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Introduction Occlusion of the internal carotid artery (ICA), caused by atherosclerotic thrombosis, arterial embolism, or dissection, is associated with high morbidity and mortality of acute stroke. Commonly, these lesions are managed with aggressive medical treatment due to their chronic and usually irreversible nature. Spontaneous recanalization of the occluded ICA has been described in rare instances. Methods We present a report here on three cases with spontaneous recanalization of complete occluded carotid arteries. Results Our first patient was a 62‐year‐old male with a history of hypertension, who presented with transient left eye vision loss. CT angiography of the head and neck (CTA HN) demonstrated left ICA complete occlusion while the left middle cerebral artery (MCA) and anterior cerebral arteries (ACA) were patent. He was treated with apixaban. At the two‐month follow‐up, the repeat CTA HN demonstrated complete recanalization of the left ICA. The etiology of the occlusion remained cryptogenic. Our second patient was a 71‐year‐old male with a prior history of right carotid endarterectomy, peripheral vascular disease, coronary artery disease, hypertension, and dyslipidemia, who presented with acute right MCA stroke. Work‐up with CTA HN demonstrated right ICA complete occlusion. He was treated medically with aspirin and clopidogrel. Six months later, he presented with a two‐week history of intermittent confusion and left‐sided weakness. His MRI brain was negative foracute stroke. Interestingly, CTA HN demonstrated that the right ICA had complete recanalization. The cause of carotid thrombosis remained cryptogenic. Our third patient was a 46‐year‐old female with a history of hypertension, hyperlipidemia, remote low‐speed vehicle collision, and cervical spine chiropractic treatment (the last neck manipulation was about two years prior), presenting with sudden onset dizziness, right‐sided neck pain, and left homonymous hemianopia. Brain MRI showed acute right posterior cerebral artery (PCA) stroke. CTA HN revealed occlusion of the right ICA with a flare‐up appearance suggestive of a carotid dissection. She also had a right fetal PCA. She was treated medically with rivaroxaban. Four months later, a follow‐up MR angiogramof the neck showed a fully revascularized right ICA. Her hypercoagulable workup revealed that she had a rare form of breast cancer. Conclusions Although ICA occlusion is generally considered chronic and irreversible, our case series suggests that the lesion can have spontaneous recanalization with medical treatment. Further studies of characterizing carotid occlusion to predict recanalization are warranted.

Abstract The Guanine-nucleotide binding protein 2 (GNB2) encodes for β2 subunit (Gβ2) of the G-protein complex. Keeping in view the increased demand of reliable biomarkers in cancer, the current study was planned to extensively explored GNB2 expression variation and its roles in different cancers using online available databases and diverse methodology. In view of our results, the GNB2 was notably up-regulated relative to corresponding controls in twenty three cancer types. As well, the elevated expression of GNB2 was found to be associated with the reduced overall survival (OS) of the Liver Hepatocellular Carcinoma (LIHC) and Rectum Adenocarcinoma (READ) only out of all analyzed cancer types. This implies GNB2 plays vital role in the tumorigenesis of LIHC and READ. Several additional analysis also explored six critical pathways and few important correlations related to GNB2 expression and different other parameters such as promoter methylation, tumor purity, CD8+ T immune cells infiltration, and genetic alteration, and chemotherapeutic drugs. In conclusion, GNB2 gene has been identified in this study as a shared potential biomarker (diagnostic and prognostic) of LIHC and READ.

An experimental study was designed to asses the humoral and cell mediated immune response in the broiler chicks double vaccinated against Newcastle disease (ND) using Lasota strain of ND virus vaccine. Double vaccination 7 days following Ist vaccination gave haemagglutination inhibition (HI) titers ranging from 1:16 to 1:128, that was significantly higher than the HI antibody titer recorded after single vaccination. Similarly, macrophage migration inhibition (MMI) activity ranged from 28.57 to 40.86%, with mean activity of 36.07%. No correlation was found between HI titer and MMI test.

(−)-Sparteine and TMEDA dramatically lower both enthalpy and entropy of activation for the barrier to enantiomerization of N-Boc-2-lithiopyrrolidine in diethyl ether, whereas N,N′-diisopropylbispidine has little effect; the entropy of activation for enantiomerization is zero in the presence of TMEDA and slightly negative in the presence of sparteine; these data suggest a subtle change in mechanism of enantiomerization in the presence of TMEDA and sparteine. [ABSTRACT FROM AUTHOR]

Brain tumours are a leading cause of death and disability, impacting individuals across all ages, genders, and ethnicities. They are primarily diagnosed using MRI but a precise diagnosis is dependent on the molecular biology of the tumour studied on the pathological specimen. Artificial intelligence and machine learning are forging new paths through diagnostic obstacles, offering the intriguing benefits of non-invasive diagnosis, pattern recognition, and outcome prediction from imaging data. Here, we present a literature review on the role of machine learning in tumour mutations using imaging alone.

Subacute sclerosing panencephalitis (SSPE) is a lethal neurological disorder occurring several years after measles. Reconstruction of the evolution of the measles virus (MeV) genome in an SSPE case suggested that the matrix (M) protein mutation M-F50S, when added to other mutations, drove neuropathogenesis. However, whether and how M-F50S would promote spread independently from other mutations was in question. We investigated here the cell specificity of MeV spread in this brain and documented that both neurons and astrocytes were heavily infected. We then generated recombinant MeV with individual mutations in the three proteins of the viral membrane fusion apparatus, M, fusion (F), and hemagglutinin (H). These viruses reached similar titers as the parental wild-type virus, kept the respective mutations upon passage, and infected cells expressing the tissue-specific MeV receptors SLAM and nectin-4 with similar efficiencies. However, after inoculation of receptor-negative neurons and astrocytes differentiated from human induced pluripotent stem cells, only MeV M-F50S spread with moderate efficiency; the parental virus and its derivatives coding for a hyperfusogenic F protein, or for a cytoplasmic tail-mutated H protein, did not spread. When delivered to primary mouse neurons by cell-mediated neurite overlay, MeV M-F50S frequently reached the cell bodies and occasionally formed small infectious centers, while the other MeV reached the cell bodies only sporadically. These results demonstrate that, in neuronal cell cultures, M-F50S can enable receptor-independent spread in the absence of other mutations, and validate the inference that this single amino acid change initiated ubiquitous MeV brain spread.IMPORTANCEMeasles virus (MeV), a non-integrating negative-strand RNA virus, rarely causes subacute sclerosing panencephalitis (SSPE) several years after acute infection. During brain adaptation, the MeV genome acquires multiple mutations reducing the dependence of its membrane fusion apparatus (MFA) from an activating receptor. It was proposed that one of these mutations, matrix protein F50S, drove neuropathogenesis in an SSPE case. We report here that, in two types of neuronal cultures, a recombinant MeV with only this mutation gained receptor-independent spread, whereas viruses expressing MFA proteins with other mutations acquired during brain adaptation did not. Our results validate the inference that M-F50S initiated ubiquitous MeV brain spread resulting in lethal disease. They also prompt studies of the impact of analogous amino acid changes of the M proteins of other nonsegmented negative-strand RNA viruses on their interactions with membrane lipids and cytoskeletal components.

During virus replication in cultured cells, copy-back defective viral genomes (cbDVGs) can arise. CbDVGs are powerful inducers of innate immune responses in vitro , but their occurrence and impact on natural infections of human hosts remain poorly defined. We asked whether cbDVGs were generated in the brain of a patient who succumbed to subacute sclerosing panencephalitis (SSPE) about 20 years after acute measles virus (MeV) infection. Previous analyses of 13 brain specimens of this patient indicated that a collective infectious unit (CIU) drove lethal MeV spread. In this study, we identified 276 replication-competent cbDVG species, each present in over 100 copies in the brain. Six species were detected in multiple forebrain locations, implying that they travelled long-distance with the CIU. The cbDVG to full-length genomes ratio was often close to 1 (0.6-1.74). Most cbDVGs were 324-2,000 bases in length, corresponding to 2%-12% of the full-length genome; all are predicted to have complementary terminal sequences. If improperly encapsidated, these sequences have the potential to form double-stranded structures that can induce innate immune responses. To assess this, we examined the transcriptome of all brain specimens. Several interferon and inflammatory response genes were upregulated, but upregulation levels did not correlate with cbDVG levels in the specimens. Thus, the CIU that drove MeV pathogenesis in this brain includes, in addition to two complementary full-length genome populations, many locally restricted and few widespread cbDVG species. The widespread cbDVG species may have been positively selected but how they impacted pathogenesis remains to be determined.IMPORTANCECopy-back defective viral genomes (cbDVGs) can drive virus-host interactions. They can suppress virus replication directly, by competing with full-length genomes, or indirectly by stimulating antiviral immunity. In vitro , cbDVG can slow down infections and promote persistence, but there is limited documentation of their presence in human hosts or of their impact on disease. We had the unique opportunity to analyze the brain of a patient who succumbed to subacute sclerosing panencephalitis, a rare but lethal consequence of measles. We detected more than 270 distinct cbDVG species; most were restricted to one specimen, but several reached all lobes of the forebrain, suggesting positive selection. Our analyses provide the missing knowledge of the diversity of cbDVG in a natural infection of a human host. They also reveal that a collective infectious unit that caused lethal human brain disease includes few widespread cbDVG, in addition to two ubiquitous complementary full-length genome populations., Competing Interests: The authors declare no conflict of interest.

Invasive aspergillosis (IA) is a rare occurrence, but it should be considered in cases involving pituitary or sellar masses. Here, we present a unique case report of IA affecting the sellar region with para-sellar extension and bilateral carotid artery impingement, notably with minimal involvement of paranasal sinuses. The patient, a 16-year-old immunocompetent female from a developing country, presented without any comorbidities or classic risk factors typically associated with IA. Her initial symptoms included headaches, diplopia, and nausea. Clinically and radiologically, the patient was initially diagnosed with either craniopharyngioma or pituitary macroadenoma. Hormonal studies revealed panhypopituitarism. Previous reports of IA have not described cases with these specific presentations, particularly in this age group and immune status., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Shaukat Khanum Memorial Cancer Hospital & Research Centre issued approval EX-05-04-24-11. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Tariq et al.)

Rhinoviruses (RV) are the major cause of chronic obstructive pulmonary disease and are associated with exacerbation development as well as community-acquired pneumonia in children, leading to substantial morbidity, mortality, and hospital admission. Here we have examined how changes at the amino terminal of the conserved VP4 epitope of different RV serotypes may affect pulmonary cytokine and chemokine responses and disease severity. Samples positive for rhinovirus were used for genetic characterization, followed by profiling gene expression of pulmonary Th1 and Th2 cytokines/chemokines by RT-PCR arrays. Genetic sequencing and homology 3D modeling revealed changes at the amino terminal of the conserved viral protein 4 (VP4) epitope in the RV-A101 serotype, especially serine at several positions that are important for interactive binding with the host immune cells. We found dysregulation of pulmonary gene expression of Th1- and Th2-related cytokines and chemokines in RV-A 101 and RV-C 8 pneumonia patients. These findings might contribute to a better understanding of RV immunity and the potential mechanisms underlying the pathogenesis of severe RV infections, but further functional studies are needed to confirm the causal relationship.

Traditionally, public health surveillance relied on individual-level data but recently wastewater-based epidemiology (WBE) for the detection of infectious diseases including COVID-19 became a valuable tool in the public health arsenal. Here, we use WBE to follow the course of the COVID-19 pandemic in Rochester, Minnesota (population 121,395 at the 2020 census), from February 2021 to December 2022. We monitored the impact of SARS-CoV-2 infections on public health by comparing three sets of data: quantitative measurements of viral RNA in wastewater as an unbiased reporter of virus level in the community, positive results of viral RNA or antigen tests from nasal swabs reflecting community reporting, and hospitalization data. From February 2021 to August 2022 viral RNA levels in wastewater were closely correlated with the oscillating course of COVID-19 case and hospitalization numbers. However, from September 2022 cases remained low and hospitalization numbers dropped, whereas viral RNA levels in wastewater continued to oscillate. The low reported cases may reflect virulence reduction combined with abated inclination to report, and the divergence of virus levels in wastewater from reported cases may reflect COVID-19 shifting from pandemic to endemic. WBE, which also detects asymptomatic infections, can provide an early warning of impending cases, and offers crucial insights during pandemic waves and in the transition to the endemic phase., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

The management of medulloblastoma, a pediatric brain tumor, has evolved significantly with the advent of genomic subgrouping, yet morbidity and mortality remain high in LMICs like Pakistan due to inadequate multidisciplinary care infrastructure. This paper aims to establish evidence-based guidelines tailored to the constraints of such countries. An expert panel comprising neuro-oncologists, neurosurgeons, radiologists, radiation oncologists, neuropathologists, and pediatricians collaborated to develop these guidelines, considering the specific challenges of pediatric brain tumor care in Pakistan. The recommendations cover various aspects of medulloblastoma treatment, including pre-surgical workup, neurosurgery, neuropathology, chemotherapy, radiation therapy, and supportive care. They offer both minimum required and additional optional protocols for more advanced centers, ensuring comprehensive patient management with attention to complications and complexities encountered in Pakistan. The paper's consensus guidelines strive for uniformity in healthcare delivery and address significant gaps in diagnosis, treatment, and follow-up of pediatric medulloblastoma patients.

Key Clinical Message: This case highlights the need for tailored strategies to address issues like brain herniation, subdural hygroma, and cerebrospinal fluid leak, which, if not managed promptly, can lead to long-term neurological deficits. Additionally, the role of specialized facilities in delivering highly specialized care for managing such intricate cases cannot be understated., Abstract: Decompressive craniectomy-induced subdural hygroma (SDH) frequently coexists with external cerebral herniation, resulting in neurological impairments. The incidence of brain herniation through a craniectomy defect postoperatively is 25%. Brain herniation (BH), SDH, and cerebrospinal fluid leak require urgent neurosurgical management as they can lead to irreversible long-term neurological deficits. We report a case of a 42-year-old male who presented with headache and grand mal seizures. He was diagnosed with herniation of brain parenchyma through the surgical defect with a displacement of the bone flap by a heterogeneously enhancing lesion in the left parietal lobe along with SDH in the left frontoparietal region post partial resection of high-grade glioma. In this report, we discuss the pathogenesis and management strategies of brain herniation, wound infection, cerebrospinal fluid (CSF) leak, ipsilateral SDH, floating bone flap, and communicating hydrocephalus in an adult patient following partial resection of high-grade glioma. This particular case emphasizes the value of an individualized patient-centered surgical approach to minimize the risk of postoperative complications., (© 2024 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.)

It is increasingly appreciated that pathogens can spread as infectious units constituted by multiple, genetically diverse genomes, also called collective infectious units or genome collectives. However, genetic characterization of the spatial dynamics of collective infectious units in animal hosts is demanding, and it is rarely feasible in humans. Measles virus (MeV), whose spread in lymphatic tissues and airway epithelia relies on collective infectious units, can, in rare cases, cause subacute sclerosing panencephalitis (SSPE), a lethal human brain disease. In different SSPE cases, MeV acquisition of brain tropism has been attributed to mutations affecting either the fusion or the matrix protein, or both, but the overarching mechanism driving brain adaptation is not understood. Here we analyzed MeV RNA from several spatially distinct brain regions of an individual who succumbed to SSPE. Surprisingly, we identified two major MeV genome subpopulations present at variable frequencies in all 15 brain specimens examined. Both genome types accumulated mutations like those shown to favor receptor-independent cell-cell spread in other SSPE cases. Most infected cells carried both genome types, suggesting the possibility of genetic complementation. We cannot definitively chart the history of the spread of this virus in the brain, but several observations suggest that mutant genomes generated in the frontal cortex moved outwards as a collective and diversified. During diversification, mutations affecting the cytoplasmic tails of both viral envelope proteins emerged and fluctuated in frequency across genetic backgrounds, suggesting convergent and potentially frequency-dependent evolution for modulation of fusogenicity. We propose that a collective infectious unit drove MeV pathogenesis in this brain. Re-examination of published data suggests that similar processes may have occurred in other SSPE cases. Our studies provide a primer for analyses of the evolution of collective infectious units of other pathogens that cause lethal disease in humans., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Introduction: Headache is a widely prevalent illness that negatively impacts people's lives, leaving them functionally incapable of performing regular everyday tasks. The global burden of headache is 40%, of which migraine accounts for 47%., Objective: This study aims to determine the frequency of migraine among medical students of Lahore and its characteristics, associated triggers, and relievers among medical students., Methodology: A cross-sectional study was conducted in medical colleges after obtaining ethical approval. Migraine was diagnosed using the criteria provided in the International Classification of Headache Disorders, Third Edition (ICHD-3), and data on triggers, relief, and demographics were collected. The information is analyzed using SPSS 22., Result: The data were collected from 522 medical students. The average age of the students was 21.3 ± 2.0 SD (in years). About 146 (28.0%) of the medical students have migraine according to ICHD-3 criteria and were diagnosed initially. Gender was insignificantly associated with migraine ( P -value=0.32). Students with psoriasis, hypertension, and polycystic ovarian syndrome were statistically significantly related to migraines with a P -value=0.002. Dehydration is the most frequent aggravator, and adequate sleep is the most frequent reliever of migraine., Conclusion: The findings show a high frequency of migraine. They are similar in both genders, depicting that stressful lifestyles, inadequate sleep patterns, and bizarre dietary habits make them more prone to migraine episodes. So, further, detailed studies should be done on evaluating triggers and relievers of migraine and their interrelations with migraine so we can focus on preventive strategies, diagnosis, and treatment of migraine., Competing Interests: No conflicts of interest to be declared.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives  The 2021 WHO Classification of Central Nervous System Tumors taxonomy laid further stress on molecular classification and prognostication of glial tumors in comparison to histopathological grading. Research shows that low-grade gliomas (LGGs) can go through malignant differentiation and lead to severe disability and death. Data from various populations will be necessary to ascertain the exact interplay between genotypic predictors of LGG and outcomes. Materials and Methods  To assess the molecular pathology for glial tumors in the Pakistani population, the Shaukat Khanum Memorial Cancer Hospital carried out a retrospective chart review of electronic health records from 2008 to 2018, with immunohistochemistry analysis findings from 2010 to 2018. Patients with a pathological diagnosis of a glioma were included. Statistical Analysis  Analysis was performed using IBM SPSS Statistics Version 23 and STATA Version 16. A p -value of less than 0.05 was considered statistically significant with 95% confidence intervals reported. Results  In all, 281 operable tumors were recorded. The most common procedure was a subtotal resection, and astrocytomas (64.77%) were the most common tumors. Radiation therapy and PCV (procarbazine, CCNU, and vincristine) was received by 85 patients, while radiation therapy and temozolomide were administered to 15 patients. Conclusions  Isocitrate dehydrogenase (IDH) wild-type LGG had a lower survival time, while improved survival times were seen for alpha-thalassemia X-linked intellectual disability syndrome (ATRX) retained and 1p19q co-deleted LGGs. Further studies are required to gain a better understanding of lower-grade glial tumor treatment and survival in Pakistan., Competing Interests: Conflict of Interest None declared., (Asian Congress of Neurological Surgeons. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Objective: To determine the Frequency of psychiatric illnesses in patients with neurological conditions, and to take their opinion about psychiatric disorders., Methods: The cross-sectional study was conducted from June 1 to August 30, 2021, at the Neurology Outpatient Department of Allied Hospital, Faisalabad, Pakistan, and comprised patients of either gender aged 12-70 years from among those visiting the outpatient clinic. Data was collected through interviews and the 41-item Depression Anxiety Stress Scale. Data was analysed using SPSS 21., Results: Of the 201 patients, 160(79.6%) were females and 41(20.4%) were males. The overall mean age was 34.5+/- 9.38 years. Primary neurological problem was headache 119(59.2%). Overall, 155(77.2%) patients met the criteria of psychiatric disorders; 55(27.4%) anxiety, 37(19.4%) had depressive disorder, 42(20.8%) mixed anxiety depressive disorder, and 19(9.5%) had other psychiatric illnesses. Also, 101(50.2%) patients lacked awareness about psychiatry illnesses, 35(17.4%) had fear of stigma, and 28(13.9%) had misconceptions., Conclusions: The frequency of psychiatric disorders among those visiting the neurology outpatient department was high, and was associated with negative views about such illnesses.

Objective  The interplay of static factors and their effect on metastatic brain tumor survival, especially in low-to-middle-income countries (LMICs), has been rarely studied. To audit our experience, and explore novel survival predictors, we performed a retrospective analysis of brain metastases (BM) patients at Shaukat Khanum Memorial Cancer Hospital (SKMCH), Pakistan. Materials and Methods  A retrospective review was conducted of consecutive patients who presented with BM between September 2014 and September 2019 at SKMCH. Patients with incomplete records were excluded. Statistical Analysis  SPSS (v.25 IBM, Armonk, New York, United States) was used to collect and analyze data via Cox-Regression and Kaplan-Meier curves. Results  One-hundred patients (mean age 45.89 years) with confirmed BM were studied. Breast cancer was the commonest primary tumor. Median overall survival (OS) was 6.7 months, while the median progression-free survival (PFS) was 6 months. Age ( p  = 0.001), gender ( p  = 0.002), Eastern Cooperative Oncology Group ( p  < 0.05), anatomical site ( p  = 0.002), herniation ( p  < 0.05), midline shift ( p  = 0.002), treatment strategies ( p  < 0.05), and postoperative complications (p < 0.05) significantly impacted OS, with significantly poor prognosis seen with extremes of age, male gender (hazard ratio [HR]: 2.0; 95% confidence interval [CI]: 1.3-3.1; p  = 0.003), leptomeningeal lesions (HR: 5.7; 95% CI: 1.1-29.7; p  = 0.037), and patients presenting with uncal herniation (HR: 3.5; 95% CI: 1.9-6.3; p  < 0.05). Frontal lobe lesions had a significantly better OS (HR: 0.5; 95% CI: 0.2-1.0; p = 0.049) and PFS (HR: 0.08; 95% CI: 0.02-0.42; p  = 0.003). Conclusion  BM has grim prognoses, with comparable survival indices between developed countries and LMICs. Early identification of both primary malignancy and metastatic lesions, followed by judicious management, is likely to significantly improve survival., Competing Interests: Conflict of Interest None declared., (Asian Congress of Neurological Surgeons. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

We examine the connectedness of the COVID vaccination with the economic policy uncertainty, oil, bonds, and sectoral equity markets in the US within time and frequency domain. The wavelet-based findings show the positive impact of COVID vaccination on the oil and sector indices over various frequency scales and periods. The vaccination is evidenced to lead the oil and sectoral equity markets. More specifically, we document strong connectedness of vaccinations with communication services, financials, health care, industrials, information technology (IT) and real estate equity sectors. However, weak interactions exist within the vaccination-IT-services and vaccination-utilities pairs. Moreover, the effect of vaccination on the Treasury bond index is negative, whereas the economic policy uncertainty shows an interchanging lead and lag relation with vaccination. It is further observed that the interrelation between vaccination and the corporate bond index is insignificant. Overall, the impact of vaccination on the sectoral equity markets and economic policy uncertainty is higher than on oil and corporate bond prices. The study offers several important implications for investors, government regulators, and policymakers., (© The Author(s) 2023.)