Biology subjects

Shimada, K.

Publications and source records attributed to Shimada, K..

At least 19 recordsLinked to original sources

bioRxiv2026

Light Guiding in Scattering Media Using Focused Laser-Induced Acoustic Waves with an Open Elliptical Reflector

Light scattering in biological tissue limits deep optical imaging. Acoustic waves can modulate optical properties and enhance photon delivery, but source-positioning requirements can complicate integration with other imaging modalities. Here, we present an open elliptical reflector that focuses laser-induced acoustic waves at a spatially separated target while maintaining open optical access. We characterized the spatiotemporal optical modulation induced by the localized acoustic focus. The system increased the local transmitted-light intensity by a factor of 2.57-fold through a 2-mm-thick 1% intralipid hydrogel and enhanced fluorescence signal under two-photon excitation through a 1.5-mm-thick scattering sample. These results demonstrate spatially separated, reflector-based acoustically assisted light guiding for enhanced light delivery and fluorescence excitation through scattering media.

bioengineering↗

bioRxiv2026

TALAVE in Breast Cancer: BRCA1/2 Mutation-Dependent Immune Remodeling after PARP Inhibition with Limited Checkpoint Engagement

PARP inhibitors (PARPi) drive efficacy in BRCA-mutant breast cancer (BC) via DNA damage-induced synthetic lethality and immune activation, supporting their combination with immune checkpoint blockade. In the TALAVE study, patients with advanced BRCA-mutant or wild-type (WT) HER2-negative BC received talazoparib followed by talazoparib plus avelumab. Only BRCA-mutant BC responded clinically. Serial multi-omic profiling revealed BRCA-dependent tumor-immune remodeling, including sustained H2AX-pTBK1 signaling with increased CD8+ T cells, tumor cell depletion, and enrichment of CD163+ macrophages. In contrast, BRCA-WT tumors remained compact and immunosuppressed with reduced T cells after therapy. PD-1+ T cells localized to CD4+-rich neighborhoods and correlated with longer progression-free survival in BRCA-mutant tumors. However, PD-L1+ cells were rapidly depleted or confined to immune-excluded regions, spatially segregating them from PD-1+ T cells, impairing effective checkpoint blockade. These findings suggest limited benefit of PD-1/PD-L1 blockade in augmenting PARPi activity and highlight the need for alternative strategies to sustain PARPi-induced immunity.

cancer biology↗

bioRxiv2026

Spatial/molecular heterogeneity and treatment response in HER2+ early breast cancer: Translational analyses from the DAPHNe trial

Given the heterogeneity of HER2-positive breast cancer, reliable biomarkers to guide treatment are needed. We conducted multi-platform biomarker analyses of baseline tumor tissue from the DAPHNe trial of neoadjuvant paclitaxel/trastuzumab/pertuzumab (THP) for HER2-positive early breast cancer to characterize inter- and intra-tumor heterogeneity and to identify molecular predictors of response. A total of 98 patients with stage II-III HER2-positive breast cancer received neoadjuvant THP followed by surgery. Gene expression profiling, spatial protein profiling, and single-cell imaging (cyclic immunofluorescence) were performed on pre-treatment biopsies and a subset of residual disease specimens. Pathologic response was assessed using the residual cancer burden (RCB) score. Among HER2-positive patients included in the biomarker analysis, 34% of patients had node-positive breast cancer, and 66% had hormone receptor (HR)-positive tumors. HR-positive and HR-negative tumors differed significantly across gene expression, protein expression, and single-cell profiling. High ERBB2 gene signature, p53 gene signature, and HER2 protein expression predicted favorable response (RCB 0/1), while ESR1/PGR gene, estrogen receptor (ER) signaling gene signature, and ER alpha protein expression were associated with unfavorable response (RCB 2/3). Single-cell spatial analysis revealed that cancer cells clustered by shared HER2, ER, and PR expression, suggesting local expansion of phenotypically distinct subpopulations. ER-positive cancer cells were associated with lower HLA-A and PD-L1 expression, suggesting a less immunologically active tumor cell state. Baseline HER2 and ER expression are key predictors of response to neoadjuvant HER2-targeted therapy. Single-cell spatial profiling highlights intra-tumoral heterogeneity and suggests ER-driven immune exclusion as a potential mechanism of resistance.

cancer biology↗

bioRxiv2026

Necroptotic Signalling Diverts Keratinocyte Fate to Promote Differentiation and Slow Wound Healing

Necroptosis is best known as a lytic, proinflammatory cell-death pathway mediated by RIPK3 and MLKL. Effective wound repair requires the rapid resolution of inflammation, and ongoing necroptotic activity would only exacerbate tissue damage, delaying healing. However, damaged skin presents a trigger-rich environment for necroptotic signalling, an apparent paradox that remains unresolved. Using genetic ablation and pharmacological inhibition across multiple wound models, we show that inhibiting necroptosis accelerates wound closure, revealing that necroptotic signalling normally restrains repair. Surprisingly, we found that MLKL activation in wild-type keratinocytes induces differentiation and membrane repair rather than cell lysis. This adaptive, non-lethal mode of necroptotic signalling preserves barrier integrity but slows re-epithelialisation. Our findings redefine epidermal necroptotic signalling as a stress-responsive program that modulates keratinocyte fate in a trigger-rich environment. Temporarily dampening this pathway may enhance regeneration after barrier loss without compromising immune defence, revealing necroptosis as a tunable mechanism balancing tissue repair and inflammation.

cell biology↗

bioRxiv2026

Pathway-Centric Integration of CRISPR Fitness with Molecular Features Draws Cancer State Maps

Cancer cells display heterogeneous pathway activity that shapes therapeutic vulnerability, but mapping it remains challenging. Transcriptomic scores do not directly measure functional activity, and CRISPR knockout data alone lack molecular interpretability. We introduce StateMap, a pathway-centric framework integrating gene expression and genome-wide CRISPR knockout fitness data from the Cancer Dependency Map. For a given pathway, StateMap selects features by co-dependency and mutual information, then projects cell lines into a low-dimensional space reflecting pathway activity and molecular state. Applied to the Hippo pathway, it resolved five functional states refining the YAP-on/YAP-off dichotomy. Notably, the Hippo-strong state showed selective dependence on integrin V{beta}5; ITGAV depletion triggered Hippo-dependent cell aggregation and G1 arrest via enhanced cell-cell adhesion. Machine learning transfer to TCGA identified a matching subtype with poor prognosis, nominated NNMT as a biomarker, and predicted sensitivity to the V inhibitor Cilengitide. StateMap enables pathway-specific state mapping and discovery of state-selective therapeutic vulnerabilities.

cancer biology↗

bioRxiv2026

Fossil-based analyses of clades' diversification patterns require taxonomic expertise and appropriate methodology

SummaryEstimating deep-time diversification patterns and the establishment of extant biodiversity represent major challenges in macroevolution. Fossil record data provide essential information to address these topics, but their heterogeneous temporal and geographical distributions require using analytical approaches to process these data. Gardiner et al.1 (hereafter GEA) used a deep-learning model2 and a fossil-occurrences dataset3 to estimate neoselachian richness over the last 145 myr. Results and DiscussionGEA1 found that neoselachian diversity increased throughout the Cretaceous, was little impacted by the Cretaceous-Paleogene (K/Pg) mass extinction ([~]10% species loss), and peaked in the mid-Eocene but declined until the Present. While the Cretaceous increase in neoselachian richness is well known4, the other findings of GEA1 are at odds with current knowledge. With the exception of lamniform sharks, the perceived decrease in species richness in the recent past is most likely due to a drop in available fossil record data combined with difficulties in identifying extant species in the fossil record5. Similarly, all previous analyses of the impact of the K/Pg mass extinction on elasmobranch diversification have reported high extinction rates, a marked diversity drop, and delayed recovery6-7, despite heterogeneity across clades, ecology, and geographical distribution7. Taking the K/Pg as an example, we demonstrate that the discrepancies between GEA1s results and current consensus is most likely due to a combination of incomplete, unverified, and incorrect fossil-occurrence data with inappropriate methodology.

paleontology↗

bioRxiv2025

Mapping the latent CRBN-molecular glue degrader interactome

Molecular glue degraders (MGDs) are a transformative modality in drug discovery. MGDs that work in concert with the E3 ligase CRL4CRBN can degrade a range of substrates through tailored MGDs. To explore CRL4CRBN reprogrammability, we tested whether reported CRBN-MGD substrates are part of a network of latent CRBN interactors, detectable with generic CRBN-MGDs. Leveraging highly parallel interaction measurement (GluePCA) between CRL4CRBN and human zinc-fingers (ZFs), we identified [~]210 ZFs bound to CRBN-pomalidomide, where top binders are already reported as degraded by dedicated MGDs. To map latent CRBN-MGDs interactions proteome-wide, and thus define the immediately accessible CRBN target space, we combined AI-derived protein surface queries (MaSIF-mimicry) with GluePCA. This pipeline identified 6 known and 43 novel CRBN-pomalidomide binders, thereby providing privileged starting points for MGD development. We expect this binding-focused, highly parallel workflow to be readily applicable to other MGD/E3 ligase systems, extending the target landscape of this emerging drug class.

molecular biology↗

bioRxiv2025

APOE Tumor-Associated Macrophages and CD4-DOCK4 T Cells Reveal Distinct Microenvironmental Features in HER2-Low and HER2-0 Hormone Receptor-Positive Breast Cancer

Novel anti-HER2 antibody-drug conjugates (ADCs), such as trastuzumab deruxtecan (T-DXd), have shown efficacy in tumors with varying HER2 expression, including HER2-low and even tumors with minimal HER2 presence. This has sparked interest in the biology underlying the HER2 expression spectrum. Using molecular and multiplexed imaging, we revealed distinct immune and stromal features in treatment-naive, hormone receptor-positive (HR+) HER2-low versus HER2-0 tumors. HER2-0 tumors exhibit inflammatory and tissue remodeling gene signatures, with enrichment of APOE tumor-associated macrophages (TAMs) and DOCK4 CD4 T cells. In contrast, HER2-low tumors are more immunosuppressed, with elevated cell cycle, metabolic, and estrogen signaling pathways, suggesting increased proliferative activity. These findings underscore key biological differences between HR+ HER2-low and HER2-0 breast cancers, and may inform more tailored therapeutic strategies. Statement of significanceThis study revealed the distinct biological profiles of HR+ HER2-low and HER2-0 breast tumors. HER2-0 tumors exhibit inflammatory and tissue remodeling signatures, whereas HER2-low tumors have elevated cell cycle, metabolic, and estrogen signaling. These insights may help refine therapeutic approaches to improve outcomes for breast cancer patients.

cancer biology↗

bioRxiv2025

The genetic architecture of the human bZIP family

Generative biology holds the promise to transform our ability to design and understand living systems by creating novel proteins, pathways, and organisms with tailored functions that address challenges in medicine, sustainability, and technology. However, training generative models requires large quantities of data that captures the genetic architecture of protein function in all its complexity, but these are currently scarce. Here, we systematically mutagenized all 54 human basic-leucine zipper (bZIP) domains and quantified their interactions with each other using bindingPCA, a quantitative deep mutational scanning assay. This resulted in [~]2 million interaction measurements, capturing the effect of all single amino acid substitutions at each of the 35 interfacial positions. We found that mutation effects are largely additive in the vicinity of each wild-type bZIPs, but diverge across the family, indicating strong context dependency. A global additive thermodynamic model provided moderate prediction of mutation effects, while individual models per bZIP achieved higher performance, supporting a model of local simplicity and global complexity. Our results therefore suggest that the genetic architecture of protein function is more complex than previously anticipated, which could hinder predictability. However, a convolutional neural network trained on this dataset could accurately predict binding scores from sequence alone. Furthermore, the model enabled the design of synthetic bZIPs with high target specificity, demonstrating practical applicability for bioengineering purposes. Our study shows that capturing family-wide diversity is essential to reveal context dependencies and train accurate quantitative models of protein-protein interactions.

biophysics↗

bioRxiv2024

An estrogen receptor signaling transcriptional program linked to immune evasion in human hormone receptor-positive breast cancer

T cells are generally sparse in hormone receptor-positive (HR+) breast cancer, potentially due to limited antigen presentation, but the driving mechanisms of low T cell abundance remains unclear. Therefore, we defined and investigated programs ( gene modules), related to estrogen receptor signaling (ERS) and immune signaling using bulk and single-cell transcriptome and multiplexed immunofluorescence of breast cancer tissues from multiple clinical sources and human cell lines. The ERS gene module, dominantly expressed in cancer cells, was negatively associated with immune-related gene modules TNF/NF-{kappa}B signaling and type-I interferon (IFN-I) response, which were expressed in distinct stromal and immune cell types, but also, in part, expressed and preserved as a cancer cell-intrinsic mechanisms. Spatial analysis revealed that ERS strongly correlated with reduced T cell infiltration, potentially due to its association with suppression of TNF/NF-{kappa}B-induced angiogenesis and IFN-I-induced HLA expression in macrophages. Preoperative endocrine therapy in ER+/HER2-breast cancer patients produced better responses in ERS-high patients, with TNF/NF-{kappa}B expression associated with reduced ERS. Targeting these pathways may enhance T cell infiltration in HR+ breast cancer patients. Statement of SignificanceThis study elucidates the immunosuppressive role of ER signaling in breast cancer, highlighting a complex interplay between cancer, stromal, and immune cells and reveals potential approaches to enhance immunogenicity in HR+ breast cancer. These findings offer crucial insights into immune evasion in breast cancer and identify strategies to enhance T cell abundance.

cancer biology↗

bioRxiv2024

Hypothermia protects against ventilator-induced lung injury by limiting IL-1beta release and NETs formation

Although mechanical ventilation is a critical intervention for acute respiratory distress syndrome (ARDS), it can trigger an IL-1{beta}-associated complication known as ventilator-induced lung injury. In mice, we found that LPS and high-volume ventilation, LPS-HVV, leads to hypoxemia with neutrophil extracellular traps (NETs) formation in the alveoli. Furthermore, Il1r1-/- LPS-HVV mice did not develop hypoxemia and had reduced NETs, indicating that IL-1R1 signaling is important for NETs formation and hypoxemia. Therapeutic hypothermia (TH) is known to reduce the release of inflammatory mediators. In LPS-HVV mice, TH (32 {degrees}C body temperature) prevented hypoxemia development, reducing albumin leakage, IL-1{beta}, gasdermin D (GSDMD) and NETs formation. We also observed that LPS-primed macrophages, when stimulated at 32{degrees}C with ATP or nigericin, release less IL-1{beta} associated with reduced GSDMD cleavage. Thus, hypothermia is an important modulating factor in the NLRP3 inflammasome activation, IL-1{beta} release and NETs formation, preventing LPS-HVV-induced acute respiratory failure.

immunology↗

bioRxiv2024

The intestinal microbiota contributes to the development of immune-mediated cardiovascular inflammation and vasculitis in mice.

Alterations in the intestinal microbiota contribute to the pathogenesis of various cardiovascular disorders, but how they affect the development of Kawasaki disease (KD), an acute pediatric vasculitis, remains unclear. We report that depleting the gut microbiota reduces the development of cardiovascular inflammation in a murine model mimicking KD vasculitis. The development of cardiovascular lesions was associated with alterations in the intestinal microbiota composition and, notably, a decreased abundance of Akkermansia muciniphila and Faecalibacterium prausnitzii. Oral supplementation with either of these live or pasteurized individual bacteria, or with short-chain fatty acids (SCFAs) produced by them, attenuated cardiovascular inflammation. Treatment with Amuc_1100, the TLR-2 signaling outer membrane protein from A. muciniphila, also decreased the severity of vascular inflammation. This study reveals an underappreciated gut microbiota-cardiovascular inflammation axis in KD vasculitis pathogenesis and identifies specific intestinal commensals that regulate vasculitis in mice by producing metabolites or via extracellular proteins acting on gut barrier function. IN BRIEFIt remains unclear whether changes in the intestinal microbiota composition are involved in the development of cardiovascular lesions associated with Kawasaki disease (KD), an immune-mediated vasculitis. Jena et al. observe alterations in the intestinal microbiota composition of mice developing vasculitis, characterized by reduced A. muciniphila and F. prausnitzii. Oral supplementation with either of these bacteria, live or pasteurized, or with bacteria-produced short-chain fatty acids (SCFAs) or Amuc_1100, the TLR-2 signaling outer membrane protein of A. muciniphila, was sufficient to alleviate the development of cardiovascular lesions in mice by promoting intestinal barrier function. HIGHLIGHTSO_LIAbsence or depletion of the microbiota decreases the severity of vasculitis in a murine model mimicking KD vasculitis. C_LIO_LISupplementation of B. wadsworthia and B. fragilis promotes murine KD vasculitis. C_LIO_LIDecreased abundances of F. prausnitzii and A. muciniphila are associated with the development of cardiovascular lesions in mice. C_LIO_LISupplementation with either live or pasteurized A. muciniphila and F. prausnitzii, or the TLR-2 signaling Amuc_1100, reduces the severity of vasculitis by promoting gut barrier function. C_LI

immunology↗

bioRxiv2024

Generation of human-pig chimeric renal organoids using iPSC technology

The potential of using porcine organs and human induced pluripotent stem cell (iPSC)-derived organoids as alternative organs for human transplantation has garnered growing attention. However, both approaches still face technological challenges. Interspecies chimeric organ production using human iPSCs is expected to be another promising approach that addresses the challenges associated with organ production. Our research group successfully generated human-mouse chimeric renal organoids by utilizing human iPSC-derived nephron progenitor cells (NPCs) and fetal mouse kidneys. However, the current technology has limited engraftment and development capabilities for human NPCs, and there have been no reports of generating interspecies chimeric renal organoids in larger animals, limited only to rodents. Therefore, in this study, we embarked on the production of human-pig chimeric renal organoids using the pig kidney, which is considered the most promising source of organs for interspecies transplantation to humans. To construct a human-pig chimeric renal organoid culture system, we first modified the existing human-mouse chimeric renal organoid culture system and developed a method that enables the survival and continued renal development of both species. This method was found to be applicable to porcine fetal kidney cells, and ultimately, we successfully produced human-pig chimeric renal organoids. Furthermore, this culture method can also be applied to the generation of human interspecies chimeric kidneys for future clinical applications. The findings of this study serve as a foundational technology that will greatly accelerate future research in humanized pig kidney production for clinical purposes, and are also expected to be used as an evaluation technique to ensure the quality of human NPCs for xenotransplantation.

bioengineering↗

bioRxiv2023

FBXO24 ensures male fertility by preventing abnormal accumulation of membraneless granules in sperm flagella

Ribonucleoprotein (RNP) granules are membraneless electron-dense structures rich in RNAs and proteins, and involved in various cellular processes. Two RNP granules in male germ cells, intermitochondrial cement and the chromatoid body (CB), are associated with PIWI-interacting RNAs (piRNAs) and are required for transposon silencing and spermatogenesis. Other RNP granules in male germ cells, the reticulated body and CB remnants, are also essential for spermiogenesis. In this study, we disrupted FBXO24, a testis-enriched F-box protein, in mice and found numerous membraneless electron-dense granules accumulated in sperm flagella. Fbxo24 knockout (KO) mice exhibited malformed flagellar structures, impaired sperm motility, and male infertility, likely due to the accumulation of abnormal granules. The amount and localization of known RNP granule-related proteins were not disrupted in Fbxo24 KO mice, suggesting that the accumulated granules were distinct from known RNP granules. Further studies revealed that RNAs and two importins, IPO5 and KPNB1, abnormally accumulated in Fbxo24 KO spermatozoa and that FBXO24 could ubiquitinate IPO5. In addition, IPO5 and KPNB1 were recruited to stress granules, RNP complexes, when cells were treated with oxidative stress or a proteasome inhibitor. These results suggest that FBXO24 is involved in the degradation of IPO5, disruption of which may lead to the accumulation of abnormal RNP granules in sperm flagella.

developmental biology↗

bioRxiv2023

Optimization of a deep mutational scanning workflow to improve quantification of mutation effects on protein-protein interactions

Deep Mutational Scanning (DMS) assays are powerful tools to study sequence-function relationships by measuring the effects of thousands of sequence variants on protein function. During a DMS experiment, several technical artefacts might distort non-linearly the functional score obtained, potentially biasing the interpretation of the results. We therefore tested several technical parameters in the deepPCA workflow, a DMS assay for protein-protein interactions, in order to identify technical sources of non-linearities. We found that parameters common to many DMS assays such as amount of transformed DNA, timepoint of harvest and library composition can cause non-linearities in the data. Designing experiments in a way to minimize these non-linear effects will improve the quantification and interpretation of mutation effects.

systems biology↗

bioRxiv2023

The genetic architecture of protein interaction affinity and specificity

Proteins function in crowded cellular environments in which they must bind to specific target proteins but also avoid binding to many other off-target proteins. In large protein families this task is particularly challenging because many off-target proteins have very similar structures. How this specificity of physical protein-protein interactions in cellular networks is encoded and evolves is not very well understood. Here we address the question of specificity-encoding by comprehensively quantifying the effects of all mutations in one protein, JUN, on its binding to all other members of a protein family, the 54 human basic leucine zipper transcription factors. Fitting a global thermodynamic model to the data reveals that most affinity changing mutations equally affect JUNs propensity to bind to all its interaction partners. Mutations that alter the specificity of binding are much rarer. These specificity-altering mutations are, however, distributed throughout the JUN interaction interface. JUNs interaction specificity is encoded by both positive determinants that promote on-target interactions and negative determinants that prevent off-target interactions. Indeed, about half of the specificity-defining residues in JUN have dual functions and both promote on-target binding and prevent off-target binding. Whereas nearly all mutations that alter specificity are pleiotropic and also alter the affinity of binding to all interaction partners, the converse is not true with mutations outside of the interface able to tune affinity without affecting specificity. Our results provide the first global view of how mutations in a protein affect binding to all its potential interaction partners and reveal the distributed encoding of specificity and affinity in an interaction interface. They also show how the modular architecture of coiled-coils provides an elegant solution to the challenge of optimising specificity and affinity in a large protein family.

systems biology↗

bioRxiv2023

Affinity-tagged SMAD1 and SMAD5 mouse lines reveal transcriptional reprogramming mechanisms during early pregnancy

Endometrial decidualization, a prerequisite for successful pregnancies, relies on transcriptional reprogramming driven by progesterone receptor (PR) and bone morphogenetic protein (BMP)-SMAD1/SMAD5 signaling pathways. Despite their critical roles in early pregnancy, how these pathways intersect in reprogramming the endometrium into a receptive state remains unclear. To define how SMAD1 and/or SMAD5 integrate BMP signaling in the uterus during early pregnancy, we generated two novel transgenic mouse lines with affinity tags inserted into the endogenous SMAD1 and SMAD5 loci (Smad1HA/HAand Smad5PA/PA). By profiling the genome-wide distribution of SMAD1, SMAD5, and PR in the mouse uterus, we demonstrated the unique and shared roles of SMAD1 and SMAD5 during the window of implantation. We also showed the presence of a conserved SMAD1, SMAD5, and PR genomic binding signature in the uterus during early pregnancy. To functionally characterize the translational aspects of our findings, we demonstrated that SMAD1/5 knockdown in human endometrial stromal cells suppressed expressions of canonical decidual markers (IGFBP1, PRL, FOXO1) and PR-responsive genes (RORB, KLF15). Here, our studies provide novel tools to study BMP signaling pathways and highlight the fundamental roles of SMAD1/5 in mediating both BMP signaling pathways and the transcriptional response to progesterone (P4) during early pregnancy.

molecular biology↗

bioRxiv2022

SARS-CoV-2 causes brain inflammation via impaired neuro-immune interactions

The brain inflammation that frequently occurs in SARS-CoV-2 is the cause of neurological complications1,2 and long COVID 3,4,5. However, many aspects of its pathogenesis mechanism remain unknown 6, 7 and no method of treatment has been established 8. By administering a non-proliferating adenovirus vector expressing SARS-CoV-2 S1 protein into the nasal cavity of mice, we developed a mouse model (S1 mouse) reproducing brain inflammation, fatigue, depressive symptoms, and lung inflammation. Having intracellular calcium elevating activity, S1 protein increased olfactory bulb apoptosis, and reduced the number of acetylcholine producing cells in the medial septal and the diagonal band of Broca as well as the amount of acetylcholine in the brain. This resulted in disrupting the cholinergic anti-inflammatory pathway (CAP) 9 and enhancing inflammation in the brain. Previously, nothing was known about anti-inflammatory factors in the CAP but we discovered that, in the inflammation occurring in the S1 mouse brain, the action of the RNA binding protein ZFP36 10 in degrading inflammatory cytokine mRNA was impaired. The symptoms exhibited by the S1 mouse were improved by administering donepezil, a drug with a cholinergic action used in the treatment of dementia. These findings clarify the mechanism of brain inflammation in COVID-19 and indicate the possibility of applying donepezil in the treatment of neurological complications in COVID-19 and long COVID.

microbiology↗