Beyond-local neural information processing in neuronal networks.

While there is much knowledge about local neuronal circuitry, considerably less is known about how neuronal input is integrated and combined across neuronal networks to encode higher order brain functions. One challenge lies in the large number of complex neural interactions. Neural networks use oscillating activity for information exchange between distributed nodes.

Antibody selection and automated quantification of TRPV1 immunofluorescence on human skin.

Assessing localization of the transient receptor potential vanilloid-1 (TRPV1) in skin nerve fibers is crucial for understanding its role in peripheral neuropathy and pain. However, information on the specificity and sensitivity of TRPV1 antibodies used for immunofluorescence (IF) on human skin is currently lacking. To find a reliable TRPV1 antibody and IF protocol, we explored antibody candidates from different manufacturers, used rat DRG sections and human skin samples for screening and human TRPV1-expressing HEK293 cells for further validation.

Medicine Access Programmes: what do patients think - a patient-reported outcome study on ribociclib in metastatic breast cancer in Australia.

This study evaluated patient-reported outcomes (PROs) of Medicine Access Programmes (MAPs) for Australian metastatic breast cancer patients on ribociclib. Limited patient awareness of MAP enrolment was identified, emphasising the need for improved education and consent processes. Most patients expressed gratitude for accessing non-funded medications and perceived enhanced medication adherence as a key benefit.

Re-analysis of CLAP data affirms PRC2 as an RNA binding protein.

Using halo-tagged PRC2 and "CLAP" methodology, Guo et al. recently came to the conclusion that PRC2 is not an RNA binding protein (RBP). They suggested that previous findings are CLIP artifacts and argue that RNA cannot play a direct role in PRC2 regulation.

Stage-Specific Guideline Concordant Treatment Impacts on Survival in Nonsmall Cell Lung Cancer: A Novel Quality Indicator.

Background: Lung cancer in Australia contributes 9% of all new cancer diagnoses and is the leading cause of cancer death and burden. Clinical practice guidelines provide evidence-based treatment recommendations for best practice management. We aimed to determine the extent of delivery of guideline-concordant treatment (GCT) and to identify modifiable variables influencing receipt of GCT and survival.

Trends in Adolescent Health: Successes and Challenges From 2010 to the Present.

Purpose: This review considers trends in some of the major adolescent health outcomes and contextual influences since 2010, and explores the relevance of recent cultural, societal, and public health developments on adolescent well-being.

Methods: Based on a review of major reports published since 2010, we identified key topics of impact on adolescent health and development across several domains (education, economic opportunity, sexual and reproductive health, nutrition, and mental health) and ecological levels (from individual- to macro-level influences). Within these areas, we synthesized findings to describe recent trends, noting variation across countries/regions, gender/sex, and other social stratifications when possible.

Risk and Protective Factors for the Sexual and Reproductive Health of Young Adolescents: Lessons Learnt in the Past Decade and Research Priorities Moving Forward.

Purpose: To review the published literature on what has been reported on risk and protective factors for early adolescent sexual and reproductive health (SRH) in the recent decade.

Methods: A scoping review of English language, peer-reviewed literature on risk and protective factors for early adolescent (aged 10-14 years) SRH published between January 2010 and January 2023 using Medline, Web of Science, PsycInfo, CINAHL, and Google Scholar. Articles reporting only on nonmodifiable demographic factors, or on the effect of interventions, were beyond the scope of this review.

Ultraviolet astronomical spectrograph calibration with laser frequency combs from nanophotonic lithium niobate waveguides.

Astronomical precision spectroscopy underpins searches for life beyond Earth, direct observation of the expanding Universe and constraining the potential variability of physical constants on cosmological scales. Laser frequency combs can provide the required accurate and precise calibration to the astronomical spectrographs. For cosmological studies, extending the calibration with such astrocombs to the ultraviolet spectral range is desirable, however, strong material dispersion and large spectral separation from the established infrared laser oscillators have made this challenging.

Standardized wireless deep brain stimulation system for mice.

Deep brain stimulation (DBS) has emerged as a revolutionary technique for accessing and modulating brain circuits. DBS is used to treat dysfunctional neuronal circuits in neurological and psychiatric disorders. Despite over two decades of clinical application, the fundamental mechanisms underlying DBS are still not well understood.

Atypical cellular responses mediated by intracellular constitutive active TrkB (NTRK2) kinase domains and a solely intracellular NTRK2-fusion oncogene.

Trk (NTRK) receptor and NTRK gene fusions are oncogenic drivers of a wide variety of tumors. Although Trk receptors are typically activated at the cell surface, signaling of constitutive active Trk and diverse intracellular NTRK fusion oncogenes is barely investigated. Here, we show that a high intracellular abundance is sufficient for neurotrophin-independent, constitutive activation of TrkB kinase domains.

G-quadruplex folding in Xist RNA antagonizes PRC2 activity for stepwise regulation of X chromosome inactivation.

How Polycomb repressive complex 2 (PRC2) is regulated by RNA remains an unsolved problem. Although PRC2 binds G-tracts with the potential to form RNA G-quadruplexes (rG4s), whether rG4s fold extensively in vivo and whether PRC2 binds folded or unfolded rG4 are unknown. Using the X-inactivation model in mouse embryonic stem cells, here we identify multiple folded rG4s in Xist RNA and demonstrate that PRC2 preferentially binds folded rG4s.

Prevalence of adolescent mental disorders in Kenya, Indonesia, and Viet Nam measured by the National Adolescent Mental Health Surveys (NAMHS): a multi-national cross-sectional study.

Background: Mental disorders are the leading global cause of health burden among adolescents. However, prevalence data for mental disorders among adolescents in low-income and middle-income countries are scarce with often limited generalisability. This study aimed to generate nationally representative prevalence estimates for mental disorders in adolescents in Kenya, Indonesia, and Viet Nam.

Management of an Ingested Foreign Body in a COVID-Positive Patient.

This case report describes a 51-year-old man who swallowed an amalgam fragment dislodged during dental treatment performed without a throat screen. The patient was transferred to the emergency department, where the foreign body was confirmed to be in the esophagus following radiographic imaging. Foreign body removal from the esophagus is routinely achieved via esophagogastroduodenoscopy (EGD).

Vitamin D and depressive symptoms in an early adolescent cohort.

Background: To explore the cross-sectional and longitudinal association between vitamin D and depressive symptoms across early adolescence.

Methods: This longitudinal study included 1607 early adolescents [mean (s.d.

Measuring deliberate reflection in residents: validation and psychometric properties of a measurement tool.

Purpose: Reflective capacity is "the ability to understand critical analysis of knowledge and experience to achieve deeper meaning." In medicine, there is little provision for post-graduate medical education to teach deliberate reflection. The feasibility, scoring characteristics, reliability, validation, and adaptability of a modified previously validated instrument was examined for its usefulness assessing reflective capacity in residents as a step toward developing interventions for improvement.

"You Look Young! Are You a Doctor?" A Qualitative Content Analysis of Anesthesiology Resident Responses to Ageism in Clinical Encounters.

Background: Healthcare trainees frequently report facing comments from their patients pertaining to their age. Exposure to ageist comments from patients may be related to greater stress and/or burnout in residents and may impact the quality of the resident-patient relationship. However, little empirical work has examined ageism expressed toward anesthesiology residents in clinical care, and therefore not much is known about how residents respond to these comments in practice.

Adolescent-Parent Relationships and Communication: Consequences for Pregnancy Knowledge and Family Planning Service Awareness.

Purpose: We explore three dimensions of parent-adolescent relationships (sexual and reproductive health (SRH) communications, connectedness, and parental monitoring) from the perspective of young adolescents as they relate to pregnancy knowledge and family planning service awareness in four diverse geographic areas ranging from low to high income settings and stratified by sex.

Methods: Analyses utilized baseline data from four Global Early Adolescent Study sites (Shanghai, China; Kinshasa, Democratic Republic of the Congo; Denpasar and Semarang, Indonesia; and New Orleans, United States). Multiple linear regressions were conducted to assess the relationships between key characteristics of parent-adolescent relationships and pregnancy knowledge.

DRD1 signaling modulates TrkB turnover and BDNF sensitivity in direct pathway striatal medium spiny neurons.

Disturbed motor control is a hallmark of Parkinson's disease (PD). Cortico-striatal synapses play a central role in motor learning and adaption, and brain-derived neurotrophic factor (BDNF) from cortico-striatal afferents modulates their plasticity via TrkB in striatal medium spiny projection neurons (SPNs). We studied the role of dopamine in modulating the sensitivity of direct pathway SPNs (dSPNs) to BDNF in cultures of fluorescence-activated cell sorting (FACS)-enriched D1-expressing SPNs and 6-hydroxydopamine (6-OHDA)-treated rats.

Bortezomib induced peripheral neuropathy and single nucleotide polymorphisms in PKNOX1.

We analyzed single nucleotide polymorphisms (SNPs) in PKNOX1 (rs2839629) and in the intergenic region between PKNOX1 and CBS (rs915854) by Sanger sequencing in 88 patients with multiple myeloma treated with bortezomib. All patients (n = 13) harboring a homozygous mutation in PKNOX1 (rs2839629) also had a homozygous mutated rs915854 genotype. Homozygous mutated genotypes of rs2839629 and rs915854 were significantly enriched in patients with painful peripheral neuropathy (PNP) (P < 0.

A chimeric antigen receptor uniquely recognizing MICA/B stress proteins provides an effective approach to target solid tumors.

Background: The advent of chimeric antigen receptor (CAR) T cell therapies has transformed the treatment of hematological malignancies; however, broader therapeutic success of CAR T cells has been limited in solid tumors because of their frequently heterogeneous composition. Stress proteins in the MICA and MICB (MICA/B) family are broadly expressed by tumor cells following DNA damage but are rapidly shed to evade immune detection.

Methods: We have developed a novel CAR targeting the conserved α3 domain of MICA/B (3MICA/B CAR) and incorporated it into a multiplexed-engineered induced pluripotent stem cell (iPSC)-derived natural killer (NK) cell (3MICA/B CAR iNK) that expressed a shedding-resistant form of the CD16 Fc receptor to enable tumor recognition through two major targeting receptors.