New Guinea has the world's richest island flora.

New Guinea is the world's largest tropical island and has fascinated naturalists for centuries1,2. Home to some of the best-preserved ecosystems on the planet3 and to intact ecological gradients-from mangroves to tropical alpine grasslands-that are unmatched in the Asia-Pacific region4,5, it is a globally recognized centre of biological and cultural diversity6,7. So far, however, there has been no attempt to critically catalogue the entire vascular plant diversity of New Guinea. Here we present the first, to our knowledge, expert-verified checklist of the vascular plants of mainland New Guinea and surrounding islands. Our publicly available checklist includes 13,634 species (68% endemic), 1,742 genera and 264 families-suggesting that New Guinea is the most floristically diverse island in the world. Expert knowledge is essential for building checklists in the digital era: reliance on online taxonomic resources alone would have inflated species counts by 22%. Species discovery shows no sign of levelling off, and we discuss steps to accelerate botanical research in the 'Last Unknown'8.

RETRACTED: Cost-effectiveness of chemotherapy and dostarlimab for advanced or recurrent endometrial cancer.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/policies/article-withdrawal). This article has been retracted at the request of the Authors. The authors have independently identified an error in the formula that was utilized to calculate the Quality Adjusted Life Years which invalidates the data and the conclusion of the paper. The authors have contacted the journal requesting to retract the article. Apologies are offered to the readers of the journal for any confusion or inconvenience that may have resulted from the publication of this article.

Glassy cell carcinoma of the cervix: Findings from a combined National Cancer Database analysis and single institution review of treatment patterns and outcomes.

OBJECTIVES: To describe stage, treatment patterns, and survival for glassy cell carcinoma of the cervix (GCCC), a poorly understood rare tumor. METHODS: Clinical data and survival were compared between GCCC and more common histologic types using the National Cancer Database (NCDB) from 2004 to 2017. A retrospective review of GCCC cases at our institution from 2012 to 2020 was simultaneously performed with staging updated according to 2018 FIGO staging. Descriptive statistics and survival analyses were performed, and outcomes compared to historical references. RESULTS: 143/89,001 (0.16%) NCDB cervical cancer cases were GCCC. Compared to other histologies, GCCC cases were younger, with 74.8% diagnosed before age 50. Stage distribution was similar. Stage I cases were less commonly treated with surgery alone (19/69, 27%). 79.4% of locally advanced (stage II-IVA) cases were treated with definitive chemoradiation. GCCC demonstrated worse OS for early-stage and locally-advanced disease. No survival differences were observed for patients with stage IVB disease. Our institutional review identified 14 GCCC cases. Median age at diagnosis was 34 years. All nine early-stage cases underwent radical hysterectomy. Adjuvant radiation was given for cases meeting Sedlis criteria (4/9, 44%). All five advanced stage cases were stage IIIC and received definitive chemoradiation. Recurrence rate was 0% (0/9) for early-stage and 60% (3/5) for advanced-stage cases. 3-year PFS was 100% for early-stage and 40% for advanced-stage. 3-year OS was 100% for early-stage and 60% for advanced-stage GCCC. CONCLUSIONS: GCCC presents at earlier ages than other cervical cancer histologic types. Although NCDB showed worse OS, our more contemporary institutional review, which incorporates updated staging and newer treatment modalities found outcomes more similar to historical references of more common histologic subtypes.

Safety and feasibility of same-day discharge following minimally invasive hysterectomy in the morbidly obese patient population.

OBJECTIVES: To determine whether morbid obesity should serve as an independent factor in the decision for same day discharge following minimally invasive hysterectomy. METHODS: Retrospective review was performed of patients with BMI ≥ 40 who underwent minimally invasive hysterectomy within a single comprehensive cancer center between January 2018 - August 2020. Demographics, perioperative factors, post-operative monitoring, complications, and readmissions were compared between patients who underwent same day discharge and overnight observation using Fisher's exact tests and Wilcoxon rank-sum tests. RESULTS: 374 patients with BMI ≥ 40 were included. Eighty-three (22.2%) patients underwent same day discharge, and 291 (77.8%) patients underwent overnight observation. Factors associated with increased likelihood of same day discharge included younger age (median age 53 vs 58; p = 0.001), lower BMI (median BMI 45 vs 47; p = 0.005), and fewer medical co-morbidities (Charlson Co-Morbidity Index 2 vs 3; p < 0.001). On multivariate regression analysis, frailty (OR 2.16 [1.14-4.11], p = 0.019) and surgical completion time after 12 PM (OR 3.67 [2.16-6.24], p < 0.001) were associated with increased risk of overnight observation. Few patients admitted for routine overnight observation required medical intervention (n = 14, 4.8%); most of these patients were frail (64.3%). The overall hospital readmission rate within 30 days of discharge was 3.2% (n = 12), with no patients discharged on the day of surgery being readmitted. CONCLUSIONS: Morbid obesity alone should not serve as a contraindication to same day discharge following minimally invasive hysterectomy. Admission for observation was associated with low rates of clinically meaningful intervention, and patients who underwent same day discharge were not at increased risk of adverse outcome.

Pembrolizumab with or without bevacizumab for recurrent or metastatic cervical cancer: A cost-effectiveness analysis.

OBJECTIVE: To determine the cost-effectiveness of the addition of pembrolizumab in various combinations in patients with recurrent/metastatic cervical cancer. METHODS: A decision-analysis model evaluated the cost-effectiveness of chemotherapy plus pembrolizumab and bevacizumab (CPB) relative to chemotherapy plus pembrolizumab (CP) and chemotherapy plus bevacizumab (CB) in cervical cancer patients. Data from KEYNOTE-826 was used to estimate quality-adjusted life-years (QALYs). Drug cost estimates were obtained using average wholesale prices. Incremental cost-effectiveness ratios (ICERs) were calculated to determine cost/QALY. The willingness-to-pay threshold (WTP) was set a $100,000/QALY. Sensitivity analyses were performed on cost and effectiveness for pembrolizumab-containing regimens. RESULTS: Cost of treatment with CB, CP, and CPB were $416 million (M), $713 M, and $1.51 billion, respectively. Relative to CB, the ICER for CP was $92,678. CPB was dominated. Sensitivity analyses were performed varying the cost and efficacy of CP and CPB. If overall survival (OS) with CP decreased from 24.4 months to 23.4 months, the ICER would exceed the WTP. If the OS from CP is assumed to be 20.4 months, the ICER increases to $187,746. The ICER for CP improves to $63,670 when the model is restricted to PD-L1 positive cancers. With CP eliminated, CPB becomes cost-effective relative to CB if the cost of pembrolizumab per cycle decreases from $12,080 to $2913 for the baseline model and to $4644 for the PD-L1 model. CONCLUSIONS: CP is cost-effective relative to CB for recurrent or metastatic cervical cancer. The efficacy of CPB would need to far exceed both CB and CP to be cost-effective. Restricting the model to patients with PD-L1 positive tumors dramatically improves the ICER for CP relative to CB by $30,000/QALY.

Does the addition of radiation improve survival compared to chemotherapy alone in women with stage IV endometrial carcinoma? Analysis of the NCDB and SEER databases.

OBJECTIVE: To evaluate whether the addition of radiation to adjuvant chemotherapy is associated with improved survival in women with stage IV endometrial cancer following surgery. METHODS: The National Cancer Database (NCDB) and Surveillance, Epidemiology, and End Results Program (SEER) registries were queried for patients with stage IV endometrial cancer from 2004 to 2017. Treatment was categorized as chemotherapy alone, chemotherapy with external beam radiation therapy (EBRT), chemotherapy with vaginal brachytherapy (VBT), or chemotherapy with EBRT+VBT. Multivariable Cox regression models assessed associations between treatment modality and overall survival (OS). RESULTS: This analysis included 17,890 (NCDB: 12,812, SEER: 5078) women with stage IV endometrial cancer, including 1757 (9.8%) with IVA disease and 16,133 (90.2%) with IVB. The majority of stage IV patients received chemotherapy alone (NCDB 78.8%, SEER 77.0%). When radiation was utilized in addition to chemotherapy, EBRT was most common (NCDB 15.8%, SEER: 15.4%). In both databases, use of any radiation in addition to chemotherapy was associated with improved OS. Stage IV patients treated with chemotherapy plus EBRT had better survival than those receiving chemotherapy alone [NCDB: HR 0.75 (95% CI 0.70, 0.79), SEER: HR 0.85 (95% CI 0.77, 0.94)]. This benefit was more pronounced in patients with IVA disease [NCDB: HR 0.66 (95% CI 0.55, 0.79), SEER: HR 0.63 (95% CI 0.46, 0.85)]. In histology-stratified analyses, the addition of radiation to chemotherapy was associated with improved OS in all histologies, except clear cell. CONCLUSIONS: In this analysis of the NCDB and SEER registries, the use of multimodality treatment with radiation and chemotherapy was associated with improved OS compared to chemotherapy alone in women with stage IVA and IVB endometrial cancer.

Racial and ethnic disparities in readmission risk following the surgical management of endometrial cancer.

OBJECTIVE: Most women diagnosed with endometrial cancer undergo primary surgical management with hysterectomy. Although racial disparities in readmission risk following hysterectomy for non-cancerous conditions have been reported, data among women with endometrial cancer are absent. This study evaluates racial differences in readmission risk among women undergoing endometrial cancer-related hysterectomy. METHODS: In the National Cancer Database, women who underwent surgical management for endometrial cancer from 2004 to 2018 were identified. Readmission and minimally invasive hysterectomy (MIH) proportions were plotted according to year of diagnosis and race/ethnicity. Multivariable logistic regression models were used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for associations between readmission risk and epidemiological, facility, tumor, and surgical characteristics. A base model was sequentially adjusted to incorporate significant covariates. RESULTS: There were 350,631 patients included in the study. The proportion of MIH increased among all race/ethnicities over the study period; however, MIH rates were lower among Black women. Readmission proportions were 2.7% among White, 4.2% among Black, 2.9% among Hispanic, 2.4% among Asian, 2.1% among American Indian/Alaska Native, and 3.1% among Native Hawaiian/Pacific Islander women. In the fully adjusted model incorporating surgical approach, Black women (OR: 1.20, 95% CI = 1.13, 1.28) and Native Hawaiian/Pacific Islander women (OR: 1.54, 95% CI = 1.09, 2.18) were more commonly readmitted compared to White women. CONCLUSIONS: In this study, Black and Native Hawaiian/Pacific Islander women with endometrial cancer had significantly higher readmission risk than White women. Optimizing perioperative care for minority women is an essential component of overcoming racially disparate endometrial cancer outcomes.

Implementing universal upfront multi-gene panel testing in endometrial cancer: From cost to practical considerations.

OBJECTIVES: The routine use of upfront universal germline genetic testing among patients with newly diagnosed endometrial cancer (EC) has been proposed to improve diagnosis of Lynch syndrome (LS) and discover pathogenic variants (PVs) in other cancer susceptibility genes. We propose an algorithm prioritizing upfront multi-gene panel testing (MGPT) for newly diagnosed EC patients. METHODS: A decision analysis compared the cost of the current algorithm of universal mismatch repair (MMR) immunohistochemistry (IHC) for all EC cases to a new MGPT algorithm that employs upfront MGPT for all EC cases and reserves MMR IHC for the recurrent setting. The increase in the number of LS diagnoses using upfront MGPT, and the number of patients with PVs in BRCA1 and BRCA2 are also estimated. RESULTS: The MGPT algorithm demonstrated a cost savings of $259 per patient. Assuming 66,950 new cases of EC per year, this would represent $17.1 M of cost savings per year. When applied to all new diagnoses of EC in one year, the MGPT algorithm identified 660 (1%) additional cases of LS that would have been missed with the current algorithm. An additional 660 (1%) EC patients with BRCA1 or BRCA2 PVs would be diagnosed only through implementation of universal MGPT. CONCLUSIONS: The use of universal upfront MGPT is a practical consideration for patients with newly diagnosed EC for cost savings and improved diagnosis of highly penetrant cancer syndromes. Incorporation of germline genetic testing in the upfront setting represents an opportunity to improve access to genetic counseling and testing, and ultimately an avenue to achieve equity and improve the lives of our patients with EC and their families.

Less is more: Abdominal closure protocol does not reduce surgical site infection after hysterectomy.

OBJECTIVES: To determine rates of surgical site infection (SSI) with and without an abdominal closure protocol for gynecologic oncology patients undergoing abdominal hysterectomy. METHODS: Consecutive patients were identified using CPT codes who underwent total abdominal hysterectomy by gynecologic oncologists at a tertiary care center from January 1, 2015 to December 31, 2019, and stratified by use of the abdominal closure protocol. Demographic, perioperative, and pathologic variables were collected. Fisher's exact and Chi squared tests were used for categorical variables, logistic regression and student t-tests for continuous variables. Multiple logistic regression was used to analyze the relationships between these variables, use of the closure protocol, and development of SSI. RESULTS: 739 patients were included over the study period (n = 393 pre-implementation, n = 346 post-implementation of the abdominal closure protocol,). Baseline demographics including ASA score, BMI, diabetes, and smoking were similar between these groups (P = 0.14-0.94). The rate of SSI within 30 days was 5.9% (23/393) in the pre-protocol group and 8.1% (28/346) under the abdominal closure protocol (P = 0.25). On univariate analysis, factors associated with SSI were BMI >40, diabetes, bowel resection, ASA score 3 or 4, hypertension, and contaminated wound class (uOR 2.31-4.09). On multivariate analysis BMI >40, diabetes, and bowel resection remained independent risk factors (aOR 2.27-2.99), with the closure protocol not achieving significance (aOR 1.43, 95% CI 0.79-2.59). There were no potentially high-risk sub-groups in whom the closing protocol showed benefit. CONCLUSION: The abdominal closure protocol in isolation did not decrease SSI in those undergoing TAH by a gynecologic oncologist.

Beyond mismatch repair deficiency? Pre-treatment neutrophil-to-lymphocyte ratio is associated with improved overall survival in patients with recurrent endometrial cancer treated with immunotherapy.

OBJECTIVE: To determine the association of pre-treatment neutrophil-to-lymphocyte ratio (NLR) with progression-free survival (PFS) and overall survival (OS) for patients with recurrent endometrial cancer (EC) treated with immunotherapy. METHODS: Recurrent EC patients treated with immunotherapy alone or in combination from 2016 to 2021 were included. Demographics, pre-treatment laboratory results, pathologic data, response at first radiographic assessment, and cancer outcomes were obtained from the medical record. Kaplan-Meier curves were generated to compare PFS and OS stratified by NLR. RESULTS: The 106 patients included in the study were stratified by NLR <6 (n = 77, 72.6%) or NLR ≥6 (n = 29, 27.3%). Most had endometrioid pathology (59%), widely metastatic disease, and 36.8% had received ≥2 treatment lines before initiating immunotherapy. Mismatch repair deficiency (dMMR) was noted in 52 (49.1%) tumors. Most dMMR patients (94.3%) were treated with single-agent pembrolizumab, and most MMR proficient patients (78.7%) were treated with lenvatinb plus pembrolizumab. In the overall cohort, 40.2% (partial response (PR) 29.9%, complete response (CR) 10.4%) of patients with a NLR <6 responded at first radiographic assessment, compared to 31% (PR 27.5%, CR 3.4%) of patients with NLR ≥6 (p 0.691). Kaplan-Meier curves stratified by NLR <6 vs. ≥6 showed no difference in PFS. However, NLR <6 was associated with improved OS (p < 0.05). In the NLR < 6 group, the probability of survival at one year was 69% (95% CI: 58%, 82%), compared to 41% (95% CI: 26%, 67%) for the NLR > 6 group. CONCLUSIONS: Pre-treatment NLR <6 was associated with improved OS for recurrent EC patients treated with immunotherapy. NLR holds promise as a predictive biomarker for survival after immunotherapy treatment for patients with recurrent EC.

More than treatment refusal: a National Cancer Database analysis of adjuvant treatment refusal and racial survival disparities among women with endometrial cancer.

BACKGROUND: Disparities in adjuvant treatment between Black and White women with endometrial cancer exist and contribute to worse outcomes among Black women. However, factors leading to disparate treatment receipt are understudied. OBJECTIVE: We examined whether patient refusal of adjuvant treatment (chemotherapy or radiation) differed between Black and White women and whether treatment refusal mediated racial disparities in survival among women with endometrial cancer. STUDY DESIGN: We used the National Cancer Database, a hospital-based cancer registry, to identify non-Hispanic Black and non-Hispanic White women diagnosed with endometrial cancer from 2004 to 2016 who either received or refused recommended radiation or chemotherapy. We used logistic regression to estimate multivariable-adjusted odds ratios and 95% confidence intervals for associations between race and treatment refusal. We also examined predictors of treatment refusal in race-specific models. Accelerated failure time models were used to estimate absolute differences in overall survival by race. We used causal mediation analysis to estimate the proportion of racial differences in overall survival attributable to racial differences in adjuvant treatment refusal. We considered the overall study population and strata defined by histology, and adjusted for sociodemographic, tumor, and facility characteristics. RESULTS: Our analysis included 75,447 endometrial cancer patients recommended to receive radiation and 60,187 endometrial cancer patients recommended to receive chemotherapy, among which 6.4% and 11.4% refused treatment, respectively. Among Black women recommended for radiation or chemotherapy, 6.4% and 9.6% refused, respectively. Among White women recommended for radiation or chemotherapy, 6.4% and 11.8% refused, respectively. After adjusting for sociodemographic variables, facility characteristics, and tumor characteristics, Black women were more likely to refuse chemotherapy than White women (adjusted odds ratio, 1.26; 95% confidence interval, 1.15-1.37), but no difference in radiation refusal was observed (adjusted odds ratio, 1.00; 95% confidence interval, 0.91-1.11). Some predictors of radiation refusal varied by race, namely income, education, histology, stage, and chemotherapy receipt (P interactions<.05), whereas predictors of chemotherapy refusal were generally similar between Black and White women. Among women recommended for radiation, Black women survived an average of 4.3 years shorter than White women, which did not seem attributable to differences in radiation refusal. Among women recommended for chemotherapy, Black women survived an average of 3.2 years shorter than White women of which 1.9 months (4.9%) could potentially be attributed to differences in chemotherapy refusal. CONCLUSION: We observed differences in chemotherapy refusal by race, and those differences may be responsible for up to about 2 months of the overall 3.2-year survival disparity between White and Black women. Radiation refusal did not explain any of the 4.3-year disparity among women recommended for radiation. Treatment refusal accounts for, at most, a small fraction of the total racial disparity in endometrial cancer survival. Although a better understanding of the reasons for patient treatment refusal and subsequent intervention may help improve outcomes for some women, other causes of disparate outcomes, particularly those reflecting the social determinants of health, must be investigated.

Help wanted: low provider density is associated with advanced stage cervical cancer.

BACKGROUND: Patients in rural areas have a higher incidence of cervical cancer with increased rates of metastatic disease than their urban counterparts. OBJECTIVE: To evaluate whether medical provider density, acting as a surrogate for screening availability, is associated with the incidence of cervical cancer or proportion diagnosed with advanced stage disease. METHODS: Cervical cancer cases by county from 2015 were retrieved from the SEER database. The numbers of primary obstetric-gynecologists (OB-GYN), family practice, and internal medicine providers were obtained from the Area Health Resource File, and population estimates for each county were used to calculate provider to resident ratios. Spearman rank correlations were used to compare the number of providers per 100 000 residents with the overall incidence of cervical cancer as well as the proportion diagnosed at an advanced stage. Multivariable logistic regression was performed to assess factors independently associated with advanced stage disease, accounting for county of residence. Mortality was compared across different OB-GYN provider density categories. RESULTS: A total of 3505 cases of cervical cancer from 405 counties were included. Spearman correlation demonstrated a significant inverse association between the number of OB-GYN providers per 100 000 residents and the incidence of cervical cancer (p<0.0001) as well as the proportion diagnosed at an advanced stage (p=0.003). Compared with those living in counties with ≤5 OB-GYN providers per 100 000 residents, those living in counties with >10 providers had a 29% reduction in the odds of presenting with advanced stage disease (OR=0.71; 95% CI 0.55 to 0.91). An inverse association between cervical cancer-related mortality and OB-GYN provider density was also noted. CONCLUSION: A significant inverse correlation between provider density and incidence of cervical cancer, proportion with advanced stage disease, and cervical cancer-related mortality was observed. Increasing provider density in these underserved, high-risk areas may improve timely cancer detection.

Determinants of Surgical Approach and Survival Among Women with Endometrial Carcinoma.

STUDY OBJECTIVE: To investigate determinants of surgical approach among women with endometrial carcinoma (EC) and associations between surgical approach and overall survival (OS). DESIGN: Retrospective cohort. SETTING: The National Cancer Database, 2010 to 2015. PATIENTS: A total of 140 470 patients with histologically confirmed EC who underwent hysterectomy. INTERVENTIONS: Patients were grouped according to surgical approach. MEASUREMENTS AND MAIN RESULTS: A total of 140 470 patients with EC were included. Robotic-assisted laparoscopy (RAL) was the most common surgical approach (48.8%), followed by laparotomy (33.6%) and traditional laparoscopy (17.6%). Use of RAL increased over the study period, and the percentages of cases managed by laparotomy decreased. Older women, those with insurance, residing in ZIP codes with lower proportions of individuals who did not graduate from high school, and those treated at noncommunity cancer programs were less likely to undergo laparotomy than RAL, and non-white women, those diagnosed with high-grade histology, and those with advanced-stage EC were more likely to undergo laparotomy than RAL. Compared with RAL, all other surgical approaches were associated with worse OS (laparotomy: hazard ratio 1.21; 95% confidence interval, 1.18-1.25; traditional laparoscopy: hazard ratio 1.06; 95% confidence interval, 1.02-1.09). Significant effect modification of the surgical approach and OS relationship according to age, race, histology, stage, and adjuvant treatment was observed. CONCLUSION: RAL increased in frequency over the study period and was associated with improved OS, supporting the continued use of RAL for EC management.

Lenvatinib plus pembrolizumab in advanced recurrent endometrial cancer: A cost-effectiveness analysis.

OBJECTIVE: To determine the cost-effectiveness of lenvatinib plus pembrolizumab (LP) in patients with microsatellite stable (MSS), recurrent, pretreated endometrial cancer (EC). METHODS: A decision analysis model was created to evaluate the cost-effectiveness of LP relative to doxorubicin, pegylated liposomal doxorubicin (PLD), and bevacizumab in patients with recurrent pretreated MSS EC. Published data was used to estimate quality adjusted life years (QALYs) and drug cost estimates were obtained using average wholesale prices. A health state utility (HSU) penalty of -0.10 was applied to the LP group to account for treatment toxicity. Incremental cost-effectiveness ratios (ICERs) were calculated to determine cost/QALY. The willingness to pay threshold (WTP) was set at $100,000 per QALY saved. Sensitivity analyses were performed on cost, effectiveness, and HSU penalty for LP. RESULTS: Costs of treatment with doxorubicin, PLD, and bevacizumab are $23.7 million (M), $56.9 M, and $250.8 M respectively. Cost of treatment with LP is $1.8 billion. Relative to doxorubicin, the ICERs for PLD, bevacizumab, and LP are $56,808, $345,824, and $1.6 M respectively. A sensitivity analysis varying the cost of LP shows that if the combined drug cost decreases from over $58,000 to less than $11,000 per cycle, this strategy would be cost-effective. Eliminating the HSU penalty for LP decreased the ICER $1.0 M while increasing the penalty to -0.20 increased the ICER to $3.7 M. CONCLUSIONS: LP is not cost-effective in patients with recurrent pretreated, MSS EC. A dramatic reduction in cost of LP is required for this novel strategy to be cost-effective.

Impact of Molecular Classification on Treatment Paradigms in Uterine Cancers.

PURPOSE OF REVIEW: This article will discuss the recent data on the prognostic significance of molecular classification of endometrial carcinoma, as well as its impact on directing treatment decisions. RECENT FINDINGS: Molecular classification has emerged as a complement to the current paradigm of endometrial cancer (EC) risk stratification. POLE mutations appear to portend favorable prognoses, but data are insufficient to indicate withholding treatment based on this signature. Copy number high (CNH) EC carries a worse prognosis and may benefit from more aggressive therapy. MMRd tumors are likely to have other prognostic features that indicate adjuvant treatment and many recurrences respond favorably to pembrolizumab. Progression of molecular profiling may allow further discrimination of the no specific molecular profile (NSMP) group. Treatment for this group remains largely based on conventional risk factors. For both the NSMP and the CNH groups, treatment with lenvatinib and pembrolizumab is an attractive contemporary option for recurrence management. Molecular classification is a useful adjunct to conventional risk stratification paradigms for both prognostic counseling and treatment selection. Clinical trials incorporating molecular signatures in assigning treatment strategies may further elucidate the value of this classification system.

New insights into the evolution of the fern family Dennstaedtiaceae from an expanded molecular phylogeny and morphological analysis.

Dennstaedtiaceae has 270 species, a worldwide distribution, and an edge-colonizing habit that is unusual among ferns. Aneuploidy, polyploidy, and hybrids are common in the family. Combining morphology, anatomy, chromosome number, and geographical distributions with our newly generated molecular phylogeny, we provide new insights into the evolution of the family. We paid special attention to Hypolepis. Our molecular dataset of five cpDNA markers is the most comprehensive to date, comprising 72 species (and a total of 98 taxa), of which 33 are Hypolepis (45 taxa). We also generated divergence-time estimates through BEAST with four fossil calibrations. We recovered three sub-families in Dennstaedtiaceae: Monachosoroideae (monogeneric), Dennstaedtioideae, and Hypolepidoideae. Monachosoroideae has a chromosome base number of x = 28; Hypolepidoideae of x = 26; while in Dennstaedtioideae this is still obscure, with different numbers ranging from 30 to 47. Dennstaedtioideae genera require re-circumscriptions because Dennstaedtia is polyphyletic. In Hypolepidoideae, the six genera are monophyletic. Within Hypolepis, seven geographically distinct clades were recovered; but we found no strong morphological characters to define them. Within the family, the long-creeping rhizome evolved with a change in habit: from shade-tolerant to edge-colonizers, to thicket-formers. Short or extremely large leaves are derived conditions. Sorus shape and position, glandular hairs, and prickles are homoplastic. Hybridization/allotetraploidy in Hypolepis can be suggested by the combined data. In our phylogenetic hypothesis, Dennstaedtiaceae originated around 135 Ma, with the split of Monachosoroideae around 94 Ma, and the split between Dennstaedtioideae/Hypolepidoideae around 78 Ma. All extant genera are inferred to be relatively young. Hypolepis started to diversify around 10 Ma, and it probably originated in east Asia and/or Oceania. Hypolepis reached the Neotropics twice: through elements of the Hypolepis rugosula clade (which originated at 7 Ma), and through the ancestor of the Neotropical clade, which originated at 3.1 Ma and was prickly.

Where you live matters: A National Cancer Database study of Medicaid expansion and endometrial cancer outcomes.

OBJECTIVE: To determine associations between adoption of Medicaid expansion (ME) and changes in insurance status, early stage diagnosis, and cancer survival among women with endometrial carcinoma (EC). METHODS: The National Cancer Database (NCDB) was queried for patients diagnosed with EC between the age 40-64 from 2004 to 2015. Difference-in-differences analysis quantified the impact of ME on the proportion of new EC diagnoses with insurance (vs. uninsured), the proportion diagnosed with stage I (vs. II-IV), and overall survival. RESULTS: 156,253 patients were included. Among 65,019 women living in ME states, ME is associated with an increase in the percent of EC cases who are insured of 1.4% (95% CI 0.9-2.0%, p < 0.0001), with strongest effects among Hispanic women, women in the lowest income quartile, and women in the second age quartile (age 53-57). There was no overall impact of ME on stage, though an increase of early stage diagnoses by 2.4% (95% CI 0.3-4.5%, p = 0.022) was observed among women age 53-57. There was a trend towards improved overall survival with ME, which was strongest in women age 53-57 (HR = 0.83, 95% CI 0.70-0.99, p = 0.037). CONCLUSIONS: Among women with EC, ME positively impacted insurance coverage, an important hurdle in accessing health care. In women aged 53-57, ME was associated with earlier stage at diagnosis and improved survival, suggesting that the magnitude of the improvement in insurance coverage may correlate with important clinical outcomes. Efforts should continue to understand the complexity of barriers to health care access and to develop effective strategies to surmount them.

Niraparib maintenance in frontline management of ovarian cancer: a cost effectiveness analysis.

OBJECTIVES: Niraparib maintenance after frontline chemotherapy for advanced ovarian cancer extends progression free survival. The objective of this study was to determine the cost effectiveness of niraparib maintenance therapy in patients with newly diagnosed ovarian cancer. METHODS: Decision analysis models compared the cost of observation versus niraparib maintenance following chemotherapy for five groups: all newly diagnosed ovarian cancer patients (overall), those with homologous recombination deficiency, those harboring BRCA mutations (BRCA), homologous recombination deficiency patients without BRCA mutations (homologous recombination deficiency non-BRCA), and non-homologous recombination deficiency patients. Drug costs were estimated using average wholesale prices. Progression free survival was estimated from published data and used to estimate projected overall survival. Incremental cost effectiveness ratios per quality adjusted life year were calculated. Sensitivity analyses varying the cost of niraparib were performed. The willingness-to-pay threshold was set at US$100 000 per quality adjusted life year saved. RESULTS: For the overall group, the cost of observation was US$5.8 billion versus $20.5 billion for niraparib maintenance, with an incremental cost effectiveness ratio of $72 829. For the homologous recombination deficiency group, the observation cost was $3.0 billion versus $14.8 billion for niraparib maintenance (incremental cost effectiveness ratio $56 329). Incremental cost effectiveness ratios for the BRCA, homologous recombination deficiency non-BRCA, and non-homologous recombination deficiency groups were $58 348, $50 914, and $88 741, respectively. For the overall and homologous recombination deficiency groups, niraparib remained cost effective if projected overall survival was 2.2 and 1.5 times progression free survival, respectively. CONCLUSIONS: For patients with newly diagnosed ovarian cancer, maintenance therapy with niraparib was cost effective. Cost effectiveness was improved when analyzing those patients with homologous recombination deficiency and BRCA mutations. Efforts should continue to optimize poly-ADP-ribose polymerase utilization strategies.

Vacuolar Protein Sorting 26C encodes an evolutionarily conserved large retromer subunit in eukaryotes that is important for root hair growth in Arabidopsis thaliana.

The large retromer complex participates in diverse endosomal trafficking pathways and is essential for plant developmental programs, including cell polarity, programmed cell death and shoot gravitropism in Arabidopsis. Here we demonstrate that an evolutionarily conserved VPS26 protein (VPS26C; At1G48550) functions in a complex with VPS35A and VPS29 necessary for root hair growth in Arabidopsis. Bimolecular fluorescence complementation showed that VPS26C forms a complex with VPS35A in the presence of VPS29, and this is supported by genetic studies showing that vps29 and vps35a mutants exhibit altered root hair growth. Genetic analysis also demonstrated an interaction between a VPS26C trafficking pathway and one involving the SNARE VTI13. Phylogenetic analysis indicates that VPS26C, with the notable exception of grasses, has been maintained in the genomes of most major plant clades since its evolution at the base of eukaryotes. To test the model that VPS26C orthologs in animal and plant species share a conserved function, we generated transgenic lines expressing GFP fused with the VPS26C human ortholog (HsDSCR3) in a vps26c background. These studies illustrate that GFP-HsDSCR3 is able to complement the vps26c root hair phenotype in Arabidopsis, indicating a deep conservation of cellular function for this large retromer subunit across plant and animal kingdoms.

The rise of the Andes promoted rapid diversification in Neotropical Phlegmariurus (Lycopodiaceae).

Tropical mountains are disproportionately biodiverse relative to their surface area, but the processes underlying their exceptional diversity require further study. Here, we use comparative phylogenetic methods to examine the impact of the Andean orogeny on the diversification of Neotropical Phlegmariurus, a species-rich lycophyte clade. We generated a time-calibrated phylogeny of 105 species of Neotropical Phlegmariurus and estimated lineage diversification rates. We tested for correlations between lineage diversification rates and species range size, niche breadth, elevational range amplitude, and mean elevation of occurrence. A recently developed macroevolutionary model was used to incorporate geological data and test for an association between diversification rates and the Andean uplift. Diversification rates of Neotropical Phlegmariurus are negatively correlated with species range size and positively correlated with mean elevation of species occurrence. The rise of the Andes is strongly associated with increased rates of diversification in Neotropical Phlegmariurus during the last 10 Myr. Our study demonstrates the importance of mountain-building events and geographical isolation of alpine populations as drivers of rapid diversification, even in spore-dispersed plants. This work also highlights the usefulness of combined phylogenetic, geological and ecological datasets, and the promise of comparative environment-dependent diversification models in better understanding the evolutionary origins of biodiversity.