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Hematoxylin and Eosin (H&E) staining is a cornerstone of pathological analysis, offering reliable visualization of cellular morphology and tissue architecture for cancer diagnosis, subtyping, and grading. Immunohistochemistry (IHC) staining provides molecular insights by detecting specific proteins within tissues, enhancing diagnostic accuracy, and improving treatment planning. However, IHC staining is costly, time-consuming, and resource-intensive, requiring specialized expertise. To address these limitations, this study proposes HistoStainAlign, a novel deep learning framework that predicts IHC staining patterns directly from H&E whole-slide images (WSIs) by learning joint representations of morphological and molecular features. The framework integrates paired H&E and IHC embeddings through a contrastive training strategy, capturing complementary features across staining modalities without patch-level annotations or tissue registration. The model was evaluated on gastrointestinal and lung tissue WSIs with three commonly used IHC stains: P53, PD-L1, and Ki-67. HistoStainAlign achieved weighted F1 scores of 0.735 [95% Confidence Interval (CI): 0.670-0.799], 0.830 [95% CI: 0.772-0.886], and 0.723 [95% CI: 0.607-0.836], respectively for these three IHC stains. Embedding analyses demonstrated the robustness of the contrastive alignment in capturing meaningful cross-stain relationships. Comparisons with a baseline model further highlight the advantage of incorporating contrastive learning for improved stain pattern prediction. This study demonstrates the potential of computational approaches to serve as a pre-screening tool, helping prioritize cases for IHC staining and improving workflow efficiency.

Purpose: This article describes prelinguistic vocal development in 2 prelingually deaf children who received multichannel cochlear implants at 10 and 28 months of age, respectively. Methods: Vocalizations were recorded in half-hour mother- child interactions before and after implantation and then classified into three levels of development: precanonical, canonical, and postcanonical. Results: One child made rapid progress in vocal development after her implant was activated. The other child showed slower progress with continued dominance of precanonical vocalizations throughout the first year of implant experience. Increases in vowel, diphthong, and consonant diversity; the establishment of canonical vocalizations; and the emergence of postcanonical forms were found to be indicators of progress in vocal development. Clinical Implications: Observed differences in the rate and completeness of vocal development between the 2 children suggest that some young implant recipients may need specialized intervention strategies to stimulate speech development. The rationale and procedures for implementing Short Periods of Prelinguistic Input (SPPI), a potentially useful approach for stimulating vocal development, are presented.

Several important systematic reviews and meta-analyses focusing on psychosocial interventions have been undertaken in the last decade. However, they have not focused specifically on the treatment of individual behavioral and psychological symptoms of dementia (BPSD) with personalized interventions. This updated systematic review will focus on studies reporting the effect of personalized psychosocial interventions on key BPSD in care homes. Systematic review of the evidence for psychosocial interventions for BPSD, focusing on papers published between 2000 and 2012. All care home and nursing home studies including individual and cluster randomized controlled trials (RCTs) and pre-/post-test studies with control conditions were included. 641 studies were identified, of which 40 fulfilled inclusion and exclusion criteria. There was good evidence to support the value of personalized pleasant activities with and without social interaction for the treatment of agitation, and reminiscence therapy to improve mood. The evidence for other therapies was more limited. There is a growing body of evidence indicating specific effects of different personalized psychosocial interventions on individual BPSD and mood outcomes.

Group A Streptococcus (GAS) is a major pathogen that causes simple and invasive infections. GAS requires iron for metabolic processes and pathogenesis, and heme is its preferred iron source. We previously described the iron-regulated hupZ in GAS, showing that a recombinant HupZ-His 6 protein binds and degrades heme. The His 6 tag was later implicated in heme iron coordination by HupZ-His 6 . Hence, we tested several recombinant HupZ proteins, including a tag-free protein, for heme binding and degradation in vitro . We established that HupZ binds heme but without coordinating the heme iron. Heme-HupZ readily accepted exogenous imidazole as its axial heme ligand, prompting degradation. Furthermore, HupZ bound a fragment of heme c (whose iron is coordinated by the cytochrome histidine residue) and exhibited limited degradation. GAS, however, did not grow on a heme c fragment as an iron source. Heterologous HupZ expression in Lactococcus lactis increased heme b iron use. A GAS hupZ mutant showed reduced growth when using hemoglobin as an iron source, increased sensitivity to heme toxicity, and decreased fitness in a murine model for vaginal colonization. Together, the data demonstrate that HupZ contributes to heme metabolism and host survival, likely as a heme chaperone. HupZ is structurally similar to the recently described heme c-degrading enzyme, Pden_1323, suggesting that the GAS HupZ might be divergent to play a new role in heme metabolism.

In clinical and translational research, data science is often and fortuitously integrated with data collection. This contrasts to the typical position of data scientists in other settings, where they are isolated from data collectors. Because of this, effective use of data science techniques to resolve translational questions requires innovation in the organization and management of these data. We propose an operational framework that respects this important difference in how research teams are organized. To maximize the accuracy and speed of the clinical and translational data science enterprise under this framework, we define a set of eight best practices for data management. In our own work at the University of Rochester, we have strived to utilize these practices in a customized version of the open source LabKey platform for integrated data management and collaboration. We have applied this platform to cohorts that longitudinally track multidomain data from over 3000 subjects. We argue that this has made analytical datasets more readily available and lowered the bar to interdisciplinary collaboration, enabling a team-based data science that is unique to the clinical and translational setting.

Polar bears ( Ursus maritimus ) and brown bears ( Ursus arctos ) are sister species possessing distinct physiological and behavioural adaptations that evolved over the last 500,000 years. However, comparative and population genomics analyses have revealed that several extant and extinct brown bear populations have relatively recent polar bear ancestry, probably as the result of geographically localized instances of gene flow from polar bears into brown bears. Here, we generate and analyse an approximate 20X paleogenome from an approximately 100,000-year-old polar bear that reveals a massive prehistoric admixture event, which is evident in the genomes of all living brown bears. This ancient admixture event was not visible from genomic data derived from living polar bears. Like more recent events, this massive admixture event mainly involved unidirectional gene flow from polar bears into brown bears and occurred as climate changes caused overlap in the ranges of the two species. These findings highlight the complex reticulate paths that evolution can take within a regime of radically shifting climate. A paleogenome from an approximately 100,000-year-old polar bear shows massive prehistoric, and largely unidirectional, gene flow from polar bears into brown bears at a time of climate change-induced overlap in the ranges of the two species. This admixture event cannot be detected using genomic data from living polar bears.

Objective: Attention-deficit/hyperactivity disorder (ADHD) symptoms, including inattention and over activity, occur in approximately one-third of children with autism spectrum disorder (ASD). We describe the rate and duration of adverse events in a randomized controlled trial of atomoxetine (ATX) and parent training (PT) for ADHD symptoms and noncompliance in children with ASD. Methods: We conducted a 10-week, double-blind, 2 × 2 trial of ATX and PT with 128 children (ages 5–14) randomized to ATX alone, ATX+PT, placebo+PT, or placebo alone. For 6 weeks, ATX (or placebo) doses were clinically adjusted to a maximum of 1.8 mg/(kg·day) and maintained for an additional 4 weeks. An average of seven PT sessions were conducted in the two PT arms. Adverse events (AEs) were assessed through parent ratings of common symptoms on a seven-point Likert severity scale and through direct interviews with study medical staff. Results: ATX was associated with decreased appetite and fatigue, but was otherwise well tolerated. Most reported AEs lasted 4 weeks or less. Unlike reports with typically developing (TD) children, there were no concerns with QTc changes or suicidal ideation. Conclusions: This study extends the findings of previous studies of ATX in ASD by documenting that the type of AEs was similar to that of TD children, with no significant safety concerns.

Several important systematic reviews and meta-analyses focusing on psychosocial interventions have been undertaken in the last decade. However, they have not focused specifically on the treatment of individual behavioral and psychological symptoms of dementia (BPSD) with personalized interventions. This updated systematic review will focus on studies reporting the effect of personalized psychosocial interventions on key BPSD in care homes. Systematic review of the evidence for psychosocial interventions for BPSD, focusing on papers published between 2000 and 2012. All care home and nursing home studies including individual and cluster randomized controlled trials (RCTs) and pre-/post-test studies with control conditions were included. 641 studies were identified, of which 40 fulfilled inclusion and exclusion criteria. There was good evidence to support the value of personalized pleasant activities with and without social interaction for the treatment of agitation, and reminiscence therapy to improve mood. The evidence for other therapies was more limited. There is a growing body of evidence indicating specific effects of different personalized psychosocial interventions on individual BPSD and mood outcomes.