bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of Synthetic Modulator Enabling Long-Term Propagation and Neurogenesis of Human-Derived Neural Progenitor Cells
Authors: Liao Ceheng , Guan Ying , Zheng Jihui , Wang Xue , Wang Meixia , Zhu Zhouhai , Peng Qiyuan , Wang Hong-Hui , Li Meng
Published: May 2023

Neural progenitor cells (NPCs) are important cells for in vitro drug screening and the cell-based therapy for brain-related disorders, which requires well-defined and reproducible culture systems. Current strategy the use of protein growth factors presents challenges in terms of reproducibility and cost. In this study, we have developed a novel DNA-based modulator to regulate FGFR signaling of NPCs, enabling maintenance of the stemness over 50 passages and neurogenesis towards neurons. The DNA-based FGFR-agonist effectively promoted FGFR1 phosphorylation and activated the downstream ERK signaling pathway in FGFR1-positive cells. Using human embryonic stem cell lines, we differentiated them into NPCs and replaced basic fibroblast growth factor (bFGF) in the regulator culture medium with DNA-based FGFR-agonist for artificially elicited FGFR signaling. The results demonstrated that the FGFR-agonist could promote NPCs proliferation and neurosphere formation, recapitulating the function of bFGF. Notably, transcriptomic analysis revealed that FGFR-agonist could customize the stemness-associated transcription program, while decouples the neuronal differentiation program, highly resembling that the native ligand, bFGF. Moreover, our culture condition facilitated the successful propagation of NPCs for over 50 passages, while retaining their ability to efficiently differentiate into neurons. Overall, our approach provides a highly effective method for expanding NPCs, offering new opportunities for disease-in-dish research and drug screening for neural degeneration.
UBL3 Interacts with Alpha-synuclein in Cells and the Interaction is Downregulated by the EGFR Pathway Inhibitor Osimertinib
Authors: Chen Bin , Hasan Md. Mahmudul , Zhang Hengsen , Zhai Qing , Waliullah A.S.M. , Ping Yashuang , Zhang Chi , Oyama Soho , Mimi Mst. Afsana , Tomochika Yuna , Nagashima Yu , Nakamura Tomohiko , Kahyo Tomoaki , Ogawa Kenji , Kaneda Daita , Yoshida Minoru , Setou Mitsutoshi
Published: May 2023

Ubiquitin-like 3 (UBL3) acts as a post-translational modification (PTM) factor and regulates protein sorting into small extracellular vesicles (sEVs). sEVs have been reported as vectors for the pathology propagation of neurodegenerative diseases, such as α-synucleinopathies. Alpha-synuclein (α-syn) has been widely studied for its involvement in α-synucleinopathies. However, it is still unknown whether UBL3 interacts with α-syn, and is influenced by drugs or compounds. In this study, we investigated the interaction between UBL3 and α-syn, and any ensuing possible functional and pathological implications. We found that UBL3 can interact with α-syn by theGaussia princepsbased split luciferase complementation assay in cells and immunoprecipitation, while cysteine residues at its C-terminal, which are considered important as PTM factors for UBL3, were not essential for the interaction. The interaction was upregulated by 1-methyl-4-phenylpyridinium exposure. In drug screen results, the interaction was significantly downregulated by the treatment of osimertinib. These results suggest that UBL3 interacts with α-syn in cells and be significantly downregulated by epidermal growth factor receptor (EGFR) pathway inhibitor osimertinib. Therefore, the UBL3 pathway may be a new therapeutic target for α-synucleinopathies in the future.
Spatial subdomains in the Optic Tectum for the encoding of visual information
Authors: Shallcross Thomas , Diana Giovanni , Burrone Juan , Meyer Martin
Published: May 2023

1

Neurons across the visual system provide estimates of the visual features they encode. However, the reliability of those estimates can vary across the neuronal population. Here, we use information theory to provide a spatial map of how well neurons can distinguish ethologically-relevant visual stimuli across the entire larval zebrafish optic tectum, a brain region responsible for driving visually guided behaviour. We find that the ability of neurons to discriminate between stimuli is non-uniformly distributed across the tectum. Specifically, we show that information about local motion is preferentially encoded in the posterior tectum, whilst information about whole-field motion is preferentially encoded in the anterior tectum. This is achieved through two systematic changes along the anterior-posterior axis of the tectum: (i) a change in the number of neurons that discriminate between stimuli and (ii) a change in how well each neuron can discriminate between stimuli. By classifying neurons into distinct subtypes based on their response properties we uncovered a small group of neurons that are spatially localised to specific regions of the tectum and are able to discriminate between visual stimuli in a highly reliable manner. Our results highlight the importance of implementing information theoretic approaches to assess visual responses and provide a novel description of regional specialisation in the zebrafish optic tectum.
Cellular Bioenergetics Effects of Sirolimus on the Gonads of BALB/c Mice
Authors: Narchi Hassib , Al Bawardi Alia , Thachillath Pramathan , Souid Abdul-Kader
Published: May 2023

Background

Sirolimus, an immunosuppressive drug widely used in organ transplantation, inhibits the mechanistic target of rapamycin (mTOR), decreases cellular respiration, stops cell cycle progression and causes apoptosis. It has been linked to cytotoxicity in the gonads, but the cause is unknown.

Aims

To understand the effects of sirolimus on the gonads by measuring cellular respiration and ATP as indicators of cellular damage, and examining histological changes.

Material and Methods

We used 6-8 week old male and female BALB/c mice. They received 5 µg/g sirolimus via intraperitoneal injections for 5 consecutive days per week for up to 3 weeks (treated group) or DMSO (control group). Upon euthanasia, the gonads were promptly removed while the heart was still beating, weighed, and processed for cellular respiration, ATP measurement, and histological studies. Cellular respiration was measured using a phosphorescence oxygen analyzer and ATP using a bioluminescent assay system. Histology was performed using processed tissue fragments stained with hematoxylin and eosin (H&E).

Results

Cellular ATP levels in testicular tissue were higher than ovarian tissue in both groups, but this was not significant (p=0.4 and 0.2). Although the sirolimus group had higher cellular ATP levels, no significant difference was observed in either testicular (p=0.6) or ovarian (p=0.9) tissue. Both DMSO (p=0.01) and sirolimus groups (p=0.008) showed lower cellular respiration in ovarian than testicular tissue. Cellular respiration was lower in sirolimus group than DMSO group in both testicular (p=0.6) and ovarian (p=0.2) tissue. Testicular cellular respiration remained unchanged up to day 11 before declining, while ovarian respiration reduced up to day 11 and remained unchanged. Testicular histopathology showed normal sperm production and normal follicular development in ovarian tissue.

Conclusion

The results suggest that the 5 µg/g dose of sirolimus does not cause significant short-term changes in the cellular bioenergetics of the gonads or produce noticeable histopathological changes.
Dysfunctional Mitochondria in Cardiac Fibers of a Williams-Beuren Syndrome Mouse Model
Authors: Abdalla Noura , Tobías-Baraja Ester , Gonzalez Alejandro , Garrabou Gloria , Egea Gustavo , Campuzano Victoria
Published: May 2023

Williams-Beuren Syndrome (WBS) is a rare neurodevelopmental disorder that, together with a rather characteristic neurocognitive profile, presents a strong cardiovascular phenotype. The cardiovascular features of WBS are mainly related to a gene dosage effect due to hemizygosity of the elastin (ELN) gene; however, the phenotypic variability between WBS patients indicates the presence of important modulators of the clinical impact of elastin deficiency. Recently, two genes within the WBS region have been linked to mitochondrial dysfunction. Numerous cardiovascular diseases are related to mitochondrial dysfunction; therefore, it could be a modulator of the phenotype present in WBS. Here, we analyze mitochondrial function and dynamics in cardiac tissue from a WBS complete deletion (CD) model. Our research reveals that cardiac fiber mitochondria from CD animals have altered mitochondrial dynamics, accompanied by respiratory chain dysfunction with decreased ATP production, reproducing alterations observed in fibroblasts from WBS patients. Our results highlight two major factors; on the one hand, that mitochondrial dysfunction is probably a relevant mechanism underlying several risk factors associated with WBS disease; on the other, the CD murine model mimics the mitochondrial phenotype of WBS and could be a great model for carrying out preclinical tests on drugs targeting the mitochondria.
Optogenetic spatial patterning of cooperation in yeast populations
Authors: Le Bec Matthias , Pouzet Sylvain , Cordier Céline , Barral Simon , Scolari Vittore , Sorre Benoit , Banderas Alvaro , Hersen Pascal
Published: May 2023

Microbial communities are a siege of complex metabolic interactions such as cooperation and competition for resources. Methods to control such interactions could lead to major advances in our ability to engineer microbial consortia for bioproduction and synthetic biology applications. Here, we used optogenetics to control invertase production in yeast, thereby creating landscapes of cooperator and cheater cells. Yeast cells behave as cooperators (i.e.,transform sucrose into glucose, a public “good”) upon blue light illumination or cheaters (i.e.,consume glucose produced by cooperators to grow) in the dark. We show that cooperators benefit best from the hexoses they produce when their domain size is constrained between two cut-off length-scales. From an engineering point of view, the system behaves as a band pass filter. The lower limit is the trace of cheaters’ competition for hexoses, while the upper limit is defined by cooperators’ competition for sucrose. Hence, cooperation mostly occurs at the frontiers with cheater cells, which not only compete for hexoses but also cooperate passively by letting sucrose reach cooperators. We anticipate that this optogenetic method could be applied to shape metabolic interactions in a variety of microbial ecosystems.
Dual control of host actin polymerization by aLegionellaeffector pair
Authors: Pillon M. , Michard C. , Baïlo N. , Bougnon J. , Picq K. , Dubois O. , Andrea C. , Attaiech L. , Daubin V. , Jarraud S. , Kay E. , Doublet P.
Published: May 2023

Host actin cytoskeleton is often targeted by pathogenic bacteria through the secretion of effectors.Legionella pneumophilavirulence relies on the injection of the largest known arsenal of bacterial proteins, over 300 Dot/Icm Type 4 Secretion System effectors, into the host cytosol. Here we define the functional interactions between VipA and LegK2, two effectors with antagonistic activities towards actin polymerization that have been proposed to interfere with the endosomal pathway. We confirmed the prominent role of LegK2 effector inLegionellainfection, as the deletion oflegK2results in defects in the inhibition of actin polymerization at theLegionellaContaining Vacuole, as well as in endosomal escape of bacteria and subsequent intracellular replication. More importantly, we observed the restoration of theΔlegK2mutant defects, upon deletion ofvipAgene, making LegK2/VipA the first example of effector-effector suppression pair that targets the actin cytoskeleton and whose functional interaction impactsL. pneumophilavirulence. We demonstrated that LegK2 and VipA do not modulate each other’s activity in a ‘metaeffector’ relationship. Instead, the antagonistic activities of the LegK2/VipA effector pair would target different substrates, Arp2/3 for LegK2 and G-actin for VipA, to temporally control actin polymerization at the LCV and interfere with phagosome maturation and endosome recycling, thus contributing to the intracellular life cycle of the bacterium. Strikingly, the functional interaction between LegK2 and VipA is consolidated by an evolutionary history that has refined the best effector repertoire for the benefit ofL. pneumophilavirulence.
Cell Width inEscherichia coli: Interrogating Coupling to Nucleoid Structure
Authors: Howard Charles B , Rabinovitch Avinoam , Yehezkel Galit , Zaritsky Arieh
Published: May 2023

Cell dimensions of rod-shaped bacteria such asEscherichia coliare connected to mass growth and chromosome replication. It divides ≈20 min after termination of the replication cycle that initiates ≈40 min earlier at a relatively constant mass. Cells enlarge by elongation only, but at faster growth in richer media they are also wider. Width determination occurs in the divisome during the division process, coupled, temporally and spatially, to the ratio between the rates of growth and replication. The elusive signal directing the mechanism for width determination is related to the tightly linked duplications of the nucleoid (DNA) and the sacculus (peptidoglycan), the only two structures (macro-molecules) existing in a single copy. Six biologically meaningful parameters related to the key number of replication positions are reasonable candidates to convey such a signal. The current analysis discovered that of these, nucleoid complexity is the most likely parameter affecting cell width. As a corollary, a new, indirect approach to estimate replication rate is revealed.
Paradoxical relationship between esports toxicity and toxicity tolerance: moderated mediation by gender and positive reappraisal coping
Authors: Chang Kun , Uhm Jun-Phil , Kim Sanghoon , Lee Hyun-Woo
Published: May 2023

Purpose

Despite the negative effects of toxicity on various aspects of esports communities, gamers continue to enthusiastically show their pride and engage with the game. Based on the stress and coping theory, the current study aims to shed light on how esports gamers cope with toxicity to develop toxicity tolerance by the mediation effect of positive reappraisal coping strategy.

Design/methodology/approach

A total of 456 gamers were included in the analysis. Structural equation modeling was performed to evaluate the hypothesized model. Gender differences in the toxicity-coping process were investigated using multi-group analysis.

Findings

The findings revealed the full mediation effect of positive reappraisal on the relationship between toxicity and toxicity tolerance, especially for male gamers. The empirical evidence of this study contributes to theorizing the transformative role of positive reappraisal in developing positive consumption outcomes when esports gamers experience toxicity in the game. The multi-group analysis provided further insights into differentiating the applicability and effectiveness of positive reappraisal based on gender.

Originality/value

The findings contributed to sport management and communication literature by allowing researchers and practitioners to move beyond a preventive coping mindset by facilitating a positive coping environment that encourages gamers to interpret the conversation and messages in a more positive manner.
The nonlinear nexus between renewable energy consumption and economic growth in OECD countries: evidence from PTR and PSTR estimates
Authors: Ferhi Afifa , Kamel Helali
Published: May 2023

Purpose

Today, the increasing use of fossil fuels, energy security, concerns and the great importance of achieving sustainable economic growth underscore the urgent need to transition to a green energy system as soon as possible. To shed light on the relationship between the economy and renewable energy, this study assesses the nonlinear relationship between renewable energy consumption and economic growth for 24 OECD countries between 1990 and 2015.

Design/methodology/approach

The authors apply two nonlinear models: panel threshold regression (PTR) and panel smooth transition regression (PSTR).

Findings

The results show that the positive effect of renewable energy consumption on economic growth is conditional. On the one hand, the results of the nonlinear PTR model yielded a threshold value for renewable energy consumption of about 251.17. Below this threshold, the authors find a negative impact of renewable energy consumption on economic growth. However, above this threshold, renewable energy consumption becomes a favorable source of economic growth. Using the nonlinear PSTR model based on the gamma transition parameter of 2.014, the transition from low renewable energy consumption regime to higher is abrupt.

Originality/value

Referring to previous studies analyzing linear causality between renewable energy and economic growth, most of the results show various mixed and non-stable effects over the study period. The contributions of this study consist in conduct a series of empirical tests of the nonlinear effects of renewable energy use on economic growth using two nonlinear approaches such as the PTR and PSTR models. If the authors show that such a relationship is nonlinear, it is essential to check whether the transition from one weak regime to another strong regime is abrupt or smooth, using the PSTR approach.
Domestic intercultural experiential learning: a case study working with the Afghan refugee population
Authors: Hawes Frances , Jones Christopher
Published: May 2023

Purpose

Civic engagement involves working to make a difference in one’s community. Experiential learning enhances civic knowledge and promotes the process of reflection that students can take beyond their educational experiences. The purpose of this paper is to identify whether civic engagement may be increased through domestic experiential learning experiences and to inform future educators about how a domestic immersion experience can be used to increase civic engagement among students.

Design/methodology/approach

Twenty-five students who participated in a domestic immersion experience in January 2022 were sampled. Reflection and changes in civic engagement were measured with student responses to questions before, during and after the immersion.

Findings

During the preimmersion, students showed a desire to learn about the Afghan refugee population and considered preimmersion anxiety mitigation strategies. Using the Association of American Colleges and Universities’ Civic engagement VALUE rubric, the four main themes were diversity of communities and cultures, civic identity and commitment, civic communication and civic action and reflection. The main themes yielded post immersion were increased civic engagement and aptitude to apply knowledge and skills. The subcategories of continued civic engagement were career planning, volunteering and educating others.

Originality/value

The findings provide guidelines to future work in civic engagement. This case study provides insights into the impacts of domestic immersion experiences and how it allows the opportunity for experiential learning.
The impact of dynamic capabilities on circular economy: the mediating effect of the industrial Internet of things
Authors: AL-Khatib Ayman wael
Published: May 2023

Purpose

The current study aimed to identify the impact of the dynamic capabilities on the circular economy in Jordan's small- and medium-sized manufacturing enterprises sector as and the mediating role of industrial Internet of things.

Design/methodology/approach

This study surveyed small and medium manufacturing enterprises operating in Jordan and collected 459 responses through an online self-administered questionnaire. The effects of dynamic capabilities and the industrial Internet of things on the circular economy were analyzed using covariance-based structural equation modeling (CB-SEM).

Findings

Empirical results showed that all hypotheses are accepted. The results also revealed that the relationship between dynamic capabilities (sensing, seizing and reconfiguring) on a circular economy is mediated by the industrial Internet of things.

Originality/value

This work expanded the application of the dynamic capabilities view to investigate the antecedent effects of the industrial Internet of things and the circular economy and deepened understanding of the dynamic capabilities view theory in assessing the dynamic activities of these firms based on the three dimensions of sensing, seizing and reconfiguring. In general, this study made a theoretical and managerial contribution to supply chain and circular economy literature.
Performance of steel beam with welded top-seat angle connections at elevated temperatures
Authors: Rezaeian Abbas , Mansoori Mona , Khajehdezfuly Amin
Published: May 2023

Purpose

Top-seat angle connection is known as one of the usual uncomplicated beam-to-column joints used in steel structures. This article investigates the fire performance of welded top-seat angle connections.

Design/methodology/approach

A finite element (FE) model, including nonlinear contact interactions, high-temperature properties of steel, and material and geometric nonlinearities was created for accomplishing the fire performance analysis. The FE model was verified by comparing its simulation results with test data. Using the verified model, 24 steel-framed top-seat angle connection assemblies are modeled. Parametric studies were performed employing the verified FE model to study the influence of critical factors on the performance of steel beams and their welded angle joints.

Findings

The results obtained from the parametric studies illustrate that decreasing the gap size and the top angle size and increasing the top angles thickness affect fire behavior of top-seat angle joints and decrease the beam deflection by about 16% at temperatures beyond 570 °C. Also, the fire-resistance rating of the beam with seat angle stiffener increases about 15%, compared to those with and without the web stiffener. The failure of the beam happens when the deflections become more than span/30 at temperatures beyond 576 °C. Results also show that load type, load ratio and axial stiffness levels significantly control the fire performance of the beam with top-seat angle connections in semi-rigid steel frames.

Originality/value

Development of design methodologies for these joints and connected beam in fire conditions is delayed by current building codes due to the lack of adequate understanding of fire behavior of steel beams with welded top-seat angle connections.
Research on ERS point registration of large-size measurement field based on neural network non-uniform temperature field
Authors: Huang Lulu , Huang Xiang , Li Shuanggao
Published: May 2023

Purpose

Large size of aircraft assembly tooling structure and complex measurement environment exist. The laid enhanced reference points (ERS) are subject to a combination of nonuniform temperature fields and measurement errors, resulting in increased measurement registration errors. In view of the nonuniform temperature field and measurement errors affecting the ERS point registration problem, the purpose of this paper is to propose a neural network-based ERS point registration compensation method for large-size measurement fields under a nonuniform temperature field.

Design/methodology/approach

The approach is to collect ERS point information and temperature data, normalize the collected data to complete the data structure design and complete the construction of the neural network prediction model by data training. The data learning is performed to complete the prediction model construction, and the prediction model is used to complete the compensation analysis of ERS points. Finally, the algorithm is verified through experiments and engineering practice.

Findings

Experimental results show that the proposed neural network-based ERS point prediction and compensation method for nonuniform temperature fields effectively predicts ERS point deformation under nonuniform temperature fields compared with the conventional method. After the compensation analysis, the registration error is effectively reduced to improve registration accuracy. Reducing the combined effect of environmental nonuniform temperature field and measurement error has apparent advantages.

Originality/value

The method reduces the registration error caused by combining a nonuniform temperature field and measurement error. It can be used for aircraft assembly site prediction and registration error compensation analysis, which is essential to improve measurement accuracy further.
Investigation into tensile behavior of 3D printed nylon-based low and high-volume fraction carbon fiber composite
Authors: Kumar Mishra Pradeep , T. Jagadesh
Published: May 2023

Purpose

The tensile behavior of additively manufactured nylon-based carbon fiber-reinforced composites (CFRP) is an important criterion in aerospace and automobile structural design. So, this study aims to evaluate and validate the tensile stiffness of printed CFRP composites (low- and high-volume fraction fiber) using the volume average stiffness (VAS) model in consonance with experimental results. In specific, the tensile characterization of printed laminate composites is studied under the influence of raster orientations and process-induced defects.

Design/methodology/approach

CFRP composite laminates of low- and high-volume fraction carbon fiber of different raster orientations (0°, ± 45° and 0/90°) were fabricated using the continuous fiber 3D printing technique, and tensile characteristics of laminates were done on a universal testing machine with the crosshead speed of 2 mm/min. The induced fracture surface of laminates due to tensile load was examined using the scanning electron microscopy technique.

Findings

The VAS model can predict the tensile stiffness of printed CFRP composites with different raster orientations at an average prediction error of 5.94% and 10.58% for low- and high-volume fiber fractions, respectively. The unidirectional CFRP laminate composite with a high-volume fraction (50%) of carbon fiber showed 50.79% more tensile stiffness and 63.12% more tensile strength than the low-volume fraction (26%) unidirectional composite. Fiber pullout, fiber fracture and ply delamination are the major failure appearances observed in fracture surfaces of laminates under tensile load using scanning electron microscopy.

Originality/value

This investigation demonstrates the novel methodology to study specific tensile characteristics of low- and high-volume fraction 3D printed CFRP composite.
Mycenaspecies can be opportunist‐generalist plant root invaders
Authors: Harder Christoffer Bugge , Hesling Emily , Botnen Synnøve S. , Lorberau Kelsey E. , Dima Bálint , von Bonsdorff‐Salminen Tea , Niskanen Tuula , Jarvis Susan G. , Ouimette Andrew , Hester Alison , Hobbie Erik A. , Taylor Andy F. S. , Kauserud Håvard
Published: May 2023

Traditional strict separation of fungi into ecological niches as mutualist, parasite or saprotroph is increasingly called into question. Sequences of assumed saprotrophs have been amplified from plant root interiors, and several saprotrophic genera can invade and interact with host plants in laboratory growth experiments. However, it is uncertain if root invasion by saprotrophic fungi is a widespread phenomenon and if laboratory interactions mirror field conditions. Here, we focused on the widespread and speciose saprotrophic genusMycenaand performed (1) a systematic survey of their occurrences (in ITS1/ITS2 datasets) in mycorrhizal roots of 10 plant species, and (2) an analysis of natural abundances of13C/15N stable isotope signatures ofMycenabasidiocarps from five field locations to examine their trophic status. We found thatMycenawas the only saprotrophic genus consistently found in 9 out of 10 plant host roots, with no indication that the host roots were senescent or otherwise vulnerable. Furthermore,Mycenabasidiocarps displayed isotopic signatures consistent with published13C/15N profiles of both saprotrophic and mutualistic lifestyles, supporting earlier laboratory‐based studies. We argue thatMycenaare widespread latent invaders of healthy plant roots and thatMycenaspecies may form a spectrum of interactions besides saprotrophy also in the field.
Host switching by an ambrosia beetle fungal mutualist: Mycangial colonization of indigenous beetles by the invasive laurel wilt fungal pathogen
Authors: Joseph Ross , Bansal Kamaldeep , Keyhani Nemat O.
Published: May 2023

Ambrosia beetles require their fungal symbiotic partner as their cultivated (farmed) food source in tree galleries. While most fungal‐beetle partners do not kill the host trees they inhabit, since their introduction (invasion) into the United states around ~2002, the invasive beetle Xyleborus glabratus has vectored its mutualist partner (but plant pathogenic) fungus, Harringtonia lauricola, resulting in the deaths of over 300 million trees. Concerningly, indigenous beetles have been caught bearing H. lauricola. Here, we show colonization of the mycangia of the indigenous X. affinis ambrosia beetle by H. lauricola. Mycangial colonization occurred within 1 h of feeding, with similar levels seen for H. lauricola as found for the native X. affinis‐R. arxii fungal partner. Fungal mycangial occupancy was stable over time and after removal of the fungal source, but showed rapid turnover when additional fungal cells were available. Microscopic visualization revealed two pre‐oral mycangial pouches of ~100–200 × 25–50 μm/each, with narrow entry channels of 25–50 × 3–10 μm. Fungi within the mycangia underwent a dimorphic transition from filamentous/blastospore growth to yeast‐like budding with alterations to membrane structures. These data identify the characteristics of ambrosia beetle mycangial colonization, implicating turnover as a mechanism for host switching of H. lauricola to other ambrosia beetle species.
Implicit States of Connectivity in the Clinical Practice of Jungian Psychoanalysis and Andean Shamanism
Authors: Bryon Deborah
Published: May 2023

This paper will describe the spiritual states of “oneness” experienced by Andean shamans in relation to oceanic states in early infancy and working with trauma in Jungian analysis. The author’s work exploring implicit energetic experience with Andean shamans will be referenced with comparisons made to depth psychology, in both theory and in practice. Definitions of Q’echua terms describing different psychic meditative states that Andean shamans enter into will be provided as Andean medicine people have a much more developed language for conceptualizing these experiences. A clinical vignette will be presented that demonstrates how the spaces of implicit connection that occur between an analyst and analysand in the analytic setting can be a catalyst for healing.
Duration‐dependent transaction tax effects on sellers and their behaviors
Authors: Zhang Yanjiang , Tu Yong , Deng Yongheng
Published: May 2023

We identify three interrelated behavioral outcomes of the duration‐dependent seller's stamp duty (SSD) implemented in the Singaporean private housing market and examine how it reduces market liquidity. An SSD lowers lock‐in home sellers’ opportunity cost of holding their properties through the lock‐in period thresholds. Consequently, their selling prices are higher than non–lock‐in home sellers. An SSD lowers their probability of home sales; the magnitude of this effect depends on the SSD's tax rate and tax rate deduction across a threshold. Moreover, an SSD drives some lock‐in home sellers to lease out the properties at lowerents.
Effect of controlled blood pressure increase on cerebral blood flow velocity and oxygenation in patients with subarachnoid haemorrhage
Authors: Olsen Markus Harboe , Capion Tenna , Riberholt Christian Gunge , Bache Søren , Ebdrup Søren Røddik , Rasmussen Rune , Mathiesen Tiit , Berg Ronan M. G. , Møller Kirsten
Published: May 2023

Background

Patients with aneurysmal subarachnoid haemorrhage (SAH) might have impaired cerebral autoregulation, that is, CBF – and thereby oxygen delivery – passively increase with an increase in CPP. This physiological study aimed to investigate the cerebral haemodynamic effects of controlled blood pressure increase in the early phase after SAH before any signs of delayed cerebral ischaemia (DCI) occurred.

Methods

The study was carried out within 5 days after ictus. Data were recorded at baseline and after 20 min of noradrenaline infusion to increase mean arterial blood pressure (MAP) by a maximum of 30 mmHg and to an absolute level of no more than 130 mmHg. The primary outcome was the difference in middle cerebral artery blood flow velocity (MCAv) measured by transcranial Doppler (TCD), while differences in intracranial pressure (ICP), brain tissue oxygen tension (PbtO2), and microdialysis markers of cerebral oxidative metabolism and cell injury were assessed as exploratory outcomes. Data were analysed using Wilcoxon signed‐rank test with correction for multiplicity for the exploratory outcomes using the Benjamini‐Hochberg correction.

Results

Thirty‐six participants underwent the intervention 4 (median, IQR: 3–4.75) days after ictus. MAP was increased from 82 (IQR: 76–85) to 95 (IQR: 88–98) mmHg (p‐value: <.001). MCAv remained stable (baseline, median 57, IQR: 46–70 cm/s; controlled blood pressure increase, median: 55, IQR: 48–71 cm/s;p‐value: .054), whereas PbtO2increased significantly (baseline, median: 24, 95%CI: 19–31 mmHg; controlled blood pressure increase, median: 27, 95%CI: 24–33 mmHg;p‐value <.001). The remaining exploratory outcomes were unchanged.

Conclusion

In this study of patients with SAH, MCAv was not significantly affected by a brief course of controlled blood pressure increase; despite this, PbtO2increased. This suggests that autoregulation might not be impaired in these patients or other mechanisms could mediate the increase in brain oxygenation. Alternatively, a CBF increase did occur that, in turn, increased cerebral oxygenation, but was not detected by TCD.

Trial registration:clinicaltrials.gov(NCT03987139; 14 June 2019).
Trends in aetiology‐based hospitalisation for cirrhosis before and during the COVID‐19 pandemic in the United States
Authors: Kim Donghee , Perumpail Brandon J. , Wijarnpreecha Karn , Manikat Richie , Cholankeril George , Ahmed Aijaz
Published: May 2023

Background

Patients with pre‐existing cirrhosis and COVID‐19 may have a poor prognosis.

Aim

To evaluate the temporal trends in aetiology‐based hospitalisations and potential predictors of in‐hospital mortality during hospitalisation with cirrhosis before and during the COVID‐19 pandemic.

Methods

Based on the US National Inpatient Sample 2019–2020, we determined quarterly trends in aetiology‐based hospitalisations with cirrhosis and decompensated cirrhosis, and identified predictors of in‐hospital mortality during hospitalisation with cirrhosis.

Results

We analysed 316,418 hospitalisations, representing 1,582,090 hospitalisations with cirrhosis. Hospitalisations for cirrhosis increased at a relatively higher rate during the COVID‐19 era. Hospitalisation rates for alcohol‐related liver disease (ALD)‐related cirrhosis increased significantly (quarterly percentage change [QPC]: 3.6%, 95% CI: 2.2%–5.1%), with a notably higher rate during the COVID‐19 era. In contrast, hospitalisation rates for hepatitis C virus (HCV)‐related cirrhosis decreased steadily with a trend of −1.4% of QPC (95% CI: −2.5% to −0.1%). Quarterly trends in the proportion of ALD‐ (QPC: 1.7%, 95% CI: 0.9%–2.6%) and nonalcoholic fatty liver disease‐related (QPC: 0.7%, 95% CI: 0.1%–1.2%) hospitalisations with cirrhosis increased significantly but declined steadily for viral hepatitis. The COVID‐19 era and COVID‐19 infection were independent predictors of in‐hospital mortality during hospitalisation with cirrhosis and decompensated cirrhosis. Compared with HCV‐related cirrhosis, ALD‐related cirrhosis was associated with a 40% higher risk of in‐hospital mortality.

Conclusion

In‐hospital mortality in cirrhosis was higher in the COVID‐19 era than in the pre‐COVID‐19 era. ALD is the leading aetiology‐specific cause of in‐hospital mortality in cirrhosis with an independent detrimental impact of COVID‐19 infection.
Cost‐effectiveness of polatuzumab vedotin in combination with chemoimmunotherapy (pola‐R‐CHP) in previously untreated diffuse large B‐cell lymphoma in Germany
Authors: Thiruvengadam Swetha Kambhampati , Shumilov Evgenii , Saumoy Monica , Herrera Alex F. , Tilly Hervé , Lenz Georg , Thiruvengadam Nikhil R.
Published: May 2023

We evaluated the cost‐effectiveness of frontline polatuzumab vedotin‐R‐CHP (pola‐R‐CHP) treatment for patients with diffuse large B‐cell lymphoma (DLBCL) in Germany by using a Markov model (lifetime horizon). Progression rates and survival outcomes were extrapolated from the POLARIX trial. Outcomes were measured in incremental cost‐effectiveness ratios (ICERS) with a willingness‐to‐pay (WTP) threshold of €80 000/quality‐adjusted life‐years (QALY). Assuming, 69.6% 5‐year PFS with pola‐R‐CHP and 62.6% 5‐year PFS with R‐CHOP, the addition of polatuzumab vedotin resulted in an additional 0.52 life‐years and an incremental 0.65 QALYs but €31 988 additional cost. Based on this, pola‐R‐CHP was cost‐effective (€49 238/QALY) at a WTP of €80 000/QALY. The cost‐effectiveness of pola‐R‐CHP is highly dependent on its long‐term outcomes and cost. Our analysis is limited by the fact that the long‐term outcomes of pola‐R‐CHP are unknown at this time.
Plasma miR‐1254 as a predictive biomarker of chemosensitivity and a target of nucleic acid therapy in esophageal cancer
Authors: Takashima Yusuke , Komatsu Shuhei , Ohashi Takuma , Kiuchi Jun , Nishibeppu Keiji , Kamiya Hajime , Arakawa Hiroshi , Ishida Ryo , Shimizu Hiroki , Arita Tomohiro , Konishi Hirotaka , Shiozaki Atsushi , Kubota Takeshi , Fujiwara Hitoshi , Otsuji Eigo
Published: May 2023

This study investigated novel tumor suppressor microRNAs (miRNAs) that decrease in plasma and predict chemosensitivity to neoadjuvant chemotherapy (NAC) for esophageal squamous cell carcinoma (ESCC) and revealed their usefulness as novel therapeutic agents. We selected four miRNA candidates (miR‐323, 345, 409, and 1254) based on the microRNA microarray comparing pre‐treatment plasma levels in ESCC patients with high and low histopathological responses to NAC and an NCBI database review. Among these miRNA candidates, miR‐1254 was more highly elevated in pre‐treatment plasma of ESCC patients with a high histopathological response than in those with a low histopathological response (P = 0.0021, area under the receiver‐operating characteristic curve 0.7621). High plasma miR‐1254 levels tended to correlate with the absence of venous invasion (P = 0.0710) and were an independent factor predicting a higher response to chemotherapy (P = 0.0022, odds ratio 7.86) and better prognosis (P = 0.0235, hazard ratio 0.23). Overexpressing miR‐1254 in ESCC cells significantly enhanced chemosensitivity to cisplatin through the transcriptional regulation of ABCC1 in vitro. Moreover, increased plasma miR‐1254 levels by subcutaneous injection significantly improved responses to cisplatin in mice. Plasma miR‐1254 might be a useful biomarker for predicting responses to NAC, and the restoration of plasma miR‐1254 levels might improve chemosensitivity in ESCC.
A founder PPIL1 variant underlies a recognizable form of microlissencephaly with pontocerebellar hypoplasia
Authors: Abdel‐Salam Ghada M. H. , Abdel‐Hamid Mohamed S.
Published: May 2023

Biallelic variants in PPIL1 have been recently found to cause a very rare type of pontocerebellar hypoplasia and congenital microcephaly in which simplified gyral pattern was not observed in all of the patients. Here, we describe a series of nine patients from eight unrelated Egyptian families in whom whole exome sequencing detected a previously reported homozygous missense variant (c.295G>A, p.Ala99Thr) in PPIL1. Haplotype analysis confirmed that this variant has a founder effect in our population. All our patients displayed early onset drug‐resistant epilepsy, profound developmental delay, and visual impairment. Remarkably, they presented with recognizable imaging findings showing profound microcephaly, hypoplastic frontal lobe and posteriorly predominant pachygyria, agenesis of corpus callosum with colpocephaly, and pontocerebellar hypoplasia. In addition, Dandy–Walker malformation was evident in three patients. Interestingly, four of our patients exhibited hematopoietic disorder (44% of cases). We compared the phenotype of our patients with other previously reported PPIL1 patients. Our results reinforce the hypothesis that the alterative splicing of PPIL1 causes a heterogeneous phenotype. Further, we affirm that hematopoietic disorder is a common feature of the condition and underscore the role of major spliceosomes in brain development.
Home visits to identify the roles lifestyle and stress play in families of children with obesity
Authors: Gmeinder Ricarda , Heldt Katrin , Velde Anneco Dintheer‐ter , Büchter Dirk , Brogle Björn , Schmid Hanna , Laimbacher Josef , l'Allemand Dagmar
Published: May 2023

One‐sixth of Swiss children are affected by overweight, and despite the implementation of an evidence‐based multiprofessional approach, there has only been moderate therapeutic success. An unfavourable home environment and psychosocial stresses on the family may impede lifestyle changes. This longitudinal observational study included children with obesity (body mass index [BMI] ≥97th percentile [P.]) or overweight (BMI ≥ 90th P.) with a comorbidity, and who were participating in a regional 12‐month multiprofessional group programme (MGP). Two health professionals routinely visited the family home at baseline (T0) to identify obesogenic environmental factors and psychosocial stress using an observation and question checklist and the Heidelberger stress scale (HSS). At T0 and after an 8‐month intensive intervention phase (T1), the BMI standard deviation score (BMI‐SDS) and its associations with the environmental and psychosocial factors were assessed. Twenty‐eight children (17 male) met the criteria for participation in the MGP. At T0, age was 11.2 ± 1.71 years, BMI 28.1 ± 4.7 kg/m2 and BMI‐SDS 2.9 ± 0.8, means ±SD. By T1, the mean BMI‐SDS had decreased significantly, by −0.11 (p < .05). The stress scores (30.46 ± 17.8) were elevated and the subcategories of financial and social stress showed a trend towards predicting BMI or BMI‐SDS at T0 and T1, but none of the other supposed obesogenic risk factors significantly predicted weight status. Conducting home visits allowed health professionals to identify obesity‐promoting home conditions and, more importantly, otherwise undisclosed high psychosocial stress and resource limitations in families that impacted the children's obesity before and after the MGP intervention.
Reproducibility of the pupillary light reflex over short intervals in psychiatric patients and community volunteers
Authors: McCall William V. , Dinsmore Jessica T. , Brown Alicia , Ribbens Lucas T. , Rosenquist Peter B. , McCloud Laryssa , Miller Brian J.
Published: May 2023

The pupillary light reflex (PLR) is a method for measuring dynamic responses within the autonomic nervous system, and would have potential value as a point‐of‐care test in a psychiatry clinic if reproducible results could be obtained in a short period of time. We collected PLR from adult community volunteers and depressed outpatients with the purpose of demonstrating (1) that valid data could be obtained >90% of the time from both the community volunteers and the patients, and (2) that reproducible results could be obtained with repeated measurement over short periods of time. Valid data were captured for 90.3% of 76 participants, allowing for two attempts of the PLR per participant. Success rates were similar for depressed patients and community volunteers. Eighteen of these 76 participants provided repeated paired measurements after 5 and 10 min of dark adaptation, producing high correlations for maximum constriction velocity (MCV) between assay 1 and 2 (Pearson's r = 0.71, p < 0.001), but there was a significant 8% increase in velocity for MCV between assay 1 and 2 (∆ = 0.34 ± 0.59 mm/s, p < 0.05). In contrast, PLR measurements were stable when tested in a separate cohort of 21 additional participants at 10 and 15 min of dark adaptation with an MCV Pearson's correlation of r = 0.84, p < 0.001, with a nonsignificant 1% difference between the two time points. These findings indicate an acceptable rate of collecting valid and reproducible PLR data when contrasting two measurements of PLR after 10 or 15 min of dark adaptation in depressed and suicidal patients.
Using network analysis to validate domains of the modified telephone interview for cognitive status
Authors: Truong Quoc Cuong , Cervin Matti , Choo Carol C. , Numbers Katya , Bentvelzen Adam C. , Merkin Alexander G. , Sachdev Perminder S. , Feigin Valery L. , Brodaty Henry , Kochan Nicole A. , Medvedev Oleg N.
Published: May 2023

Background

The modified Telephone Interview for Cognitive Status (TICS‐M) is a widely used tool for assessing global cognitive functions and screening for cognitive impairments. The tool was conceptualised to capture various cognitive domains, but the validity of such domains has not been investigated against comprehensive neuropsychological assessments tools. Therefore, this study aimed to explore the associations between the TICS‐M domains and neuropsychological domains to evaluate the validity of the TICS‐M domains using network analysis.

Materials and Methods

A longitudinal research design was used with a large sample of older adults (aged above 70 years; n = 1037 at the baseline assessment) who completed the TICS‐M and comprehensive neuropsychological assessments biennially. We applied network analysis to identify unique links between the TICS‐M domains and neuropsychological test scores.

Results

At baseline, there were weak internal links between the TICS‐M domains. The TICS‐M memory and language domains were significantly related to their corresponding neuropsychological domains. The TICS‐M attention domain had significant associations with executive function and visuospatial abilities. The TICS‐M orientation domain was not significantly associated with any of the five neuropsychological domains. Despite an attrition of almost 50% at wave four, weak internal links between the TICS‐M domains and most associations between TICS‐M and neuropsychological domains that were found initially, remained stable at least over two waves within the 6‐year period.

Conclusions

This study supports the overall structural validity of the TICS‐M screener in assessing enduring global cognitive function. However, separate TICS‐M cognitive domains should not be considered equivalent to the analogous neuropsychological domains.