Etravirine (ETR) is a nonnucleoside reverse transcriptase inhibitor (NNRTI) used in treatment-experienced individuals. Genotypic resistance test-interpretation systems can predict ETR resistance; however, genotype-based algorithms are derived primarily from HIV-1 subtype B and may not accurately predict resistance in non-B subtypes. The frequency of ETR resistance among recombinant subtype C HIV-1 and the accuracy of genotypic interpretation systems were investigated. HIV-1_LAI containing full-length RT from HIV-1 subtype C-positive individuals experiencing virologic failure (>10,000 copies/ml and >1 NNRTI resistance-associated mutation) were phenotyped for ETR susceptibility. Fold change (FC) was calculated against a composite 50% effective concentration (EC₅₀) from treatment-naive individuals and three classifications were assigned: (i) <2.9-FC, susceptible; (ii) ≥2.9- to 10-FC, partially resistant; and (iii) >10-FC, fully resistant. The Stanford HIVdb-v8.4 was used for genotype predictions merging the susceptible/potential low-level and low-level/intermediate groups for 3 x 3 comparison. Fifty-four of a hundred samples had reduced ETR susceptibility (≥2.9-FC). The FC correlated with HIVdb-v8.4 (Spearman’s rho = 0.62; P < 0.0001); however, 44% of samples were partially (1 resistance classification difference) and 4% completely discordant (2 resistance classification differences). Of the 34 samples with an FC of >10, 26 were HIVdb-v8.4 classified as low-intermediate resistant. Mutations L100I, Y181C, or M230L were present in 27/34 (79%) of samples with an FC of >10 but only in 2/46 (4%) of samples with an FC of <2.9. No other mutations were associated with ETR resistance. Viruses containing the mutation K65R were associated with reduced ETR susceptibility, but 65R reversions did not increase ETR susceptibility. Therefore, genotypic interpretation systems were found to misclassify ETR susceptibility in HIV-1 subtype C samples. Modifications to genotypic algorithms are needed to improve the prediction of ETR resistance for the HIV-1 subtype C.

In the past few decades, enterovirus A71 (EVA71) has caused devastating outbreaks in the Asia-Pacific region, resulting in serious sequelae in infected young children. No preventive or therapeutic interventions are currently available for curing EVA71 infection, highlighting a great unmet medical need for this disease. Here, we showed that one novel single-domain antibody (sdAb), F1, isolated from an immunized llama, could alleviate EVA71 infection both in vitro and in vivo. We also confirmed that the sdAb clone F1 recognizes EVA71 through a novel conformational epitope comprising the highly conserved region of VP3 capsid protein by using competitive-binding and overlapping-peptide enzyme-linked immunosorbent assays (ELISAs). Because of the virion’s icosahedral structure, we reasoned that adjacent epitopes must be clustered within molecular ranges that may be simultaneously bound by an engineered antibody with multiple valency. Therefore, two single-domain binding modules (F1) were fused to generate an sdAb-in-tandem design so that the capture of viral antigens could be further increased by valency effects. We showed that the tetravalent construct F1xF1-hFc, containing two sdAb-in-tandem on a fragment crystallizable (Fc) scaffold, exhibits more potent neutralization activity against EVA71 than does the bivalent sdAb F1-hFc by at least 5.8-fold. We also demonstrated that, using a human scavenger receptor class B member 2 (hSCARB2) transgenic mouse model, a half dose of the F1xF1-hFc provided better protection against EVA71 infection than did the F1-hFc. Thus, our study furnishes important insights into multivalent sdAb engineering against viral infection and provides a novel strategic deployment approach for preparedness of emerging infectious diseases such as EVA71.

Tilorone is a 50-year-old synthetic small-molecule compound with antiviral activity that is proposed to induce interferon after oral administration. This drug is used as a broad-spectrum antiviral in several countries of the Russian Federation. We have recently described activity in vitro and in vivo against the Ebola virus. After a broad screening of additional viruses, we now describe in vitro activity against Chikungunya virus (CHIK) and Middle Eastern respiratory syndrome coronavirus (MERS-CoV).

Amplification of and oncogenic mutations in ERBB2, the gene encoding the HER2 receptor tyrosine kinase, promote receptor hyperactivation and tumor growth. Here we demonstrate that HER2 ubiquitination and internalization, rather than its overexpression, are key mechanisms underlying endocytosis and consequent efficacy of the anti-HER2 antibody–drug conjugates (ADC) ado-trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd) in lung cancer cell lines and patient-derived xenograft models. These data translated into a 51% response rate in a clinical trial of T-DM1 in 49 patients with ERBB2-amplified or -mutant lung cancers. We show that cotreatment with irreversible pan-HER inhibitors enhances receptor ubiquitination and consequent ADC internalization and efficacy. We also demonstrate that ADC switching to T-DXd, which harbors a different cytotoxic payload, achieves durable responses in a patient with lung cancer and corresponding xenograft model developing resistance to T-DM1. Our findings may help guide future clinical trials and expand the field of ADC as cancer therapy.

This study was an analysis of a national sample of U.S. medical office visits from 2014 to 2016, a period when evidence of effectiveness was emerging for a variety of beneficial type 2 diabetes agents with regard to potential reduction in diabetes comorbidities. Ideal therapy was defined as an American Diabetes Association–identified beneficial agent plus metformin. The associations between atherosclerotic cardiovascular disease or obesity and use of these agents were explored.

BACKGROUND AND PURPOSE:

Conventional nonadhesive liquid embolic agents currently are the criterion standard for endovascular embolization of cerebral AVMs. However, inadequate distal penetration into the nidus and unstable proximal plug formation are the major limitations of this approach and of the currently available embolic materials. The aim of this study was to evaluate the hypothetic efficacy of combining liquid embolic agents with different properties and viscosities for use in endovascular embolization of cerebral AVMs.

Business Insider asked real-estate agents across the U.S., and they point out 11 reason that prevent your home from being sold.

The OpenAI project demonstrated "emergent behavior" by the AI players, including surfing

Final season picks up where S6's cliffhanger finale left off.

'I knew that I could not portray this gay man honestly without letting you all know that I am gay myself'

The agents of Thomas Partey have apologised after a post which listed the Atletico Madrid star's potential next clubs appeared on their Instagram page.

Jose Mourinho is expecting to be limited to free agents and swap deals in the next transfer window, as the top-flight prepares for a drastically changed financial outlook brought on by the coronavirus pandemic.

A federal indictment was unsealed today in U.S. District Court for the District of Oregon charging Harold James Nicholson, 58, of Sheridan, Ore., and Nathaniel James Nicholson, 24, of Eugene, Ore., with two counts of Conspiracy, one count of Acting as Agents of a Foreign Government, and four counts of Money Laundering.

A former State Department official and his wife have been arrested on charges of serving as illegal agents of the Cuban government for nearly 30 years and conspiring to provide classified U.S. information to the Cuban government.

Sheri Redekker Barry and Warren Thomas Barry, a wife and husband who are both real estate agents in Fort Myers, Fla., have been sentenced to prison for conspiracy and failure to file tax returns. U.S. District Court Judge John E. Steele on Monday sentenced Sheri Barry to 36 months in prison and Warren Barry to 24 months in prison. The court also ordered the Barrys to pay restitution in the amount of $555,728.

While no words can lessen the sorrow being felt today by these families, I hope their loved ones know they have the unending respect and gratitude of this nation. They certainly have mine.

As part of the Department of Justice’s ongoing initiative to confront intellectual property (IP) crimes, Acting Deputy Attorney General Gary G. Grindler announced today the appointment of 15 new Assistant U.S. Attorney (AUSA) positions and 20 FBI Special Agents to be dedicated to combating domestic and international IP crimes.

Eight individuals were arrested Sunday for allegedly carrying out long-term, “deep-cover” assignments in the United States on behalf of the Russian Federation.

Ten individuals pleaded guilty today in Manhattan federal court to conspiring to serve as unlawful agents of the Russian Federation within the United States and will be immediately expelled from the United States.

Secretary of Homeland Security Janet Napolitano and Attorney General Eric Holder today met to discuss the shooting by unknown assailants of two U.S. Immigration and Customs Enforcement (ICE) special agents in the line of duty yesterday while driving in Mexico.

The Departments of Justice, State and Homeland Security today jointly announced a reward of up to $5 million for information leading to the arrest and/or conviction of individuals allegedly responsible for the murder of U.S. Immigration and Customs Enforcement (ICE) Homeland Security Investigations (HSI) Special Agent Jaime Zapata and the attempted murder of ICE HSI Special Agent Victor Avila.

The Justice Department’s National Security Division today announced the launch of a system for the electronic filing of registration statements and supplements with the Justice Department under the Foreign Agents Registration Act (FARA).

Two individuals have been charged with participating in a long-term conspiracy to act as agents of the Pakistani government in the United States without disclosing their affiliation with the Pakistani government as required by law.

Yumeitrius Manuel and Margaret Kirksey, both of Montgomery, Ala., were indicted by a federal grand jury today on charges of conspiracy, identity theft, wire fraud, false claims and lying to federal agents.

Eight former executives and agents of Siemens AG and its subsidiaries have been charged for allegedly engaging in a decade-long scheme to bribe senior Argentine government officials to secure, implement and enforce a $1 billion contract with the Argentine government to produce national identity cards.

Julian Zapata Espinoza, also known as “Piolin,” 32, pleaded guilty today to the murder of U.S. Immigration and Customs Enforcement (ICE) Special Agent Jaime Zapata and the attempted murder of ICE Special Agent Victor Avila in Mexico.

Southfield, Mich., resident Bashar Saroki pleaded guilty to filing a false tax return and selling drug paraphernalia, the Justice Department and the Internal Revenue Service (IRS) announced today.

Federal agents arrested Bryan D’Antonio and Charles Wayne Farris for operating the Rodis Law Group and America’s Law Group, businesses that allegedly offered bogus loan modification assistance to struggling homeowners; and Attorney Ronald Rodis surrendered to federal agents on for his alleged role in the operation.

Two former Miami real estate agents were sentenced today for their roles in a $2.4 million mortgage fraud scheme.

Bashar Saroki, a resident of Southfield, Mich., was sentenced today in the U.S. District Court for the Eastern District of Michigan to serve 30 months in prison to be followed by one year of supervised release, the Justice Department and the Internal Revenue Service announced.

Following his recent visit to Chicago where he participated in a roundtable discussion with Mayor Emanuel on recent reductions in youth violence, Attorney General Eric Holder today announced plans to send seven additional Bureau of Alcohol, Tobacco, Firearms and Explosives (ATF), agents to the field division office in Chicago

They created their own path. Will you create yours?

They created their own path. Will you create yours?

Imports - Coloring Agents & Photographic Chemicals (Census) in the United States increased to 1236.45 USD Million in March from 1180.53 USD Million in February of 2020. Imports - Coloring Agents & Photographic Chemicals in the United States averaged 632.30 USD Million from 1989 until 2020, reaching an all time high of 1260.98 USD Million in December of 2018 and a record low of 160.16 USD Million in March of 1989. This page includes a chart with historical data for the United States Imports of Coloring Agents & Photographic Chemica.

Imports Intra Eu - Soaps, Organic Agents, Lubricants, Waxes in the United Kingdom decreased to 119.70 GBP Million in February from 135.12 GBP Million in January of 2020. Imports Intra Eu - Soaps, Organic Agents, Lubrican in the United Kingdom averaged 79.98 GBP Million from 1996 until 2020, reaching an all time high of 162.57 GBP Million in October of 2019 and a record low of 28.96 GBP Million in December of 1996. This page includes a chart with historical data for the United Kingdom Imports of Intra EU - Soaps, Organic Agents, Lubr.

The Argentine has become one of the most-sought after players on the planet after shining for Inter Milan this season - scoring 16 goals and providing four assists in just 31 appearances.

OLIVER HOLT - CHIEF SPORTS WRITER: The Premier League, we are told, is worried that it is looking 'petulant' and 'ridiculous' in the face of the coronavirus crisis. It is right to be worried.

A dozen Russian intelligence officers are facing new U.S. federal indictments alleging they hacked into American computers with the intention of interfering with the 2016 election.

News of the indictments was announced at the Justice Department in Washington, DC during a press conference held by Deputy Attorney General Rod Rosenstein.

Savills predicts that the coronavirus crisis could mean a drop in London house values of up to 10 per cent, bringing the average price from £483,922 down to £435,529.

Erick Diaz, a 26-year-old Mexican national, was shot by the immigration and customs agents in Brooklyn on Thursday as they were trying to arrest his mother's boyfriend.

Verónica Carmen Lara-Márquez, who is three months pregnant, was briefly detained by ICE last week in Philadelphia moments after leaving her four-year-old daughter at a school.

Maria De Los Angel Sanz Pimentel, a Dominican woman who is allegedly in the United States without a work visa, was taken into custody by several ICE agents after a raid in Brooklyn on March 1.

Border patrol agents at the Chula Vista Border Patrol Station near San Diego, California, have come under fire over the treatment of a 27-year-old Guatemalan woman when she delivered her baby.

CBP agents detained and quickly deported two Honduran migrants who were found hiding in the trunk of a car that was stopped Sunday near Gila Bend, Arizona.

MATT HUGHES - AHEAD OF THE GAME: The prospects for Saudi Arabia's proposed £340million takeover of Newcastle have not been helped by Mike Ashley receiving financial advice.

MATT HUGHES - AHEAD OF THE GAME: We round up hidden stories as agents attempt to sign up Rashford and Arsenal ban stewards from drinking coffee from their club sponsor to cut costs.

Gareth Bale has no intention of departing Real Madrid in the near future and even plans on having another full season in LaLiga, according to his agent.

There has been 'a noticeable pick-up' in the housing market since Boris Johnson defeated Labour's Jeremy Corbyn in December, the Royal Institution of Chartered Surveyors said.

Monday's new Inspector General report on the FBI showcased messages shared between pro-Trump officials too.