Abemaciclib plus a nonsteroidal aromatase inhibitor as initial therapy for HR+, HER2- advanced breast cancer: final overall survival results of MONARCH 3.

BACKGROUND: In MONARCH 2, the addition of abemaciclib to fulvestrant significantly improved both progression-free survival (PFS) and overall survival (OS) in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) with disease progression on prior endocrine therapy. In MONARCH 3, the addition of abemaciclib to a nonsteroidal aromatase inhibitor (NSAI) as initial therapy for HR+, HER2- ABC significantly improved PFS. Here, we present the prespecified final OS results for MONARCH 3. PATIENTS AND METHODS: MONARCH 3 is a randomized, double-blind, phase III study of abemaciclib plus NSAI (anastrozole or letrozole) versus placebo plus NSAI in postmenopausal women with HR+, HER2- ABC without prior systemic therapy in the advanced setting. The primary objective was investigator-assessed PFS; OS was a gated secondary endpoint, and chemotherapy-free survival was an exploratory endpoint. RESULTS: A total of 493 women were randomized 2 : 1 to receive abemaciclib plus NSAI (n = 328) or placebo plus NSAI (n = 165). After a median follow-up of 8.1 years, there were 198 OS events (60.4%) in the abemaciclib arm and 116 (70.3%) in the placebo arm (hazard ratio, 0.804; 95% confidence interval 0.637-1.015; P = 0.0664, non-significant). Median OS was 66.8 versus 53.7 months for abemaciclib versus placebo. In the subgroup with visceral disease, there were 113 OS events (65.3%) in the abemaciclib arm and 65 (72.2%) in the placebo arm (hazard ratio, 0.758; 95% confidence interval 0.558-1.030; P = 0.0757, non-significant). Median OS was 63.7 months versus 48.8 months for abemaciclib versus placebo. The previously demonstrated PFS benefit was sustained, and chemotherapy-free survival numerically improved with the addition of abemaciclib. No new safety signals were observed. CONCLUSIONS: Abemaciclib combined with an NSAI resulted in clinically meaningful improvement in median OS (intent-to-treat population: 13.1 months; subgroup with visceral disease: 14.9 months) in patients with HR+ HER2- ABC; however, statistical significance was not reached.

Interventions for thrombosed haemodialysis arteriovenous fistulas and grafts.

BACKGROUND: Patients who present with problems with definitive dialysis access (arteriovenous fistula (AVF) or arteriovenous graft (AVG)) become catheter dependent (temporary access), a condition that often carries a higher risk of infections, central venous occlusions and recurrent hospitalisations. For AVG, primary patency rates are reported to be 30% to 90% in patients undergoing thrombectomy or thrombolysis. According to the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (NKF-KDOQI) guidelines, surgery is preferred when the cause of the thrombosis is a stenosis at the site of the anastomosis in thrombosed AVF. The European Best Practice Guidelines (EBPG) reported that thrombosed AVF may be preferably treated with endovascular techniques, but when the cause of thrombosis is in the anastomosis, surgery provides better results with re-anastomosis. Therefore, there is a need to carry out a systematic review to determine the effectiveness and safety of the intervention for thrombosed fistulae. OBJECTIVES: This review aims to establish the efficacy and safety of interventions for failed AVF and AVG in patients receiving haemodialysis (HD). SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 28 January 2024 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, EMBASE, conference proceedings, the International Clinical Trials Registry Portal (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: The review included randomised controlled trials (RCTs) and quasi-RCTs in people undergoing HD treatment using AVF or AVG presenting with clinical or haemodynamic evidence of thrombosis. Patients had to have used an AVF or AVG at least once. DATA COLLECTION AND ANALYSIS: Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: Our search strategy identified 14 eligible studies (1176 randomised participants) for inclusion in this review. We included three types of interventions for the treatment of thrombosed AVF and AVG: (1) types of thrombectomy, (2) types of thrombolysis and (3) surgical procedures. Most of the included studies had a high risk of bias due to a poor study design, a low number of patients and industry involvement. Overall, there was insufficient evidence to suggest that a specific intervention was better than another for the outcomes of failure, primary patency at 30 days, technical success and adverse events (both major and minor). Primary patency at 30 days may improve with surgical compared to mechanical thrombectomy (3 studies, 404 participants: RR 1.36, 95% CI 1.07 to 1.67); however, the evidence is very uncertain. Death, access dysfunction, successful dialysis, and SONG (Standards Outcomes in Nephrology) outcomes were rarely reported. The current review is limited by the small number of available studies with a limited number of patients enrolled. Most of the studies included in this review have a high risk of bias and a low or very low certainty of evidence. Further research is required to define the most effective and clinically appropriate technique for access dysfunction. AUTHORS' CONCLUSIONS: It remains unclear whether any intervention therapy affects the patency at 30 days or failure in any thrombosed HD AV access (very low certainty of evidence). Future research will very likely change the evidence base. Based on the importance of HD access to these patients, future studies of these interventions among people receiving HD should be a priority.

Predicting post-discharge complications in cardiothoracic surgery: A clinical decision support system to optimize remote patient monitoring resources.

Cardiac surgery patients are highly prone to severe complications post-discharge. Close follow-up through remote patient monitoring can help detect adverse outcomes earlier or prevent them, closing the gap between hospital and home care. However, equipment is limited due to economic and human resource constraints. This issue raises the need for efficient risk estimation to provide clinicians with insights into the potential benefit of remote monitoring for each patient. Standard models, such as the EuroSCORE, predict the mortality risk before the surgery. While these are used and validated in real settings, the models lack information collected during or following the surgery, determinant to predict adverse outcomes occurring further in the future. This paper proposes a Clinical Decision Support System based on Machine Learning to estimate the risk of severe complications within 90 days following cardiothoracic surgery discharge, an innovative objective underexplored in the literature. Health records from a cardiothoracic surgery department regarding 5 045 patients (60.8% male) collected throughout ten years were used to train predictive models. Clinicians' insights contributed to improving data preparation and extending traditional pipeline optimization techniques, addressing medical Artificial Intelligence requirements. Two separate test sets were used to evaluate the generalizability, one derived from a patient-grouped 70/30 split and another including all surgeries from the last available year. The achieved Area Under the Receiver Operating Characteristic curve on these test sets was 69.5% and 65.3%, respectively. Also, additional testing was implemented to simulate a real-world use case considering the weekly distribution of remote patient monitoring resources post-discharge. Compared to the random resource allocation, the selection of patients with respect to the outputs of the proposed model was proven beneficial, as it led to a higher number of high-risk patients receiving remote monitoring equipment.

High-resolution 3-dimensional tomography may be a useful tool for understanding the anatomy of hiatal hernias and surgical planning of patients eligible for laparoscopic or robotic antireflux surgery.

BACKGROUND: 3D computed tomography (CT) has been seldom used for the evaluation of hiatal hernias (HH) in surgical patients. This study aims to describe the 3D CT findings in candidates for laparoscopic or robotic antireflux surgery or HH repair and compare them with other tests. METHODS: Thirty patients with HH and/or gastroesophageal reflux disease (GERD) who were candidates for surgical treatment and underwent high-resolution CT were recruited. The variables studied were distance from the esophagogastric junction (EGJ) to the hiatus; total gastric volume and herniated gastric volume, percentage of herniated volume in relation to the total gastric volume; diameters and area of the esophageal hiatus. RESULTS: HH was diagnosed with CT in 21 (70%) patients. There was no correlation between the distance EGJ-hiatus and the herniated gastric volume. There was a statistically significant correlation between the distance from the EGJ to the hiatus and the area of the esophageal hiatus of the diaphragm. There was correlation between tomographic and endoscopic findings for the presence and size of HH. HH was diagnosed with manometry in 9 (50%) patients. There was no correlation between tomographic and manometric findings for the diagnosis of HH and between hiatal area and lower esophageal sphincter basal pressure. There was no correlation between any parameter and DeMeester score. CONCLUSIONS: The anatomy of HH and the hiatus can be well defined by 3D CT. The EGJ-hiatus distance may be equally measured by 3D CT or upper digestive endoscopy. DeMeester score did not correlate with any anatomical parameter.

Somatic mutation detection and KRAS amplification in testicular germ cell tumors.

Background: Testicular Germ Cell Tumors (TGCT) are the most common cancer among young adult men. The TGCT histopathology is diverse, and the frequency of genomic alterations, along with their prognostic role, remains largely unexplored. Herein, we evaluate the mutation profile of a 15-driver gene panel and copy number variation of KRAS in a large series of TGCT from a single reference cancer center. Materials and methods: A cohort of 97 patients with TGCT, diagnosed at the Barretos Cancer Hospital, was evaluated. Real-time PCR was used to assess copy number variation (CNV) of the KRAS gene in 51 cases, and the mutation analysis was performed using the TruSight Tumor 15 (Illumina) panel (TST15) in 65 patients. Univariate analysis was used to compare sample categories in relation to mutational frequencies. Survival analysis was conducted by the Kaplan-Meier method and log-rank test. Results: KRAS copy number gain was a very frequent event (80.4%) in TGCT and presented a worse prognosis compared with the group with no KRAS copy gain (10y-OS, 90% vs. 81.5%, p = 0.048). Among the 65 TGCT cases, different variants were identified in 11 of 15 genes of the panel, and the TP53 gene was the most recurrently mutated driver gene (27.7%). Variants were also detected in genes such as KIT, KRAS, PDGFRA, EGFR, BRAF, RET, NRAS, PIK3CA, MET, and ERBB2, with some of them potentially targetable. Conclusion: Although larger studies incorporating collaborative networks may shed the light on the molecular landscape of TGCT, our findings unveal the potential of actionable variants in clinical management for applying targeted therapies.

The butterflies (Lepidoptera, Papilionoidea) of the Parque Estadual Intervales and surroundings, São Paulo, Brazil / As borboletas (Lepidoptera, Papilionoidea) do Parque Estadual Intervales e arredores, São Paulo, Brasil

Abstract The Global South has witnessed increasing sampling of its immense biological diversity during the past century. However, the diversity of many regions remains unknown, even at pristine and highly threatened places, such as in the Atlantic Forest; and for bioindicator, umbrella, and flagship groups. The present study reports the first butterfly list of the Parque Estadual Intervales, São Paulo, Brazil and surroundings, a key protected area in the last massive continuous of the Atlantic Forest. We compiled data from museums and four years of field work, under three sampling methods. We also aimed at providing resources to support conservation efforts by analyzing 27 years of climatic data (detailed in the Supplementary Material, in English and in Portuguese), discussing our results also for non-academics, and producing scientific outreach and educational material. A companion article dealt with the experiences of science outreach and capacity development, and illustrated the butterfly catalogue of the species sampled in the park. We found 312 species that sum to 2,139 records. The museum had 229 species (432 records), and we sampled 142 species (1,682 individuals), in a total effort of 36,679 sampling hours (36,432 trap and 247 net and observation hours). The richest families were Nymphalidae (148 species) and Hesperiidae (100 species). Most species were sampled exclusively by active methods (79.8%), but other sources (passive sampling, citizen science, etc.) also found unique records. We found the highest diversity metrics from January to May, and we demonstrated that winter months had less richness and abundance. We illustrated the 20 species common to all regions, and listed those that were found more than seven months in the year, as well as the most abundant species in trap sampling, with forest dwellers as well as species common to open and fragmented areas. The dominant species in our trap datasets was the iridescent white morpho, Morpho epistrophus (Fabricius, 1796), and we suggest it to become the park butterfly mascot.

Resumo O Sul Global testemunhou crescente amostragem de sua imensa diversidade biológica durante o século passado. Entretanto, a diversidade de muitas regiões permanece desconhecida, mesmo em locais pristinos e altamente ameaçados, como na Mata Atlântica; e para grupos bioindicadores, guarda-chuva e emblemáticos. O presente estudo reporta a primeira lista de borboletas do Parque Estadual Intervales, São Paulo, Brasil e arredores, uma unidade de conservação chave no último maciço contínuo de Mata Atlântica. Compilamos dados de museus e quatro anos de campo, sob três métodos de amostragem. Também visamos oferecer recursos para apoiar os esforços de conservação, analisando 27 anos de dados climáticos (detalhados no Material Suplementar, em inglês e em português), discutindo nossos resultados numa linguagem também para não acadêmicos, e produzindo material de divulgação científica e educativos. Um artigo irmão tratou das experiências de divulgação científica e capacitação, e ilustrou o catálogo de borboletas das espécies amostradas no parque. Encontramos 312 espécies em 2.139 registros. O museu tinha 229 espécies (432 registros), e amostramos 142 espécies (1.682 indivíduos), em um esforço total de 36.679 horas de amostragem (36.432 armadilhas e 247 horas de rede e observação). As famílias mais ricas foram Nymphalidae (148 espécies) e Hesperiidae (100 espécies). A maioria das espécies foi amostrada exclusivamente por métodos ativos (79,8%), mas outras fontes (passiva, ciência cidadã, etc.) também encontraram registros únicos. Encontramos as maiores métricas de diversidade de janeiro a maio, e demonstramos que os meses de inverno tiveram menos riqueza e abundância. Ilustramos as 20 espécies comuns a todas as regiões, e listamos aquelas que foram encontradas em mais de sete meses no ano, bem como as espécies mais abundantes em armadilhas, com espécies florestais e também comuns em áreas abertas e fragmentadas. A espécie dominante em nossas armadilhas foi a morfo branca iridescente, Morpho epistrophus (Fabricius, 1796), e sugerimos que se torne a borboleta mascote do parque.

Butterflies (Lepidoptera: Papilionoidea) of Iguaçu National Park and surrounding areas in southern Brazil: a long-term survey, with six new records for the Brazilian fauna / As Borboletas (Lepidoptera: Papilionoidea) do Parque Nacional do Iguaçu e arredores no Sul do Brasil: um inventário de longo prazo, com seis novos registros para a fauna brasileira

Abstract Iguaçu National Park is the second largest (1852.62 km²) protected area in the Atlantic Forest domain and harbors the largest area of semideciduous seasonal forest in Brazil. In this study, we present 795 subspecies and 787 species of butterflies that occur in this protected area and its surrounding areas, collected over 15 years and ten months using different non-standardized sampling methods. We also searched for additional records in the literature, entomological collections, and citizen science platforms on the internet. Among the sampled taxa, six are recorded for the first time in Brazil: Emesis orichalceus Stichel, 1916, Theope p. pakitza Hall & Harvey, 1998 (Riodinidae), Elbella v. viriditas (Skinner, 1920), Apaustus gracilis ssp. n. (Hesperiidae), Deltaya sp. n. (Nymphalidae), and Symbiopsis sp. n. (Lycaenidae). Another six are listed as endangered in lists of butterflies of conservation concern. The records for some species significantly increase previously documented distributions.

Resumo O Parque Nacional do Iguaçu é a segunda maior Unidade de Conservação (1.852,62 km²) no domínio Mata Atlântica, abrigando a maior área de Floresta Estacional Semidecídua no Brasil. Neste estudo apresentamos uma lista com 795 subespécies e 787 espécies de borboletas que ocorrem nesta Unidade de Conservação e seus arredores, coligida ao longo de 15 anos e dez meses através do uso de diferentes métodos de amostragem não padronizados. Nós também procuramos por registros adicionais na literatura, coleções entomológicas e plataformas de ciência cidadã na internet. Dentre os táxons amostrados, seis são registrados pela primeira vez para o Brasil: Emesis orichalceus Stichel, 1916, Theope p. pakitza Hall & Harvey, 1998 (Riodinidae), Elbella v. viriditas (Skinner, 1920), Apaustus gracilis ssp. n. (Hesperiidae), Deltaya sp. n. (Nymphalidae) e Symbiopsis sp. n. (Lycaenidae). Outras seis espécies são consideradas ameaçadas de extinção em listas de borboletas de interesse para a conservação. Os registros de algumas espécies aumentam significativamente as suas distribuições previamente documentadas.

Cryptosporidium spp. and Giardia spp. in wild rodents: using occupancy models to estimate drivers of occurrence and prevalence in native forest and exotic Pinus radiata plantations from Central Chile.

The conversion of native forest to forestry plantations is a worldwide practice, affecting biodiversity and host-parasite interactions. One of the most common timber plantations in the world are monocultures of Monterey pine (Pinus radiata). Using occupancy models, we analyzed the occurrence and prevalence of Cryptosporidium spp. oocysts and Giardia spp. cysts in fecal samples of wild rodents from a landscape dominated by extensive Monterey pine plantations in central Chile. We aimed to assess drivers of parasite infection such as habitat type, abundance of rodent hosts, species richness, and season. Small mammals were sampled seasonally for two years in three habitat types: native forests, adult pine plantations and young pine plantations. A total of 1091 fecal samples from seven small mammal species were analyzed by coprological analysis. Occurrence probability of Cryptosporidium spp. and Giardia spp. was similar for the most abundant rodent species (Abrothrix longipilis, A. olivacea, and Oligoryzomys longicaudatus) and for all habitat types. For Cryptosporidium spp., variation in prevalence was mostly explained by season with higher prevalence during winter season and lower during spring. For Giardia spp., the prevalence was significantly higher in young pine plantations, followed by adult pine plantations and native forests. In addition, higher prevalence of Giardia spp. was associated with lower host richness, suggesting a possible dilution effect. Our findings reveal that Monterey pine plantations increase Giardia spp. transmission among rodents, but has no clear effect on Cryptosporidium spp., providing evidence that the impact of land use on parasitism can be idiosyncratic. Since both parasites have zoonotic potential, our findings may be useful for land use planning and management considering health issues.

Magnetoliposomes Containing Multicore Nanoparticles and a New Antitumor Thienopyridine Compound with Potential Application in Chemo/Thermotherapy.

Multicore magnetic nanoparticles of manganese ferrite were prepared using carboxymethyl dextran as an agglutinating compound or by an innovative method using melamine as a cross-coupling agent. The nanoparticles prepared using melamine exhibited a flower-shape structure, a saturation magnetization of 6.16 emu/g and good capabilities for magnetic hyperthermia, with a specific absorption rate (SAR) of 0.14 W/g. Magnetoliposome-like structures containing the multicore nanoparticles were prepared, and their bilayer structure was confirmed by FRET (Förster Resonance Energy Transfer) assays. The nanosystems exhibited sizes in the range of 250-400 nm and a low polydispersity index. A new antitumor thienopyridine derivative, 7-[4-(pyridin-2-yl)-1H-1,2,3-triazol-1-yl]thieno[3,2-b]pyridine, active against HeLa (cervical carcinoma), MCF-7 (breast adenocarcinoma), NCI-H460 (non-small-cell lung carcinoma) and HepG2 (hepatocellular carcinoma) cell lines, was loaded in these nanocarriers, obtaining a high encapsulation efficiency of 98 ± 2.6%. The results indicate that the new magnetoliposomes can be suitable for dual cancer therapy (combined magnetic hyperthermia and chemotherapy).

Influence of solvents on the morphology of Langmuir and Langmuir-Schaefer films of PCBM and PCBM-based oligomers and polymers.

Fullerene-based polymers and oligomers combined with non-fullerene acceptors show extremely high efficiencies in organic photovoltaic devices. Furthermore, fullerene-based materials are of interest for use in anti-cancer and anti-viral treatments, where their presence can enhance the efficacy of medication considerably. Therefore, it remains important to understand their morphology and electronic properties to improve devices and technological applications. The main goal of this study is to prepare and characterize Langmuir and Langmuir-Schaefer films of PCBM-based materials to investigate the influence of different solvents such as chloroform, toluene, and xylene, and co-components on their morphology. PCBM-based materials were thus studied either alone or in mixtures with a polythiophene derivative (poly(3-hexythiophene), P3HT) commonly used in organic photovoltaic devices. The formation of Langmuir films was studied using surface pressure isotherms and Brewster's angle microscopy (BAM), where the homogeneity, phase behavior, and morphology of the films were investigated. In addition, Langmuir-Schaefer films were characterized by UV-visible absorption spectroscopy, atomic force microscopy (AFM), and Raman spectroscopy, providing information on the morphology of the solid films. This study has shown that it is possible to successfully fabricate Langmuir and Langmuir-Schaefer films of PCBM and PCBM-based oligomers and polymers, both pure and in mixtures with P3HT, to compare their organization, roughness, and optical properties. With the Langmuir films, it was possible to estimate the area of the molecules and visualize their aggregation through BAM images, establishing a relationship between the area occupied by these materials and the solvent used. All characterization techniques corroborate that the use of chloroform significantly reduced the roughness of the LS films mixed with P3HT and also presented a higher ordering compared to films prepared with xylene solutions.

Grapiprant or carprofen following ovariohysterectomy in the cat: analgesic efficacy, hematological, biochemical and urinalysis evaluation.

OBJECTIVES: This study aimed to compare the analgesic effect between carprofen and grapiprant every 12 or 24 h on postoperative pain in cats undergoing ovariohysterectomy, in addition to the effects on the hematological, biochemical and urinalysis variables. METHODS: A total of 32 female cats were randomly divided into three groups, according to the treatment administered with the first dose given orally 90 mins before surgery, as follows: CAR (cats received 4 mg/kg carprofen, n = 11); GRA1 (cats received 2 mg/kg grapiprant, n = 10); and GRA2 (cats received 2 mg/kg grapiprant q12h, n = 11). Pain was assessed by UNESP-Botucatu Multidimensional Composite Pain Scale (UNESP) and Glasgow Feline Composite Measure Pain Scale (GLASGOW) for cats preoperatively (baseline) and at 1, 3, 6, 8, 12 and 24 h after extubation. Venous blood was collected at baseline, and 12 and 24 h after the administration of carprofen or grapiprant to perform a complete blood count (CBC), the percentage of Heinz bodies and serum biochemistry (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyltransferase, creatinine and urea). Urinalysis was performed at baseline and 24 h after extubation. Glucose levels were evaluated at baseline and 1 h postoperatively. RESULTS: Pain scores were not significantly different among groups in both scales, although pain was higher at 3 h in comparison with 24 h in all groups. In the GRA1 and GRA2 groups, 67% (14/21) of cats needed rescue analgesia compared with 18% (2/11) in the CAR group. Glucose increased from baseline to 1 h in the GRA1 and GRA2 groups. None of the CBC, serum biochemistry and urinalysis variables differed among groups. CONCLUSIONS AND RELEVANCE: Grapiprant did not promote adequate analgesia during the first 3 h postoperatively in cats undergoing ovariohysterectomy compared with carprofen, and no benefits were observed by administering grapiprant every 12 h.

Roux-en-O: How It Happens and How to Fix It.

The Roux-en-Y gastric bypass surgery improper technique can cause complications such as Roux-en-O, which is caused by an inadvertent anastomosis of the biliopancreatic limb to the gastric pouch, creating an "O" form to the bypass. We present intraoperative images of a mistaken Roux-en-Y's technique that caused the "O" anatomy and its successful reconstruction.

The butterflies of Cristalino Lodge, in the Brazilian southern Amazonia: An updated species list with a significant contribution from citizen science / As borboletas do Cristalino Lodge, no sul da Amazônia: Uma lista atualizada de espécies com contribuição significativa da ciência cidadã

Abstract The richest butterfly communities in the world are found in the Amazon rainforest. Despite of this, and the importance of species inventories for the knowledge of diversity patterns, there are few comprehensive lists of butterflies for localities in the Brazilian Amazon. Here, we present an updated list of the butterflies of Cristalino Lodge (Alta Floresta, Mato Grosso, Brazil), in southern Amazonia, based on specimens collected by researchers and photographic records taken by ecotourists, butterfly watchers, and tour guides. With 1010 species recorded, this is currently the largest list of butterflies published for a single locality in Brazil and the first to reach (and surpass) 1000 species, with more than one third of the records coming from citizen science. The region has about 29% of the butterfly species in Brazil and one of the greatest richnesses known in the country, inferior only to areas in the western Amazon. Its fauna is mainly composed of species widely distributed in lowland Amazonia, with the addition of some species typical of the Cerrado. It has a relatively low number of species of the tribe Ithomiini (Nymphalidae: Danainae), generally considered a good indicator of the total butterfly diversity in neotropical forests, which points to the need for caution when using a single taxonomic group as a surrogate of richness of entire communities. The present work highlights the importance of citizen science and ecotourism centers for inventories and data on species distribution in diverse tropical forests.

Resumo As comunidades de borboletas mais ricas do mundo são encontradas na Amazônia. Apesar disso, e da importância dos inventários de espécies para o conhecimento dos padrões de diversidade, existem poucas listas abrangentes de borboletas para localidades da Amazônia brasileira. Aqui, apresentamos uma lista atualizada das borboletas do Cristalino Lodge (Alta Floresta, Mato Grosso, Brasil), no sul da Amazônia, baseada em espécimes coletados por pesquisadores e em registros fotográficos feitos por ecoturistas, observadores de borboletas e guias turísticos. Com 1010 espécies registradas, essa é atualmente a maior lista de borboletas publicada para uma localidade no Brasil e a primeira a atingir 1000 espécies, sendo mais de um terço dos registros provenientes da ciência cidadã. A região apresenta cerca de 29% das espécies de borboletas do Brasil e uma das maiores riquezas conhecidas no país, inferior apenas a áreas no oeste da Amazônia. Sua fauna é composta principalmente por espécies amplamente distribuídas na planície amazônica, com adição de algumas típicas do Cerrado. Possui um número relativamente baixo de espécies da tribo Ithomiini (Nymphalidae: Danainae), que é geralmente considerada uma boa indicadora da riqueza total de borboletas em florestas neotropicais, o que aponta para a necessidade de cautela ao se usar um grupo taxonômico como previsor da riqueza de comunidades inteiras. O presente trabalho destaca a importância da ciência cidadã e dos centros de ecoturismo para inventários e dados sobre distribuição de espécies em florestas tropicais diversas.

The contribution of the BIOTA/FAPESP Program to the advancement of the knowledge on terrestrial invertebrates / A contribuição do Programa BIOTA/FAPESP para o avanço no conhecimento sobre os invertebrados terrestres

Abstract The variability of the organisms living in a given area constitute what is referred to as biodiversity, one of nature's fundamental properties, responsible for the balance and stability of ecosystems. The loss of biodiversity has been of great concern to scientists, especially because of the role played by human activities in this regard, able to lead to irreversible circumstances. The São Paulo Research Foundation (Fundação de Amparo à Pesquisa do Estado de São Paulo, FAPESP) plays a major role in supporting research efforts in the most diverse branches of science. In the late 1990´s, FAPESP launched a major program to promote research on biodiversity, named BIOTA/FAPESP. So far, this program has financed the conduction of 26 projects, involving research activities in most of Brazil, while focusing mainly the State of São Paulo. These projects have generated about 1140 publications in peer-reviewed journals of high standard, providing relevant information, including the original description of 1187 species and 76 genera, the complementary description of 350 species, as well as a number of inventory works, biological studies, etc. The program has also been instrumental in the establishment or adequacy of research facilities and training of new taxonomists. Most extensively studied groups of terrestrial invertebrates include Insecta of the orders Hymenoptera, Lepidoptera and Diptera, and Arachnida of the subclasses Araneae and Acari. Distinct projects have also contributed to the detection of organisms potentially useful as biological control agents and in the determination of maps of major interest for the establishment of public policies. In the future, priority groups for study should include the Annelida and the Nematoda, for the potential both have as beneficial organisms, or for the potential some Nematoda have as organisms harmful to plants and animals.

Resumo A variabilidade dos organismos em uma determinada área constitui o que se denomina biodiversidade, uma das propriedades fundamentais da natureza, responsável pelo equilíbrio e estabilidade dos ecossistemas. A perda da biodiversidade tem sido uma grande preocupação para os cientistas, principalmente pelo papel desempenhado pelas atividades humanas, com potencial para desencadear circunstâncias irreversíveis. A Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) desempenha um papel importante no apoio às pesquisas nos mais diversos ramos da ciência. No final da década de 1990, a FAPESP lançou um grande programa de fomento à pesquisa em biodiversidade, denominado BIOTA/FAPESP. Até o momento, este programa financiou a realização de 26 projetos, envolvendo atividades na maior parte do Brasil, embora tenham como foco principal o estado de São Paulo. Esses projetos geraram cerca de 1.140 publicações em periódicos de alto impacto, fornecendo informações relevantes que incluem a descrição original de 1.187 espécies e 76 gêneros e a descrição complementar de 350 espécies, além de diversos trabalhos de inventário, estudos biológicos etc. O programa também tem sido fundamental para o estabelecimento ou adequação de instalações de pesquisa científica e o treinamento de novos taxonomistas. Os grupos de invertebrados terrestres mais estudados incluem os Insecta das ordens Hymenoptera, Lepidoptera e Diptera, e os Arachnida das subclasses Araneae e Acari. Projetos distintos também têm contribuído para a detecção de organismos potencialmente úteis como agentes de controle biológico e na determinação de mapas de áreas preferenciais para o estabelecimento de políticas públicas. No futuro, os grupos prioritários de estudo devem incluir os Annelida e os Nematoda, pelo potencial que ambos têm como organismos benéficos, ou pelo potencial que alguns Nematoda têm como organismos prejudiciais a plantas e animais.

Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: updated efficacy and Ki-67 analysis from the monarchE study.

BACKGROUND: Adjuvant abemaciclib combined with endocrine therapy (ET) previously demonstrated clinically meaningful improvement in invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) in hormone receptor-positive, human epidermal growth factor receptor 2-negative, node-positive, high-risk early breast cancer at the second interim analysis, however follow-up was limited. Here, we present results of the prespecified primary outcome analysis and an additional follow-up analysis. PATIENTS AND METHODS: This global, phase III, open-label trial randomized (1 : 1) 5637 patients to adjuvant ET for ≥5 years ± abemaciclib for 2 years. Cohort 1 enrolled patients with ≥4 positive axillary lymph nodes (ALNs), or 1-3 positive ALNs and either grade 3 disease or tumor ≥5 cm. Cohort 2 enrolled patients with 1-3 positive ALNs and centrally determined high Ki-67 index (≥20%). The primary endpoint was IDFS in the intent-to-treat population (cohorts 1 and 2). Secondary endpoints were IDFS in patients with high Ki-67, DRFS, overall survival, and safety. RESULTS: At the primary outcome analysis, with 19 months median follow-up time, abemaciclib + ET resulted in a 29% reduction in the risk of developing an IDFS event [hazard ratio (HR) = 0.71, 95% confidence interval (CI) 0.58-0.87; nominal P = 0.0009]. At the additional follow-up analysis, with 27 months median follow-up and 90% of patients off treatment, IDFS (HR = 0.70, 95% CI 0.59-0.82; nominal P < 0.0001) and DRFS (HR = 0.69, 95% CI 0.57-0.83; nominal P < 0.0001) benefit was maintained. The absolute improvements in 3-year IDFS and DRFS rates were 5.4% and 4.2%, respectively. Whereas Ki-67 index was prognostic, abemaciclib benefit was consistent regardless of Ki-67 index. Safety data were consistent with the known abemaciclib risk profile. CONCLUSION: Abemaciclib + ET significantly improved IDFS in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative, node-positive, high-risk early breast cancer, with an acceptable safety profile. Ki-67 index was prognostic, but abemaciclib benefit was observed regardless of Ki-67 index. Overall, the robust treatment benefit of abemaciclib extended beyond the 2-year treatment period.

Enhancing adoptive CD8 T cell therapy by systemic delivery of tumor associated antigens.

Adoptive T-cell transfer (ACT) offers a curative therapeutic option for subsets of melanoma and hematological cancer patients. To increase response rates and broaden the applicability of ACT, it is necessary to improve the post-infusion performance of the transferred T cells. The design of improved treatment strategies includes transfer of cells with a less differentiated phenotype. Such T cell subsets have high proliferative potential but require stimulatory signals in vivo to differentiate into tumor-reactive effector T cells. Thus, combination strategies are needed to support the therapeutic implementation of less differentiated T cells. Here we show that systemic delivery of tumor-associated antigens (TAAs) facilitates in vivo priming and expansion of previously non-activated T cells and enhance the cytotoxicity of activated T cells. To achieve this in vivo priming, we use flexible delivery vehicles of TAAs and a TLR7/8 agonist. Contrasting subcutaneous delivery systems, these vehicles accumulate TAAs in the spleen, thereby achieving close proximity to both cross-presenting dendritic cells and transferred T cells, resulting in robust T-cell expansion and anti-tumor reactivity. This TAA delivery platform offers a strategy to safely potentiate the post-infusion performance of T cells using low doses of antigen and TLR7/8 agonist, and thereby enhance the effect of ACT.

Ultrasound-assisted transesterification of soybean oil using low power and high frequency and no external heating source.

In this work, high frequency and low power ultrasound without external heating source and mechanical stirring in biodiesel production were studied. Transesterification of soybean oil with methanol and catalyzed by KOH was investigated using ultrasound equipment and ultrasonic transducer. The effect of ultrasonic output power (3 W-9 W), ultrasonic frequency (1 MHz and 3 MHz), and alcohol to oil molar ratio (6:1 and 8:1) have been investigated. The increase in ultrasonic power provided higher conversion rates. In addition, higher conversion rates were obtained by increasing the ultrasonic frequency from 1 MHz to 3 MHz (48.7% to 79.5%) for the same reaction time. Results also indicate that the speed of sound can be used to evaluate the produced biodiesel qualitatively. Further, the ultrasound system presented electric consumption (46.2W∙h) four times lower than achieved using the conventional method (211.7W∙h and 212.3W∙h). Thus, biodiesel production using low power ultrasound in the MHz frequency range is a promising technology that could contribute to biodiesel production processes.

Long-term outcomes of pediatric laparoscopic needled-assisted inguinal hernia repair: A 10-year experience.

PURPOSE: Laparoscopic inguinal hernia repair (LIHR) has gained wide acceptance over the past decade, although studies with longer term follow-up are lacking. We present one of the largest cohorts of children undergoing laparoscopic needle-assisted repair (LNAR) with long-term follow-up. METHODS: A clinical quality database was maintained for children ≤14 years of age who underwent laparoscopic needle-assisted repair between 2009 and 2017 with review of follow-up through 2019. De-identified data was reviewed. RESULTS: 1023 patients with 1457 LNAR were included during the 10-year period. Mean age at surgery was 2.56 years (2 days to14 years). The overall hernia recurrence rate was 0.75% (11/1457). A total of four postoperative hydroceles required intervention. Preterm infant repair done <60w post conceptional age had a significantly lower recurrence rate (0.63%) than other patients (0.82%) (p < 0.01). 64.2% of patients had clinical follow-up over a period of 11 years with a mean follow-up of 5.97 years. CONCLUSION: We present a large cohort study of consecutive pediatric laparoscopic hernia repairs followed over an 11-year period. LNAR is safe and effective for term and preterm patients with similar complication rates to other techniques, including open repair. Additionally, our results suggest that preterm infants may have superior outcomes with this method. LEVEL OF EVIDENCE: Level III - Retrospective Comparative Study.