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J Clin Pathol 2003;56:736-741 Aims: To investigate the immunohistochemical expression of a panel of biologically relevant markers in patients with non-small cell lung cancer using fresh frozen specimens and to [...]

Abstract Background Different molecular therapies like the EGFR-inhibiting antibody cetuximab have come into clinical practice. Cetuximab is EMEA-approved for metastatic colorectal cancer and advanced squamous-cell head and neck cancer. Administration is said to be safe and well tolerated with common, usually mild dermatologic side effects. Case presentation We present the case of a patient with fatal complications after oesophagectomy and neoadjuvant chemotherapy including cetuximab for squamous-cell esophageal cancer. A transthoracic en-bloc oesophagectomy was performed. Few days later the patient died due to gas exchange dysfunction and circulation instability after a previously unseen combination of drain-erosion of the stomach with subsequent pleurisy and air leak of the left main bronchus. Conclusion So far we have never observed this fatal combination of drain erosion of the stomach with fibrinous pleurisy and unmanageable progressive tracheal defect before. The role of cetuximab in the multifactorial aetiology of damages of stomach and trachea after oesophagectomy remains unclear since we are not able to link the complication directly to cetuximab or definitely exclude it as a sole surgical complication. Clinicians should be aware of the possibility of fatal side effects and careful recording of all complications is necessary in ongoing and planned studies to obtain more evidence about safety and tolerance of targeted therapies.

The black abalone, Haliotis cracherodii , is a large, long-lived marine mollusc that inhabits rocky intertidal habitats along the coast of California and Mexico. In 1985, populations were impacted by a bacterial disease known as withering syndrome (WS) that wiped out >90% of individuals, leading to the species' designation as critically endangered. Current conservation strategies include restoring diminished populations by translocating healthy individuals. However, population collapse on this scale may have dramatically lowered genetic diversity and strengthened geographic differentiation, making translocation-based recovery contentious. Additionally, the current prevalence of WS is unknown. To address these uncertainties, we sequenced and analyzed the genomes of 133 black abalone individuals from across their present range. We observed no spatial genetic structure among black abalone, with the exception of a single chromosomal inversion that increases in frequency with latitude. Genetic divergence between sites is minimal, and does not scale with either geographic distance or environmental dissimilarity. Genetic diversity appears uniformly high across the range. Despite this, however, demographic inference confirms a severe population bottleneck beginning around the time of WS onset, highlighting the temporal offset that may occur between a population collapse and its potential impact on genetic diversity. Finally, we find the bacterial agent of WS is equally present across the sampled range, but only in 10% of individuals. The lack of genetic structure, uniform diversity, and prevalence of WS bacteria indicates that translocation could be a valid and low-risk means of population restoration for black abalone species' recovery.

Objective: Implantable cardiovascular therapeutic devices (CTD) including stents, percutaneous heart valves and ventricular assist devices, while lifesaving, impart supraphysiologic shear stress to platelets resulting in thrombotic and bleeding device-related coagulopathy. We previously demonstrated that shear-mediated platelet dysfunction is associated with downregulation of platelet GPIb-IX-V and αIIbβ3 receptors via generation of platelet-derived microparticles (PDMPs). Here, we test the hypothesis that shear-generated PDMPs manifest phenotypical heterogeneity of their morphology and surface expression of platelet receptors, and modulate platelet hemostatic function., Approach and Results: Human gel-filtered platelets were exposed to continuous shear stress and sonication. Alterations of platelet morphology were visualized using transmission electron microscopy. Surface expression of platelet receptors and PDMP generation were quantified by flow cytometry. Thrombin generation was quantified spectrophotometrically, and platelet aggregation in plasma was measured by optical aggregometry. We demonstrate that platelet exposure to shear stress promotes notable alterations in platelet morphology and ejection of several distinctive types of PDMPs. Shear-mediated microvesiculation is associated with the differential remodeling of platelet receptors with PDMPs expressing significantly higher levels of both adhesion (α IIb β 3 , GPIX, PECAM-1, P-selectin, and PSGL-1) and agonist-evoked receptors (P 2 Y 12 & PAR1). Shear-mediated PDMPs have a bidirectional effect on platelet hemostatic function, promoting thrombin generation and inhibiting platelet aggregation induced by collagen and ADP., Conclusions: Shear-generated PDMPs demonstrate phenotypic heterogeneity as to morphologic features and defined patterns of surface receptor alteration, and impose a bidirectional effect on platelet hemostatic function. PDMP heterogeneity suggests that a range of mechanisms are operative in the microvesiculation process, contributing to CTD coagulopathy and posing opportunities for therapeutic manipulation.

Thymic epithelial tumours (TETs) represent a rare disease, yet they are the most common tumours of the anterior mediastinum. Due to the rare occurrence of TETs, evidence on optimal treatment is limited. Surgery is the treatment of choice in the management of TETs, while the role of postoperative radiotherapy (PORT) remains unresolved. PORT remains debated for thymomas, especially in completely resected stage II tumours, for which PORT may be more likely to benefit in the presence of aggressive histology (WHO subtype B2, B3) or extensive transcapsular invasion (Masaoka-Koga stage IIB). For stage III thymoma, evidence suggests an overall survival (OS) benefit for PORT after complete resection. For incompletely resected thymomas stage II or higher PORT is recommended. Thymic carcinomas at any stage with positive resection margins should be offered PORT. Radiotherapy plays an important role in the management of unresectable locally advanced TETs. Induction therapy (chemotherapy or chemoradiation) followed by surgery may be useful for locally advanced thymic malignancies initially considered as unresectable. Chemotherapy only is offered in patients with unresectable, metastatic tumours in palliative intent, checkpoint inhibitors may be promising for refractory diseases. Due to the lack of high-level evidence and the importance of a multidisciplinary approach, TETs should be discussed within a multidisciplinary team and the final recommendation should reflect individual patient preferences., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tlcr-20-458). The focused issue “Radiotherapy in thoracic malignancies” was commissioned by the editorial office without any funding or sponsorship. Paul Martin Putora reports research support and educational grants to the department: AstraZeneca, Celgene, Takeda. The authors have no other conflicts of interest to declare., (2021 Translational Lung Cancer Research. All rights reserved.)

Two -omics studies on genetically modified maize and Roundup-fed rats, recently published in the journal Scientific Reports, contain serious flaws in the experimental design, methodology and interpretation of results, which we point out here. The use of -omics technologies are of increasing importance in research, however we argue for a cautious approach to the potential application in food safety assessments as these exceptionally sensitive and complex methods require a thorough and detailed evaluation of the biological significance of obtained results. Arising from: Mesnage et al. Sci Rep 7:39328 (2017), Mesnage et al. Sci Rep 6:37855 (2016).

In this review, current EU GMO regulations are subjected to a point-by point analysis to determine their suitability for agriculture in modern Europe. Our analysis concerns present GMO regulations as well as suggestions for possible new regulations for genome editing and New Breeding Techniques (for which no regulations presently exist). Firstly, the present GMO regulations stem from the early days of recombinant DNA and are not adapted to current scientific understanding on this subject. Scientific understanding of GMOs has changed and these regulations are now, not only unfit for their original purpose, but, the purpose itself is now no longer scientifically valid. Indeed, they defy scientific, economic, and even common, sense. A major EU regulatory preconception is that GM crops are basically different from their parent crops. Thus, the EU regulations are "process based" regulations that discriminate against GMOs simply because they are GMOs. However current scientific evidence shows a blending of classical crops and their GMO counterparts with no clear demarcation line between them. Canada has a "product based" approach and determines the safety of each new crop variety independently of the process used to obtain it. We advise that the EC re-writes it outdated regulations and moves toward such a product based approach.  Secondly, over the last few years new genomic editing techniques (sometimes called New Breeding Techniques) have evolved. These techniques are basically mutagenesis techniques that can generate genomic diversity and have vast potential for crop improvement. They are not GMO based techniques (any more than mutagenesis is a GMO technique), since in many cases no new DNA is introduced. Thus they cannot simply be lumped together with GMOs (as many anti-GMO NGOs would prefer). The EU currently has no regulations to cover these new techniques. In this review, we make suggestions as to how these new gene edited crops may be regulated. The EU is at a turning point where the wrong decision could destroy European agricultural competitively for decades to come.

While the upward shift of plant species has been observed on many alpine and nival summits, the reaction of the subalpine and lower alpine plant communities to the current warming and lower snow precipitation has been little investigated so far. To this aim, 63 old, exhaustive plant inventories, distributed along a subalpine-alpine elevation gradient of the Swiss Alps and covering different plant community types (acidic and calcareous grasslands; windy ridges; snowbeds), were revisited after 25-50 years. Old and recent inventories were compared in terms of species diversity with Simpson diversity and Bray-Curtis dissimilarity indices, and in terms of community composition with principal component analysis. Changes in ecological conditions were inferred from the ecological indicator values. The alpha-diversity increased in every plant community, likely because of the arrival of new species. As observed on mountain summits, the new species led to a homogenization of community compositions. The grasslands were quite stable in terms of species composition, whatever the bedrock type. Indeed, the newly arrived species were part of the typical species pool of the colonized community. In contrast, snowbed communities showed pronounced vegetation changes and a clear shift toward dryer conditions and shorter snow cover, evidenced by their colonization by species from surrounding grasslands. Longer growing seasons allow alpine grassland species, which are taller and hence more competitive, to colonize the snowbeds. This study showed that subalpine-alpine plant communities reacted differently to the ongoing climate changes. Lower snow/rain ratio and longer growing seasons seem to have a higher impact than warming, at least on plant communities dependent on long snow cover. Consequently, they are the most vulnerable to climate change and their persistence in the near future is seriously threatened. Subalpine and alpine grasslands are more stable, and, until now, they do not seem to be affected by a warmer climate.

Samples of the lichen Parmelia sulcata Taylor were collected in the vicinity of 17 air pollution monitoring stations in the northern part of Switzerland and its bordering area. Net photosynthesis, dark respiration, and the content of [ 35 S]-sulphate and [ 35 S]-protein after cultivation with 35 SO 4 2- , as well as the chlorophyll and protein contents were measured. Mean values of dark respiration and protein content were not significantly different in the plant material from the various locations. Most of the mean values of net photosynthesis differed less than the average standard deviation. The rates of sulphate uptake and protein synthesis were lowest and chlorophyll content was highest at the most polluted sites. The values differed by a factor of 3.5-7 between the various locations. Multiple regression analysis gave a linear correlation between the three physiological parameters [ 35 S]-sulphate, [ 35 S]-protein and chlorophyll content and a combination of the annual mean concentrations of the air pollutants NO, NO 2 , SO 2 and O 3 . The highest multiple correlation coefficient (R 2 ) was estimated for chlorophyll (0-84). Its linear correlation coefficient (r) with NO 2 alone was 0.91, and with SO 2 alone 0.85.