Breast cancer outcomes in women with ovarian cancer and a pathogenic germline BRCA mutation.

Background: Women with ovarian cancer (OC) and a pathogenic variant in the BRCA1 or BRCA2 genes are at increased risk of developing breast cancer (BC). Evidence for long term outcomes in these patients who undergo bilateral risk reduction mastectomy (RRM) after ovarian cancer is sparse. The aim of this study was to analyse the long-term breast cancer-related outcomes of patients who have been diagnosed with ovarian cancer and found to have BRCA1 or 2 pathogenic variants.

Neural mechanisms of reward processing in preadolescent irritability: Insights from the ABCD study.

Elevated youth irritability is characterized by increased proneness to frustration relative to peers when rewards are blocked, and is a transdiagnostic symptom that predicts multiple forms of psychopathology and poorer socioeconomic outcomes in adulthood. Although mechanistic models propose that irritability is the result of aberrant reward-related brain function, youth irritability as it relates to multiple components of reward processes, including reward anticipation, gain, and loss, has yet to be examined in large, population-based samples. Data from the Adolescent Brain and Cognitive Development (ABCD) baseline sample (N = 5923) was used to examine associations between youth irritability (measured by parent-report) and reward-related brain activation and connectivity in a large, preadolescent sample.

Identification of a Novel Antiviral Lectin against SARS-CoV-2 Omicron Variant from Shiitake-Mushroom-Derived Vesicle-like Nanoparticles.

Lectins are a class of carbohydrate-binding proteins that may have antiviral activity by binding to the glycans on the virion surface to interfere with viral entry. We have identified a novel lectin (named Shictin) from Shiitake mushroom ()-derived vesicle-like nanoparticles (VLNs, or exosomes) that exhibits strong activity against the SARS-CoV-2 Omicron variant with an IC value of 87 nM. Shictin contains 298 amino acids and consists of two unique domains (N-terminal and C-terminal domain).

Neural mechanisms of inhibitory control in preadolescent irritability: Insights from the ABCD study.

Objective: Elevated pediatric irritability is a transdiagnostic symptom that predicts multiple mental health problems in adolescence and adulthood. Altered top-down regulatory networks, such as inhibitory control networks that suppress an impulse in favor of goal-directed behavior, are thought to contribute to high levels of youth irritability. Nevertheless, little work has examined links between youth irritability and neural processes supporting inhibitory control in large diverse samples, nor have they focused on the key period ramping up to adolescence (i.

Reactions and Biological Activities of Hydrazonoyl Halides.

This review covers the literature information on the chemistry of hydrazonoyl halides with different substrates to give heterocyclic compounds. From the foregoing survey, it seems this provides a useful and convenient strategy for the synthesis of numerous heterocyclic derivatives. The subject of such reactions is still ongoing and undoubtedly will provide new fused functionalized compounds of both industrial and biological interest.

Making it "EASI" for pediatricians to determine when toddler tantrums are "more than the terrible twos": Proof-of-concept for primary care screening with the Multidimensional Assessment Profiles-Early Assessment Screener for Irritability (MAPS-EASI).

Background: Up to 20% of youth have impairing mental health problems as early as age 3. Early identification and intervention of mental health risks in pediatric primary care could mitigate this crisis via prevention prior to disease onset. The purpose of this study was to establish the feasibility and acceptability of implementing a brief transdiagnostic screening instrument in pediatric primary care for irritability and corollary impairment.

What I see, what you say: How cross-method variation sharpens characterization of irritability in early childhood.

Objectives: Identification of clinically significant irritability in preschool age is important to implement effective interventions. However, varying informant and measurement methods display distinct patterns. These patterns are associated with concurrent and future mental health concerns.

Sex-specific threat responding and neuronal engagement in carbon dioxide associated fear and extinction: Noradrenergic involvement in female mice.

Difficulty in appropriately responding to threats is a key feature of psychiatric disorders, especially fear-related conditions such as panic disorder (PD) and posttraumatic stress disorder (PTSD). Most prior work on threat and fear regulation involves exposure to external threatful cues. However, fear can also be triggered by aversive, within-the-body, sensations.

RBD-Protein/Peptide Vaccine UB-612 Elicits Mucosal and Fc-Mediated Antibody Responses against SARS-CoV-2 in Cynomolgus Macaques.

Antibodies provide critical protective immunity against COVID-19, and the Fc-mediated effector functions and mucosal antibodies also contribute to the protection. To expand the characterization of humoral immunity stimulated by subunit protein-peptide COVID-19 vaccine UB-612, preclinical studies in non-human primates were undertaken to investigate mucosal secretion and the effector functionality of vaccine-induced antibodies in antibody-dependent monocyte phagocytosis (ADMP) and antibody-dependent NK cell activation (ADNKA) assays. In cynomolgus macaques, UB-612 induced potent serum-neutralizing, RBD-specific IgG binding, ACE2 binding-inhibition antibodies, and antibodies with Fc-mediated effector functions in ADMP and ADNKA assays.

VXX-401, a novel anti-PCSK9 vaccine, reduces LDL-C in cynomolgus monkeys.

Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of disease burden in the world and is highly correlated with chronic elevations of LDL-C. LDL-C-lowering drugs, such as statins or monoclonal antibodies against proprotein convertase subtilisin/kexin type 9 (PCSK9), are known to reduce the risk of cardiovascular diseases; however, statins are associated with limited efficacy and poor adherence to treatment, whereas PCSK9 inhibitors are only prescribed to a "high-risk" patient population or those who have failed other therapies. Based on the proven efficacy and safety profile of existing monoclonal antibodies, we have developed a peptide-based vaccine against PCSK9, VXX-401, as an alternative option to treat hypercholesterolemia and prevent ASCVD.

Lactic acid bacterial surface display of scytovirin inhibitors for anti-ebolavirus infection.

Scytovirin (SVN) is a lectin from cyanobacteria which has a strong inhibitory activity against Ebola virus infection. We engineered scytovirin as the inhibitor for surface display of lactic acid bacteria to block Ebola virus infection. Two different bacterial strains ( and ) were successfully engineered for scytovirin expression on the bacterial surface.

Toward an optimized assessment of adolescent psychopathology risk: Multilevel environmental profiles and child irritability as predictors.

Background: Adolescence is a developmental period during which youth experience vulnerability to psychopathology. To build the foundation for a parsimonious psychopathology risk calculator while capturing the complexity and dynamic nature of the environment, the current study aimed to identify distinct risk and resilience profiles with a wide range of environmental factors guided by Bronfenbrenner's biopsychosocial ecological system theory. The association between the early-mid childhood risk profiles and psychopathology in adolescence were examined.

Co-design of patient information leaflets for germline predisposition to cancer: recommendations for clinical practice from the UK Cancer Genetics Group (UKCGG), Cancer Research UK (CRUK) funded CanGene-CanVar Programme and the Association of Genetic Nurse Counsellors (AGNC).

Background: Testing for germline pathogenic variants (GPVs) in cancer predisposition genes is increasingly offered as part of routine care for patients with cancer. This is often urgent in oncology clinics due to potential implications on treatment and surgical decisions. This also allows identification of family members who should be offered predictive genetic testing.

Characterizing the spectrum of irritability in preadolescence: Dimensional and pragmatic applications.

Objectives: Characterize the dimensional spectrum of preadolescent (PA) irritability, a robust transdiagnostic vulnerability marker, using the youth version of the Multidimensional Assessment Profiles Temper Loss (MAPS-TL-Youth) scale including common and with developmentally specific items. Based on this, derive and validate a clinically optimized irritability screener to flag psychopathology risk in preadolescents.

Methods: The normal:abnormal irritability spectrum was modeled using MAPS-TL-Youth data from the Multidimensional Assessment of Preschoolers Study (MAPS) Study PA wave (n = 340) via item response theory.

Prevalence, stability, and predictive utility of the Multidimensional Assessment of Preschoolers Scales clinically optimized irritability score: Pragmatic early assessment of mental disorder risk.

Objectives: Characterizing the scope and import of early childhood irritability is essential for real-world actualization of this reliable indicator of transdiagnostic mental health risk. Thus, we utilize pragmatic assessment to establish prevalence, stability, and predictive utility of clinically significant early childhood irritability.

Methods: Data included two independent, diverse community samples of preschool age children (N = 1857; N = 1490), with a subset enriched for risk (N = 425) assessed longitudinally from early childhood through preadolescence (∼4-9 years old).

Advancing earlier transdiagnostic identification of mental health risk: A pragmatic approach at the transition to toddlerhood.

Objectives: In light of the youth mental health crisis, as 1 in 5 children have a mental disorder diagnosis by age 3, identification of transdiagnostic behavioral vulnerability prior to impairing psychopathology must occur at an earlier phase of the clinical sequence. Here, we lay the groundwork for a pragmatic irritability measure to identify at-risk infant-toddlers.

Methods: Data comprised N = 350 diverse infant-toddlers and their mothers assessed at ∼14 months old for irritability (Multidimensional Assessment Profiles- Temper Loss-Infant/Toddler (MAPS-TL-IT) and impairment (Early Childhood Irritability-Related Impairment Interview, E-CRI; and Family Life Impairment Scale (FLIS).

Developmentally specified characterization of the irritability spectrum at early school age: Implications for pragmatic mental health screening.

Objectives: Developmentally specified measures that identify clinically salient irritability are needed for early school-age youth to meaningfully capture this transdiagnostic risk factor for psychopathology. Thus, the current study modeled the normal:abnormal irritability spectrum and generated a clinically optimized screening tool for this population.

Methods: The irritability spectrum was modeled via the youth version of the Multidimensional Assessment Profile Scales-Temper Loss Scale (MAPS-TL-Youth) in children (n = 474; 6.

A pragmatic, clinically optimized approach to characterizing adolescent irritability: Validation of parent- and adolescent reports on the Multidimensional Assessment Profile Scales-Temper Loss Scale.

Objectives: Heightened irritability in adolescence is an impairing symptom that can lead to negative outcomes in adulthood, but effective screening tools are lacking. This study aimed to derive clinically-optimized cutoff scores using the Multidimensional Assessment Profile Scales-Temper Loss (MAPS-TL) to pragmatically identify adolescents with impairing irritability.

Methods: A diverse sample of 79 adolescents and their parents completed the MAPS-TL-Youth version.

MAPping affective dimensions of behavior: Methodologic and pragmatic advancement of the Multidimensional Assessment Profiles scales.

Rigorous validation of the full developmentally sensitive normal:abnormal spectrum, including evaluating the incremental value of age-specific behaviors, is necessary for nuanced characterization of dimensional features of psychopathology. To maximize the clinical utility of transdiagnostic approaches to risk identification, derivation of psychometrically sound, pragmatic versions with empirically derived cutoffs is also key. This special section has a central focus on rigorous, developmentally-based measurement of irritability as an exemplar of this theory- and pragmatically-based approach.

Aberrant p16, p53 and Ki-67 immunohistochemistry staining patterns can distinguish solitary keratoacanthoma from cutaneous squamous cell carcinoma.

Keratoacanthoma (KA) is widely considered a benign, usually self-resolving, neoplasm distinct from cutaneous squamous cell carcinoma (cSCC), while some consider KA to be indistinguishable from cSCC. Published studies indicate utility for p16, p53, Ki-67 immunostaining and elastic van Gieson (EVG) in the assessment of KA and cSCC. We compared clinical features and staining patterns for p16, p53, Ki-67 and EVG in fully excised KA, cSCC with KA-like features (cSCC-KAL) and other cSCC (cSCC-OTHER).

The State of Diversity, Equity, Inclusion, and Justice in Pediatric Fellowship Programs.

Diversity, equity, inclusion, and justice (DEIJ) lie at the center of excellent patient care and safety. The way we interact with our pediatric patients and families and develop and discuss treatment plans should all be done under the lens of DEIJ. The foundation of DEIJ begins in medical school and is further honed during general pediatric residency training by ensuring residents are exposed to diverse patient populations.