Perioperative Estrogen Hormonal Therapy Does Not Increase Venous Thromboembolism Risk In Facial Feminization Surgery.

BACKGROUND: Conflicting data exist regarding increased perioperative VTE risk while on feminizing hormone therapy. The effect has been poorly studied within the transgender population. Acute perioperative cessation of feminizing hormone therapy often leads to unpleasant side effects and exacerbates gender dysphoria in the perioperative period. We seek to identify the VTE incidence in patients undergoing facial feminization while continuing HRT throughout the time of surgery. METHODS: A 38-year retrospective cohort study within a two-surgeon practice (D.K.O. and J.C.D.) was designed to evaluate postoperative VTE in patients continuing hormone therapy. The primary outcome variable was identified as suffering a VTE postoperatively. RESULTS: 1,715 patients underwent facial feminization surgery within our search window. 953 patients met final inclusion criteria. 1 patient (0.10%) was diagnosed with a VTE postoperatively, comparable to reported literature rates for similar cosmetic and orthognathic procedures. The average Caprini score of all patients was 3.1±1.0 and the average case length was 491.9±111.0 minutes. Subgroup analysis of patients before and after internal practice changes identified 714 (77.7%) patients continuing full dose hormonal therapy perioperatively, 197 (20.7%) patients undergoing hormonal dose reduction to 25-50% perioperatively, and 8 patients who were either not taking hormonal therapy or stopped in the perioperative period. There was no significant difference in VTE incidence between the 3 subgroups (p > 0.99). CONCLUSIONS: Perioperative use of feminizing hormonal therapy does not increase risk for perioperative VTE in patients undergoing facial feminization surgery. Therefore, it is reasonable to continue these medications through the time of surgery.

Infantile Myofibromatosis of the Femoral Neck: A Case Report.

CASE: A 15-month-old boy who was being followed for developmental dysplasia of the hip because of breech presentation was discovered to have a solitary infantile myofibroma in the left femoral neck. The patient was avoiding weight-bearing on the affected extremity; thus, stabilization of the femoral neck was performed using a proximal femur locking plate. Postoperatively, he achieved all gross motor developmental milestones. CONCLUSION: This report is the first to describe a solitary infantile myofibroma in the femoral neck and demonstrates the utility of operative stabilization of these lesions.

Identification and targeting of treatment resistant progenitor populations in T-cell Acute Lymphoblastic Leukemia.

Refractoriness to initial chemotherapy and relapse after remission are the main obstacles to cure in T-cell Acute Lymphoblastic Leukemia (T-ALL). Biomarker guided risk stratification and targeted therapy have the potential to improve outcomes in high-risk T-ALL; however, cellular and genetic factors contributing to treatment resistance remain unknown. Previous bulk genomic studies in T-ALL have implicated tumor heterogeneity as an unexplored mechanism for treatment failure. To link tumor subpopulations with clinical outcome, we created an atlas of healthy pediatric hematopoiesis and applied single-cell multiomic (CITE-seq/snATAC-seq) analysis to a cohort of 40 cases of T-ALL treated on the Children's Oncology Group AALL0434 clinical trial. The cohort was carefully selected to capture the immunophenotypic diversity of T-ALL, with early T-cell precursor (ETP) and Near/Non-ETP subtypes represented, as well as enriched with both relapsed and treatment refractory cases. Integrated analyses of T-ALL blasts and normal T-cell precursors identified a bone-marrow progenitor-like (BMP-like) leukemia sub-population associated with treatment failure and poor overall survival. The single-cell-derived molecular signature of BMP-like blasts predicted poor outcome across multiple subtypes of T-ALL within two independent patient cohorts using bulk RNA-sequencing data from over 1300 patients. We defined the mutational landscape of BMP-like T-ALL, finding that NOTCH1 mutations additively drive T-ALL blasts away from the BMP-like state. We transcriptionally matched BMP-like blasts to early thymic seeding progenitors that have low NR3C1 expression and high stem cell gene expression, corresponding to a corticosteroid and conventional cytotoxic resistant phenotype we observed in ex vivo drug screening. To identify novel targets for BMP-like blasts, we performed in silico and in vitro drug screening against the BMP-like signature and prioritized BMP-like overexpressed cell-surface (CD44, ITGA4, LGALS1) and intracellular proteins (BCL-2, MCL-1, BTK, NF-κB) as candidates for precision targeted therapy. We established patient derived xenograft models of BMP-high and BMP-low leukemias, which revealed vulnerability of BMP-like blasts to apoptosis-inducing agents, TEC-kinase inhibitors, and proteasome inhibitors. Our study establishes the first multi-omic signatures for rapid risk-stratification and targeted treatment of high-risk T-ALL.

Multiomic Mapping of Acquired Chromosome 1 Copy-Number and Structural Variants to Identify Therapeutic Vulnerabilities in Multiple Myeloma.

PURPOSE: Chromosome 1 (chr1) copy-number abnormalities (CNA) and structural variants (SV) are frequent in newly diagnosed multiple myeloma (NDMM) and are associated with a heterogeneous impact on outcomes, the drivers of which are largely unknown. EXPERIMENTAL DESIGN: A multiomic approach comprising CRISPR, gene mapping of CNAs and SVs, methylation, expression, and mutational analysis was used to document the extent of chr1 molecular variants and their impact on pathway utilization. RESULTS: We identified two distinct groups of gain(1q): focal gains associated with limited gene-expression changes and a neutral prognosis, and whole-arm gains, which are associated with substantial gene-expression changes, complex genetics, and an adverse prognosis. CRISPR identified a number of dependencies on chr1 but only limited variants associated with acquired CNAs. We identified seven regions of deletion, nine of gain, three of chromothripsis (CT), and two of templated insertion (TI), which contain a number of potential drivers. An additional mechanism involving hypomethylation of genes at 1q may contribute to the aberrant gene expression of a number of genes. Expression changes associated with whole-arm gains were substantial and gene set enrichment analysis identified metabolic processes, apoptotic resistance, signaling via the MAPK pathway, and upregulation of transcription factors as being key drivers of the adverse prognosis associated with these variants. CONCLUSIONS: Multiple layers of genetic complexity impact the phenotype associated with CNAs on chr1 to generate its associated clinical phenotype. Whole-arm gains of 1q are the critically important prognostic group that deregulate multiple pathways, which may offer therapeutic vulnerabilities.

Incidence and Risk Factors for Retinal Detachment and Retinal Tear after Cataract Surgery: IRIS® Registry (Intelligent Research in Sight) Analysis.

Objective: To report the incidence of and evaluate demographic, ocular comorbidities, and intraoperative factors for rhegmatogenous retinal detachment (RRD) and retinal tear (RT) after cataract surgery in the American Academy of Ophthalmology IRIS® Registry (Intelligent Research in Sight). Design: Retrospective cohort study. Participants: Patients aged ≥ 40 years who underwent cataract surgery between 2014 and 2017. Methods: Multivariable logistic regression was used to evaluate demographic, comorbidity, and intraoperative factors associated with RRD and RT after cataract surgery. Main Outcome Measures: Incidence and risk factors for RRD or RT within 1 year of cataract surgery. Results: Of the 3 177 195 eyes of 1 983 712 patients included, 6690 (0.21%) developed RRD and 5489 (0.17%) developed RT without RRD within 1 year after cataract surgery. Multivariable logistic regression odds ratios (ORs) showed increased risk of RRD and RT, respectively, among men (OR 3.15; 95% confidence interval [CI], 2.99-3.32; P < 0.001 and 1.79; 95% CI, 1.70-1.89; P < 0.001), and younger ages compared with patients aged > 70, peaking at age 40 to 50 for RRD (8.61; 95% CI, 7.74-9.58; P < 0.001) and age 50 to 60 for RT (2.74; 95% CI, 2.52-2.98; P < 0.001). Increased odds of RRD were observed for procedure eyes with lattice degeneration (LD) (10.53; 95% CI, 9.82-11.28; P < 0.001), hypermature cataract (1.61; 95% CI, 1.06-2.45; P = 0.03), complex cataract surgery (1.52; 95% CI, 1.4-1.66; P < 0.001), posterior vitreous detachment (PVD) (1.24; 95% CI, 1.15-1.34; P < 0.001), and high myopia (1.2; 95% CI, 1.14-1.27; P < 0.001). Lattice degeneration conferred the highest odds of RT (43.86; 95% CI, 41.39-46.49; P < 0.001). Conclusion: In the IRIS Registry, RRD occurs in approximately 1 in 500 cataract surgeries in patients aged > 40 years within 1 year of surgery. The presence of LD conferred the highest odds for RRD and RT after surgery. Additional risk factors for RRD included male gender, younger age, hypermature cataract, PVD, and high myopia. These data may be useful during the informed consent process for cataract surgery and help identify patients at a higher risk of retinal complications. Financial Disclosures: The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Hydrophobic-Hydrophilic Block Copolymer Mediated Tuning of Halide Perovskite Photosensitive Device Stability and Efficiency.

The polymer additive strategy provides a facile and cost-effective way for passivating defects and trap sites at the grain boundaries and interfaces and acting as a barrier against the external degradation factors in perovskite-based devices. However, limited literature exists discussing the integration of hydrophobic and hydrophilic polymer additives in the form of a copolymer within the perovskite films. The inherent difference in the chemical structure of these polymers and their interaction with perovskite components and the environment leads to critical differences in the respective polymer-perovskite films. The current work utilizes both homopolymer and copolymer strategies to understand the effect of polystyrene (PS) and polyethylene glycol (PEG), two common commodity polymers, over the physicochemical and electro-optical properties of the as-fabricated devices and the distribution of polymer chains across the depth of perovskite films. The hydrophobic PS integrated perovskite devices PS-MAPbI3, 36 PS-b-1.4-PEG-MAPbI3, and 21.5 PS-b-20-PEG-MAPbI3 outperform hydrophilic PEG-MAPbI3 and pristine MAPbI3 devices and exhibit higher photocurrent, lower dark currents, and greater stability. A critical difference is also observed in the stability of devices, where rapid decay of performance is observed in the pristine MAPbI3 films. The deterioration in performance is highly limited for hydrophobic polymer-MAPbI3 films as they maintain 80% of their initial performance.

Full-Quantum Treatment of Molecular Systems Confirms Novel Supracence Photonic Properties.

Our understanding of molecules has stagnated at a single quantum system, with atoms as Newtonian particles and electrons as quantum particles. Here, however, we reveal that both atoms and electrons in a molecule are quantum particles, and their quantum-quantum interactions create a previously unknown, newfangled molecular property-supracence. Molecular supracence is a phenomenon in which the molecule transfers its potential energy from quantum atoms to photo-excited electrons so that the emitted photon has more energy than that of the absorbed one. Importantly, experiments reveal such quantum energy exchanges are independent of temperature. When quantum fluctuation results in absorbing low-energy photons, yet still emitting high-energy photons, supracence occurs. This report, therefore, reveals novel principles governing molecular supracence via experiments that were rationalized by full quantum (FQ) theory. This advancement in understanding predicts the super-spectral resolution of supracence, and molecular imaging confirms such innovative forecasts using closely emitting rhodamine 123 and rhodamine B in living cell imaging of mitochondria and endosomes.

Defining Key Features in Patient Perspectives of Hand Aesthetics.

BACKGROUND: The hand is highly visible and contributes to an individual's aesthetic image and perceived age. Current perspectives on hand aesthetics are primarily based on expert opinion rather than on lay population perspectives, which are less understood. Our study explores general population perceptions on the features that contribute most to an attractive hand. METHODS: Participants rated the attractiveness of 20 standardized hands as well as the appearance based on each characteristic: freckles, hair presence, skin tone, wrinkles, vein appearance, and soft tissue volume. The relative importance of each feature was assessed by comparison with overall attractiveness scores through multivariate analysis of variance. RESULTS: A total of 223 participants completed the survey. Soft tissue volume ( r = 0.73) was most strongly correlated with overall attractiveness, followed by wrinkles ( r = 0.71), skin tone consistency ( r = 0.69), veins ( r = 0.65), freckles ( r = 0.61), and hair ( r = 0.47). Female hands were perceived as more attractive, with a mean rating of 4.7 of 10, compared with 4.4 in males ( P < 0.001). Participants correctly identified the gender of 90.4% of male hands and 65.0% of female hands. Age was strongly inversely correlated with attractiveness ( r = -0.80). CONCLUSIONS: Soft tissue volume is the most important factor in lay perception of hand aesthetics. Female and younger hands were perceived as more attractive. Hand rejuvenation may be optimized by prioritizing soft tissue volume with filler or fat grafting, with secondary priority on resurfacing to address skin tone and wrinkling. An understanding of the factors most important to patients in aesthetic appearance is critical to achieving a pleasing result.

Open-Globe Injury Repairs in the American Academy of Ophthalmology IRIS® Registry 2014 - 2018: Incidence, Risk Factors, and Visual Outcomes.

PURPOSE: To estimate incidence and evaluate demographic risk factors and visual acuity (VA) outcomes of open-globe injuries requiring surgical repair in the IRIS® Registry (Intelligent Research in Sight). DESIGN: Retrospective cohort study. PARTICIPANTS: Patients with open-globe injury repairs (OGRs) were identified by Current Procedural Terminology codes (65275, 65280, 65285, 65286, 65235, 65260, and 65265) from 2014 through 2018 in the IRIS Registry. METHODS: Logistic regression models adjusting for age, sex, race, ethnicity, United States region, concurrent and subsequent surgeries, and baseline VA. MAIN OUTCOME MEASURES: Outcomes included annual and 5-year incidence rates per 100 000 people and factors associated with OGR, VA better than 20/40, and VA of 20/200 or worse at final follow-up (3-12 months after OGR). RESULTS: Thirteen thousand seven hundred sixty-six OGRs were identified; 5-year cumulative incidence was 28.0 per 100 000 patients. Open-globe repair was associated with age 21 to 40 years compared with younger than 21 years (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.5-1.7]), male sex (OR, 2.8; 95% CI, 2.7-2.9), Black versus White race (OR, 1.3; 95% CI, 1.2-1.4), Hispanic versus non-Hispanic ethnicity (OR, 1.7; 95% CI, 1.6-1.8), and South (OR, 1.4; 95% CI, 1.3-1.5) and West (OR, 1.3; 95% CI, 1.2-1.4) versus Midwest regions and associated inversely with Asian versus White race (OR, 0.6; 95% CI, 0.6-0.7). Visual acuity outcomes, analyzed in a subset of 2966 patients with VA data available, showed vision impairment (VA < 20/40) at final follow-up was associated with VA of 20/200 or worse at presentation (20/200 better than 20/40; OR, 11.1; 95% CI, 8.0-15.7), older age (e.g., > 80 years vs. < 21 years; OR, 5.8; 95% CI, 3.2-10.7), and Black versus White race (OR, 1.8; 95% CI, 1.3-2.6). Risk factors were similar for VA of 20/200 or worse after OGR. Among the 1063 patients undergoing OGR with VA of 20/200 or worse at presentation, VA did not improve to better than 20/200 at follow-up in 35% of patients (1063/2996). CONCLUSIONS: Our findings bring to light racial disparities in risk of OGR and poor visual outcomes that warrant further exploration. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Approach to Complex Upper Extremity Reconstruction.

The management of complex upper extremity trauma can be overwhelming in its urgency and complexity. Having a systematic approach that maintains a clear set of priorities focused on hand and upper extremity function, operative efficiency, and long-term planning for future operations allows the reconstructive extremity surgeon to effectively treat these complex injuries. This article addressed these overall clinical considerations and details the approach taken at the Buncke Clinic including replantation and revascularization as well as osseous and soft tissue reconstruction.

Microsurgical Breast Reconstruction: Maximizing Success.

Breast reconstruction is becoming increasingly recognized as a fundamental component in comprehensive breast cancer treatment. The primary goal for any reconstruction is to safely restore a natural appearing breast. When it comes to achieving the elements of size, shape, symmetry, and softness, the use of autologous tissue has many advantages. The approach to autologous breast reconstruction has changed substantially over the years as microsurgical free tissue transplants become more routine and accessible. While a variety of flap donor sites exist, careful flap selection based on surgical history and the availability of donor tissue is critical in achieving reliable results. This article reviews the clinical considerations in patient evaluation, donor site selection, and surgical approach taken at the Buncke Clinic.

ANGPTL7, a therapeutic target for increased intraocular pressure and glaucoma.

Glaucoma is a leading cause of blindness. Current glaucoma medications work by lowering intraocular pressure (IOP), a risk factor for glaucoma, but most treatments do not directly target the pathological changes leading to increased IOP, which can manifest as medication resistance as disease progresses. To identify physiological modulators of IOP, we performed genome- and exome-wide association analysis in >129,000 individuals with IOP measurements and extended these findings to an analysis of glaucoma risk. We report the identification and functional characterization of rare coding variants (including loss-of-function variants) in ANGPTL7 associated with reduction in IOP and glaucoma protection. We validated the human genetics findings in mice by establishing that Angptl7 knockout mice have lower (~2 mmHg) basal IOP compared to wild-type, with a trend towards lower IOP also in heterozygotes. Conversely, increasing murine Angptl7 levels via injection into mouse eyes increases the IOP. We also show that acute Angptl7 silencing in adult mice lowers the IOP (~2-4 mmHg), reproducing the observations in knockout mice. Collectively, our data suggest that ANGPTL7 is important for IOP homeostasis and is amenable to therapeutic modulation to help maintain a healthy IOP that can prevent onset or slow the progression of glaucoma.

Melanoma: Molecular genetics, metastasis, targeted therapies, immunotherapies, and therapeutic resistance.

Cutaneous melanoma is a common cancer and cases have steadily increased since the mid 70s. For some patients, early diagnosis and surgical removal of melanomas is lifesaving, while other patients typically turn to molecular targeted therapies and immunotherapies as treatment options. Easy sampling of melanomas allows the scientific community to identify the most prevalent mutations that initiate melanoma such as the BRAF, NRAS, and TERT genes, some of which can be therapeutically targeted. Though initially effective, many tumors acquire resistance to the targeted therapies demonstrating the need to investigate compensatory pathways. Immunotherapies represent an alternative to molecular targeted therapies. However, inter-tumoral immune cell populations dictate initial therapeutic response and even tumors that responded to treatment develop resistance in the long term. As the protocol for combination therapies develop, so will our scientific understanding of the many pathways at play in the progression of melanoma. The future direction of the field may be to find a molecule that connects all of the pathways. Meanwhile, noncoding RNAs have been shown to play important roles in melanoma development and progression. Studying noncoding RNAs may help us to understand how resistance - both primary and acquired - develops; ultimately allow us to harness the true potential of current therapies. This review will cover the basic structure of the skin, the mutations and pathways responsible for transforming melanocytes into melanomas, the process by which melanomas metastasize, targeted therapeutics, and the potential that noncoding RNAs have as a prognostic and treatment tool.

Demographics of Common Compressive Neuropathies in the Upper Extremity.

BACKGROUND: The purpose of this study was to compare the demographic differences of the most common peripheral nerve compressions in the upper extremity-carpal tunnel syndrome (CTS), ulnar nerve compression (UNC) at the elbow, combined CTS and UNC, radial tunnel syndrome (RTS), and posterior interosseous nerve syndrome (PINS)-as a means to better understand the etiologies of each. METHODS: A retrospective chart review was performed of all patients over the age of 18 years seen at our institution in the 2018 calendar year. International Classification of Diseases, Tenth Revision codes were used to identify patients with diagnoses of upper extremity peripheral nerve compressions. Demographic details and relevant comorbidities were recorded for each patient and compared with controls, who were seen the same calendar year with no neuropathies. χ2 analyses, independent-samples t tests, and multivariate logistic regressions were performed (P < .05). RESULTS: A total of 7448 patients were identified. Those with CTS were mainly women, former smokers, and diabetic (all P < .001) and with a greater average body mass index (BMI) (P = .006) than controls. Patients with UNC were more often men and younger when compared with controls (both P < .001). A history of smoking, diabetes, and average BMI were similar between patients with UNC and controls (all P > .05). Those patients with combined CTS/UNC were mainly men, former smokers, and diabetic (all P < .001) when compared with controls. Patients with RTS/PINS were also mostly men (P = .007), diabetic (P = .042), and were more often current smokers (P < .001). CONCLUSIONS: The demographics of patients with various compressive neuropathies were not homogeneous, suggesting different etiologies.

Total hip and knee arthroplasty after lower extremity amputation in a military population.

INTRODUCTION: The military includes lower extremity amputees requiring arthroplasty; however, there is little literature on this population. The primary aim of this study was to report demographics and clinical factors in amputees who undergo total hip or knee arthroplasty (THA/TKA) in the Military Health System (MHS). Second, patient-reported outcome measures (PROMs) are reported. METHODS: The Military Data Repository was queried for patients with lower extremity amputations and TKA or THA between 1 October 2014 and 12 October 2020. The medical records were reviewed and patients were contacted to complete PROMs. Mean follow-up for TKA and THA was 5.5 and 2.5 years, respectively. RESULTS: Nineteen TKAs (76%) and eight THAs (28%) were performed in 25 patients. Mean age of TKA and THA patients at the time of arthroplasty was 57 years old. A majority of TKA (68%) and THA (57%) patients underwent amputations secondary to trauma. Nearly all TKAs were performed on the contralateral side to the amputation (95%), while half of THAs were performed on the ipsilateral side (50%). Two THAs (29%) were revised due to periprosthetic fractures, whereas six TKAs (32%) were revised or reoperated on due to infection. Ten TKA patients completed PROMs. The mean score on Knee Osteoarthritis Outcome Score for Joint Replacement (KOOS JR) was 41.8 and Patient-Reported Outcomes Measurement Information System Global-10 (PROMIS-10) was 41.6 (Global Physical Health) and 49.6 (Global Mental Health). CONCLUSIONS: Most TKAs were performed on the contralateral limb, suggesting increased demand on the joint. The most common indication for amputation and post-TKA complication was trauma and infection, respectively. KOOS JR may not accurately capture the outcomes of this population, or they simply do worse. However, PROMIS-10 scores were similar to the non-amputee population, suggesting that the PROMIS-10 may be more useful than the KOOS JR.

Genome-wide analysis provides genetic evidence that ACE2 influences COVID-19 risk and yields risk scores associated with severe disease.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters human host cells via angiotensin-converting enzyme 2 (ACE2) and causes coronavirus disease 2019 (COVID-19). Here, through a genome-wide association study, we identify a variant (rs190509934, minor allele frequency 0.2-2%) that downregulates ACE2 expression by 37% (P = 2.7 × 10-8) and reduces the risk of SARS-CoV-2 infection by 40% (odds ratio = 0.60, P = 4.5 × 10-13), providing human genetic evidence that ACE2 expression levels influence COVID-19 risk. We also replicate the associations of six previously reported risk variants, of which four were further associated with worse outcomes in individuals infected with the virus (in/near LZTFL1, MHC, DPP9 and IFNAR2). Lastly, we show that common variants define a risk score that is strongly associated with severe disease among cases and modestly improves the prediction of disease severity relative to demographic and clinical factors alone.

Ambient sampling of real-world residential wood combustion plumes.

Wood smoke contains large quantities of carbonaceous aerosols known to increase climate forcing and be detrimental to human health. This paper reports the findings from our ambient sampling of fresh residential wood combustion (RWC) plumes in two heating seasons (2015-2016, 2016-2017) in Upstate New York. An Aethalometer (AE33) and a pDR-1500 were employed to monitor residential wood smoke plumes in Ithaca, NY through a hybrid mobile-stationary method. Fresh wood smoke plumes were captured and characterized at 13 different RWC sources in the city, all without significant influence from other combustion sources or atmospheric aging. Wood smoke absorption Ångström exponent (AAE) was estimated using both a one-component model, AAEWB, and a two-component model, AAEBrC (assuming AAEBC = 1.0). Consistent with the recent laboratory studies, our results show that AAEs were highly variable for residential wood smoke for the same source and across different sources, with AAEWB values ranging from 1.3 to 5.0 and AAEBrC values ranging from 2.2 to 7.4. This finding challenges the use of using a single AAE wood smoke value within the range of 1 to 2.5 for source apportionment studies. Furthermore, the PM2.5/BC ratio measured using optical instruments was demonstrated to be potentially useful to characterize burning conditions. Different wood smoke sources can be distinguished by their PM2.5/BC ratio, which range between 15 and 150. This shows promise as an in-situ, cost-effective, ambient sampling-based method to characterize wood burning conditions.Implications: There are two main implications from this paper. First, the large variability in wood smoke absorption Ångström exponent (AAE) values revealed from our real-world, ambient sampling of residential wood combustion plumes indicated that it is not appropriate to use a single AAE wood smoke value for source apportionment studies. Second, the PM2.5/BC ratio has been shown to serve as a promising in-situ, cost-effective, ambient sampling-based indicator to characterize wood burning conditions. This has the potential to greatly reduce the costs of insitu wood smoke surveillance.

Ferroptosis as a novel form of regulated cell death: Implications in the pathogenesis, oncometabolism and treatment of human cancer.

The treatment of cancer mainly involves surgical excision supplemented by radiotherapy and chemotherapy. Chemotherapy drugs act by interfering with tumor growth and inducing the death of cancer cells. Anti-tumor drugs were developed to induce apoptosis, but some patient's show apoptosis escape and chemotherapy resistance. Therefore, other forms of cell death that can overcome the resistance of tumor cells are important in the context of cancer treatment. Ferroptosis is a newly discovered iron-dependent, non-apoptotic type of cell death that is highly negatively correlated with cancer development. Ferroptosis is mainly caused by the abnormal increase in iron-dependent lipid reactive oxygen species and the imbalance of redox homeostasis. This review summarizes the progression and regulatory mechanism of ferroptosis in cancer and discusses its possible clinical applications in cancer diagnosis and treatment.