Coronavirus disease 2019 (COVID-19) is a global pandemic. In the USA, the burden of mortality and morbidity has fallen on minority populations. The understanding of the impact of this pandemic has been limited in Asian-Americans and Pacific Islanders (AAPIs), though disaggregated data suggest disproportionately high mortality rates. AAPIs are at high risk for COVID-19 transmission, in part due to their over-representation in the essential workforce, but also due to cultural factors, such as intergenerational residency, and other social determinants of health, including poverty and lack of health insurance. Some AAPI subgroups also report a high comorbidity burden, which may increase their susceptibility to more severe COVID-19 infection. Furthermore, AAPIs have encountered rising xenophobia and racism across the country, and we fear such discrimination only serves to exacerbate these rapidly emerging disparities in this community. We recommend interventions including disaggregation of mortality and morbidity data, investment in community-based healthcare, advocacy against discrimination and the use of non-inflammatory language, and a continued emphasis on underlying comorbidities, to ensure the protection of vulnerable communities and the navigation of this current crisis.
Background: There is growing evidence to support the hypothesis that radical treatment of pulmonary oligometastatic disease with stereotactic body radiation therapy (SBRT) can improve oncological outcomes. However, some reports suggest colorectal cancer (CRC) pulmonary metastases are associated with radioresistance. The present systematic review aimed to assess the local control (LC), overall survival (OS), and progression-free survival (PFS) of patients with CRC pulmonary metastases treated by SBRT. Secondary outcomes included assessment of peri-procedural complications and identification of prognostic factors on LC. Methods: Electronic databases were systematically searched from their dates of inception using predefined criteria. Summative statistical analysis was performed for patients with CRC pulmonary metastases, and comparative meta-analysis was performed for patients with CRC versus non-CRC pulmonary metastases. Results: Using predefined criteria, 18 relevant studies were identified from the existing literature. LC for CRC pulmonary metastases treated by SBRT at 1-, 2-, and 3-year were estimated to be 81%, 66%, and 60%, respectively. OS and PFS at 3-year were 52% and 13%, respectively. Patients with CRC pulmonary metastases were associated with significantly lower LC compared to non-CRC pulmonary metastases [HR, 2.93; 95% confidence interval (CI), 1.93-4.45; P<0.00001], but higher OS (HR, 0.61; 95% CI, 0.45-0.82; P=0.001). There were no reported periprocedural mortalities and low incidences of periprocedural morbidities. Conclusions: These findings may have implications for patient and treatment selection, dose fractionation, and support the hypothesis that CRC pulmonary metastases may require higher biological effective doses while respecting normal tissue constraints when treated with SBRT.
Objective: Stereotactic body radiation therapy (SBRT) is the preferred treatment modality for patients with inoperable early-stage non-small cell lung cancer. However, comparative outcomes between SBRT and surgery for high-risk patients remain controversial. The primary aim of the present meta-analysis was to assess overall survival in matched and unmatched patient cohorts undergoing SBRT or surgery. Secondary endpoints included cancer-specific survival, diseasefree survival, disease recurrence, and perioperative outcomes. Methods: A systematic review of relevant studies was performed through online databases using predefined criteria. The most updated studies were selected for meta-analysis according to unmatched and matched patient cohorts. Results: Thirty-two studies were identified in the systematic review, and 23 were selected for quantitative analysis. Surgery was associated with superior overall survival in both unmatched (odds ratio [OR], 2.49; 95% confidence interval [CI], 2.10–2.94; p<0.00001) and matched (OR, 1.71; 95% CI, 1.52–1.93; p<0.00001) cohorts. Subgroup analysis demonstrated superior overall survival for lobectomy and sublobar resection, compared with SBRT. In unmatched and matched cohorts, cancer-specific survival, disease-free survival, and freedom from locoregional recurrence were superior after surgery. However, SBRT was associated with fewer perioperative deaths. Conclusions: The current evidence suggests surgery is superior to SBRT in terms of mid- and long-term clinical outcomes; SBRT is associated with lower perioperative mortality. The improved outcomes after surgery, however, may be attributable at least in part to an imbalance of baseline characteristics. Future studies should aim to provide histopathological confirmation of malignancy and compare SBRT with minimally invasive anatomical resections.
Protein crosslinks occur endogenously such as modifications by ubiquitin‐like proteins for signaling, or exogenously through genetically encoded chemical crosslinkers (GECX) for studying elusive protein–protein interactions. However, it remains challenging to identify these protein crosslinks efficiently at the proteomic scale. Herein, software OpenUaa is developed for identifying protein crosslinks generated by genetically encoded unnatural amino acids and endogenous protein conjugation. OpenUaa features inclusive and open search capability, dramatically improving identification sensitivity and coverage. Integrating GECX with OpenUaa, the direct interactome of thioredoxin is identified in Escherichia coli cells, yielding 289 crosslinked peptides and corresponding to 205 direct binding protein of thioredoxin. These identified direct binders provide evidence for thioredoxin's regulation of redox state and mitochondria energy metabolism. When identifying endogenous conjugation of small ubiquitin‐like modifier (SUMO), OpenUaa also markedly improves coverage of SUMOylated peptides by ≈92%, revealing new SUMO targets. GECX–OpenUaa will enable efficient identification of direct interactomes of various proteins in live cells.
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