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Abstract The count of mitotic figures (MFs) observed in hematoxylin and eosin (H&E)-stained slides is an important prognostic marker, as it is a measure for tumor cell proliferation. However, the identification of MFs has a known low inter-rater agreement. In a computer-aided setting, deep learning algorithms can help to mitigate this, but they require large amounts of annotated data for training and validation. Furthermore, label noise introduced during the annotation process may impede the algorithms’ performance. Unlike H&E, where identification of MFs is based mainly on morphological features, the mitosis-specific antibody phospho-histone H3 (PHH3) specifically highlights MFs. Counting MFs on slides stained against PHH3 leads to higher agreement among raters and has therefore recently been used as a ground truth for the annotation of MFs in H&E. However, as PHH3 facilitates the recognition of cells indistinguishable from H&E staining alone, the use of this ground truth could potentially introduce an interpretation shift and even label noise into the H&E-related dataset, impacting model performance. This study analyzes the impact of PHH3-assisted MF annotation on inter-rater reliability and object level agreement through an extensive multi-rater experiment. Subsequently, MF detectors, including a novel dual-stain detector, were evaluated on the resulting datasets to investigate the influence of PHH3-assisted labeling on the models’ performance. We found that the annotators’ object-level agreement significantly increased when using PHH3-assisted labeling (F1: 0.53 to 0.74). However, this enhancement in label consistency did not translate to improved performance for H&E-based detectors, neither during the training phase nor the evaluation phase. Conversely, the dual-stain detector was able to benefit from the higher consistency. This reveals an information mismatch between the H&E and PHH3-stained images as the cause of this effect, which renders PHH3-assisted annotations not well-aligned for use with H&E-based detectors. Based on our findings, we propose an improved PHH3-assisted labeling procedure.

Introdução: O tétano é uma doença causada por toxinas produzidas pela bactéria Clostridium tetani. É uma doença muito prevalente em países em desenvolvimento e prevenível por vacinação, a qual, no Brasil, é distribuída gratuitamente pelo SUS. Apesar disso, a incidência do tétano tem se mostrado alta e letal, se comparado a outros países. Isso ocorre devido à falha na cobertura vacinal nacional, a qual, não atinge índice de vacinação de 95% preconizado. Sendo assim, esses indivíduos tornam-se suscetíveis à infecção. Objetivo: Analisar o histórico de casos de tétano dos últimos 10 anos no Hospital Universitário de Londrina (HUL). Método: Foi realizado um levantamento dos casos de tétano internados no HUL através de revisão de prontuários médicos. O número de pacientes total foi de 19. Resultados: Nesse sentido, é possível estabelecer que o perfil do paciente com tétano atendido no HUL é: Homem de meia idade (Me: 54 anos, x¯: 58,26 anos e σ: 18,58 anos). A maioria não conhece seu status vacinal ou não é vacinado. Ocupação dos pacientes: pedreiro, eletricista, morador de rua e trabalhador do campo. Todos com contágio acidental, esses pacientes apresentaram um curto período de incubação (cerca de uma semana), desenvolvendo, logo após, sintomas referentes ao tétano generalizado, sendo os mais presentes trismo, febre, rigidez muscular, disfagia e espasmos musculares. O manejo do paciente foi similar em relação ao uso de antibiótico, em todos foram utilizados penicilina e/ou metronidazol. Em contrapartida, o uso de Soro Antitetânico (SAT) e Imunoglobulina (IGHAT) variou entre pacientes: quatro utilizaram SAT e/ou IGHAT e três nenhum. Além disso, durante a internação, 6 pacientes necessitaram de debridamento da ferida contaminada. O Tempo de internação é de 1 a 14 semanas, sendo o tempo de internação em UTI, quando necessário, em média de 48 dias. Houve presença de infecções secundárias na maioria dos pacientes internados. O desfecho da maioria dos casos se dá em alta (57,89%). Conclusão: Portanto, fica clara a importância da conscientização, a fim de despertar a percepção da população acerca da gravidade da doença e da ação da atenção primária no processo de imunização nacional, principalmente entre adultos que não fazem o reforço.

Abstract Azobenzene is one of the most studied light‐controlled molecular switches and it has been incorporated in a large variety of supramolecular systems to control their structural and functional properties. Given the peculiar isomeric distribution at the photoexcited state (PSS), azobenzene derivatives have been used as photoactive framework to build metastable supramolecular systems that are out of the thermodynamic equilibrium. This could be achieved exploiting the peculiar E/Z photoisomerization process that can lead to isomeric ratios that are unreachable in thermal equilibrium conditions. The challenge in the field is to find molecular architectures that, under given external circumstances, lead to a given isomeric ratio in a reversible and predictable manner, ensuring an ultimate control of the configurational distribution and system composition. By reviewing early and recent works in the field, this review aims at describing photoswitchable systems that, containing an azobenzene dye, display a controlled configurational equilibrium by means of a molecular recognition event. Specifically, examples include programmed photoactive molecular architectures binding cations, anions and H‐bonded neutral guests. In these systems the non‐covalent molecular recognition adds onto the thermal and light stimuli, equipping the supramolecular architecture with an additional external trigger to select the desired configuration composition.

In everyday life, goal-oriented motor behaviour relies on the estimation of the rewards/costs associated with alternative actions and on the appropriate selection of movements. Motor decision making is defined as the process by which a motor plan is chosen among a set of competing actions based on the expected value. In the present literature review we discuss evidence from transcranial magnetic stimulation (TMS) studies of motor control. We focus primarily on studies of action selection for instructed movements and motor decision making. In the first section, we delve into the usefulness of various TMS paradigms to characterise the contribution of motor areas and distributed brain networks to cued action selection. Then, we address the influence of motivational information (e.g., reward and biomechanical cost) in guiding action choices based on TMS findings. Finally, we conclude that TMS represents a powerful tool for elucidating the neurophysiological mechanisms underlying action choices in humans.

New pathologies are causing dramatic declines and extinctions of multiple amphibian species. In 2013, in one fire salamander population of Northern Italy, we found individuals with undescribed cysts at the throat level, a malady whose existence has not previously been reported in amphibians. With the aim of describing this novel disease, we performed repeated field surveys to assess the frequency of affected salamanders from 2014 to 2020, and integrated morphological, histological, and molecular analyses to identify the pathogen. The novel disease affected up to 22% of salamanders of the study population and started spreading to nearby populations. Cysts are formed by mucus surrounding protist-like cells about 30 µm long, characterized by numerous cilia/undulipodia. Morphological and genetic analyses did not yield a clear match with described organisms. The existence of this pathogen calls for the implementation of biosecurity protocols and more studies on the dynamics of transmission and the impact on wild populations.

"The progress of the practice and the debate on architecture in the Alpine region of Trentino, in the last fifty years, has been characterised by a pivotal role of the Autonomous Province, the local authority with key competencies in environmental matters and spatial organisation, on the one hand, and by the experimentation and the promotion of discussion events on architecture, on the other. In the Sixties, spatial planning was conceived as a key instrument to support the development of a mountain province. Change was the perspective, and this required the activation of landscape control procedures centred on the control of the quality of architectural projects. This was not enough to qualify the professional practice, although some architects were able to propose innovative projects and began to animate the cultural debate, to establish supra-local relationships and to consolidate the awareness of the role of the architectural project. The contributions proposed are aimed at critically examine such issues, with a particular focus on the experience of institutions such as the “Scuola per il Governo del Territorio e del Paesaggio” within the Trentino School of Management, the “Osservatorio per il Paesaggio” within the Autonomous Province and the “Circolo Trentino Architettura Contemporanea”. Factors that led a decisive evolution of the spatial planning framework in the last decade, characterised by a new attention to the landscape and to the quality of architectural design, thanks to cultural initiatives, occasions of debate, and training paths."

"The “Premio triennale Giulio Andreolli – Fare Paesaggio” was inaugurated in 2016 with the aim of enhancing landscape experiences in the European Alpine area. It is composed of three sections: territorial planning and programming initiatives, architectural and landscape interventions, and education and participation actions. The success of the award shows the growing and transversal interest in landscape issues, at both institutional and professional level, in the context of spontaneous and “bottom-up” initiatives. One emergent aspect of interest during the various editions of the award is the emergence of a large number of activities related to the management of traditional rural landscapes, and oriented to the knowledge of territories and to the involvement of inhabitants. These local communities are often engaged in new organizational methods, driven by sincere enthusiasm and civic engagement. That is the reason why one of the most interesting elements emerging from the award experience must be sought in this intersection between popular initiatives and both professional and institutional approaches. By bounding this reflection to the regeneration-driven production, which is the main topic of this issue, it is possible to isolate, among the many cases nominated for the award, some interesting experiences. With different outcomes, various designers and clients have dealt with contemporary architecture and explored important themes related to the transformation of Alpine landscapes."

O objetivo principal deste estudo foi identificar quais atributos varejistas explicam a intenção de recompra dos consumidores. Este framework de pesquisa se justifica dada a importância do segmento varejista para a economia brasileira e pela relativa incongruência nos resultados dos estudos conduzidos anteriormente. Para tanto, conduzimos um survey, junto a uma amostra de 802 consumidores, que mensurou a avaliação de 12 atributos varejistas, como foi proposto por Rathod e Bhatt (2014), e que foram analisados por meio de regressão linear múltipla. Os resultados indicam que a localização da loja, a política de preços praticada pelo varejista e o layout da loja avaliada explicam a maior parte da intenção de recompra. Além disso, a variedade de marcas disponível, a imagem da marca própria do varejista e o tamanho da loja também apresentaram relação positiva e significante com a intenção de compra declarada. Palavras-chave: varejo; atributos varejistas; intenção de recompra.

Cytology represents a useful diagnostic tool in the preliminary clinical approach to canine splenic lesions, and may prevent unnecessary splenectomy. However, few studies have evaluated diagnostic accuracy of cytology in the diagnosis of canine splenic neoplasms. The aim of this study was to determine overall accuracy, sensitivity, specificity, positive and negative predictive values (i.e. diagnostic accuracy indexes) of cytology for canine splenic neoplasms following Standards for the Reporting of Diagnostic Accuracy Studies (STARD) guidelines. A consecutive series of canine splenic cytological samples was retrospectively retrieved from the database of the Diagnostic Pathology Service of the Department of Veterinary Medicine (DIMEVET-University of Milan). Histopathology was set as the diagnostic reference standard. Cytological cases were enrolled when slides were available for review and when the same lesion was submitted for histopathology. Seventy-eight (78) lesions were included in the study. By histopathology, 56 were neoplastic and 22 were non-neoplastic. Cytology had an overall accuracy of 73.08% (95% C.I. 61.84%-82.50%), sensitivity of 64.29% (95% C.I. 50.36%-76.64%), specificity of 95.45% (95% C.I. 77.16%-99.88%), and positive and negative predictive values of 97.3% (95% C.I. 84.01%-99.60%) and 51.22% (95% C.I. 42.21%-60.15%), respectively. Low sensitivity and negative predictive value were balanced by very high specificity and positive predictive value. When positive for neoplasia, cytology represents a useful diagnostic tool to rule in splenic neoplasia, prompting surgery independently from other diagnostic tests. Conversely, a negative cytological result requires additional investigations to confirm the dog to be disease free.

Background and aims: Cerebrospinal fluid (CSF) protein content presents a sexual dimorphism in humans. We investigated sex-related differences in CSF IgG levels and in the quantification of intrathecal IgG synthesis (IIS). Methods: CSF, serum albumin and IgG were measured in 1519 neurological patients and both linear and hyperbolic formulas were used for the quantification of IIS. CSF-restricted oligoclonal IgG bands (OCBs) were used as “gold standard”. Results: The linear IgG Index showed a weak agreement with OCBs in males and females (k = 0.559, k = 0.587, respectively), while the hyperbolic Reiber’s formulas had a moderate agreement with OCBs in females (k = 0.635) and a weak agreement in males (k = 0.565). Higher CSF albumin and IgG levels were found in men than in women in the whole population and in subjects without IIS after adjusting for age and for serum concentrations of albumin and IgG, respectively (Quade statistics, p < 0.000001). CSF and serum albumin and IgG levels positively correlated to age in both sexes. CSF total protein content did not correlate with CSF leukocyte numbers but was higher in patients with marked pleocytosis. Conclusions: In neurological patients, men have higher levels of CSF serum-derived proteins, such as albumin and IgG.

O objetivo do artigo foi buscar entende quais as mudanças ocorreram nos setores empresariais Brasileiros, por meio da utilização doss dados do CAGED, utilizando analise de variância (ANOVA), a qual encontrou diferenças entre os empregados dos setores 1=Agricultura e 2= Indústria e também entre os setores 2 e 3=Serviços, no entanto o teste encontrou diferenças na entrada de profissionais apenas nos setores 3 e 4, indicando que a construção civil, recebeu mais novos empregados do que o setor de serviços, enquanto que em relação as saídas, o setor que vem perdendo empregados em relação ao setor de serviços é a indústria, um dado intrigante é que o setor que melhor remunera atualmente é o setor da construção civil, talvez devido ao crescimento que este setor vem experimento nos últimos anos.

We report the first de novo sequence assembly and analysis of the genome of Testudinid herpesvirus 3 (TeHV3), one of the most pathogenic chelonian herpesviruses. The genome of TeHV3 is at least 150,080 nucleotides long, is arranged in a type D configuration and comprises at least 102 open reading frames extensively co-linear with those of Human herpesvirus 1. Consistently, the phylogenetic analysis positions TeHV3 among the Alphaherpesvirinae, closely associated with Chelonid herpesvirus 5, a Scutavirus. To date, there has been limited genetic characterization of TeHVs and a resolution beyond the genotype was not feasible because of the lack of informative DNA sequences. To exemplify the potential benefits of the novel genomic information provided by this first whole genome analysis, we selected the glycoprotein B (gB) gene, for detailed comparison among different TeHV3 isolates. The rationale for selecting gB is that it encodes for a well-conserved protein among herpesviruses but is coupled with a relevant antigenicity and is consequently prone to accumulate single nucleotide polymorphisms. These features were considered critical for an ideal phylogenetic marker to investigate the potential existence of distinct TeHV3 genogroups and their associated pathology. Fifteen captive tortoises presumptively diagnosed to be infected with TeHVs or carrying compatible lesions on the basis of either the presence of intranuclear inclusions (presumptively infected) and/or diphtheronecrotic stomatitis-glossitis or pneumonia (compatible lesions) were selected for the study. Viral isolation, TeHV identification, phylogenetic analysis and pathological characterization of the associated lesions, were performed. Our results revealed 1) the existence of at least two distinct TeHV3 genogroups apparently associated with different pathologies in tortoises and 2) the first evidence for a putative homologous recombination event having occurred in a chelonian herpesvirus. This novel information is not only fundamental for the genetic characterization of this virus but is also critical to lay the groundwork for an improved understanding of host-pathogen interactions in chelonians and contribute to tortoise conservation.

Although the term nanozymes was coined by us in 2004 to highlight the enzyme-like properties of gold nanoparticles passivated with a monolayer of Zn(II)-complexes in the cleavage of phosphate diesters, systems resembling those metallo-nanoparticles, like micelles and vesicles, have been the subject of investigation since the mid-eighties of the last century. This paper reviews what has been done in the field and compares the different nanosystems highlighting the source of catalysis and frequent misconceptions found in the literature.

The heterogeneous morphologic features of canine plasmacytomas (PCTs) can make their differentiation from other round cell tumors challenging. Immunohistochemistry (IHC) for lambda (λ) and kappa (к) immunoglobulin (Ig) light chains is often equivocal because of high background staining. The chromogenic in situ hybridization (CISH) technique for light chains has shown higher sensitivity compared to IHC in human plasma cell tumors. Therefore, we aimed to validate automated CISH for light chains in canine tissues and to evaluate its diagnostic potential in canine PCTs, in conjunction with routinely used IHC markers. CISH for light chains demonstrated a clear signal in plasma cell populations of canine control tissues (lymph nodes, lymphoplasmacytic inflammation) showing a polyclonal pattern with a prevalence of λ-producing cells. CISH detected monotypic light chain expression in 33 of 53 (62%) PCTs, 31 expressing λ and 2 expressing к. CISH was more sensitive than IHC for λ light chain (58% vs. 47%, respectively) and more easily interpretable given the absence of confounding background staining. The absence of CISH staining for both λ and к in a considerable subset of tumors may be the result of lower light chain production by neoplastic cells. Multiple myeloma oncogene 1 (MUM1) was expressed by all but 2 PCTs (96%), which showed λ expression by CISH and IHC. The identification of poorly differentiated canine PCTs requires the assessment of a panel of IHC markers, with the potential support of CISH for Ig light chains. [ABSTRACT FROM AUTHOR]

Regenerative medicine has gained a strong interest in reptile practice, with transposition of techniques widely used in human and mammal medicine. Specifically, Platelet Rich Plasma (PRP) and derived products have shown to be safe and promising tools to improve soft and bone tissue healing in this class. Hereby we present two cases of oral cavity disorders treated with heterologous Thrombocyte-Leukocyte Rich Plasma (TLRP). In the first case, TLRP was used on one ball python (Python regius) with chronic facial cellulitis, to adjuvate post-surgical wound healing. In the second case, it was the elected therapy to treat one veiled chameleon (Chamaeleo calyptratus) with severe maxillary osteolysis secondary to chronic periodontal disease. Repeated CT scans were performed to evaluate healing progression. In both cases, single administration of TLRP was able to stop bone lysis progression, but was not enough to promote new bone formation. Our experience suggests that the use of thrombocyte-derived products, thanks to their regenerative and antimicrobial properties, could represent a useful tool to adjuvate traditional therapies in reptile reconstructive medicine. [ABSTRACT FROM AUTHOR]

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Summary A 14-year-old red-ear slider turtle (Trachemys scripta elegans) with no history of pre-existing clinical disease died and was referred for necropsy examination. Grossly, oesophageal prolapse, bilateral renal cysts and a paraduodenal cystic mass were detected. Tissues were processed routinely for histology and immunohistochemistry (IHC) with primary antibodies specific for Wilm's tumour suppressor gene-1 (WT-1), insulin, glucagon and pancytokeratins. Microscopically, renal medullary cysts and medullary atrophy resembled the changes associated with polycystic kidney disease (PKD). The cysts of the paraduodenal mass were lined by ciliated epithelial cells resembling embryonal cells and were intensely positive for glucagon and insulin by IHC. There was no cytokeratin expression in either lesion. WT-1 expression in the paraduodenal mass was cytoplasmic and appeared non-specific. Lesions were consistent with renal PKD-like disease and a pancreatic cystic hamartoma. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

Heterotopic ossification (HO) is a rare condition characterized by abnormal bone production in soft tissue. Very few cases of HO have been reported in animals (e.g., dogs and horses) and this disease process is often a consequence of a traumatic incident. A 5-year-old, male European ferret ( Mustela putorius furo ) was referred for anorexia, generalized weakness, and weight loss. Clinical examination revealed multiple abdominal masses. An explorative laparotomy identified omental, white/tan, nodular to coalescing hard lesions. The omentum and spleen were surgically removed during the surgical procedure, with both subsequently submitted for histopathologic evaluation. Microscopically, the omental masses were composed of a meshwork of lamellar and woven bone admixed with islands of cartilage and lacunae containing either blood, fat, and/or bone marrow. Multifocal mineralization and bone lamellae were also present in the grossly normal omentum. The finding of multiple bone nodules containing bone marrow and/or adipose tissue, with no Harversian system, and minimal intratrabecular connective tissue favored a diagnosis of HO. [ABSTRACT FROM AUTHOR]