Explore the vast range of titles available.

New molecular technologies have helped unveil previously unexplored facets of the genome beyond the canonical proteome, including microproteins and short ORFs, products of alternative splicing, regulatory non-coding RNAs, as well as transposable elements, cis -regulatory DNA, and other highly repetitive regions of DNA. In this Review, we highlight what is known about this ‘hidden genome’ within the fungal kingdom. Using well-established model systems as a contextual framework, we describe key elements of this hidden genome in diverse fungal species, and explore how these factors perform critical functions in regulating fungal metabolism, stress tolerance, and pathogenesis. Finally, we discuss new technologies that may be adapted to further characterize the hidden genome in fungi. New molecular technologies have helped unveil facets of the genome beyond the canonical proteome, such as microproteins and short ORFs, products of alternative splicing, regulatory non-coding RNAs, transposable elements, and cis-regulatory DNA. In this Review, Gervais & Shapiro highlight what is known about this ‘hidden genome’ in fungi.

Pediatric acute myeloid leukemia (AML) is a rare disease whose prognosis is highly variable according to factors such as chromosomal abnormalities. Recurrent genomic rearrangements are detected in half of pediatric AML by karyotype. NUcleoPorin 98 ( NUP98 ) gene is rearranged with 31 different fusion partner genes. These rearrangements are frequently undetected by conventional cytogenetics, as the NUP98 gene is located at the end of the chromosome 11 short arm (11p15). By screening a series of 574 pediatric AML, we detected a NUP98 rearrangement in 22 cases (3.8%), a frequency similar to CBFB-MYH11 fusion gene (4.0%). The most frequent NUP98 fusion gene partner is NSD1 . These cases are homogeneous regarding their biological and clinical characteristics, and associated with bad prognosis only improved by bone marrow transplantation. We detailed the biological characteristics of these AML by exome sequencing which demonstrated few recurrent mutations ( FLT3 ITD, WT1 , CEBPA , NBPF14 , BCR and ODF1 ). The analysis of the clonal structure in these cases suggests that the mutation order in the NUP98 -rearranged pediatric AML begins with the NUP98 rearrangement leading to epigenetic dysregulations then followed by mutations of critical hematopoietic transcription factors and finally, activation of the FLT3 signaling pathway.

Depuis plus de 40 ans, les chercheurs portent une attention particulière au rôle des pères au sein des familles, en particulier sous l’angle de l’engagement paternel. Il est reconnu que l’engagement des pères contribue au développement cognitif et langagier de l’enfant, de même qu’à son développement social et affectif. L’engagement paternel contribue aussi au bien-être des deux parents en diminuant le stress ressenti par les mères et les affects dépressifs chez les pères. Cet engagement génère de saines trajectoires de développement pour les enfants, les pères, leur partenaire et leur famille. Force est de constater toutefois qu’en dépit de la pertinence scientifique et sociale de la promotion de l’engagement paternel, les pères déplorent le peu d’espace accordé à leurs préoccupations, à leur vécu et à leurs ressources lors de leurs interactions avec le personnel soignant en périnatalité. Le programme novateur « Initiative Amis des pères au sein des familles » (IAP) fut développé et implanté dans trois régions du Québec (Canada), afin d’accompagner les intervenants de la santé, des services sociaux et communautaires, ainsi que leurs gestionnaires dans le développement ou la consolidation de pratiques, de services et d’environnements Amis des pères. Cet article décrira le contexte théorique et social appuyant le développement de ce programme. Le programme IAP sera présenté en s’attardant sur les activités réalisées et à leur portée et en portant une attention particulière aux ateliers implantés auprès des médecins obstétriciens et gynécologues. Quelques constats émanant des effets de ce programme sur la place des pères en périnatalité concluront ce texte. For more than forty years, researchers have paid special attention to the role of fathers within families, particularly in terms of father involvement. It is recognized that father’s engagement helps in children’s cognitive and language development, as well as their social and emotional development. Paternal engagement also contributes to the well-being of both parents by reducing stress among mothers and depressive effects among fathers. This engagement leads to healthy developmental trajectories for children, fathers, their partners, and their families. It is clear, however, that despite the scientific and social relevance of promoting paternal engagement, fathers still lament the little space given to their concerns, experience, and resources in their interactions with perinatal caregivers. The innovative and original program, Father-Friendly Initiative within Families (FFIF) was developed and implemented in three regions of Quebec (Canada) in order to support stakeholders from the health, community and social services, as well as their managers, in the development and consolidation of Father-Friendly practices, services, and environments. This article presents a brief description of the theoretical and social context supporting the development of this program. The FFIF program is described, with special attention to workshops held with doctors, obstetricians, and gynecologists. The text concludes with some observations emerging from the effects of this program on the role of fathers in the perinatal period.

Background: We report a case of distal right radial cutaneous sensory neuropathy secondary to participation in Pickle Ball. Methods: Case Report & Review of the LiteratureResults: Our 67yoF patient developed acute onset persistent numbness and dysesthesia in the distal right radial sensory distribution while participating in Pickle Ball, a sport undergoing rapid growth of popularity over the past decade. Nerve conduction studies (NCS) were performed in our lab following symptom onset, and the patient had previous NCS that allowed for comparison. NCS in our lab demonstrated asymmetrically reduced amplitude of right distal radial sensory responses (14.5 uV), in comparison to normal (42 uV) radial sensory responses from her previous NCS using the same protocol. All remaining NCS were normal in both studies. Conclusions: This study represents the first reported case within the literature of a Pickle Ball induced distal radial cutaneous sensory neuropathy demonstrated objectively using comparative nerve conduction studies. It is important that clinicians be aware of this entity and the possibility that it can manifest in the context of activities involving repetitive extension of the wrist. We present this case along with a review of the current literature of focal neuropathies involving the upper & lower extremities.

Androgen deprivation therapy (ADT) in prostate cancer (PCa) is associated with an increased risk of bone fragility including bone loss, osteoporosis and fractures. Although international recommendations suggest performing dual-energy x-ray absorptiometry (DXA) at the initiation of treatment, less than 10% of patients do it. The implementation of a standardised clinical care pathway could help prevent bone-related complications in patients starting ADT. To improve screening for bone fragility in patients starting ADT for PCa by setting up a clinical care pathway. To describe the characteristic of patients with PCa starting ADT. The radiation oncologists, medical oncologists or urologists from a tertiary center systematically referred all patients starting any ADT for PCa to our rheumatology department for a bone-health assessment including a DXA and clinics with a bone specialist. The effectiveness of the pathway was assessed by the number of patients who performed DXA at the initiation of ADT. Between March and December 2022, 116 of the 119 patients (97%) referred to our department were able to have a bone assessment within an average of 36 +/- 15 days. The three patients not seen in the care pathway did not wish to come for a new medical appointment. Among the 116 patients, mean age at first visit was 75+/-7 years old, mean BMI 26.9 +/- 4.7 kg/m2, 56% were previous or current smoker and Charlson Comorbidity Index was 4.75 +/- 2.5 with 20% diabetes, 15% peripheral vascular disease, 11% coronaropathy and 10% chronic kidney disease. Regarding PCa, 65% were on a localized or locally-advanced stage while 35% were metastatic and overall, 44% presented with a high risk histo-pronostic score (ISUP 4 or 5). Sixty-four patients (55%) were scheduled to concomitant prostatic external beam radiation, as initial or salvage therapy. Median PSA at diagnosis was 16 ng/ml (8.8-38.5) At inclusion, 70% of patients were newly-diagnosed PCa while 30% were recurrent PCa. ADT was prescribed alone for 65% of patients or in combination with new hormone-therapy (NHT) for 35% of patients and 26% with concomitant corticosteroids with a mean dose of 10 +/-4 mg. The mean duration of previous ADT for relapsing patients was 16 +/- 20 months. Regarding bone disease, 11% patients had previous bone fracture mainly in the spine, 15% had familial history of hip fracture and 20% reported a fall within the past year. Forty-two percent of patients had vitamin D supplementation but only one was previously treated with an anti-osteoporotic agent. Finally, 114 patients had a DXA. A lumbar BMD T-score ≤-2.5 was found for 9 patients, ≤ -2 for 17 patients. A hip BMD T-score ≤ -2.5 was found for 12 patients and ≤ -2 for 35 patients. A T-score ≤ -2.5 to at least one site was found in 18 patients (16%) and ≤ -2 for 41 patients (35%). After BMD assessment, an anti-osteoporotic treatment was prescribed in 40% of patients with bisphosphonate (71%) or denosumab (29%). This clinical care pathway allowed 97% of patients to have a bone assessment when starting ADT for PCa. This cohort of 116 patients confirms the high prevalence of low BMD among these patients and the need to screen and treat patients to prevent bone-related complications. I thanks Mioranirainy DERAHARIJAONA and Catherine LE BOURLOUT for their help in collecting clinical data. None Declared.

For the fungal pathogen Candida albicans, genetic overexpression readily occurs via a diversity of genomic alterations, such as aneuploidy and gain-of-function mutations, with important consequences for host adaptation, virulence, and evolution of antifungal drug resistance. Given the important role of overexpression on C. albicans biology, it is critical to develop and harness tools that enable the analysis of genes expressed at high levels in the fungal cell. Here, we describe the development, optimization, and application of a novel, single-plasmid-based CRISPR activation (CRISPRa) platform for targeted genetic overexpression in C. albicans, which employs a guide RNA to target an activator complex to the promoter region of a gene of interest, thus driving transcriptional expression of that gene. Using this system, we demonstrate the ability of CRISPRa to drive high levels of gene expression in C. albicans, and we assess optimal guide RNA targeting for robust and constitutive overexpression. We further demonstrate the specificity of the system via RNA sequencing. We highlight the application of CRISPR activation to overexpress genes involved in pathogenesis and drug susceptibility, and contribute toward the identification of novel phenotypes. Consequently, this tool will facilitate a broad range of applications for the study of C. albicans genetic overexpression.

Temperature can impact embryonic development in nearly all vertebrates. [...]hatching, the eggs can be restricted to their local thermal environment. Temperature can affect development rates, and skeletal abnormalities and abnormal colouration and patterns (e.g., snakes; Vinegar 1974) can result from elevated temperatures. See PDF.] Normal pattern development of a neonate epaulette shark (i.e., defined epaulette spot) reared in ovo (28 °C) at 14 days post-hatch (a) and 120 days post-hatch (c) in contrast to patterns of a neonate reared in ovo at 32 °C at 14 days post-hatch (b) and then transitioned to 28 °C (at 30 days post-hatch) until 120 days post-hatch (d) Although it is known that some adult elasmobranchs change skin tone in response to environmental conditions (Visconti et al. 1999), the impact of prolonged exposure to elevated temperatures on elasmobranch development has not been investigated.

Introduction/Background*Because of inter-tumor heterogeneity of endometrial carcinoma (EC), prognostication remains challenging. We aimed to develop a RNAseq signature to stratify EC patient prognosis beyond molecular subtyping.MethodologyA prognostic signature was identified using a LASSO-penalized Cox regression model on TCGA (N=543 patients). A polyA-RNAseq-based method was developed for validation of the signature in a cohort of stage I-IV EC patients treated in two Paris Hospitals between 2010 and 2017. Model performances were evaluated using time-dependent ROC curves (prediction of disease-specific-survival (DSS)). The additional value of the RNAseq signature was evaluated using uni/multivariable Cox models (hazard ratio (HR) with [95% confidence interval]) and Kaplan-Meier analysis.Result(s)*Among 209 patients included in the validation cohort (median follow-up 55 months IQR [41-69]), 61 (30%), 10 (5%), 52 (25%), and 82 (40%), had mismatch repair-deficient, POLE-mutated, TP53-mutated tumors, and tumors with no specific molecular profile, respectively. The 38-genes signature accurately predicted DSS (AUC=80%). Using a composite classifier accounting for the RNAseq signature and the TP53-mutated group, three groups were identified: good prognosis tumors based on RNAseq signature and without TP53 mutation, characterized by excellent outcome (N=103 patients, 5-years DSS rates of 99%) (reference), poor prognosis tumors based on RNAseq signature and without TP53 mutation (N=49 patients, 5-years DSS rates of 81%; HR: 5.86 [1.16; 29.7]), and TP53-mutated tumors whatever the RNAseq signature (N=52 patients, 5-years DSS rates of 52%; HR: 11.14 [2.40; 51.7]) (HR adjusted on FIGO stage). In 81 (38%) patients with adverse features (2020 ESGO/ESTRO/ESP guidelines: non-endometrioid histology or stage III-IVA or TP53-mutated tumors), TP53-mutated molecular group was not significantly associated with poor prognosis (p=0.18). A The composite classifier identified three classes within this subgroup: RNAseq-good prognosis (N=24), non-TP53/RNAseq-poor prognosis (N=16), and TP53-mutated tumors (N=41), with 5-years DSS rates of 100%, 59%, and 71%, respectively (p=0.015). Transcriptome analyses suggested the underlying involvement of immune deprivation and wound healing processes in tumors with poor prognosis.Conclusion*We demonstrate that RNAseq characterization can refine prognostication in EC beyond molecular subgroups and main prognostic features, and warrants validation for potential RNAseq-based adjuvant therapeutic strategies in EC.

SPI-077 and SPI-077 B103 are formulations of cisplatin encapsulated in pegylated STEALTH liposomes that accumulate in tumors. However, the extent to which active platinum (Pt) is released from the liposome is unknown. Thus, we evaluated the disposition of encapsulated and released Pt in plasma and tumors after administration of STEALTH liposomal and nonliposomal cisplatin. Cisplatin (10 mg/kg), SPI-077 (10 mg/kg), and SPI-077 B103 (5 mg/kg) were administered i.v. to mice bearing B16 murine melanoma tumors. Microdialysis probes were placed into the right and left sides of each tumor, and serial samples were collected from tumor extracellular fluid (ECF) after administration of each agent. After each microdialysis procedure, tumor samples were obtained at each probe site to measure total Pt and Pt-DNA adducts. In a separate study, serial plasma samples (three mice per time point) were obtained. Unbound Pt in tumor ECF and plasma, and total Pt in tumor homogenates were measured by flameless atomic absorption spectrophotometry. Area under the tumor ECF (AUC(ECF)) concentration versus time curves of unbound Pt were calculated. Intrastrand GG (Pt-GG) and AG (Pt-AG) Pt-DNA adducts were measured via (32)P-postlabeling. Mean+/-SD peak concentrations of total Pt in tumor homogenates after administration of cisplatin, SPI-077, and SPI-077 B-103 were 3.2+/-1.9, 11.9+/-3.0, and 3.5+/-0.3 microg/g, respectively. After cisplatin, mean+/-SD AUC(ECF) of unbound Pt was 0.72+/-0.46 microg/ml.h. There was no detectable unbound Pt in tumor ECF after SPI-077 or SPI-077 B-103 treatment. Mean+/-SD peak concentration of Pt-GG DNA adducts after administration of cisplatin, SPI-077, and SPI-077 B-103 were 13.1+/-3.3, 3.5+/-1.3, and 2.1+/-0.3 fmol Pt/microg DNA, respectively. This study suggests that more SPI-077 and SPI-077 B103 distribute into tumors, but release less Pt into tumor ECF, and form fewer Pt-DNA adducts than does cisplatin.