A Strategy for Simultaneous Engineering of Interspecies Cross-Reactivity, Thermostability, and Expression of a Bispecific 5T4 x CD3 DART Molecule for Treatment of Solid Tumors.

Bispecific antibodies represent a promising class of biologics for cancer treatment. However, their dual specificity and complex structure pose challenges in the engineering process, often resulting in molecules with good functional but poor physicochemical properties. To overcome limitations in the properties of an anti-5T4 x anti-CD3 (α5T4 x αCD3) DART molecule, a phage-display method was developed, which succeeded in simultaneously engineering cross-reactivity to the cynomolgus 5T4 ortholog, improving thermostability and the elevating expression level.

Can Contrast-Enhanced Mammography Improve Positive Predictive Value for Diagnostic Workup of Suspicious Findings? A Single-Arm Prospective Study.

Objective: To assess the positive predictive value-3 (PPV3) and negative predictive value (NPV) of contrast-enhanced mammography (CEM) when added to the diagnostic workup of suspicious breast findings.

Methods: This prospective study was IRB approved. We recruited 99 women with abnormal findings on digital breast tomosynthesis (DBT) and/or US to undergo CEM prior to biopsy.

Synthesis, crystal structure and Hirshfeld surface analysis of sulfamethoxazolium methyl-sulfate monohydrate.

The mol-ecular salt sulfamethoxazolium {or 4-[(5-methyl-1,2-oxazol-3-yl)sulf-amo-yl]anilinium methyl sulfate monohydrate}, CHNOS·CHOS·HO, was prepared by the reaction of sulfamethoxazole and HSO in methanol and crystallized from methanol-ether-water. Protonation takes place at the nitro-gen atom of the primary amino group. In the crystal, N-H⋯O hydrogen bonds (water and methyl-sulfate anion) and inter-molecular N-H⋯N inter-actions involving the sulfonamide and isoxazole nitro-gen atoms, link the components into a tri-dimensional network, additional cohesion being provided by face-to-face π-π inter-actions between the phenyl rings of adjacent mol-ecules.

Navigating the school transition: Within- and between-person associations between adolescents' academic self-efficacy, school relatedness, and intrinsic academic motivation.

Adolescents with higher levels of the basic psychological needs of competence, autonomy, and relatedness report better school functioning compared to their peers with lower levels of these needs. This study extended previous work by examining associations in within-person changes of these psychological needs in the school context, with a special focus on the secondary school transition period. We examined within-person relations between academic self-efficacy, intrinsic academic motivation, and school relatedness.

A rhodium-catalyzed C-H activation/cyclization approach toward the total syntheses of cassiarin C and 8--methylcassiarin A from a common intermediate.

Three short and efficient total syntheses of cassiarin C are reported, from a chromanone common key intermediate. A C-H activation strategy, under rhodium catalysis on its pivaloyl oxime, enabled the installation of the pyridine ring. Dehydrogenation of 8--methylcassiarin C afforded 8--methylcassiarin A.

Evidence and Structural Insights into a Ligand-Mediated Phase Transition in the Solvated Ligand Shell of Quantum Dots.

As synthesized, nanocrystal surfaces are typically covered in coordinating organic ligands, and the degree of packing and order of these ligands are ongoing questions in the field of colloidal nanocrystals, particularly in the solution state. Recently, isothermal titration calorimetry coupled with H NMR has been used to probe ligand exchanges on colloidal quantum dots, revealing the importance of the composition of the ligand shell on exchange thermodynamics. Previous work has shown that the geometry and length of a ligand's aliphatic chain can influence the thermodynamics of exchange.

LP-118 is a novel B-cell lymphoma 2 / extra-large inhibitor that demonstrates efficacy in models of venetoclaxresistant chronic lymphocytic leukemia.

Patients with chronic lymphocytic leukemia (CLL) respond well to initial treatment with the B-cell lymphoma 2 (BCL2) inhibitor venetoclax. Upon relapse, they often retain sensitivity to BCL2 targeting, but durability of response remains a concern. We hypothesize that targeting both BCL2 and B-cell lymphoma-extra large (BCLXL) will be a successful strategy to treat CLL, including for patients who relapse on venetoclax.

Peer victimization in early adolescence and maladjustment in adulthood.

Studies report different effect sizes for associations between peer victimization and later maladjustment. A possible origin of this heterogeneity is the length of the interval between victimization and maladjustment assessments. Effect sizes might also vary as a function of reporter.

Peer Bullying Victimization Trajectories for Sexually and Gender Diverse Youth from Early Childhood to Late Adolescence.

Sexually and gender diverse (SGD) youth experience more peer bullying victimization than heterosexual, cisgender youth during adolescence, yet the emergence and persistence of these disparities remain underexplored. Also, it is unclear which factors are associated with these disparities across development, and how these disparities are linked to late adolescent health discrepancies. This study utilized the sample from the Millennium Cohort Study in Britain (N = 10,080; 51.

Relevant Developments in the Use of Three-Component Reactions for the Total Synthesis of Natural Products. The last 15 Years.

Multicomponent reactions (MCRs) offer a highly useful and valuable strategy that can fulfill an important role in synthesizing complex polysubstituted compounds, by simplifying otherwise long sequences and increasing their efficiency. The total synthesis of selected natural products employing three-component reactions as their common strategic MCR approach, is reviewed on a case-by-case basis with selected targets conquered during the last 15 years. The revision includes detailed descriptions of the selected successful sequences; relevant information on the isolation, and bioactivity of the different natural targets is also briefly provided.

Gender Sexuality Alliances and School Safety: Who Benefits Most, and Do Additive School-Led Practices Strengthen the Link?

While Gender and Sexuality Alliances (GSAs) are associated with higher acceptance of sexual diversity and lower bullying-victimization, it is unclear which individual and school-level attributes strengthen these associations. Nationally representative data (N = 1,567 students; Mage = 15.4, SD = 0.

A Latent Profile Analysis of Social Support, Online Contacts, and Preference for Online Communication Among Same- and Both-Sex Attracted and Other-Sex Attracted Adolescents.

This study aimed to assess differences between other-sex attracted and same- and both-sex attracted adolescents in profiles of peer and family social support, online contacts, and preferences for online communication. Data stem from the 2017 Dutch "Health and Behavior in School-Aged Children" (HBSC) survey ( = 6,823; 4.0% same- and both-sex attracted; age14.

Trends in Bullying Victimization and Social Unsafety for Sexually and Gender Diverse Students.

Research has documented trends in bullying victimization for sexually diverse adolescents in the US, but trends regarding school social unsafety are understudied and there is a dearth of research examining these trends for gender diverse adolescents. This study aimed to identify disparities in bullying victimization and feelings of social unsafety in schools for sexually and gender diverse adolescents. Data stem from the 2014 (N = 15,800; M age = 14.

Recent developments in the total synthesis of natural products using the Ugi multicomponent reactions as the key strategy.

The total syntheses of selected natural products using different versions of the Ugi multicomponent reaction is reviewed on a case-by-case basis. The revision covers the period 2008-2023 and includes detailed descriptions of the synthetic sequences, the use of state-of-the-art chemical reagents and strategies, as well as the advantages and limitations of the transformation and some remedial solutions. Relevant data on the isolation and bioactivity of the different natural targets are also briefly provided.

The Longitudinal Associations Between Parental Autonomy Support, Autonomy and Peer Resistance.

Adolescents' autonomy is considered to be shaped within family and peer contexts. However, the specific dynamics of the within-person associations between parental autonomy support, adolescents' general autonomy, and peer resistance over time remain unclear. To address this, random-intercept cross-lagged panel models were employed in a sample of 290 Dutch youth in early adolescence (M = 11.

Development of a Predictive Multiple Reaction Monitoring (MRM) Model for High-Throughput ADME Analyses Using Learning-to-Rank (LTR) Techniques.

Multiple Reaction Monitoring (MRM) is an important MS/MS technique commonly used in drug discovery and development, allowing for the selective and sensitive quantification of compounds in complex matrices. However, compound optimization can be resource intensive and requires experimental determination of product ions for each compound. In this study, we developed a Learning-to-Rank (LTR) model to predict the product ions directly from compound structures, eliminating the requirement for MRM optimization experiments.

The effectiveness of the Dutch Meaningful Roles program in children: a study protocol for a cluster randomized controlled study.

Background: A positive, prosocial classroom climate is associated with improved social competence and academic achievement, as well as with decreased internalizing problems and antisocial behavior in children. It is expected that motivation to behave prosocially is needed to achieve a prosocial climate in the classroom, and that such motivation can be enhanced through three components of self-determination theory (SDT): competence, relatedness, and autonomy. The goal of this protocol is to describe the design of a study aiming to evaluate the effectiveness of a classroom-based program based on SDT components promoting a prosocial classroom climate.

Step-Economic Total Synthesis of Melosatin A from Eugenol.

An efficient and straightforward route toward the isatin-type natural product melosatin A is reported, employing a trisubstituted aniline as a key intermediate. The latter was synthesized in 4 steps and 60% overall yield from eugenol, through its regioselective nitration, sequentially followed by a Williamson methylation, an olefin cross-metathesis with 4-phenyl-1-butene and the simultaneous reduction of olefin and nitro groups. The final step, a Martinet cyclocondensation of the key aniline with diethyl 2-ketomalonate, provided the natural product with 68% yield.

Sexual Orientation and Gender Identity/Expression in Adolescent Research: Two Decades in Review.

There is a long history of research among adolescents who are minoritized and marginalized for their sexual orientation and gender identity/expression (SOGIE). However, it remains unclear how we can best conceptualize and assess SOGIE in adolescence, resulting in different subpopulations and findings across studies. Addressing this issue, we present a narrative literature review of the conceptualization and assessment of SOGIE, and provide recommendations for conceptualizing and operationalizing these concepts.

Efficient Buchwald-Hartwig and nitrene-mediated five-membered ring closure approaches to the total synthesis of quindoline. Unexpected direct conversion of a nitro group into a phosphazene.

Two total syntheses of quindoline, which take place through the intermediacy of 3-nitroquinoline derivatives, are reported. The general synthetic sequence involves construction of the latter by mechanochemical condensation of benzaldehydes with 2-amino-nitrostyrene, followed either by reduction of the nitro group of the heterocycle and Buchwald-Hartwig cyclization or by a nitrene-mediated cyclization under solventless conditions. Use of PPh to generate the nitrene resulted in the unprecedented formation of a phosphazene in place of quindoline.

Depression Socialization in Early Adolescent Friendships: The Role of Baseline Depressive Symptoms and Autonomous Functioning.

There is mixed evidence for depression socialization, a process by which friends affect each other's level of depressive symptoms. The current study examined whether adolescents' baseline depressive symptoms and three dimensions of autonomous functioning (autonomy, peer resistance, and friend adaptation) make adolescents more or less sensitive to depression socialization, and how these dimensions of autonomous functioning were connected. In this preregistered, two-wave longitudinal study, participants completed questionnaires on depressive symptoms, autonomy, and peer resistance and participated in a task to assess friend adaptation.

Longitudinal associations of parental psychological control and friend support with autonomy during early adolescence.

Although theories suggest transactional associations between adolescents' autonomy and relationships with parents and friends, few studies have examined these within-person effects. This longitudinal study examined the within-person co-development of adolescents' autonomy and relationships with parents and friends. Adolescents (N = 244 M  = 11.