Streptophytes are one of the major groups of the green lineage (Chloroplastida or Viridiplantae). During one billion years of evolution, streptophytes have radiated into an astounding diversity of ...uni- and multicellular green algae as well as land plants. Most divergent from land plants is a clade formed by Mesostigmatophyceae,
spp. and Chlorokybophyceae. All three lineages are species-poor and the Chlorokybophyceae consist of a single described species,
In this study, we used phylogenomic analyses to shed light into the diversity within
using a sampling of isolates across its known distribution. We uncovered a consistent deep genetic structure within the
isolates, which prompted us to formally extend the Chlorokybophyceae by describing four new species. Gene expression differences among
species suggest certain constitutive variability that might influence their response to environmental factors. Failure to account for this diversity can hamper comparative genomic studies aiming to understand the evolution of stress response across streptophytes. Our data highlight that future studies on the evolution of plant form and function can tap into an unknown diversity at key deep branches of the streptophytes.
The continuing need to protect food and fiber production to address the demands of an expanding global population requires new pest management tools for crop protection. Natural products (NPs) have ...been and continue to be a key source of inspiration for new active ingredients (AIs) for crop protection, accounting for 17% of all crop protection AIs. However, potentially 50% of all crop protection compounds have or could have a NP origin if NP synthetic equivalents (NPSEs, synthetic compounds discovered by other approaches but for which a NP model also happens to exist) are also considered. The real and hypothetical NPs have their greatest impact as insight for new classes of crop protection compounds. Among the different product areas, NPs have their largest influence on the discovery of new insecticides, while herbicides have been the least affected by mining NPs for new AIs. While plants have historically been the largest (60% of the total) source of NPs of AIs for crop protection, in the last 30 years, bacterial NPs have become the largest source (42% of the total) of new classes (first in class) of NP-inspired crop protection AIs. Interest in NPs for crop protection continues, an aspect that is highlighted by the notable rise in the numbers of publications and patents on this topic, especially in the last 20 years. The present analysis further illustrates the continuing interest and value in NPs as sources of and inspiration for new classes of crop protection compounds.
We report patient outcomes from esophageal resection with respect to morbidity and cancer survival comparing open thoracotomy and laparotomy (Open), with a thoracoscopic/laparotomy approach ...(Thoracoscopic-Assisted) and a total thoracoscopic/laparoscopic approach (Total MIE).
From a prospective database of all patients managed with cancer of the esophagus or esophagogastric junction, patients who had a resection using one of three techniques were analyzed to assess postoperative variables, adequacy of cancer clearance, and survival.
The number of patients for each procedure was as follows: Open, 114; Thoracoscopic-Assisted, 309; and Total MIE, 23. The groups were comparable with respect to preoperative variables. The differences in the postoperative variables were: less median blood loss in the Thoracoscopic-Assisted (400 mL) and Total MIE (300 mL) groups versus Open (600 mL); longer time for Total MIE (330 minutes) versus Thoracoscopic-Assisted (285 minutes) and Open (300 minutes); longer median time in hospital for Open (14 days) versus Thoracoscopic-Assisted (13 days), Total MIE (11 days) and less stricture formation in the Open (6.1%) versus Thoracoscopic-Assisted (21.6%), Total MIE (36%). There were no differences in lymph node retrieval for each of the approaches. Open had more stage III patients (65.8%) versus Thoracoscopic-Assisted (34.4%), Total MIE (52.1%). There was no difference in survival when the groups were compared stage for stage for overall median or 3-year survival.
Minimally invasive techniques to resect the esophagus in patients with cancer were confirmed to be safe and comparable to an open approach with respect to postoperative recovery and cancer survival.
SummaryBackgroundEndocrine therapy-based neoadjuvant treatment for luminal breast cancer allows efficient testing of new combinations before surgery. The activation of the ...phosphatidylinositol-3-kinase (PI3K) pathway is a known mechanism of resistance to endocrine therapy. Taselisib is an oral, selective PI3K inhibitor with enhanced activity against PIK3CA-mutant cancer cells. The LORELEI trial tested whether taselisib in combination with letrozole would result in an increased proportion of objective responses and pathological complete responses. MethodsIn this multicentre, randomised, double-blind, parallel-cohort, placebo-controlled phase 2, study, we enrolled postmenopausal women (aged ≥18 years) with histologically confirmed, oestrogen receptor (ER)-positive, HER2-negative, stage I–III, operable breast cancer, from 85 hospitals in 22 countries worldwide. To be eligible, patients had have an Eastern Cooperative Oncology Group (ECOG) performance status 0–1, adequate organ function, and had to have evaluable tumour tissue for PIK3CA genotyping. Patients were randomly assigned (1:1) by means of a permuted block algorithm (block size of four) via an interactive voice or web-based response system, to receive letrozole (2·5 mg/day orally, continuously) with either 4 mg of oral taselisib or placebo (on a 5 days-on, 2 days-off schedule) for 16 weeks, followed by surgery. Randomisation was stratified by tumour size and nodal status. Site staff, patients, and the sponsor were masked to treatment assignment. Coprimary endpoints were the proportion of patients who achieved an objective response by centrally assessed breast MRI and a locally assessed pathological complete response in the breast and axilla (ypT0/Tis, ypN0) at surgery in all randomly assigned patients and in patients with PIK3CA-mutant tumours. Analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT02273973, and is closed to accrual. FindingsBetween Nov 12, 2014, and Aug 12, 2016, 334 participants were enrolled and randomly assigned to receive letrozole and placebo (n=168) or letrozole and taselisib (n=166). Median follow-up was 4·9 months (IQR 4·7–5·1). The study met one of its primary endpoints: the addition of taselisib to letrozole was associated with a higher proportion of patients achieving an objective response in all randomly assigned patients (66 39% of 168 patients in the placebo group vs 83 50% of 166 in the taselisib group; odds ratio OR 1·55, 95% CI 1·00–2·38; p=0·049) and in the PIK3CA-mutant subset (30 38% of 79 vs 41 56% of 73; OR 2·03, 95% CI 1·06–3·88; p=0·033). No significant differences were observed in pathological complete response between the two groups, either in the overall population (three 2% of 166 in the taselisib group vs one 1% of 168 in the placebo group; OR 3·07 95% CI 0·32–29·85, p=0·37) or in the PIK3CA-mutant cohort (one patient 1%) vs none 0%; OR not estimable, p=0·48). The most common grade 3–4 adverse events in the taselisib group were gastrointestinal (13 8% of 167 patients), infections (eight 5%), and skin–subcutaneous tissue disorders (eight 5%). In the placebo group, four (2%) of 167 patients had grade 3 or worse vascular disorders, two (1%) had gastrointestinal disorders, and two (1%) patients had grade 3 or worse infections and infestations. There was no grade 4 hyperglycaemia and grade 3 cases were asymptomatic. Serious adverse events were more common in the taselisib group (eight 5% patients with infections and seven 4% with gastrointestinal effects) than in the placebo group (one 1% patient each with grade 3 postoperative wound and haematoma infection, grade 4 hypertensive encephalopathy, grade 3 acute cardiac failure, and grade 3 breast pain). One death occurred in the taselisib group, which was not considered to be treatment-related. InterpretationThe increase in the proportion of patients who achieved an objective response from the addition of taselisib to endocrine therapy in a neoadjuvant setting is consistent with the clinical benefit observed in hormone receptor-positive, HER2-negative, metastatic breast cancer. FundingGenentech and F Hoffmann-La Roche.
Streptophytes are best known as the clade containing the teeming diversity of embryophytes (land plants).1,2,3,4 Next to embryophytes are however a range of freshwater and terrestrial algae that bear ...important information on the emergence of key traits of land plants. Among these, the Klebsormidiophyceae stand out. Thriving in diverse environments—from mundane (ubiquitous occurrence on tree barks and rocks) to extreme (from the Atacama Desert to the Antarctic)—Klebsormidiophyceae can exhibit filamentous body plans and display remarkable resilience as colonizers of terrestrial habitats.5,6 Currently, the lack of a robust phylogenetic framework for the Klebsormidiophyceae hampers our understanding of the evolutionary history of these key traits. Here, we conducted a phylogenomic analysis utilizing advanced models that can counteract systematic biases. We sequenced 24 new transcriptomes of Klebsormidiophyceae and combined them with 14 previously published genomic and transcriptomic datasets. Using an analysis built on 845 loci and sophisticated mixture models, we establish a phylogenomic framework, dividing the six distinct genera of Klebsormidiophyceae in a novel three-order system, with a deep divergence more than 830 million years ago. Our reconstructions of ancestral states suggest (1) an evolutionary history of multiple transitions between terrestrial-aquatic habitats, with stem Klebsormidiales having conquered land earlier than embryophytes, and (2) that the body plan of the last common ancestor of Klebsormidiophyceae was multicellular, with a high probability that it was filamentous whereas the sarcinoids and unicells in Klebsormidiophyceae are likely derived states. We provide evidence that the first multicellular streptophytes likely lived about a billion years ago.
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•Comprehensive phylogenomic analyses for 38 taxonomically diverse Klebsormidiophyceae•Three-order system for the Klebsormidiophyceae, resilient land colonizers•Deep divergence, 830 million years ago—long before embryophytes emerged•Evidence that multicellularity emerged in streptophytes about a billion years ago
Bierenbroodspot et al. use comprehensive phylogenomic analyses to propose a three-order system for Klebsormidiophyceae, streptophyte algae that colonize terrestrial habitats but are distantly related to land plants. They trace the occurrence of multicellular growth that, based on molecular dating, might have emerged about a billion years ago.
Plasma cell disorders (PCD) are a group of conditions characterized by disproportionate proliferation of a single clone of B lymphocytes. Multiple myeloma (MM) is a malignant type of PCD. ...Improvements in MM survival have led patients and physicians to pursue strategies to improve quality of life for those living longer with this disease. Bone disease and instability associated with MM have made physicians reluctant to recommend physical activity (PA) to this patient population. The goal of this study was to examine the relationship between PA and physical and psychosocial patient-reported outcomes (PRO) in patients with MM and precursor conditions.
We employed a cross-sectional study design. Questionnaires on PA, demographics, fatigue, distress, and other aspects of quality of life were posted on the HealthTree® Cure Hub website, a patient portal through which individuals with MM and related disorders obtain support, track labs and other information about their diseases, and participate in research.
A total of 794 individuals, including 664 with MM, are included in the current analysis. We observed potential inverse associations between PA and poor quality of life, including problems with sleep, fatigue, neuropathy, distress, and several psychosocial states. On average, patients reported that their PA levels have declined since diagnosis and that they would like to be even more active in the future than they were prior to their diagnosis.
In our cross-sectional study, regular physical activity was associated with multiple quality-of-life indicators and other PROs, including better sleep and less fatigue, neuropathy, and distress. The findings of this study can help guide the design of prospective studies of the role of PA in MM survivorship.
Atherosclerotic plaque formation is fueled by the persistence of lipid-laden macrophages in the artery wall. The mechanisms by which these cells become trapped, thereby establishing chronic ...inflammation, remain unknown. Here we found that netrin-1, a neuroimmune guidance cue, was secreted by macrophages in human and mouse atheroma, where it inactivated the migration of macrophages toward chemokines linked to their egress from plaques. Acting via its receptor, UNC5b, netrin-1 inhibited the migration of macrophages directed by the chemokines CCL2 and CCL19, activation of the actin-remodeling GTPase Rac1 and actin polymerization. Targeted deletion of netrin-1 in macrophages resulted in much less atherosclerosis in mice deficient in the receptor for low-density lipoprotein and promoted the emigration of macrophages from plaques. Thus, netrin-1 promoted atherosclerosis by retaining macrophages in the artery wall. Our results establish a causative role for negative regulators of leukocyte migration in chronic inflammation.
Abstract Introduction Preoperative chemotherapy (CT) and preoperative chemoradiation therapy (CRT) for resectable oesophageal cancer have been shown to improve overall survival in meta-analyses. ...There are limited data comparing these preoperative therapies. We report the outcomes of a randomised phase II trial comparing preoperative CT and CRT for resectable adenocarcinoma of the oesophagus and gastro-oesophageal junction. Methods Patients were randomised to receive preoperative CT with cisplatin (80 mg/m2 ) and infusional 5 fluorouracil (1000 mg/m2 /d) on days 1 and 21, or preoperative CRT with the same drugs accompanied by concurrent radiation therapy commencing on day 21 of chemotherapy and the 5 fluorouracil reduced to 800 mg/m2 /d. The radiation dose was 35 Gy in 15 fractions over 3 weeks. The endpoints were toxicity, response rates, resection (R) status, progression-free survival (PFS), overall survival (OS) and quality of life. Results Seventy-five patients were enroled on the study: 36 received preoperative CT and 39 preoperative CRT. Toxicity was similar for CT and CRT. Eight patients (11%) did not proceed to resection. The histopathological response rate (CRT 31% versus CT 8%, p = 0.01) and R1 resection rate (CRT 0% versus CT 11%, p = 0.04) favoured those receiving CRT. The median PFS was 14 and 26 months for CT and CRT respectively ( p = 0.37). The median OS was 29 months for CT compared with 32 months for CRT ( p = 0.83). Conclusions Despite no difference in survival, the improvement from preoperative CRT with respect to margin involvement makes this treatment a reasonable option for bulky, locally advanced resectable adenocarcinoma of the oesophagus.
A genetically-engineered strain of the dengue mosquito vector Aedes aegypti, designated OX3604C, was evaluated in large outdoor cage trials for its potential to improve dengue prevention efforts by ...inducing population suppression. OX3604C is engineered with a repressible genetic construct that causes a female-specific flightless phenotype. Wild-type females that mate with homozygous OX3604C males will not produce reproductive female offspring. Weekly introductions of OX3604C males eliminated all three targeted Ae. aegypti populations after 10-20 weeks in a previous laboratory cage experiment. As part of the phased, progressive evaluation of this technology, we carried out an assessment in large outdoor field enclosures in dengue endemic southern Mexico.
OX3604C males were introduced weekly into field cages containing stable target populations, initially at 10:1 ratios. Statistically significant target population decreases were detected in 4 of 5 treatment cages after 17 weeks, but none of the treatment populations were eliminated. Mating competitiveness experiments, carried out to explore the discrepancy between lab and field cage results revealed a maximum mating disadvantage of up 59.1% for OX3604C males, which accounted for a significant part of the 97% fitness cost predicted by a mathematical model to be necessary to produce the field cage results.
Our results indicate that OX3604C may not be effective in large-scale releases. A strain with the same transgene that is not encumbered by a large mating disadvantage, however, could have improved prospects for dengue prevention. Insights from large outdoor cage experiments may provide an important part of the progressive, stepwise evaluation of genetically-engineered mosquitoes.
OBJECTIVE:The aim of this study was to assess long-term health-related quality of life (HRQL) in patients after thoracoscopic and open esophagectomy.
SUMMARY OF BACKGROUND DATA:Trials comparing ...minimally invasive with open transthoracic esophagectomy have shown improved short-term outcomes; however, long-term HRQL data are lacking. This prospective nonrandomized study compared HRQL and survival after thoracoscopically assisted McKeown esophagectomy (TAMK) and open transthoracic Ivor Lewis esophagectomy (TTIL) for esophageal or gastroesophageal junction (GEJ) cancer.
METHODS:Patients with esophageal or GEJ cancer selected for TAMK or TTIL completed baseline and follow-up HRQL assessments for up to 24 months using the EORTC generic and disease-specific measures, QLQ-C30 and QLQ-OES18. Baseline clinical variables were examined between the treatment groups and changes in mean HRQL scores over time estimated and tested using generalised estimating equations with propensity score (generated by boosted regression) adjustment.
RESULTS:Of the 487 patients, 377 underwent TAMK and 110 underwent TTIL. Most clinical variables were similar in the 2 groups; however, there were significantly more patients with AJCC stage 3 disease who underwent TTIL than TAMK (54% vs 32%, P < 0.01) and this was reflected in the survival data.Mean symptom scores for pain were significantly higher in the TTIL group than in TAMK for 2 years postoperatively (P = 0.036). In addition, mean constipation scores were significantly higher for the TTIL group, with a 15-point difference in mean score at 3 months postoperatively (P = 0.037).
CONCLUSIONS:This large comprehensive nonrandomized analysis of longitudinal HRQL shows that TTIL is associated with more pain and constipation than TAMK.
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