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Abstract Citizen and community science datasets are typically collected using flexible protocols. These protocols enable large volumes of data to be collected globally every year; however, the consequence is that these protocols typically lack the structure necessary to maintain consistent sampling across years. This can result in complex and pronounced interannual changes in the observation process, which can complicate the estimation of population trends because population changes over time are confounded with changes in the observation process. Here we describe a novel modelling approach designed to estimate spatially explicit species population trends while controlling for the interannual confounding common in citizen science data. The approach is based on Double machine learning, a statistical framework that uses machine learning (ML) methods to estimate population change and the propensity scores used to adjust for confounding discovered in the data. ML makes it possible to use large sets of features to control for confounding and to model spatial heterogeneity in trends. Additionally, we present a simulation method to identify and adjust for residual confounding missed by the propensity scores. To illustrate the approach, we estimated species trends using data from the citizen science project eBird. We used a simulation study to assess the ability of the method to estimate spatially varying trends when faced with realistic confounding and temporal correlation. Results demonstrated the ability to distinguish between spatially constant and spatially varying trends. There were low error rates on the estimated direction of population change (increasing/decreasing) at each location and high correlations on the estimated magnitude of population change. The ability to estimate spatially explicit trends while accounting for confounding inherent in citizen science data has the potential to fill important information gaps, helping to estimate population trends for species and/or regions lacking rigorous monitoring data.

Abstract Large‐scale monitoring of seasonal animal movement is integral to science, conservation and outreach. However, gathering representative movement data across entire species ranges is frequently intractable. Citizen science databases collect millions of animal observations throughout the year, but it is challenging to infer individual movement behaviour solely from observational data. We present BirdFlow, a probabilistic modelling framework that draws on citizen science data from the eBird database to model the population flows of migratory birds. We apply the model to 11 species of North American birds, using GPS and satellite tracking data to tune and evaluate model performance. We show that BirdFlow models can accurately infer individual seasonal movement behaviour directly from eBird relative abundance estimates. Supplementing the model with a sample of tracking data from wild birds improves performance. Researchers can extract a number of behavioural inferences from model results, including migration routes, timing, connectivity and forecasts. The BirdFlow framework has the potential to advance migration ecology research, boost insights gained from direct tracking studies and serve a number of applied functions in conservation, disease surveillance, aviation and public outreach.

In this work, CIP2A is discovered as a TOPBP1-interacting protein that regulates TOPBP1 localization specifically in mitosis. Cells lacking CIP2A display increased radio-sensitivity, micronuclei formation and chromosomal instability.

Infantile onset Pompe disease (IOPD) is a rare devastating disease that presents in early infancy with rapidly progressive hypertrophic cardiomyopathy, severe generalized myopathy and death within the first year of life. The emergence of enzyme replacement therapy (ERT) with recombinant human acid alpha glucosidase (rhGAA) has improved the natural course of IOPD with a significant impact on cardiomyopathy but has a more limited effect on the progression of myopathy and consequently the later deterioration of the disease. Possible reasons for reduced ERT efficacy include insufficient enzyme, partial targeting of skeletal muscle and the development of IgG rhGAA antibodies especially in patients who are cross-reactive immunological material (CRIM) negative. We report a CRIM-negative IOPD female patient who started treatment upon diagnosis at 4.5 months with ERT at 20 mg/kg every other week and a course of combined immunomodulation with rituximab, methotrexate and IVIG according to the published Duke protocol and increased ERT within a month to 40 mg/kg/week. Despite initial good clinical response to ERT and immunomodulation, monthly monitoring identified a gradual increase of serum antibody titers to rhGAA necessitating a second course of immunomodulation with bortezomib and maintenance rituximab and methotrexate. A gradual reduction in frequency of immunotherapy was instituted and over a period of 14 months was discontinued. Serum anti-rhGAA antibody titers remained negative for 5 months since cessation of immunomodulation and the patient is now immune tolerant with recovery of CD19. At the age of 30 months the patient is walking independently and has normal cardiac function and anatomy. We recommend initiating ERT at 40 mg/kg/week in CRIM-negative IOPD patients, concomitant with immunomodulation and monthly monitoring of serum anti-rhGAA IgG titers upon confirmation of the diagnosis.

Abstract Migratory connectivity describes the spatial linkage among migrating individuals through time. Accounting for it is necessary for full annual cycle conservation planning, to avoid uneven protection leading to overall population declines. However, conventional methods used to study migratory connectivity usually demand substantial fiscal and human resources. We present a methodology that infers patterns of migratory connectivity for songbirds using relative abundance models created from eBird, a global community science program. We compare our inferences with previously described patterns of migratory connectivity for two species assumed to exhibit broadscale parallel migration strategies: wood thrush (Hylocichla mustelina) and Wilson's warbler (Cardellina pusilla). Initial findings suggest that our method has the potential to be a rapid and inexpensive way to infer broad patterns of connectivity for species that do not engage in leapfrog migration nor deviate much from parallel migration. Our flexible framework can be used to guide sampling designs for studies of migratory connectivity and to generate hypotheses for species in need of urgent conservation planning for which migratory connectivity has not yet been established.

Abstract Artificial light at night (ALAN) is adversely affecting natural systems worldwide, including the disorienting influence of ALAN on nocturnally migrating birds. Understanding how ALAN trends are developing across species' seasonal distributions will inform mitigation efforts, such as Lights Out programs. Here, we intersect ALAN annual trend estimates (1992–2013) with weekly estimates of relative abundance for 42 nocturnally migrating passerine bird species that breed in North America using observations from the eBird community science database for the combined period 2005–2020. We use a cluster analysis to identify species with similar weekly associations with ALAN trends. Our results identified three prominent clusters. Two contained species that occurred in northeastern and western North America during the breeding season. These species were associated with moderate ALAN levels and weak negative ALAN trends during the breeding season, and low ALAN levels and strong positive ALAN trends during the nonbreeding season. The difference between the breeding and nonbreeding seasons was lower for species that occurred in northern South America and greater for species that occurred in Central America during the nonbreeding season. For species that occurred in South America during the nonbreeding season, positive ALAN trends increased in strength as species migrated through Central America, especially in the spring. The third cluster contained species whose associations with positive ALAN trends remained high across the annual cycle, peaking during migration, especially in the spring. These species occurred in southeastern North America during the breeding season where they were associated with high ALAN levels, and in northern South America during the nonbreeding season where they were associated with low ALAN levels. Our findings suggest reversing ALAN trends in Central America during migration, especially in the spring, would benefit the most individuals of the greatest number of species. Reversing ALAN trends in southeastern North America during the breeding season and Central America during the nonbreeding season would generate the greatest benefits outside of migration.

DNA double-strand breaks in ribosomal DNA repeats is associated with repression of ribosomal RNA synthesis. Here the authors reveal a cooperation between TOPBP1 and Treacle in the signaling cascade that triggers transcriptional inhibition and nucleolar segregation in response to rDNA breaks.

Conservation decisions to protect land used by migratory birds rely on understanding species’ dynamic habitat associations. Here the authors identify conservation scenarios needed to maintain >30% of the abundances of 117 migratory birds across the Americas, considering spatial and temporal patterns of species abundance.

Abstract Background Matrix metalloproteinases (MMPs), especially the gelatinases MMP-2 and MMP-9, play a crucial role in the pathogenesis of endometriosis by enabling invasion. Doxycycline is a well-tolerated antibiotic and a potent MMP-inhibitor in subantimicrobial doses. Methods Gelatin zymography and activity assays were used to detect latent and active MMP-2 and -9 in cell culture supernatants of immortalized epithelial (12Z) and two isolates of primary endometriotic stromal cells treated with doxycycline. The invasiveness of 12Z endometriotic cells treated with doxycycline was assessed in matrigel-coated invasion chambers. The effect on latent and active MMP-2 expression of the combination of progesterone and doxycycline was tested in 12Z. Results Doxycycline significantly reduced the MMP-2 activity and pro-MMP-2 expression in 12Z and the MMP-2 and -9 activity as well as expression of pro-MMP-2 and -9 in primary endometriotic stromal cells. The percentage of 12Z cells invading through a matrigel-coated membrane was reduced to 65 and 22% of the control after treatment with doxycycline at doses of 1 μg/ml and 10 μg/ml, respectively. Furthermore, a combination of progesterone and doxycycline showed an additive effect in low doses on the reduction of MMP-2 activity and pro-MMP2 expression in 12Z endometriotic cells. Conclusions In conclusion, the MMP-inhibiting features of subantimicrobial-dose doxycycline may be further evaluated as a well-tolerable additional therapeutic approach, e.g. in combination with progestins such as dienogest, in patients with infiltrative endometriosis with insufficient response to current medical treatment options.

The practice of AI-powered Urban Analytics is taking off within the real estate industry. Data science and algorithmic logic are close to the forefront of new urban development practices. How close? is the question — experts predict that digitization will go far beyond intelligent building management systems. New analytical tools with predictive capabilities will dramatically affect the future of urban development, reshaping the real estate industry in the process.

Background: Uterine Tumors Resembling Ovarian Sex Cord Tumors (UTROSCT) are rare tumors of low malignancy. In the past, these tumors were mainly treated by hysterectomy. More recently, some authors have proposed conservative surgical management for women wishing to preserve fertility. This article is the first to report on organ-preserving treatment in the case of recurrence or disease persistence. Cases: We report on three patients with UTROSCT, two of them young, not having completed family planning. One even gave birth to a healthy child after fertility-preserving treatment of a persistent UTROSCT. To our knowledge, this is the first pregnancy reported after surgical treatment of a persistent UTROSCT so far. Conclusion: A fertility-sparing approach should always be considered in young women with UTROSCT who wish to preserve their fertility, also in cases of recurrence or disease persistence.

BACKGROUND Since the advent of high-throughput sequencing technologies, organised germline screening, independent of the personal and family cancer history, has been frequently proposed. Since ethnic and geographic populations significantly differ in their mutation spectra and prevalence, one critical prerequisite would be the knowledge of the expected carrier frequencies. OBJECTIVE For the first time, in a retrospective non-cancer related cohort from a single Swiss genetic centre, we systematically assessed the prevalence of secondary findings in 19 genes (BRCA1/2 plus 17 non-BRCA genes) previously designated by the US National Comprehensive Cancer Network (NCCN) for hereditary breast and ovarian cancer (HBOC) germline testing. DESIGN A total of 400 individuals without a cancer diagnosis undergoing whole-exome sequencing (WES) analysis for neurodevelopmental disorders (NDDs) from 2015 to 2017 at IMG Zurich were included after quality assessment. Among these, 180 were unaffected parental couples, 27 unaffected parental singles and 13 NDD index patients (mean age 43 years). The majority of the cohort was of Caucasian ethnicity (n = 336, 84.0%) and of Northwest European ancestry (n = 202, 50.5%), for 70 of whom (42.5%) an autochthonous Swiss descent was assumed. For WES filtering of rare, potentially actionable secondary variants in HBOC genes, an overall minor allele frequency (MAF) below 0.65% was used as cut-off. Each rare variant was manually evaluated according to the recommended ACGM-AMP standards, with some adaptations including “hypomorphic” as an additional distinct pathogenicity class. RESULTS Overall, 526 rare secondary variants (339 different variants) were encountered, with the BRCA1/2 genes accounting for 27.2% of the total variant yield. If stratified for variant pathogenicity, for BRCA1/2, three pathogenic variants were found in three females of Italian ancestry (carrier frequency of 0.8%). In the non-BRCA genes, five carriers of (likely) pathogenic variants (1.3%) were identified, with two Swiss individuals harbouring the same CHEK2 Arg160Gly variant known to be recurrent among Caucasians. Hence, the overall carrier rate added up to 2.0%. Additionally, seven various hypomorphic HBOC predisposing alleles were detected in 22 individuals (5.5%). CONCLUSION We provide the first evidence of a high prevalence of HBOC-related cancer susceptibility in the heterogeneous Swiss general population and relevant subpopulations, particularly in individuals of Italian descent. These pioneering data may substantiate population-based HBOC screening in Switzerland.

Squamous cell carcinoma (SCC) of the neovagina after genital reconstruction surgery is a rare occurrence with only very few cases published up to the present. We report a case of a 43-year-old transgender woman who developed neovaginal SCC 23 years after vaginoplasty. The patient tested positive for high-risk human papillomavirus (HPV). At the time of diagnosis, radiological investigations revealed already existing lymph node and osseous metastases. The treatment consisted of various cycles of chemotherapy and radiation therapy. Unfortunately, the formation of additional metastases, including cerebral, pulmonary, and hepatic metastases, could not be prevented. After comparing the literature on the topic, we conclude that neovaginal carcinoma often appears years and decades after genital reconstruction surgery. We therefore recommend the continuation of regular clinical follow-up for transgender women after postoperative follow-up is completed. With this approach, potential lesions may be detected at an earlier stage and a better outcome may be achieved. Follow-up should include neovaginal examination and cytological smear testing. At a later age, we recommend additional regular prostate-specific antigen (PSA) testing and digital rectal examination (DRE). Moreover, transgender women are advised to take part in mammography screening starting at the age of 50, especially when additional risk factors are present.

Cystic lymphangioma is an uncommon benign tumor that occurs primarily in children in the cervical region. We report the first case of a pleural-based cystic lymphangioma in an infant. The patient was admitted for RUL pneumonia. Because of the persistence of the radiographic findings despite clinical improvement, a computed tomography (CT) and a magnetic resonance imaging (MRI) scan were performed. They showed a multiloculated cystic lesion in the superior posterior right hemithorax. A surgical procedure was performed with complete resection of the tumor. Histopathological examination showed a pleural-based intrathoracic multicystic lymphangioma. One year after the surgery, the patient feels well without any sign of recurrence.

Ibrutinib is a small-molecule inhibitor of Bruton’s tyrosine kinase, an enzyme central in B cell development. It is indicated as a therapy for certain hematological diseases such as chronic lymphocytic leukemia (CLL), but also exerts off-target effects on several receptors and kinases. In this paper, we hypothesize that ibrutinib may suppress the tumor marker CA-125 in ovarian cancer. The hypothesis is based on an observation of CA-125 normalization in a patient with low-grade serous ovarian cancer who received ibrutinib for concurrent CLL. We propose a mechanistic model explaining this possible drug effect as a foundation for further research.

The relationship between ABO blood groups (BG) and risk of incidence in cancers including gynecological cancers has been widely studied, showing increased incidence risk for BG A patients. As available data are inconsistent we investigated whether BG and their anti-glycan antibodies (anti-A and anti-B) have prognostic values in gynecological cancers. We retrospectively evaluated 974 patients with gynecological cancers in three cancer centers (Switzerland and Australia) between 1974 and 2014 regarding the relationships between clinico-pathological findings and the BG. Time to disease recurrence was significantly influenced by BG in patients with ovarian (n = 282) and vulvar (n = 67) cancer. BG O or B patients showed a significantly increased risk for ovarian cancer relapse compared to A, 59% and 82%, respectively (p = 0.045; HR O vs A = 1.59 (CI 1.01-2.51) and (p = 0.036; HR A vs B = 0.55 (CI 0.32-0.96). Median time to relapse for advanced stage (n = 126) ovarian cancer patients was 18.2 months for BG O and 32.2 for A (p = 0.031; HR O vs A = 2.07 (CI 1.07-4.02)). BG also significantly influenced relapse-free survival in patients with vulvar cancer (p = 0.002), with BG O tending to have increased relapse risk compared to A (p = 0.089). Blood groups hence associate with recurrence in ovarian and vulvar cancer: women with BG O seem to have a lower ovarian cancer incidence, however are more likely to relapse earlier. The significance of the BG status as a prognostic value is evident and may be helpful to oncologists in prognosticating disease outcome and selecting the appropriate therapy.

Chlamydia trachomatis is the most common bacterial cause of sexually transmitted disease and can cause pelvic inflammatory disease (PID), leading to severe outcomes such as ectopic pregnancy, infertility, or pelvic pain. We report a case of a 38-year-old patient with abdominal pain and dyspareunia. Clinical examination revealed diffuse abdominal tenderness. Vaginal and abdominal sonography showed substantial ascites and CA-125 level was elevated. Therefore, the attendant physician performed an abdominal CT scan for further diagnosis. Radiographically diffuse peritoneal enhancement, consistent with peritoneal carcinomatosis, 4-quadrant ascites, and slightly enlarged ovaries with solid and cystic structures were diagnosed, leading to the suspicion of ovarian cancer. In addition, the results of the cervical smear PCR for chlamydia were positive. Due to the positive chlamydia result, the suspicious CT scan, and the young age, we decided to perform a diagnostic laparoscopy as a first step. Intraoperatively, the ovaries were of normal aspect without any cancerous lesions. However, the ascites and the yellow-reddish jelly-like deposits were consistent with acute PID. Thus, chlamydia infection may simulate the presentation of ovarian cancer. Therefore, especially in young patients, we recommend careful scrutiny of every diagnosis of ovarian cancer even if its presentation seems to be typical.

This contribution, based on a statistical approach, undertakes to link data on resources (personnel and financial means) and the working of the administration of penal justice (prosecution, sentencing) taking into account the nationality of those prosecuted. In order to be able to distinguish prosecution and sentencing practices of judicial authorities and possible processes of discrimination, diverse sources have been used such as data from court administrations, public finances and police forces, collected by the Swiss Federal Statistical Office and the Swiss Federal administration of finances. The authors discuss discrimination in prosecution and sentencing between Swiss residents and foreigners taking into account localization and resources regarding personnel and public finances.

BACKGROUND: Trastuzumab (Herceptin®, Roche) has significantly improved the prognosis of patients with HER2-positive metastatic breast cancer. Some patients remain in remission for many years. However, there are no prognostic markers associated with long-term survival. This study aimed to analyse treatment patterns of HER2-positive metastatic breast cancer at a single institution and explore prognostic factors for long-term survival after HER2-targeted treatment. PATIENTS AND METHODS: This was a retrospective cohort study of all patients with HER2-positive metastatic breast cancer receiving first-line treatment with HER2-targeted therapy between 2004 and 2014 at the University Hospital of Zurich (n = 81). Overall survival (OS) and other time-to-event endpoints were determined with Kaplan-Meier curves and clinicopathological factors predicting long-term outcome were identified by use of the log-rank test. RESULTS: The median OS for the cohort was 5.9 years (95% confidence interval [CI] 3.5–8.3). Twenty patients (28.6%) remained in complete remission after 1 year, 11 (15.7%) after 2 years and 4 (5.7%) beyond 5 years. The median progression-free survival was 13.6 months (95% CI 9.0–18.3). The objective response rate (ORR) was 60.5% with 16 (19.8%) complete responses and 33 (40.8%) partial responses. Six (7.4%) patients had brain metastases as first site of relapse and they had a median OS of 1.9 years (95% CI 1.7–2.2 years). Thirty-four of all 81 patients (42%) had developed brain metastases by the time of death or last follow-up. Median OS after diagnosis of brain metastases was 26 months (95% CI 19.9–32.0). Only primary brain metastases were found to be a prognostic marker associated with shorter overall survival. Hormone-receptor status and presence of visceral metastases at primary diagnosis were not associated with prognosis. Only four patients (4.9%) developed some degree of left ventricular dysfunction under treatment with trastuzumab. CONCLUSIONS: HER2-targeted treatment has improved the overall survival of patients with HER2-postive metastatic breast cancer with median OS exceeding 5 years. There are, however, no predictive markers for a long-term survival. Only the absence of primary brain metastases seems to be an indicator of a good prognosis. Clinical trial number: SNCTP000001431

Endometriosis is a common gynecological disease affecting 6%–10% of women of reproductive age and is characterized by the presence of endometrial-like tissue in localizations outside of the uterine cavity as, e.g., endometriotic ovarian cysts. Mainly, two epithelial ovarian carcinoma subtypes, the ovarian clear cell carcinomas (OCCC) and the endometrioid ovarian carcinomas (EnOC), have been molecularly and epidemiologically linked to endometriosis. Mutations in the gene encoding the AT-rich interacting domain containing protein 1A (ARID1A) have been found to occur in high frequency in OCCC and EnOC. The majority of these mutations lead to a loss of expression of the ARID1A protein, which is a subunit of the SWI/SNF chromatin remodeling complex and considered as a bona fide tumor suppressor. ARID1A mutations frequently co-occur with mutations, leading to an activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, such as mutations in PIK3CA encoding the catalytic subunit, p110α, of PI3K. In combination with recent functional observations, these findings strongly suggest cooperating mechanisms between the two pathways. The occurrence of ARID1A mutations and alterations in the PI3K/AKT pathway in endometriosis and endometriosis-associated ovarian carcinomas, as well as the possible functional and clinical implications are discussed in this review.

Federal States, their administration of justice and their justice administrations, are characterized by differences in organizational settings, deficiencies in policy implementation, variations of policy outcomes as well as a dearth of information. Defendants of federal States claim that these well-known negative aspects of federalism are – largely – outbalanced by the speedier processes, efficacy and the efficiency of its largely autonomous units. In the field of the administration of justice, especially in penal justice and correctional programs, federalism must however also be considered with regard to the respect of principles of equal treatment, of equality before the law, of the state of law, all presumably protected by the Constitution.

Volunteers are increasingly being recruited into citizen science projects to collect observations for scientific studies. An additional goal of these projects is to engage and educate these volunteers. Thus, there are few barriers to participation resulting in volunteer observers with varying ability to complete the project's tasks. To improve the quality of a citizen science project's outcomes it would be useful to account for inter-observer variation, and to assess the rarely tested presumption that participating in a citizen science projects results in volunteers becoming better observers. Here we present a method for indexing observer variability based on the data routinely submitted by observers participating in the citizen science project eBird, a broad-scale monitoring project in which observers collect and submit lists of the bird species observed while birding. Our method for indexing observer variability uses species accumulation curves, lines that describe how the total number of species reported increase with increasing time spent in collecting observations. We find that differences in species accumulation curves among observers equates to higher rates of species accumulation, particularly for harder-to-identify species, and reveals increased species accumulation rates with continued participation. We suggest that these properties of our analysis provide a measure of observer skill, and that the potential to derive post-hoc data-derived measurements of participant ability should be more widely explored by analysts of data from citizen science projects. We see the potential for inferential results from analyses of citizen science data to be improved by accounting for observer skill.

Wind plays a significant role in the flight altitudes selected by nocturnally migrating birds. At mid-latitudes in the Northern Hemisphere, atmospheric conditions are dictated by the polar-front jet stream, whose amplitude increases in the autumn. One consequence for migratory birds is that the region’s prevailing westerly winds become progressively stronger at higher migration altitudes. We expect this seasonality in wind speed to result in migrants occupying progressively lower flight altitudes, which we test using density estimates of nocturnal migrants at 100 m altitudinal intervals from 12 weather surveillance radar stations located in the northeastern USA. Contrary to our expectations, median migration altitudes deviated little across the season, and the variance was lower during the middle of the season and higher during the beginning and especially the end of the season. Early-season migrants included small- to intermediate-sized long-distance migrants in the orders Charadriiformes and Passeriformes, and late-season migrants included large-bodied and intermediate-distance migrants in the order Anseriformes. Therefore, seasonality in the composition of migratory species, and related variation in migration strategies and behaviours, resulted in a convex–concave bounded distribution of migration altitudes. Our results provide a basis for assessing the implications for migratory bird populations of changes in mid-latitude atmospheric conditions probably occurring under global climate change.

INTRODUCTION:The G protein-coupled estrogen receptor (GPER) is a novel estrogen receptor that mediates proliferative effects induced by estrogen but also by tamoxifen. The aim of our study was to analyze the frequency of GPER in a large collective of primary invasive breast carcinomas, with special emphasis on the subcellular expression and to evaluate the association with clinicopathological parameters and patient overall survival. METHODS:The tissue microarrays from formalin-fixed, paraffin embedded samples of primary invasive breast carcinomas (n = 981) were analyzed for GPER expression using immunohistochemistry. Expression data were compared to the clinicopathological parameters and overall survival. GPER localization was also analyzed in two immortalized breast cancer cell lines T47D and MCF7 by confocal immunofluorescence microscopy. RESULTS:A predominantly cytoplasmic GPER expression was found in 189 carcinomas (19.3%), whereas a predominantly nuclear expression was observed in 529 cases (53.9%). A simultaneous comparable positive expression of both patterns was found in 32 of 981 cases (3.2%), and negative staining was detected in 295 cases (30%). Confocal microscopy confirmed the occurrence of cytoplasmic and nuclear GPER expression in T47D and MCF7. Cytoplasmic GPER expression was significantly associated with non-ductal histologic subtypes, low tumor stage, better histologic differentiation, as well as Luminal A and B subtypes. In contrast, nuclear GPER expression was significantly associated with poorly differentiated carcinomas and the triple-negative subtype. In univariate analysis, cytoplasmic GPER expression was associated with better overall survival (p = 0.012). CONCLUSION:Our data suggest that predominantly cytoplasmic and/or nuclear GPER expression are two distinct immunohistochemical patterns in breast carcinomas and may reflect different biological features, reason why these patterns should be clearly distinguished in histological evaluations. Prospective studies will be needed to assess whether the expression status of GPER in breast carcinomas should be routinely observed by clinicians, for instance, before implementing endocrine breast cancer treatment.

AIM OF THE STUDY:To evaluate the frequency of MRE11/RAD50/NBS1 (MRN)-complex loss of protein expression in endometrial cancers (EC) and to determine whether loss of MRE11 renders the cancer cells sensitive to Poly(ADP-ribose) polymerase (PARP)-inhibitory treatment. METHODS:MRN expression was examined in 521 samples of endometrial carcinomas and in 10 cancer cell lines. A putative mutation hotspot in the form of an intronic poly(T) allele in MRE11 was sequenced in selected cases (n = 26). Sensitivity to the PARP-inhibitor, BMN673 was tested in colony formation assays before and after MRE11 silencing using siRNA. Homologous recombination (HR) DNA repair was evaluated by RAD51-foci formation assay upon irradiation and drug treatment. RESULTS:Loss of MRE11 protein was found in 30.7% of EC tumours and significantly associated with loss of RAD50, NBS1 and mismatch repair protein expression. One endometrial cell line showed a markedly reduced MRE11 expression due to a homozygous poly(T) mutation of MRE11, thereby exhibiting an increased sensitivity to BMN673. MRE11 depletion sensitizes MRE11 expressing EC cell lines to the treatment with BMN673. The increased sensitivity to PARP-inhibition correlates with reduced RAD51 foci formation upon ionizing radiation in MRE11-depleted cells. CONCLUSION:Loss of the MRE11 protein predicts sensitivity to PARP-inhibitor sensitivity in vitro, defining it as an additional synthetic lethal gene with PARP. The high incidence of MRE11 loss in ECs can be potentially exploited for PARP-inhibitor therapy. Furthermore, MRE11 protein expression using immunohistochemistry could be investigated as a predictive biomarker for PARP-inhibitor treatment.

"Checklists" of organisms --- records of the species seen in a specific area during a relatively short time period --- are routinely collected by hobbyists for some taxa of organisms, most notably birds. Gathering and curating these checklists creates a data resource that we believe is underutilized by macroecologists and biogeographers. In this paper, we describe what we perceive to be the strengths of these data as well as caveats for their use. While our comments apply widely to data of this type, we focus on data from eBird, a program that collects checklist data on birds around the world, although principally in the Western Hemisphere.

How do you successfully engage an audience in a citizen-science project? The processes developed by eBird (www.ebird.org), a fast-growing web-based tool that now gathers millions of bird observations per month, offers a model.