Artificial intelligence for automated detection and measurements of carpal instability signs on conventional radiographs.

OBJECTIVES: To develop and validate an artificial intelligence (AI) system for measuring and detecting signs of carpal instability on conventional radiographs. MATERIALS AND METHODS: Two case-control datasets of hand and wrist radiographs were retrospectively acquired at three hospitals (hospitals A, B, and C). Dataset 1 (2178 radiographs from 1993 patients, hospitals A and B, 2018-2019) was used for developing an AI system for measuring scapholunate (SL) joint distances, SL and capitolunate (CL) angles, and carpal arc interruptions. Dataset 2 (481 radiographs from 217 patients, hospital C, 2017-2021) was used for testing, and with a subsample (174 radiographs from 87 patients), an observer study was conducted to compare its performance to five clinicians. Evaluation metrics included mean absolute error (MAE), sensitivity, and specificity. RESULTS: Dataset 2 included 258 SL distances, 189 SL angles, 191 CL angles, and 217 carpal arc labels obtained from 217 patients (mean age, 51 years ± 23 [standard deviation]; 133 women). The MAE in measuring SL distances, SL angles, and CL angles was respectively 0.65 mm (95%CI: 0.59, 0.72), 7.9 degrees (95%CI: 7.0, 8.9), and 5.9 degrees (95%CI: 5.2, 6.6). The sensitivity and specificity for detecting arc interruptions were 83% (95%CI: 74, 91) and 64% (95%CI: 56, 71). The measurements were largely comparable to those of the clinicians, while arc interruption detections were more accurate than those of most clinicians. CONCLUSION: This study demonstrates that a newly developed automated AI system accurately measures and detects signs of carpal instability on conventional radiographs. CLINICAL RELEVANCE STATEMENT: This system has the potential to improve detections of carpal arc interruptions and could be a promising tool for supporting clinicians in detecting carpal instability.

Musculoskeletal radiologist-level performance by using deep learning for detection of scaphoid fractures on conventional multi-view radiographs of hand and wrist.

OBJECTIVES: To assess how an artificial intelligence (AI) algorithm performs against five experienced musculoskeletal radiologists in diagnosing scaphoid fractures and whether it aids their diagnosis on conventional multi-view radiographs. METHODS: Four datasets of conventional hand, wrist, and scaphoid radiographs were retrospectively acquired at two hospitals (hospitals A and B). Dataset 1 (12,990 radiographs from 3353 patients, hospital A) and dataset 2 (1117 radiographs from 394 patients, hospital B) were used for training and testing a scaphoid localization and laterality classification component. Dataset 3 (4316 radiographs from 840 patients, hospital A) and dataset 4 (688 radiographs from 209 patients, hospital B) were used for training and testing the fracture detector. The algorithm was compared with the radiologists in an observer study. Evaluation metrics included sensitivity, specificity, positive predictive value (PPV), area under the characteristic operating curve (AUC), Cohen's kappa coefficient (κ), fracture localization precision, and reading time. RESULTS: The algorithm detected scaphoid fractures with a sensitivity of 72%, specificity of 93%, PPV of 81%, and AUC of 0.88. The AUC of the algorithm did not differ from each radiologist (0.87 [radiologists' mean], p ≥ .05). AI assistance improved five out of ten pairs of inter-observer Cohen's κ agreements (p < .05) and reduced reading time in four radiologists (p < .001), but did not improve other metrics in the majority of radiologists (p ≥ .05). CONCLUSIONS: The AI algorithm detects scaphoid fractures on conventional multi-view radiographs at the level of five experienced musculoskeletal radiologists and could significantly shorten their reading time. KEY POINTS: • An artificial intelligence algorithm automatically detects scaphoid fractures on conventional multi-view radiographs at the same level of five experienced musculoskeletal radiologists. • There is preliminary evidence that automated scaphoid fracture detection can significantly shorten the reading time of musculoskeletal radiologists.

Association between P-pulmonale and respiratory morbidity in COPD: a secondary analysis of the BLOCK-COPD trial.

RATIONALE: Pulmonary hypertension (PH) in COPD confers increased risk of exacerbations (ECOPD). Electrocardiogram (ECG) indicators of PH are prognostic both in PH and COPD. In the Beta-Blockers for the Prevention of Acute Exacerbations of COPD (BLOCK-COPD) trial, metoprolol increased risk of severe ECOPD through unclear mechanisms. OBJECTIVE: We evaluated whether an ECG indicator of PH, P-pulmonale, would be associated with ECOPD and whether participants with P-pulmonale randomized to metoprolol were at higher risk of ECOPD and worsened respiratory symptoms given the potential detrimental effects of beta-blockers in PH. METHODS: ECGs of 501 participants were analyzed for P-pulmonale (P wave enlargement in lead II). Cox proportional hazards models evaluated for associations between P-pulmonale and time to ECOPD (all and severe) for all participants and by treatment assignment (metoprolol vs. placebo). Linear mixed-effects models evaluated the association between treatment assignment and P-pulmonale on change in symptom scores (measured by CAT and SOBQ). RESULTS: We identified no association between P-pulmonale and risk of any ECOPD or severe ECOPD. However, in individuals with P-pulmonale, metoprolol was associated with increased risk for ECOPD (aHR 2.92, 95% CI: 1.45-5.85). There was no association between metoprolol and ECOPD in individuals without P-pulmonale (aHR 1.01, 95% CI: 0.77-1.31). Individuals with P-pulmonale assigned to metoprolol experienced worsening symptoms (mean increase of 3.95, 95% CI: 1.32-6.58) whereas those assigned to placebo experienced a mean improvement in CAT score of -2.45 (95% CI: -0.30- -4.61). CONCLUSIONS: In individuals with P-pulmonale, metoprolol was associated with increased exacerbation risk and worsened symptoms. These findings may explain the findings observed in BLOCK-COPD.

Predicting vasovagal reactions to a virtual blood donation using facial image analysis.

BACKGROUND: People with needle fear experience not only anxiety and stress but also vasovagal reactions (VVR), including nausea, dizziness, sweating, pallor changes, or even fainting. However, the mechanism behind needle fear and the VVR response are not yet well understood. The aim of our study was to explore whether fluctuations in facial temperature in several facial regions are related to the level of experienced vasovagal reactions, in a simulated blood donation. STUDY DESIGN AND METHODS: We recruited 45 students at Tilburg University and filmed them throughout a virtual blood donation procedure using an Infrared Thermal Imaging (ITI) camera. Participants reported their fear of needles and level of experienced vasovagal reactions. ITI data pre-processing was completed on each video frame by detecting facial landmarks and image alignment before extracting the mean temperature from the six regions of interest. RESULTS: Temperatures of the chin and left and right cheek areas increased during the virtual blood donation. Mixed-effects linear regression showed a significant association between self-reported vasovagal reactions and temperature fluctuations in the area below the nose. DISCUSSION: Our results suggest that the area below the nose may be an interesting target for measuring vasovagal reactions using video imaging techniques. This is the first in a line of studies, which assess whether it is possible to automatically detect levels of fear and vasovagal reactions using facial imaging, from which the development of e-health solutions and interventions can benefit.

Randomised, controlled trial of erenumab for the prevention of episodic migraine in patients from Asia, the Middle East, and Latin America: The EMPOwER study.

OBJECTIVE: EMPOwER, a double-blind, randomised, phase 3 study, evaluated the efficacy and safety of erenumab in adults with episodic migraine from Asia, the Middle East, and Latin America. METHODS: Randomised patients (N = 900) received monthly subcutaneous injections of placebo, erenumab 70 mg, or 140 mg (3:3:2) for 3 months. Primary endpoint was change from baseline in monthly migraine days at Month 3. Other endpoints included achievement of ≥50%, ≥75%, and 100% reduction in monthly migraine days, change in monthly acute migraine-specific medication treatment days, patient-reported outcomes, and safety assessment. RESULTS: At baseline, mean (standard deviation) age was 37.5 (9.9) years, 81.9% were women, and monthly migraine days was 8.2 (2.8). At Month 3, change from baseline in monthly migraine days (primary endpoint) was -3.1, -4.2, and -4.8 days for placebo, erenumab 70 mg, and erenumab 140 mg, respectively, with a statistically significant difference for erenumab versus placebo (P = 0.002 [70 mg], P < 0.001 [140 mg]). Both erenumab doses were also significantly superior to placebo on all secondary endpoints, including the proportion of patients achieving ≥50% reduction from baseline in monthly migraine days, change from baseline in monthly acute migraine-specific medication treatment days and change from baseline in the Headache Impact Test-6™ scores. The safety profile of erenumab was comparable with placebo; no new safety signals were observed. CONCLUSIONS: This study of erenumab in patients with episodic migraine from Asia, the Middle East, and Latin America met all primary and secondary endpoints. A consistent numerical benefit was observed with erenumab 140 mg versus erenumab 70 mg across all efficacy endpoints. These findings extend evidence of erenumab's efficacy and safety to patients under-represented in previous trials.ClinicalTrials.gov identifier: NCT03333109.

Calibrated dynamic borrowing using capping priors.

Multisource exchangeability models (MEMs), a BayeTsian approach for dynamically integrating information from multiple clinical trials, are a promising approach for gaining efficiency in randomized controlled trials. When the supplementary trials are considerably larger than the primary trial, care must be taken when integrating supplementary data to avoid overwhelming the primary trial. In this paper, we propose "capping priors," which controls the extent of dynamic borrowing by placing an a priori cap on the effective supplemental sample size. We demonstrate the behavior of this technique via simulation, and apply our method to four randomized trials of very low nicotine content cigarettes.

Neuroblastoma patient-derived cultures are enriched for a mesenchymal gene signature and reflect individual drug response.

Ex vivo evaluation of personalized models can facilitate individualized treatment selection for patients, and advance the discovery of novel therapeutic options. However, for embryonal malignancies, representative primary cultures have been difficult to establish. We developed patient-derived cell cultures (PDCs) from chemo-naïve and post-treatment neuroblastoma tumors in a consistent and efficient manner, and characterized their in vitro growth dynamics, histomorphology, gene expression, and functional chemo-response. From 34 neuroblastoma tumors, 22 engrafted in vitro to generate 31 individual PDC lines, with higher engraftment seen with metastatic tumors. PDCs displayed characteristic immunohistochemical staining patterns of PHOX2B, TH, and GD2 synthase. Concordance of MYCN amplification, 1p and 11q deletion between PDCs and patient tumors was 83.3%, 72.7%, and 80.0% respectively. PDCs displayed a predominantly mesenchymal-type gene expression signature and showed upregulation of pro-angiogenic factors that were similarly enriched in culture medium and paired patient serum samples. When tested with standard-of-care cytotoxics at human Cmax -equivalent concentrations, MYCN-amplified and non-MYCN-amplified PDCs showed a differential response to cyclophosphamide and topotecan, which mirrored the corresponding patients' responses, and correlated with gene signatures of chemosensitivity. In this translational proof-of-concept study, early-phase neuroblastoma PDCs enriched for the mesenchymal cell subpopulation recapitulated the individual molecular and phenotypic profile of patient tumors, and highlighted their potential as a platform for individualized ex vivo drug-response testing.

Geographical Differences in Trigger Factors of Tension-Type Headaches and Migraines.

In this review, we discussed the types and frequencies of trigger factors of primary headache [migraine and tension-type headache (TTH)] among adult patients. We assessed the influence of geographical location, ethnicity and gender on the various trigger factors of a migraine and a TTH. We also evaluated the trigger factors among the multi-ethnic Southeast Asian adult patients. In a recent study, odor triggered more migrainous headaches compared to the other primary headaches. Odor was observed to be specific of migraines. Moreover, stress is one of the most common trigger factors for patients with migraines and TTHs worldwide. Migrainous patients have an increased sensitivity in comparison to non-migrainous patients. Furthermore, these patients have much difficulty in adapting to the high level of sensitivity, and the sensitized brain is therefore more vulnerable to trigger factors. In addition, the presence of one trigger factor may increase the exposure of other trigger factors. This phenomenon is more marked in the patients with migraines who have stress and menstruation as triggers, predisposing them to be more sensitive to other triggers. In conclusion, the geographical location factor has an influence on the trigger factors of headaches. Ethnicity may have an effect due to the cultural differences. Change in weather and sunlight are important commonly identified trigger factors for headaches. Moreover, gender differences in some trigger factors are present among the patients with headaches, especially sunlight and sleep deprivation. More research studies can be conducted to have a better understanding on trigger factors in the future. This will enable proper identification of trigger factors, leading to a decrease in the number of headache episodes and an improvement in quality of life for patients.

Ocular perfusion pressure and ophthalmic artery flow in patients with normal tension glaucoma.

BACKGROUND: Vascular insufficiency has been reported to be a cause of normal tension glaucoma (NTG). The aim of this study was to compare ocular perfusion pressure (OPP) and ophthalmic artery flow (OAF) between patients with NTG and those without glaucoma. METHODS: We considered one eye each from 31 NTG and 15 non-glaucoma control patients. Blood pressure and intraocular pressure (IOP) were measured in the sitting position, for calculation of OPP. Humphrey visual field (HVF) assessment was then carried out on NTG patients. All patients then underwent Transcranial Doppler ultrasound measurements of OAF parameters, including mean flow velocity (MFV), end diastolic velocity (EDV), peak systolic velocity (PSV) and resistive index (RI). We looked at differences in OPP and OAF parameters between the two groups, and their correlations in NTG patients. T-tests, χ (2), ANOVA and Pearson Correlation tests were performed, with p < 0.05 considered statistically significant. RESULTS: There were no statistically significant differences in OPP between the NTG and control groups (60.5+/-8.7 mmHg and 62.9+/-10.2 mmHg respectively, p = 0.393), and also no statistically significant differences in MFV, EDV, PSV and RI (all p > 0.05). In the NTG group, there were positive correlations between OPP and both MFV (r = 0.416, p = 0.020) and EDV (r = 0.369, p = 0.041). There were no statistically significant correlations between HVF mean deviation and OPP or OAF parameters (all p > 0.05). CONCLUSION: There is no difference in OPP and OAF parameters between patients with NTG and non-glaucoma controls, suggesting that vascular insufficiency or dysregulation by themselves may not account for the pathogenesis of NTG.

Association between serum 25-hydroxyvitamin D levels and carotid atherosclerosis in chronic kidney disease patients.

BACKGROUND: Epidemiological studies have shown an inverse relationship between vitamin D levels and cardiovascular diseases. However, this does not infer a causal relationship between the two. Chronic kidney disease (CKD) patients have a high prevalence of vitamin D deficiency and carotid atherosclerosis. Therefore, in this study we have aimed to determine the association between serum 25-hydroxyvitamin D levels and carotid atherosclerosis in the CKD population. METHODS: 100 CKD stage 3-4 patients were included in the study. Direct chemiluminesent immunoassay was used to determine the level of serum 25-hydroxyvitamin D. All subjects underwent a carotid ultrasound to measure common carotid artery intima-media thickness (CCA-IMT) and to assess the presence of carotid plaques or significant stenosis (≥50 %). Vitamin D deficiency was defined as serum 25-hydroxyvitamin D < 25 nmol/L. Abnormal CCA-IMT was defined as CCA-IMT ≥ 0.8 mm. Plaque was defined as a focal structure that encroaches into the arterial lumen of ≥ 0.5 mm or 50 % of the surrounding IMT value. Significant stenosis was defined as peak-systolic velocities ≥ 125 cm/s and end-diastolic velocities ≥ 40 cm/s. RESULTS: The vitamin D deficiency and non-deficiency groups did not differ significantly in terms of abnormal CCA-IMT (P = 0.443), carotid plaque (P = 0.349), and carotid stenosis (P = 0.554). No significant correlation between serum 25-hydroxyvitamin D levels and CCA-IMT (P = 0.693) was found. On a backward multiple linear regression model, serum 25-hydroxyvitamin D levels was not associated with CCA-IMT, abnormal CCA-IMT, or plaque presence. CONCLUSIONS: No important association between serum 25-hydroxyvitamin levels and carotid atherosclerosis was found in CKD patients.

Associations Between Coronary Artery Calcium Score and Exacerbation Risk in BLOCK-COPD.

Introduction: In 2019, the Beta-Blockers for the Prevention of Acute Exacerbations of Chronic Obstructive Pulmonary Disease study (BLOCK-COPD) evaluated the effect of metoprolol on exacerbation risk and mortality in a COPD population without indications for beta-blocker use. We hypothesized that an imaging metric of coronary artery disease (CAD), the coronary artery calcium (CAC) score, would predict exacerbation risk and identify a differential response to metoprolol treatment. Methods: The study population includes participants in the BLOCK-COPD study from multiple study sites. Participants underwent clinically indicated thoracic computed tomography (CT) scans ± 12 months from enrollment. The Weston scoring system quantified CAC. Adjusted Cox proportional hazards models evaluated for associations between CAC and time to exacerbation. Results: Data is included for 109 participants. The mean CAC score was 5.1±3.7, and 92 participants (84%) had CAC scores greater than 0. Over a median (interquartile range) follow-up time of 350 (280 to 352) days, there were 61 mild exacerbations and 19 severe/very severe exacerbations. No associations were found between exacerbations of any severity and CAC>0 or total CAC. Associations were observed between total CAC and CAC>0 in the left circumflex (LCx) and time to exacerbation of any severity (adjusted hazard ratio [aHR]=1.39, confidence interval [CI]: 1.08-1.79, p=0.01) and (aHR=1.96, 95% CI: 1.04-3.70, p=0.04), respectively. Conclusions: CAD is a prevalent comorbidity in COPD accounting for significant mortality. Our study confirms the high prevalence of CAD using the CAC score; however, we did not discover an association between CAC and exacerbation risk. We did find novel associations between CAC in the LCx and exacerbation risk which warrant further investigation in larger cohorts.

Primary headache in the elderly in South-East Asia.

Headache aetiology and presentation are considerably different in elderly individuals. However, literature on headache characteristics among Asians is limited. The objective of this study was to evaluate the headache characteristics among elderly in an outpatient clinic setting in Malaysia, a South-East Asian country with diverse ethnicity. In this prospective cross-sectional study, patients presenting with headache to Neurology and Primary Care Clinics of University Malaya Medical Centre between February 2010 and July 2010 were included. Data for consecutive eligible adult patients were entered in a prospective headache registry. International Headache Criteria II (ICHD-II) were used to classify various headache subtypes. Patients with headache due to intracranial space occupying lesions were excluded. Patient were divided into two age groups-elderly (55 years and above) and younger (less than 55 years of age). Of the 175 screened patients, 165 were included in the study-70 in elderly age group and 95 in younger group. Tension-type headache was the commonest subtype (45.7 %) among the elderly while Migraine without aura (54.7 %) was more common in young adults. More elderly patients suffered from chronic daily headache as compared to younger patients (47.1 vs. 28.4 %; p = 0.015). Headache subtypes and frequency differ considerably among elderly South East Asian patients.

Lung Function and the Risk of Exacerbation in the ß-Blockers for the Prevention of Acute Exacerbations of Chronic Obstructive Pulmonary Disease Trial.

Rationale: The BLOCK COPD (ß-Blockers for the Prevention of Acute Exacerbations of Chronic Obstructive Pulmonary Disease) study found that metoprolol was associated with a higher risk of severe exacerbation. Objectives: To determine the mechanism underlying these results, we compared changes in lung function over the course of the study between treatment groups and evaluated whether baseline bronchodilator response or early reduction in forced expiratory volume in 1 second (FEV1) or forced vital capacity (FVC) was associated with exacerbation risk. Methods: We compared changes in lung function (FEV1 and FVC) over the treatment period between treatment groups using linear mixed-effect models. Cox proportional hazards models were used to evaluate the association between baseline bronchodilator responsiveness (FEV1, FVC, and combined FEV1 and FVC), early post-randomization (14 d) change in lung function, and the interaction between treatment assignment and these measures with risk of any or severe or very severe exacerbations. Negative binomial models were used to evaluate the relationship between bronchodilator responsiveness, the interaction between bronchodilator responsiveness and treatment assignment, and exacerbation rate. Results: Over the 336-day treatment period, individuals in the metoprolol group had a significantly greater decrease in logarithmic FEV1 from baseline to visit on Day 28 than individuals in the placebo group. Individuals in the metoprolol group had a significantly greater decrease in FVC from baseline to visits on Days 14 and 28, and also a significantly greater decrease in logarithmic FVC from baseline to visits on Days 42 and 112 than individuals in the placebo group. There were no associations between early lung function reduction or interactions between lung function reduction and treatment assignment and time to any or severe or very severe exacerbations. There were no interactions between treatment arm and baseline bronchodilator responsiveness measures on risk or rate of exacerbations. However, those with baseline FVC bronchodilator responsiveness had a higher rate of severe or very severe exacerbations (adjusted rate ratio, 1.62; 95% confidence interval, 1.04-2.48). Conclusions: Metoprolol was associated with reduced lung function during the early part of the treatment period, but these effects were modest and did not persist. Early lung function reduction and baseline bronchodilator responsiveness did not interact with the treatment arm to predict exacerbations; however, baseline FVC bronchodilator responsiveness was associated with a 60% higher rate of severe or very severe exacerbations. Clinical trial registered with www.clinicaltrials.gov (NCT02587351).

Heart Rate Variability on 10-Second Electrocardiogram and Risk of Acute Exacerbation of COPD: A Secondary Analysis of the BLOCK COPD Trial.

Introduction: Autonomic dysfunction is common in chronic obstructive pulmonary disease (COPD), and worse autonomic function may be a marker of risk for acute exacerbations of COPD (AECOPD). Heart rate variability (HRV) is a measure of autonomic function. Our objective was to test whether lower (worse) HRV is a risk factor for AECOPD. Methods: We measured standard deviation of normal RR intervals (SDNN) and root mean square of successive RR interval differences (RMSSD) on 10-second electrocardiograms (ECGs) performed at screening and day 42 in participants in the Beta Blockers for the Prevention of Acute Exacerbations of COPD trial ( BLOCK-COPD), a placebo-controlled trial of metoprolol for prevention of AECOPD. We used Cox-proportional hazards models to test if these HRV measures were associated with risk of any AECOPD, and separately, hospitalized AECOPD. We tested associations using baseline HRV measures and incorporating HRV measures from day 42 as a time-varying covariate. We also tested for interactions with metoprolol assignment. Results: Of 532 trial participants, 529 (forced expiratory volume in 1 second [FEV1 ]41 ± 16.3 % predicted) were included in this analysis. We did not find a significant association between HRV measures and risk of AECOPD when all participants were analyzed together. There was a significant interaction between RMSSD and assignment to metoprolol on time to first hospitalized AECOPD; in the placebo group greater RMSSD was associated with a lower risk of hospitalized AECOPD (adjusted hazard ratio0.71, 95% confidence interval: 0.52 to 0.96, per 10 ms increase) but there was no association in the metoprolol group. Conclusions: Autonomic dysfunction as measured by HRV may be a risk factor for AECOPD. Future studies should analyze longer HRV recordings and their performance in broader samples of people with COPD, including those on beta-blockers.

Rapid Evaluation of Vaccine Booster Effectiveness against SARS-CoV-2 Variants.

As the COVID-19 pandemic continues, countries around the world are switching toward vaccinations and boosters to combat the pandemic. However, waning immunity against SARS-CoV-2 wild-type (WT) and variants have been widely reported. Booster vaccinations have shown to be able to increase immunological protection against new variants; however, the protection observed appears to decrease quickly over time suggesting a second booster shot may be appropriate. Moreover, heterogeneity and waning of the immune response at the individual level was observed suggesting a more personalized vaccination approach should be considered. To evaluate such a personalized strategy, it is important to have the ability to rapidly evaluate the level of neutralizing antibody (nAbs) response against variants at the individual level and ideally at a point of care setting. Here, we applied the recently developed cellulose pulled-down virus neutralization test (cpVNT) to rapidly assess individual nAb levels to WT and variants of concerns in response to booster vaccination. Our findings confirmed significant heterogeneity of nAb responses against a panel of SARS-CoV-2 variants, and indicated a strong increase in nAb response against variants of concern (VOCs) upon booster vaccination. For instance, the nAb response against current predominant omicron variant was observed with medians of 88.1% (n = 6, 95% CI = 73.2% to 96.2%) within 1-month postbooster and 70.7% (n = 22, 95% CI = 66.4% to 81.8%) 3 months postbooster. Our data show a point of care (POC) test focusing on nAb response levels against VOCs can guide decisions on the potential need for booster vaccinations at individual level. Importantly, it also suggests the current booster vaccines only give a transient protective response against some VOC and new more targeted formulations of a booster vaccine against specific VOC may need to be developed in the future. IMPORTANCE Vaccination against SARS-CoV-2 induces protection through production of neutralization antibodies (nAb). The level of nAb is a major indicator of immunity against SARS-CoV-2 infection. We developed a rapid point-of-care test that can monitor the nAb level from a drop of finger stick blood. Here, we have implemented the test to monitor individual nAb level against wild-type and variants of SARS-CoV-2 at various time points of vaccination, including post-second-dose vaccination and postbooster vaccination. Huge diversity of nAb levels were observed among individuals as well as increment in nAb levels especially against Omicron variant after booster vaccination. This study evaluated the performance of this point-of-care test for personalized nAb response tracking. It verifies the potential of using a rapid nAb test to guide future vaccination regimens at both the individual and population level.

Investigating Psychological Differences Between Nurses and Other Health Care Workers From the Asia-Pacific Region During the Early Phase of COVID-19: Machine Learning Approach.

BACKGROUND: As the COVID-19 pandemic evolves, challenges in frontline work continue to impose a significant psychological impact on nurses. However, there is a lack of data on how nurses fared compared to other health care workers in the Asia-Pacific region. OBJECTIVE: This study aims to investigate (1) the psychological outcome characteristics of nurses in different Asia-Pacific countries and (2) psychological differences between nurses, doctors, and nonmedical health care workers. METHODS: Exploratory data analysis and visualization were conducted on the data collected through surveys. A machine learning modeling approach was adopted to further discern the key psychological characteristics differentiating nurses from other health care workers. Decision tree-based machine learning models (Light Gradient Boosting Machine, GradientBoost, and RandomForest) were built to predict whether a set of psychological distress characteristics (ie, depression, anxiety, stress, intrusion, avoidance, and hyperarousal) belong to a nurse. Shapley Additive Explanation (SHAP) values were extracted to identify the prominent characteristics of each of these models. The common prominent characteristic among these models is akin to the most distinctive psychological characteristic that differentiates nurses from other health care workers. RESULTS: Nurses had relatively higher percentages of having normal or unchanged psychological distress symptoms relative to other health care workers (n=233-260 [86.0%-95.9%] vs n=187-199 [74.8%-91.7%]). Among those without psychological symptoms, nurses constituted a higher proportion than doctors and nonmedical health care workers (n=194 [40.2%], n=142 [29.5%], and n=146 [30.3%], respectively). Nurses in Vietnam showed the highest level of depression, stress, intrusion, avoidance, and hyperarousal symptoms compared to those in Singapore, Malaysia, and Indonesia. Nurses in Singapore had the highest level of anxiety. In addition, nurses had the lowest level of stress, which is the most distinctive psychological outcome characteristic derived from machine learning models, compared to other health care workers. Data for India were excluded from the analysis due to the differing psychological response pattern observed in nurses in India. A large number of female nurses emigrating from South India could not have psychologically coped well without the support from family members while living alone in other states. CONCLUSIONS: Nurses were least psychologically affected compared to doctors and other health care workers. Different contexts, cultures, and points in the pandemic curve may have contributed to differing patterns of psychological outcomes amongst nurses in various Asia-Pacific countries. It is important that all health care workers practice self-care and render peer support to bolster psychological resilience for effective coping. In addition, this study also demonstrated the potential use of decision tree-based machine learning models and SHAP value plots in identifying contributing factors of sophisticated problems in the health care industry.

Mechanistic insights into mRNA export through structures of Dbp5.

Nuclear export of mRNA is a critical event in mRNA biogenesis. Passage of mature messenger ribonucleoproteins (mRNPs) through nuclear pore complexes (NPCs) is facilitated by the Mex67/Mtr2 heterodimer. At the NPC cytoplasmic face, the DEAD-box RNA helicase Dbp5 remodels mRNPs by removing Mex67/Mtr2. This remodeling process prevents mRNPs from returning to the nucleus, thereby imposing unidirectionality on mRNA export. Biochemical studies show that Gle1 and inositol hexaphosphate (IP6) activate Dbp5's ATPase activity at the cytoplasmic face of NPC, therefore providing critical spatial regulation of mRNP remodeling during directional transport. Recent structural studies on Dbp5 in free form and in complex with its ligands (ADP, AMPPNP/RNA) as well as with cytoplasmic nucleoporin Nup214 reveal that the binding of ADP or AMPPNP/RNA induces large conformational changes of Dbp5, and RNA and NUP214 bind to Dbp5 in a mutually exclusive manner. These structural data combined with complementary functional analysis significantly advance our understanding on the mechanism governing mRNA export albeit some key issues remain elusive.

Acute Ischaemic Stroke Successfully Treated with Thrombolytic Therapy and Endovascular Thrombectomy with Non-Contrast Computed Tomography and Computed Tomography Angiogram Protocol.

Early endovascular thrombectomy leads to improved outcomes for patients with proximal occlusions when started within 6 h from onset of symptoms. We present a case illustrating the flow of events for a patient who underwent endovascular thrombectomy in our centre after conventional imaging - a brain non-contrast computed tomography (NCCT) and CT angiogram (CTA) - achieving a door-to-groin time of 195 min. The patient is a 65-year-old who presented with signs and symptoms of a left middle cerebral artery (MCA) territory infarct. His National Institute of Health Stroke Scale (NIHSS) score was 15 on presentation and his brain NCCT showed an Alberta Stroke Programme Early CT Score (ASPECTS) of 8. His CTA showed a left MCA distal M1 occlusion with focal calcification and stenosis of the proximal left internal carotid artery. He was subsequently thrombosed and underwent thrombectomy successfully, with a door-to-groin-puncture time of 195 min. A TICI 2b reperfusion was achieved. His NIHSS score improved to 9 over the next 2 days. For cases with straightforward NCCT and CTA with no contraindications, endovascular thrombectomy should be pursued without delay. A review of the current available literature for the usage of NCCT and CTA as well as the importance of ASPECTS scoring in patient selection for endovascular thrombectomy was included.