Revisiting the druggable genome using predicted structures and data mining.

Identification of novel drug targets is a key component of modern drug discovery. While antimalarial targets are often identified through the mechanism of action studies on phenotypically derived inhibitors, this method tends to be time- and resource-consuming. The discoverable target space is also constrained by existing compound libraries and phenotypic assay conditions.

Historical data provide new insights into inheritance of traits important for diploid potato breeding.

Using a diploid potato diversity panel of 246 breeding lines, a genotyping-by-sequencing and a GWAS approach, we mapped QTL for ten traits important to potato breeders, including two previously unmapped traits: boiled tuber taste and pollen fertility. Potato breeding at the diploid level has a long history and has gained new impetus recently, when F1 hybrid breeding was made possible with the discovery of a dominant gene for self-compatibility. Our study deploys a unique diploid diversity panel with a broadened cultivated potato gene pool obtained as a result of introgressing valuable traits from wild potato relatives into the Solanum tuberosum background.

Neuroscience-informed psychoeducation for addiction: a conceptual and feasibility study.

Over the past few decades, our understanding of substance use disorders (SUD) has been reshaped by evidence from neuroscience, which suggests that SUD are characterized by specific neuromarkers that transcend traditional diagnostic boundaries and act as pre-diagnostic markers that could be targeted through preventive attempts. Connectivity-based neuromarkers or brain networks have emerged as a promising framework, providing new insights into the neurocognitive mechanisms of SUD. Utilizing this data-driven framework assists prevention and intervention developers in offering a non-judgmental insight for adolescents regarding the potential vulnerability of neurocognitive systems to continued substance use.

Multimodal machine learning to predict surgical site infection with healthcare workload impact assessment.

Remote monitoring is essential for healthcare digital transformation, however, this poses greater burdens on healthcare providers to review and respond as the data collected expands. This study developed a multimodal neural network to automate assessments of patient-generated data from remote postoperative wound monitoring. Two interventional studies including adult gastrointestinal surgery patients collected wound images and patient-reported outcome measures (PROMs) for 30-days postoperatively.

Assessing STI and HIV risks among autistic individuals: Implications for healthcare access and intervention.

Background: Sexually transmitted infections (STIs) are prevalent in the general population. Autistic individuals, both with and without intellectual disability (ID), are potentially at increased risk due to gaps in sexual health education, increased vulnerability to sexual abuse, victimization, and disparities in access to primary and reproductive health care.

Objective: This study aims to identify the prevalence of STIs and HIV among a national sample of Medicaid-enrolled autistic individuals and their peers, identifying opportunities for intervention.

Prevalence of Functional Food Use for Self-Reported Type 2 Diabetes Management in a Cohort of Hispanic Adults: Results of an Online Survey.

Background: Hispanic adults are disproportionately diagnosed with type 2 diabetes mellitus (T2DM) and are more likely to use functional foods for T2DM management compared with non-Hispanic White adults. Functional foods contain biologically active ingredients associated with physiological health benefits for preventing and managing chronic disease. Understanding which functional foods are used for T2DM management among Hispanic adults is essential for planning interventions.

Tumor Suppressors Condition Differential Responses to the Selective CDK2 Inhibitor BLU-222.

CDK2 inhibitors have recently been developed and entered clinical trials. Combination approaches can help broaden the use of therapeutic agents and establish more effective treatments. Here, we evaluated the selective CDK2 inhibitor BLU-222 for mechanisms of response in the context of ovarian and breast cancer models.

Discrete vulnerability to pharmacological CDK2 inhibition is governed by heterogeneity of the cancer cell cycle.

Cyclin dependent kinase 2 (CDK2) regulates cell cycle and is an emerging target for cancer therapy. There are relatively small numbers of tumor models that exhibit strong dependence on CDK2 and undergo G1 cell cycle arrest following CDK2 inhibition. The expression of P16INK4A and cyclin E1 determines this sensitivity to CDK2 inhibition.

Validation of a Demography-Based Adaptive QT Correction Formula Using Pediatric and Adult Datasets Acquired From Humans and Guinea Pigs.

Background: QT correction (QTc) formulae are widely used in clinical and research settings but often underperform, possibly due to demographic influences on the QT-heart rate (HR) relationship. To address this limitation, we developed an adaptive QTc (QTcAd) formula, which adjusts for demographic factors like age, and compared its efficacy to other standard formulae.

Methods: The QTcAd formula was tested across diverse age groups with different HR in both humans and guinea pigs.

Cultural humility strategies for recruitment and retention of minoritised participants: a scoping review protocol.

Introduction: Cultural humility practices are shown to be effective when working with diverse populations in healthcare settings. Research recruitment and retention among minoritised groups are essential to address health inequities. Given the successful application to healthcare settings, cultural humility practices may hold promise for recruiting and retaining minoritised individuals.

Genome Sequence of Three Siphoviruses in the EE, GA and EA5 Actinobacteriophage Clusters: Biscayne, Bush and GreenIvy.

Bacteriophages Biscayne, Bush and GreenIvy were isolated from soil samples in Miami, FL using NRRL B-24224 as host. Transmission electron microscopy shows siphoviral morphologies for all three phages. Based on gene content similarity to other actinobacteriophages, they are assigned to the EE, GA and EA5 clusters, respectively.

Fragment-based development of small molecule inhibitors targeting cholesterol metabolism.

() is the world's most deadly infectious pathogen and new drugs are urgently required to combat the emergence of multi- (MDR) and extensively- (XDR) drug resistant strains. The bacterium specifically upregulates sterol uptake pathways in infected macrophages and the metabolism of host-derived cholesterol is essential for long-term survival Here, we report the development of antitubercular small molecules that inhibit the cholesterol oxidases CYP125 and CYP142, which catalyze the initial step of cholesterol metabolism. An efficient biophysical fragment screen was used to characterize the structure-activity relationships of CYP125 and CYP142, and identify a non-azole small molecule that can bind to the heme cofactor of both enzymes.

Cataract surgery has minimal effect on corneal shape.

Purpose: To quantify the effect of cataract surgery on cornea shape.

Methods: Patients undergoing cataract surgery with standardised 2.75 mm surgical incisions at 110 degrees with a side port at 50 degrees were included.

COVID-19 vaccine anxieties: exploring social and political drivers of vaccine attitudes in Kono District, Sierra Leone.

As COVID-19 spread rapidly during the early months of the pandemic, many communities around the globe anxiously waited for a vaccine. At the start of the pandemic, it was widely believed that Africa would be a significant source of infection, and thus, vaccinating African communities became a primary goal among local and global health authorities. However, when the COVID-19 vaccine became available in March 2021 in Sierra Leone, many people viewed it with scepticism and hesitation.

Perceptions of sexual assault perpetrators, victims, and event depend on system justification beliefs and perpetrator atonement.

When accused of wrongdoing, a sexual assault perpetrator may express atonement, i.e., he may acknowledge harm done, take responsibility, and make amends.

International Symposium on Ruminant Physiology: Paternal Nutrient Supply: Impacts on Physiological and Whole Animal Outcomes in Offspring.

Recent evidence suggests that environmental factors experienced by sires can be transmitted through the ejaculate (seminal plasma + sperm) into the female reproductive tract, influencing fertilization, embryo development, and postnatal offspring outcomes. This concept is termed paternal programming. In rodents, sire nutrition was shown to directly alter offspring outcomes through sperm epigenetic signatures, DNA damage/oxidative stress, cytokine profiles, and/or the seminal microbiome.

Revisiting the Plasmodium falciparum druggable genome using predicted structures and data mining.

The identification of novel drug targets for the purpose of designing small molecule inhibitors is key component to modern drug discovery. In malaria parasites, discoveries of antimalarial targets have primarily occurred retroactively by investigating the mode of action of compounds found through phenotypic screens. Although this method has yielded many promising candidates, it is time- and resource-consuming and misses targets not captured by existing antimalarial compound libraries and phenotypic assay conditions.

Methods to reduce fraudulent participation and highlight autistic voices in research.

Over the last decade, especially since the pandemic, more research has been happening online. Conducting research online can create opportunities to include autistic people across the world and make our studies more diverse. However, conducting research online had led to scammers, or people pretending to be autistic, participating in autism research studies.

Integrating systems of power and privilege in the study of resilience.

Although current approaches to the study of resilience acknowledge the role of context, rarely do those conceptualizations attend to societal systems and structures that include hierarchies of power and privilege-namely systems of racism, colonialism, patriarchy, and capitalism-nor do they articulate how these structural realities are embedded within individual experiences. We offer critiques of the current literature from this structural lens, using the concept of master narratives to articulate the incomplete and, at times, damaging story that the discipline of psychology has told about resilience. We then provide three models that center history, systems, and structures of society that can be employed in the study of resilience.

Implementation of digital remote postoperative monitoring in routine practice: a qualitative study of barriers and facilitators.

Introduction: Remote monitoring can strengthen postoperative care in the community and minimise the burden of complications. However, implementation requires a clear understanding of how to sustainably integrate such complex interventions into existing care pathways. This study aimed to explore perceptions of potential facilitators and barriers to the implementation of digital remote postoperative monitoring from key stakeholders and derive recommendations for an implementable service.

Challenges and Opportunities in Transitioning Autistic Individuals Into Adulthood.

Background And Objectives: Approximately 1.2 million autistic youth will reach the legal age of adulthood over the next decade. Given dynamic changes in the socioecological context of the transition to adulthood, we produced an updated transitions research agenda reflecting the perspectives of autistic young adults, care partners (parents), and professionals who use autism research.

Changes in vaginal cytokines concentrations during artificial insemination and natural service in beef heifers.

Objective: Heifer development is crucial for the optimization of reproductive efficiency in beef production. Heifer development is largely influenced by nutrition. Nutritional status of these heifers can influence immunological responses that are crucial for reproduction.

The story of 'us' is the story of 'me': A cross-sectional test of the influence of insecure attachment on narratives of romantic transgressions and high points.

Narratives play an important role in the development of the self-identity. Romantic relationships offer a powerful context in which to develop these narratives about the self through the good and the bad experiences people have with their partners. However, the stories we tell can also be colored by how we already see ourselves.