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On Twitter, there have been 113 million unique authors sharing everything from messages from news reports and commentary on COVID-19, to views on quarantining measures, speculation on the source of the virus and details of home-brewed cures. (Neither works.) As scientists rushed to investigate the new virus, conspiracy theories started to circulate about whether it was a naturally evolved new pathogen, one that inadvertently slipped out of a high-security laboratory in Wuhan, China, or one that was deliberately created for biowarfare - an idea deemed plausible by some in the current context of geopolitics and deepening tensions between the United States and China. On 30 December, Li Wenliang, a young ophthalmologist in Wuhan posted a message to colleagues that tried to call attention to a severe acute respiratory syndrome (SARS)-like illness that was brewing in his hospital.

Post-curing is intended to improve strength, elevate glass transition, and reduce residual stress and outgassing in thermosets. Also, experiments indicate post-curing temperatures lead to ether crosslinks and backbone dehydration. These results informed molecular dynamics methods to represent them and compare the resulting thermomechanical effects. Diglycidyl ether of bisphenol A (DGEBA)-diamino diphenyl sulfone (DDS) systems were examined. Independent variables were resin length, stoichiometry, and reaction type (i.e., amine addition, etherification, and dehydration). Etherification affected excess epoxide systems most. These were strengthened and became strain hardening. Systems which were both etherified and dehydrated were most consistent with results of post-curing experiments. Dehydration stiffened and strengthened systems with the longer resin molecules due to their intermediate hydroxyl groups for crosslinking. Changes in the concavity of functions fit to the specific volume versus temperature were used to detect thermal transitions. Etherification generally increased transition temperatures. Dehydration resulted in more transitions.

Material jetting (MJ) technology is an additive manufacturing method that selectively cures liquid photopolymer to build functional parts. The use of MJ technology has increased in popularity and been adapted by different industries, ranging from biomedicine and dentistry to manufacturing and aviation, thanks to its advantages in printing parts with high dimensional accuracy and low surface roughness. To better understand the MJ technology, it is essential to address the capabilities, applications and the usage areas of MJ. Additionally, the comparison of MJ with alternative methods and its limitations need to be explained. Moreover, the parameters influencing the dimensional accuracy and mechanical properties of MJ printed parts should be stated. This paper aims to review these critical aspects of MJ manufacturing altogether to provide an overall insight into the state of the art of MJ.

Although the Office of The National Coordinator for Health Information Technology’s (ONC) Information Blocking Provision in the Cures Act Final Rule is an important step forward in providing patients free and unfettered access to their electronic health information (EHI), in the contexts of multiuser electronic health record (EHR) access and proxy access, concerns on the potential for harm in adolescent care contexts exist. We describe how the provision could erode patients’ (both adolescent and older patients alike) trust and willingness to seek care. The rule’s preventing harm exception does not apply to situations where the patient is a minor and the health care provider wishes to restrict a parent’s or guardian’s access to the minor’s EHI to avoid violating the minor’s confidentiality and potentially harming patient-clinician trust. This may violate previously developed government principles in the design and implementation of EHRs for pediatric care. Creating legally acceptable workarounds by means such as duplicate “shadow charting” will be burdensome (and prohibitive) for health care providers. Under the privacy exception, patients have the opportunity to request information to not be shared; however, depending on institutional practices, providers and patients may have limited awareness of this exception. Notably, the privacy exception states that providers cannot “improperly encourage or induce a patient’s request to block information.” Fearing being found in violation of the information blocking provisions, providers may feel that they are unable to guide patients navigating the release of their EHI in the multiuser or proxy access setting. ONC should provide more detailed guidance on their website and targeted outreach to providers and their specialty organizations that care for adolescents and other individuals affected by the Cures Act, and researchers should carefully monitor charting habits in these multiuser or proxy access situations.

[Display omitted] •Cure indicators estimated from the French cancer registries database.•Time-to-cure: time at which the probability of belonging to the cured group is 95%.•Time-to-cure less than 10 years for most of the 27 studied cancer sites.•Time-to-cure less than 5 years for thyroid and testis cancers and skin melanoma.•Cancer survivors should access to credit without being overtaxed. In cancer care, the cure proportion (P) and time-to-cure (TTC) are important indicators for practitioners, patients, and healthcare policy makers. The recent definition of TTC as the time at which the probability of belonging to the cured group reaches 95% was used for the first time. The data stem from the common database of French cancer registries including 335,358 solid tumours diagnosed between 1995 and 2009 at 27 sites. P and TTC were estimated through a flexible parametric net survival cure model for each cancer site, sex, and age at diagnosis with acceptable assumption of cure (excess mortality rate ≤0.05). TTC was ≤5 years and P was >80% for skin melanoma and thyroid and testis cancers. It was 0 for testis cancer in men <55 and for thyroid cancer in men <45 and women <65. TTC was between 5 and 10 years for all digestive cancers except small intestine and all gynaecologic cancers except breast. It was ≥10 years in prostate, breast, and urinary tract. The range of P according to age and sex was 37–79% for urinary tract 72–88% for prostate and breast, 4–16% for pancreatic and 47–62% for colorectal cancer. Time-to-cure was estimated for the first time from a large national database and individual probabilities of cure. It was 0 in the younger patients with testis or thyroid cancer and <12 years in most cancer sites. These results should help improve access to credit and insurance for patients still alive past the estimated TTCs.

35 years since identification of HIV as the causative agent of AIDS, and 35 million deaths associated with this disease, significant effort is now directed towards the development of potential cures. Current anti-retroviral (ART) therapies for HIV/AIDS can suppress virus replication to undetectable levels, and infected individuals can live symptom free so long as treatment is maintained. However, removal of therapy allows rapid re-emergence of virus from a highly stable reservoir of latently infected cells that exist as a barrier to elimination of the infection with current ART. Prospects of a cure for HIV infection are significantly encouraged by two serendipitous cases where individuals have entered remission following stem cell transplantation from compatible HIV-resistant donors. However, development of a routine cure that could become available to millions of infected individuals will require a means of specifically purging cells harboring latent HIV, preventing replication of latent provirus, or destruction of provirus genomes by gene editing. Elimination of latently infected cells will require a means of exposing this population, which may involve identification of a natural specific biomarker or therapeutic intervention to force their exposure by reactivation of virus expression. Accordingly, the proposed “Shock and Kill” strategy involves treatment with latency-reversing agents (LRA) to induce HIV provirus expression thus exposing these cells to killing by cellular immunity or apoptosis. Current efforts to enable this strategy are directed at developing improved combinations of LRA to produce broad and robust induction of HIV provirus and enhancing the elimination of cells where replication has been reactivated by targeted immune modulation. Alternative strategies may involve preventing re-emergence virus from latently infected cells by “Lock and Block” intervention, where transcription of provirus is inhibited to prevent virus spread or disruption of the HIV provirus genome by genome editing.

KRAS is the most frequently mutated oncogene in cancer and encodes a key signalling protein in tumours 1 , 2 . The KRAS(G12C) mutant has a cysteine residue that has been exploited to design covalent inhibitors that have promising preclinical activity 3 – 5 . Here we optimized a series of inhibitors, using novel binding interactions to markedly enhance their potency and selectivity. Our efforts have led to the discovery of AMG 510, which is, to our knowledge, the first KRAS(G12C) inhibitor in clinical development. In preclinical analyses, treatment with AMG 510 led to the regression of KRAS G12C tumours and improved the anti-tumour efficacy of chemotherapy and targeted agents. In immune-competent mice, treatment with AMG 510 resulted in a pro-inflammatory tumour microenvironment and produced durable cures alone as well as in combination with immune-checkpoint inhibitors. Cured mice rejected the growth of isogenic KRAS G12D tumours, which suggests adaptive immunity against shared antigens. Furthermore, in clinical trials, AMG 510 demonstrated anti-tumour activity in the first dosing cohorts and represents a potentially transformative therapy for patients for whom effective treatments are lacking. Treatment of KRAS G12C -mutant cancer cells with the KRAS(G12C) inhibitor AMG 510 leads to durable response in mice, and anti-tumour activity in patients suggests that AMG 510 could be effective in patients for whom treatments are currently lacking.

This study investigates the effect of the curing mode (dual-cure vs. self-cure) of resin cements (four self-adhesive and seven conventional cements) on their flexural strength and flexural modulus of elasticity, alongside their shear bond strength to lithium disilicate ceramics (LDS). The study aims to determine the relationship between the bond strength and LDS, and the flexural strength and flexural modulus of elasticity of resin cements. Twelve conventional or adhesive and self-adhesive resin cements were tested. The manufacturer’s recommended pretreating agents were used where indicated. The shear bond strengths to LDS and the flexural strength and flexural modulus of elasticity of the cement were measured immediately after setting, after one day of storage in distilled water at 37 °C, and after 20,000 thermocycles (TC 20k). The relationship between the bond strength to LDS, flexural strength, and flexural modulus of elasticity of resin cements was investigated using a multiple linear regression analysis. For all resin cements, the shear bond strength, flexural strength, and flexural modulus of elasticity were lowest immediately after setting. A clear and significant difference between dual-curing and self-curing modes was observed in all resin cements immediately after setting, except for ResiCem EX. Regardless of the difference of the core-mode condition of all resin cements, flexural strengths were correlated with the LDS surface upon shear bond strengths (R2 = 0.24, n = 69, p < 0.001) and the flexural modulus of elasticity was correlated with them (R2 = 0.14, n = 69, p < 0.001). Multiple linear regression analyses revealed that the shear bond strength was 17.877 + 0.166, the flexural strength was 0.643, and the flexural modulus was (R2 = 0.51, n = 69, p < 0.001). The flexural strength or flexural modulus of elasticity may be used to predict the bond strength of resin cements to LDS.

When I draw, I make connections full of tides in this confusion of emotions. It frees me to think that I have created living solutions for today. I feel as if I have found a cure for despair.

Herpes simplex virus type 1 (HSV-1) is a leading cause of infectious blindness. Current treatments for HSV-1 do not eliminate the virus from the site of infection or latent reservoirs in the trigeminal ganglia. Here, we target HSV-1 genomes directly using mRNA-carrying lentiviral particles that simultaneously deliver SpCas9 mRNA and viral-gene-targeting guide RNAs (designated HSV-1-erasing lentiviral particles, termed HELP). We show that HELP efficiently blocks HSV-1 replication and the occurrence of herpetic stromal keratitis (HSK) in three different infection models. HELP was capable of eliminating the viral reservoir via retrograde transport from corneas to trigeminal ganglia. Additionally, HELP inhibited viral replication in human-derived corneas without causing off-target effects, as determined by whole-genome sequencing. These results support the potential clinical utility of HELP for treating refractory HSK. CRISPR–Cas9 eliminates herpes simplex virus both in the corneal infection site and in the viral reservoir of the trigeminal ganglia.