Patient-derived xenograft (PDX) models in basic and translational breast cancer research

Patient-derived xenograft (PDX) models of a growing spectrum of cancers are rapidly supplanting long-established traditional cell lines as preferred models for conducting basic and translational preclinical research. In breast cancer, to complement the now curated collection of approximately 45 long-established human breast cancer cell lines, a newly formed consortium of academic laboratories, currently from Europe, Australia, and North America, herein summarizes data on over 500 stably transplantable PDX models representing all three clinical subtypes of breast cancer (ER+, HER2+, and "Triple-negative" (TNBC)). Many of these models are well-characterized with respect to genomic, transcriptomic, and proteomic features, metastatic behavior, and treatment response to a variety of standard-of-care and experimental therapeutics. These stably transplantable PDX lines are generally available for dissemination to laboratories conducting translational research, and contact information for each collection is provided. This review summarizes current experiences related to PDX generation across participating groups, efforts to develop data standards for annotation and dissemination of patient clinical information that does not compromise patient privacy, efforts to develop complementary data standards for annotation of PDX characteristics and biology, and progress toward "credentialing" of PDX models as surrogates to represent individual patients for use in preclinical and co-clinical translational research. In addition, this review highlights important unresolved questions, as well as current limitations, that have hampered more efficient generation of PDX lines and more rapid adoption of PDX use in translational breast cancer research

Metabolic Syndrome and Acute Respiratory Distress Syndrome in Hospitalized Patients With COVID-19

Importance: Obesity, diabetes, and hypertension are common comorbidities in patients with severe COVID-19, yet little is known about the risk of acute respiratory distress syndrome (ARDS) or death in patients with COVID-19 and metabolic syndrome. Objective: To determine whether metabolic syndrome is associated with an increased risk of ARDS and death from COVID-19. Design, setting, and participants: This multicenter cohort study used data from the Society of Critical Care Medicine Discovery Viral Respiratory Illness Universal Study collected from 181 hospitals across 26 countries from February 15, 2020, to February 18, 2021. Outcomes were compared between patients with metabolic syndrome (defined as ≥3 of the following criteria: obesity, prediabetes or diabetes, hypertension, and dyslipidemia) and a control population without metabolic syndrome. Participants included adult patients hospitalized for COVID-19 during the study period who had a completed discharge status. Data were analyzed from February 22 to October 5, 2021. Exposures: Exposures were SARS-CoV-2 infection, metabolic syndrome, obesity, prediabetes or diabetes, hypertension, and/or dyslipidemia. Main outcomes and measures: The primary outcome was in-hospital mortality. Secondary outcomes included ARDS, intensive care unit (ICU) admission, need for invasive mechanical ventilation, and length of stay (LOS). Results: Among 46 441 patients hospitalized with COVID-19, 29 040 patients (mean [SD] age, 61.2 [17.8] years; 13 059 [45.0%] women and 15713 [54.1%] men; 6797 Black patients [23.4%], 5325 Hispanic patients [18.3%], and 16 507 White patients [57.8%]) met inclusion criteria. A total of 5069 patients (17.5%) with metabolic syndrome were compared with 23 971 control patients (82.5%) without metabolic syndrome. In adjusted analyses, metabolic syndrome was associated with increased risk of ICU admission (adjusted odds ratio [aOR], 1.32 [95% CI, 1.14-1.53]), invasive mechanical ventilation (aOR, 1.45 [95% CI, 1.28-1.65]), ARDS (aOR, 1.36 [95% CI, 1.12-1.66]), and mortality (aOR, 1.19 [95% CI, 1.08-1.31]) and prolonged hospital LOS (median [IQR], 8.0 [4.2-15.8] days vs 6.8 [3.4-13.0] days; P \u3c .001) and ICU LOS (median [IQR], 7.0 [2.8-15.0] days vs 6.4 [2.7-13.0] days; P \u3c .001). Each additional metabolic syndrome criterion was associated with increased risk of ARDS in an additive fashion (1 criterion: 1147 patients with ARDS [10.4%]; P = .83; 2 criteria: 1191 patients with ARDS [15.3%]; P \u3c .001; 3 criteria: 817 patients with ARDS [19.3%]; P \u3c .001; 4 criteria: 203 patients with ARDS [24.3%]; P \u3c .001). Conclusions and relevance: These findings suggest that metabolic syndrome was associated with increased risks of ARDS and death in patients hospitalized with COVID-19. The association with ARDS was cumulative for each metabolic syndrome criteria present

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Metabolic Syndrome and Acute Respiratory Distress Syndrome in Hospitalized Patients With COVID-19.

Obesity, diabetes, and hypertension are common comorbidities in patients with severe COVID-19, yet little is known about the risk of acute respiratory distress syndrome (ARDS) or death in patients with COVID-19 and metabolic syndrome. To determine whether metabolic syndrome is associated with an increased risk of ARDS and death from COVID-19. This multicenter cohort study used data from the Society of Critical Care Medicine Discovery Viral Respiratory Illness Universal Study collected from 181 hospitals across 26 countries from February 15, 2020, to February 18, 2021. Outcomes were compared between patients with metabolic syndrome (defined as ≥3 of the following criteria: obesity, prediabetes or diabetes, hypertension, and dyslipidemia) and a control population without metabolic syndrome. Participants included adult patients hospitalized for COVID-19 during the study period who had a completed discharge status. Data were analyzed from February 22 to October 5, 2021. Exposures were SARS-CoV-2 infection, metabolic syndrome, obesity, prediabetes or diabetes, hypertension, and/or dyslipidemia. The primary outcome was in-hospital mortality. Secondary outcomes included ARDS, intensive care unit (ICU) admission, need for invasive mechanical ventilation, and length of stay (LOS). Among 46 441 patients hospitalized with COVID-19, 29 040 patients (mean [SD] age, 61.2 [17.8] years; 13 059 [45.0%] women and 15713 [54.1%] men; 6797 Black patients [23.4%], 5325 Hispanic patients [18.3%], and 16 507 White patients [57.8%]) met inclusion criteria. A total of 5069 patients (17.5%) with metabolic syndrome were compared with 23 971 control patients (82.5%) without metabolic syndrome. In adjusted analyses, metabolic syndrome was associated with increased risk of ICU admission (adjusted odds ratio [aOR], 1.32 [95% CI, 1.14-1.53]), invasive mechanical ventilation (aOR, 1.45 [95% CI, 1.28-1.65]), ARDS (aOR, 1.36 [95% CI, 1.12-1.66]), and mortality (aOR, 1.19 [95% CI, 1.08-1.31]) and prolonged hospital LOS (median [IQR], 8.0 [4.2-15.8] days vs 6.8 [3.4-13.0] days; P < .001) and ICU LOS (median [IQR], 7.0 [2.8-15.0] days vs 6.4 [2.7-13.0] days; P < .001). Each additional metabolic syndrome criterion was associated with increased risk of ARDS in an additive fashion (1 criterion: 1147 patients with ARDS [10.4%]; P = .83; 2 criteria: 1191 patients with ARDS [15.3%]; P < .001; 3 criteria: 817 patients with ARDS [19.3%]; P < .001; 4 criteria: 203 patients with ARDS [24.3%]; P < .001). These findings suggest that metabolic syndrome was associated with increased risks of ARDS and death in patients hospitalized with COVID-19. The association with ARDS was cumulative for each metabolic syndrome criteria present

Impact Craters and Meteorites: The Egyptian Record

This chapter provides an account of the present Egyptian impact cratering record as well as an overview of the Egyptian meteorite collection. The 45-m-diameter Kamil crater in the East Uweinat District in southwestern Egypt is so far the only confirmed impact crater in Egypt. Due to its exceptional state of preservation Kamil can be considered a typestructure for small-scale impacts on Earth. Enigmatic types of natural glasses including the Libyan Desert glass found in the Great Sand Sea and the Dakhleh glass found near Dakhla Oasis (note that Dakhla, Dakhleh and Dakhla are synonyms) may be products of low-altitude airbursts of large and fragile cometary or asteroidal impactors. A number of circular, cratershaped geological structures superficially resembling impact craters are discussed. To date the Egyptian meteorite collection totals 2 falls, including the ~10 kg Martian meteorite Nakhla that has served as a keystone for the understanding of magmatic differentiation processes on Mars, and 76 finds. With the exception of a minority of incidental findings, most Egyptian meteorite finds (~75%) were recovered over the last ~30 years from three dense meteorite collection areas, namely the El-Shaik Fedl, Great Sand Sea and Marsa Alam fields. The exceptional exposures of the Precambrian basement and Paleozoic to Cenozoic sedimentary covers in Egypt offer a good opportunity for the identification of new impact structures. Likewise, Egypt’s vast rocky desert surfaces are of great potential for the collection of meteorites through systematic searches. These prospects are fundamental ingredients for fostering the ongoing development of meteoritics and planetary science in Egypt as disciplines for future scientific endeavor in Africa