bluuebunny/crossref_metadata_2025 huggingface dataset:
The feedback cycles between glucose, amino acids and lipids and alpha cell secretion and their role in metabolic fatty liver disease
Authors: Winther-Sørensen Marie , Holst Jens J. , Wewer Albrechtsen Nicolai J.
Published: November 2022

Purpose of review

Glucagon increases hepatic glucose production and in patients with metabolic diseases, glucagon secretion is increased contributing to diabetic hyperglycemia. This review explores the role of amino acids and lipids in the regulation of glucagon secretion and how it may be disturbed in metabolic diseases such as obesity and metabolic associated fatty liver disease (MAFLD).

Recent findings

Human and animal studies have shown that MAFLD is associated with glucagon resistance towards amino acid catabolism, resulting in elevated plasma levels of amino acids. A recent clinical study showed that MAFLD is also associated with glucagon resistance towards lipid metabolism. In contrast, MAFLD may not decrease hepatic sensitivity to the stimulatory effects of glucagon on glucose production.

Elevated plasma levels of amino acids and lipids associated with MAFLD may cause diabetogenic hyperglucagonemia. MAFLD and glucagon resistance may therefore be causally linked to hyperglycemia and the development of type 2 diabetes.
Parental Childhood Adversity and Pediatric Emergency Department Utilization
Authors: Weigert Rachel M. , McMichael Brianna S. , VanderVelden Heidi A. , Lee Daniel B. , Cutler Gretchen J. , Troy Mike F. , Bergmann Kelly R.
Published: November 2022

Objectives

Adverse childhood experiences (ACEs) including physical, emotional, or sexual abuse; neglect; and/or exposure to household instability have been associated with adult emergency department utilization, but the impact of parental ACEs on pediatric emergency department (PED) utilization has not been studied. The primary aim was to determine if parental ACEs impact resource utilization as measured by (1) frequency of PED utilization, (2) acuity of PED visits, and (3) 72-hour PED return rates. The secondary aim was to determine if resilience interacts with the impact of parental ACEs on PED utilization.

Methods

This study is a cross-sectional survey using previously validated measures of ACEs, resiliency, and social determinants of health screening. Surveys were administered from October 17, 2019, to November 27, 2019, via iPad by research assistants in our institution's PEDs. Survey responses were linked to data abstracted from the electronic health record. Descriptive statistics were used to characterize our study population. Pearson correlation was used to identify correlation between ACEs, social determinants of health, and PED utilization measures.

Results

A total of 251 parents had complete data. Parental ACEs were positively associated with frequency of PED visits (incidence rate ratio, 1.013). In addition, high levels of parental resilience attenuated the association between parental ACEs and the number of severe acuity visits and were associated with fewer 72-hour return visits (incidence rate ratio, 0.49).

Conclusions

Parental ACEs appear to be positively associated with frequency of PED utilization and inversely associated with higher-acuity PED visits and parental resiliency.
Perioperative Hormone Management in Gender-Affirming Mastectomy: Is Stopping Testosterone Before Top Surgery Really Necessary?
Authors: Robinson Isabel S. , Rifkin William J. , Kloer Carmen , Parker Augustus , Blasdel Gaines , Shaker Nabeel , Zhao Lee C. , Bluebond-Langner Rachel
Published: November 2022

BACKGROUND:

Gender-affirming mastectomy, or “top surgery,” has become one of the most frequently performed procedures for transgender and nonbinary patients. However, management of perioperative testosterone therapy remains controversial. Despite a lack of supporting evidence, many surgeons require cessation of testosterone prior to top surgery. This represents the first study to compare complication rates in patients undergoing gender-affirming mastectomy with and without discontinuation of perioperative testosterone.

METHODS:

Retrospective review identified patients undergoing top surgery by the senior author between 2017 and 2020. Reflecting a change in the senior author’s practice, prior to May 2019, all patients were required to discontinue testosterone prior to surgery, while all patients treated after this point continued their testosterone regimens throughout the perioperative period. Patients were stratified according to testosterone regimen and perioperative hormone management, with demographics and postoperative outcomes compared between groups.

RESULTS:

490 patients undergoing gender-affirming mastectomy during the study period were included. Testosterone was held perioperatively in 175 patients and continued in 211 patients, while 104 patients never received testosterone therapy. Demographics were similar between groups, and there was no difference in rates of hematoma (2.9% vs. 2.8% vs 2.9% respectively, p=0.99), seroma (1.1% vs. 0% vs 1%, p=0.31), venous thromboembolism (0% vs. 0.5% vs 0%, p=0.99), or overall complications (6.9% vs. 4.3% vs 5.8%, p=0.54).

CONCLUSIONS:

Our results demonstrate no difference in postoperative complication rates between groups. While further investigation is warranted, our data suggest that routine cessation of testosterone in the perioperative period is not necessary for patients undergoing gender-affirming mastectomy.
Delayed Cerebrospinal Fluid Leaks Complicating Endoscopic Orbital Surgeries
Authors: Yang Muyue , Ma Liang , Zhuang Ai
Published: November 2022

Objective:

To report cerebrospinal fluid leak as an uncommon but noteworthy delayed complication after endoscopic orbital surgeries and to describe its incidence, mechanism, prevention, diagnosis, and management.

Methods:

Case series of 3 patients who underwent endoscopic orbital surgery in the Department of Ophthalmology, Shanghai Ninth People’s Hospital affiliated to Shanghai JiaoTong University School of Medicine from January 2003 to December 2020. A review of the literature was also conducted.

Results:

Three cases of delayed cerebrospinal fluid leaks occurred 10 years, 3 months, and 4 months after endoscopic orbital surgeries, respectively, were reviewed and reported. Two patients developed cerebrospinal fluid leaks after surgical repair of orbital blowout fractures with titanium mesh and porous polyethylene (Medpor), respectively, and 1 patient developed cerebrospinal fluid leak after transantral optic canal decompression. In the first case, head computed tomography (CT) cisternography and magnetic resonance imaging confirmed the site of the leak that required surgical repair. In the second case, a coronal CT showed that the implanted titanium mesh was tightly against the cribriform plate, which might cause defect of skull base and dura. In the third case, orbital CT identified a dehiscence on the sphenoidal wall as the leak site, which was repaired in a secondary endoscopic surgery.

Conclusions:

A cerebrospinal fluid leak, as an uncommon but noteworthy complication, can occur as delayed as 10 more years after surgery. For patients with specific anatomic characteristics, such as Kero type III, surgeons should perform meticulous preoperative evaluation and intraoperative procedures to prevent this complication.
Hepatitis E Virus Infection, a Risk for Liver Transplant Recipients in Sweden
Authors: Frankal Miriam , Skoglund Catarina , Castedal Maria , Lagging Martin , Norder Heléne
Published: November 2022

Background.

Following exposure to hepatitis E virus (HEV), liver transplant (LT) recipients have an increased risk of developing chronic infection, which may rapidly progress to severe liver damage if not treated. The prevalence of HEV infection after LT is unclear and likely varies geographically. The aim of this study was to investigate the prevalence of acute and chronic HEV infection among LT recipients in an HEV endemic region.

Methods.

During 2013 to 2015, 109 of 152 prospectively enrolled patients listed for LT received a liver graft and completed the study protocol. They were evaluated for anti-HEV IgM, HEV IgG, and HEV RNA at the time of LT assessment and 3 and 12 mo post-LT. Medical records were reviewed.

Results.

Twelve (11%) LT recipients acquired markers of HEV infection during the study period. Seven patients (6%) had detectable HEV RNA, 1 before LT and 3 at the 3-mo and another 3 at the 12-mo follow-up post-LT. All resolved their infections without treatment and had undetectable HEV RNA at the succeeding follow-up. Another 5 (5%) patients developed anti-HEV antibodies without detectable HEV RNA as an indication of HEV infection during follow-up. Signs and symptoms of HEV infection were subtle‚ and none were diagnosed in routine clinical care.

Conclusion.

A substantial proportion of LT recipients in Sweden are at risk of acquiring HEV infection, both before and after LT. The results highlight the frequency of silent, spontaneously resolving HEV infections and do not support universal screening of LT recipients in Sweden, despite HEV being a potentially treatable infection.
A systems approach framework for evaluating tree restoration interventions for social and ecological outcomes in rural tropical landscapes
Authors: Pfeifer Marion , Sallu Susannah M. , Marshall Andrew R. , Rushton Stephen , Moore Eleanor , Shirima Deo D. , Smit Josephine , Kioko Esther , Barnes Lauren , Waite Catherine , Raes Leander , Braunholtz Laura , Olivier Pieter I. , Ishengoma Evodius , Bowers Sam , Guerreiro-Milheiras Sergio
Published: November 2022

The science guiding design and evaluation of restoration interventions in tropical landscapes is dominated by ecological processes and outcomes and lacks indicators and methods that integrate human wellbeing into the restoration process. We apply a new systems approach framework for tree restoration in forest-agricultural landscapes to show how this shortcoming can be addressed. Demonstrating ‘proof of concept’, we tested statistical models underlying the framework pathways with data collected from a case study in Tanzania. Local community perceptions of nature's values were not affected by levels of self-reported wildlife-induced crop damage. But mapped predictions from the systems approach under a tree restoration scenario suggested differential outcomes for biodiversity indicators and altered spatial patterns of crop damage risk, expected to jeopardize human wellbeing. The predictions map anticipated trade-offs in costs and benefits of restoration scenarios, which we have started to explore with stakeholders to identify restoration opportunities that consider local knowledge, value systems and human wellbeing. We suggest that the framework be applied to other landscapes to identify commonalities and differences in forest landscape restoration outcomes under varying governance and land use systems. This should form a foundation for evidence-based implementation of the global drive for forest landscape restoration, at local scales.

This article is part of the theme issue ‘Understanding forest landscape restoration: reinforcing scientific foundations for the UN Decade on Ecosystem Restoration’.
Realizing the potential of restoration science
Authors: Lewis Simon L.
Published: November 2022

Restoration science is growing fast. The restoration of habitats is increasingly part of the discussion over how to tackle the challenges of climate change, biodiversity loss and rural development. With this increasing role and attendant visibility, restoration science has seen increasing controversy. Here I describe six aspects of robust restoration science that should be kept in mind to help realize its potential: do data-driven studies; focus on robust results; improve reproducibility; contextualize the results; give attention to economics; consider the wider goals of restoration. Realizing the potential of restoration science, via robust scientific studies, will provide society with the knowledge and tools to make better choices about which habitats to restore and where.

This article is part of the theme issue ‘Understanding forest landscape restoration: reinforcing scientific foundations for the UN Decade on Ecosystem Restoration’.
Analysis of functional connectivity using machine learning and deep learning in multimodal data from patients with schizophrenia
Authors: Alves Caroline L. , Toutain Thaise G. L. de O. , Porto Joel Augusto Moura , Aguiar Patricia de Carvalho , Pineda Aruane M. , Rodrigues Francisco A. , de Sena Eduardo Pondé , Thielemann Christiane
Published: November 2022

Schizophreniais a severe mental disorder associated with persistent or recurrent psychosis, hallucinations, delusions, and thought disorders that affect approximately 26 million people worldwide, according to the World Health Organization (WHO). Several studies encompass machine learning and deep learning algorithms to automate the diagnosis of this mental disorder. Others study schizophrenia brain networks to get new insights into the dynamics of information processing in patients suffering from the condition. In this paper, we offer a rigorous approach with machine learning and deep learning techniques for evaluating connectivity matrices and measures of complex networks to establish an automated diagnosis and comprehend the topology and dynamics of brain networks in schizophrenia patients. For this purpose, we employed an fMRI and EEG dataset in a multimodal fashion. In addition, we combined EEG measures, i.e., Hjorth mobility and complexity, to complex network measurements to be analyzed in our model for the first time in the literature. When comparing the schizophrenia group to the control group, we found a high positive correlation between the left superior parietal lobe and the left motor cortex and a positive correlation between the left dorsal posterior cingulate cortex and the left primary motor. In terms of complex network measures, the diameter, which corresponds to the longest shortest path length in a network, may be regarded as a biomarker because it is the most important measure in a multimodal fashion. Furthermore, the schizophrenia brain networks exhibit less segregation and lower distribution of information. As a final result, EEG measures outperformed complex networks in capturing the brain alterations associated with schizophrenia. As a result, our model achieved an AUC of 100%, an accuracy of 98% for the fMRI, an AUC of 95 %, and an accuracy of 95% for the EEG data set. These are excellent classification results. Furthermore, we investigated the impact of specific brain connections and network measures for these results, which helped us better describe changes in the diseased brain.
Network topology enables efficient response to environment inPhysarum polycephalum
Authors: Chen Siyu , Alim Karen
Published: November 2022

The network-shaped body plan distinguishes the unicellular slime mouldPhysarum polycephalumin body architecture from other unicellular organisms. Yet, network-shaped body plans dominate branches of multi-cellular life such as in fungi. What survival advantage does a network structure provide when facing a dynamic environment with adverse conditions? Here, we probe how network topology impactsP. polycephalum’s avoidance response to an adverse blue light. We stimulate either an elongated, I-shaped amoeboid or a Y-shaped networked specimen and subsequently quantify the evacuation process of the light-exposed body part. The result shows that Y-shaped specimen complete the avoidance retraction in a comparable time frame, even slightly faster than I-shaped organisms, yet, at a lower almost negligible increase in migration velocity. Contraction amplitude driving mass motion is further only locally increased in Y-shaped specimen compared to I-shaped providing further evidence that Y-shaped’s avoidance reaction is energetically more efficient than in I-shaped amoeboid organisms. The difference in the retraction behaviour suggests that the complexity of network topology provides a key advantage when encountering adverse environments. Our findings could lead to a better understanding of the transition from unicellular to multicellularity.
Pulsed stimulated Brillouin microscopy enables high-sensitivity mechanical imaging of live and fragile biological specimens
Authors: Yang Fan , Bevilacqua Carlo , Hambura Sebastian , Neves Ana , Gopalan Anusha , Watanabe Koki , Govendir Matt , Bernabeu Maria , Ellenberg Jan , Diz-Muñoz Alba , Köhler Simone , Rapti Georgia , Jechlinger Martin , Prevedel Robert
Published: November 2022

Brillouin microscopy is an emerging optical elastography technique capable of assessing mechanical properties of biological samples in a 3D, all-optical and hence non-contact fashion. The typically weak Brillouin scattering signal can be substantially enhanced via a stimulated photon-phonon process, which improves the signal-to-background ratio (SBR) as well as provides higher spectral resolution. However, current implementations of stimulated Brillouin spectroscopy (SBS) require high pump powers, which prohibit applications in many areas of biology, especially when studying photosensitive samples, or when live-imaging in 3D and/or over extended time periods. Here, we present a pulsed SBS scheme that takes full advantage of the non-linearity of the pump-probe interaction in SBS. In particular, we show that through quasi-pulsing and diligent optimization of signal detection parameters, the required pump laser power can be decreased ~20-fold without affecting the signal levels or spectral precision. Moreover, we devise a custom analysis approach that facilitates the analysis of complex, multi-peaked Brillouin spectra in order to harness the high spectral resolution of SBS for the specific identification of biomechanical components inside the point-spread function of the microscope. We then demonstrate the low-phototoxicity and high-specificity of our pulsed SBS approach by imaging sensitive single cells, zebrafish larvae, and mouse embryos as well as adultC. eleganswith sub-cellular detail. Furthermore, our method permits observing the mechanics of organoids andC. elegansembryos over time. We expect that the substantially lower photo-burden and improved SBR of pulsed SBS will facilitate studying biomechanics in 3D at high spatio-temporal resolution in living biological specimens in a non-invasive manner, opening up exciting new possibilities for the field of mechanobiology.
A physiologically-based model of bile acid metabolism in mice
Authors: Kister Bastian , Viehof Alina , Rolle-Kampczyk Ulrike , Schwentker Annika , Treichel Nicole Simone , Jennings Susan , Wirtz Theresa H. , Blank Lars M. , Hornef Mathias W. , von Bergen Martin , Clavel Thomas , Kuepfer Lars
Published: November 2022

Bile acid (BA) metabolism is a complex system that includes a wide variety of primary and secondary, as well as conjugated and unconjugated BAs that undergo continuous enterohepatic circulation (EHC). Alterations in both composition and dynamics of BAs have been associated with various diseases. However, a mechanistic understanding of the relationship between altered BA metabolism and related diseases is lacking. Computational modeling may support functional analyses of the physiological processes involved in the EHC of BAs along the gut-liver axis. In this study, we developed a physiologically-based model of murine BA metabolism describing synthesis, conjugation, microbial transformations, systemic distribution, excretion and EHC of BAs at the whole-body level. For model development, BA metabolism of specific pathogen-free (SPF) mice was characterized in vivo by measuring BA levels and composition in various organs, expression of transporters along the gut and cecal microbiota composition. We found significantly different BA levels between male and female mice that could only be explained by adjusted expression of the hepatic enzymes and transporters in the model. Of note, this finding was in agreement with experimental observations. The model for SPF mice could also describe equivalent experimental data in germ-free mice by specifically switching of microbial activity in the intestine. The here presented model can therefore facilitate and guide functional analyses of BA metabolism in mice, e.g., the effect of pathophysiological alterations on BA metabolism and translation of results from mouse studies to a clinically relevant context through cross-species extrapolation.
Consortium bibliometric analysis of hotspots and frontiers of immunotherapy in pancreatic cancer
Authors: Xu Qiong , Zhou Yan , Zhang Heng , Li Haipeng , Qin Haoren , Wang Hui
Published: November 2022

Background

Pancreatic cancer is one of the most common malignant neoplasms with an increasing incidence, low rate of early diagnosis, and high degree of malignancy. In recent years, immunotherapy has made remarkable achievements in various cancer types including pancreatic cancer, due to the long-lasting antitumor responses elicited in human body. Immunotherapy mainly relies on mobilizing the host’s natural defense mechanisms to regulate the body state and exert anti-tumor effects. However, no bibliometric research about pancreatic cancer immunotherapy has been reported to date. This study aimed to assess research trends and offer possible new research directions in pancreatic cancer immunotherapy.

Methods

The articles and reviews related to the pancreatic cancer immunotherapy were collected from the Web of Science Core Collection. CiteSpace, VOSviewer and an online platform were used to analyse co-authorship, citation, co-citation, and co-occurrence of terms retrieved from literatures highlighting the scientific advances in pancreatic cancer immunotherapy.

Results

We collected 2475 publications and the number of articles was growing year by year. The United States had a strong presence worldwide with the most articles. The most contributing institution was Johns Hopkins University (103 papers). EM Jaffee was the most productive researcher with 43 papers, L Zheng and RH Vonderheide ranked second and third, with 34 and 29 papers, respectively. All the keywords were grouped into four clusters: “immunotherapy”, “clinical treatment study”, “tumor immune cell expression”, “tumor microenvironment”. In the light of promising hotspots, keywords with recent citation bursts can be summarized into four aspects: immune microenvironment, adaptive immunotherapy, immunotherapy combinations, and molecular and gene therapy.

Conclusions

In recent decades, immunotherapy showed great promise for many cancer types, so various immunotherapy approaches have been introduced to treat pancreatic cancer. Understanding the mechanisms of immunosuppressive microenvironment, eliminating immune suppression and blocking immune checkpoints, and combining traditional treatments will be hotspots for future research.
3MDR, a microcomputer-controlled visual stimulation device for psychotherapy-like treatments of mice
Authors: Jauch Isa , Kamm Jan , Benn Luca , Rettig Lukas , Friederich Hans-Christoph , Tesarz Jonas , Kuner Thomas , Wieland Sebastian
Published: November 2022

Post-traumatic stress disorder and other mental disorders can be treated by an established psychotherapy called Eye Movement Desensitization and Reprocessing (EMDR). In EMDR, patients are confronted with traumatic memories while they are stimulated with alternating bilateral stimuli (ABS). How ABS affect the brain and whether ABS could be adapted to different patients or mental disorders is unknown. Interestingly, ABS reduced conditioned fear in mice. Yet, an approach to systematically test complex visual stimuli and compare respective differences in emotional processing based on (semi-)automated behavioral analysis is lacking. We developed 3MDR (Model for MultiModal visual stimulation to Desensitize Rodents) - a novel, open-source, low-cost, customizable device that can be integrated in and TTL-controlled by commercial rodent behavioral setups. 3MDR allows to design and precisely steer multimodal visual stimuli in the head direction of freely-moving mice. Optimized videography allows to semi-automatically analyze rodent behavior during visual stimulation. Detailed building, integration, and treatment instructions along with open-source software provide easy access for inexperienced users. Using 3MDR, we confirmed that EMDR-like ABS persistently improve fear extinction in mice and showed for the first time that ABS-mediated anxiolytic effects strongly depend on physical stimulus properties such as ABS brightness. 3MDR not only enables researchers to interfere with mouse behavior in an EMDR-like setting, but demonstrates that visual stimuli can be used as a noninvasive brain stimulation to differentially alter emotional processing in mice.

SIGNIFICANCE STATEMENT

Alternating bilateral stimuli (ABS) reduce fear in post-traumatic stress disorder patients and in mice. The mechanism of how classic ABS – typically used in Eye Movement Desensitization and Reprocessing (EMDR) - reduce fear is enigmatic. We provide detailed resources to build a cost-effective, computer-controlled device called 3MDR to perform and semi-automatically analyze EMDR-like treatments in freely-moving mice and to test behavioral effects of multiple ABS variants. Using the 3MDR device, this study confirmed that classic ABS strongly and persistently improve the extinction of conditioned fear in mice – an effect that depended on the brightness of ABS. This novel method may ultimately contribute to a deeper translational and neurobiological understanding of how visual stimuli affect emotional processing in mice.
Enhanced protein synthesis is a defining requirement for neonatal B cell development
Authors: Åkerstrand Hugo , Boldrin Elena , Montano Giorgia , Vanhee Stijn , Olsson Karin , Krausse Niklas , Vergani Stefano , Cieśla Maciej , Bellodi Cristian , Yuan Joan
Published: November 2022

The LIN28B RNA binding protein exhibits a ontogenically restricted expression pattern and is a key molecular regulator of fetal and neonatal B lymphopoiesis. It enhances the positive selection of CD5+ immature B cells early in life through amplifying the CD19/PI3K/c-MYC pathway and is sufficient to reinitiate self-reactive B-1a cell output when ectopically expressed in the adult. In this study, interactome analysis in primary B cell precursors showed direct binding by LIN28B to numerous ribosomal protein transcripts, consistent with a regulatory role in cellular protein synthesis. Induction of LIN28B expression in the adult setting is sufficient to promote enhanced protein synthesis during the small Pre-B and immature B cell stages, but not during the Pro-B cell stage. This stage dependent effect was dictated by IL-7 mediated signaling, which masked the impact of LIN28B through an overpowering stimulation on the c-MYC / protein synthesis axis in Pro-B cells. Importantly, elevated protein synthesis was a distinguishing feature between neonatal and adult B cell development that was critically supported by endogenousLin28bexpression early in life. Finally, we used a ribosomal hypomorphic mouse model to demonstrate that subdued protein synthesis is specifically detrimental for neonatal B lymphopoiesis and the output of B-1a cells, without affecting B cell development in the adult. Taken together, we identify elevated protein synthesis as a defining requirement for early-life B cell development that critically depends onLin28b. Our findings offer new mechanistic insights into the layered formation of the complex adult B cell repertoire.
The impact of culture variables on 3D humanin vitrobone remodeling; a design of experiments approach
Authors: de Wildt Bregje W.M. , Cuypers Lizzy A.B. , Cramer Esther E.A. , Wentzel Annelieke S. , Ito Keita , Hofmann Sandra
Published: November 2022

Humanin vitrobone remodeling models, using osteoclast-osteoblast co-cultures, could facilitate the investigation of human healthy (i.e., balanced) and pathological (i.e., unbalanced) bone remodeling while reducing the need for animal experiments. Although currentin vitroosteoclast-osteoblast co-cultures have improved our understanding of bone remodeling, they lack culture method and outcome measurement standardization, which is hampering reproducibility and translatability. Therefore,in vitrobone remodeling models could benefit from a thorough evaluation of the impact of culture variables on functional and translatable outcome measures, with the aim to reach ‘healthy’ balanced osteoclast and osteoblast activity. Using a resolution III fractional factorial design, we identified the main effects of commonly used culture variables on bone turnover markers in a robustin vitrohuman bone remodeling model. Our model was able to capture physiological quantitative resorption – formation coupling along all conditions, whereby remodeling could be enhanced by external stimuli. Especially culture conditions of two runs showed promising results, where conditions of one run could be used as a high bone turnover system and conditions of another run as a self-regulating system as the addition of osteoclastic and osteogenic differentiation factors was not required for remodeling. The results generated with ourin vitromodel allow for better translation betweenin vitrostudies and towardsin vivostudies, for improved preclinical bone remodeling drug development.

Graphical abstract
Thalamic nucleus reuniens coordinates prefrontal-hippocampal synchrony to suppress extinguished fear
Authors: Totty Michael S. , Ramanathan Karthik R. , Jin Jingji , Peters Shaun E. , Maren Stephen
Published: November 2022

Traumatic events result in vivid and enduring fear memories. Suppressing the retrieval of these memories is central to behavioral therapies for pathological fear. The medial prefrontal cortex (mPFC) and hippocampus (HPC) have been implicated in retrieval suppression, but how mPFC-HPC activity is coordinated during extinction retrieval is unclear. Here we show that after extinction training, coherent theta oscillations (6-9 Hz) in the HPC and mPFC are correlated with the suppression of conditioned freezing in male and female rats. Inactivation of the nucleus reuniens (RE), a thalamic hub interconnecting the mPFC and HPC, reduces extinction-related Fos expression in both the mPFC and HPC, dampens mPFC-HPC theta coherence, and impairs extinction retrieval. Conversely, theta-paced optogenetic stimulation of RE augments fear suppression and reduces relapse of extinguished fear. Collectively, these results demonstrate a novel role for RE in coordinating mPFC-HPC interactions to suppress fear memories after extinction.
Systematic analysis of cellular crosstalk reveals a role for SEMA6D-TREM2 regulating microglial function in Alzheimer’s disease
Authors: Albanus Ricardo D'Oliveira , Finan Gina M , Brase Logan , Chen Shuo , Guo Qi , Kannan Abhirami , Acquarone Mariana , You Shih-Feng , Novotny Brenna C , Ribeiro Pereira Patricia M , Morris John C , Holtzman David M , McDade Eric , Farlow Martin , Chhatwal Jasmeer P ,   Dominantly Inherited Alzheimer Network (DIAN), Mace Emily E , Benitez Bruno A , Piccio Laura , Sutherland Greg T , Ma Qin , Fu Hongjun , Karch Celeste M , Harari Oscar , Kim Tae-Wan
Published: November 2022

Cellular crosstalk, mediated by membrane receptors and their ligands, is crucial for brain homeostasis and can contribute to neurodegenerative diseases such as Alzheimer’s disease (AD). To discover crosstalk dysregulations in AD, we reconstructed crosstalk networks from single-nucleus transcriptional profiles from 67 clinically and neuropathologically well-characterized controls and AD brain donors. We predicted a significant role for TREM2 and additional AD risk genes mediating neuron-microglia crosstalk in AD. The gene sub-network mediating SEMA6D-TREM2 crosstalk is activated near Aβ plaques andSEMA6D-expressing cells and is disrupted in late AD stages. Using CRISPR-modified human induced pluripotent stem cell-derived microglia, we demonstrated that SEMA6D induces microglial activation in aTREM2-dependent manner. In summary, we demonstrate that characterizing cellular crosstalk networks can yield novel insights into AD biology.

One Sentence Summary

We investigate cell-to-cell communication in Alzheimer’s disease to characterize disease biology and suggest new avenues for therapeutic intervention.
Biomimetic microstimulation of sensory cortices
Authors: Hughes Christopher , Kozai Takashi
Published: November 2022

Background

Intracortical microstimulation (ICMS) is an emerging approach to restore sensation to people with neurological injury or disease. Biomimetic microstimulation, or stimulus trains that mimic neural activity in the brain through encoding of onset and offset transients, could improve the utility of ICMS for BCI applications, but how biomimetic microstimulation affects neural activation is not understood. Stimulus induced depression of neural activity (decreases in evoked intensity over time) is also a potential barrier to clinical implementation of sensory feedback, and biomimetic microstimulation may reduce this effect.

Objective

We evaluated how biomimetic trains change the calcium response, spatial distribution, and depression of neurons in the somatosensory and visual cortices.

Methods

Calcium responses of neurons were measured in Layer 2/3 of visual and somatosensory cortices of anesthetized GCaMP6s mice in response to ICMS trains with fixed amplitude and frequency (Fixed) and three biomimetic ICMS trains that increased the stimulation intensity during the onset and offset of stimulation by modulating the amplitude (BioAmp), frequency (BioFreq), or amplitude and frequency (BioBoth). ICMS was provided for either 1-s with 4-s breaks (Short) or for 30-s with 15-s breaks (Long).

Results

BioAmp and BioBoth trains evoked distinct onset and offset transients in recruited neural populations, while BioFreq trains evoked population activity similar to Fixed trains. Individual neurons had heterogeneous responses primarily based on how quickly they depressed to ICMS, where neurons farther from the electrode depressed faster and a small subpopulation (1-5%) were modulated by BioFreq trains. Neurons that depressed to Short trains were also more likely to depress to Long trains, but Long trains induced more depression overall due to the increased stimulation length. Increasing the amplitude during the hold phase resulted in an increase in recruitment and intensity which resulted in more depression and reduced offset responses. Biomimetic amplitude modulation reduced stimulation induced depression by 14.6±0.3% for Short and 36.1±0.6% for Long trains. Ideal observers were 0.031±0.009 s faster for onset detection and 1.33±0.21 s faster for offset detection with biomimetic amplitude encoding.

Conclusions

Biomimetic amplitude modulation evokes distinct onset and offset transients, reduces depression of neural calcium activity, and decreases total charge injection for sensory feedback in brain-computer interfaces by lowering recruitment of neurons during long maintained periods of ICMS. In contrast, biomimetic frequency modulation evokes distinct onset and offset transients in a small subpopulation of neurons but also reduces depression in recruited neurons by reducing the rate of activation.
Monkey-to-human transfer of brain-computer interface decoders
Authors: Rizzoglio Fabio , Altan Ege , Ma Xuan , Bodkin Kevin L. , Dekleva Brian M. , Solla Sara A. , Kennedy Ann , Miller Lee E.
Published: November 2022

Intracortical brain-computer interfaces (iBCIs) enable paralyzed persons to generate movement, but current methods require large amounts of both neural and movement-related data to be collected from the iBCI user for supervised decoder training. We hypothesized that the low-dimensional latent neural representations of motor behavior, known to be preserved across time, might also be preserved across individuals, and allow us to circumvent this problem. We trained a decoder to predict the electromyographic (EMG) activity for a “source” monkey from the latent signals of motor cortex. We then used Canonical Correlation Analysis to align the latent signals of a “target” monkey to those of the source. These decoders were as accurate across monkeys as they were across sessions for a given monkey. Remarkably, the same process with latent signals from a human participant with tetraplegia was within 90% of the with-monkey decoding across session accuracy. Our findings suggest that consistent representations of motor activity exist across animals and even species. Discovering this common representation is a crucial first step in designing iBCI decoders that perform well without large amounts of data and supervised subject-specific tuning.
Catch bonds in sickle cell disease: shear-enhanced adhesion of red blood cells to laminin
Authors: Goreke Utku , Iram Shamreen , Singh Gundeep , Domínguez-Medina Sergio , Man Yuncheng , Bode Allison , An Ran , Little Jane A. , Wirth Christopher L. , Hinczewski Michael , Gurkan Umut A.
Published: November 2022

Could the phenomenon of catch bonding—force-strengthened cellular adhesion—play a role in sickle cell disease, where abnormal red blood cell (RBC) adhesion obstructs blood flow? Here we investigate the dynamics of sickle RBCs adhering to a surface functionalized with the protein laminin (a component of the extracellular matrix around blood vessels) under physiologically relevant micro-scale flow. First, using total internal reflectance microscopy we characterize the spatial fluctuations of the RBC membrane above the laminin surface before detachment. The complex dynamics we observe suggest the possibility of catch bonding, where the mean detachment time of the cell from the surface initially increases to a maximum and then decreases as a function of shear force. We next conduct a series of shear-induced detachment experiments on blood samples from 25 sickle cell disease patients, quantifying the number and duration of adhered cells under both sudden force jumps and linear force ramps. The experiments reveal that a subset of patients does indeed exhibit catch bonding. By fitting the data to a theoretical model of the bond dynamics, we can extract the mean bond lifetime versus force for each patient. The results show a striking heterogeneity among patients, both in terms of the qualitative behavior (whether or not there is catch bonding) and in the magnitudes of the lifetimes. Patients with large bond lifetimes at physiological forces are more likely to have certain adverse clinical features, like a diagnosis of pulmonary arterial hypertension and intracardiac shunts. By introducing anin vitroplatform for fully characterizing RBC-laminin adhesion dynamics, our approach could contribute to the development of patient-specific anti-adhesive therapies for sickle cell disease. The experimental setup is also easily generalizable to studying adhesion dynamics in other cell types, for example leukocytes or cancer cells, and can incorporate disease-relevant environmental conditions like oxygen deprivation.

SIGNIFICANCE

Abnormal red blood cell adhesion to the walls of blood vessels is a central feature of sickle cell disease. We study this adhesion by experimentally measuring how long on average red blood cells adhere to a protein-covered surface, and how the strength of the cell-protein bond depends on the force resulting from the surrounding fluid flow. The results vary widely from patient to patient, with some cases showing an unusual regime where the mean bond strength increases with force. We connect these measurements to clinical aspects of the disease, which may aid in the design of individualized therapies in the future.
Cardiac Events Following JYNNEOS Vaccination for Prevention of Monkeypox
Authors: Sharff Katie A , Tandy Thomas K , Lewis Paul F , Johnson Eric S
Published: November 2022

Purpose

The JYNNEOS vaccine is an FDA-approved vaccine indicated for prevention of smallpox and monkeypox that is currently being distributed to high-risk individuals to combat the monkeypox public health emergency. The FDA safety data for JYNNEOS vaccine notes potential cardiac adverse events of special interest (AESI) following vaccination. The Advisory Committee on Immunization Practices (ACIP) stated that people with underlying heart disease or three or more major cardiac risk factors should be counseled about the theoretical risk for myopericarditis following vaccination with JYNNEOS. Our objective was to describe the incidence of cardiac AESIs in the Kaiser Permanente Northwest (KPNW) population who received a JYNNEOS vaccination for prevention of monkeypox.

Methods

We conducted a retrospective cohort study of 2,126 KPNW patients aged 12 or older who were vaccinated with at least 1 dose of JYNNEOS vaccine between July 14th2022 and October 10th2022. We searched KPNW databases, including the electronic health record (EHR), for diagnoses of elevated troponins, chest pain, myocarditis, pericarditis, myopericarditis, acute myocardial infarction, cardiac dysrhythmia, cardiac arrest, or ventricular fibrillation that were documented during any encounter (visit) using ICD-10-CM diagnosis codes. Two KPNW physicians reviewed all possible cases in the EHR to adjudicate cases as cardiac AESIs in alignment with the case definition used in the FDA safety data.

Results

There were 2,126 KPNW members who received a total of 3,235 JYNNEOS vaccine doses between July 14thand October 10th. Encounter ICD10 diagnosis codes and troponin values identified 24 possible cardiac AESI cases. After physician adjudication, there were 10 confirmed cardiac AESI for an incidence of 3.1 per 1000 doses given with (exact 95% CI, 1.5 to 5.7). Of these 10 events, none could be attributed directly to the vaccination.

Conclusion

The incidence of cardiac adverse events following JYNNEOS vaccination for prevention of monkeypox is unknown and this is the first study to evaluate cardiac AESI following JYNNEOS vaccination in the 2022 monkeypox public health emergency. This retrospective cohort study of JYNNEOS vaccination for prevention of monkeypox identified 10 cardiac events that all had alternative explanations; and no hospitalizations or serious adverse outcomes were attributed to vaccination. This initial study provides timely information for the clinician counseling their patient with underlying cardiac risk factors on the low observed risk of cardiac events with JYNNEOS vaccination during the 2022 monkeypox public health emergency.
Taurine, a non-proteinous essential amino acid for human body systems: an overview
Authors: Rais Nadeem , Ved Akash , Shadab Mohd. , Ahmad Rizwan , Shahid Mohammad
Published: November 2022

Purpose

Taurine (2-aminoethane sulfonic acid; C2H7NO3S) is a nonprotein sulfur-containing β-amino acid present in nearly all mammalian tissues and the most ubiquitous free endogenous biomolecule in human cells. Taurine is commonly known as a conditionally essential amino acid because taurine is one of the few amino acids that are not incorporated in protein synthesis. The purpose of this study is to review the existing articles related to taurine and to give an account how useful is taurine to the different body systems. In this thorough overview, taurine is covered in terms of its essentiality, sources, advantages for neonates and the elderly, the effects of taurine deficiency, and the safety and toxicity of taurine supplements.

Design/methodology/approach

This is a narrative review into the subject matter. Published articles were searched on different portals like PubMed, EMBASE, Scopus, Google Scholar, PubChem etc. The authors also evaluated the availability of taurine in commercially available energy drinks.

Findings

This comprehensive review, presents the potential clinical benefits and functional properties of taurine as a conditionally essential amino acid. Energy drinks containing taurine (and their concentration) are also reported in this review.

Originality/value

This is the first data that the authors are aware of that shows taurine content in a variety of energy drinks on the market.
The influences of telecommunication technology and gender differences on private savings in the Asia–Pacific region
Authors: Tang Chor Foon , Abosedra Salah
Published: November 2022

Purpose

The purpose of this study is to examine empirically the impacts of gender differences, telecommunication technology (ICT) and other determinants on private savings in 28 selected Asia–Pacific countries.

Design/methodology/approach

This study employs the panel data from 2010 to 2017 across 28 selected Asia–Pacific countries. To enhance robustness and address the possibility of endogeneity issue, the present study utilises the fixed effect instrumental variable (IV) estimator to estimate the private savings model for Asia–Pacific region.

Findings

The present study finds that private savings is positively related to disposable income and ICT, but it is negatively associated with the degree of dependency. However, the association between interest rates and private savings are inconclusive as both positive substitution and negative income effects on private savings were observed. Moreover, the results also indicate that working females tend to save less than working males and that of the educated female, despite their impacts are varied across educational attainment levels.

Originality/value

This study provides a novel insight into private savings patterns by focussing upon the gender differences and ICT aspects. In stark contrast to previous literature on the issue, the authors find that working and educated females negatively impact private savings in Asia–Pacific economies due to income inequality and consumption habits. However, the results show that ICT accelerates private savings as it provides easy access to financial services and the requisite frameworks, such as e-business platforms, for generating passive income as well as provide the modalities for more cost-efficient shopping such as price and product comparison frames that yield costs savings which can then be potentially channelled into private savings.
Creating discursive channels: generating and disseminating impactful research insights into the strategic sales enablement of retail technology
Authors: Montecchi Matteo , Bonetti Francesca , Plangger Kirk , Schau Hope Jensen
Published: November 2022

Purpose

To meet the complex technology needs of retail clients, technology providers must work in a close partnership with their clients and co-envisage a strategic vision for the role that technology should play in the client’s value chain. However, many providers lack the sales capabilities needed to do this. This study aims to examine the need for providers to transition from transaction-oriented to solution selling-oriented approaches. To do so, this study explores the impact outcomes of a knowledge-exchange intervention co-designed with a partner from industry.

Design/methodology/approach

Building on empirical insights from an ongoing research programme that examines retail technology implementations, this study developed a knowledge exchange intervention consisting of planning discursive channels, co-defining the scope, co-developing knowledge, executing the intervention and assessing impact outcomes. Discursive channels – multi-lateral communication channels that allow researchers to work collaboratively with the research partner and other stakeholders – emerge as a critical knowledge-exchange mechanism to generate impact outcomes.

Findings

The knowledge-exchange intervention provides impact by enabling the industry partner to establish cross-functional solutions teams, assess retail clients’ technological needs, aid decision-making, define barriers to implementation and develop a coaching approach to support clients’ technological investments. Impact outcomes vary in magnitude, intensity, scope and duration and can also be unintentional where unplanned changes are embedded into practice.

Originality/value

This impact framework offers a roadmap to orchestrate impact outcomes that emerge from academic enquiries.