Biologic Diversity Research Articles

Metabolic capabilities are highly conserved among human nasal-associated Corynebacterium species in pangenomic analyses.

Pangenomic analysis with estimation of functional capabilities facilitates our understanding of the full biologic diversity of bacterial species. We performed systematic genomic, phylogenomic, and pangenomic analyses with qualitative estimation of the metabolic capabilities of four common human nasal Corynebacterium species, along with focused experimental validations, generating a foundational resource. The prevalence of each species in human nasal microbiota is consistent with the common coexistence of at least two species. We identified a notably high level of metabolic conservation within and among species indicating limited options for species to occupy distinct metabolic niches, highlighting the importance of investigating interactions among nasal Corynebacterium species. Comparing strains from two continents, C. pseudodiphtheriticum had restricted geographic strain distribution characterized by an evolutionarily recent loss of assimilatory sulfate reduction in U.S. strains. Our findings contribute to understanding the functions of Corynebacterium within human nasal microbiota and to evaluating their potential for future use as biotherapeutics.

Simultaneous single-nucleus RNA sequencing and single-nucleus ATAC sequencing of neuroblastoma cell lines

Neuroblastoma is the most common extracranial solid tumor in children, and a leading cause of childhood cancer deaths. All neuroblastomas arise from neural crest-derived sympathetic neuronal progenitors, but numerous mutations, the most common of which is MYCN amplification, give rise to these lesions. Epigenetic aberrations also play a role in oncogenesis and tumor progression. To better understand biologic diversity of neuroblastomas, we performed joint single-nucleus ATAC sequencing and single-nucleus RNA sequencing on six neuroblastoma cell lines, three of which are MYCN amplified. After standard filtering for high-quality nuclei, we obtained chromatin accessibility and transcript abundance data from 41,733 neuroblastoma tumor cells. Preliminary analysis reveals significant diversity in chromatin landscape and gene expression across neuroblastoma cell lines. This dataset is a valuable resource for studying the transcriptional and epigenetic mechanisms of this deadly childhood disease.

A multi-model approach integrating whole-slide imaging and clinicopathologic features to predict breast cancer recurrence risk.

Breast cancer is the most common malignancy affecting women worldwide and is notable for its morphologic and biologic diversity, with varying risks of recurrence following treatment. The Oncotype DX Breast Recurrence Score test is an important predictive and prognostic genomic assay for estrogen receptor positive/HER2 negative breast cancer that guides therapeutic strategies; however, such tests can be expensive, delay care, and are not widely available. The aim of this study was to develop a multi-model approach integrating the analysis of whole-slide images and clinicopathologic data to predict their associated breast cancer recurrence risks and categorize these patients into two risk groups according to the predicted score: low-risk and high-risk. The proposed novel methodology uses convolutional neural networks for feature extraction and vision transformers for contextual aggregation, complemented by a logistic regression model that analyzes clinicopathologic data for classification into two risk categories. This method was trained and tested on 956 hematoxylin and eosin-stained whole-slide images of 950 ER+/HER2- breast cancer patients with corresponding clinicopathological features that had prior Oncotype DX testing. The model's performance was evaluated using an internal test set of 192 patients from Dartmouth Health and an external test set of 405 patients from the University of Chicago. The multi-model approach achieved an AUC of 0.91 (95% CI: 0.87-0.95) on the internal set and an AUC of 0.84 (95% CI: 0.78-0.89) on the external cohort for predicting low- and high-breast cancer recurrence risk categories based on the Oncotype DX recurrence score. With further validation, the proposed methodology could provide an alternative to assist clinicians in personalizing treatment for breast cancer patients and potentially improving their outcomes.

Metabolic capabilities are highly conserved among human nasal-associated Corynebacterium species in pangenomic analyses.

Corynebacterium species are globally ubiquitous in human nasal microbiota across the lifespan. Moreover, nasal microbiota profiles typified by higher relative abundances of Corynebacterium are often positively associated with health. Among the most common human nasal Corynebacterium species are C. propinquum, C. pseudodiphtheriticum, C. accolens, and C. tuberculostearicum. To gain insight into the functions of these four species, we identified genomic, phylogenomic, and pangenomic properties and estimated the metabolic capabilities of 87 distinct human nasal Corynebacterium strain genomes: 31 from Botswana and 56 from the USA. C. pseudodiphtheriticum had geographically distinct clades consistent with localized strain circulation, whereas some strains from the other species had wide geographic distribution spanning Africa and North America. All species had similar genomic and pangenomic structures. Gene clusters assigned to all COG metabolic categories were overrepresented in the persistent versus accessory genome of each species indicating limited strain-level variability in metabolic capacity. Based on prevalence data, at least two Corynebacterium species likely coexist in the nasal microbiota of 82% of adults. So, it was surprising that core metabolic capabilities were highly conserved among the four species indicating limited species-level metabolic variation. Strikingly, strains in the USA clade of C. pseudodiphtheriticum lacked genes for assimilatory sulfate reduction present in most of the strains in the Botswana clade and in the other studied species, indicating a recent, geographically related loss of assimilatory sulfate reduction. Overall, the minimal species and strain variability in metabolic capacity implies coexisting strains might have limited ability to occupy distinct metabolic niches.

The Biologic Diversity of Colorectal Carcinoma (CRC) is Present in the Early Stage: Quantitative Analysis of Malignant Polyps

Abstract Introduction/Objective Risk factors in malignant polyps to predict recurrence in T1 colorectal carcinoma (CRC) include depth of invasion, margin status, lymphovascular invasion, tumor differentiation and budding. However, the effect of other factors, such as tumor volume and tumor cellularity, are not well studied. We quantitatively, using image analysis, determined the strength and interdependence of the depth of invasion, margin status, tumor volume and tumor cell density on the probability of having residual adenocarcinoma on resection and long term patient outcomes. Methods/Case Report Endoscopic mucosal resection (EMR) specimens of polyps with T1 CRC were identified by retrospective search of the pathology database over a 14-year period (01/01/2008 to 05/05/2022). Depth of invasion, distance of tumor to margin, tumor volume (defined by the invasive area comprising the tumor cells and associated others cells) and cellularity (number of adenocarcinoma cells/area) were measured using Aperio eSlide Manager Leica Biosystems Imaging, Inc. The depth of invasion was measured from the muscularis mucosa. Available outcome data was collected from subsequent segmental resection and oncology consultations and imaging from the patient charts. Results (if a Case Study enter NA) 22 patients of malignant polyps with EMR were identified; 11 patients underwent subsequent resection with residual tumor in 4 and lymph node metastasis in 1. Follow-up period was from 3 to 12 yrs, with recurrence in none. The median tumor cellularity was 2712 cells/mm2 with SD 1421 cells/mm2 and was similar in residual versus non residual tumors with no correlation with LVI. Distance of tumor (um) from deep margin was measured in 20 cases and by Receiver Operator Characteristic analysis and calculation of the area under the curve (AUC) was a good test of residual tumor (AUC = 0.88) while depth of invasion was not a good test (AUC =0.5). Tumor volume and adenocarcinoma cells/area were not correlated; however, interestingly, tumor volume and depth of invasion were linearly correlated (p<0.001). Conclusion The distance of tumor to the margin is a better predictor for residual cancer than depth of invasion. The linear correlation of tumor volume and depth of invasion implies the same shape of invasion which is interestingly independent of tumor cellularity. This finding further strengthens the hypothesis that cancer associated cells in the tumor microenvironment are important in driving the biological behavior of malignant polyps.

Latissimus Dorsi Myocutaneous Flap Reconstruction Post Resection of a Giant Malignant Phyllodes Tumor of the Breast: A Case Report

Phyllodes tumors (PTs) are a rare group of mammary fibroepithelial lesions accounting for up to 1% of breast tumors. They display biologic diversity, ranging from benign to malignant. PTs of the breast are mostly found in females aged 35–55 years and are rare in adolescents and the elderly. They usually present as a fast growing, painless breast mass. The treatment of choice for PTs is complete excision with clear margins. In patients with large PTs, breast reconstruction results in better outcome and increased satisfaction.Our patient, a 39-year-old female presented with an enlarging breast mass over a period of 6 months. Physical examination showed a large, ulcerated mass involving the entire right breast. Histopathology revealed features of a malignant PT. Total mastectomy and immediate reconstruction with a pedicled latissimus dorsi myocutaneous flap and symmetrization reduction mastopexy of the left breast was done. At 6 months, the patient has not shown any gross tumor recurrence with acceptable cosmesis.

Transcriptomic Heterogeneity of Expansile Cribriform and Other Gleason Pattern 4 Prostate Cancer Subtypes

BackgroundProstate cancers featuring an expansile cribriform (EC) pattern are associated with worse clinical outcomes following radical prostatectomy (RP). However, studies of the genomic characteristics of Gleason pattern 4 subtypes are limited. ObjectiveTo explore transcriptomic characteristics and heterogeneity within Gleason pattern 4 subtypes (fused/poorly formed, glomeruloid, small cribriform, EC/intraductal carcinoma [IDC]) and the association with biochemical recurrence (BCR)-free survival. Design, setting, and participantsThis was a retrospective cohort study including 165 men with grade group 2–4 prostate cancer who underwent RP at a single academic institution (2016–2020) and Decipher testing of the RP specimen. Patients with Gleason pattern 5 were excluded. IDC and EC patterns were grouped. Median follow-up was 2.5 yr after RP for patients without BCR. Outcomes measurements and statistical analysisPrompted by heterogeneity within pattern 4 subtypes identified via exploratory analyses, we investigated transcriptomic consensus clusters using partitioning around medoids and hallmark gene set scores. The primary clinical outcome was BCR, defined as two consecutive prostate-specific antigen measurements >0.2 ng/ml at least 8 wk after RP, or any additional treatment. Multivariable Cox proportional-hazards models were used to determine factors associated with BCR-free survival. Results and limitationsIn this cohort, 99/165 patients (60%) had EC and 67 experienced BCR. Exploratory analyses and clustering demonstrated transcriptomic heterogeneity within each Gleason pattern 4 subtype. In the multivariable model controlled for pattern 4 subtype, margin status, Cancer of the Prostate Risk Assessment Post-Surgical score, and Decipher score, a newly identified steroid hormone–driven cluster (hazard ratio 2.35 95% confidence interval 1.01–5.47) was associated with worse BCR-free survival. The study is limited by intermediate follow-up, no validation cohort, and lack of accounting for intratumoral and intraprostatic heterogeneity. ConclusionsTranscriptomic heterogeneity was present within and across each Gleason pattern 4 subtype, demonstrating there is additional biologic diversity not captured by histologic subtypes. This heterogeneity can be used to develop novel signatures and to classify transcriptomic subtypes, which may help in refining risk stratification following RP to further guide decision-making on adjuvant and salvage treatments. Patient summaryWe studied prostatectomy specimens and found that tumors with similar microscopic appearance can have genetic differences that may help to predict outcomes after prostatectomy for prostate cancer. Our results demonstrate that further gene expression analysis of prostate cancer subtypes may improve risk stratification after prostatectomy. Future studies are needed to develop novel gene expression signatures and validate these findings in independent sets of patients.

Outcomes of Childhood Noninfant Acute Lymphoblastic Leukemia With 11q23/KMT2A Rearrangements in a Modern Therapy Era: A Retrospective International Study.

We aimed to study prognostic factors and efficacy of allogeneic hematopoietic stem-cell transplantation (allo-HSCT) in first remission of patients with noninfant childhood acute lymphoblastic leukemia (ALL) with 11q23/KMT2A rearrangements treated with chemotherapy regimens between 1995 and 2010. Data were retrospectively retrieved from 629 patients with 11q23/KMT2A-rearranged ALL from 17 members of the Ponte-di-Legno Childhood ALL Working Group. Clinical and biologic characteristics, early response assessed by minimal residual disease at the end of induction (EOI) therapy, and allo-HSCT were analyzed for their impact on outcomes. A specific 11q23/KMT2A translocation partner gene was identified in 84.3% of patients, with the most frequent translocations being t(4;11)(q21;q23) (n = 273; 51.5%), t(11;19)(q23;p13.3) (n = 106; 20.0%), t(9;11)(p21_22;q23) (n = 76; 14.3%), t(6;11)(q27;q23) (n = 20; 3.8%), and t(10;11)(p12;q23) (n = 14; 2.6%); 41 patients (7.7%) had less frequently identified translocation partner genes. Patient characteristics and early response varied among subgroups, indicating large biologic heterogeneity and diversity in therapy sensitivity among 11q23/KMT2A-rearranged ALL. The EOI remission rate was 93.2%, and the 5-year event-free survival (EFS) for the entire cohort was 69.1% ± 1.9%, with a range from 41.7% ± 17.3% for patients with t(9;11)-positive T-ALL (n = 9) and 64.8% ± 3.0% for patients with t(4;11)-positive B-ALL (n = 266) to 91.2% ± 4.9% for patients with t(11;19)-positive T-ALL (n = 34). Low EOI minimal residual disease was associated with favorable EFS, and induction failure was particularly predictive of nonresponse to further therapy and relapse and poor EFS. In addition, EFS was not improved by allo-HSCT compared with chemotherapy only in patients with both t(4;11)-positive B-ALL (n = 64 v 51; P = .10) and 11q23/KMT2A-rearranged T-ALL (n = 16 v 10; P = .69). Compared with historical data, prognosis of patients with noninfant 11q23/KMT2A-rearranged ALL has improved, but allo-HSCT failed to affect outcome. Targeted therapies are needed to reduce relapse and treatment-related mortality rates.

Landscape of homologous recombination reversion mutations in gynecologic malignancies.

5576 Background: Homologous recombination (HR) reversion mutations (REV) are biomarkers for predicting resistance to platinum and PARP inhibitor therapies. The biologic diversity of REV represents a diagnostic challenge. An automated computational approach was used to detect REV for analysis of genomic features of REV-positive ovarian epithelial, fallopian tube, and peritoneal cancers. Methods: Retrospective study of tissue (n = 23,612) and liquid biopsy (n = 869) samples from patients undergoing hybrid-capture comprehensive genomic profiling during routine clinical care 11/2012-03/2021. A proprietary algorithm tested for seven distinct REV mechanisms in BRCA1, BRCA2, PALB2, RAD51C, or RAD51D. For subjects with multiple samples, the earliest REV-positive sample was used for downstream analyses. Results: Among 23,866 ovarian epithelial, fallopian tube, and peritoneal cancers, 16.4% (n = 3,920) had at least one pathogenic variant (PV) in BRCA1 (10%, n = 2,383), BRCA2 (5.5%, n = 1,320), PALB2 (0.67%, n = 160), RAD51C (0.64%, n = 152), or RAD51D (0.47%, n = 113). 3.9% (154/3,920) of patients with one or more PV had REV. REV were found in tumors with PV in BRCA2 at twice the frequency of BRCA1 (6.0%, [79/1,320] vs 3.0% [71/2,383]; p < 0.001). REV involving RAD51D (1.8%, 2/113), RAD51C (0.7%, 1/152), or PALB2 (0.6%, 1/160) were rarer. A total of 193 REV pairs were identified. The most frequent REV mechanism was an exonic non-frameshift deletion completely encompassing a PV (45%, 87/193). Other recurrent mechanisms included restoration of the reading frame of a frameshift PV (21%, 42/193), replacement of a PV with a benign missense substitution at the same codon (16%, 32/193), and deletion with intronic breakpoints encompassing a PV (15%, 29/193). REV were significantly more prevalent in liquid biopsies than in tissue samples with PV (16% [20/124] vs. 3.5% [134/3,796]; p < 0.001). A range of 1-6 REV pairs were found per sample (liquid: 1-6, tissue: 1-3). Multiple REV per sample was more common in liquid biopsies (35% [7/20] vs. 11% [15/134]; p = 0.011). These differences likely reflect stage of disease and sampling of multiple subclones. Conclusions: BRCA2 PV are most frequently reverted in gynecologic tumors. REV are also common in tumors with BRCA1 PV and can more rarely occur in other HR genes. Liquid biopsy is enriched for detection of polyclonal resistance. Diverse REV mechanisms highlight a need for robust detection to incorporate REV in identifying treatment resistance and guiding downstream therapy selection.

Integrando disciplinas para a predição da biodiversidade da Floresta Atlântica no Brasil

Abstract: We briefly describe selected results from our thematic project focused on the biodiversity of the Atlantic Forest (“AF BIOTA”), which was jointly funded by FAPESP’s BIOTA Program, the U.S. National Science Foundation Dimensions of Biodiversity Program, and the National Aeronautics and Space Administration (NASA). As one of the five most important hotspots of biodiversity in the world, the Atlantic Forest (AF) holds less than 16% of its vegetation cover, yet, amongst the hotspots, it still harbors one of the highest numbers of species, including endemics. By gathering specialists across multiple disciplines (biology, geology, engineering), we aimed to understand how this megabiodiversity was built through time, informing biodiversity science and conservation. Among the results, we trained 18 Master’s and 26 Ph.D. students, published more than 400 peer-reviewed papers that improved our knowledge about the forest’s biologic and climatic diversity and dynamics through time, developed new analytical methods, produced outreach videos and articles, and provided data to help define biodiversity conservation policies.

Triple-negative Breast Cancer (TNBC) and Its Luminal Androgen Receptor (LAR) Subtype: A Clinicopathologic Review of Cases in a University Hospital in Northwestern Nigeria.

Breast cancer (BC) is a common malignancy; the most frequent in Nigeria. BC characteristically exhibits great biologic diversity. Amongst its variants, the triple-negative subtype is also characterized by heterogeneity (thus making it a study in diversity within diversity) and also by some unique clinicopathologic features including clinical aggressiveness, lack of response to current targeted therapies, and tendency to cluster amongst young premenopausal women especially in populations of women of African ancestry. The objective of this study was to conduct a retrospective clinicopathologic survey of all breast carcinomas to profile the triple-negative breast cancers (TNBCs) amongst them and illustrate their immunohistochemical pattern of luminal androgen receptors (LARs) expression. All the cases entered into the departmental records as breast carcinomas over the study period were extracted including patients' request cards, hematoxylin and eosin-stained slides, and paraffin-embedded tissue blocks of those diagnosed as triple-negative cancers. These were immunohistochemically stained using a monoclonal antibody for androgen receptor (AR). The whole data were analyzed and presented in tabular formats. A total of 660 breast carcinomas of which 89 (13.48%) cases were identified as TNBCs with a mean age of occurrence of 42.89 ± 11.88 years. Most TNBCs (95.5%) were carcinoma no special type and 61.8% had low or intermediate histologic grading. LAR expression was noted in 11.24% of the TNBCs. Triple-negative cancer in this study shares some of the known characteristics but also portrays some divergence from the commonly described features.

Molecular Update and Evolving Classification of Large B-Cell Lymphoma.

Simple SummaryThe development of high-throughput technologies in recent years has increased our understanding of the molecular complexity of lymphomas, providing new insights into the pathogenesis of large B-cell neoplasms and identifying different molecular biomarkers with prognostic impact, that lead to the revision of the World Health Organization consensus classification of lymphomas. This review addresses the main histopathological and molecular features of large B-cells lymphomas, providing an overview of the main recent novelties introduced by the last update of the consensus classification.Diffuse large B-cell lymphomas (DLBCLs) are aggressive B-cell neoplasms with considerable clinical, biologic, and pathologic diversity. The application of high throughput technologies to the study of lymphomas has yielded abundant molecular data leading to the identification of distinct molecular identities and novel pathogenetic pathways. In light of this new information, newly refined diagnostic criteria have been established in the fourth edition of the World Health Organization (WHO) consensus classification of lymphomas, which was revised in 2016. This article reviews the histopathological and molecular features of the various aggressive B-cell lymphoma subtypes included in the updated classification.

BIODIVERSIDADE, DIREITOS E PRODUÇÃO CAMPONESA DE ALIMENTOS

A conservação da biodiversidade consiste em uma das mais importantes questões ambientais do século XXI. O artigo analisa a contradição existente e expressa pelo Direito entre proteção e conservação da biodiversidade e desenvolvimento da biotecnologia. Em tese, o desenvolvimento da biotecnologia deveria favorecer a conservação da biodiversidade, mas da maneira em que está sendo utilizado, não conserva. O Direito, protetor da propriedade individual, se vê na contingência de proteger a biodiversidade como direito da coletividade que se confronta com os direitos individuais. A análise desta antinomia se faz a partir dos conceitos sociojurídicos de biodiversidade e sua conservação ex situ ou in situ, extraídos da Lei n. 13.123/15 e da Convenção de Diversidade Biológica (CDB). A opção por uma ou outra forma prevalente de conservação leva a situações opostas e de grande riscos para a produção de alimentos e para a biodiversidade. Fica demonstrada a importância da conservação in situ para a proteção da biodiversidade, assim como que tal estratégia é possível a partir da conservação, multiplicação e diversificação da produção camponesa e de povos tradicionais. A produção camponesa baseada em consciência e organização protege a biodiversidade, como fica claro em muitas iniciativas do MST e nas Jornadas de Agroecologia. Com isso passa a ser possível não só a proteção da biodiversidade, mas a produção de alimentos saudáveis em quantidade para a promoção da soberania alimentar da população, que devem ser apoiadas pela biotecnologia.

A synopsis of prostate organoid methodologies, applications, and limitations.

Current in vitro modeling systems donot fully reflect the biologic and clinical diversity of prostate cancer (PCa). Organoids are 3D in vitro cell cultures that recapitulate disease heterogeneity, retain prostate gland architecture, and mirror parental tumor characteristics. To make better use of organoid models in the PCa research field, we provide a review of cutting-edge prostate organoid methodologies, applications, and limitations. We summarize methodologies for the establishment of benign prostate and PCa organoids and describe some of the model's practical applications and challenges. We highlight the patient-derived xenograft (PDX)-organoid interface model, which may allow for the generation of organoids from primary and rare PCa subtypes. Finally, we discuss potential future utilizations of PCa organoids in the realms of drug development and precision oncology. Organoids represent a quasi in vivo modeling system that can be easily amenable to genetic modification and functional studies. As such, organoids may serve as an intermediate preclinical model for studying PCa. Future directions may include the refinement of culturing conditions to increase drug response fidelity in PCa organoids. The PDX-organoid interface model may enable the future establishment of primary and rare subtype PCa organoid lines.

Multimodal Therapy for Sinonasal Malignancies: Updates and Review of Current Treatment.

Sinonasal malignancies pose a significant challenge in management due to their low incidence, biologic diversity, and significant symptom burden. Even though surgery remains the primary therapeutic modality, a multi-modality approach has been shown to benefit a significant proportion of patients and its success depends largely on stage and histologic type. Non-surgical approaches such as novel radiation approaches as well as intensification with systemic therapy hold promise in altering the organ preservation rate as well as overall survival for patients. Practice changing randomized trials to test these novel modalities are overdue and desperately needed.

Influenza A Virus Subpopulations and Their Implication in Pathogenesis and Vaccine Development.

The concept of influenza A virus (IAV) subpopulations emerged approximately 75 years ago, when Preben von Magnus described "incomplete" virus particles that interfere with the replication of infectious virus. It is now widely accepted that infectious particles constitute only a minor portion of biologically active IAV subpopulations. The IAV quasispecies is an extremely diverse swarm of biologically and genetically heterogeneous particle subpopulations that collectively influence the evolutionary fitness of the virus. This review summarizes the current knowledge of IAV subpopulations, focusing on their biologic and genomic diversity. It also discusses the potential roles IAV subpopulations play in virus pathogenesis and live attenuated influenza vaccine development.

Clinicopathologic and Racial/Ethnic Differences of Colorectal Cancer Among Adolescents and Young Adults.

OBJECTIVES:Despite overall reductions in colorectal cancer burden, incidence rates continue to rise among younger patients, and causes remain unknown. We examined differences in clinicopathologic and racial/ethnic characteristics within the adolescent and young adult (AYA) population diagnosed with colorectal cancer in the United States.METHODS:Using the National Cancer Institute's Surveillance, Epidemiology, and End Results program data, we identified individuals diagnosed with first primary colorectal cancer between ages 15 and 39 years from 2010 to 2015. Adjusted multivariable logistic regression models were used to quantify clinicopathologic and racial/ethnic differences across age at onset subgroups (15–19, 20–24, 25–29, 30–34, and 35–39 years).RESULTS:We identified 5,350 AYA patients diagnosed with colorectal cancer. Of note, 28.6% of AYA cases were diagnosed with right-sided tumors (cecum to transverse colon). The proportion of right-sided colorectal cancers differed significantly by age group at diagnosis (38.3% vs 27.3% of AYAs aged 15–19 vs 35–39 years, respectively; P trend = 0.01). Proportions of cases with mucinous adenocarcinoma and signet ring cell carcinoma histopathologic subtypes significantly increased with younger age at onset (P trends = 0.01 and 0.03, respectively). Differences in clinical stage were observed across AYA age groups, with stage II disease increasing with younger age (P trend = 0.01). The proportion of Hispanic AYAs was higher within younger patients, accounting for 21.0% of the AYA population aged 35–39 years up to 28.3% of 15–19-year-old individuals (P trend = 0.003).DISCUSSION:Within the AYA population, colorectal cancers differ by clinicopathologic and racial/ethnic characteristics. Further investigation of the clinical and biologic diversity of colorectal cancers that partially underlie age- and race-related differences in cancer susceptibility and outcomes is warranted.

Distribuição e Importância das Unidades de Conservação no Domínio Caatinga

The Caatinga is a characteristic phytogeographic domain of the Brazilian semiarid, being one of the least studied areas and one of the Brazilian natural regions less protected. The Caatinga has undergone a rapid process of environmental deterioration, due to deforestation. Therefore, the present study aimed to show the current distribution and quantities of Conservation Units in the Caatinga Domain. Several books, journals, theses and periodicals were consulted for its accomplishment, regarding the conservation units and the consultations of the numbers of UCs, by states and biomes, were done through the website of the National Registry of Conservation Unit of the Ministry of the Environment. Presently, the Caatinga own 166 UCs indexed, that preserves a 63.677 km 2 area, corresponding to 7,7% of domain, being 1,2% of this protected area belonging to Integral Protection group and 6,5% to Sustentable Use. The states that most own Caatinga areas, are Bahia, Piaui e Ceara, but Piaui is the only state that has little more than 10% of the destined area to conservation of this domain. Yet Rio Grande do Norte, Sergipe, Paraiba e Alagoas own less than 1% of your Caatinga area for conservation, the others has between 6 and 9,5%. Until 2008 more 45% of Caatinga area was already deforested, therefore it is necessary to increase the quantities of UCs, since that the process to deforested, consequently loss of biologic diversity, in this area, is pretty fast and occur not just by antropics actions, but also by natural phenomena.

Paradoxical reversed plantar involvement during ixekizumab therapy for psoriasis

Palmoplantar psoriasis is a particularly challenging variant of psoriasis. Psoriasis at this location has a significant impact on health-related quality of life and is often recalcitrant. However, difficult cases may respond to biologic therapies. Paradoxical reactions during treatment with biological agents have been described, mostly during anti-tumor necrosis factor therapy. These typically present as a change in morphology or distribution of lesions. We present a patient with palmoplantar psoriasis treated with ixekizumab who achieved a favorable response that was coupled with a rare paradoxical reaction, reversed plantar involvement. The reason for this phenomenon and its clinical course are uncertain, but these new lesions are proving recalcitrant to complementary therapies. Provided the increasingly widespread use of biologic therapies, the incidence and diversity of paradoxical reactions are expected to increase.

Adjuvant Therapy for Biliary Tract Cancers.

Biliary tract cancers, including gallbladder cancer, intrahepatic, perihilar, and distal cholangiocarcinomas, although anatomically contiguous, represent a heterogeneous group of cancers with extensive biologic and genetic diversity. With early disease, surgical resection is the preferred option for all subtypes; however, relapse rates remain high, and survival outcomes are poor. Data to guide the use of adjuvant therapy have been limited to retrospective series, population-based studies, and meta-analyses, all with their associated limitations. The number of prospective trials ongoing or completed is increasing, and these results will ultimately dictate optimal treatment of this group of diseases. This review summarizes the data for adjuvant therapy in biliary tract cancers.