Non-bacterial thrombotic endocarditis (NBTE) denotes the presence of sterile non-infective vegetation on structurally normal, or subtly degenerate cardiac valves and is often associated with advanced malignancies. In gynaecological cancer in particular, NBTE has been most commonly associated with ovarian cancer.1,2 Here we report a rare but interesting case of NBTE in a patient with locally advanced cervical adenocarcinoma.

Objective: In Malaysia, a cytology based program for cervical screening was implemented in 1969. Unfortunately, pap smear uptake has been low. The most common barriers to screening were embarrassment, time constraint and poor awareness to screening. As Malaysia is transitioning from a cytology-based screening to self-sampling human papillomavirus (HPV) testing as the primary screening method, it is therefore important to assess the acceptability of this screening approach in this multiethnic setting. Methods: This was a cross-sectional study which recruited women aged 30–65 from several community-based cervical screening programs using self-sampling HPV testing across urban and suburban areas in all over Malaysia from April 2018 to May 2022. All women were instructed to self-collect vaginal samples for HPV testing using a dry flocked swab. All samples were genotyped on a clinically validated platform which allowed the detection of any high-risk HPV DNA. Approximately 2,000 women were randomly selected and interviewed to document their screening experience after the self-sampling procedure. Results: A total of 19,835 women participated in the community-based cervical screening program using self-sampling HPV testing. The major ethnic group was Malay (68.4%) followed by Chinese (16.4%) and Indians (9.9%). Of these, 1,113 (5.7%) were positive for any high-risk HPV infection whereas 371 (1.9%) did not yield valid HPV results due to insufficient human DNA. A total of 2,012 participants responded to an interview regarding their screening experience using self-sampling HPV testing. Among these women, 1,179 (58.5%) did not attend regular Pap smear screening. Out of those who had ever performed Pap smear, 83.2% of them indicated a preference towards self-sampling HPV testing over Pap smear. Furthermore, 99% of them were willing to repeat this screening test as a routine screening method in the future. More than 95% of women perceived self-sampling HPV testing as easy, convenient and not embarrassing. Additionally, more than 80% of women felt comfortable and confident collecting their vaginal samples. This implies that self-sampling HPV testing is highly acceptable in our setting. Conclusion HPV testing via self-collection method is highly acceptable and preferred over Pap smear in the Malaysian multiethnic population. It is a promising approach to increase screening coverage which is an essential key target to be achieved in order to eliminate cervical cancer in Malaysia.

The emergence of SARS-CoV-2 variants of concern and repeated outbreaks of coronavirus epidemics in the past two decades emphasize the need for next-generation pan-coronaviral therapeutics. Drugging the multi-functional papain-like protease (PLpro) domain of the viral nsp3 holds promise. However, none of the known coronavirus PLpro inhibitors has been shown to be in vivo active. Herein, we screened a structurally diverse library of 50,080 compounds for potential coronavirus PLpro inhibitors and identified a noncovalent lead inhibitor F0213 that has broad-spectrum anti-coronaviral activity, including against the Sarbecoviruses (SARS-CoV-1 and SARS-CoV-2), Merbecovirus (MERS-CoV), as well as the Alphacoronavirus (hCoV-229E and hCoV-OC43). Importantly, F0213 confers protection in both SARS-CoV-2-infected hamsters and MERS-CoV-infected human DPP4-knockin mice. F0213 possesses a dual therapeutic functionality that suppresses coronavirus replication via blocking viral polyprotein cleavage, as well as promoting antiviral immunity by antagonizing the PLpro deubiquitinase activity. Despite the significant difference of substrate recognition, mode of inhibition studies suggest that F0213 is a competitive inhibitor against SARS2-PLpro via binding with the 157K amino acid residue, whereas an allosteric inhibitor of MERS-PLpro interacting with its 271E position. Our proof-of-concept findings demonstrated that PLpro is a valid target for the development of broad-spectrum anti-coronavirus agents. The orally administered F0213 may serve as a promising lead compound for combating the ongoing COVID-19 pandemic and future coronavirus outbreaks.
Animals ; Coronavirus Papain-Like Proteases/antagonists & inhibitors* ; Cricetinae ; Humans ; Mice ; Pandemics ; SARS-CoV-2/enzymology* ; COVID-19 Drug Treatment