Pluripotency of a founding field: rebranding developmental biology.

The field of developmental biology has declined in prominence in recent decades, with off-shoots from the field becoming more fashionable and highly funded. This has created inequity in discovery and opportunity, partly due to the perception that the field is antiquated or not cutting edge. A 'think tank' of scientists from multiple developmental biology-related disciplines came together to define specific challenges in the field that may have inhibited innovation, and to provide tangible solutions to some of the issues facing developmental biology. The community suggestions include a call to the community to help 'rebrand' the field, alongside proposals for additional funding apparatuses, frameworks for interdisciplinary innovative collaborations, pedagogical access, improved science communication, increased diversity and inclusion, and equity of resources to provide maximal impact to the community.

PITX2 as a Sensitive and Specific Marker of Midgut Neuroendocrine Tumors: Results from a Cohort of 1157 Primary Neuroendocrine Neoplasms.

As neuroendocrine tumors (NETs) often present as metastatic lesions, immunohistochemical assignment to a site of origin is one of the most important tasks in their pathologic assessment. Because a fraction of NETs eludes the typical expression profiles of their primary localization, additional sensitive and specific markers are required to improve diagnostic certainty. We investigated the expression of the transcription factor Pituitary Homeobox 2 (PITX2) in a large-scale cohort of 909 NET and 248 neuroendocrine carcinomas (NEC) according to the immunoreactive score (IRS) and correlated PITX2 expression groups with general tumor groups and primary localization. PITX2 expression (all expression groups) was highly sensitive (98.1%) for midgut-derived NET, but not perfectly specific, as non-midgut NET (especially pulmonary/duodenal) were quite frequently weak or moderately positive. The specificity rose to 99.5% for a midgut origin of NET if only a strong PITX2 expression was considered, which was found in only 0.5% (one pancreatic/one pulmonary) of non-midgut NET. In metastases of midgut-derived NET, PITX2 was expressed in all cases (87.5% strong, 12.5% moderate), whereas CDX2 was negative or only weakly expressed in 31.3% of the metastases. In NEC, a fraction of cases (14%) showed a weak or moderate PITX2 expression, which was not associated with a specific tumor localization. Our study independently validates PITX2 as a very sensitive and specific immunohistochemical marker of midgut-derived NET in a very large collective of neuroendocrine neoplasms. Therefore, our data argue toward implementation into diagnostic panels applied for NET as a firstline midgut marker.

The complete mitochondrial genome of a species of Cirrhipathes de Blainville, 1830 from Kaua'i, Hawai'i (Hexacorallia: Antipatharia).

This study reports the first mitogenome from the antipatharian (black coral) genus Cirrhipathes (GenBank accession number ON653414). The 20,452 bp mitochondrial genome of Cirrhipathes cf. anguina LS-2022 consists of 13 protein-coding genes, two rRNA genes, and two tRNA genes (trnM and trnW). The mitogenome is typical of other antipatharian families, including an A + T biased (64.1%) base composition and cytochrome c oxidase subunit I (COX1) intron with embedded homing endonuclease gene (HEG). A phylogenetic tree based on complete mitogenome sequences of currently available antipatharians indicates Cirrhipathes cf. anguina LS-2022 is sister and closely related to Stichopathes sp. SCBUCN-8849. However, it seems unlikely that intergeneric taxa share 99.97% similarity across their complete mitogenomes, raising questions about the current taxonomy of this group. This study highlights the need for additional vouchered antipatharian species to be sequenced so phylogenetic relationships can be compared with accepted taxonomy.

Fine structural analysis of degummed fibroin fibers reveals its superior mechanical capabilities.

Silk fibers constitute a class of protein building blocks capable of functionalization and reprocessing into various material formats. The properties of these fibers are typically affected by the intense thermal treatments needed to remove the sericin gum coating layer. Additionally, their mechanical characteristics are often misinterpreted by assuming the cross-sectional area is a perfect circle. The thermal treatments impact not only the mechanics of the fibers but also the structure of the resolubilized protein, thereby limiting the performance of the resulting silk-based materials. To mitigate these limitations, we explored varying alkali conditions at low temperatures for surface treatment, effectively removing the sericin gum layer while preserving the molecular structure of the fibroin protein, thus, maintaining the hierarchical integrity of the exposed fibroin microfiber core. The precise determination of the initial CSA of the asymmetrical silk fibers led to a comprehensive analysis of their mechanical properties. Our findings indicate that the alkali surface treatment raised the Young's modulus and tensile strength by increasing the fibers' crystallinity by approximately 40% and 50%, respectively, without compromising their strain. We have shown that this treatment facilitated further production of high-purity soluble silk with rheological and self-assembly characteristics comparable to those of native silk.

Fragility fractures of the pelvis: First 48 cases of surgical treatment at a level 1 trauma center in France.

INTRODUCTION: Longer life expectancy is accompanied by a higher incidence of fragility fractures of the pelvis (FFP), which has repercussions on mortality and nursing home admissions. Given the paucity of data at French healthcare facilities, we carried out a retrospective study to (1) evaluate how surgical treatment of FFP with posterior displacement (type III and IV according to Rommens and Hofmann) affects a patient's pain, functional status and ability to stay at home and (2) evaluate the postoperative complications and mortality rate. HYPOTHESIS: Surgery for posteriorly displaced FFP will relieve pain and preserve the patient's independence. METHODS: All the patients over 65 years of age who were operated on for a posterior FFP between January 2015 and August 2020 were included in this prospective, single-center study. The demographics, fracture type, details of the surgical treatment, complications and mortality were analyzed. Pain (visual analog scale, VAS), functional status (Activity of Daily Living [ADL] and Instrumental Activity of Daily Living [IADL]), mobility (Parker score) and rates of nursing home admissions were compared before the fracture, after surgery and at a mean follow-up of 28 months (minimum follow-up of 1 year). RESULTS: Forty-eight patients with a mean age of 75 years were included. Twenty-four of these patients (50%) had at least two comorbidities. The FFPs were either type IV (31/48; 65%) or type III (17/48; 35%). The mean VAS for pain was significantly lower on the first day postoperative (3.5 versus 4.8; p=0.02). This significant reduction continued upon discharge from the hospital (1.95; p=0.003) and persisted at the mean follow-up of 28 months (2.2; p=0.64). The complication rate was 15% (7/48) and the mortality rate at the final review was 15% (7/48). Among the surviving patients, 81% (29/36) returned to living at home. The ADL (5.1 versus 5.8; p=0.09), IADL (5.9 versus 6.9; p=0.15) and Parker score (6.8 versus 8.2; p=0.08) at the final review were not significantly different from the values before the fracture. CONCLUSION: This is the first French study of patients operated on for an FPP. Fixation of posteriorly displaced fractures allows surviving patients to retain their mobility. Pain relief is achieved quickly and maintained during the follow-up period. Thus, our initial hypothesis is affirmed. The complication rate is not insignificant; given the complexity of this surgery, percutaneous treatment is preferable. LEVEL OF EVIDENCE: IV; retrospective study.

PD-L1 Immunohistochemistry in Gastric Cancer: Comparison of Combined Positive Score and Tumor Area Positivity Across 28-8, 22C3, and SP263 Assays.

PURPOSE: The clinical application of PD-L1 immunohistochemistry (IHC) testing is complicated by the availability of multiple IHC assays, scoring algorithms, and cutoffs. This study assessed the analytical comparability of three commercially available PD-L1 assays and two scoring algorithms used to assess PD-L1 status in gastric cancer (GC) samples. METHODS: Serial sections of 100 resected GC samples, with PD-L1 expression levels across the dynamic range, were stained with three in vitro diagnostic-grade PD-L1 assays (28-8, 22C3, and SP263). Three trained pathologists blindly and independently scored slides using combined positive score (CPS) and tumor area positivity (TAP) algorithms. Comprehensive statistical analyses were performed to evaluate analytical concordance. Digital image analysis (DIA) was used to objectively compare the technical performance of each assay by simulating CPS and TAP. RESULTS: Comparable staining patterns were observed with these three PD-L1 assays. Despite discernible variation in staining intensity, reproducible evaluations of PD-L1 positivity were observed. Inter- and intra-assay assessments of all three assays, using either CPS or TAP and the same PD-L1 cutoffs, demonstrated moderate to almost-perfect (interassay Cohen's kappa [κ] range, 0.47-0.83) and substantial to almost-perfect (intra-assay κ range, 0.77-1.00) agreement. Interpathologist assessment exhibited a significant level of concordance (intraclass correlation coefficient ≥0.92). No difference in technical performance was observed using DIA. CONCLUSION: This study highlights analytical concordance in PD-L1 testing between three major PD-L1 assays when TAP and CPS are applied. Comparability of the technical assay performance was further supported by independent DIA. These observations support cross-application flexibility of the different PD-L1 assays and scoring algorithms to characterize PD-L1 expression in GC.

A prospective longitudinal study shows putamen volume is associated with moderate amphetamine use and resultant cognitive impairments.

Background: Amphetamine-type stimulants (ATS) have become a critical public health issue. Animal models have indicated a clear neurotoxic potential of ATSs. In humans, chronic use has been associated with cognitive deficits and structural brain abnormalities. However, cross-sectional retrospective designs in chronic users cannot truly determine the causal direction of the effects. Objective: To prospectively determine effects of occasional ATS use on cognitive functioning and brain structure. Methods: In a prospective longitudinal study design, cognitive functioning and brain structure were assessed at baseline and at 12-month follow-up in occasional ATS users (cumulative lifetime use <10 units at baseline). Results: Examination of change scores between the initial examination and follow-up revealed declined verbal memory performance and putamen volume in users with high relative to low interim ATS exposure. In the entire sample, interim ATS use, memory decline, and putamen volume reductions were strongly associated. Conclusions: The present findings support the hypothesis that ATS use is associated with deficient dorsal striatal morphology that might reflect alterations in dopaminergic pathways. More importantly, these findings strongly suggest that even occasional, low-dose ATS use disrupts striatal integrity and cognitive functioning.

Mortalidade por suicídio na 5a mesorregião de perícia Santa Catarina: Análise dos casos / Mortalidad por suicidio en el mesoregion experto de la 5a fronteira de Santa Catarina / Mortality by suicide in the 5th fronteira de Santa Catarina expert mesoregion

Objetivo: analisar o perfil dos óbitos por suicídio necropsiados pelo Instituto Geral de Perícias/Chapecó, entre janeiro 2007 e dezembro 2016. Método: estudo exploratório descritivo retrospectivo, obteve aprovação ética do Comitê de Ética em Pesquisa com Seres Humanos (CEP/UFFS) sob parecer no 1.826.221. Dados obtidos nos registros de necropsia e declarações de óbito de mortes por suicídio, organizados em planilhas eletrônicas, analisados pelo teste qui quadrado, e discutidos com base na literatura. Resultados: analisados 335 óbitos. À análise estatística univariada, significância para sexo, faixa etária, escolaridade e situação conjugal. Análise de tendência temporal apontou incremento nas taxas entre 30-39 anos e acima de 60 anos. Conclusão: o fortalecimento de políticas públicas voltadas à saúde mental é necessário.(AU)

Objective: to analyze the profile of deaths by suicide autopsied by the Instituto Geral de Perícias/Chapecó, between January 2007 and December 2016. Method: a retrospective descriptive exploratory study, which obtained ethical approval from the Ethics Committee for Research with Human Beings (CEP/UFFS) under opinion No. 1,826,221. Data obtained from autopsy records and death certificates of deaths by suicide, organized in electronic spreadsheets, analyzed by the chi-square test, and discussed based on the literature. Results: analyzed 335 deaths. Univariate statistical analysis revealed significance for sex, age group, education and marital status. Time trend analysis showed an increase in rates between 30-39 years and over 60 years. Conclusion: the strengthening of public policies aimed at mental health is necessary.(AU)

Objetivo: analizar el perfil de las muertes por suicidio autopsiadas por el Instituto Geral de Perícias/Chapecó, entre enero de 2007 y diciembre de 2016. Método: estudio exploratorio descriptivo retrospectivo, obtuvo aprobación ética del Comité de Ética en Investigación con Seres Humanos (CEP/ UFFS) bajo dictamen N° 1.826.221. Datos obtenidos de autopsias y certificados de defunción de muertes por suicidio, organizados en hojas de cálculo electrónicas, analizados por la prueba de chi-cuadrado y discutidos con base en la literatura. Resultados: se analizaron 335 defunciones. El análisis estadístico univariado reveló significancia para sexo, grupo de edad, educación y estado civil. El análisis de tendencia temporal mostró un aumento en las tasas entre 30-39 años y mayores de 60 años. Conclusión: es necesario el fortalecimiento de las políticas públicas dirigidas a la salud mental.(AU)

Presumed cytomegalovirus retinitis late after kidney transplant / Retinite presumida por citomegalovírus tardiamente após um transplante renal

Abstract Cytomegalovirus (CMV) retinitis is a rare manifestation of CMV invasive disease and potentially threatening to vision in immunocompromised individuals. Clinical suspicion is fundamental since it is an unusual entity with a progressive and often asymptomatic installation over a long period. The authors report a 70-year-old man with diabetic nephropathy who underwent a kidney transplant (KT) in August 2014 with good clinical evolution. No previous CMV infection or episodes of acute rejection were reported. Five years after transplant, he was admitted due to a reduced visual acuity of the left eye with seven days of evolution with associated hyperemia, without exudate. The ophthalmologic evaluation was compatible with acute necrosis of the retina and presumed associated with CMV infection. He had a progressive improvement after ganciclovir initiation. CMV retinitis is one of the most serious ocular complications in immune-suppressed individuals and can lead to irreversible blindness, and because of that, early diagnosis and treatment remains crucial in obtaining the best visual prognosis in affected patients. Secondary prophylaxis with ganciclovir is not consensual, neither is the safety of reintroducing the antimetabolite in these cases.

Resumo A retinite por citomegalovírus (CMV) é uma manifestação rara de doença invasiva por CMV e potencialmente ameaçadora para a visão em indivíduos imunocomprometidos. A suspeita clínica é fundamental, uma vez que se trata de uma entidade incomum, com uma instalação progressiva e frequentemente assintomática durante um longo período. Os autores relatam um homem de 70 anos de idade com doença renal do diabetes que foi submetido a um transplante renal (KT) em Agosto de 2014 com boa evolução clínica. Nenhuma infecção anterior por CMV ou episódios de rejeição aguda foram relatados. Cinco anos após o transplante, ele foi internado devido a uma acuidade visual reduzida do olho esquerdo com sete dias de evolução com hiperemia associada, sem exsudato. A avaliação oftalmológica foi compatível com a necrose aguda da retina e presumivelmente associada à infecção por CMV. Ele teve uma melhora progressiva após o início do ganciclovir. A retinite por CMV é uma das complicações oculares mais graves em indivíduos imunossuprimidos e pode levar à cegueira irreversível e, por isso, o diagnóstico e o tratamento precoces continuam sendo cruciais para obter o melhor prognóstico visual em pacientes afetados. A profilaxia secundária com ganciclovir não é consensual, tampouco a segurança de reintroduzir o antimetabólito nestes casos.

Reabilitação de mandíbula severamente reabsorvida com implantes curtos e prótese fixa total parafusada / Rehabilitation of severely resorbed mandible with short dental implants and a total fixed, screw-retained prosthesis

Pacientes com atrofia óssea avançada dos maxilares ainda consistem em um desafio para a reabilitação oral. A literatura sugere várias opções de tratamento e cabe ao profissional escolher qual é a mais indicada conforme as condições psicossomáticas e financeiras do paciente. Este artigo relata e discute, embasado na literatura pertinente, o caso de uma paciente portadora das características ósseas acima, onde o tratamento escolhido foi a confecção de uma prótese total superior convencional e uma prótese fixa inferior suportada por implantes curtos com minipilares angulados devido à perda óssea vertical severa e ao prognatismo mandibular.

Patients with advanced bone jaw atrophy still consist of a challenge for oral rehabilitation. The literature suggests several treatment options, and clinicians must choose which is the most appropriate according to financial and psychological conditions. This article reports and discusses, based on relevant literature, the case of a patient with those characteristics, where the treatment of choice was the construction of a conventional denture and a lower fixed screw-retained, implant-supported prosthesis with short implants and mini-abutments due to the severe vertical bone loss and mandibular prognathism