynDLP, the dynamin-like protein of the cyanobacterium Synechocystis sp. PCC 6803, forms ordered oligomers in solution. The 3.7 Å resolution cryo-EM structure of SynDLP oligomers reveals the presence of oligomeric stalk interfaces typical for eukaryotic dynamin-like proteins. The bundle signaling element domain shows distinct features, such as an intramolecular disulfide bridge that affects the GTPase activity, or an expanded intermolecular interface with the GTPase domain. In addition to typical GD-GD contacts, such atypical GTPase domain interfaces might be a GTPase activity regulating tool in oligomerized SynDLP. Furthermore, we show that SynDLP interacts with and intercalates into membranes containing negatively charged thylakoid membrane lipids independent of nucleotides. The structural characteristics of SynDLP oligomers suggest it to be the closest known bacterial ancestor of eukaryotic dynamin.
Homology directed telomere clustering, ultrabright telomere formation and nuclear envelope rupture in cells lacking TRF2B and RAP1
Authors: Rai Rekha , Biju Kevin , Sun Wenqi , Sodeinde Tori , Al-Hiyasat Amer , Morgan Jaida , Ye Xianwen , Li Xueqing , Chen Yong , Chang Sandy
Published: April 2023

Double-strand breaks (DSBs) due to genotoxic stress represent potential threats to genome stability. Dysfunctional telomeres are recognized as DSBs and are repaired by distinct DNA repair mechanisms. RAP1 and TRF2 are telomere binding proteins essential to protect telomeres from engaging in homology directed repair (HDR), but how this occurs remains unclear. In this study, we examined how the basic domain of TRF2 (TRF2B) and RAP1 cooperate to repress HDR at telomeres. Telomeres lacking TRF2B and RAP1 cluster into structures termed ultrabright telomeres (UTs). HDR factors localize to UTs, and UT formation is abolished by RNaseH1, DDX21 and ADAR1p110, suggesting that they contain DNA-RNA hybrids. Interaction between the BRCT domain of RAP1 and KU70/KU80 is also required to repress UT formation. Expressing TRF2∆B in Rap1–/– cells resulted in aberrant lamin A localization in the nuclear envelope and dramatically increased UT formation. Expressing lamin A phosphomimetic mutants induced nuclear envelope rupturing and aberrant HDR-mediated UT formation. Our results highlight the importance of shelterin and proteins in the nuclear envelope in repressing aberrant telomere-telomere recombination to maintain telomere homeostasis.
A distributed and efficient population code of mixed selectivity neurons for flexible navigation decisions
Authors: Kira Shinichiro , Safaai Houman , Morcos Ari S. , Panzeri Stefano , Harvey Christopher D.
Published: April 2023

Decision-making requires flexibility to rapidly switch one’s actions in response to sensory stimuli depending on information stored in memory. We identified cortical areas and neural activity patterns underlying this flexibility during virtual navigation, where mice switched navigation toward or away from a visual cue depending on its match to a remembered cue. Optogenetics screening identified V1, posterior parietal cortex (PPC), and retrosplenial cortex (RSC) as necessary for accurate decisions. Calcium imaging revealed neurons that can mediate rapid navigation switches by encoding a mixture of a current and remembered visual cue. These mixed selectivity neurons emerged through task learning and predicted the mouse’s choices by forming efficient population codes before correct, but not incorrect, choices. They were distributed across posterior cortex, even V1, and were densest in RSC and sparsest in PPC. We propose flexibility in navigation decisions arises from neurons that mix visual and memory information within a visual-parietal-retrosplenial network.
Advancing research on compound weather and climate events via large ensemble model simulations
Authors: Bevacqua Emanuele , Suarez-Gutierrez Laura , Jézéquel Aglaé , Lehner Flavio , Vrac Mathieu , Yiou Pascal , Zscheischler Jakob
Published: April 2023

Societally relevant weather impacts typically result from compound events, which are rare combinations of weather and climate drivers. Focussing on four event types arising from different combinations of climate variables across space and time, here we illustrate that robust analyses of compound events — such as frequency and uncertainty analysis under present-day and future conditions, event attribution to climate change, and exploration of low-probability-high-impact events — require data with very large sample size. In particular, the required sample is much larger than that needed for analyses of univariate extremes. We demonstrate that Single Model Initial-condition Large Ensemble (SMILE) simulations from multiple climate models, which provide hundreds to thousands of years of weather conditions, are crucial for advancing our assessments of compound events and constructing robust model projections. Combining SMILEs with an improved physical understanding of compound events will ultimately provide practitioners and stakeholders with the best available information on climate risks.
Legionella para-effectors target chromatin and promote bacterial replication
Authors: Schator Daniel , Mondino Sonia , Berthelet Jérémy , Di Silvestre Cristina , Ben Assaya Mathilde , Rusniok Christophe , Rodrigues-Lima Fernando , Wehenkel Annemarie , Buchrieser Carmen , Rolando Monica
Published: April 2023

Legionella pneumophila replicates intracellularly by secreting effectors via a type IV secretion system. One of these effectors is a eukaryotic methyltransferase (RomA) that methylates K14 of histone H3 (H3K14me3) to counteract host immune responses. However, it is not known how L. pneumophila infection catalyses H3K14 methylation as this residue is usually acetylated. Here we show that L. pneumophila secretes a eukaryotic-like histone deacetylase (LphD) that specifically targets H3K14ac and works in synergy with RomA. Both effectors target host chromatin and bind the HBO1 histone acetyltransferase complex that acetylates H3K14. Full activity of RomA is dependent on the presence of LphD as H3K14 methylation levels are significantly decreased in a ∆lphD mutant. The dependency of these two chromatin-modifying effectors on each other is further substantiated by mutational and virulence assays revealing that the presence of only one of these two effectors impairs intracellular replication, while a double knockout (∆lphD∆romA) can restore intracellular replication. Uniquely, we present evidence for “para-effectors”, an effector pair, that actively and coordinately modify host histones to hijack the host response. The identification of epigenetic marks modulated by pathogens has the potential to lead to the development of innovative therapeutic strategies to counteract bacterial infection and strengthening host defences.
Big Field of View MRI T1w and FLAIR Template - NMRI225
Authors: Kreilkamp Barbara A. K. , Martin Pascal , Bender Benjamin , la Fougère Christian , van de Velden Daniel , Stier Christina , Ethofer Silke , Kotikalapudi Raviteja , Marquetand Justus , Rauf Erik H. , Loose Markus , Focke Niels K.
Published: April 2023

Image templates are a common tool for neuroscience research. Often, they are used for spatial normalization of magnetic resonance imaging (MRI) data, which is a necessary procedure for analyzing brain morphology and function via voxel-based analysis. This allows the researcher to reduce individual shape differences across images and make inferences across multiple subjects. Many templates have a small field-of-view typically focussed on the brain, limiting the use for applications requiring detailed information about other extra-cranial structures in the head and neck area. However, there are several applications where such information is important, for example source reconstruction of electroencephalography (EEG) and/or magnetoencephalography (MEG). We have constructed a new template based on 225 T1w and FLAIR images with a big field-of-view that can serve both as target for across subject spatial normalization as well as a basis to build high-resolution head models. This template is based on and iteratively re-registered to the MNI152 space to provide maximal compatibility with the most commonly used brain MRI template.
Afro-TB dataset as a large scale genomic data of Mycobacterium tuberuclosis in Africa
Authors: Laamarti Meriem , El Fathi Lalaoui Yasmine , Elfermi Rachid , Daoud Rachid , El Allali Achraf
Published: April 2023

Mycobacterium tuberculosis (MTB) is a pathogenic bacterium accountable for 10.6 million new infections with tuberculosis (TB) in 2021. The fact that the genetic sequences of M. tuberculosis vary widely provides a basis for understanding how this bacterium causes disease, how the immune system responds to it, how it has evolved over time, and how it is distributed geographically. However, despite extensive research efforts, the evolution and transmission of MTB in Africa remain poorly understood. In this study, we used 17,641 strains from 26 countries to create the first curated African Mycobacterium tuberculosis (MTB) classification and resistance dataset, containing 13,753 strains. We identified 157 mutations in 12 genes associated with resistance and additional new mutations potentially associated with resistance. The resistance profile was used to classify strains. We also performed a phylogenetic classification of each isolate and prepared the data in a format that can be used for phylogenetic and comparative analysis of tuberculosis worldwide. These genomic data will extend current information for comparative genomic studies to understand the mechanisms and evolution of MTB drug resistance.
ALAN is a computational approach that interprets genomic findings in the context of tumor ecosystems
Authors: Bergom Hannah E. , Shabaneh Ashraf , Day Abderrahman , Ali Atef , Boytim Ella , Tape Sydney , Lozada John R. , Shi Xiaolei , Kerkvliet Carlos Perez , McSweeney Sean , Pitzen Samuel P. , Ludwig Megan , Antonarakis Emmanuel S. , Drake Justin M. , Dehm Scott M. , Ryan Charles J. , Wang Jinhua , Hwang Justin
Published: April 2023

Gene behavior is governed by activity of other genes in an ecosystem as well as context-specific cues including cell type, microenvironment, and prior exposure to therapy. Here, we developed the Algorithm for Linking Activity Networks (ALAN) to compare gene behavior purely based on patient -omic data. The types of gene behaviors identifiable by ALAN include co-regulators of a signaling pathway, protein-protein interactions, or any set of genes that function similarly. ALAN identified direct protein-protein interactions in prostate cancer (AR, HOXB13, and FOXA1). We found differential and complex ALAN networks associated with the proto-oncogene MYC as prostate tumors develop and become metastatic, between different cancer types, and within cancer subtypes. We discovered that resistant genes in prostate cancer shared an ALAN ecosystem and activated similar oncogenic signaling pathways. Altogether, ALAN represents an informatics approach for developing gene signatures, identifying gene targets, and interpreting mechanisms of progression or therapy resistance.
Carbide-mediated catalytic hydrogenolysis: defects in graphene on a carbonaceous lithium host for liquid and all-solid-state lithium metal batteries
Authors: Kim Namhyung , Cha Hyungyeon , Chae Sujong , Lee Taeyong , Lee Yoonkwang , Kim Yujin , Sung Jaekyung , Cho Jaephil
Published: April 2023

Reaction pathway of isothermal growth of defective graphene shell on Fe catalyst by the carbide-mediated catalytic hydrogenolysis. This defective graphene shell promotes a reversible Li plating/stripping behavior.
A practical perspective on the potential of rechargeable Mg batteries
Authors: Blázquez J. Alberto , Maça Rudi R. , Leonet Olatz , Azaceta Eneko , Mukherjee Ayan , Zhao-Karger Zhirong , Li Zhenyou , Kovalevsky Aleksey , Fernández-Barquín Ana , Mainar Aroa R. , Jankowski Piotr , Rademacher Laurin , Dey Sunita , Dutton Siân E. , Grey Clare P. , Drews Janina , Häcker Joachim , Danner Timo , Latz Arnulf , Sotta Dane , Palacin M. Rosa , Martin Jean-Frédéric , Lastra Juan Maria García , Fichtner Maximilian , Kundu Sumana , Kraytsberg Alexander , Ein-Eli Yair , Noked Malachi , Aurbach Doron
Published: April 2023

Emerging energy storage systems based on abundant and cost-effective materials are key to overcome the global energy and climate crisis of the 21st century.
A minor metabolite fromCurcuma longaeffective against metabolic syndrome: results from a randomized, double-blind, placebo-controlled clinical study
Authors: Majeed Muhammed , Nagabhushanam Kalyanam , Devarajan T. V. , Saklecha Santhosh , Reddy S. Venkata Krishna , Mundkur Lakshmi
Published: April 2023

Randomized clinical trials show higher efficacy of Calebin A in managing metabolic syndrome in obese individuals.
The effects of pectin on the gut microbiota and serum metabolites in mice fed with a high fat diet and exposed to low-dose antibiotics
Authors: Xiao Qianhuang , Huang Wenqi , Wu Quanyong , Xu Hedi , Zhang Yanli , Yang Jingrui , Bian Shuigen , Tan Huizi , Nie Shaoping
Published: April 2023

Pectin with various esterification degrees showed differential effects on the metabolic disorder and inflammation induced by a long-term high-fat diet and low-dose antibiotic exposure, which were possibly related to the enrichment ofLactobacillus.
Facile engineering of resveratrol nanoparticles loaded with 20(S)-protopanaxadiol for the treatment of periodontitis by regulating the macrophage phenotype
Authors: Huangfu Huimin , Du Shulin , Zhang Hao , Wang Hanchi , Zhang Yi , Yang Zhen , Zhang Xinwei , Ren Sicong , Chen Siyu , Wang Cuizhu , Zhang Yidi , Zhou Yanmin
Published: April 2023

Scheme illustration of RES@PPD NPs in the principle of synthesis and therapeutic mechanism. RES@PPD NPs can treat periodontitis by promoting the polarization of macrophages from M1 to M2.
Non-destructive diagnostic testing of cardiac myxoma by serum confocal Raman microspectroscopy combined with multivariate analysis
Authors: Chen Qiang , Shi Tao , Du Dan , Wang Bo , Zhao Sha , Gao Yang , Wang Shuang , Zhang Zhanqin
Published: April 2023

An adjunct and promising tool for cardiac myxoma diagnosis is performed by Raman spectroscopy analysis combined with multivariate algorithms.
Chiral amplification induced by self-assembly of different aggregation states in liquid crystal block copolymer films with chiral response
Authors: Yuan Jianan , Lu Xuemin , He Xiaojie , Zheng Feng , Lu Qinghua
Published: April 2023

The gabs of the J-type stacking helix assembly induced by DiBTA was an order of magnitude larger than that of the H-type column assembly induced by DiBETA.
A novel bilayer heterogeneous poly(ionic liquid) electrolyte for high-performance flexible supercapacitors with ultraslow self-discharge
Authors: Dong Keyi , Liu Yanan , Chen Zilin , Lv Tian , Tang Weiyang , Cao Shaokui , Chen Tao
Published: April 2023

A novel bilayer heterogeneous poly(ionic liquid) electrolyte consisting of a polycation complex and a polyanion complex is designed for highly flexible supercapacitors, which exhibit a high working potential of 3.0 V, energy density of 33 W h kg−1and a long self-discharge time of 23.2 h.
Cyclization of N-Boc-(E)-α,β-unsaturated γ-amino acid active esters into N-Boc-(Z)-α,β-unsaturated γ-lactams through E → Z isomerization
Authors: Singh Manjeet , Kumar Manish , Nalawade Sachin A. , Puneeth Kumar DRGKoppalu R. , Gopi Hosahudya N.
Published: April 2023

A weak base mediated spontaneous transformation of the active esters of N-protected (E)-α,β-unsaturated γ-amino acids into N-protected (Z)-α,β-unsaturated γ-lactams is described.
Transgender Health Care Primer for Clinical Audiologists
Authors: Kirjava Shade Avery
Published: April 2023

Purpose:

Transgender people have been increasingly visible in society. Recent research has indicated that millions of Americans, 0.7% of the total population, identify as transgender. Although transgender people experience all the same auditory and vestibular disorders as people who are not transgender, there is a dearth of information about transgender issues in audiology graduate education and continuing education. The author discusses their positionality as a transgender audiologist and provides guidance on working with transgender patients from their experience and from the published literature.

Conclusion:

This tutorial provides an overview of transgender identity for clinical audiologists and summarizes the social, legal, and medical landscape of transgender identity as it relates to audiology.
Exploring the Clinical Feasibility of Alternative Word-Understanding Measures for Autistic Children With Minimal Spoken Language
Authors: Muller Kristen
Published: April 2023

Purpose:

The primary aim of this study was to explore the clinical feasibility of using alternate word-understanding assessment modalities for autistic children who have minimal verbal skills. Specifically, assessment duration, occurrence of disruptive behavior, and no-response trials were examined across three word-understanding assessment conditions: a low-tech condition, a touchscreen condition, and a condition that used real-object stimuli. A secondary aim was to examine the relationship between disruptive behavior and assessment outcomes.

Method:

Twenty-seven autistic children between the ages of 3 and 12 years who had minimal verbal skills completed 12 test items on the three assessment conditions. Repeated-measures analyses of variance with post hoc Bonferroni procedures were used to describe and compare assessment duration, occurrence of disruptive behavior, and no-response trials across conditions. A Spearman rank-order correlation coefficient was used to examine the relationship between disruptive behavior and assessment outcomes.

Results:

The real-object assessment condition took significantly longer than the low-tech and touchscreen conditions. Participants engaged in disruptive behavior most frequently during the low-tech condition; however, differences among conditions were not significant. There were significantly more no-response trials in the low-tech condition than in the touchscreen condition. There was a significant, weak negative correlation between disruptive behavior and experimental assessment outcomes.

Conclusion:

Results show there is promise in using real objects and touchscreen devices to assess word understanding in autistic children who have minimal verbal skills.
Crowdsourced Perceptual Ratings of Voice Quality in People With Parkinson's Disease Before and After Intensive Voice and Articulation Therapies: Secondary Outcome of a Randomized Controlled Trial
Authors: McAllister Tara , Nightingale Christopher , Moya-Galé Gemma , Kawamura Ava , Ramig Lorraine Olson
Published: April 2023

Purpose:

Limited research has examined the suitability of crowdsourced ratings to measure treatment effects in speakers with Parkinson's disease (PD), particularly for constructs such as voice quality. This study obtained measures of reliability and validity for crowdsourced listeners' ratings of voice quality in speech samples from a published study. We also investigated whether aggregated listener ratings would replicate the original study's findings of treatment effects based on the Acoustic Voice Quality Index (AVQI) measure.

Method:

This study reports a secondary outcome measure of a randomized controlled trial with speakers with dysarthria associated with PD, including two active comparators (Lee Silverman Voice Treatment [LSVT LOUD] and LSVT ARTIC), an inactive comparator (untreated PD), and a healthy control group. Speech samples from three time points (pretreatment, posttreatment, and 6-month follow-up) were presented in random order for rating as “typical” or “atypical” with respect to voice quality. Untrained listeners were recruited through the Amazon Mechanical Turk crowdsourcing platform until each sample had at least 25 ratings.

Results:

Intrarater reliability for tokens presented repeatedly was substantial (Cohen's κ = .65–.70), and interrater agreement significantly exceeded chance level. There was a significant correlation of moderate magnitude between the AVQI and the proportion of listeners classifying a given sample as “typical.” Consistent with the original study, we found a significant interaction between group and time point, with the LSVT LOUD group alone showing significantly higher perceptually rated voice quality at posttreatment and follow-up relative to the pretreatment time point.

Conclusions:

These results suggest that crowdsourcing can be a valid means to evaluate clinical speech samples, even for less familiar constructs such as voice quality. The findings also replicate the results of the study by Moya-Galé et al. (
2022
) and support their functional relevance by demonstrating that the effects of treatment measured acoustically in that study are perceptually apparent to everyday listeners.
Ergebnisse und Vergleich des Videotrainings mit dem Heimtraining
Authors: Haag Stefanie
Published: April 2023

Das Peritonealdialyse-Training (PD-Training) erfolgt traditionell im Dialysezentrum oder bei den Betroffenen zu Hause in Anwesenheit einer Pflegekraft. Zeit, Räumlichkeiten, die Dauer und Methodik können das Trainingsergebnis beeinflussen. Es erfolgte ein retrospektiver Vergleich zwischen einem Video- und einem Heimtraining. Untersucht wurden die Gesamtdauer, Anzahl der Hausbesuche, Verfahrenswechsel, Peritonitisrate und das Überleben der Technik zwischen der Heim- und Video-Trainings-Gruppe. Es zeigte sich, dass eine Videotraining genauso effektiv wie ein Heimtraining ist und niedrigere Peritonitisraten und Verfahrenswechsel aufweist.
Lebensqualität bei chronischer Niereninsuffizienz in Abhängigkeit von der Dialysemethode
Authors: Bartoldus Regina
Published: April 2023

Einerseits sichern eine Hämo- oder eine Peritonealdialyse das Überleben von Patienten mit einer chronischen Nierenerkrankung, andererseits beeinflussen diese Dialysemethoden die Lebensqualität der Betroffenen. Ziel dieser Studie ist es, die Auswirkungen der Hämo- und Peritonealdialyse auf die Lebensqualität von chronisch nierenkranken Menschen aufzuzeigen und Zusammenhänge bezüglich des Alters, Geschlechts und des Zeitraums der Dialysebehandlung zu untersuchen. Hierzu wurde ein quantitativ-deskriptives Studiendesign gewählt. Die Ergebnisse zeigen, dass die Lebensqualität von Menschen mit einer chronischen Niereninsuffizienz, die eine Peritonealdialyse durchführen, insgesamt signifikant höher ist als bei Personen, die einer Hämodialyse bedürfen. Im Gegensatz zum Status quo der Forschung konnte der Einfluss der Faktoren Alter, Geschlecht und Dauer der Behandlung auf die Lebensqualität nicht bestätigt werden. Die Studiendaten indizieren für die vermehrte Durchführung der Peritonealdialyse, da diese eine bessere Lebensqualität für die Betroffenen bietet.
Die vegetative Befunderhebung
Authors: Abend Annika
Published: April 2023

Vegetative Dysregulationen haben ein komplexes Erscheinungsbild. Infolgedessen
gestalten sich auch Erhebung und Beurteilung dieser Symptomatik
vielfältig. Wie Therapeuten dabei strukturiert vorgehen können
und was die Befundergebnisse für die anschließende Behandlung
bedeuten, verrät Physiotherapeutin Annika Abend.
Ohne Sauerstoff wird die Luft dünn – auch in der
Handrehabilitation
Authors: Dawils Michael
Published: April 2023

Unzureichende bzw. mangelhafte Bewegung, ein geblähter Bauch, zu vieles
Sitzen oder Stress sind beispielhafte Veränderungen, die sich auf
unterschiedlichen Ebenen umgehend auf die Atmung auswirken. Lesen Sie, wie diese
aussehen und welche Folgen für den Organismus möglich sind –
auch in Zusammenhang mit typischen Handpathologien. Erfahren Sie zudem, welche
Benefits gezielte Atemübungen in der Handtherapie haben und wie diese
aussehen können.
Integrative Medizin an den Beispielen Krankenhaus für Naturheilweisen (KfN) München und LIMed
Authors: Schmidt Robert
Published: April 2023

Der wichtigste Grundsatz der Integrativen Medizin ist die Verbindung der konventionellen ärztlichen Medizin und der ärztlichen Komplementärmedizin zu einem sinnvollen Gesamtkonzept. Ziel ist es, die individuell beste Therapie für die Patient*innen zu finden und Nebenwirkungen so weit wie möglich zu reduzieren. Entscheidender Faktor sind hier auch explizit die Patient*innen, die nach ausführlicher Aufklärung über alle zur Verfügung stehenden Therapieoptionen in die Lage versetzt werden sollen, aktiv und mitverantwortlich über ein medizinisches Gesamtkonzept für ihre Behandlung mitzuentscheiden. Der Beitrag stellt mit dem Krankenhaus für Naturheilweisen (KfN) in München und der Liste Integrative Medizin zwei Beispiele vor, die sich für die Verbindung von konventioneller und Komplementärmedizin in der Öffentlichkeit und in der Praxis starkmachen.
51. EDTNA/ERCA-Konferenz vom 14.–17.10.2023 in Vilinius (Litauen)
Authors: Nipshagen Sabine
Published: April 2023

Die Vorbereitungen für die diesjährige Konferenz laufen auf Hochtouren. Uns erwarten wieder interessante Vorträge und Workshops sowie ein gewinnbringender Austausch mit internationalen Kolleg*innen.