Non-coding 7S RNA inhibits transcription via mitochondrial RNA polymerase dimerization.

The mitochondrial genome encodes 13 components of the oxidative phosphorylation system, and altered mitochondrial transcription drives various human pathologies. A polyadenylated, non-coding RNA molecule known as 7S RNA is transcribed from a region immediately downstream of the light strand promoter in mammalian cells, and its levels change rapidly in response to physiological conditions. Here, we report that 7S RNA has a regulatory function, as it controls levels of mitochondrial transcription both in vitro and in cultured human cells. Using cryo-EM, we show that POLRMT dimerization is induced by interactions with 7S RNA. The resulting POLRMT dimer interface sequesters domains necessary for promoter recognition and unwinding, thereby preventing transcription initiation. We propose that the non-coding 7S RNA molecule is a component of a negative feedback loop that regulates mitochondrial transcription in mammalian cells.

Mechanisms and regulation of human mitochondrial transcription.

The expression of mitochondrial genes is regulated in response to the metabolic needs of different cell types, but the basic mechanisms underlying this process are still poorly understood. In this Review, we describe how different layers of regulation cooperate to fine tune initiation of both mitochondrial DNA (mtDNA) transcription and replication in human cells. We discuss our current understanding of the molecular mechanisms that drive and regulate transcription initiation from mtDNA promoters, and how the packaging of mtDNA into nucleoids can control the number of mtDNA molecules available for both transcription and replication. Indeed, a unique aspect of the mitochondrial transcription machinery is that it is coupled to mtDNA replication, such that mitochondrial RNA polymerase is additionally required for primer synthesis at mtDNA origins of replication. We discuss how the choice between replication-primer formation and genome-length RNA synthesis is controlled at the main origin of replication (OriH) and how the recent discovery of an additional mitochondrial promoter (LSP2) in humans may change this long-standing model.

The human mitochondrial genome contains a second light strand promoter.

The human mitochondrial genome must be replicated and expressed in a timely manner to maintain energy metabolism and supply cells with adequate levels of adenosine triphosphate. Central to this process is the idea that replication primers and gene products both arise via transcription from a single light strand promoter (LSP) such that primer formation can influence gene expression, with no consensus as to how this is regulated. Here, we report the discovery of a second light strand promoter (LSP2) in humans, with features characteristic of a bona fide mitochondrial promoter. We propose that the position of LSP2 on the mitochondrial genome allows replication and gene expression to be orchestrated from two distinct sites, which expands our long-held understanding of mitochondrial gene expression in humans.

Early Triple-Negative Breast Cancers in a Singapore Cohort Exhibit High PIK3CA Mutation Rates Associated With Low PD-L1 Expression.

Mutations in the PI3K pathway, particularly PIK3CA, were reported to be intimately associated with triple-negative breast cancer (TNBC) progression and the development of treatment resistance. We profiled PIK3CA and other genes on 166 early-stage TNBC tumors from Singapore for comparison to publicly available TNBC cohorts. These tumors were profiled transcriptionally using a NanoString panel of immune genes and multiplex immunohistochemistry, then manually scored for PD-L1-positivity using 2 clinically relevant clones, SP142 and 22C3. We discovered a higher rate of PIK3CA mutations in our TNBC cohort than in non-Asian cohorts, along with TP53, BRCA1, PTPN11, and MAP3K1 alterations. PIK3CA mutations did not affect overall or recurrence-free survival, and when compared with PIK3CAWT tumors, there were no differences in immune infiltration. Using 2 clinically approved antibodies, PIK3CAmut tumors were associated with PD-L1 negativity. Analysis of comutation frequencies further revealed that PIK3CA mutations tended to be accompanied by MAP kinase pathway mutation. The mechanism and impact of PIK3CA alterations on the TNBC tumor immune microenvironment and PD-L1 positivity warrant further study.

Barriers and facilitators to exercise among adult cancer survivors in Singapore.

PURPOSE: Exercise can help cancer survivors manage sequela, treatment side effects, improve overall quality of life, and is recommended for most. The purpose of this study was to investigate exercise behavior and factors influencing exercise engagement among cancer survivors at the National Cancer Centre, Singapore (NCCS). METHODS: This cross-sectional study was inclusive of survivors of all cancer types and stages who were at least 21 years of age and had undergone chemotherapy at the NCCS. Surveys were utilized to assess survivor barriers and facilitators to exercise and to retrospectively assess physical activity and exercise behaviors at 4 cancer-related time periods (pre-diagnosis and post-diagnosis before, during, or after chemotherapy). RESULTS: A total of 102 cancer survivors were enrolled; 60% were diagnosed with stage IV cancer. Predominant cancer types included lower gastrointestinal tract (25.5%) and breast cancer (21.6%). Prior to cancer diagnosis, 90.2% of participants reported aerobic activity satisfying NCCN guidelines. Significant reductions in reported exercise, and physical activity, were observed following cancer diagnosis that persisted during chemotherapy. Key exercise facilitators included the desire to remain healthy (86.3%) and to improve sleep and mental well-being (73.5%). Key barriers included side effects of treatment (52.0%). Only 46.1% of survivors reported receiving exercise guidance from healthcare professionals following diagnosis. CONCLUSION: Overall, even among this notably active cohort of Singaporean survivors, opportunities for increased exercise engagement throughout the survivorship continuum remain. Increased education regarding the benefits of exercise to survivors as well as guidance regarding exercise modalities including resistance training is greatly needed as well.

Length heterogeneity at conserved sequence block 2 in human mitochondrial DNA acts as a rheostat for RNA polymerase POLRMT activity.

The guanine (G)-tract of conserved sequence block 2 (CSB 2) in human mitochondrial DNA can result in transcription termination due to formation of a hybrid G-quadruplex between the nascent RNA and the nontemplate DNA strand. This structure can then influence genome replication, stability and localization. Here we surveyed the frequency of variation in sequence identity and length at CSB 2 amongst human mitochondrial genomes and used in vitro transcription to assess the effects of this length heterogeneity on the activity of the mitochondrial RNA polymerase, POLRMT. In general, increased G-tract length correlated with increased termination levels. However, variation in the population favoured CSB 2 sequences which produced efficient termination while particularly weak or strong signals were avoided. For all variants examined, the 3' end of the transcripts mapped to the same downstream sequences and were prevented from terminating by addition of the transcription factor TEFM. We propose that CSB 2 length heterogeneity allows variation in the efficiency of transcription termination without affecting the position of the products or the capacity for regulation by TEFM.

Safety and Effectiveness of Factor VIII Inhibitor Bypassing Activity (FEIBA) and Fresh Frozen Plasma in Oral Anticoagulant-Associated Intracranial Hemorrhage: A Retrospective Analysis.

BACKGROUND: Oral anticoagulant (OAT)-associated intracranial hemorrhage (ICH) is a life-threatening emergency for which prothrombin complex concentrates (PCC) are considered first-line reversal agents. The only approved PCC in the USA for warfarin-associated ICH is non-activated PCC. Little data are available regarding the safety and effectiveness of factor VIII inhibitor bypassing activity (FEIBA) which is an activated prothrombin complex concentrate (aPCC). The aim of this analysis was to assess the safety and effectiveness of FEIBA compared to fresh frozen plasma (FFP) for reversal of OAT-associated ICH. METHODS: Data were retrospectively collected to compare coagulation markers and in-hospital clinical outcomes in patients who received aPCC with or without FFP versus FFP alone for the reversal of OAT-associated ICH. RESULTS: Eighty-four patients met inclusion criteria; 50 patients received FFP alone, and 34 patients received FEIBA (mean dose 20 U/kg) with or without FFP for OAT-associated ICH. The proportion of diagnosed thrombotic events during hospitalization was similar in both groups (8% in the FFP group vs. 12% in the FEIBA group; P = 0.56). Median time to INR < 1.5 was achieved faster in the FEIBA group versus the FFP group (0.5 h [IQR 0.5-1.] vs. 10 h [IQR 5-16.3], respectively; P < 0.001) reflecting a trend toward shorter median time to neurosurgical intervention. Hematoma expansion, length of stay, and all-cause mortality were similar between both groups. CONCLUSIONS: Administration of FEIBA does not appear to increase the risk of thrombotic events compared with FFP. FEIBA administration resulted in faster INR reversal with a trend toward shorter time to neurosurgical intervention. However, there was no difference in hematoma expansion, mortality or length of stay.

Tension-referenced measures of gastrocnemius slack length and stiffness in Parkinson's disease.

BACKGROUND: It is not known how passive muscle length and stiffness contribute to rigidity in Parkinson's disease. The objective of this study was to compare passive gastrocnemius muscle-tendon slack length and stiffness at known tension in Parkinson's disease subjects with ankle rigidity and in able-bodied people. METHODS: Passive ankle torque-angle curves were obtained from 15 Parkinson's disease subjects with rigidity and 15 control subjects. Torque-angle data were used to derive passive gastrocnemius length-tension data and calculate slack length and stiffness of the gastrocnemius muscle. Between-group comparisons were made with linear models. RESULTS: Gastrocnemius muscle-tendon slack lengths (adjusted between-group difference, 0.01 m; 95% CI, -0.02 to 0.04 m; P = 0.37) and stiffness (adjusted between-group difference, 15.7 m-1 ; 95% CI, -8.5 to 39.9 m-1 ; P = 0.19) were not significantly different between groups. CONCLUSIONS: Parkinson's disease subjects with ankle rigidity did not have significantly shorter or stiffer gastrocnemius muscles compared with control subjects. © 2016 International Parkinson and Movement Disorder Society.

Conformational and thermodynamic hallmarks of DNA operator site specificity in the copper sensitive operon repressor from Streptomyces lividans.

Metal ion homeostasis in bacteria relies on metalloregulatory proteins to upregulate metal resistance genes and enable the organism to preclude metal toxicity. The copper sensitive operon repressor (CsoR) family is widely distributed in bacteria and controls the expression of copper efflux systems. CsoR operator sites consist of G-tract containing pseudopalindromes of which the mechanism of operator binding is poorly understood. Here, we use a structurally characterized CsoR from Streptomyces lividans (CsoR(Sl)) together with three specific operator targets to reveal the salient features pertaining to the mechanism of DNA binding. We reveal that CsoR(Sl) binds to its operator site through a 2-fold axis of symmetry centred on a conserved 5'-TAC/GTA-3' inverted repeat. Operator recognition is stringently dependent not only on electropositive residues but also on a conserved polar glutamine residue. Thermodynamic and circular dichroic signatures of the CsoR(Sl)-DNA interaction suggest selectivity towards the A-DNA-like topology of the G-tracts at the operator site. Such properties are enhanced on protein binding thus enabling the symmetrical binding of two CsoR(Sl) tetramers. Finally, differential binding modes may exist in operator sites having more than one 5'-TAC/GTA-3' inverted repeat with implications in vivo for a mechanism of modular control.

Injury and illness surveillance at the International Sailing Federation Sailing World Championships 2014.

BACKGROUND/AIM: The Sailing World Championships 2014 was contested by 1167 sailors in all 10 Olympic classes. Our objective was to characterise sailing-related injuries and illnesses in sailors participating in this regatta. METHODS: We conducted 2 surveys: (1) prior to the World Championships, sailors answered a 12-month recall questionnaire on sailing-related injuries and illnesses and (2) during the Championships, injuries and illnesses were documented. RESULTS: There were 760 respondents (65% of all participants) for the 12-month recall questionnaire (58% male, 42% female), of whom 244 participants reported 299 injuries (0.59 injuries per 1000 h of sailing). Injuries were most prevalent in the 49erFX (64%), RS:X Women (39%), 49er (37%) and Nacra 17 (36%). Lower back (29% of sailors), knee (13%), shoulder (12%) and ankle (10%) injuries were most prevalent; most (58% of all injuries) were overuse injuries; and 56% of sailors lost sailing time. Most illnesses (40%) were infections, primarily of the respiratory system (43%). During the Championships, there were 67 injuries (4 per 1000 days of sailing). The 49er (24% of all injuries), 470 Men and Women (24%), and 49erFX (19%) had the highest incidence. Injuries to the hand/fingers (22% of all injuries), back (18%), and foot (12%) were most common, as were contusions (37% of all injuries), cuts/lacerations (24%), and sprains (9%). Of the 29 illnesses (2 per 1000 days of sailing), 9 (31%) were gastrointestinal and 6 (21%) respiratory, while 2 (7%) were gout attacks. CONCLUSIONS: The Olympic classes introduced since 2000 (49erFX, 49er, Nacra 17) have resulted in a rise in injuries.

Consensus statements and guideline for the diagnosis and management of plantar fasciitis in Singapore.

Introduction: Plantar fasciitis (PF) is a common cause of heel pain among the general population. The lack of standard practice guideline in Singapore presents challenges in education and clinical practice for this painful condition. These consensus statements and guideline were developed to streamline and improve the management of PF, covering key aspects such as diagnosis, investigations, risk factors, treatment modalities, monitoring and return to work/play. Method: A multidisciplinary expert panel consisting of 6 sports physicians, 2 orthopaedic surgeons, 2 podiatrists and 1 physiotherapist from SingHealth Duke-NUS Sport & Exercise Medicine Centre (SDSC) was convened based on their clinical and academic experience with PF. The Grading of Recommen-dations, Assessment, Development and Evaluations (GRADE) approach was used to evaluate the quality of the evidence and subsequently prepare a set of clinical recommen-dations pertaining to the manage-ment of PF. A modified Delphi process was used to reach consensus. Results: Eighteen consensus statements were developed to cover key components of PF management, from initial diagnosis to treatment modalities and finally, clinical progression. They were subsequently consolidated under a proposed treatment pathway guideline for PF. Conclusion: The SDSC consensus statements and guideline provide concise recommendations for the management of PF in Singapore.

Fostering citizen-engaged HIV implementation science.

INTRODUCTION: Successful implementation of evidence-based practices depends on contextual factors like stakeholder engagement, the socio-political environment, resource availability, and stakeholders' felt needs and preferences. Nevertheless, inequities in implementation exist and undermine efforts to address HIV in marginalized key populations. Implementation science shows promise in addressing such inequities in the HIV response, but can be limited without meaningful engagement from citizens or communities. DISCUSSION: We define the concept of a citizen-engaged HIV implementation science as one that involves citizens and communities deeply in HIV implementation science activities. In this commentary, we discuss how citizen science approaches can be leveraged to spur equity in HIV implementation science. Drawing on three areas previously defined by Geng and colleagues that serve to drive impactful implementation science in the HIV response, we discuss how citizens can be engaged when considering "whose perspectives?", "what questions are being asked?" and "how are questions asked?". With respect to "whose perspectives?" a citizen-engaged HIV implementation science would leverage participatory methods and tools, such as co-creation, co-production and crowdsourcing approaches, to engage the public in identifying challenges, solve health problems and implement solutions. In terms of "what questions are being asked?", we discuss how efforts are being made to synthesize citizen or community-led approaches with existing implementation science frameworks and approaches. This also means that we ensure communities have a say in interrogating and deconstructing such frameworks and adapting them to local contexts through participatory approaches. Finally, when considering "how are questions asked?", we argue for the development and adoption of broad, guiding principles and frameworks that account for dynamic contexts to promote citizen-engaged research in HIV implementation science. This also means avoiding narrow definitions that limit the creativity, innovation and ground-up wisdom of local citizens. CONCLUSIONS: By involving communities and citizens in the development and growth of HIV implementation science, we can ensure that our implementation approaches remain equitable and committed to bridging divides and ending AIDS as a public health threat. Ultimately, efforts should be made to foster a citizen- and community-engaged HIV implementation science to spur equity in our global HIV response.

Mid-term safety and efficacy in small intracranial aneurysm coiling: results from TARGET® nano prospective independent core lab adjudicated multicenter registry.

Background: The primary objective is to evaluate the safety and effectiveness of Stryker second generation Target® Nano Coils in the treatment of ruptured and unruptured small (<7 mm) intracranial aneurysms. Methods: The TARGET Registry is a prospective, two-arm study with independent medical event monitoring and core-lab adjudication. This paper describes the second arm of the TARGET registry. Patients with de novo intracranial aneurysms were embolized with 2nd generation TARGET Nano coils in 12 US centers. The primary efficacy outcome was adequate aneurysm occlusion (RR occlusion grade I-II) on follow-up. Primary safety outcome was treatment-related morbidity and mortality. Secondary outcomes included aneurysm packing density immediately post-procedure, immediate adequate occlusion, aneurysm re-access rate, retreatment rate and clinical outcomes using modified ranking scale. A secondary analysis investigated the influence of using Nano-predominant coils (≥2/3 of total coil-length) vs. non-Nano-predominant coils (<2/3 of total length). Results: 150 patients with 155 aneurysms met the inclusion and exclusion criteria. (31%) patients with ruptured and (69%) with unruptured aneurysms were treated using TARGET coils. Median age was 58.8 (SD 12.7), 74.7% were females, and 80% were Caucasians. Mean follow-up was 5.23 (SD 2.27) months. Peri-procedural mortality was seen in 2.0% of patients. Good outcome at discharge (mRS 0-2) was seen in 81.3% of the cohort. The median packing density (SD) was 29.4% (14.9). Mid-term complete/near complete occlusion rate was seen in 96% of aneurysms and complete obliteration was seen in 75.2% of aneurysms. Patients treated predominantly with Nano coils had higher PD (32.6% vs. 26.1%, p < 0.001). There was no significant difference in clinical and angiographic outcomes. The mid-term mRS0-2 was achieved in 106/109 (97.2%) patients. All-cause mortality was 5/115 (4.3%). Conclusion: In the multicenter TARGET Registry, 75.8% of aneurysms achieved mid-term complete occlusion, and 96% achieved complete/near complete occlusion with excellent independent functional outcome.

Comparing effects of low- and high-volume moderate-intensity exercise on sexual function and testosterone in obese men.

INTRODUCTION: Obesity and inactivity are associated with erectile dysfunction and hypogonadism. AIM: To compare the effects of low volume (LV) and high volume (HV) of moderate-intensity exercise on sexual function, testosterone, lower urinary tract symptoms (LUTS), endothelial function, and quality of life (QoL) in obese men. MAIN OUTCOME MEASURES: Weight, waist circumference (WC), body composition, International Index of Erectile Function 5-item (IIEF-5), International Prostate Symptom Scale (IPSS) (for LUTS), and 36-item Short Form Survey version 2 Instrument (SF-36) (for QoL) scores, plasma testosterone, sex-hormone binding globulin, glucose, insulin and lipids, and endothelial function (by Reactive Hyperaemia Index [RHI] using finger plethysmography) were measured at baseline and 24 weeks. METHODS: Ninety abdominally obese (body mass index > 27.5 kg/m(2), WC > 90 cm), sedentary (exercise ≈ 80 minutes/week) Asian men (mean age 43.6 years, range 30-60) were prescribed a diet to reduce daily intake by ≈ 400 kcal below calculated requirement and randomized to perform moderate-intensity exercise of LV (<150 minutes/week) or HV (200-300 minutes/week) (n = 45 each) for 24 weeks. Seventy-five men (83.3%) completed the study. RESULTS: Weekly exercise volume was significantly greater in the HV (236 ± 9 minutes) than the LV (105 ± 9 minutes) group. The HV group had significantly greater increases in IIEF-5 score (2.6 ± 0.5 points) and testosterone (2.06 ± 0.46 nmol/L) and reductions in weight (-5.9 ± 0.7 kg, -6.2%), WC (-4.9 ± 0.8 cm, -4.9%), and fat mass (-4.7 ± 1.0 kg, -14.5%) than the LV group (-2.9 ± 0.7 kg, -3.0%; -2.7 ± 0.7 cm, -2.5%; -1.1 ± 0.8 kg, -3.2%; 0.79 ± 0.46 nmol/L; and 1.8 ± 0.5 points). Improvements in IPSS and SF-36 scores, and RHI, were similar. CONCLUSIONS: Moderate-intensity HV aerobic exercise > 200 minutes/week produces greater improvements in sexual function, testosterone, weight, WC, and fat mass than smaller exercise volume.

Comparison of four electrocardiographic criteria for the detection of cardiac abnormalities in Singapore athletes.

Introduction: Sudden cardiac death in athletes is a rare occurrence, the most common cause being hypertrophic cardiomyopathy, which increases the risk of sustained ventricular tachycardia or ventricular fibrillation. Most of these young athletes are asymptomatic prior to the cardiac arrest. Several electrocardiogram criteria such as the European Society of Cardiology group 2 Criteria changes, Seattle Criteria, Refined Criteria, and most recently the 2017 International Criteria, have sought to improve the accuracy of identifying these at-risk athletes during pre-participation screening while minimising unnecessary investigations for the majority of athletes at low risk.We aimed to compare the above four criteria in our Singapore athlete population to identify which criterion performed the best in detecting cardiac abnormalities on echocardiography. Method: Out of 1,515 athletes included in Changi General Hospital, Singapore registry between June 2007 and June 2014, the electrocardiograms of 270 athletes with further cardiac investigations were analysed. We compared the above four electrocardiographic criteria to evaluate which performed best for detecting cardiac abnormalities on echocardiography in our Southeast Asian athlete population. Results: The European Society of Cardiology, Seattle, Refined and 2017 International Criteria had a sensitivity of 20%, 0%, 20% and 5%, respectively; a specificity of 64%, 93%, 84% and 97%, respectively; a positive predictive value of 4%, 0%, 9% and 11%, respectively; and a negative predictive value of 91%, 92%, 93% and 93%, respectively for detecting abnormalities on echocardiography. Conclusion: The latest 2017 International Criteria performed the best as it had the highest specificity and positive predictive value, joint highest negative predictive value, and lowest false positive rate.

Treatment of a ruptured shallow trilobed cerebral aneurysm with the novel saccular endovascular aneurysm lattice (SEAL) device: A case report with one year follow-up.

Intrasaccular flow disruption is a viable alternative to other endovascular treatments for saccular or wide-necked bifurcation intracranial aneurysms; however, wide neck aneurysms with irregular shapes or shallow depth may not be amenable to treatment currently available intrasaccular devices. Here, we present the first ever case report of the novel Saccular Endovascular Aneurysm Lattice Embolization System (SEAL™). The versatile utility of the SEAL™ device is demonstrated in a patient with acute subarachnoid hemorrhage (SAH) from a ruptured, complex, left middle cerebral artery (MCA) trilobed shallow wide-necked bifurcation aneurysm. Deployment and implantation of the SEAL device were technically feasible, safe, and conformed well to the irregular shape of the complex, ruptured aneurysm. Immediate total aneurysm occlusion was observed after implantation. Importantly, 1-year angiographic follow-up demonstrated durable, complete occlusion with no safety concerns. The SEAL device is a promising new novel technology which has the potential to treat very shallow aneurysms with limited height and irregular, multilobulated aneurysms.

Development and testing of a multi-lingual Natural Language Processing-based deep learning system in 10 languages for COVID-19 pandemic crisis: A multi-center study.

Purpose: The COVID-19 pandemic has drastically disrupted global healthcare systems. With the higher demand for healthcare and misinformation related to COVID-19, there is a need to explore alternative models to improve communication. Artificial Intelligence (AI) and Natural Language Processing (NLP) have emerged as promising solutions to improve healthcare delivery. Chatbots could fill a pivotal role in the dissemination and easy accessibility of accurate information in a pandemic. In this study, we developed a multi-lingual NLP-based AI chatbot, DR-COVID, which responds accurately to open-ended, COVID-19 related questions. This was used to facilitate pandemic education and healthcare delivery. Methods: First, we developed DR-COVID with an ensemble NLP model on the Telegram platform (https://t.me/drcovid_nlp_chatbot). Second, we evaluated various performance metrics. Third, we evaluated multi-lingual text-to-text translation to Chinese, Malay, Tamil, Filipino, Thai, Japanese, French, Spanish, and Portuguese. We utilized 2,728 training questions and 821 test questions in English. Primary outcome measurements were (A) overall and top 3 accuracies; (B) Area Under the Curve (AUC), precision, recall, and F1 score. Overall accuracy referred to a correct response for the top answer, whereas top 3 accuracy referred to an appropriate response for any one answer amongst the top 3 answers. AUC and its relevant matrices were obtained from the Receiver Operation Characteristics (ROC) curve. Secondary outcomes were (A) multi-lingual accuracy; (B) comparison to enterprise-grade chatbot systems. The sharing of training and testing datasets on an open-source platform will also contribute to existing data. Results: Our NLP model, utilizing the ensemble architecture, achieved overall and top 3 accuracies of 0.838 [95% confidence interval (CI): 0.826-0.851] and 0.922 [95% CI: 0.913-0.932] respectively. For overall and top 3 results, AUC scores of 0.917 [95% CI: 0.911-0.925] and 0.960 [95% CI: 0.955-0.964] were achieved respectively. We achieved multi-linguicism with nine non-English languages, with Portuguese performing the best overall at 0.900. Lastly, DR-COVID generated answers more accurately and quickly than other chatbots, within 1.12-2.15 s across three devices tested. Conclusion: DR-COVID is a clinically effective NLP-based conversational AI chatbot, and a promising solution for healthcare delivery in the pandemic era.