bluuebunny/crossref_metadata_2025 huggingface dataset:
Excitatory brain stimulation over the left dorsolateral prefrontal cortex enhances voluntary distraction in depressed patients
Authors: Li Sijin , Chen Jingxu , Gao Kexiang , Xu Feng , Zhang Dandan
Published: March 2023

Background

While implicit distraction could ameliorate negative feelings in patients with major depressive disorders (MDD), it remains unclear whether patients could benefit from explicit, voluntary distraction. Meanwhile, though the dorsolateral prefrontal cortex (DLPFC) is established as a crucial brain region involved in attentional control, the causal relationship between the DLPFC and voluntary distraction is unexplored in patients.

Methods

Combing explicit distraction and transcranial magnetic stimulation (TMS), this study investigated whether TMS-activated DLPFC facilitates voluntary distraction in MDD patients. Eighty patients diagnosed with current MDD underwent either active (n = 40) or sham (n = 40) TMS sessions, followed by receiving negative social feedback from other patients, during which they were requied to use distraction strategy to down-regulate their painful feelings. Electroencephalogram was recorded during the task.

Results

Both the subjective emotional rating and the amplitude of late positive potential showed that depressed patients successfully down-regulate their negative emotions via voluntary distraction, and the TMS-activated left DLPFC produced a larger benefit of emotion regulation compared to the sham TMS group. Results also revealed that while emotion regulation effect was negatively associated with depressive symptoms in the sham TMS group, this correlation was largely diminished when patients' left DLPFC was activated by TMS during the voluntary distraction.

Conclusions

These findings demonstrated that distraction is valuable for emotion regulation in MDD patients and they could be beneficial in voluntary distraction by activating their left DLPFC using neural modulation techniques. This study has valuable implications for clinical treatement of emotional dysregulation in MDD patients.
The Unlikely Heroes of Progressive Taxation: CEOs’ Support for Bill Clinton’s Tax Increase Package in 1993
Authors: HAYASAKI SEITO
Published: March 2023

On August 10, 1993, President Bill Clinton signed the Omnibus Budget Reconciliation Act of 1993, one of the largest fiscal deficit-reduction packages in US fiscal history. This law raised the top individual income tax rate from 31% to 39.6%, which increased the average effective tax rate for high-income earners and shifted the federal fiscal balance from deficit to surplus by the end of the century. Given major business interest groups’ criticism of the Omnibus Budget Reconciliation Act of 1993’s heavy reliance on tax increases over spending cuts, how was the Democrat-controlled Congress able to pass this legislation? Drawing on archival evidence from the Clinton Presidential Library, this paper shows that the administration and Democratic committee chairs mobilized support from corporate CEOs, including Fortune 500 executives, asking them to lobby key legislators to support the bill. Thus, with business leaders’ support and lobbying efforts, the legislation was passed with a very slight majority.
Taking care of who cares: Evaluation of a training program for home palliative care professionals
Authors: Parise Miriam , Mulé Marica , Di Noto Daniela , Maiorana Luigi , Asaro Adelaide , Zammitti Mariagrazia , Bertoni Anna
Published: March 2023

Objectives

To evaluate an enrichment training program targeted at home palliative care professionals in terms of its effects and participants’ satisfaction. The program had 2 main aims: give voice to professionals’ emotional fatigue and promote their personal resources.

Methods

One hundred twenty-three home palliative care professionals participated in 12 parallel training courses; each course consisted of four 3-hour meetings led by 2 trainers and involved about 10–15 participants. The program adopted the method and tools typical of the enrichment approach, with the insertion of an art therapy exercise in the central meetings. The topics addressed were the following: emotional awareness in care relationship; the recognition of the needs of the patient, the family, and the professional himself; the inevitability of the death of the patient; and the challenges and resources of the multidisciplinary care team. At the first (T1) and last (T2) meetings, participants filled in a self-report questionnaire assessing work emotional fatigue, empowerment, generativity, and satisfaction with the course.

Results

Participants were highly satisfied with the course. They reported a higher level of work emotional fatigue and a higher perception of personal resources, in terms of empowerment (both individual-oriented and relationship-oriented) and generativity at the end of the program than before.

Significance of results

Results confirm the need to provide home palliative care professionals with trainings in which they can express, share, and deal with personal and professional needs. This course gave voice to professionals’ work emotional fatigue and promoted their personal resources, while enhancing collaboration in the multidisciplinary team.
How governance shaped military responses to the COVID-19 pandemic
Authors: Dietrich Nick , Eck Kristine , Ruffa Chiara
Published: March 2023

Most countries deployed their military in some capacity to combat the COVID-19 pandemic. We present original data on early pandemic-related deployments, identifying seven types of deployment: logistic operations, enforcement, international involvement, border protection, information provision, intelligence operations, and domestic protection. We find that military deployments are shaped by capacity and electoral considerations, even after accounting for cross-country differences in perceptions of the military. Countries with elected leaders were significantly more likely to deploy the military for border protection. Incumbents facing reelection were especially sensitive to electoral concerns, becoming significantly less likely to deploy the military for domestic enforcement when facing an imminent election.
Dispersion properties of glide-symmetric corrugated metasurface waveguides
Authors: Fischer Boris , Valerio Guido
Published: March 2023

In this paper, a mode-matching procedure is used to prove for the first time the dispersionless behavior of glide symmetry (GS) in corrugated metasurface waveguides. Depending on their field symmetry, the Floquet harmonics have a different impact onto the frequency dispersion, which is reduced with GS when the gap between the surfaces is small. Indeed, the glide-symmetric waveguide is shown to have the same effective propagation features as a scaled mirror-symmetric waveguide with half the period and a doubled gap. We propose closed-form formulas for the effective refractive index of the glide-symmetric waveguide in the first Brillouin zone, having a small groove compared to the period. The closed-form expressions analytically prove the dispersionless behavior of GS.
The Future of Cancer Immunotherapy
Authors: Mach Nicolas
Published: March 2023

Abstract. This article describes three emerging, novel cancer immunotherapies: BITE, TIL and cancer vaccines are therapies that recognize specific targets on cancer cells and trigger a specific immune response. So far, not all tumor types can benefit from these approaches the best results have been observed in hematological malignancies, melanoma, and lung cancer. These novel biological products are currently being tested in several cancer centers in Switzerland, and physicians must be familiar with these procedures, as some of their patients might be treated with such therapies in the near future.
Endocrine and Neurological Toxicities of Immunotherapies
Authors: Boydell Emma , Fernandez Eugenio
Published: March 2023

Abstract. Immunotherapy has revolutionized cancer care but exposes patients to a new spectrum of complications that mimic autoimmune diseases, which are referred to as immune-related adverse events (irAEs). Endocrine complications are among the most common and involve nearly all endocrine tissues. Corticosteroids are not useful in endocrine irAEs, and definitive hormonal substitution is often indicated. Neurological irAEs can involve the central nervous system, the peripheral nervous system or the neuromuscular junction. Neurological irAEs are among the rarer complications but are associated with a higher morbidity and fatality. Therefore, prompt recognition and treatment are crucial. In this article, we discuss incidence, presentation, work-up, management, and common pitfalls in endocrine and neurological irAEs.
Quantitative Evaluation of Wavelet Analysis Method for Turbulent Flux Calculation of Non‐Stationary Series
Authors: Li Yubin , Wu Yujie , Tang Jie , Zhu Ping , Gao Zhiqiu , Yang Yuanjian
Published: March 2023

This study evaluates the uncertainties of turbulent flux calculation using eddy covariance (EC) and wavelet analysis (WA) methods. First, a non‐stationary data set is concocted by adding periodic waves and random perturbations which mimic the large eddies, turbulent intermittency, and asymmetry into an observational stationary data set, and the theoretical “true” fluxes are used to quantitatively evaluate the accuracy of these methods. Results show that EC and Morlet‐wavelet generate biases ranging 50%–100% of the “true” values at different non‐stationarity grades, whereas the Mexican hat (Mexhat) wavelet has a bias of about half of them. Furthermore, there is a high correlation of the Mexhat‐derived fluxes to the benchmark values, the regression slopes of the values of these two can be improved to almost 1 by adding a correction coefficient. The results suggest the potential of using the Mexhat‐wavelet method to calculate turbulent fluxes with high accuracy under non‐stationary conditions.
Investigation of the Southern Hemisphere Mid‐High Latitude Thermospheric ∑O/N2 Responses to the Space‐X Storm
Authors: Cai Xuguang , Wang Wenbin , Lin Dong , Eastes Richard W. , Qian Liying , Zhu Qingyu , Correira J. , McClintock William E. , Gan Quan , Aryal Saurav , Laskar F. I. , Karan D. K.
Published: March 2023

The geomagnetic storm on February 3, 2022 caused the loss of 38 Starlink satellites of Space‐X. The Global‐scale Observations of the Limb and Disk (GOLD) observations and Multi‐Scale Atmosphere Geospace Environment (MAGE) model simulations are utilized to investigate the thermospheric composition responses to the Space‐X storm. The percentage difference of the GOLD observed thermospheric O and N2 column density ratio (∑O/N2) between the storm time (February 3, Day‐of‐Year [DOY] 34) and quiet time (DOY 32) shows a depletion region in the local noon sector mid‐high latitudes in the southern hemisphere, which corresponds to the east side of GOLD field‐of‐view (FOV). This is different from the classic theory of thermospheric composition disturbance during geomagnetic storms, under which the ∑O/N2 depletion is usually generated at local midnight and high latitudes, and thus, appear on the west side of GOLD FOV. MAGE simulations reproduce the observations qualitatively and indicate that the ∑O/N2 depletion is formed due to strong upwelling in the local morning caused by strong Joule heating. Interestingly, enhanced equatorward winds appear near local midnight, but also in the local morning sector, which transports ∑O/N2 depletion equatorward. The depletion corotates toward the local afternoon and is observed in the GOLD FOV. The equatorward winds in the local morning are due to the ion‐neutral coupling under the conditions of a dominant positive interplanetary magnetic field east‐west component (By) during the storm.
Horizontal Correlation Functions of Wind Fluctuations in the Mesosphere and Lower Thermosphere
Authors: Poblet Facundo L. , Vierinen Juha , Avsarkisov Victor , Conte J. Federico , Charuvil Asokan Harikrishnan , Jacobi Christoph , Chau Jorge L.
Published: March 2023

Measurements of kinetic energy in vortical and divergent fluctuations in the mesosphere and lower thermosphere can be used to study stratified turbulence (ST) and gravity waves. This can be done using horizontal correlation functions of the fluctuating component of velocity. This study introduces a novel method for estimating these correlation functions using radars that observe Doppler shifts of ionized specular meteor trails. The technique solves the correlation functions directly on a longitudinal‐transverse‐up coordinate system, assuming axial symmetry. This procedure is more efficient and leads to smaller uncertainties than a previous approach. The new technique is applied to a year‐long data set from a multistatic specular meteor radar network in Germany, to study the annual variability of kinetic energy within turbulent fluctuations at 87–93 km of altitude. In monthly averages, the kinetic energy is found to be nearly equipartitioned between vortical and divergent modes. Turbulent fluctuations maximize during the winter months with approximately 25% more energy in these months than at other times. The horizontal correlation functions are in agreement with the inertial subrange of ST, exhibiting a 2/3 power law in the horizontal lag direction, with an outermost scale of ST to be about 380 km. This suggests that horizontal correlation functions could be used to estimate turbulent energy transfer rates.
Novel developments in computational spectropolarimeter
Authors: Hsiang En-Lin , Wu Shin-Tson
Published: March 2023

Compared to conventional bulky spectropolarimeters, computational spectropolarimeters which reconstruct light-field information such as polarization and spectrum in a compact form factor, are critical equipment enabling new applications. The key component of a computational spectropolarimeter is a tunable light-field modulator, in which liquid crystal-based device is a promising candidate. By varying the applied voltage, the tunable liquid crystal metasurface can modulate the phase and spectral information of the incident light, and after a few trials, this important information can be decoded mathematically. Such a novel approach paves the foundation for developing compact and low-cost spectropolarimetric imaging devices with widespread applications in biomedical imaging, remote sensing, and optical communications.
Epigenetic regulation in metabolic diseases: mechanisms and advances in clinical study
Authors: Wu Yan-Lin , Lin Zheng-Jun , Li Chang-Chun , Lin Xiao , Shan Su-Kang , Guo Bei , Zheng Ming-Hui , Li Fuxingzi , Yuan Ling-Qing , Li Zhi-hong
Published: March 2023

Epigenetics regulates gene expression and has been confirmed to play a critical role in a variety of metabolic diseases, such as diabetes, obesity, non-alcoholic fatty liver disease (NAFLD), osteoporosis, gout, hyperthyroidism, hypothyroidism and others. The term ‘epigenetics’ was firstly proposed in 1942 and with the development of technologies, the exploration of epigenetics has made great progresses. There are four main epigenetic mechanisms, including DNA methylation, histone modification, chromatin remodelling, and noncoding RNA (ncRNA), which exert different effects on metabolic diseases. Genetic and non-genetic factors, including ageing, diet, and exercise, interact with epigenetics and jointly affect the formation of a phenotype. Understanding epigenetics could be applied to diagnosing and treating metabolic diseases in the clinic, including epigenetic biomarkers, epigenetic drugs, and epigenetic editing. In this review, we introduce the brief history of epigenetics as well as the milestone events since the proposal of the term ‘epigenetics’. Moreover, we summarise the research methods of epigenetics and introduce four main general mechanisms of epigenetic modulation. Furthermore, we summarise epigenetic mechanisms in metabolic diseases and introduce the interaction between epigenetics and genetic or non-genetic factors. Finally, we introduce the clinical trials and applications of epigenetics in metabolic diseases.
Notch3 regulates Mybl2 via HeyL to limit proliferation and tumor initiation in breast cancer
Authors: Brahim Sonia , Negulescu Ana-Maria , Geneste Clara , Schott Thomas , Lin Shuheng , Morel Louis-Oscar , Rama Nicolas , Gadot Nicolas , Treilleux Isabelle , Mehlen Patrick , Meurette Olivier
Published: March 2023

Notch signaling is a conserved signaling pathway that participates in many aspects of mammary gland development and homeostasis, and has extensively been associated with breast tumorigenesis. Here, to unravel the as yet debated role of Notch3 in breast cancer development, we investigated its expression in human breast cancer samples and effects of its loss in mice. Notch3 expression was very weak in breast cancer cells and was associated with good patient prognosis. Interestingly, its expression was very strong in stromal cells of these patients, though this had no prognostic value. Mechanistically, we demonstrated that Notch3 prevents tumor initiation via HeyL-mediated inhibition of Mybl2, an important regulator of cell cycle. In the mammary glands of Notch3-deficient mice, we observed accelerated tumor initiation and proliferation in a MMTV-Neu model. Notch3-null tumors were enriched in Mybl2 mRNA signature and protein expression. Hence, our study reinforces the anti-tumoral role of Notch3 in breast tumorigenesis.
Immunogenicity and protection of a variant nanoparticle vaccine that confers broad neutralization against SARS-CoV-2 variants
Authors: Logue James , Johnson Robert M. , Patel Nita , Zhou Bin , Maciejewski Sonia , Foreman Bryant , Zhou Haixia , Portnoff Alyse D. , Tian Jing-Hui , Rehman Asma , McGrath Marisa E. , Haupt Robert E. , Weston Stuart M. , Baracco Lauren , Hammond Holly , Guebre-Xabier Mimi , Dillen Carly , Madhangi M. , Greene Ann M. , Massare Michael J. , Glenn Greg M. , Smith Gale , Frieman Matthew B.
Published: March 2023

SARS-CoV-2 variants have emerged with elevated transmission and a higher risk of infection for vaccinated individuals. We demonstrate that a recombinant prefusion-stabilized spike (rS) protein vaccine based on Beta/B.1.351 (rS-Beta) produces a robust anamnestic response in baboons against SARS-CoV-2 variants when given as a booster one year after immunization with NVX-CoV2373. Additionally, rS-Beta is highly immunogenic in mice and produces neutralizing antibodies against WA1/2020, Beta/B.1.351, and Omicron/BA.1. Mice vaccinated with two doses of Novavax prototype NVX-CoV2373 (rS-WU1) or rS-Beta alone, in combination, or heterologous prime-boost, are protected from challenge. Virus titer is undetectable in lungs in all vaccinated mice, and Th1-skewed cellular responses are observed. We tested sera from a panel of variant spike protein vaccines and find broad neutralization and inhibition of spike:ACE2 binding from the rS-Beta and rS-Delta vaccines against a variety of variants including Omicron. This study demonstrates that rS-Beta vaccine alone or in combination with rS-WU1 induces antibody-and cell-mediated responses that are protective against challenge with SARS-CoV-2 variants and offers broader neutralizing capacity than a rS-WU1 prime/boost regimen alone. Together, these nonhuman primate and murine data suggest a Beta variant booster dose could elicit a broad immune response to fight new and future SARS-CoV-2 variants.
Identification of a physiologic vasculogenic fibroblast state to achieve tissue repair
Authors: Pal Durba , Ghatak Subhadip , Singh Kanhaiya , Abouhashem Ahmed Safwat , Kumar Manishekhar , El Masry Mohamed S , Mohanty Sujit K. , Palakurti Ravichand , Rustagi Yashika , Tabasum Saba , Khona Dolly K. , Khanna Savita , Kacar Sedat , Srivastava Rajneesh , Bhasme Pramod , Verma Sumit S. , Hernandez Edward , Sharma Anu , Reese Diamond , Verma Priyanka , Ghosh Nandini , Gorain Mahadeo , Wan Jun , Liu Sheng , Liu Yunlong , Castro Natalia Higuita , Gnyawali Surya C. , Lawrence William , Moore Jordan , Perez Daniel Gallego , Roy Sashwati , Yoder Mervin C. , Sen Chandan K.
Published: March 2023

Tissue injury to skin diminishes miR-200b in dermal fibroblasts. Fibroblasts are widely reported to directly reprogram into endothelial-like cells and we hypothesized that miR-200b inhibition may cause such changes. We transfected human dermal fibroblasts with anti-miR-200b oligonucleotide, then using single cell RNA sequencing, identified emergence of a vasculogenic subset with a distinct fibroblast transcriptome and demonstrated blood vessel forming function in vivo. Anti-miR-200b delivery to murine injury sites likewise enhanced tissue perfusion, wound closure, and vasculogenic fibroblast contribution to perfused vessels in a FLI1 dependent manner. Vasculogenic fibroblast subset emergence was blunted in delayed healing wounds of diabetic animals but, topical tissue nanotransfection of a single anti-miR-200b oligonucleotide was sufficient to restore FLI1 expression, vasculogenic fibroblast emergence, tissue perfusion, and wound healing. Augmenting a physiologic tissue injury adaptive response mechanism that produces a vasculogenic fibroblast state change opens new avenues for therapeutic tissue vascularization of ischemic wounds.
Disease-relevant β2-microglobulin variants share a common amyloid fold
Authors: Wilkinson Martin , Gallardo Rodrigo U. , Martinez Roberto Maya , Guthertz Nicolas , So Masatomo , Aubrey Liam D. , Radford Sheena E. , Ranson Neil A.
Published: March 2023

β2-microglobulin (β2m) and its truncated variant ΔΝ6 are co-deposited in amyloid fibrils in the joints, causing the disorder dialysis-related amyloidosis (DRA). Point mutations of β2m result in diseases with distinct pathologies. β2m-D76N causes a rare systemic amyloidosis with protein deposited in the viscera in the absence of renal failure, whilst β2m-V27M is associated with renal failure, with amyloid deposits forming predominantly in the tongue. Here we use cryoEM to determine the structures of fibrils formed from these variants under identical conditions in vitro. We show that each fibril sample is polymorphic, with diversity arising from a ‘lego-like’ assembly of a common amyloid building block. These results suggest a ‘many sequences, one amyloid fold’ paradigm in contrast with the recently reported ‘one sequence, many amyloid folds’ behaviour of intrinsically disordered proteins such as tau and Aβ.
Insights into pulmonary phosphate homeostasis and osteoclastogenesis emerge from the study of pulmonary alveolar microlithiasis
Authors: Uehara Yasuaki , Tanaka Yusuke , Zhao Shuyang , Nikolaidis Nikolaos M. , Pitstick Lori B. , Wu Huixing , Yu Jane J. , Zhang Erik , Hasegawa Yoshihiro , Noel John G. , Gardner Jason C. , Kopras Elizabeth J. , Haffey Wendy D. , Greis Kenneth D. , Guo Jinbang , Woods Jason C. , Wikenheiser-Brokamp Kathryn A. , Kyle Jennifer E. , Ansong Charles , Teitelbaum Steven L. , Inoue Yoshikazu , Altinişik Göksel , Xu Yan , McCormack Francis X.
Published: March 2023

Pulmonary alveolar microlithiasis is an autosomal recessive lung disease caused by a deficiency in the pulmonary epithelial Npt2b sodium-phosphate co-transporter that results in accumulation of phosphate and formation of hydroxyapatite microliths in the alveolar space. The single cell transcriptomic analysis of a pulmonary alveolar microlithiasis lung explant showing a robust osteoclast gene signature in alveolar monocytes and the finding that calcium phosphate microliths contain a rich protein and lipid matrix that includes bone resorbing osteoclast enzymes and other proteins suggested a role for osteoclast-like cells in the host response to microliths. While investigating the mechanisms of microlith clearance, we found that Npt2b modulates pulmonary phosphate homeostasis through effects on alternative phosphate transporter activity and alveolar osteoprotegerin, and that microliths induce osteoclast formation and activation in a receptor activator of nuclear factor-κB ligand and dietary phosphate dependent manner. This work reveals that Npt2b and pulmonary osteoclast-like cells play key roles in pulmonary homeostasis and suggest potential new therapeutic targets for the treatment of lung disease.
Retinol dehydrogenase 10 reduction mediated retinol metabolism disorder promotes diabetic cardiomyopathy in male mice
Authors: Wu Yandi , Huang Tongsheng , Li Xinghui , Shen Conghui , Ren Honglin , Wang Haiping , Wu Teng , Fu Xinlu , Deng Shijie , Feng Ziqi , Xiong Shijie , Li Hui , Gao Saifei , Yang Zhenyu , Gao Fei , Dong Lele , Cheng Jianding , Cai Weibin
Published: March 2023

Diabetic cardiomyopathy is a primary myocardial injury induced by diabetes with complex pathogenesis. In this study, we identify disordered cardiac retinol metabolism in type 2 diabetic male mice and patients characterized by retinol overload, all-trans retinoic acid deficiency. By supplementing type 2 diabetic male mice with retinol or all-trans retinoic acid, we demonstrate that both cardiac retinol overload and all-trans retinoic acid deficiency promote diabetic cardiomyopathy. Mechanistically, by constructing cardiomyocyte-specific conditional retinol dehydrogenase 10-knockout male mice and overexpressing retinol dehydrogenase 10 in male type 2 diabetic mice via adeno-associated virus, we verify that the reduction in cardiac retinol dehydrogenase 10 is the initiating factor for cardiac retinol metabolism disorder and results in diabetic cardiomyopathy through lipotoxicity and ferroptosis. Therefore, we suggest that the reduction of cardiac retinol dehydrogenase 10 and its mediated disorder of cardiac retinol metabolism is a new mechanism underlying diabetic cardiomyopathy.
Zika virus RNA structure controls its unique neurotropism by bipartite binding to Musashi-1
Authors: Chen Xiang , Wang Yan , Xu Zhonghe , Cheng Meng-Li , Ma Qing-Qing , Li Rui-Ting , Wang Zheng-Jian , Zhao Hui , Zuo Xiaobing , Li Xiao-Feng , Fang Xianyang , Qin Cheng-Feng
Published: March 2023

Human RNA binding protein Musashi-1 (MSI1) plays a critical role in neural progenitor cells (NPCs) by binding to various host RNA transcripts. The canonical MSI1 binding site (MBS), A/GU(1-3)AG single-strand motif, is present in many RNA virus genomes, but only Zika virus (ZIKV) genome has been demonstrated to bind MSI1. Herein, we identified the AUAG motif and the AGAA tetraloop in the Xrn1-resistant RNA 2 (xrRNA2) as the canonical and non-canonical MBS, respectively, and both are crucial for ZIKV neurotropism. More importantly, the unique AGNN-type tetraloop is evolutionally conserved, and distinguishes ZIKV from other known viruses with putative MBSs. Integrated structural analysis showed that MSI1 binds to the AUAG motif and AGAA tetraloop of ZIKV in a bipartite fashion. Thus, our results not only identified an unusual viral RNA structure responsible for MSI recognition, but also revealed a role for the highly structured xrRNA in controlling viral neurotropism.
Cell specialization in cyanobacterial biofilm development revealed by expression of a cell-surface and extracellular matrix protein
Authors: Frenkel Alona , Zecharia Eli , Gómez-Pérez Daniel , Sendersky Eleonora , Yegorov Yevgeni , Jacob Avi , Benichou Jennifer I. C. , Stierhof York-Dieter , Parnasa Rami , Golden Susan S. , Kemen Eric , Schwarz Rakefet
Published: March 2023

Cyanobacterial biofilms are ubiquitous and play important roles in diverse environments, yet, understanding of the processes underlying the development of these aggregates is just emerging. Here we report cell specialization in formation of Synechococcus elongatus PCC 7942 biofilms—a hitherto unknown characteristic of cyanobacterial social behavior. We show that only a quarter of the cell population expresses at high levels the four-gene ebfG-operon that is required for biofilm formation. Almost all cells, however, are assembled in the biofilm. Detailed characterization of EbfG4 encoded by this operon revealed cell-surface localization as well as its presence in the biofilm matrix. Moreover, EbfG1-3 were shown to form amyloid structures such as fibrils and are thus likely to contribute to the matrix structure. These data suggest a beneficial ‘division of labor’ during biofilm formation where only some of the cells allocate resources to produce matrix proteins—‘public goods’ that support robust biofilm development by the majority of the cells. In addition, previous studies revealed the operation of a self-suppression mechanism that depends on an extracellular inhibitor, which supresses transcription of the ebfG-operon. Here we revealed inhibitor activity at an early growth stage and its gradual accumulation along the exponential growth phase in correlation with cell density. Data, however, do not support a threshold-like phenomenon known for quorum-sensing in heterotrophs. Together, data presented here demonstrate cell specialization and imply density-dependent regulation thereby providing deep insights into cyanobacterial communal behavior.
Deep learning for exploring ultra-thin ferroelectrics with highly improved sensitivity of piezoresponse force microscopy
Authors: Sriboriboon Panithan , Qiao Huimin , Kwon Owoong , Vasudevan Rama K. , Jesse Stephen , Kim Yunseok
Published: March 2023

Hafnium oxide-based ferroelectrics have been extensively studied because of their existing ferroelectricity, even in ultra-thin film form. However, studying the weak response from ultra-thin film requires improved measurement sensitivity. In general, resonance-enhanced piezoresponse force microscopy (PFM) has been used to characterize ferroelectricity by fitting a simple harmonic oscillation model with the resonance spectrum. However, an iterative approach, such as traditional least squares (LS) fitting, is sensitive to noise and can result in the misunderstanding of weak responses. In this study, we developed the deep neural network (DNN) hybrid with deep denoising autoencoder (DDA) and principal component analysis (PCA) to extract resonance information. The DDA/PCA-DNN improves the PFM sensitivity down to 0.3 pm, allowing measurement of weak piezoresponse with low excitation voltage in 10-nm-thick Hf0.5Zr0.5O2 thin films. Our hybrid approaches could provide more chances to explore the low piezoresponse of the ultra-thin ferroelectrics and could be applied to other microscopic techniques.
Autologous dendritic cell vaccination against HIV-1 induces changes in natural killer cell phenotype and functionality
Authors: Laeremans Thessa , den Roover Sabine , Lungu Cynthia , D’haese Sigrid , Gruters Rob A. , Allard Sabine D. , Aerts Joeri L.
Published: March 2023

Although natural killer (NK) cells have been studied in connection with dendritic cell (DC)-based vaccination in the field of cancer immunology, their role has barely been addressed in the context of therapeutic vaccination against HIV-1. In this study, we evaluated whether a therapeutic DC-based vaccine consisting of monocyte-derived DCs electroporated with Tat, Rev and Nef encoding mRNA affects NK cell frequency, phenotype and functionality in HIV-1-infected individuals. Although the frequency of total NK cells did not change, we observed a significant increase in cytotoxic NK cells following immunisation. In addition, significant changes in the NK cell phenotype associated with migration and exhaustion were observed together with increased NK cell-mediated killing and (poly)functionality. Our results show that DC-based vaccination has profound effects on NK cells, which highlights the importance of evaluating NK cells in future clinical trials looking at DC-based immunotherapy in the context of HIV-1 infection.
Cardiogenic control of affective behavioural state
Authors: Hsueh Brian , Chen Ritchie , Jo YoungJu , Tang Daniel , Raffiee Misha , Kim Yoon Seok , Inoue Masatoshi , Randles Sawyer , Ramakrishnan Charu , Patel Sneha , Kim Doo Kyung , Liu Tony X. , Kim Soo Hyun , Tan Longzhi , Mortazavi Leili , Cordero Arjay , Shi Jenny , Zhao Mingming , Ho Theodore T. , Crow Ailey , Yoo Ai-Chi Wang , Raja Cephra , Evans Kathryn , Bernstein Daniel , Zeineh Michael , Goubran Maged , Deisseroth Karl
Published: March 2023

Emotional states influence bodily physiology, as exemplified in the top-down process by which anxiety causes faster beating of the heart1–3. However, whether an increased heart rate might itself induce anxiety or fear responses is unclear3–8. Physiological theories of emotion, proposed over a century ago, have considered that in general, there could be an important and even dominant flow of information from the body to the brain9. Here, to formally test this idea, we developed a noninvasive optogenetic pacemaker for precise, cell-type-specific control of cardiac rhythms of up to 900 beats per minute in freely moving mice, enabled by a wearable micro-LED harness and the systemic viral delivery of a potent pump-like channelrhodopsin. We found that optically evoked tachycardia potently enhanced anxiety-like behaviour, but crucially only in risky contexts, indicating that both central (brain) and peripheral (body) processes may be involved in the development of emotional states. To identify potential mechanisms, we used whole-brain activity screening and electrophysiology to find brain regions that were activated by imposed cardiac rhythms. We identified the posterior insular cortex as a potential mediator of bottom-up cardiac interoceptive processing, and found that optogenetic inhibition of this brain region attenuated the anxiety-like behaviour that was induced by optical cardiac pacing. Together, these findings reveal that cells of both the body and the brain must be considered together to understand the origins of emotional or affective states. More broadly, our results define a generalizable approach for noninvasive, temporally precise functional investigations of joint organism-wide interactions among targeted cells during behaviour.
Modified variational autoencoder for inversely predicting plasmonic nanofeatures for generating structural color
Authors: Pillai Prajith , Rai Beena , Pal Parama
Published: March 2023

We apply a modified variational autoencoder (VAE) regressor for inversely retrieving the topological parameters of the building blocks of plasmonic composites for generating structural colors as per requirement. We demonstrate results of a comparison study between inverse models based on generative VAEs as well as conventional tandem networks that have been favored traditionally. We describe our strategy for improving the performance of our model by filtering the simulated dataset prior to training. The VAE- based inverse model links the electromagnetic response expressed as the structural color to the geometrical dimensions from the latent space using a multilayer perceptron regressor and shows better accuracy over a conventional tandem inverse model.
A suture anchor-based repair technique for type IV jersey finger injuries: a biomechanical investigation
Authors: Halát Gabriel , Negrin Lukas Leopold , Hoppe Paul Lennart , Unger Ewald , Koch Thomas , Hirtler Lena , Hajdu Stefan
Published: March 2023

The aim of this biomechanical investigation was to evaluate a repair technique for type IV FDP tendon avulsions using a suture anchor, addressing the bony and the tendinous aspect of this injury simultaneously. In 45 distal phalanges from human anatomical specimens the injury was simulated and repairs were performed with a suture anchor using an innovative technique, interosseous sutures and a combination of screws and an interosseous suture. Repetitive loading for 500 cycles simulated postoperative mobilization. Repairs were loaded to failure thereafter. Elongation of the tendon-suture complex, gap formation at the bone-bone contact line and at the bone-tendon insertion line, load at first noteworthy displacement (2 mm), load at failure and the mechanism of failure were assessed. The suture anchor technique was superior biomechanically considering load at failure (mean: 72.8 N), bony gap formation (mean: 0.1 mm) as well as tendinous gap formation (mean: 0.7 mm), implying a preferable stability of the repair. Overall, this study demonstrates good ex vivo mechanical stability for a proposed suture anchor repair technique for type IV FDP tendon avulsion injuries, which might enable early postoperative mobilization in patients. The technique's subcutaneous implant placement and low implant load are expected to reduce potential complications observed in other commonly used repair techniques. This approach warrants further evaluation in vivo.
Zinc oxide nanoparticles induce oxidative stress, genotoxicity, and apoptosis in the hemocytes of Bombyx mori larvae
Authors: Belal Rania , Gad Abir
Published: March 2023

The expanded uses of zinc oxide nanoparticles (ZnO-NPs) have grown rapidly in the field of nanotechnology. Thus, the increased production of nanoparticles (NPs) increases the potential risks to the environment and occupationally exposed humans. Hence, safety and toxicity assessment including genotoxicity of these NPs is indispensable. In the present study, we have evaluated the genotoxic effect of ZnO-NPs on 5th larval instar of Bombyx mori after feeding on mulberry leaves treated with ZnO-NPs at concentrations 50 and 100 μg/ml. Moreover, we evaluated its effects on total and different hemocyte count, antioxidant potential and catalase activity on the hemolymph of treated larvae. Results showed that ZnO-NPs at concentrations of 50 and 100 µg/ml have significantly decreased the total hemocyte count (THC) and different hemocyte count (DHC) except the number of oenocytes as they were significantly increased. Gene expression profile also showed up-regulation of GST, CNDP2 and CE genes suggesting increase in antioxidant activity and alteration in cell viability as well as cell signaling.
Resolving hidden pixels beyond the resolution limit of projection imaging by square aperture
Authors: Xu Kelvin J. , Xu Gu
Published: March 2023

Projection imaging has been employed widely in many areas, such as x-ray radiography, due to its penetration power and ballistic geometry of their paths. However, its resolution limit remains a major challenge, caused by the conflict of source intensity and source size associated with image blurriness. A simple yet robust scheme has been proposed here to solve the problem. An unconventional square aperture, rather than the usual circular beam, is constructed, which allows for the straightforward deciphering of a blurred spot, to unravel hundreds originally hidden pixels. With numerical verification and experimental demonstration, our proposal is expected to benefit multiple disciplines, not limited to x-ray imaging.
The role of defense styles and psychopathological symptoms on adherence to conspiracy theories during the COVID-19 pandemic
Authors: Gioia Francesca , Imperato Chiara , Boursier Valentina , Franceschini Christian , Schimmenti Adriano , Musetti Alessandro
Published: March 2023

Due to the unpredictability of the COVID-19 pandemic situation, individuals felt uncertain and insecure. As a consequence, conspiracy theories flourished and quickly spread. In the current study, we examine the relationship between general and COVID-19-related conspiracy theories, cognitive reflection, psychopathological symptoms, and defense styles in a sample of Italian adults. A total of 450 participants (50.2% male; mean age = 40.89 years, SD = 12.15) took part in an online survey. Two linear regression models on the general (explained variance 22.6%) and COVID-19-related (explained variance 33.0%) conspiracy theories have been tested. Among the predictive factors, older age, mania symptoms, and immature defenses facilitate adherence to conspiracy theories; on the opposite side, higher education, cognitive reflection, and mature defenses protected from adherence to conspiracy theories. The study provides some novel findings about factors that are significantly associated with general and COVID-19-related conspiracy theories, and highlights the pivotal role of individuals’ psychological defenses in conspiracy theories.
Maximum dose, safety, tolerability and ketonemia after triheptanoin in glucose transporter type 1 deficiency (G1D)
Authors: Málaga Ignacio , Avila Adrian , Primeaux Sharon , Kallem Raja Reddy , Roe Charles R. , Putnam William C. , Park Jason Y. , Shinnar Shlomo , Ahn Chul , Pascual Juan M.
Published: March 2023

Augmentation of anaplerosis, or replenishment of carbon lost during intermediary metabolic transitions, is desirable in energy metabolism defects. Triheptanoin, the triglyceride of 7-carbon heptanoic acid, is anaplerotic via direct oxidation or 5-carbon ketone body generation. In this context, triheptanoin can be used to treat Glucose transporter type 1 deficiency encephalopathy (G1D). An oral triheptanoin dose of 1 g/Kg/day supplies near 35% of the total caloric intake and impacted epilepsy and cognition in G1D. This provided the motivation to establish a maximum, potentially greater dose. Using a 3 + 3 dose-finding approach useful in oncology, we studied three age groups: 4–6, 6.8–10 and 11–16 years old. This allowed us to arrive at a maximum tolerated dose of 45% of daily caloric intake for each group. Safety was ascertained via analytical blood measures. One dose-limiting toxicity, occurring in 1 of 6 subjects, was encountered in the middle age group in the context of frequently reduced gastrointestinal tolerance for all groups. Ketonemia following triheptanoin was determined in another group of G1D subjects. In them, β-ketopentanoate and β-hydroxypentanoate concentrations were robustly but variably increased. These results enable the rigorous clinical investigation of triheptanoin in G1D by providing dosing and initial tolerability, safety and ketonemic potential.

ClinicalTrials.gov registration: NCT03041363, first registration 02/02/2017.
Community detection in brain connectomes with hybrid quantum computing
Authors: Wierzbiński Marcin , Falcó-Roget Joan , Crimi Alessandro
Published: March 2023

Recent advancements in network neuroscience are pointing in the direction of considering the brain as a small-world system with an efficient integration-segregation balance that facilitates different cognitive tasks and functions. In this context, community detection is a pivotal issue in computational neuroscience. In this paper we explored community detection within brain connectomes using the power of quantum annealers, and in particular the Leap’s Hybrid Solver in D-Wave. By reframing the modularity optimization problem into a Discrete Quadratic Model, we show that quantum annealers achieved higher modularity indices compared to the Louvain Community Detection Algorithm without the need to overcomplicate the mathematical formulation. We also found that the number of communities detected in brain connectomes slightly differed while still being biologically interpretable. These promising preliminary results, together with recent findings, strengthen the claim that quantum optimization methods might be a suitable alternative against classical approaches when dealing with community assignment in networks.
Electrical and thermal characterisation of liquid metal thin-film Ga$$_2$$O$$_3$$–SiO$$_2$$ heterostructures
Authors: Petkov Alexander , Mishra Abhishek , Cattelan Mattia , Field Daniel , Pomeroy James , Kuball Martin
Published: March 2023

Heterostructures of Ga$$_2$$

2

O$$_3$$

3

with other materials such as Si, SiC or diamond, are a possible way of addressing the low thermal conductivity and lack of p-type doping of Ga$$_2$$

2

O$$_3$$

3

for device applications, as well as of improving device reliability. In this work we study the electrical and thermal properties of Ga$$_2$$

2

O$$_3$$

3

–SiO$$_2$$

2

heterostructures. Here, thin-film gallium oxide with thickness ranging between 8 and 30 nm was deposited onto a silicon substrate with a thermal oxide by means of oxidised liquid gallium layer delamination. The resulting heterostructure is then characterised by means of X-ray photoelectron spectroscopy and transient thermoreflectance. The thin-film gallium oxide valence band offset with respect to the SiO$$_2$$

2

is measured as 0.1 eV and predicted as $$-2.3$$

-
2.3

eV with respect to diamond. The thin-film’s out-of-plane thermal conductivity is determined to be 3 ±0.5 Wm$$^{-1}$$

-
1

 K$$^{-1}$$

-
1

, which is higher than what has been previously measured for other polycrystalline Ga$$_2$$

2

O$$_3$$

3

films of comparable thickness.
The effect of linagliptin on microalbuminuria in patients with diabetic nephropathy: a randomized, double blinded clinical trial
Authors: Karimifar Mozhgan , Afsar Jamileh , Amini Massoud , Moeinzadeh Firouzeh , Feizi Awat , Aminorroaya Ashraf
Published: March 2023

The aim of the present study was to investigate the effect of linagliptin on microalbuminuria in patients with diabetic nephropathy (DN). The present double-blind randomized placebo-controlled clinical trial was performed on 92 patients with DN who were divided into two groups. The intervention and control groups received linagliptin 5 mg and placebo for 24 weeks, respectively. Blood pressure, lipid profile, liver enzymes, fasting plasma glucose (FPG), and urine albumin-creatinine ratio (UACR) were assessed and recorded before, 12 weeks, and 24 weeks after the beginning of the intervention. The mean value of UACR decrease was significant over time in both groups, with higher decrease in linagliptin group, however, the differences between two groups were not, statistically significant (P > 0.05). However, the percentage of improvement in microalbuminuria (UACR < 30 mg/g) in the linagliptin group was significantly higher than that of the control group during 24 weeks of intervention (68.3% vs. 25%; P-value < 0.001). There was no statistically significant difference in the mean value of the UACR and other parameters between linagliptin treated and placebo treated patients with diabetic nephropathy. Further studies, with longer periods of follow-up are suggested to examine these patients’ renal outcomes.
A thermophilic chemolithoautotrophic bacterial consortium suggests a mutual relationship between bacteria in extreme oligotrophic environments
Authors: Pinheiro Yuri , Faria da Mota Fabio , Peixoto Raquel S. , van Elsas Jan Dirk , Lins Ulysses , Mazza Rodrigues Jorge L. , Rosado Alexandre Soares
Published: March 2023

A thermophilic, chemolithoautotrophic, and aerobic microbial consortium (termed carbonitroflex) growing in a nutrient-poor medium and an atmosphere containing N2, O2, CO2, and CO is investigated as a model to expand our understanding of extreme biological systems. Here we show that the consortium is dominated by Carbonactinospora thermoautotrophica (strain StC), followed by Sphaerobacter thermophilus, Chelatococcus spp., and Geobacillus spp. Metagenomic analysis of the consortium reveals a mutual relationship among bacteria, with C. thermoautotrophica StC exhibiting carboxydotrophy and carbon-dioxide storage capacity. C. thermoautotrophica StC, Chelatococcus spp., and S. thermophilus harbor genes encoding CO dehydrogenase and formate oxidase. No pure cultures were obtained under the original growth conditions, indicating that a tightly regulated interactive metabolism might be required for group survival and growth in this extreme oligotrophic system. The breadwinner hypothesis is proposed to explain the metabolic flux model and highlight the vital role of C. thermoautotrophica StC (the sole keystone species and primary carbon producer) in the survival of all consortium members. Our data may contribute to the investigation of complex interactions in extreme environments, exemplifying the interconnections and dependency within microbial communities.