A case study to engage students in the research design and ethics of high-throughput metagenomics.

Case studies present students with an opportunity to learn and apply course content through problem solving and critical thinking. Supported by the High-throughput Discovery Science & Inquiry-based Case Studies for Today's Students (HITS) Research Coordination Network, our interdisciplinary team designed, implemented, and assessed two case study modules entitled "You Are What You Eat." Collectively, the case study modules present students with an opportunity to engage in experimental research design and the ethical considerations regarding microbiome research and society. In this manuscript, we provide instructors with tools for adopting or adapting the research design and/or the ethics modules. To date, the case has been implemented using two modalities (remote and in-person) in three courses (Microbiology, Physiology, and Neuroscience), engaging over 200 undergraduate students. Our assessment data demonstrate gains in content knowledge and students' perception of learning following case study implementation. Furthermore, when reflecting on our experiences and student feedback, we identified ways in which the case study could be modified for different settings. In this way, we hope that the "You Are What You Eat" case study modules can be implemented widely by instructors to promote problem solving and critical thinking in the traditional classroom or laboratory setting when discussing next-generation sequencing and/or metagenomics research.

High-risk Escherichia coli clones that cause neonatal meningitis and association with recrudescent infection.

Neonatal meningitis is a devastating disease associated with high mortality and neurological sequelae. Escherichia coli is the second most common cause of neonatal meningitis in full-term infants (herein NMEC) and the most common cause of meningitis in preterm neonates. Here, we investigated the genomic relatedness of a collection of 58 NMEC isolates spanning 1974-2020 and isolated from seven different geographic regions. We show NMEC are comprised of diverse sequence types (STs), with ST95 (34.5%) and ST1193 (15.5%) the most common. No single virulence gene profile was conserved in all isolates; however, genes encoding fimbrial adhesins, iron acquisition systems, the K1 capsule, and O antigen types O18, O75, and O2 were most prevalent. Antibiotic resistance genes occurred infrequently in our collection. We also monitored the infection dynamics in three patients that suffered recrudescent invasive infection caused by the original infecting isolate despite appropriate antibiotic treatment based on antibiogram profile and resistance genotype. These patients exhibited severe gut dysbiosis. In one patient, the causative NMEC isolate was also detected in the fecal flora at the time of the second infection episode and after treatment. Thus, although antibiotics are the standard of care for NMEC treatment, our data suggest that failure to eliminate the causative NMEC that resides intestinally can lead to the existence of a refractory reservoir that may seed recrudescent infection.

Pharmacological induction of chromatin remodeling drives chemosensitization in triple-negative breast cancer.

Targeted therapies have improved outcomes for certain cancer subtypes, but cytotoxic chemotherapy remains a mainstay for triple-negative breast cancer (TNBC). The epithelial-to-mesenchymal transition (EMT) is a developmental program co-opted by cancer cells that promotes metastasis and chemoresistance. There are no therapeutic strategies specifically targeting mesenchymal-like cancer cells. We report that the US Food and Drug Administration (FDA)-approved chemotherapeutic eribulin induces ZEB1-SWI/SNF-directed chromatin remodeling to reverse EMT that curtails the metastatic propensity of TNBC preclinical models. Eribulin induces mesenchymal-to-epithelial transition (MET) in primary TNBC in patients, but conventional chemotherapy does not. In the treatment-naive setting, but not after acquired resistance to other agents, eribulin sensitizes TNBC cells to subsequent treatment with other chemotherapeutics. These findings provide an epigenetic mechanism of action of eribulin, supporting its use early in the disease process for MET induction to prevent metastatic progression and chemoresistance. These findings warrant prospective clinical evaluation of the chemosensitizing effects of eribulin in the treatment-naive setting.

Focused stimulation of dorsal versus ventral subthalamic nucleus enhances action-outcome learning in patients with Parkinson's disease.

Deep brain stimulation of the subthalamic nucleus is an effective treatment for the clinical motor symptoms of Parkinson's disease, but may alter the ability to learn contingencies between stimuli, actions and outcomes. We investigated how stimulation of the functional subregions in the subthalamic nucleus (motor and cognitive regions) modulates stimulus-action-outcome learning in Parkinson's disease patients. Twelve Parkinson's disease patients with deep brain stimulation of the subthalamic nucleus completed a probabilistic stimulus-action-outcome task while undergoing ventral and dorsal subthalamic nucleus stimulation (within subjects, order counterbalanced). The task orthogonalized action choice and outcome valence, which created four action-outcome learning conditions: action-reward, inhibit-reward, action-punishment avoidance and inhibit-punishment avoidance. We compared the effects of deep brain stimulation on learning rates across these conditions as well as on computed Pavlovian learning biases. Dorsal stimulation was associated with higher overall learning proficiency relative to ventral subthalamic nucleus stimulation. Compared to ventral stimulation, stimulating the dorsal subthalamic nucleus led to a particular advantage in learning to inhibit action to produce desired outcomes (gain reward or avoid punishment) as well as better learning proficiency across all conditions providing reward opportunities. The Pavlovian reward bias was reduced with dorsal relative to ventral subthalamic nucleus stimulation, which was reflected by improved inhibit-reward learning. Our results show that focused stimulation in the dorsal compared to the ventral subthalamic nucleus is relatively more favourable for learning action-outcome contingencies and reduces the Pavlovian bias that could lead to reward-driven behaviour. Considering the effects of deep brain stimulation of the subthalamic nucleus on learning and behaviour could be important when optimizing stimulation parameters to avoid side effects like impulsive reward-driven behaviour.

#lowbackpain on TikTok: A New Frontier for Orthopaedic Medical Education.

INTRODUCTION: Low back pain has become a substantial health problem in all developed countries. Many healthcare professionals and content creators have begun sharing their treatment methods and opinions through social media, especially the video-based platform TikTok. TikTok has been downloaded more than 2.6 billion times with over a billion daily users. Its influence on public health makes it imperative that information be accurate and safe. This study aims to analyze TikTok's most popular content on lower back pain and how orthopaedic surgeons contribute on this growing platform. OBJECTIVES: To analyze TikTok's most popular content on lower back pain and how orthopaedic surgeons are and can contribute on this growing platform. METHODS: A TikTok search conducted on April 22, 2023, using the terms '#lowerbackpain'and '#lowbackpainrelief,' resulted in numerous videos, 100 of which met inclusion criteria. Videos were included if they were related to the content, had more than 1000 views, were in English, and were not duplicates. Video characteristics were recorded and evaluated for quality by two reviewers using DISCERN. A two-sample t-test was used to assess differences. RESULTS: Overall, the top videos on lower back pain had an average of 2,061,396 views, with a mean DISCERN score of 34. The mean total DISCERN score was 36 and 34 for physicians and nonphysicians, respectively, while the video by the orthopaedic surgeon (n = 1) scored 31. The most recommended treatments included at-home exercises (n = 75) and visiting a chiropractor (n = 4). CONCLUSION: We find that the information presented by nonphysicians offered quick, at-home fixes to medical problems without offering any research or proven data to support their claims. We cannot overlook Tiktok's immense influence in the realm of orthopaedic health as it has become a sphere of information dissemination and education. Thus, we suggest that there is not necessarily a need for a greater number of surgeons and/or resident physicians to involve themselves on the platform, but rather the involvement of governing bodies and spine societies to put out position statements for our patients.

Emergency Medicine Postgraduate Year, Laryngoscopic View, and Endotracheal Tube Placement Success.

STUDY OBJECTIVE: Prior work has found first-attempt success improves with emergency medicine (EM) postgraduate year (PGY). However, the association between PGY and laryngoscopic view - a key step in successful intubation - is unknown. We examined the relationship among PGY, laryngoscopic view (ie, Cormack-Lehane view), and first-attempt success. METHODS: We performed a retrospective analysis of the National Emergency Airway Registry, including adult intubations by EM PGY 1 to 4 resident physicians. We used inverse probability weighting with propensity scores to balance confounders. We used weighted regression and model comparison to estimate adjusted odds ratios (aOR) with 95% confidence intervals (CIs) between PGY and Cormack-Lehane view, tested the interaction between PGY and Cormack-Lehane view on first-attempt success, and examined the effect modification of Cormack-Lehane view on the association between PGY and first-attempt success. RESULTS: After exclusions, we included 15,453 first attempts. Compared to PGY 1, the aORs for a higher Cormack-Lehane grade did not differ from PGY 2 (1.01; 95% CI 0.49 to 2.07), PGY 3 (0.92; 0.31 to 2.73), or PGY 4 (0.80; 0.31 to 2.04) groups. The interaction between PGY and Cormack-Lehane view was significant (P-interaction<0.001). In patients with Cormack-Lehane grade 3 or 4, the aORs for first-attempt success were higher for PGY 2 (1.80; 95% CI 1.17 to 2.77), PGY 3 (2.96; 1.66 to 5.27) and PGY 4 (3.10; 1.60 to 6.00) groups relative to PGY 1. CONCLUSION: Compared with PGY 1, PGY 2, 3, and 4 resident physicians obtained similar Cormack-Lehane views but had higher first-attempt success when obtaining a grade 3 or 4 view.

Influences of amyloid-ß and tau on white matter neurite alterations in dementia with Lewy bodies.

Dementia with Lewy bodies (DLB) is a neurodegenerative condition often co-occurring with Alzheimer's disease (AD) pathology. Characterizing white matter tissue microstructure using Neurite Orientation Dispersion and Density Imaging (NODDI) may help elucidate the biological underpinnings of white matter injury in individuals with DLB. In this study, diffusion tensor imaging (DTI) and NODDI metrics were compared in 45 patients within the dementia with Lewy bodies spectrum (mild cognitive impairment with Lewy bodies (n = 13) and probable dementia with Lewy bodies (n = 32)) against 45 matched controls using conditional logistic models. We evaluated the associations of tau and amyloid-ß with DTI and NODDI parameters and examined the correlations of AD-related white matter injury with Clinical Dementia Rating (CDR). Structural equation models (SEM) explored relationships among age, APOE ε4, amyloid-ß, tau, and white matter injury. The DLB spectrum group exhibited widespread white matter abnormalities, including reduced fractional anisotropy, increased mean diffusivity, and decreased neurite density index. Tau was significantly associated with limbic and temporal white matter injury, which was, in turn, associated with worse CDR. SEM revealed that amyloid-ß exerted indirect effects on white matter injury through tau. We observed widespread disruptions in white matter tracts in DLB that were not attributed to AD pathologies, likely due to α-synuclein-related injury. However, a fraction of the white matter injury could be attributed to AD pathology. Our findings underscore the impact of AD pathology on white matter integrity in DLB and highlight the utility of NODDI in elucidating the biological basis of white matter injury in DLB.

Pathogenesis of sleep disordered breathing in the setting of opioid use: A multiple mediation analysis using physiology.

STUDY OBJECTIVES: Opioid medications are commonly used and are known to impact both breathing and sleep, and are linked with adverse health outcomes including death. Clinical data indicate that chronic opioid use causes central sleep apnea, and might also worsen obstructive sleep apnea. The mechanisms by which opioids influence sleep-disordered breathing pathogenesis are not established. METHODS: Patients who underwent clinically-indicated polysomnography confirming sleep-disordered breathing (SDB) (AHI≥5/hr) were included. Each patient using opioids was matched by sex, age, and BMI to three control individuals not using opioids. Physiology known to influence SDB pathogenesis were determined from validated polysomnography-based signal analysis. PSG and physiology paramters of interest were compared between opioid and control individuals, adjusted for covariates. Mediation analysis was used to evaluate the link between opioids, physiology, and polysomnographic metrics. RESULTS: 178 individuals using opioids were matched to 534 controls (median [IQR] age 59 [50,65] years, BMI 33 [29,41] kg/m2, 57% female, daily morphine equivalent 30 [20,80] mg). Compared with controls, opioids were associated with increased central apneas (2.8 vs 1.7 events/hr; p=0.001) and worsened hypoxemia (5 vs 3% sleep with SpO2<88%; p=0.013), with similar overall AHI. Use of opioids was associated with higher loop gain, a lower respiratory rate and higher respiratory rate variability. Higher loop gain and increased respiratory rate variability mediated the effect of opioids on central apnea, but did not mediate the effect on hypoxemia. CONCLUSIONS: Opioids have multi-level effects impacting SDB. Targeting these factors may help mitigate deleterious respiratory consequences of chronic opioid use.

Gradients in embolism resistance within stems driven by secondary growth in herbs.

The stems of some herbaceous species can undergo basal secondary growth, leading to a continuum in the degree of woodiness along the stem. Whether the formation of secondary growth in the stem base results in differences in embolism resistance between the base and the upper portions of stems is unknown. We assessed the embolism resistance of leaves and the basal and upper portions of stems simultaneously within the same individuals of two divergent herbaceous species that undergo secondary growth in the mature stem bases. The species were Solanum lycopersicum (tomato) and Senecio minimus (fireweed). Basal stem in mature plants of both species displayed advanced secondary growth and greater resistance to embolism than the upper stem. This also resulted in significant vulnerability segmentation between the basal stem and the leaves in both species. Greater embolism resistance in the woodier stem base was found alongside decreases in the pith-to-xylem ratio, increases in the proportion of secondary xylem, and increases in lignin content. We show that there can be considerable variation in embolism resistance across the stem in herbs and that this variation is linked to the degree of secondary growth present. A gradient in embolism resistance across the stem in herbaceous plants could be an adaptation to ensure reproduction or basal resprouting during episodes of drought late in the lifecycle.

PET Quantification of [18F]VAT in Human Brain and Its Test-Retest Reproducibility and Age Dependence.

Molecular imaging of brain vesicular acetylcholine transporter provides a biomarker to explore cholinergic systems in humans. We aimed to characterize the distribution of, and optimize methods to quantify, the vesicular acetylcholine transporter-specific tracer (-)-(1-(8-(2-[18F]fluoroethoxy)-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)-piperidin-4-yl)(4-fluorophenyl)methanone ([18F]VAT) in the brain using PET. Methods: Fifty-two healthy participants aged 21-97 y had brain PET with [18F]VAT. [3H]VAT autoradiography identified brain areas devoid of specific binding in cortical white matter. PET image-based white matter reference region size, model start time, and duration were optimized for calculations of Logan nondisplaceable binding potential (BPND). Ten participants had 2 scans to determine test-retest variability. Finally, we analyzed age-dependent differences in participants. Results: [18F]VAT was widely distributed in the brain, with high striatal, thalamic, amygdala, hippocampal, cerebellar vermis, and regionally specific uptake in the cerebral cortex. [3H]VAT autoradiography-specific binding and PET [18F]VAT uptake were low in white matter. [18F]VAT SUVs in the white matter reference region correlated with age, requiring stringent erosion parameters. Logan BPND estimates stabilized using at least 40 min of data starting 25 min after injection. Test-retest variability had excellent reproducibility and reliability in repeat BPND calculations for 10 participants (putamen, 6.8%; r > 0.93). We observed age-dependent decreases in the caudate and putamen (multiple comparisons corrected) and in numerous cortical regions. Finally, we provide power tables to indicate potential mean differences that can be detected between 2 groups of participants. Conclusion: These results validate a reference region for BPND calculations and demonstrate the viability, reproducibility, and utility of using the [18F]VAT tracer in humans to quantify cholinergic pathways.

Borotropic shifting of the [hydrotris(2'-furyl)pyrazol-1-yl]borate ligand in high-coordinate lanthanide complexes.

The coordination of hydrotris[3-(2'-furyl)pyrazol-1-yl]borate (Tp2-Fu, C21H16BN6O3) to lanthanide(III) ions is achieved for the first time with the complex [Ln(Tp2-Fu)2](BPh4)·xCH2Cl2 (1-Ln has Ln = Ce and x = 2; 1-Dy has Ln = Dy and x = 1). This was accomplished via both hydrous (Ln = Ce) and anhydrous methods (Ln = Dy). When isolating the dysprosium analogue, the filtrate produced a second crop of crystals which were revealed to be the 1,2-borotropic-shifted product [Dy(κ4-Tp2-Fu)(κ5-Tp2-Fu*)](BPh4) (2) {Tp2-Fu* = hydrobis[3-(2'-furyl)pyrazol-1-yl][5-(2'-furyl)pyrazol-1-yl]borate}. We conclude that the presence of a strong Lewis acid and a sterically crowded coordination environment are contributing factors for the 1,2-borotropic shifting of scorpionate ligands in conjunction with the size of the conical angle with the scorpionate ligand.

Is informal practice associated with outcomes in loving-kindness and compassion training? Evidence from pre-post and daily diary assessments.

We investigated whether informal meditation practice (i.e., self-reported application of meditative techniques outside a period of formal meditation) was associated with outcomes in smartphone-based loving-kindness and compassion training. Meditation-naïve participants (n = 351) with clinically elevated symptoms completed measures of psychological distress, loneliness, empathy, and prosociality at baseline and following a two-week intervention. Informal practice, psychological distress, and loneliness were also assessed daily. Steeper increases in informal practice had small associations with pre-post improvements in distress (r = -.18, p = .008) and loneliness (r = -.19, p = .009) but not empathy or prosociality. Using a currently recommended approach for establishing cross-lagged effects in longitudinal data (latent curve model with structured residuals), higher current-day informal practice was associated with decreased next-day distress with a very small effect size (ßs = -.06 to -.04, p = .018) but not decreased next-day loneliness. No cross-lagged associations emerged from distress or loneliness to informal practice. Findings suggest that further investigation into a potential causal role of informal practice is warranted. Future studies experimentally manipulating informal practice are needed.

New Oldowan locality Sare-Abururu (ca. 1.7 Ma) provides evidence of diverse hominin behaviors on the Homa Peninsula, Kenya.

The Homa Peninsula, in southwestern Kenya, continues to yield insights into Oldowan hominin landscape behaviors. The Late Pliocene locality of Nyayanga (∼3-2.6 Ma) preserves some of the oldest Oldowan tools. At the Early Pleistocene locality of Kanjera South (∼2 Ma) toolmakers procured a diversity of raw materials from over 10 km away and strategically reduced them in a grassland-dominated ecosystem. Here, we report findings from Sare-Abururu, a younger (∼1.7 Ma) Oldowan locality approximately 12 km southeast of Kanjera South and 18 km east of Nyayanga. Sare-Abururu has yielded 1754 artifacts in relatively undisturbed low-energy silts and sands. Stable isotopic analysis of pedogenic carbonates suggests that hominin activities were carried out in a grassland-dominated setting with similar vegetation structure as documented at Kanjera South. The composition of a nearby paleo-conglomerate indicates that high-quality stone raw materials were locally abundant. Toolmakers at Sare-Abururu produced angular fragments from quartz pebbles, representing a considerable contrast to the strategies used to reduce high quality raw materials at Kanjera South. Although lithic reduction at Sare-Abururu was technologically simple, toolmakers proficiently produced cutting edges, made few mistakes and exhibited a mastery of platform management, demonstrating that expedient technical strategies do not necessarily indicate a lack of skill or suitable raw materials. Lithic procurement and reduction patterns on the Homa Peninsula appear to reflect variation in local resource contexts rather than large-scale evolutionary changes in mobility, energy budget, or toolmaker cognition.

Tumor Size Is Not Everything: Advancing Radiomics as a Precision Medicine Biomarker in Oncology Drug Development and Clinical Care. A Report of a Multidisciplinary Workshop Coordinated by the RECIST Working Group.

Radiomics, the science of extracting quantifiable data from routine medical images, is a powerful tool that has many potential applications in oncology. The Response Evaluation Criteria in Solid Tumors Working Group (RWG) held a workshop in May 2022, which brought together various stakeholders to discuss the potential role of radiomics in oncology drug development and clinical trials, particularly with respect to response assessment. This article summarizes the results of that workshop, reviewing radiomics for the practicing oncologist and highlighting the work that needs to be done to move forward the incorporation of radiomics into clinical trials.

Trends in workplace homicides in the U.S., 1994-2021: An end to years of decline.

Workplace and non-workplace homicides in the United States (U.S.) have declined for over 30 years until recently. This study was conducted to address the change in trends for both workplace and non-workplace homicides and to evaluate the homogeneity of the change in workplace homicides by specified categories. Joinpoint and autoregressive models were used to assess trends of U.S. workplace and non-workplace homicides utilizing surveillance data collected by the Bureau of Labor Statistics and the Federal Bureau of Investigation from 1994 through 2021. Both workplace and non-workplace homicides decreased significantly from 1994 through 2014. Workplace homicides showed no significant trend from 2014 through 2021 (p = 0.79), while non-workplace homicides showed a significant average annual increase of 4.1% from 2014 through 2020 (p = 0.0013). The large decreases in the trend of workplace homicides occurring during a criminal act, such as robbery, leveled off and started to increase by the end of the study period (p < 0.0001). Declines in workplace homicides due to shootings also leveled off and started to increase by the end of the study period (p < 0.0001). U.S. workplace and non-workplace homicide rates declined from the 1990s until around 2014. Trends in workplace homicides varied by the types of the homicide committed and by the type of employee that was the victim. Criminal-intent-related events, such as robbery, appear to be the largest contributor to changes in workplace homicides. Researchers and industry leaders could develop and evaluate interventions that further address criminal-intent-related workplace homicides.

Structural mechanisms of mitochondrial uncoupling protein 1 regulation in thermogenesis.

In mitochondria, the oxidation of nutrients is coupled to ATP synthesis by the generation of a protonmotive force across the mitochondrial inner membrane. In mammalian brown adipose tissue (BAT), uncoupling protein 1 (UCP1, SLC25A7), a member of the SLC25 mitochondrial carrier family, dissipates the protonmotive force by facilitating the return of protons to the mitochondrial matrix. This process short-circuits the mitochondrion, generating heat for non-shivering thermogenesis. Recent cryo-electron microscopy (cryo-EM) structures of human UCP1 have provided new molecular insights into the inhibition and activation of thermogenesis. Here, we discuss these structures, describing how purine nucleotides lock UCP1 in a proton-impermeable conformation and rationalizing potential conformational changes of this carrier in response to fatty acid activators that enable proton leak for thermogenesis.

Structural characterization of fatty acid anions via gas-phase charge inversion using Mg(tri-butyl-terpyridine)2 2+ reagent ions.

RATIONALE: Free fatty acids and lipid classes containing fatty acid esters are major components of lipidome. In the absence of a chemical derivatization step, FA anions do not yield all of the structural information that may be of interest under commonly used collision-induced dissociation (CID) conditions. A line of work that avoids condensed-phase derivatization takes advantage of gas-phase ion/ion chemistry to charge invert FA anions to an ion type that provides the structural information of interest using conventional CID. This work was motivated by the potential for significant improvement in overall efficiency for obtaining FA chain structural information. METHODS: A hybrid triple quadrupole/linear ion-trap tandem mass spectrometer that has been modified to enable the execution of ion/ion reaction experiments was used to evaluate the use of 4,4',4″-tri-tert-butyl-2,2':6',2″-terpyridine (ttb-Terpy) as the ligand in divalent magnesium complexes for charge inversion of FA anions. RESULTS: Mg(ttb-Terpy)2 2+ complexes provide significantly improved efficiency in producing structurally informative products from FA ions relative to Mg(Terpy)2 2+ complexes, as demonstrated for straight-chain FAs, branched-chain FAs, unsaturated FAs, and cyclopropane-containing FAs. It was discovered that most of the structurally informative fragmentation from [FA-H + Mg(ttb-Terpy)]+ results from the loss of a methyl radical from the ligand followed by radical-directed dissociation (RDD), which stands in contrast to the charge-remote fragmentation (CRF) believed to be operative with the [FA-H + Mg(Terpy)]+ ions. CONCLUSIONS: This work demonstrates that a large fraction of product ions from the CID of ions of the form [FA-H + Mg(ttb-Terpy)]+ are derived from RDD of the FA backbone, with a very minor fraction arising from structurally uninformative dissociation channels. This ligand provides an alternative to previously used ligands for the structural characterization of FAs via CRF.

Middle East and North Africa: Updated Surveillance Metrics and History of the COVID-19 Pandemic (2020-2023)This study updates the COVID-19 pandemic surveillance in the Middle East and North Africa we first conducted in 2020 with two additional years of data for the region.

BACKGROUND: This study updates the COVID-19 pandemic surveillance in the Middle East and North Africa we first conducted in 2020 with two additional years of data for the region. OBJECTIVE: The objective of this study is to determine whether the Middle East and North Africa region meets the criteria for moving from a pandemic to endemic. In doing so, this study considers pandemic trends, dynamic and genomic surveillance methods, and region-specific historical context for the pandemic. These considerations continue through the World Health Organization (WHO) declaration of the end of the public health emergency for the COVID-19 pandemic on May 5, 2023. METHODS: In addition to updates of traditional surveillance data and dynamic panel estimates from the original study Post et al. (2021), this study used data on sequenced SARS-CoV-2 variants from the Global Initiative on Sharing All Influenza Data (GISAID) to identify the appearance and duration of variants of concern. We used Nextclade nomenclature to collect clade designations from sequences and Pangolin nomenclature for lineage designations of SARS-CoV-2. Finally, we conducted a one-sided t-test for whether regional weekly speed of COVID-19 spread was greater than an outbreak threshold of ten. We ran the test iteratively with six months of data from September 4, 2020, to May 12, 2023. RESULTS: The speed of COVID-19 spread for the region had remained below the outbreak threshold for seven continuous months by the time of the WHO declaration. Acceleration and jerk were also low and stable. While the 1- and 7-day persistence coefficients remained statistically significant and positive, the weekly shift parameters suggested the coefficients had most recently turned negative, meaning the clustering effect of new COVID-19 cases became even smaller in the two weeks around the WHO declaration. From December of 2021 onward, Omicron was the predominant variant of concern in sequenced viral samples. The rolling t-test of speed of spread equal to ten became entirely insignificant from October 2022 onward. CONCLUSIONS: The COVID-19 pandemic had far-reaching effects on MENA, impacting healthcare systems, economies, and social well-being. While COVID-19 continues to circulate in the Middle East and North Africa, the rate of transmission remained well below the threshold of an outbreak for over one year ahead of the WHO declaration. COVID-19 is endemic in the region and no longer reaches the threshold of the pandemic definition. Both standard and enhanced surveillance metrics confirm that the pandemic had transitioned to endemic by the time of the WHO declaration.

European Surveillance and History of the COVID-19 Pandemic: Updated Epidemiological Assessment.

BACKGROUND: COVID-19 surveillance plays a crucial role in monitoring the pandemic's progression and comprehending its impact on diverse regions. In this study, we build upon our initial research published in 2020 by incorporating an additional two years of data for Europe. We assess whether COVID-19 had shifted from pandemic to endemic in the region when the World Health Organization (WHO) declared the end of the public health emergency for the COVID-19 pandemic on May 5, 2023. OBJECTIVE: First, we measure whether there was an expansion or contraction in the pandemic in Europe at the time of the WHO declaration. Second, we use dynamic and genomic surveillance methods to describe the history of the pandemic in the region and situate the window of the WHO declaration within the broader history. Third, we provide the historical context for the course of the pandemic in Europe in terms of policy and disease burden at the country and region levels. METHODS: In addition to updates of traditional surveillance data and dynamic panel estimates from the original study Post et al. (2021), this study used data on sequenced SARS-CoV-2 variants from the Global Initiative on Sharing All Influenza Data (GISAID) to identify the appearance and duration of variants of concern. We used Nextclade nomenclature to collect clade designations from sequences and Pangolin nomenclature for lineage designations of SARS-CoV-2. Finally, we conducted a one-sided t-test for whether regional weekly speed was greater than an outbreak threshold of ten. We ran the test iteratively with six months of data across the sample period. RESULTS: Speed for the region had remained below the outbreak threshold for four months by the time of the WHO declaration. Acceleration and jerk were also low and stable. While the 1- and 7-day persistence coefficients remained statistically significant, the coefficients were moderate in magnitude (0.404 and 0.547, respectively). The shift parameters for the two weeks around the WHO declaration were small and insignificant, suggesting little change in the clustering effect of cases on future cases at the time. From December of 2021 onward, Omicron was the predominant variant of concern in sequenced viral samples. The rolling t-test of speed equal to ten became insignificant for the first time in April 2023. CONCLUSIONS: While COVID-19 continues to circulate in Europe, the rate of transmission remained below the threshold of an outbreak for four months ahead of the WHO declaration. The region had previously been in a nearly continuous state of outbreak. The more recent trend suggest COVID-19 was endemic in the region and no longer reached the threshold of the pandemic definition. However, several countries remained in a state of outbreak, and the conclusion that COVID-19 was no longer pandemic in Europe at the time is unclear.