Making Community-Based Palliative Care Eligibility Determinations: Palliative Care Team Member Perspectives on Access to Information and Algorithm Use.

Background: Seriously ill older adults have high risk of mortality, symptom burden, and compromised functional status, and may benefit from community-based palliative care ("palliative care"). However, identifying potentially eligible individuals is challenging.

Objectives: Identify how a palliative care team makes eligibility determinations, including the use of a mortality risk algorithm.

Multicriteria Measures to Assess the Sustainability of Diets: A Systematic Review.

Context: Assessing the overall sustainability of a diet is a challenging undertaking requiring a holistic approach capable of addressing the multicriteria nature of this concept.

Objective: The aim was to identify and summarize the multicriteria measures used to assess the sustainability characteristics of diets reported at the individual level by healthy adults.

Data Sources: Articles were identified via PubMed, Scopus, and Web of Science.

BioPrint meets the AI age: development of artificial intelligence-based ADMET models for the drug-discovery platform SAFIRE.

To prioritize compounds with a higher likelihood of success, artificial intelligence models can be used to predict absorption, distribution, metabolism, excretion and toxicity (ADMET) properties of molecules quickly and efficiently. Models were trained with BioPrint database proprietary data along with public datasets to predict various ADMET end points for the SAFIRE platform. SAFIRE models performed at or above 75% accuracy and 0.

Practical Characterization Strategies for Comparison, Qualification, and Selection of Cell Viability Detection Methods for Cellular Therapeutic Product Development and Manufacturing.

Cellular therapy development and manufacturing has focused on providing novel therapeutic cell-based products for various diseases. The International Organization for Standardization (ISO) has provided guidance on critical quality attributes (CQAs) that shall be considered when testing and releasing cellular therapeutic products. Cell count and viability measurements are two of the CQAs that are determined during development, manufacturing, testing, and product release.

The Critical Importance of Molecular Biomarkers and Imaging in the Study of Electrohypersensitivity. A Scientific Consensus International Report.

Clinical research aiming at objectively identifying and characterizing diseases via clinical observations and biological and radiological findings is a critical initial research step when establishing objective diagnostic criteria and treatments. Failure to first define such diagnostic criteria may lead research on pathogenesis and etiology to serious confounding biases and erroneous medical interpretations. This is particularly the case for electrohypersensitivity (EHS) and more particularly for the so-called "provocation tests", which do not investigate the causal origin of EHS but rather the EHS-associated particular environmental intolerance state with hypersensitivity to man-made electromagnetic fields (EMF).

Infant Safe Sleep Promotion: Increasing Capacity of Child Protective Services Employees.

Sleep-related infant deaths, including Sudden Infant Death Syndrome (SIDS), are the number one cause of death in infants between 28 days and one year of life. Nearly half of families experiencing a sleep-related infant death in Kansas were involved with the Department of Children and Families Child Protective Services (CPS), making CPS staff a priority for safe sleep training. This study assessed the impact of the two-day Kansas Infant Death and SIDS (KIDS) Network Safe Sleep Instructor (SSI) train-the-trainer program on CPS staffs' knowledge of the American Academy of Pediatrics safe sleep recommendations.

A Flexible, Pooled CRISPR Library for Drug Development Screens.

Functional genomic screening with CRISPR has provided a powerful and precise new way to interrogate the phenotypic consequences of gene manipulation in high-throughput, unbiased analyses. However, some experimental paradigms prove especially challenging and require carefully and appropriately adapted screening approaches. In particular, negative selection (or sensitivity) screening, often the most experimentally desirable modality of screening, has remained a challenge in drug discovery.

Discovery of a lead series of potent benzodiazepine 5-HT receptor agonists with high selectivity in functional and binding assays.

A series of potential new 5-HT receptor scaffolds based on a simplification of the clinically studied, 5-HTR agonist vabicaserin, were designed. An in vivo feeding assay early in our screening process played an instrumental part in the lead identification process, leading us to focus on a 6,5,7-tricyclic scaffold. A subsequent early SAR investigation provided potent agonists of the 5-HT receptor that were highly selective in both functional and binding assays, had good rat PK properties and that significantly reduced acute food intake in the rat.

CRISPR: A Screener's Guide.

The discovery of CRISPR-Cas9 systems has fueled a rapid expansion of gene editing adoption and has impacted pharmaceutical and biotechnology research substantially. Here, gene editing is used at an industrial scale to identify and validate new biological targets for precision medicines, with functional genomic screening having an increasingly important role. Functional genomic strategies provide a crucial link between observed biological phenomena and the genes that influence and drive those phenomena.

Sustainability in the biopharmaceutical industry: Seeking a holistic perspective.

Biopharmaceuticals manufacturing is a critical component of the modern healthcare system, with emerging new treatments composed of increasingly complex biomolecules offering solutions to chronic and debilitating disorders. While this sector continues to grow, it strongly exhibits "boom-to-bust" performance which threatens its long-term viability. Future trends within the industry indicate a shift towards continuous production systems using single use technologies that raises sustainability issues, yet research in this area is sparse and lacks consideration of the complex interactions between environmental, social and economic concerns.

Drug checking at an electronic dance music festival during the public health overdose emergency in British Columbia.

Setting: Shambhala is a 5-day electronic dance music (EDM) festival held in rural British Columbia that annually hosts between 15,000 and 18,000 people on a 500-acre ranch. The AIDS Network Outreach & Support Society (ANKORS) has provided harm reduction services throughout the duration of the festival since 2003, including point-of-care drug checking, which allows real-time testing of illicit substances to assess their composition. Drug checking results are provided directly to clients and displayed in aggregate on a screen for all attendees to see.

Safe Sleep Practices of Kansas Birthing Hospitals.

Background: Sleep-related death is tied with congenital anomalies as the leading cause of infant mortality in Kansas, and external risk factors are present in 83% of these deaths. Hospitals can impact caregiver intentions to follow risk-reduction strategies. This project assessed the current practices and policies of Kansas hospitals with regard to safe sleep.

Expanding harm reduction to include fentanyl urine testing: results from a pilot in rural British Columbia.

Background: Harm reduction has been at the forefront of the response to the opioid overdose public health emergency in British Columbia (BC). The unprecedented number of opioid overdose deaths in the province calls for an expansion of harm reduction services. The purpose of this study was to determine the acceptability of a fentanyl urine drug test among people who use drugs (PWUD) and explore whether testing introduced any changes in participants' attitudes and behaviors towards their drug use.

Fatal collision? Are wireless headsets a risk in treating patients?

Wireless-enabled headsets that connect to the internet can provide remote transcribing of patient examination notes. Audio and video can be captured and transmitted by wireless signals sent from the computer screen in the frame of the glasses. But using wireless glass-type devices can expose the user to a specific absorption rates (SAR) of 1.

Dual direction CRISPR transcriptional regulation screening uncovers gene networks driving drug resistance.

Pooled CRISPR-Cas9 knock out screens provide a valuable addition to the methods available for novel drug target identification and validation. However, where gene editing is targeted to amplified loci, the resulting multiple DNA cleavage events can be a cause of false positive hit identification. The generation of nuclease deficient versions of Cas9 has enabled the development of two additional techniques - CRISPR interference (CRISPRi) and CRISPR activation (CRISPRa) - that enable the repression or overexpression, respectively, of target genes.

Environmental trade-offs of pig production systems under varied operational efficiencies.

Production of pork, the most consumed meat globally, is estimated to emit 668 m tonnes CO-eq of greenhouse gases each year. Amongst various production systems that comprise the pig industry, grain-based intensive production is widely regarded as the largest polluter of the environment, and thus it is imperative to develop alternative systems that can provide the right balance between sustainability and food security. Using an original dataset from the Republic of Ireland, this paper examines the life-cycle environmental impacts of representative pig farms operating under varying production efficiencies.

Factors associated with Type II trauma in occupational groups working with traumatised children: a systematic review.

Background: There is evidence that "Type II trauma" (TTT) - repeated exposure to traumatic events - can lead to the development of post-traumatic stress disorder (PTSD). TTT frequently occurs in occupational groups working with children who are themselves victims of trauma.

Aim: To conduct a systematic review identifying risk factors for/protective factors against TTT-associated mental ill-health in employees working with traumatised children and explore how this type of work impacts upon social functioning.

Electromagnetic Fields, Pulsed Radiofrequency Radiation, and Epigenetics: How Wireless Technologies May Affect Childhood Development.

Mobile phones and other wireless devices that produce electromagnetic fields (EMF) and pulsed radiofrequency radiation (RFR) are widely documented to cause potentially harmful health impacts that can be detrimental to young people. New epigenetic studies are profiled in this review to account for some neurodevelopmental and neurobehavioral changes due to exposure to wireless technologies. Symptoms of retarded memory, learning, cognition, attention, and behavioral problems have been reported in numerous studies and are similarly manifested in autism and attention deficit hyperactivity disorders, as a result of EMF and RFR exposures where both epigenetic drivers and genetic (DNA) damage are likely contributors.

Rescue of Hearing by Gene Delivery to Inner-Ear Hair Cells Using Exosome-Associated AAV.

Adeno-associated virus (AAV) is a safe and effective vector for gene therapy for retinal disorders. Gene therapy for hearing disorders is not as advanced, in part because gene delivery to sensory hair cells of the inner ear is inefficient. Although AAV transduces the inner hair cells of the mouse cochlea, outer hair cells remain refractory to transduction.

Discovery of 2-(((1r,4r)-4-(((4-Chlorophenyl)(phenyl)carbamoyl)oxy)methyl)cyclohexyl)methoxy)acetate (Ralinepag): An Orally Active Prostacyclin Receptor Agonist for the Treatment of Pulmonary Arterial Hypertension.

The design and synthesis of a new series of potent non-prostanoid IP receptor agonists that showed oral efficacy in the rat monocrotaline model of pulmonary arterial hypertension (PAH) are described. Detailed profiling of a number of analogues resulted in the identification of 5c (ralinepag) that has good selectivity in both binding and functional assays with respect to most members of the prostanoid receptor family and a more modest 30- to 50-fold selectivity over the EP3 receptor. In our hands, its potency and efficacy are comparable or superior to MRE269 (the active metabolite of the clinical compound NS-304) with respect to in vitro IP receptor dependent cAMP accumulation assays.

Tetrahydroquinoline-based tricyclic amines as potent and selective agonists of the 5-HT receptor.

The syntheses, structure-activity relationships (SARs), and biological activities of tetrahydroquinoline-based tricyclic amines as 5-HT receptor agonists are reported. An early lead containing a highly unique 6,6,7-ring system was optimized for both in vitro potency and selectivity at the related 5-HT receptor. Orally bioactive, potent, and selective 6,6,6-tricyclic 5-HT agonists were identified.

Synthetic lethality between PAXX and XLF in mammalian development.

PAXX was identified recently as a novel nonhomologous end-joining DNA repair factor in human cells. To characterize its physiological roles, we generated Paxx-deficient mice. Like Xlf mice, Paxx mice are viable, grow normally, and are fertile but show mild radiosensitivity.

microRNAs with AAGUGC seed motif constitute an integral part of an oncogenic signaling network.

microRNA (miRNA) dysregulation is a common feature of cancer cells, but the complex roles of miRNAs in cancer are not fully elucidated. Here, we used functional genomics to identify oncogenic miRNAs in non-small cell lung cancer and evaluate their impact on response to epidermal growth factor (EGFR)-targeting therapy. Our data demonstrate that miRNAs with an AAGUGC motif in their seed sequence increase both cancer cell proliferation and sensitivity to EGFR inhibitors.