bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Retina-inspired Optoelectronic Synapse Using Quantum Dots for Neuromorphic Photostimulation of Neurons
Authors: Balamur Ridvan , Eren Guncem Ozgun , Kaleli Humeyra Nur , Karatum Onuralp , Kaya Lokman , Hasanreisoglu Murat , Nizamoglu Sedat 
Published: October 2023

AbstractNeuromorphic electronics, inspired by the functions of neurons, have the potential to enable biomimetic communication with cells. Such systems require operation in aqueous environments, generation of sufficient levels of ionic currents for neurostimulation, and plasticity. However, their implementation requires a combination of separate devices, such as sensors, organic synaptic transistors, and stimulation electrodes. Here, we present a compact neuromorphic synapse that combines photodetection, memory, and neurostimulation functionalities all-in-one. The artificial photoreception is facilitated by a photovoltaic device based on cell-interfacing InP/ZnS quantum dots, which induces photo-faradaic charge-transfer mediated plasticity. The device sends excitatory post-synaptic currents exhibiting paired-pulse facilitation and post-tetanic potentiation to the hippocampal neurons via the biohybrid synapse. The electrophysiological recordings indicate modulation of the probability of action potential firing due to biomimetic temporal summation of excitatory post-synaptic currents. Our results pave the way for the development of novel bioinspired neuroprosthetics and soft robotics and highlight the potential of quantum dots for achieving versatile neuromorphic functionality in aqueous environments.
Sleepiness, not total sleep amount, increases seizure risk
Authors: Cuddapah Vishnu Anand , Hsu Cynthia T , Li Yongjun , Shah Hrishit M , Saul Christopher , Killiany Samantha , Shon Joy , Yue Zhifeng , Gionet Gabrielle , Putt Mary E , Sehgal Amita 
Published: October 2023

SummarySleep loss has been associated with increased seizure risk since antiquity. Despite this observation standing the test of time, how poor sleep drives susceptibility to seizures remains unclear. To identify underlying mechanisms, we restricted sleep inDrosophilaepilepsy models and developed a method to identify spontaneous seizures using quantitative video tracking. Here we find that sleep loss exacerbates seizures but only when flies experience increased sleep need, orsleepiness, and not necessarily with reduced sleep quantity. This is supported by the paradoxical finding that acute activation of sleep-promoting circuits worsens seizures, because it increases sleep need without changing sleep amount. Sleep-promoting circuits become hyperactive after sleep loss and are associated with increased whole-brain activity. During sleep restriction, optogenetic inhibition of sleep-promoting circuits to reduce sleepiness protects against seizures. Downregulation of the 5HT1A serotonin receptor in sleep-promoting cells mediates the effect of sleep need on seizures, and we identify an FDA-approved 5HT1A agonist to mitigate seizures. Our findings demonstrate that while homeostatic sleep is needed to recoup lost sleep, it comes at the cost of increasing seizure susceptibility. We provide an unexpected perspective on interactions between sleep and seizures, and surprisingly implicate sleep- promoting circuits as a therapeutic target for seizure control.
Expression of modified FcγRI enables myeloid cells to elicit robust tumor-specific cytotoxicity
Authors: Farhat-Younis Leen , Na Manho , Zarfin Amichai , Khateeb Aseel , Santana-Magal Nadine , Richter Alon , Gutwillig Amit , Rasoulouniriana Diana , Gleiberman Annette , Beck Lir , Giger Tamar , Ashkenazi Avraham , Barzel Adi , Rider Peleg , Carmi Yaron 
Published: October 2023

AbstractDespite the central role of T cells in tumor immunity, attempts to harness their cytotoxic capacity as a therapy have met limited efficacy, partially as a result of the suppressive microenvironment which limits their migration and activation. In contrast, myeloid cells massively infiltrate tumors and are well adapted to survive these harsh conditions. While they are equipped with cell-killing abilities, they often adopt an immunosuppressive phenotype upon migration to tumors. Therefore, the questions of how to modify their activation programming against cancer, and what signaling cascades should be activated in myeloid cells to elicit their cytotoxicity have remained unclear.Here, we found that activation of IgM-induced signaling in myeloid cells results in secretion of lytic granules and massive tumor cell death. These findings open venues for designing novel immunotherapy by equipping monocytes with chimeric receptors that target tumor antigens and consequently, signal through IgM receptor. Nonetheless, we found that myeloid cells do not express the antibody-derived portion used to recognize the tumor antigen due to the induction of an ER stress response. To overcome this limitation, we designed chimeric receptors that are based on the high-affinity FcγRI for IgG. Incubation of macrophages expressing these receptors along with tumor-binding IgG induced massive tumor cell killing and secretion of reactive oxygen species and Granzyme B.Overall, this work highlights the challenges involved in genetically reprogramming the signaling in myeloid cells and provides a framework for endowing myeloid cells with antigen-specific cytotoxicity.
Evaluation of ChatGPT’s Pathology Knowledge using Board-Style Questions
Authors: Geetha Saroja D , Khan Anam , Khan Atif , Kannadath Bijun S , Vitkovski Taisia 
Published: October 2023

AbstractObjectivesChatGPT is an artificial intelligence (AI) chatbot developed by OpenAI. Its extensive knowledge and unique interactive capabilities enable it to be utilized in various innovative ways in the medical field such as writing clinical notes, simplifying radiology reports. Through this study we aim to analyze its pathology knowledge to advocate its role in transforming pathology education.MethodsAmerican Society for Clinical Pathology (ASCP) Resident Question bank (RQB) 2022 was used to test ChatGPT v4. Practice tests were created in each sub-category and were answered based on the input provided by ChatGPT. Questions that required interpretation of images were excluded. ChatGPT’s performance was analyzed and compared with the average peer performance.ResultsThe overall performance of ChatGPT was 56.98%, lower than that of the average peer performance of 62.81%. ChatGPT performed better on clinical pathology (60.42%) than anatomic pathology (54.94%). Furthermore, its performance was better on easy questions (68.47%) compared to intermediate (52.88%) and difficult questions (37.21%).ConclusionsChatGPT has the potential to be a valuable resource in pathology education if trained on a larger, specialized medical dataset. Relying on it solely for the purpose of pathology training should be with caution, in its current form.Key pointsChatGPT is an AI chatbot, that has gained tremendous popularity in multiple industries, including healthcare. We aim to understand its role in revolutionizing pathology education.We found that ChatGPT’s overall performance in Pathology Practice Tests were lower than that expected from an AI tool, furthermore its performance was subpar compared to pathology residents in training.In its current form ChatGPT is not a reliable tool for pathology education, but with further refinement and training it has the potential of being a learning asset.
The TMPRSS2 non-protease domains regulating SARS-CoV-2 Spike in mediated virus entry
Authors: Strobelt Romano , Adler Julia , Shaul Yosef 
Published: October 2023

AbstractThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters cells by binding to the angiotensin-converting enzyme 2 (hACE2) receptor. This process is aided by the transmembrane protease serine 2 (TMPRSS2), which enhances entry efficiency and infectiousness by cleaving the SARS-CoV-2 surface glycoprotein (Spike). The cleavage primes the Spike protein, promoting membrane fusion instead of receptor-mediated endocytosis. Despite the pivotal role played by TMPRSS2, our understanding of its non-protease distinct domains remains limited. In this report, we present evidence indicating the potential phosphorylation of a minimum of six tyrosine residues within the cytosolic tail (CT) of TMPRSS2. Through the use of TMPRSS2 CT phospho-mimetic mutants, we observed a reduction in TMPRSS2 protease activity, accompanied by a decrease in SARS-CoV-2 pseudovirus infection, which was found to occur mainly via the endosomal pathway. We expanded our investigation beyond TMPRSS2 CT and discovered the involvement of other non-protease domains in regulating infection. Our co-immunoprecipitation experiments demonstrated a strong interaction between TMPRSS2 and Spike. We revealed a 21 amino acid long TMPRSS2-Spike-binding region (TSBR) within the TMPRSS2 scavenger receptor cysteine-rich (SRCR) domain that contributes to this interaction. Our study sheds light on novel functionalities associated with TMPRSS2’s cytosolic tail and SRCR region. Both of these regions have the capability to regulate SARS-CoV-2 entry pathways. These findings contribute to a deeper understanding of the complex interplay between viral entry and host factors, opening new avenues for potential therapeutic interventions.
Experimental evolution of symbiotic microbes without their partners can imply the presence of cooperative or antagonistic adaptations
Authors: Larsen Tyler J. , Jefferson Cara , Bartley Anthony , Strassmann Joan E. , Queller David C. 
Published: October 2023

ABSTRACTMicrobes adapt to the presence of other species, but the fitness consequences of specific interactions are difficult to study in their natural context. We experimentally evolved symbiotic microbes in an artificial environment without access to the partners with whom they interact in nature. As organisms will tend to lose adaptations that they do not need due to drift or pleiotropic tradeoffs, we expect normally symbiotic microbes evolved in isolation to lose adaptations to help or harm their natural partners. The direction and magnitude of such changes can suggest whether the microbes had historically been selected to help or harm one another. We apply this method to the symbiosis between the social amoebaDictyostelium discoideumand three intracellular bacterial endosymbionts,Paraburkholderia agricolaris, P. hayleyella,andP. bonniea.A minority of strains ofParaburkholderiaandD. discoideumevolved differences in their effects on one another’s fitnesses, implying the existence of adaptations to one another that were lost when no longer relevant. Our results suggest that the degree to whichD. discoideumandParaburkholderiahave adapted to help or harm one another can differ substantially between strains within each species, with some strains appearing to have a historically adversarial relationship, some strains a more benign relationship, and many strains no clear adaptations to one another at all. Our results underscore the complexity of microbial interactions in nature and suggest experimental evolution under relaxed selection is a potentially useful approach for studying adaptation in microbes.
Decision-Making Time Cells in Hippocampal Dorsal CA1
Authors: Ma M. , Simoes de Souza F. , Futia G.L. , Anderson S.R. , Riguero J. , Tollin D. , Gentile-Polese A. , Platt J.P. , Hiratani N. , Gibson E. A. , Restrepo D. 
Published: October 2023

SUMMARYSequential neural dynamics encoded by “time cells” play a crucial role in hippocampal function. However, the role of hippocampal sequential neural dynamics in associative learning is an open question. In this manuscript, we used two-photon Ca2+imaging of dorsal CA1 pyramidal neurons in head-fixed mice performing a go-no-go associative learning task. We found that pyramidal cells responded differentially to the rewarded or unrewarded stimuli. The stimuli were decoded accurately from the activity of the neuronal ensemble, and accuracy increased substantially as the animal learned to differentiate the stimuli. Decoding the stimulus from individual pyramidal cells that responded differentially revealed that decision-making took place at discrete times after stimulus presentation. Lick prediction decoded from the ensemble activity of cells in dCA1 correlated linearly with lick behavior indicating that sequential activity of pyramidal cells in dCA1 constitutes a temporal memory map used for decision-making in associative learning.
Experiences and impacts of side effects among contraceptive users in the UK: exploring individual narratives of contraceptive side effects
Authors: Stewart Catherine , Stevens Rose , Kennedy Fiona , Cecula Paulina , Rueda Carrasco Elena , Hall Jennifer 
Published: October 2023

AbstractPurposeWhile many women worldwide use contraception, there is a paucity of research on individual experiences of side effects and their impacts. To address this gap, we analysed free-text responses of contraception experiences from 337 women aged 18 to 35, based in the UK who took part in an online survey on contraception.Materials and methodsThrough a directed content analysis approach, we developed a coding framework based on existing literature and initial response review. It included six themes; method(s) of contraception, side effect(s) experienced, impact of side effect(s), timing of side effect(s), interactions with healthcare practitioners, and trial and error.ResultsSide effect experiences and impacts varied greatly between individuals and contraceptives. Most participants described negative effects, such as mental health issues and bleeding problems. Some shared positive experiences related to bleeding management and the absence of side effects. Some experienced side effects after years of use and felt unheard by practitioners.ConclusionsThis contraceptive experience variability underscores the need for further research into individual side effect variation. We advocate for a patient-centred approach to contraceptive counselling. Practitioners should play an active role in improving contraception prescription, acknowledging the diverse experiences and preferences of patients.
The hidden hand of asymptomatic infection hinders control of neglected tropical diseases
Authors: Rock Kat S. , Chapman Lloyd A.C. , Dobson Andrew P. , Adams Emily R. , Hollingsworth T. Déirdre 
Published: October 2023

AbstractNeglected tropical diseases are responsible for considerable morbidity and mortality in low-income populations. International efforts have reduced their global burden, but transmission is persistent and case-finding-based interventions rarely target asymptomatic individuals. We develop a generic mathematical modelling framework for analysing the dynamics of visceral leishmaniasis in the Indian sub-continent (VL),gambiensesleeping sickness (gHAT), and Chagas disease and use it to assess the possible contribution of asymptomatics who later develop disease (pre-symptomatics) and those who do not (non-symptomatics) to the maintenance of infection. Plausible interventions, including active screening, vector control and reduced time to detection, are simulated for the three diseases. We conclude that currently available tools could bring new infections under control for gHAT and Chagas disease – albeit over a long period of time for Chagas disease – but that VL will be more difficult to control with existing interventions. gHAT protocols that allow for treatment of parasitologically positive asymptomatics result in better control of infection compared to syndromic diagnosis required for VL. This work highlights that the high asymptomatic contribution to transmission for Chagas and gHAT and the apparently high basic reproductive number of VL may greatly undermine long-term control, but that precise predictions are hampered by uncertainty in natural history.
Respiratory viral infections do not increase risk of venous thromboembolism
Authors: Korzeniewski Steven J. , Bauer Samantha J. , Kabrhel Christopher , Mark Courtney D. , Ka ming Ngai , Kelly Christopher , Camargo Carlos A. , Kline Jeffrey A. 
Published: October 2023

ABSTRACTBackgroundA major concern in emergency departments is whether acute respiratory illness (ARI) is associated with increased risk of venous thromboembolism (VTE).MethodsThis prospective cohort study includes ARI patients from the 91-hospital, U.S. CDC- sponsored Respiratory Virus Laboratory Emergency Department Network Surveillance (RESP-LENS) program from January 2022 to June 2023. We calculated incidence rates and used multivariable regression models to test the null hypothesis that there is no association between the results or absence of laboratory viral testing and the risk of new onset VTE within 30-days.FindingsOut of 620,303 ARI encounters, 65% underwent laboratory viral testing; 13% tested positive for COVID and 3%-4% tested positive for influenza-A and/or RSV. The 30-day VTE incidence rate was 0.70% amongunique first patient encounters and 0.82%overall.The highest VTE incidence rate occurred among viral test negative patient encounters (1.13% [95%CI 1.08%-1.19%]) and the lowest VTE rate occurred among patients who tested positive for COVID, influenza-A or RSV, or who did not undergo viral testing (95%CI 0.09%-0.86%). In adjusted models, only among patients receiving any ICU care was fluA associated with heightened VTE risk.New VTE was associated with increased 30-day mortality risk (RR 2.7, 95%CI 2.3-3.2), but there was no difference in 30-day mortality risk among VTE patients grouped by the results of viral testing (interaction p > 0.05).ConclusionIn the U.S. from January 2022 to June 2023, laboratory confirmed viral infection was not associated with increased risk of short-term VTE diagnosis or death among patients seeking emergency care.
Genetic or pharmacological inactivation of CREBBP sensitizes B-cell Acute Lymphoblastic Leukemia to Ferroptotic Cell Death upon BCL2 Inhibition
Authors: Garcia-Gimenez Alicia , Ditcham Jonathan E. , Azazi Dhoyazan M.A. , Meduri Eshwar , Asby Ryan , Sakakini Nathalie , Lopez Cecile K. , Narayan Nisha , Beinortas Tumas , Bagri Jaana , Singh Shuchi Agrawal , Giotopoulos George , Murphy Michael P. , Horton Sarah J. , Huntly Brian J.P. , Richardson Simon E. 
Published: October 2023

AbstractB-cell acute lymphoblastic leukemia (B-ALL) is a leading cause of death in childhood and outcomes in adults remain dismal. There is therefore an urgent clinical need for therapies that target the highest risk cases. Mutations in the histone acetyltransferaseCREBBPassociate with high-risk features in B-ALL and have been implicated in chemoresistance. We performed a targeted drug screen in isogenic human cell lines, identifying a number of actionable small molecules that specifically targetCREBBP-mutated B-ALL. The most potent was the BCL2 inhibitor Venetoclax, which acts through a non-canonical mechanism resulting in ferroptotic cell death.CREBBP-mutated cell lines showed differences in cell-cycle, metabolism and response to oxidative stress. Lastly, we demonstrate that small-molecule inhibition of CREBBP sensitizes B-ALL cells, regardless of genotype, to Venetoclax-induced ferroptosisin-vitroandin-vivo, providing a potential novel drug combination for broader clinical translation in B-ALL.
Action observation reveals a network with divergent temporal and parietal lobe engagement in dogs compared to humans
Authors: Boch Magdalena , Karl Sabrina , Wagner Isabella C. , Lengersdorff Lukas L. , Huber Ludwig , Lamm Claus 
Published: October 2023

AbstractAction observation is a fundamental pillar of social cognition. Neuroimaging research has revealed a human and primate action observation network (AON) encompassing fronto-temporo-parietal areas with links to a species’ imitation tendencies and relative lobe expansion. Dogs (Canis familiaris)have good action perception and imitation skills and a less expanded parietal than temporal lobe, but their AON remains unexplored. We conducted a functional MRI study with 28 dogs and 40 humans and found functionally analogous involvement of somatosensory and temporal brain areas of both species’ AONs and responses to transitive and intransitive action observation in line with their imitative skills. However, activation and task-based functional connectivity measures suggested significantly less parietal lobe involvement in dogs than in humans. These findings advance our understanding of the neural bases of action understanding and the convergent evolution of social cognition, with analogies and differences resulting from similar social environments and divergent brain expansion, respectively.
Deep mutational scanning reveals a tight correlation between protein degradation and toxicity of thousands of non-native aspartoacylase protein variants
Authors: Grønbæk-Thygesen Martin , Voutsinos Vasileios , Johansson Kristoffer E. , Schulze Thea K. , Cagiada Matteo , Pedersen Line , Clausen Lene , Nariya Snehal , Powell Rachel L. , Stein Amelie , Fowler Douglas M. , Lindorff-Larsen Kresten , Hartmann-Petersen Rasmus 
Published: October 2023

AbstractWhen the structural stability of a protein is compromised, the protein may form non-native interactions with other cell proteins and thus becomes a hazard to the cell. To mitigate this danger, destabilized proteins are targeted by the cellular protein quality control (PQC) network, which either corrects the folding defect or targets the protein for degradation. However, the details of how the protein folding and degradation systems collaborate to combat potentially toxic non-native proteins are unknown. To address this issue, we performed systematic studies on destabilized variants of the cytosolic aspartoacylase, ASPA, where loss-of-function variants are linked to Canavan’s disease, an autosomal recessive and lethal neurological disorder, characterized by the spongy degeneration of the white matter in the brain. Using Variant Abundance by Massively Parallel sequencing (VAMP-seq), we determined the abundance of 6152 out of the 6260 (∼98%) possible single-site missense and nonsense ASPA variants in cultured human cells. The majority of the low abundance ASPA variants are degraded through the ubiquitin-proteasome system (UPS) and become toxic upon prolonged expression. Variant cellular abundance data correlates with predicted thermodynamic stability, evolutionary conservation, and separates most known disease-linked variants from benign variants. Systematic mapping of degradation signals (degrons) shows that inherent primary degrons in ASPA are located in buried regions, and reveals that the wild-type ASPA C-terminal region functions as a degron. Collectively, our data can be used to interpret Canavan’s disease variants and also offer mechanistic insight into how ASPA missense variants are targeted by the PQC system. These are essential steps towards future implementation of precision medicine for Canavan’s disease.