Sequence-specific targeting of intrinsically disordered protein regions.

A general approach to design proteins that bind tightly and specifically to intrinsically disordered regions (IDRs) of proteins and flexible peptides would have wide application in biological research, therapeutics, and diagnosis. However, the lack of defined structures and the high variability in sequence and conformational preferences has complicated such efforts. We sought to develop a method combining biophysical principles with deep learning to readily generate binders for any disordered sequence. Instead of assuming a fixed regular structure for the target, general recognition is achieved by threading the query sequence through diverse extended binding modes in hundreds of templates with varying pocket depths and spacings, followed by RFdiffusion refinement to optimize the binder-target fit. We tested the method by designing binders to 39 highly diverse unstructured targets. Experimental testing of ∼36 designs per target yielded binders with affinities better than 100 nM in 34 cases, and in the pM range in four cases. The co-crystal structure of a designed binder in complex with dynorphin A is closely consistent with the design model. All by all binding experiments for 20 designs binding diverse targets show they are highly specific for the intended targets, with no crosstalk even for the closely related dynorphin A and dynorphin B. Our approach thus could provide a general solution to the intrinsically disordered protein and peptide recognition problem.

The Use of Free Weight Squats in Sports: A Narrative Review-Squatting Movements, Adaptation, and Sports Performance: Physiological.

ABSTRACT: Stone, MH, Hornsby, G, Mizuguchi, S, Sato, K, Gahreman, D, Duca, M, Carroll, K, Ramsey, MW, Stone, ME, and Haff, GG. The use of free weight squats in sports: a narrative review-squatting movements, adaptation, and sports performance: physiological. J Strength Cond Res 38(8): 1494-1508, 2024-The squat and its variants can provide numerous benefits including positively affecting sports performance and injury prevention, injury severity reduction, and rehabilitation. The positive benefits of squat are likely the result of training-induced neural alterations and mechanical and morphological adaptations in tendons, skeletal muscles, and bones, resulting in increased tissue stiffness and cross-sectional area (CSA). Although direct evidence is lacking, structural adaptations can also be expected to occur in ligaments. These adaptations are thought to beneficially increase force transmission and mechanical resistance (e.g., resistance to mechanical strain) and reduce the likelihood and severity of injuries. Adaptations such as these, also likely play an important role in rehabilitation, particularly for injuries that require restricted use or immobilization of body parts and thus lead to a consequential reduction in the CSA and alterations in the mechanical properties of tendons, skeletal muscles, and ligaments. Both volume and particularly intensity (e.g., levels of loading used) of training seem to be important for the mechanical and morphological adaptations for at least skeletal muscles, tendons, and bones. Therefore, the training intensity and volume used for the squat and its variations should progressively become greater while adhering to the concept of periodization and recognized training principles.

A global perspective on the treatment and maintenance of mature skin using gentle cleansers and moisturizers.

Xerosis is highly prevalent in the population aged over 50 years and substantially impacts quality of life due to the associated stigma, related pruritus, and potential sequelae. We propose that the term mature xerosis be used for subjects over 50 who suffer from age-related xerosis and replace senile xerosis to describe the phenomenon. The etiology of xerosis depends on genetic and environmental factors that affect stratum corneum hydration and skin barrier function. Skincare to restore barrier function is essential in xerosis treatment and is relevant for maintaining and preventing its progression. Many moisturizers and cleansers are available for xerosis; however, they are underutilized by patients with mature xerosis. A panel of eight global dermatologists reviewed the unique aspects of xerosis in mature skin and discussed the specific needs, relevance, and considerations for skincare selection to prevent, treat, and maintain skin with mature xerosis. The panel selected five statements based on evidence from a literature review and the panel's clinical experience to provide clinical considerations and recommendations for dermatologists and other healthcare providers treating patients with mature xerosis. Increased recognition of the burden of xerosis in mature skin is warranted. Gentle cleansers and barrier-restoring ceramide-containing moisturizers are essential to xerosis management, reducing signs and symptoms of xerosis, including associated pruritus.

Association of PHACTR1 with Coronary Artery Calcium Differs by Sex and Cigarette Smoking.

Background: Coronary artery calcium (CAC) is a marker of subclinical atherosclerosis and is a complex heritable trait with both genetic and environmental risk factors, including sex and smoking. Methods: We performed genome-wide association (GWA) analyses for CAC among all participants and stratified by sex in the COPDGene study (n = 6144 participants of European ancestry and n = 2589 participants of African ancestry) with replication in the Diabetes Heart Study (DHS). We adjusted for age, sex, current smoking status, BMI, diabetes, self-reported high blood pressure, self-reported high cholesterol, and genetic ancestry (as summarized by principal components computed within each racial group). For the significant signals from the GWA analyses, we examined the single nucleotide polymorphism (SNP) by sex interactions, stratified by smoking status (current vs. former), and tested for a SNP by smoking status interaction on CAC. Results: We identified genome-wide significant associations for CAC in the chromosome 9p21 region [CDKN2B-AS1] among all COPDGene participants (p = 7.1 × 10-14) and among males (p = 1.0 × 10-9), but the signal was not genome-wide significant among females (p = 6.4 × 10-6). For the sex stratified GWA analyses among females, the chromosome 6p24 region [PHACTR1] had a genome-wide significant association (p = 4.4 × 10-8) with CAC, but this signal was not genome-wide significant among all COPDGene participants (p = 1.7 × 10-7) or males (p = 0.03). There was a significant interaction for the SNP rs9349379 in PHACTR1 with sex (p = 0.02), but the interaction was not significant for the SNP rs10757272 in CDKN2B-AS1 with sex (p = 0.21). In addition, PHACTR1 had a stronger association with CAC among current smokers (p = 6.2 × 10-7) than former smokers (p = 7.5 × 10-3) and the SNP by smoking status interaction was marginally significant (p = 0.03). CDKN2B-AS1 had a strong association with CAC among both former (p = 7.7 × 10-8) and current smokers (p = 1.7 × 10-7) and the SNP by smoking status interaction was not significant (p = 0.40). Conclusions: Among current and former smokers of European ancestry in the COPDGene study, we identified a genome-wide significant association in the chromosome 6p24 region [PHACTR1] with CAC among females, but not among males. This region had a significant SNP by sex and SNP by smoking interaction on CAC.

Hippo pathway-mediated YAP1/TAZ inhibition is essential for proper pancreatic endocrine specification and differentiation.

The Hippo pathway plays a central role in tissue development and homeostasis. However, the function of Hippo in pancreatic endocrine development remains obscure. Here, we generated novel conditional genetically engineered mouse models to examine the roles of Hippo pathway-mediated YAP1/TAZ inhibition in the development stages of endocrine specification and differentiation. While YAP1 protein was localized to the nuclei in bipotent progenitor cells, Neurogenin 3 expressing endocrine progenitors completely lost YAP1 expression. Using genetically engineered mouse models, we found that inactivation of YAP1 requires both an intact Hippo pathway and Neurogenin 3 protein. Gene deletion of Lats1 and 2 kinases (Lats1&2) in endocrine progenitor cells of developing mouse pancreas using Neurog3Cre blocked endocrine progenitor cell differentiation and specification, resulting in reduced islets size and a disorganized pancreas at birth. Loss of Lats1&2 in Neurogenin 3 expressing cells activated YAP1/TAZ transcriptional activity and recruited macrophages to the developing pancreas. These defects were rescued by deletion of Yap1/Wwtr1 genes, suggesting that tight regulation of YAP1/TAZ by Hippo signaling is crucial for pancreatic endocrine specification. In contrast, deletion of Lats1&2 using ß-cell-specific Ins1CreER resulted in a phenotypically normal pancreas, indicating that Lats1&2 are indispensable for differentiation of endocrine progenitors but not for that of ß-cells. Our results demonstrate that loss of YAP1/TAZ expression in the pancreatic endocrine compartment is not a passive consequence of endocrine specification. Rather, Hippo pathway-mediated inhibition of YAP1/TAZ in endocrine progenitors is a prerequisite for endocrine specification and differentiation.

Escape Velocity-the Launch of Microbiome Therapies.

Food and Drug Administration approval of the first microbiome therapies represents a true expansion the treatment paradigm for Clostridioides difficile but raises new questions about the future role of fecal microbiota transplantation. The authors outline the advances in microbiome therapeutic development that have addressed fecal microbiota transplantation's (FMT's) inherent limitations of safety and scalability. The authors also suggest that as microbiome therapeutic development continues for other indications, FMT will likely remain a necessary model of human microbiota dynamics for translational research.

RNA-seq gene expression profiling of the bladder in a mouse model of urogenital schistosomiasis.

Background: Parasitic flatworms of the Schistosoma genus cause schistosomiasis, which affects over 230 million people. Schistosoma haematobium causes the urogenital form of schistosomiasis (UGS), which can lead to hematuria, fibrosis, and increased risk of secondary infections by bacteria or viruses. UGS is also linked to bladder cancer. To understand the bladder pathology during S. haematobium infection, our group previously developed a mouse model that involves the injection of S. haematobium eggs into the bladder wall. Using this model, we studied changes in epigenetics profile, as well as changes in gene and protein expression in the host bladder tissues. In the current study, we expand upon this work by examining the expression level of both host and parasite genes using RNA sequencing (RNA-seq) in the mouse bladder wall injection model of S. haematobium infection. Methods: We used a mouse model of S. haematobium infection in which parasite eggs or vehicle control were injected into the bladder walls of female BALB/c mice. RNA-seq was performed on the RNA isolated from the bladders four days after bladder wall injection. Results/Conclusions: RNA-seq analysis of egg- and vehicle control-injected bladders revealed the differential expression of 1025 mouse genes in the egg-injected bladders, including genes associated with cellular infiltration, immune cell chemotaxis, cytokine signaling, and inflammation We also observed the upregulation of immune checkpoint-related genes, which suggests that while the infection causes an inflammatory response, it also dampens the response to avoid excessive inflammation-related damage to the host. Identifying these changes in host signaling and immune responses improves our understanding of the infection and how it may contribute to the development of bladder cancer. Analysis of the differential gene expression of the parasite eggs between bladder-injected versus uninjected eggs revealed 119 S. haematobium genes associated with transcription, intracellular signaling, and metabolism. The analysis of the parasite genes also revealed fewer transcript reads compared to that found in the analysis of mouse genes, highlighting the challenges of studying parasite egg biology in the mouse model of S. haematobium infection.

External skeletal fixation for the treatment of pelvic fractures in cats.

OBJECTIVE: To report the technique and the outcome for the repair of pelvic fractures in cats using external skeletal fixation (ESF). STUDY DESIGN: Retrospective case series. ANIMALS: Client-owned cats (n = 125). METHODS: Medical records of cats with pelvic fractures, treated with an ESF between June 2001 and June 2009, were reviewed. Preoperative, immediate postoperative, and more than 4 weeks' postoperative radiographs were compared. Clinical examination was performed 4 to 9 weeks following surgery. Longer term follow up (4 to 80 months) was conducted by client questionnaire. RESULTS: No intraoperative complications occurred. There was no change in the pelvic canal width observed on follow-up radiographs (p = .16). Implant loosening was noted on follow-up radiographs in 16/125 (13%) of cases, and 67/803 (8%) pins were palpably loose at the time of frame removal. The mean time to frame removal was 37 ± 9 days. No long-term complications were reported. Long-term mean mobility score was 95 ± 5 and median lameness was 0 (range: 0-2). CONCLUSION: An ESF may be successfully applied for the stabilization of various pelvic fractures in cats. CLINICAL SIGNIFICANCE: The application of an ESF for the management of pelvic fractures in cats provides good outcomes.

The global impact of COVID-19 on tuberculosis: A thematic scoping review, 2020-2023.

BACKGROUND: This thematic scoping review of publications sought to understand the global impact of COVID-19 on tuberculosis (TB), interpret the scope of resonating themes, and offer policy recommendations to stimulate TB recovery and future pandemic preparedness. DATA SOURCES: Publications were captured from three search engines, PubMed, EBSCO, and Google Scholar, and applicable websites written in English from January 1, 2020, to April 30, 2023. STUDY SELECTION: Our scoping review was limited to publications detailing the impact of COVID-19 on TB. Original research, reviews, letters, and editorials describing the deleterious and harmful--yet sometimes positive--impact of COVID-19 (sole exposure) on TB (sole outcome) were included. The objective was to methodically categorize the impacts into themes through a comprehensive review of selected studies to provide significant health policy guidance. DATA EXTRACTION: Two authors independently screened citations and full texts, while the third arbitrated when consensus was not met. All three performed data extraction. DATA SYNTHESIS/RESULTS: Of 1,755 screened publications, 176 (10%) covering 39 countries over 41 months met the inclusion criteria. By independently using a data extraction instrument, the three authors identified ten principal themes from each publication. These themes were later finalized through a consensus decision. The themes encompassed TB's care cascade, patient-centered care, psychosocial issues, and health services: 1) case-finding and notification (n = 45; 26%); 2) diagnosis and laboratory systems (n = 19; 10.7%) 3) prevention, treatment, and care (n = 22; 12.2%); 4) telemedicine/telehealth (n = 12; 6.8%); 5) social determinants of health (n = 14; 8%); 6) airborne infection prevention and control (n = 8; 4.6%); 7) health system strengthening (n = 22; 13%); 8) mental health (n = 13; 7.4%); 9) stigma (n = 11; 6.3%); and 10) health education (n = 10; 5.7%). LIMITATIONS: Heterogeneity of publications within themes. CONCLUSIONS: We identified ten globally generalizable themes of COVID-19's impact on TB. The impact and lessons learned from the themed analysis propelled us to draft public health policy recommendations to direct evidence-informed guidance that strengthens comprehensive global responses, recovery for TB, and future airborne pandemic preparedness.

Reinforcing effects of fentanyl analogs found in illicit drug markets.

RATIONALE: The potent synthetic opioid fentanyl, and its analogs, continue to drive opioid-related overdoses. Although the pharmacology of fentanyl is well characterized, there is little information about the reinforcing effects of clandestine fentanyl analogs (FAs). OBJECTIVES: Here, we compared the effects of fentanyl and the FAs acetylfentanyl, butyrylfentanyl, and cyclopropylfentanyl on drug self-administration in male and female rats. These FAs feature chemical modifications at the carbonyl moiety of the fentanyl scaffold. METHODS: Sprague-Dawley rats fitted with intravenous jugular catheters were placed in chambers containing two nose poke holes. Active nose poke responses resulted in drug delivery (0.2 mL) over 2 s on a fixed-ratio 1 schedule, followed by a 20 s timeout. Acquisition doses were 0.01 mg/kg/inj for fentanyl and cyclopropylfentanyl, and 0.03 mg/kg/inj for acetylfentanyl and butyrylfentanyl. After 10 days of acquisition, dose-effect testing was carried out, followed by 10 days of saline extinction. RESULTS: Self-administration of fentanyl and FAs was acquired by both male and female rats, with no sex differences in acquisition rate. Fentanyl and FAs showed partial inverted-U dose-effect functions; cyclopropylfentanyl and fentanyl had similar potency, while acetylfentanyl and butyrylfentanyl were less potent. Maximal response rates were similar across drugs, with fentanyl and cyclopropylfentanyl showing maximum responding at 0.001 mg/kg/inj, acetylfentanyl at 0.01 mg/kg/inj, and butyrylfentanyl at 0.003 mg/kg/inj. No sex differences were detected for drug potency, efficacy, or rates of extinction. CONCLUSIONS: Our work provides new evidence that FAs display significant abuse liability in male and female rats, which suggests the potential for compulsive use in humans.

A prospective longitudinal study of risk factors for abdominal aortic aneurysm.

The aim of this study was to identify risk factors for abdominal aortic aneurysm (AAA) from the largest Welsh screening cohort to date. Patients were recruited from 1993 (to 2015) as part of the South East Wales AAA screening programme through general practitioners. Demographic data and risk factors were collected by means of a self-report questionnaire. Statistical tests were performed to determine whether associations could be observed between AAA and potential risk factors. Odds ratios (OR) were also calculated for each of the risk factors identified. A total of 6879 patients were included in the study. Two hundred and seventy-five patients (4.0%) presented with AAA, of which 16% were female and 84% were male. Patients with AAA were older than the (no AAA) control group (p < 0.0001). The following risk factors were identified for AAA: family history of AAA (p < 0.0001); history of vascular surgery (p < 0.0001), cerebrovascular accident (p < 0.0001), coronary heart disease (p < 0.0001), diabetes (p < 0.0001), medication (p = 0.0018), claudication (p < 0.0001), smoking history (p = 0.0001) and chronic obstructive pulmonary disorder (p = 0.0007). AAA is associated with classical vascular risk factors, in addition to other less-well-documented risk factors including previous vascular surgery. These findings have practical implications with the potential to improve future clinical screening of patients in order to reduce AAA mortality.

Unsupervised representation learning on high-dimensional clinical data improves genomic discovery and prediction.

Although high-dimensional clinical data (HDCD) are increasingly available in biobank-scale datasets, their use for genetic discovery remains challenging. Here we introduce an unsupervised deep learning model, Representation Learning for Genetic Discovery on Low-Dimensional Embeddings (REGLE), for discovering associations between genetic variants and HDCD. REGLE leverages variational autoencoders to compute nonlinear disentangled embeddings of HDCD, which become the inputs to genome-wide association studies (GWAS). REGLE can uncover features not captured by existing expert-defined features and enables the creation of accurate disease-specific polygenic risk scores (PRSs) in datasets with very few labeled data. We apply REGLE to perform GWAS on respiratory and circulatory HDCD-spirograms measuring lung function and photoplethysmograms measuring blood volume changes. REGLE replicates known loci while identifying others not previously detected. REGLE are predictive of overall survival, and PRSs constructed from REGLE loci improve disease prediction across multiple biobanks. Overall, REGLE contain clinically relevant information beyond that captured by existing expert-defined features, leading to improved genetic discovery and disease prediction.

Circulating Tumor DNA Predicts Early Recurrence Following Locoregional Therapy for Oligometastatic Colorectal Cancer.

(1) Background: Local therapies offer a potentially curative approach for patients with oligometastatic colorectal cancer (CRC). An evidence-based consensus recommendation for systemic therapy following definitive locoregional therapy is lacking. Tumor-informed circulating tumor DNA (ctDNA) might provide information to help guide management in this setting. (2) Methods: A multi-institutional retrospective study was conducted, including patients with CRC that underwent curative-intent locoregional therapy to an isolated site of metastatic disease, followed by tumor-informed ctDNA assessment. The Kaplan-Meier method and log-rank tests were used to compare disease-free survival based on ctDNA results. ctDNA test performance was compared to carcinoembryonic antigen (CEA) test results using McNemar's test. (3) Results: Our study cohort consisted of 87 patients treated with locoregional interventions who underwent ctDNA testing. The initial ctDNA test post-intervention was positive in 28 patients and negative in 59 patients. The median follow-up time was 14.0 months. Detectable ctDNA post-intervention was significantly associated with early disease recurrence, with a median disease-free survival (DFS) of 6.63 months compared to 21.30 months in ctDNA-negative patients (p < 0.001). ctDNA detected a numerically higher proportion of recurrences than CEA (p < 0.097). Post-intervention systemic therapy was not associated with improved DFS (p = 0.745). (4) Conclusions: ctDNA results are prognostically important in oligometastatic CRC, and further prospective studies are urgently needed to define its role in guiding clinical decisions.

AI for detection, classification and prediction of loss of alignment of distal radius fractures; a systematic review.

PURPOSE: Early and accurate assessment of distal radius fractures (DRFs) is crucial for optimal prognosis. Identifying fractures likely to lose threshold alignment (instability) in a cast is vital for treatment decisions, yet prediction tools' accuracy and reliability remain challenging. Artificial intelligence (AI), particularly Convolutional Neural Networks (CNNs), can evaluate radiographic images with high performance. This systematic review aims to summarize studies utilizing CNNs to detect, classify, or predict loss of threshold alignment of DRFs. METHODS: A literature search was performed according to the PRISMA. Studies were eligible when the use of AI for the detection, classification, or prediction of loss of threshold alignment was analyzed. Quality assessment was done with a modified version of the methodologic index for non-randomized studies (MINORS). RESULTS: Of the 576 identified studies, 15 were included. On fracture detection, studies reported sensitivity and specificity ranging from 80 to 99% and 73-100%, respectively; the AUC ranged from 0.87 to 0.99; the accuracy varied from 82 to 99%. The accuracy of fracture classification ranged from 60 to 81% and the AUC from 0.59 to 0.84. No studies focused on predicting loss of thresholds alignement of DRFs. CONCLUSION: AI models for DRF detection show promising performance, indicating the potential of algorithms to assist clinicians in the assessment of radiographs. In addition, AI models showed similar performance compared to clinicians. No algorithms for predicting the loss of threshold alignment were identified in our literature search despite the clinical relevance of such algorithms.

Insect Flight: State of the Field and Future Directions.

The evolution of flight in an early winged insect ancestral lineage is recognized as a key adaptation explaining the unparalleled success and diversification of insects. Subsequent transitions and modifications to flight machinery, including secondary reductions and losses, also play a central role in shaping the impacts of insects on broadscale geographic and ecological processes and patterns in the present and future. Given the importance of insect flight, there has been a centuries-long history of research and debate on the evolutionary origins and biological mechanisms of flight. Here, we revisit this history from an interdisciplinary perspective, discussing recent discoveries regarding the developmental origins, physiology, biomechanics, and neurobiology and sensory control of flight in a diverse set of insect models. We also identify major outstanding questions yet to be addressed and provide recommendations for overcoming current methodological challenges faced when studying insect flight, which will allow the field to continue to move forward in new and exciting directions. By integrating mechanistic work into ecological and evolutionary contexts, we hope that this synthesis promotes and stimulates new interdisciplinary research efforts necessary to close the many existing gaps about the causes and consequences of insect flight evolution.

Permissible HLA mismatches in 9/10 unrelated donor pediatric stem cell transplants using HLA-EMMA, an EBMT IEWP Study.

HSCT with mismatched unrelated donors (MMUD) is associated with inferior outcome compared to matched unrelated donors. We aimed to identify permissible mismatches using HLA-EMMA, which determines permissibility by analyzing amino-acid (AA) sequences, in a single center cohort of 70 pediatric 9/10 MMUD HSCTs and 157 10/10 MUDs for comparison. AA matching was evaluated for the whole HLA protein, the α-helices, and the ß-sheets, in both Host versus Graft (HvG) and Graft vs Host (GvH) direction. Superior EFS was found in 13 patients permissibly mismatched in the HvG direction (totalHvG, 92% vs 58% at 1 year, p=0.009), and in 21 patients matched for AA on the α-helices (αHvG, 90% vs 53%, p=0.002), similar to EFS with 10/10 MUDs (90% vs 80%, p=0.60). EFS was not related to ß-sheet AA matching, nor to matching in the GvH direction. OS trended similarly as EFS for AA mismatches (totalHvG, 92% vs 74%, p=0.075 and αHvG90% vs 71%, p=0.072). These findings were reproduced in an EBMT inborn errors cohort of 271 pediatric 9/10 MMUD HSCTs and 929 10/10 MUD HSCTs, showing a significant effect of αHvG matching on both OS and EFS and similar OS and EFS between αHvG matched MMUDs and 10/10 MUDs. In summary, HvG-AA matching on the α-helices identifies 9/10 MMUD with permissible mismatches correlated with a favorable transplant outcome similar to matched donors.

Traditional radiography versus computed tomography to assess reduced distal radius fractures.

INTRODUCTION: This study compares computed tomography (CT) with plain radiography in its ability to assess distal radius fracture (DRF) malalignment after closed reduction and cast immobilization. METHODS: Malalignment is defined as radiographic fracture alignment beyond threshold values according to the Dutch guideline encompassing angulation, inclination, positive ulnar variance and intra-articular step-off or gap. After identifying 96 patients with correct alignment on initial post-reduction radiographs, we re-assessed alignment on post-reduction CT scans. RESULTS: Significant discrepancies were found between radiographs and CT scans in all measurement parameters. Notably, intra-articular step-off and gap variations on CT scans led to the reclassification of the majority of cases from correct alignment to malalignment. CT scans showed malalignment in 53% of cases, of which 73% underwent surgery. CONCLUSION: When there is doubt about post-reduction alignment based on radiograph imaging, additional CT scanning often reveals malalignment, primarily due to intra-articular incongruency.

KCL TEST: an open-source inspired asymptomatic SARS-CoV-2 surveillance programme in an academic institution.

Rapid and accessible testing was paramount in the management of the COVID-19 pandemic. Our university established KCL TEST: a SARS-CoV-2 asymptomatic testing programme that enabled sensitive and accessible PCR testing of SARS-CoV-2 RNA in saliva. Here, we describe our learnings and provide our blueprint for launching diagnostic laboratories, particularly in low-resource settings. Between December 2020 and July 2022, we performed 158277 PCRs for our staff, students, and their household contacts, free of charge. Our average turnaround time was 16 h and 37 min from user registration to result delivery. KCL TEST combined open-source automation and in-house non-commercial reagents, which allows for rapid implementation and repurposing. Importantly, our data parallel those of the UK Office for National Statistics, though we detected a lower positive rate and virtually no delta wave. Our observations strongly support regular asymptomatic community testing as an important measure for decreasing outbreaks and providing safe working spaces. Universities can therefore provide agile, resilient, and accurate testing that reflects the infection rate and trend of the general population. Our findings call for the early integration of academic institutions in pandemic preparedness, with capabilities to rapidly deploy highly skilled staff, as well as develop, test, and accommodate efficient low-cost pipelines.