How I Treat Localized Soft Tissue Sarcomas: Update on Diagnosis, Risk Stratification, and Treatment.

BACKGROUND: Adult-type soft tissue sarcomas (STSs) are rare tumors representing about 1% of all adult malignant tumors. Their extreme histological heterogeneity places them among the most challenging fields of diagnostic pathology. The variability of clinical and prognostic presentation between the various histotypes reflects the different management that should be followed on a case-by-case basis. These features make STSs the case in point of how important it is a centralized and multidisciplinary approach. SUMMARY: Surgery represents the mainstay in the treatment of localized STSs. Recently, more and more studies are making efforts to understand what the contribution of chemotherapy and radiotherapy with neoadjuvant and adjuvant intent may be both in unselected and selected histological subgroups. In fact, despite the improvement in overall survival seen in the past few years thanks to the adoption of a more radical surgical approach, mortality remains relatively high and the 5-year overall survival is around 65%. KEY MESSAGES: In this review, we comment upon the treatment of localized STSs of the extremity, trunk wall, and retroperitoneum and how surgery, radiotherapy, and chemotherapy can be integrated with each other and individually tailored. Nomograms can assist clinicians in this complex therapeutic decision-making process, through the identification of patients at higher risk of death or disease relapse.

Identification of Aneuploid Circulating Tumor Cells in Soft-Tissue Sarcoma Patients: A Pilot Study.

BACKGROUND: Circulating tumor cells (CTCs) have been identified and shown to have prognostic and predictive roles in several types of carcinoma. More recently, aneuploid CTCs have become subject of a growing interest, as aneuploidy is considered a hallmark of cancer often associated with poor prognosis. Here, we aimed to identify for the first time aneuploid CTCs in soft-tissue sarcoma (STS) patients and show supportive in silico evidence on the prognostic role of aneuploidy in mesenchymal cancers. METHODS: In our pilot study, we collected blood from 4 metastatic STS patients and 4 age- and sex-matched healthy controls. After sample processing, cells were cyto-centrifuged onto glass slides and FISH was performed using 5 probes. The in silico analysis was performed using data from The Cancer Genome Atlas cohort of STS patients, using the validated Aneuploidy Score. We divided the patients in two populations (aneuploidy-high, Ane-Hi, and aneuploidy-low, Ane-Lo) using the median value of the Aneuploidy Score as a cutoff. Kaplan-Meier curves associated with log-rank test were used to compare progression-free and overall survival between groups. GraphPad Prism 8.0 (La Jolla, CA, USA) was used for statistical analyses. RESULTS: Aneuploid CTCs were identified in all 4 STS patients and in none of the controls, with a median value of 4 (range 3-6) per 7 mL of blood. Ane-Hi patients showed a significantly worse progression-free and overall survival compared to Ane-Lo patients. The same trend was maintained when analyzing the data based on the different histologies. CONCLUSIONS: We identified for the first time aneuploid CTCs in STS patients using fluorescence in situ hybridization in a surface marker-independent way. We also showed that the Aneuploidy Score has a prognostic value both in terms of progression-free survival and overall survival in STS patients using The Cancer Genome Atlas data, regardless of the histology.

The treatment paradigm of right-sided metastatic colon cancer: harboring BRAF mutation makes the difference.

PURPOSE: BRAF mutations represent the main negative prognostic factor for metastatic colorectal cancer and a supposed negative predictive factor of response to standard chemotherapy. We have explored survival difference in right-sided colon cancer (RCC) patients according to BRAF mutations, with the aim to identify any predictive factors of response to targeted-based therapy. METHODS: A retrospective study of RCC patients, with BRAF known mutation status, treated with chemotherapy (CT) from October 2008 to June 2019 in 5 Italian centers, was conducted. RESULTS: We identified 207 advanced RCC patients: 20.3% BRAF mutant and 79.7% BRAF wild type (wt). BRAF-mutant cancers were more likely to be pT4 (50.0% v 25.7%, p = 0.016), undifferentiated (71.4% v 44.0%, p = 0.004), KRAS wt (90.5% v 38.2%, p < 0.001), and MSI-H (41.7% v 16.2%, p = 0.019) tumors, with synchronous (52.4% v 31.5%, p = 0.018) and peritoneal metastases (38.1% v 22.4%, p = 0.003). Median overall survival (OS) was 16 v 27 months in BRAF mutant and BRAF wt (P = 0.020). In first-line setting, BRAF-mutant showed a 2ys OS of 80% in clinical trials, 32% in anti-VEGF, 14% in epidermial growth factor receptor (EGFR), and 0% in chemotherapy alone regimens (P = 0.009). BRAF-mutant patients demonstrated worse survival, regardless of targeted therapy administered. However, survival difference was statistically significant in the anti-EGFR-treated subgroup (16 v 28 months, P = 0.005 in BRAF mutant v BRAF wt, respectively). CONCLUSIONS: Our study demonstrated that BRAF status makes the difference in treatment's outcome. Therefore, the anti-EGFR should not be excluded in all advanced RCC but considered on a case-by-case basis.

The galaxy of the non-Linnaean nomenclature.

Contrary to the traditional claim that needs for unambiguous communication about animal and plant species are best served by a single set of names (Linnaean nomenclature) ruled by international Codes, I suggest that a more diversified system is required, especially to cope with problems emerging from aggregation of biodiversity data in large databases. Departures from Linnaean nomenclature are sometimes intentional, but there are also other, less obvious but widespread forms of not Code-compliant grey nomenclature. A first problem is due to the circumstance that the Codes are intended to rule over the way names are applied to species and other taxonomic units, whereas users of taxonomy need names to be applied to specimens. For different reasons, it is often impossible to refer a specimen with certainty to a named species, and in those cases an open nomenclature is employed. Second, molecular taxonomy leads to the discovery of clusters of gene sequence diversity not necessarily equivalent to the species recognized and named by taxonomists. Those clusters are mostly indicated with informal names or formulas that challenge comparison between different publications or databases. In several instances, it is not even clear if a formula refers to an individual voucher specimen, or is a provisional species name. The use of non-Linnaean names and formulas must be revised and strengthened by fixing standard formats for the different kinds of objects or hypotheses and providing permanent association of 'grey names' with standardized source information such as author and year. In the context of a broad-scope revisitation of aims and scope of scientific nomenclature, it may be worth rethinking if natural objects like plant galls and lichens, although other than the 'single-entity' objects traditionally covered by biological classifications, may nevertheless deserve taxonomic names.

The tapeworm's elusive antero-posterior polarity.

Because of their sessile lifestyle and the lack of the sensory and feeding structures usually associated with the cephalic end, fixing the antero-posterior (AP) polarity of tapeworms is somewhat equivocal and has been a matter of century-long debates. Koziol et al. offer the first molecular evidence finally fixing the scolex as the animal's anterior pole.

Species diversity vs. morphological disparity in the light of evolutionary developmental biology.

BACKGROUND: Two indicators of a clade's success are its diversity (number of included species) and its disparity (extent of morphospace occupied by its members). Many large genera show high diversity with low disparity, while others such as Euphorbia and Drosophila are highly diverse but also exhibit high disparity. The largest genera are often characterized by key innovations that often, but not necessarily, coincide with their diagnostic apomorphies. In terms of their contribution to speciation, apomorphies are either permissive (e.g. flightlessness) or generative (e.g. nectariferous spurs). SCOPE: Except for Drosophila, virtually no genus among those with the highest diversity or disparity includes species currently studied as model species in developmental genetics or evolutionary developmental biology (evo-devo). An evo-devo approach is, however, potentially important to understand how diversity and disparity could rapidly increase in the largest genera currently accepted by taxonomists. The most promising directions for future research and a set of key questions to be addressed are presented in this review. CONCLUSIONS: From an evo-devo perspective, the evolution of clades with high diversity and/or disparity can be addressed from three main perspectives: (1) evolvability, in terms of release from previous constraints and of the presence of genetic or developmental conditions favouring multiple parallel occurrences of a given evolutionary transition and its reversal; (2) phenotypic plasticity as a facilitator of speciation; and (3) modularity, heterochrony and a coupling between the complexity of the life cycle and the evolution of diversity and disparity in a clade. This simple preliminary analysis suggests a set of topics that deserve priority for scrutiny, including the possible role of saltational evolution in the origination of high diversity and/or disparity, the predictability of morphological evolution following release from a former constraint, and the extent and the possible causes of a positive correlation between diversity and disparity and the complexity of the life cycle.

Cell size versus body size in geophilomorph centipedes.

Variation in animal body size is the result of a complex interplay between variation in cell number and cell size, but the latter has seldom been considered in wide-ranging comparative studies, although distinct patterns of variation have been described in the evolution of different lineages. We investigated the correlation between epidermal cell size and body size in a sample of 29 geophilomorph centipede species, representative of a wide range of body sizes, from 6 mm dwarf species to gigantic species more than 200 mm long, exploiting the marks of epidermal cells on the overlying cuticle in the form of micro-sculptures called scutes. We found conspicuous and significant variation in average scute area, both between suprageneric taxa and between genera, while the within-species range of variation is comparatively small. This supports the view that the average epidermal cell size is to some extent taxon specific. However, regression analyses show that neither body size nor the number of leg-bearing segments explain this variation, which suggests that cell size is not an usual target of change for body size evolution in this group of arthropods, although there is evidence of its correlation with other morphological variables, like cuticle thickness. Scute sizes of miniaturized geophilomorph species are well within the range of the lineage to which the species belong, suggesting recent evolutionary transitions to smaller body size.

Segmentation of the millipede trunk as suggested by a homeotic mutant with six extra pairs of gonopods.

BACKGROUND: The mismatch between dorsal and ventral trunk features along the millipede trunk was long a subject of controversy, largely resting on alternative interpretations of segmentation. Most models of arthropod segmentation presuppose a strict sequential antero-posterior specification of trunk segments, whereas alternative models involve the early delineation of a limited number of 'primary segments' followed by their sequential stereotypic subdivision into 2n definitive segments. The 'primary segments' should be intended as units identified by molecular markers, rather than as overt morphological entities. Two predictions were suggested to test the plausibility of multiple-duplication models of segmentation: first, a specific pattern of evolvability of segment number in those arthropod clades in which segment number is not fixed (e.g., epimorphic centipedes and millipedes); second, the occurrence of discrete multisegmental patterns due to early, initially contiguous positional markers. RESULTS: We describe a unique case of a homeotic millipede with 6 extra pairs of ectopic gonopods replacing walking legs on rings 8 (leg-pairs 10-11), 15 (leg-pairs 24-25) and 16 (leg-pairs 26-27); we discuss the segmental distribution of these appendages in the framework of alternative models of segmentation and present an interpretation of the origin of the distribution of the additional gonopods.The anterior set of contiguous gonopods (those normally occurring on ring 7 plus the first set of ectopic ones on ring 8) is reiterated by the posterior set (on rings 15-16) after exactly 16 leg positions along the AP body axis. This suggests that a body section including 16 leg pairs could be a module deriving from 4 cycles of regular binary splitting of an embryonic 'primary segment'. CONCLUSIONS: A very likely early determination of the sites of the future metamorphosis of walking legs into gonopods and a segmentation process according to the multiplicative model may provide a detailed explanation for the distribution of the extra gonopods in the homeotic specimen. The hypothesized steps of segmentation are similar in both a normal and the studied homeotic specimen. The difference between them would consist in the size of the embryonic trunk region endowed with a positional marker whose presence will later determine the replacement of walking legs by gonopods.

Chilopoda Geophilomorpha of Europe: a revised list of species, with taxonomic and nomenclatorial notes.

An annotated list is provided for the genera and species of Chilopoda Geophilomorpha recorded from Europe, including Macaronesia. The list derives from a critical evaluation of all published information. All synonyms are also listed and all taxonomic and nomenclatorial novelties are discussed. Additionally, all available genus-group and species-group names are listed, together with type species and type localities respectively.To date, 452 available species-group names and 95 available genus-group names have been applied to European geophilomorphs, together with another 10 unavailable names. A total of 179 species in 37 genera are provisionally recognized here, but the actual taxonomic identity of 84 of these species is uncertain because their morphology is in completely or imprecisely known. Another 5 species have been recorded from European localities but probably are not established in the wild, and another 8 species have been reported probably only erroneously. We introduce the following 116 new synonymies: Algerophilus hispanicus (Meinert, 1870) [= Geophilus arago nicus Daday, 1889], Bothriogaster signata (Kessler, 1874) [= Notiphilus taeniatus C.L. Koch, 1847, = N. sanguineus C.L. Koch, 1847, = B. affinis Sseliwanoff, 1879, = B. meinerti Sseliwanoff, 1879], Clinopodes C.L. Koch, 1847 [= Poabius C.L. Koch, 1847], Clinopodes carinthiacus (Latzel, 1880) [= Geophilus flavidus styriacus Attems, 1895, = G. trebevicensis poschiavensis Verhoeff, 1934], C. flavidus C.L. Koch, 1847 [= Geophilus flavidus pachypus Verhoeff, 1942, = G. flavidus faitanus Verhoeff, 1943, = G. flavidus improvisus Verhoeff, 1943, = G. flavidus karamani Verhoeff, 1943, = G. flavidus sorattinus Verhoeff, 1951], Dignathodon Meinert, 1870 [= Rhysonotum Attems, 1952], Escaryus retusidens Attems, 1904 [= E. retusidens pallidus Folkmanová, 1956], Geophilus Leach, 1814 [= Homalarthrus Agassiz, 1846, = Esthiomenus Gistel, 1847, = Geophilus (Anadenophilus) Verhoeff, 1928], Geophilus aetnensis Verhoeff, 1928 [= G. insculptus debilis Brolemann, 1930, = G. evisensis Verhoeff, 1943, = G. henroti Manfredi, 1956, = G. aetnensis pollinensis Manfredi, 1957], G. alpinus Meinert, 1870 [= G. impressus C.L. Koch, 1847, = G. palustris C.L. Koch, 1863, = G. insculptus tauerorum Verhoeff, 1928, = G. glacialis inermis Verhoeff, 1938, = G. glacialis unguiculatus Verhoeff, 1938, = G. proximus rhenanus Verhoeff, 1895, = G. anglicanus Bagnall, 1935, = G. langkofelanus Verhoeff, 1938], G. bobolianus Verhoeff, 1928 [= G. longicornis aternanus Verhoeff, 1934], G. carpophagus Leach, 1815 [= Arthronomalus similis Newport, 1845, = G. pachymeropus Eisen & Stuxberg, 1868, = G. luridus Meinert, 1870], G. easoni Arthur, Foddai, Kettle, Lewis, Luczynski & Minelli 2001 [= Arthronomalus crassicornis Parfitt, 1866], G. electricus (Linnaeus, 1758) [= Scolopendra phosphorica Fourcroy, 1785], G. flavus (De Geer, 1778) [= G. longicornis trisulcus Silvestri, 1895, = G. longicornis glaber Verhoeff, 1928, = G. pygmaeus styricus Verhoeff, 1895, = G. longicornis pseudotruncorum Verhoeff, 1896, = G. longicornis styricorum Verhoeff, 1934, = G. carnicus praedator Verhoeff, 1937, = Pachymerium flavum Folkmanová, 1949, = G. osquidatum  porosus Dobroruka, 1957, = Schizotaenia ornata Folkmanová & Dobroruka, 1960], G. fucorum Brölemann, 1909 [= G. longicornis taorminensis Verhoeff, 1928, = G. ruinarum Verhoeff, 1931, = Pachymerium dragani Capuse, 1975], G. gavoyi Chalande, 1910 [= G. gavoyi elongatus Chalande, 1910], G. proximus C.L. Koch, 1847 [= G. ganonotus Attems, 1901, = G. eremophilus Lignau, 1933], G. pygmaeus Latzel, 1880 [= G. cispadanus Silvestri, 1896, = G. carnicus Verhoeff, 1928], G. pyrenaicus Chalande, 1909 [= G. pyrenaicus elongatus Chalande, 1909], G. seurati Brolemann, 1924 [= G. litorivagus Verhoeff, 1943], Gnathoribautia Brölemann, 1909 [= Turkomerium Chamberlin, 1952], Haplophilus Cook, 1896 [= Bothrohaplophilus Verhoeff, 1908, = Nesoporogaster Verhoeff, 1924], Haplophilus dimidiatus (Meinert, 1870) [= Himantarium gestri Pocock, 1890, = Ital ophilus sorattinus Verhoeff, 1951], H. excavatus (Verhoeff, 1924) [= Nesoporogaster hispanica Matic & Darabantu, 1969], H. souletinus Brölemann, 1907 [= H. souletinus lusitanus Verhoeff, 1925], H. subterraneus (Shaw, 1794) [= H. subterraneus elongatus Chalande & Ribaut, 1909], H. superbus (Meinert, 1870) [= Himantarium filum Meinert, 1870], Haploschendyla Verhoeff, 1900 [= Dalmatodyla Verhoeff, 1938, = Aporophilus Attems, 1903], Haploschendyla grantii (Pocock, 1891) [= Geophilus barbaricus Meinert, 1870, = H. europaea latzeli Demange, 1959], Henia bicarinata (Meinert, 1870) [= H. bicarinata elongata Brolemann, 1930, = H. bicarinata lapadensis Verhoeff, 1938], H. illyrica (Meinert, 1870) [= Chaetechelyne herzegowinensis Verhoeff, 1938, = H. illyrica absoloni Dobroruka, 1959], H. montana (Meinert, 1870) [= Chaetechelyne vesuviana pharyngealis Verhoeff, 1928], H. valida (Attems, 1927) [= Chaetechelyne osellai Matic & Darabantu, 1968], H. vesuviana (Newport, 1845) [= Scolopendra fusca Fourcroy, 1785, = Chaetechelyne sorattina Verhoeff, 1951], Hydroschendyla submarina (Grube, 1872) [= Arthronomalus littoralis Parfitt, 1874], Pachymerium coiffaiti Demange, 1959 [= P. ferrugineum maderianum Demange, 1959], P. ferrugineum (C.L. Koch, 1835) [= Geophilus caucasicus Attems, 1903, = P. tabacarui Capuse, 1968], Schendyla Bergsøe & Meinert, 1866 [= Astenoschendyla Brolemann, 1930, = Echinoschendyla Brölemann & Ribaut, 1912, = Microschendyla Brölemann & Ribaut, 1912, = Schizoschendyla Brölemann & Ribaut, 1912], Schendyla carniolensis Verhoeff, 1902 [= Poabius bistriatus C.L. Koch, 1847, = S. nemorensis quarnerana Verhoeff, 1937, = S. carniolensis clausensis Verhoeff, 1938, = S. carniolensis nivalis Verhoeff, 1938, = S. tesselata Verhoeff, 1943], S. nemorensis (C.L. Koch, 1837) [= S. nemorensis fountaini Turk, 1944, = Brachygeophilus sinionus Manfredi, 1953], S. tyrolensis (Meinert, 1870) [= Brachyschendyla montana prominens Ribaut & Brolemann, 1927, = S. montana herculis Verhoeff, 1938, = Brachyschendyla montana balcanica Kaczmarek, 1969, = Brachyschendyla dobrogica Matic & Darabantu, 1970], S. vizzavonae Léger & Duboscq, 1903 [= S. pellicensis Verhoeff, 1934, = S. incubationum Verhoeff, 1943], S. walachica Verhoeff, 1900 [= S. walachica rhodope nsis Kaczmarek, 1969], Stigmatogaster gracilis (Meinert, 1870) [= Himantarium laevipes C.L. Koch, 1847, = Geophilus ilicis Fabre, 1855, = S. gracilis robusta Attems, 1929, = Diadenoschisma gracile tyrrhenum Verhoeff, 1934, = D. gracile quarneranum Verhoeff, 1937, = S. gracilis aeserniana Attems, 1947], Strigamia acuminata (Leach, 1815) [ =Scolioplanes acuminatus brevidentatus Verhoeff, 1928, = Sc. acuminatus microdon Attems, 1904, = Sc. acuminatus pachypus Verhoeff, 1935, = Sc. italicus Verhoeff, 1928], S. crassipes (C.L. Koch, 1835) [= Scolioplanes variabilis carniolensis Verhoeff, 1895, = Sc. mediterraneus alsaticus Verhoeff, 1928, = Sc. mediterraneus carynthiacus Verhoeff, 1928, = Sc. crassipes longaronensis Verhoeff, 1935, = Sc. crassipes pegliensis Verhoeff, 1935, = Sc. crassipes faitanus Verhoeff, 1943], Thracophilus bulgaricus Verhoeff, 1926 [= T. beroni Matic & Darabantu, 1974], T. subterraneus Verhoeff, 1943 [= T. monoporus Attems, 1947].We also propose 14 new generic combinations: Dignathodon gracilis (Attems, 1952) [from Rhysonotum], Escaryus haasei (Sseliwanoff, 1884) [from Geophilus], Geophilus ibericus (Attems, 1952) [from Brachygeophilus], Geophilus pauciporus (Machado, 1952) [from Orinophilus], Gnathoribautia syriaca (Attems, 1903) [from Geophilus], Haplophilus excavatus (Verhoeff, 1924) [from Nesoporogaster], Haploschendyla splitensis (Verhoeff, 1938) [from Dalmatodyla], Henia duboscqui (Verhoeff, 1943) and H. ruffoi (Matic & Darabantu, 1968) [both from Chaetechelyne], Pachymerium minutum (Sseliwanoff, 1884) [from Geophilus], Schendyla capusei (Darabantu & Matic, 1969), S. hispanica (Attems, 1952) and S. verneri (Folkmanová & Dobroruka, 1960) [all from Brachyschendyla], Tuoba zograffi (Brölemann, 1900) [from Geophilus].Lectotypes have been selected for two species: Geophilus pusillus Meinert, 1870 and Himantarium mediterraneum Meinert, 1870.In seven cases we suggest to conserve currently used names over senior synonyms or homonyms: Geophilus alpinus Meinert, 1870 [over G. impressus C.L. Koch, 1847 and G. palustris C.L. Koch, 1863], Geophilus easoni Arthur, Foddai, Kettle, Lewis, Luczynski & Minelli 2001 [over Arthronomalus crassicornis Parfitt, 1866], Gnathoribautia bonensis (Meinert, 1870) [over Necrophloeophagus punctiventris Newport, 1844], Bothriogaster signata (Kessler, 1874) [over Notiphilus sanguineus C.L. Koch, 1847 and N. taeniatus C.L. Koch, 1847], Schendyla carniolensis Verhoeff, 1902 [over Poabius bistriatus C.L. Koch, 1847]. Corresponding applications have been submitted to the International Commission on Zoological nomenclature for a ruling under the Plenary Powers. 

An ectopic macrochaeta in the middle of a compound eye of a field-collected anthomyiid fly.

Recording and describing animal 'monsters' collected in the field can still contribute to progress in developmental biology despite the uncontrolled conditions the specimen experienced throughout development. Comparison with model organisms and a sound phylogenetic analysis may offer a tentative explanation for the underlying developmental mechanism and suggest new targets for experimental studies. We describe a female specimen of the anthomyiid fly Hydrophoria sp. with an ectopic macrochaeta in the left eye and suggest tentative interpretations, including one in terms of a local expression, or derepression, of a proneural gene. The anthomyiid lineage has been estimated to have split ca. 65 million years ago from the dipteran clade containing Drosophila and ca. 140 million years ago from the clade containing Megaselia.

Zoological nomenclature in the digital era.

Creation and use of the scientific names of animals are ruled by the International Code of Zoological Nomenclature. Until recently, publication of new names in a work produced with ink on paper was required for their availability. A long awaited amendment to the Code issued in September 2012 by the International Commission on Zoological Nomenclature now allows publication of new names in online-only works, provided that the latter are registered with ZooBank, the Official Register of Animal Names. With this amendment, the rules of zoological nomenclature have been aligned with the opportunities (and needs) of our digital era. However, possible causes for nomenclatural instability remain. These could be completely removed if the Code-compliant publication of new names will be identified with their online registration, under suitable technological and formal (legal) conditions. Future developments of the ZooBank may provide the tool required to make this definitive leap ahead in zoological nomenclature.

The centipede fauna (Chilopoda) of the island of Cyprus, with one new lithobiomorph species.

The centipede (Chilopoda) fauna of Cyprus, which was almost unknown, has been analysed by examining more than 1,800 specimens sampled from 185 sites, besides revising critically the few published data. A total of 26 species are listed and discussed (1 Scutigeromorpha, 9 Lithobiomorpha, 3 Scolopendromorpha, 13 Geophilomorpha), 21 of which are new to the island, i.e. Scutigera coleoptrata (Linnaeus, 1758), Lithobius (Ezembius) parvicornis (Porat, 1893), L. (E.) pamukkalensis Matic, 1980, L. (E.) zeylanus (Chamberlin, 1952), L. (Lithobius) carinatus L. Koch, 1862, L. (L.) erythrocephalus C.L. Koch, 1847, L. (Lithobius?) anderssoni n. sp., L. (Monotarsobius) ferganensis Trotzina, 1880, Cryptops (Cryptops) kosswigi (Chamberlin, 1952), C. (C.) cf. trisulcatus Brölemann, 1902, Dignathodon microcephalus (Lucas, 1846), Henia (Meinertia) bicarinata (Meinert, 1870), Geophilus cf. alpinus Meinert, 1870, G cf. carpophagus Leach, 1815, Pachymerium ferrugineum (C.L. Koch, 1835), Schizotaenia sp., Stenotaenia naxia (Verhoeff, 1901), Thracophilus cilicius Attems, 1947, Nannophilus eximius (Meinert, 1870) and Schendyla cf. nemorensis (C.L. Koch, 1837), and another unidentified species of Schendylidae . As far as known, Lithobius anderssoni n. sp. is endemic to the island. Geographic distribution in Cyprus and ecological notes are given for each species. Taxonomic remarks are given for some species.

A refreshed approach to homology-Prioritizing epistemology over metaphysics.

Unease with the inclusion of "sameness" in Owen's definition of homology characterizes a substantial part of the literature on this subject, where this term has acquired an increasingly strict metaphysical flavor. Taken for granted the existence of body features that are "the same," their existence has been explained by appealing to universal laws of form, as the product of common ancestry, or in terms of proximal causes responsible for the emergence of conserved developmental modules. However, a fundamentally different approach is possible, if we shift attention from metaphysics to epistemology. We may reword Owen's statement as follows: organs of different animals, in so far as they can be described as the same despite any difference in form and function, are called homologues. The proposed framework provides an umbrella for both the traditional, all-or-nothing concept of homology, and the less fashionable alternatives of factorial or partial homology, as well as for an extension of homology from form to function. No less attractive is the prospect to handle also ghost homologues, the body parts or organs of which there is non-objective evidence in a given clade, but can nevertheless be represented, in a description that encapsulates some of the traits observable in their extant homologue in the sister clade. Stripped of its different and constraining metaphysical explanations, homology survives as an anchor concept to which different nomadic disciplines and research agendas can be associated.

Descriptive versus causal morphology: gynandromorphism and intersexuality.

In animal species with separate sexes, abnormal individuals with a mix of phenotypically male and phenotypically female body parts are generally indicated as gynandromorphs, whereas individuals with intermediate sexual phenotypic traits are generally indicated as intersexes. However, this distinction, clear as it may seem, is neither universally agreed upon, nor free of critical issues. In consideration of the role of sex anomalies in understanding normal development, we reassess these phenomena of abnormal sexual development, taking into consideration the more recent advances in the study of sex determination and sexual differentiation. We argue that a distinction between gynandromorphism and intersexuality, although useful for descriptive purposes, is not always possible or sensible. We discuss the conceptual and terminological intricacies of the literature on this subject and provide reasons for largely, although not strictly, preferring a terminology based on descriptive rather than causal morphology, that is, on the observed phenotypic patterns rather on the causal process behind them.

Treatment Settings and Outcomes with Regorafenib and Trifluridine/Tipiracil at Third-Line Treatment and beyond in Metastatic Colorectal Cancer: A Real-World Multicenter Retrospective Study.

BACKGROUND: Patients with refractory mCRC rarely undergo third-line or subsequent treatment. This strategy could negatively impact their survival. In this setting, regorafenib (R) and trifluridine/tipiracil (T) are two key new treatment options with statistically significant improvements in overall survival (OS), progression-free survival (PFS), and disease control with different tolerance profiles. This study aimed to retrospectively evaluate the efficacy and safety profiles of these agents in real-world practice. MATERIALS AND METHODS: In 2012-2022, 866 patients diagnosed with mCRC who received sequential R and T (T/R, n = 146; R/T, n = 116]) or T (n = 325]) or R (n = 279) only were retrospectively recruited from 13 Italian cancer institutes. RESULTS: The median OS is significantly longer in the R/T group (15.9 months) than in the T/R group (13.9 months) (p = 0.0194). The R/T sequence had a statistically significant advantage in the mPFS, which was 8.8 months with T/R vs. 11.2 months with R/T (p = 0.0005). We did not find significant differences in outcomes between groups receiving T or R only. A total of 582 grade 3/4 toxicities were recorded. The frequency of grade 3/4 hand-foot skin reactions was higher in the R/T sequence compared to the reverse sequence (37.3% vs. 7.4%) (p = 0.01), while grade 3/4 neutropenia was slightly lower in the R/T group than in the T/R group (66.2% vs. 78.2%) (p = 0.13). Toxicities in the non-sequential groups were similar and in line with previous studies. CONCLUSIONS: The R/T sequence resulted in a significantly longer OS and PFS and improved disease control compared with the reverse sequence. R and T given not sequentially have similar impacts on survival. More data are needed to define the best sequence and to explore the efficacy of sequential (T/R or R/T) treatment combined with molecular-targeted drugs.

Retrospective Correlation between First Drug Treatment Duration and Survival Outcomes in Sequential Treatment with Regorafenib and Trifluridine/Tipiracil in Refractory Metastatic Colorectal Cancer: A Real-World Subgroup Analysis.

Background: Patients with refractory metastatic colorectal cancer (mCRC) rarely receive third-line or further treatment. In this context, regorafenib (R) and trifluridine/tipiracil (T) are two important novel therapeutic choices with statistically significant increases in overall survival (OS), progression-free survival (PFS), and disease control, with different toxicity profiles. This study is a subgroup analysis of our larger retrospective study, already published, whose objective was to assess the outcomes of patients when R and T were given sequentially. Patients and Methods: The study involved thirteen Italian cancer centers on a 10-year retrospective observation (2012-2022). In this subgroup analysis, we focused our attention on the correlation between the first drug treatment duration (<3 months, 3 to <6 months and ≥6 months) and survival outcomes in patients who had received the sequence regorafenib-to-trifluridine/tipiracil, or vice versa. Results: The initial study included 866 patients with mCRC who received sequential T/R, or R/T, or T or R alone. This analysis is focused on evaluating the impact of the duration of the first treatment in the sequence on clinical outcomes (OS, PFS) and includes 146 and 116 patients of the T/R and R/T sequences, respectively. Based on the duration of the first drug treatment, subgroups for the T/R sequence included 27 patients (18.4%) who received T for <3 months, 86 (58.9%) treated for 3 to <6 months, and 33 (22.6%) treated for ≥6 months; in the reverse sequence (R as the first drug), subgroups included 18 patients (15.5%) who received their first treatment for <3 months, 62 (53.4%) treated for 3 to <6 months, and 35 (31.0%) treated for ≥6 months. In patients who received their first drug treatment for a period of 3 to <6 months, the R/T sequence had a significantly longer median OS (13.7 vs. 10.8 months, p = 0.0069) and a longer median PFS (10.8 vs. 8.5 months, p = 0.0003) than the T/R group. There were no statistically significant differences between groups with first drug treatment durations of <3 months and ≥6 months. Conclusions: Our analysis seems to suggest that the administration of R for a period of 3 to <6 months before that of T can prolong both OS and PFS, as compared to the opposite sequence.

The origins of larval forms: what the data indicate, and what they don't.

What is a larva, if it is not what survives of an ancestor's adult, compressed into a transient pre-reproductive phase, as suggested by Haeckel's largely disreputed model of evolution by recapitulation? A recently published article hypothesizes that larva and adult of holometabolous insects are developmental expressions of two different genomes coexisting in the same animal as a result of an ancient hybridization event between an onychophoran and a primitive insect with eventless post-embryonic development. More likely, however, larvae originated from late embryonic or early post-embryonic stages of ancestors with direct development. Evolutionary novelties would thus be intercalary rather than terminal, with respect to the ancestor's ontogenetic schedule. This scenario, supported by current research on holometabolous insects and marine invertebrates with complex life cycles, offers a serious alternative to the traditional scenario ('what is early in ontogeny is also early in phylogeny') underlying the current perception of the evolution of genetic regulatory networks.

Spatially and Temporally Distributed Complexity-A Refreshed Framework for the Study of GRN Evolution.

Irrespective of the heuristic value of interpretations of developmental processes in terms of gene regulatory networks (GRNs), larger-angle views often suffer from: (i) an inadequate understanding of the relationship between genotype and phenotype; (ii) a predominantly zoocentric vision; and (iii) overconfidence in a putatively hierarchical organization of animal body plans. Here, we constructively criticize these assumptions. First, developmental biology is pervaded by adultocentrism, but development is not necessarily egg to adult. Second, during development, many unicells undergo transcriptomic profile transitions that are comparable to those recorded in pluricellular organisms; thus, their study should not be neglected from the GRN perspective. Third, the putatively hierarchical nature of the animal body is mirrored in the GRN logic, but in relating genotype to phenotype, independent assessments of the dynamics of the regulatory machinery and the animal's architecture are required, better served by a combinatorial than by a hierarchical approach. The trade-offs between spatial and temporal aspects of regulation, as well as their evolutionary consequences, are also discussed. Multicellularity may derive from a unicell's sequential phenotypes turned into different but coexisting, spatially arranged cell types. In turn, polyphenism may have been a crucial mechanism involved in the origin of complex life cycles.

Zoology: The view from 1,000 feet.

Variability in segment numbers in the world's most-leggy millipede adds support to a multiplicative mode of segment generation in myriapods.

Italian natural history museums need specimen digitization and much more: a reply to Benvenuti et al.

We reply to the comments made by Benvenuti et al. (2022) about our paper on the Italian natural history museums and scientific collections and the need of a centralized hub and repository. While agreeing that digitization is a useful tool to valorize each museum and collection, we still believe that the suggestion of a centralized hub is valid and necessary. This would largely help in boosting coordination among museums, sharing personnel and resources, and in providing a place to deposit scientific collections that do not fit the scope of smaller museums.