Density separation of petrous bone powders for optimized ancient DNA yields.

Density separation is a process routinely used to segregate minerals, organic matter, and even microplastics, from soils and sediments. Here we apply density separation to archaeological bone powders before DNA extraction to increase endogenous DNA recovery relative to a standard control extraction of the same powders. Using nontoxic heavy liquid solutions, we separated powders from the petrous bones of 10 individuals of similar archaeological preservation into eight density intervals (2.15 to 2.45 g/cm3, in 0.05 increments). We found that the 2.30 to 2.35 g/cm3 and 2.35 to 2.40 g/cm3 intervals yielded up to 5.28-fold more endogenous unique DNA than the corresponding standard extraction (and up to 8.53-fold before duplicate read removal), while maintaining signals of ancient DNA authenticity and not reducing library complexity. Although small 0.05 g/cm3 intervals may maximally optimize yields, a single separation to remove materials with a density above 2.40 g/cm3 yielded up to 2.57-fold more endogenous DNA on average, which enables the simultaneous separation of samples that vary in preservation or in the type of material analyzed. While requiring no new ancient DNA laboratory equipment and fewer than 30 min of extra laboratory work, the implementation of density separation before DNA extraction can substantially boost endogenous DNA yields without decreasing library complexity. Although subsequent studies are required, we present theoretical and practical foundations that may prove useful when applied to other ancient DNA substrates such as teeth, other bones, and sediments.

Glycan-Driven Formation of Raft-Like Domains with Hierarchical Periodic Nanoarrays on Dendrimersome Synthetic Cells.

The accurate spatial segregation into distinct phases within cell membranes coordinates vital biochemical processes and functionalities in living organisms. One of nature's strategies to localize reactivity is the formation of dynamic raft domains. Most raft models rely on liquid-ordered L0 phases in a liquid-disordered Ld phase lacking correlation and remaining static, often necessitating external agents for phase separation. Here, we introduce a synthetic system of bicomponent glycodendrimersomes coassembled from Janus dendrimers and Janus glycodendrimers (JGDs), where lactose-lactose interactions exclusively drive lateral organization. This mechanism results in modulated phases across two length scales, yielding raft-like microdomains featuring nanoarrays at the nanoscale. By varying the density of lactose and molecular architecture of JGDs, the nanoarray type and size, shape, and spacing of the domains were controlled. Our findings offer insight into the potential primordial origins of rudimentary raft domains and highlight the crucial role of glycans within the glycocalyx.

[Oncology: what's new in 2023]. / Oncologie: ce qui a changé en 2023.

The oncology field continues its remarkable evolution over the years, with promising advances leading to innovative and individualized treatments. The development of new molecules, the identification of new therapeutic targets and the search for new sequences or combinations promise to revolutionize cancer treatments and contribute to improving survival rates, patients' quality of life and to open new perspective in oncology research. In this article, the newest data released in 2023 are reviewed.

Le domaine de l'oncologie poursuit son évolution remarquable au fil des années, avec des avancées prometteuses ouvrant la voie à des traitements novateurs et individualisés. L'élaboration de nouvelles molécules, l'identification de nouvelles cibles thérapeutiques et la recherche de nouvelles séquences ou combinaisons de traitements promettent de révolutionner la prise en charge du cancer et de contribuer à améliorer les taux de survie, la qualité de vie des patients et à ouvrir de nouvelles perspectives dans la recherche en oncologie. Dans cet article, les nouveautés parues en 2023 sont passées en revue.

Psycho-oncologists' knowledge of cancer-related fatigue and the targets for improving education and training: results from a cross-sectional survey study.

PURPOSE: To explore psycho-oncologists' knowledge of cancer-related fatigue and their self-efficacy to intervene for fatigue. We further aimed to examine the role of fatigue in psycho-oncological training and derive specific suggestions for improvements. METHODS: For this cross-sectional survey study, psycho-oncologists working in Germany were systematically recruited via an address directory or invited by training institutes or colleagues. The online survey encompassed questions on knowledge of fatigue guidelines and interventions, self-efficacy, counseling, and fatigue in professional training. Data were analyzed descriptively and using Mann-Whitney U tests. A logistic regression analysis was performed to identify variables linked to fatigue guideline knowledge. RESULTS: Seventy two percent of the 144 surveyed psycho-oncologists stated not knowing any fatigue-specific guidelines. Those unaware of guidelines reported a lower self-efficacy to intervene for fatigue. However, despite low knowledge of the guidelines, more than 80% of the participants felt well informed about fatigue and reported high self-efficacy. Most participants were aware of the empirical evidence for psychotherapeutic interventions (95%); everyday physical activity, e.g., taking a walk (98%); yoga (82%); and mindfulness-based interventions (82%). Knowledge gaps existed concerning the evidence of resistance/endurance training for treating fatigue. Knowing that resistance/endurance training is an effective treatment was related to an increased frequency to recommend it to patients. Suggestions to improve training for psycho-oncologists included raising awareness earlier in the career path and offering multidisciplinary trainings for fatigue. CONCLUSION: To improve fatigue-related guideline knowledge among psycho-oncologists and enhance implementation into clinical practice multidisciplinary trainings are needed. Psycho-oncologists should play an important role in fatigue management. TRIAL REGISTRATION: Clinicaltrials.gov , identifier: NCT04921644. Registered in June 2021.

"The Part Played by People" in Times of COVID-19: Interpersonal Communication about Media Coverage in a Pandemic Crisis.

The study presented in this article examined individuals' interpersonal communication about media coverage during the COVID-19 pandemic. In times of a severe public health crisis, people rely heavily on media coverage to stay informed. Communicating with others about this coverage can help them gain deeper insights and evaluate pandemic-related information. According to the two-step flow of communication, opinion leaders, such as health experts, play an important role in interpersonal communication by disseminating information, influencing others, and providing orientation. To examine the nature of interpersonal communication about pandemic-related media coverage, we conducted 22 semi-structured interviews. We explored: a) the communicative roles within the informal social network, b) the functions of the communication for the individual, and c) the potential transformations in the trajectory of the pandemic. Findings show that communication with close and more distant social contacts occurred largely on an equal basis, while the rare opinion leaders mainly emerged as information brokers. Communication about media coverage serves the functions of information sharing and retrieving, information validation, and coping with negative emotions. Finally, communication partners, roles, and conversational topics partly changed over time. Our study extends existing research on interpersonal communication about health topics, as well as on the COVID-19 pandemic.

[Oncology: what's new in 2022]. / Oncologie : ce qui a changé en 2022.

The past year has brought several innovations in medical oncology, opening up promising new options for many solid tumors, both localized and metastatic. Immunotherapy, a real spearhead of emerging therapies in metastatic diseases, is seeing its use extend to adjuvant and neoadjuvant modalities, particularly in colon and lung cancers. 2022 also sees a great deal of focus on targeted therapies, as well as on antibody-drug conjugates, which creates new standards in both breast and lung cancers. Here we present the major advances in solid tumors.

L'année écoulée a apporté son lot d'innovations en oncologie médicale, ouvrant de nouvelles options prometteuses pour bon nombre de tumeurs solides, qu'elles soient localisées ou métastatiques. L'immunothérapie, véritable fer de lance des thérapies émergentes dans les maladies métastatiques, voit son usage s'étendre à des modalités adjuvantes et néoadjuvantes, notamment dans les cancers du côlon et du poumon. 2022 donne également la part belle aux thérapies ciblées mais aussi aux conjuguées anticorps-médicaments qui apportent de nouveaux standards tant pour les cancers du sein que du poumon. Nous vous présentons ici les avancées majeures concernant les tumeurs solides.

Sex differences in tumor characteristics, treatment, and outcomes of gastric and esophageal cancer surgery: nationwide cohort data from the Dutch Upper GI Cancer Audit.

BACKGROUND: Sex differences in clinicopathological characteristics, treatment, and postoperative outcomes of gastric and esophageal cancer are largely undefined. This study aimed to compare tumor and treatment characteristics and outcomes of gastric and esophageal cancer surgery between male and female patients. METHODS: Patients after elective surgery for primary esophageal (EAC) or gastric adenocarcinoma (GAC) registered in the Dutch Upper GI Cancer Audit between 2011 and 2016 were included. The primary endpoint, 5-year relative survival with relative excess risk (RER), i.e., adjusted for the normal life expectancy, was compared between male and female patients with EAC and GAC. RESULTS: In total, 4937 patients were included (75% male) with a mean age of 66 years. cT and cN-stages showed a similar distribution in male and female patients. In females, antrum GAC was more frequent (47% vs. 38%, p < 0.001). Female patients with EAC less frequently received neo-adjuvant treatment (OR = 0.60, 95% CI 0.38-0.96, p = 0.033). For GAC, less postoperative morbidity (33% vs. 38% p = 0.017) and less re-interventions (12% vs. 16%, p = 0.008) were observed in females, although they had inferior 5-year relative survival (49% vs. 56%, RER = 1.31, 95% CI 1.09-1.58, p = 0.004). No differences in relative survival of EAC were observed. CONCLUSIONS: In addition to significant sex differences in tumor location, female patients with esophageal adenocarcinoma less frequently received neo-adjuvant therapy, and female patients with gastric adenocarcinoma had inferior relative survival. Further consideration and exploration of sex differences in surgical treatment and outcomes are necessary to improve tailored treatment and outcomes.

Adolescent Mental Health in Relation to Anti-Racism Critical Action.

The relation between critical action and mental health in youth is unclear, despite theory suggesting that engagement in critical action may support adaptive mental health functioning for youth experiencing oppressive systems. The current study contributed to the literature in this understudied area by analyzing the relations between youth critical anti-racism action and their depressive symptoms and psychological well-being, as well as testing two potential moderators of these relations: parent critical motivation and community anti-racism. The study sample consisted of 430 13-to-17-year-old adolescents (M age = 15.3 years, 54% girls, 48% black and 52% white). The findings suggest that critical action is often associated with negative mental health outcomes; however, parent critical motivation and community anti-racism were protective in some instances and communal anti-racism action was more frequently linked to adaptive mental health outcomes than other forms of action. The findings underscore that both psychological risks and rewards are present for youth engaging in critical action for racial justice and highlight the importance of future research to identify malleable factors that are protective for these youth.

[2021 Oncology update]. / Oncologie.

Despite COVID-19 pandemic, which is still deeply affecting world economy and global health, medical oncology specialists keep pursuing their effort for the identification of new therapeutic options to improve patients' life expectancy and quality of life. 2021 confirms the immunotherapy efficacy, alone or in combination with other modalities, across several indications. This year, we are summarizing the new approaches in the following sectors: lung, breast, melanoma, gynecological, digestive, urological and ENT areas.

En dépit de la pandémie de Covid-19 qui continue à grandement impacter l'économie mondiale et la santé, l'oncologie médicale poursuit sa quête d'identification de nouvelles options thérapeutiques ayant pour buts la prolongation de l'espérance de vie et l'amélioration de la qualité de vie de ses patients, en nombre croissant. L'année 2021 confirme également l'efficacité de l'immunothérapie, seule ou en combinaison à d'autres modalités, dans de nombreuses indications. Cette année, nous vous résumons les nouvelles approches dans les domaines suivants: poumon, sein, mélanome, sphères gynécologique, digestive, urologique et ORL.

Highlights from ASCO-GI 2021 from EORTC Gastrointestinal tract cancer group.

Last year the field of immunotherapy was finally introduced to GI oncology, with several changes in clinical practice such as advanced hepatocellular carcinoma or metastatic colorectal MSI-H. At the virtual ASCO-GI symposium 2021, several large trial results have been reported, some leading to a change of practice. Furthermore, during ASCO-GI 2021, results from early phase trials have been presented, some with potential important implications for future treatments. We provide here an overview of these important results and their integration into routine clinical practice.

Unraveling topology-induced shape transformations in dendrimersomes.

The vital functions of cell membranes require their ability to quickly change shape to perform complex tasks such as motion, division, endocytosis, and apoptosis. Membrane curvature in cells is modulated by very complex processes such as changes in lipid composition, the oligomerization of curvature-scaffolding proteins, and the reversible insertion of protein regions that act like wedges in the membrane. But, could much simpler mechanisms support membrane shape transformation? In this work, we demonstrate how the change of amphiphile topology in the bilayer can drive shape transformations of cell membrane models. To tackle this, we have designed and synthesized new types of amphiphiles-Janus dendrimers-that self-assemble into uni-, multilamellar, or smectic-ordered vesicles, named dendrimersomes. We synthesized Janus dendrimers containing a photo-labile bond that upon UV-Vis irradiation cleavage lose a part of the hydrophilic dendron. This leads to a change from a cylindrically to a wedge-shaped amphiphile. The high mobility of these dendrimers allows for the concentration of the wedge-shaped amphiphiles and the generation of transmembrane asymmetries. The concentration of the wedges and their rate of segregation allowed control of the budding and generation of structures such as tubules and high genus vesicles.

Targeting Physical Inactivity - Effects of Three Different Consequence Frames on Population Subgroups' Health-Related Perceptions and Behavioral Intentions.

Physical inactivity constitutes a major health problem in many Western societies affecting a variety of social groups. As these groups often differ in responsivity to physical inactivity messages, the strategy of message targeting, i.e. the customization of messages toward shared characteristics of a social group provides a useful framework for designing effective communication. Whereas focusing on health consequences of physical inactivity might prove useful for some social groups, it might be more effective to emphasize its social or financial consequences for others. The current examination compares the effects of three types of consequence framing (health consequences vs. social consequences vs. financial consequences of physical inactivity) on health-related perceptions and intentions for different population subgroups. An experiment with a one-factorial between subjects design based on a quota sample was conducted. 348 respondents differing in terms of age, sex, and formal education were randomly assigned to one of the three experimental conditions and read an accordingly manipulated newspaper article. Findings show that financial and social consequence frames were more effective than health consequence frames. Both frames positively influenced behavioral intentions through perceptions of susceptibility. These effects were largely independent of sociodemographic variables, although sex and education emerged as moderators in some cases.

Acute kidney injury after in-hospital cardiac arrest in a predominant internal medicine and cardiology patient population: incidence, risk factors, and impact on survival.

INTRODUCTION: Prognosis of survivors from cardiac arrest is generally poor. Acute kidney injury (AKI) is a common finding in these patients. In general, AKI is well characterized as a marker of adverse outcome. In-hospital cardiac arrest (IHCA) represents a special subset of cardiac arrest scenarios with differential predisposing factors and courses after the event, compared to out-of-hospital resuscitations. Data about AKI in survivors after in-hospital cardiac arrest are scarce. METHODS: In this study, we retrospectively analyzed patients after IHCA for incidence and risk factors of AKI and its prognostic impact on mortality. For inclusion in the analysis, patients had to survive at least 48 h after IHCA. RESULTS: A total of 238 IHCA events with successful resuscitation and survival beyond 48 h after the initial event were recorded. Of those, 89.9% were patients of internal medicine, and 10.1% of patients from surgery, neurology or other departments. In 120/238 patients (50.4%), AKI was diagnosed. In 28 patients (23.3%), transient or permanent renal replacement therapy had to be initiated. Male gender, preexisting chronic kidney disease and a non-shockable first ECG rhythm during resuscitation were significantly associated with a higher incidence of AKI in IHCA-survivors. In-hospital mortality in survivors from IHCA without AKI was 29.7%, and 60.8% in patients after IHCA who developed AKI (p < 0.01 between groups).By multivariate analysis, AKI after IHCA persisted as an independent predictor of in-hospital mortality (HR 3.7 (95% CI 2.14-6.33, p ≤ 0.01)). CONCLUSION: In this cohort of survivors from IHCA, AKI is a frequent finding, with adverse impact on outcome. Therefore, therapeutic strategies to prevent AKI in post-IHCA patients are warranted.

Landmark survival analysis and impact of anatomic site of origin in prospective clinical trials of biliary tract cancer.

BACKGROUND & AIMS: Whether all patients with advanced biliary tract cancer (aBTC) should be included in prospective trials, irrespective of the anatomic site of origin, is debated. Herein, we aimed to assess the survival impact of anatomic site of origin in prospective clinical trials of aBTC using landmark survival analysis. METHODS: Patients enrolled into prospective first-line aBTC clinical trials (Jan 97-Dec 15) were included. Overall survival (OS) was analysed using Cox proportional hazard regression; landmark survival (LS) and 95% CIs were calculated. RESULTS: Overall, 1,333 patients were included: median age 63 years (range 23-85); 46% male; 84% ECOG-PS0/1; 25% with locally advanced disease, 72% with metastatic, 3% not reported (NR). Patients were treated with mono-chemotherapy (23%), cisplatin/gemcitabine (36%), other combinations (39%), or NR (2%). Median OS was 10.2 months (95% CI 9.6-10.9). All sites (treatment-adjusted) had decreased risk of death vs. gallbladder cancer (GBC) (p <0.001). This reduced risk vs. GBC was maintained in those receiving cisplatin/gemcitabine for extrahepatic cholangiocarcinoma (p<0.001) and intrahepatic cholangiocarcinoma (IHC, p<0.001), but not in cholangiocarcinoma-not specified (CCA-NS, p = 0.82) or ampullary carcinoma (p = 0.96). One-year OS rates amongst patients who survived beyond 1, 2, 3 and 4 years post-trial registration were 37%, 45%, 61%, and 63%, respectively. For patients who survived 1 year, those receiving combination therapy vs. mono (p = 0.008) (acknowledging potential selection bias) and those with IHC and CCA-NS vs. GBC had better LS (both p <0.05). Metastatic disease was associated with shorter LS than locally advanced disease (p = 0.002). ECOG-PS and gender were not associated with LS (p >0.05, p = 0.08 respectively). CONCLUSIONS: GBC is associated with worse OS than other BTC sites and should be considered as a stratification factor in clinical trials. LS rates enable adjusted prognostication for aBTC survivors. LAY SUMMARY: Patients with gallbladder cancer have worse overall survival compared to those with biliary tract cancers of different primary origin. Thus, gallbladder cancer should be considered as a stratification factor in future clinical trials. Landmark survival rates enable adjusted prognosis prediction for patients with advanced biliary tract cancer who survive for some time.

[Advance Care Planning (ACP). A Systematic Review of ACP Behavior by Women and Men in Germany]. / Behandlung im Voraus Planen (BVP): Eine Übersichtsarbeit über das Vorsorgeverhalten von Frauen und Männern in Deutschland.

BACKGROUND: The desire to retain control over one's life until the end has become highly important in our society. Women and men of different ages and of diverse social, cultural, and educational backgrounds increasingly decide in advance about prospective medical treatment (Advance Care Planning, ACP). OBJECTIVES: Identification and analysis of literature on advance care planning behavior of men and women in Germany. The focus is on gender-specific differences. MATERIALS AND METHODS: Systematic review of empirical studies with gender-specific data on advance care planning behavior in Germany. In-depth analysis of 21 of the 479 retrieved articles. RESULTS: The analysis reveals that Advance Care Planning behavior is influenced by interacting factors such as gender, age, cultural and ethnic background, religion, and education. Gender alone does not explain the prevalence of ACP behavior. This prima facie negative result is partly due to the study designs. Heterogeneous data and a lack of gender sensitivity leave the question concerning the relationships between ACP behavior and gender mostly unanswered. CONCLUSIONS: The analyzed studies reduce gender to a dualistic classification system, dismiss individual role models and positions and also neglect geographic and cultural contexts. There is a need for studies sensitive to gender and culture.

[Advances in Oncology 2019]. / Oncologie.

Driven by highly specialized medicine, research and the quest for personalization of treatments, oncology witnessed substantial advances in 2019. This year numerous treatments have consolidated their importance and broadened their indications. Multiple innovative treatments, currently under study, brought hope for future advances, while biomarkers, such as PD-L1, microsatellite instability (MSI), tumor mutational burden (TMB), BRCA1/2 gene mutations, and homologous recombination deficiency (HRD) allowed better selection and customization of available treatments. This article provides an overview of this year's advances in oncology.

Sous l'égide de la médecine hautement spécialisée, de la personnalisation des traitements et secondée par une recherche énergique, l'oncologie a connu en 2019 des avancées considérables. Cette année, de nombreux traitements ont consolidé leur importance et élargi leurs indications. L'annonce d'une pléthore de traitements novateurs, en étude, est source d'espoir pour l'avenir. Des biomarqueurs simples ou composites, tels que l'expression PD-L1, l'instabilité de microsatellite (MSI), la charge mutationnelle tumorale (TMB), les mutations des gènes BRCA1/2 ou un déficit du mécanisme de la recombinaison homologue des bases (HRD) permettent une meilleure sélection et personnalisation des traitements disponibles. Le but du présent article est de rassembler les avancées oncologiques de l'année.

Human epidermal growth factor receptor 2-positive digestive tumors.

PURPOSE OF REVIEW: This manuscript aims at providing an update and overview on the role of Human epidermal growth factor receptor 2 (HER2) testing and HER2-directed therapies in digestive tumors. RECENT FINDINGS: Phase 3 trial data demonstrating a survival benefit of HER2-targeting treatments are limited to gastric cancer. However, HER2 positivity is also found in 5-6% of colorectal, 7% of pancreatic, and 16% of extrahepatic biliary cancers. Although phase 2 trial data support the use of the combination of trastuzumab and lapatinib with chemotherapy in HER2-positive colorectal cancer, the patient's benefit from targeted treatment of HER2-positive biliary or pancreatic neoplasms is currently unclear, and further clinical trials are necessary. SUMMARY: With the exception of gastric cancer, there are currently no defined guidelines for HER2 testing in other digestive tumors. Various HER2-targeting therapies, which are standard of care in HER2-positive breast cancer, failed in HER2-positive gastric cancers. Thus, the predictive value of HER2 overexpression depends on the tumor type, and results of breast cancer trials cannot a priori be extrapolated to digestive cancers. Next-generation sequencing panel diagnostics may furthermore identify targetable activating mutations in gastric, extrahepatic biliary, and colorectal cancer, particularly if traditional testing (immunohistochemistry/in-situ hybridization) is negative. However, their clinical relevance needs to be determined.

EORTC-1203-GITCG - the "INNOVATION"-trial: Effect of chemotherapy alone versus chemotherapy plus trastuzumab, versus chemotherapy plus trastuzumab plus pertuzumab, in the perioperative treatment of HER2 positive, gastric and gastroesophageal junction adenocarcinoma on pathologic response rate: a randomized phase II-intergroup trial of the EORTC-Gastrointestinal Tract Cancer Group, Korean Cancer Study Group and Dutch Upper GI-Cancer group.

BACKGROUND: 10-20% of patients with gastric cancer (GC) have HER2+ tumors. Addition of trastuzumab (T) to cisplatin/fluoropyrimidine-based chemotherapy (CT) improved survival in metastatic, HER2+ GC. When pertuzumab (P) was added to neoadjuvant T and CT, a significant increase in histopathological complete response rate was observed in HER2+ breast cancer. This study aims to investigate the added benefit of using both HER2 targeting drugs (T alone or the combination of T + P), in combination with perioperative CT for localized HER2+ GC. METHODS: This is a prospective, randomized, open-label, phase II trial. HER2 status from patients with resectable GC (UICC TNM7 tumor stage Ib-III) will be centrally determined. Two hundred and-fifteen patients from 52 sites in 14 countries will be centrally randomized (1:2:2 ratio) to one of the following treatment arms: 1. Standard: CT alone. CT regimens will be FLOT (5-FU, leucovorin, oxaliplatin, taxotere) CapOx (capecitabine, oxaliplatin) or FOLFOX (5-FU, leucovorin, oxaliplatin) according to investigator's choice in Europe, and cisplatin/capecitabine in Asia. 2. Experimental arm 1: CT as in control group, plus T (8 mg/kg loading dose, followed by 6 mg/kg every 3 weeks) at day 1, independent of CT chosen for 3 cycles of 3 weeks before and after surgery. 3. Experimental arm 2: CT plus T as in experimental arm 1, plus P (840 mg every 3 weeks) on day 1. Adjuvant treatment with T or T + P will continue for 17 cycles in total. Stratification factors are: histology (intestinal/non-intestinal); region (Asia vs Europe); location (GEJ vs non-GEJ); HER2 immunohistochemistry score (IHC 3+ vs IHC 2+/FISH+) and chemotherapy regimen. Primary objective is to detect an increase in the major pathological response rate from 25 to 45% either with CT plus T alone, or with CT plus the combination of T and P. DISCUSSION: Depending on the results of the INNOVATION trial, the addition of HER2 targeted treatment with either T or T and P to CT may inform future study designs or become a standard in the perioperative management HER2+ GC. TRIAL REGISTRATION: This article reports a health care intervention on human participants and was registered on July 10, 2014 under ClinicalTrials.gov identifier: NCT02205047 ; EudraCT: 2014-000722-38.

A recessive lethal chondrodysplasia in a miniature zebu family results from an insertion affecting the chondroitin sulfat domain of aggrecan.

BACKGROUND: Congenital skeletal malformations represent a heterogeneous group of disorders affecting bone and cartilage development. In cattle, particular chondrodysplastic forms have been identified in several miniature breeds. In this study, a phenotypic characterization was performed of an affected Miniature Zebu calf using computed tomography, necropsy and histopathological examinations, whole genome sequencing of the case and its parents on an Illumina NextSeq 500 in 2 × 150 bp paired-end mode and validation using Sanger sequencing and a Kompetitive Allele Specific PCR assay. Samples from the family of an affected Miniature Zebu with bulldog syndrome including parents and siblings, 42 healthy Miniature Zebu not related with members of the herd and 88 individuals from eight different taurine cattle breeds were available for validation. RESULTS: A bulldog-like Miniature Zebu calf showing a large bulging head, a short and compressed body and extremely short and stocky limbs was delivered after a fetotomy. Computed tomography and necropsy revealed severe craniofacial abnormalities including a shortening of the ventral nasal conchae, a cleft hard palate, rotated limbs as well as malformed and fused vertebrae and ribs. Histopathologic examination showed a disorganization of the physeal cartilage with disorderly arranged chondrocytes in columns and a multifocal closed epiphyseal plate. Whole-genome sequencing of this malformed Miniature Zebu calf, its dam and sire and subsequent comparative sequence analysis revealed a one base pair insertion (ACAN:c.5686insC) located within the cartilage development gene aggrecan (ACAN) exclusively homozygous in the affected calf and heterozygous in its parents. This variant was predicted to cause a frameshift (p.Val1898fsTer9) and thus a truncation of the chondroitin sulfate domain as well as a loss of the C-terminal globular domain of ACAN. It perfectly co-segregated with the lethal bulldog syndrome in Miniature Zebus. CONCLUSIONS: We found a novel mutation in ACAN causing a recessive lethal chondrodysplasia in Miniature Zebu cattle. A diagnostic test for this mutation is now available for Miniature Zebu breeders preventing further cases of bulldog syndrome by targeted matings. To the authors' best knowledge, this is the first case of a Miniature Zebu associated with an ACAN mutation.

Current management of liver metastases from gastric cancer: what is common practice? New challenge of EORTC and JCOG.

The role of multidisciplinary treatment including surgery for liver metastases from gastric cancer (LMGC) is controversial. Studies to answer this clinical question are increasing in number, but all published data thus far are based on retrospective analyses with limited sample sizes. Thus, the European Organisation for Research and Treatment of Cancer (EORTC) Gastrointestinal Tract Cancer Group (GITCG) and the Japan Clinical Oncology Group (JCOG) Stomach Cancer Study Group (SCSG) initiated a collaboration to develop an optimal treatment strategy for LMGC. Before planning a prospective study, a questionnaire was sent out to the network members of both groups in June 2016 to clarify current common practice in each region. Sixty-seven sites from 17 countries in the EORTC network and 55 sites from Japan responded. According to the survey, for patients with resectable LMGC without extrahepatic metastases, preoperative chemotherapy followed by resection of both primary (if still in place) and liver lesions was the preferred option for both the synchronous and the metachronous setting. For patients with unresectable LMGC, most of the sites recommended chemotherapy only. In this article, the detailed results of this survey are reported, shedding light on current community practice, and a joint EORTC-JCOG strategy of investigation is delineated.