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BackgroundCoronavirus disease (COVID-19) is a worldwide epidemic, and various countries have responded with different containment measures to reduce disease transmission, including stay-at-home orders, curfews, and lockdowns. Comparative studies have not yet been conducted to investigate the impact of these containment measures; these studies are needed to facilitate public health policy-making across countries. ObjectiveThe aim of this study was to describe and evaluate the impact of national containment measures and policies (stay-at-home orders, curfews, and lockdowns) on decelerating the increase in daily new cases of COVID-19 in 54 countries and 4 epicenters of the pandemic in different jurisdictions worldwide. MethodsWe reviewed the effective dates of the national containment measures (stay-at-home order, curfew, or lockdown) of 54 countries and 4 epicenters of the COVID-19 pandemic (Wuhan, New York State, Lombardy, and Madrid), and we searched cumulative numbers of confirmed COVID-19 cases and daily new cases provided by health authorities. Data were drawn from an open, crowdsourced, daily-updated COVID-19 data set provided by Our World in Data. We examined the trends in the percent increase in daily new cases from 7 days before to 30 days after the dates on which containment measures went into effect by continent, World Bank income classification, type of containment measures, effective date of containment measures, and number of confirmed cases on the effective date of the containment measures. ResultsWe included 122,366 patients with confirmed COVID-19 infection from 54 countries and 24,071 patients from 4 epicenters on the effective dates on which stay-at-home orders, curfews, or lockdowns were implemented between January 23 and April 11, 2020. Stay-at-home, curfew, and lockdown measures commonly commenced in countries with approximately 30%, 20%, or 10% increases in daily new cases. All three measures were found to lower the percent increase in daily new cases to

BACKGROUND: Exposures associated with mpox infection remain imperfectly understood. METHODS: We conducted a case-control study enrolling participants who received molecular tests for mpox/orthopoxvirus in California from November 2022 through June 2023. We collected data on behaviors during a 21-day risk period before symptom onset or testing among mpox case patients and test-negative controls. RESULTS: Thirteen of 54 case patients (24.1%) and 5 of 117 controls (4.3%) reported sexual exposure to individuals they identified as potential mpox case patients (index contacts; odds ratio [OR], 7.7 [95% confidence interval (CI), 2.5-19.3] relative to individuals who did not report exposure to potential mpox case patients). Among these participants, 10 of 13 case patients (76.9%) and 2 of 5 controls (40.0%) reported that their index contacts were not experiencing symptoms visible to participants during sex (OR, 14.9 [95% CI, 3.6-101.8]). Only 3 of 54 case patients (5.6%) reported exposure to symptomatic index contacts. Case patients reported more anal/vaginal sex partners than did controls (adjusted OR, 2.2 [95% CI, 1.0-4.8] for 2-3 partners and 3.8 [1.7-8.8] for ≥4 partners). Male case patients with penile lesions more commonly reported insertive anal/vaginal sex than those without penile lesions (adjusted OR, 9.3 [95% CI, 1.6-54.8]). Case patients with anorectal lesions more commonly reported receptive anal sex than those without anorectal lesions (adjusted OR, 14.4 [95% CI, 1.0-207.3]). CONCLUSIONS: Sexual exposure to contacts known or suspected to have experienced mpox was associated with increased risk of infection, often when index contacts lacked apparent symptoms. Exposure to more sex partners, including those whom participants did not identify as index contacts, was associated with increased risk of infection in a site-specific manner. While participants assessment of symptoms in partners may be imperfect, these findings suggest that individuals without visibly prominent mpox symptoms transmit infection.

Although learning is often viewed as a unique feature of organisms with complex nervous systems, single-celled organisms also demonstrate basic forms of learning. The giant ciliate Stentor coeruleus responds to mechanical stimuli by contracting into a compact shape, presumably as a defense mechanism. When a Stentor cell is repeatedly stimulated at a constant level of force, it will learn to ignore that stimulus but will still respond to stronger stimuli. Prior studies of habituation in Stentor reported a graded response, suggesting that cells transition through a continuous range of response probabilities. By analyzing single cells using an automated apparatus to deliver calibrated stimuli, we find that habituation occurs via a single step-like switch in contraction probability within each cell, with the graded response in a population arising from the random distribution of switching times in individual cells. This step-like response allows Stentor behavior to be represented by a simple two-state model whose parameters can be estimated from experimental measurements. We find that transition rates depend on stimulus force and also on the time between stimuli. The ability to measure the behavior of the same cell to the same stimulus allowed us to quantify the functional heterogeneity among single cells. Together, our results suggest that the behavior of Stentor is governed by a two-state stochastic machine whose transition rates are sensitive to the time series properties of the input stimuli.

Active biofluid management is central to the realization of wearable bioanalytical platforms that are poised to autonomously provide frequent, real-time, and accurate measures of biomarkers in epidermally-retrievable biofluids (e.g., sweat). Accordingly, here, a programmable epidermal microfluidic valving system is devised, which is capable of biofluid sampling, routing, and compartmentalization for biomarker analysis. At its core, the system is a network of individually-addressable microheater-controlled thermo-responsive hydrogel valves, augmented with a pressure regulation mechanism to accommodate pressure built-up, when interfacing sweat glands. The active biofluid control achieved by this system is harnessed to create unprecedented wearable bioanalytical capabilities at both the sensor level (decoupling the confounding influence of flow rate variability on sensor response) and the system level (facilitating context-based sensor selection/protection). Through integration with a wireless flexible printed circuit board and seamless bilateral communication with consumer electronics (e.g., smartwatch), contextually-relevant (scheduled/on-demand) on-body biomarker data acquisition/display was achieved.

The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca's large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.

BackgroundHIV preexposure prophylaxis (PrEP) using daily oral tenofovir-disoproxil-fumarate/emtricitabine (TDF/FTC) is effective for preventing HIV acquisition, but concerns remain about its potential kidney toxicity. This study examined kidney function in individuals using PrEP in real-world clinical settings.SettingDemonstration project in 2 sexually transmitted infection clinics and a community health center.MethodsWe evaluated kidney function among men who have sex with men and transgender women taking tenofovir-disoproxil-fumarate/emtricitabine PrEP for up to 48 weeks. Serum creatinine and urine dipstick for protein were obtained at 12-week intervals. Kidney function was estimated using creatinine clearance (CrCl) (Cockcroft-Gault) and estimated glomerular filtration rate (eGFR) (CKD-EPI).ResultsFrom October 2012 to January 2014, we enrolled 557 participants (median age 33). Mean creatinine increased from baseline to week 12 by 0.03 mg/dL (4.6%) (P < 0.0001); mean CrCl decreased by 4.8 mL/min (3.0%) (P < 0.0001). These changes remained stable through week 48 (P = 0.81, P = 0.71 respectively). There were 75/478 (15.7%) participants who developed worsening proteinuria at week 12 compared with baseline (P < 0.0001), and this percent remained stable through week 48 (P = 0.73). Twenty-five participants (5.1%) developed new-onset eGFR

ObjectivesSyphilis is endemic among men who have sex with men (MSM) and transgender women in Latin America. The objective of this study was to assess if those who screen positive for syphilis are receiving appropriate care and treatment.MethodsWe use data from the 2011 Peruvian National HIV Sentinel Surveillance to describe the syphilis care cascade among high-risk MSM and transgender women. Medical records from participants who had a positive syphilis screening test at two of the enrolment sites in Lima were reviewed to determine their subsequent course of care.ResultsWe identified a cohort of 314 syphilis seropositive participants (median age: 30, 33.7% self-identified as transgender). Only 284/314 (90.4%) participants saw a physician for evaluation within 28 days of their positive test. Of these, 72/284 (25.4%) were asked to return for confirmatory results before deciding whether or not to start treatment; however, 45/72 (62.5%) of these participants did not follow up within 28 days. Of the people prescribed three weekly doses of penicillin, 34/63 (54%) received all three doses on time.ConclusionsMany MSM and transgender women with a positive syphilis screening test are lost at various steps along the syphilis care cascade and may have persistent infection. Interventions in this population are needed to increase testing, link seropositive patients into care and ensure that they receive appropriate and timely treatment.

We have developed a process with the Biomek FX robot to construct 454 titanium libraries in order to meet the increasing library demands. All modifications in the library construction steps were made to enable the adaptation of the entire processes to work with the 96-well plate format. The key modifications include the shearing of DNA with Covaris E210 and the enzymatic reaction cleaning and fragment size selection with SPRI beads and magnetic plate holders. The construction of 96 Titanium libraries takes about 8 hours from sheared DNA to ssDNA recovery. Although this process still requires manual transfer of plates from robot to other work stations such as thermocyclers, these robotic processes represent about 12- to 24-folds increase of library capacity comparing to the manual processes. To enable the sequencing of many libraries in parallel, we have also developed sets of molecular barcodes. The requirements for the 454 library barcodes include 10 bases, 40-60percent GC, no consecutive same base, and no less than 3 bases difference between barcodes. We have used 96 of the resulted 270 barcodes to construct libraries and pool to test the ability of accurately assigning reads to the right samples. When allowing 1 base error occurred in the 10 base barcodes, we could assign 99.6percent of the total reads and 100percent of them were uniquely assigned. We have begun to assess the ability to assign reads after pooling different number of libraries. We will discuss the progress and the challenges of this scale-up process.

As the demand of constructing Illumina libraries increases, we have started to modify the library construction protocol to adapt the use of multichannel pipette and 96-well plates. With the few simple modification steps, we have doubled the library production efficiency. These modifications include the shearing of DNA with Covaris E210, and the cleaning of enzymatic reactions and fragment size selection with SPRI beads and a magnetic plate holder. We have also designed a set of molecular barcodes to enable the sequencing of many libraries in parallel. The requirements of these barcodes include 4 bases, balanced GC, and at least 2 bases difference between barcodes. The barcode is attached to the adaptor so it does not require third sequencing primer and the barcoded library can be run on the same flowcell/run with other non-barcoded libraries. We have begun to assess the ability to assign reads and the potential bias towards certain barcodes after pooling different number of libraries. We have recently programmed the Biomek FX robot to carry out the library construction process. Although this process still require manual transfer of plates from robot to other work stations, the processing of 96 Illumina libraries takes approximately 6-8 hours. This semi-automated process represents a significant increase of library capacity comparing to the manual process. We will present the progress and the challenges of these scale-up processes.