To effectively control the spread of COVID-19, it is essential that all jurisdictions have the capacity to rapidly contact trace all close contacts of each and every case. We describe the early experience in the City and County of San Francisco, where contact tracing capability was rapidly expanded to respond to COVID-19. Important prerequisites to scale up included rapid expansion of the COVID-19 contact tracing workforce, a comprehensive training and onboarding program, and the institution of effective performance management metrics. The San Francisco model for contact tracing, including focusing on rigorous training, recruiting, and partnering with community-based organizations from diverse, affected communities, is an inclusive approach relevant to other jurisdictions and settings.

Cancer cells have epigenetic alterations that are known to drive cancer progression. The reversibility of the epigenetic posttranslational modifications on chromatin and DNA renders targeting these modifications an attractive means for cancer therapy. Cellular epigenetic status interacts with cell metabolism, and we are now beginning to understand the nature of how this interaction occurs and the biological contexts that mediate its function. Given the tremendous interest in understanding and targeting metabolic reprogramming in cancer, this nexus also provides opportunities for exploring the liabilities of cancers. This review summarizes recent developments in our understanding of the interaction of cancer metabolism and epigenetics.

Improving plants' ability to survive under drought is of great importance to the horticultural industry. The plant hormone gibberellic acid (GA) mediates diverse aspects of plant growth and development. The Arabidopsis gibberellin acid insensitive mutant gai-1 displays reduced plant height, altered GA response, and enhanced drought resistance. However, over-expression of gai-1 using the constitutive 35S promoter results in dwarf plants with drought resistance. Here, we tested the hypothesis that the temporary inhibition of cell growth caused by inducible expression of the gai-1 gene would lead to better drought resistance and improve crop productivity without an undesirable dwarf phenotype. We generated transgenic plants in which the gai-1 gene was over-expressed in petunia, under a stress-inducible RD29A promoter from Arabidopsis. When these plants were subjected to limited irrigation and drought treatments, transgenic plants showed phenotypes of darker green leaves and compact flowers compared to the wild type plants. Importantly, these transgenic plants recovered sooner than wild type and the empty vector-transformed control plants. This study provides evidence that temporary inhibition of cell growth caused by over-expression of the gai-1 mutant gene with a drought stress-inducible promoter leads to better drought resistance when the plants experience drought conditions.

Since stem elongation is a gibberellic acid (GA) response, GA inhibitors are commonly used to control plant height in the production of potted ornamentals and bedding plants. In this study, we investigated interfering with GA signaling by using molecular techniques as an alternative approach. We isolated three putative GID1 genes (PhGID1A, PhGID1B and PhGID1C) encoding GA receptors from petunia. Virus-induced gene silencing (VIGS) of these genes results in stunted growth, dark-green leaves and late-flowering. We also isolated the gai mutant gene (gai-1) from Arabidopsis. We have generated transgenic petunia plants in which the gai mutant protein is over-expressed under the control of a dexamethasone-inducible promoter. This system permits induction of the dominant Arabidopsis gai mutant gene at a desired stage of plant development in petunia plants by the application of dexamethasone (Dex). The induction of gai in Dex-treated T1 petunia seedlings caused dramatic growth retardation with short internodes.

Authorship inequity exists in global health research and can be representative of unequal partnerships. Previous studies showed that low-income and middle-income country (LMIC) authors are under-represented in publications from global collaborative research between LMIC and high-income countries (HIC). However, there are little data on trends for how specific HIC institutions are performing concerning equitable authorship. We used Web of Science to find published articles affiliated with the University of California, San Francisco (UCSF), where an LMIC was referred to in the title, abstract or keywords from 2008 to 2021. The country affiliation of each author for all included articles was grouped based on World Bank data. A total of 5805 articles were included. On average, 53.6% (n=3109) of UCSF affiliated articles had at least one low-income country (LIC) or LMIC author; however, this number increased from 43.2% (n=63) in 2008 to 63.3% (n=421) in 2021. Overall, 16.3% (n=948) of UCSF affiliated articles had an LIC or LMIC researcher as the first author, 18.8% (n=1,059) had an LIC or LMIC researcher as second author, and 14.2% (n=820) had an LIC or LMIC researcher as last author. As long as manuscripts produced by UCSF have no LIC or LMIC authors included the universitys commitment to authentic equity is undermined. Global health partnerships cannot be equitable without changing authorship trends between HIC and LMIC institutions.

Background

The tuberculosis targets for the UN Sustainable Development Goals (SDGs) call for a 90% reduction in tuberculosis deaths by 2030, compared with 2015, but meeting this target now seems highly improbable. To assess the economic impact of not meeting the target until 2045, we estimated full-income losses in 120 countries, including those due to excess deaths resulting from COVID-19-related disruptions to tuberculosis services, for the period 2020-50.

Methods

Annual mortality risk changes at each age in each year from 2020 to 2050 were estimated for 120 countries. This risk change was then converted to full-income risk by calculating a population-level mortality risk change and multiplying it by the value of a statistical life-year in each country and year. As a comparator, we assumed that current rates of tuberculosis continue to decline through the period of analysis. We calculated the full-income losses, and mean life expectancy losses per person, at birth and at age 35 years, under scenarios in which the SDG targets are met in 2030 and in 2045. We defined the cost of inaction as the difference in full-income losses and tuberculosis mortality between these two scenarios.

Findings

From 2020 to 2050, based on the current annual decrease in tuberculosis deaths of 2%, 31·8 million tuberculosis deaths (95% uncertainty interval 25·2 million-39·5 million) are estimated to occur, corresponding to an economic loss of US$17·5 trillion (14·9 trillion-20·4 trillion). If the SDG tuberculosis mortality target is met in 2030, 23·8 million tuberculosis deaths (18·9 million-29·5 million) and $13·1 trillion (11·2 trillion-15·3 trillion) in economic losses can be avoided. If the target is met in 2045, 18·1 million tuberculosis deaths (14·3 million-22·4 million) and $10·2 trillion (8·7 trillion-11·8 trillion) can be avoided. The cost of inaction of not meeting the SDG tuberculosis mortality target until 2045 (vs 2030) is, therefore, 5·7 million tuberculosis deaths (5·1 million-8·1 million) and $3·0 trillion (2·5 trillion-3·5 trillion) in economic losses. COVID-19-related disruptions add $290·3 billion (260·2 billion-570·1 billion) to this cost.

Interpretation

Failure to achieve the SDG tuberculosis mortality target by 2030 will lead to profound economic and health losses. The effects of delay will be greatest in sub-Saharan Africa. Affected countries, donor nations, and the private sector should redouble efforts to finance tuberculosis programmes and research because the economic dividend of such strategies is likely to be substantial.

Funding

None.

Hepatitis C virus (HCV) is the most common blood-borne infection in the United States and is of concern in older adults. HCV infection is associated with not only hepatic but also extrahepatic comorbidities common to the aging patient including diabetes, kidney and cardiovascular diseases, and neurocognitive impairment. The effect of direct-acting antiviral agents to treat HCV on these outcomes is limited. This article summarizes the literature regarding the epidemiology and natural history of HCV infection; the impact of age on clinical outcomes in HCV-infected persons; and current knowledge regarding safety and efficacy of HCV treatment regimens in the older patient.

Flower senescence is initiated by developmental and environmental signals, and regulated by gene transcription. A homeodomain-leucine zipper transcription factor, PhHD-Zip, is up-regulated during petunia flower senescence. Virus-induced gene silencing of PhHD-Zip extended flower life by 20% both in unpollinated and pollinated flowers. Silencing PhHD-Zip also dramatically reduced ethylene production and the abundance of transcripts of genes involved in ethylene (ACS, ACO), and ABA (NCED) biosynthesis. Abundance of transcripts of senescence-related genes (SAG12, SAG29) was also dramatically reduced in the silenced flowers. Over-expression of PhHD-Zip accelerated petunia flower senescence. Furthermore, PhHD-Zip transcript abundance in petunia flowers was increased by application of hormones (ethylene, ABA) and abiotic stresses (dehydration, NaCl and cold). Our results suggest that PhHD-Zip plays an important role in regulating petunia flower senescence.

One of the hallmarks of cancer is the ability to reprogram cellular metabolism to increase the uptake of necessary nutrients such as glucose and glutamine. Driven by oncogenes, cancer cells have increased glutamine uptake to support their highly proliferative nature. However, as cancer cells continue to replicate and grow, they lose access to vascular tissues and deplete local supply of nutrients and oxygen. We previously showed that many tumor cells situate in a low glutamine microenvironment in vivo, yet the mechanisms of how they are able to adapt to this metabolic stress are still not fully understood. Here, we report that IκB-kinase β (IKKβ) is needed to promote survival and its activation is accompanied by phosphorylation of the metabolic sensor, p53, in response to glutamine deprivation. Knockdown of IKKβ decreases the level of wild-type and mutant p53 phosphorylation and its transcriptional activity, indicating a novel relationship between IKKβ and p53 in mediating cancer cell survival in response to glutamine withdrawal. Phosphopeptide mass spectrometry analysis further reveals that IKKβ phosphorylates p53 on Ser392 to facilitate its activation upon glutamine deprivation, independent of the NF-κB pathway. The results of this study offer an insight into the metabolic reprogramming in cancer cells that is dependent on a previously unidentified IKKβ-p53 signaling axis in response to glutamine depletion. More importantly, this study highlights a new therapeutic strategy for cancer treatment and advances our understanding of adaptive mechanisms that could lead to resistance to current glutamine targeting therapies.

Application of thidiazuron (N-phenyl-N'-1,2,3-thiadiazol-5-ylurea, TDZ), a cytokinin analog, to inhibit the leaf yellowing that occurs after pinching potted rose plants, resulted in compact plants with shorter shoots and thicker internodes. Two weeks after treatment with 100 μM of TDZ, new shoots were half as long as those in control plants, and stem diameters were about 40% greater. This effect of TDZ is associated with changes in cell architecture. Although TDZ treatment stimulated ethylene production by the plants, inhibitors of ethylene biosynthesis (2-aminoethoxyvinyl glycine) or action (silver thiosulfate) did not affect the response of plants to TDZ. We found that TDZ treatment significantly suppressed the expression of bioactive gibberellic acid (GA) biosynthesis genes encoding GA3 and GA20 oxidases and slightly increased the expression of GA catabolism genes encoding GA2 oxidase. Application of GA₃ and TDZ together resulted in normal elongation growth, although stem diameters were still somewhat thicker. Our results suggest that TDZ regulates shoot elongation and stem enlargement in potted rose plants through the modulation of bioactive GA biosynthesis.