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High-throughput genome-wide studies of alternatively spliced mRNA transcripts have become increasingly important in clinical research. Consequently, easy-to-use software tools are required to process data from these studies, for example, using exon and junction arrays. Here, we introduce JETTA, an integrated software package for the calculation of gene expression indices as well as the identification and visualization of alternative splicing events. We demonstrate the software using data of human liver and muscle samples hybridized on an exon-junction array. JETTA and its demonstrations are freely available at http://igenomed.stanford.edu/~junhee/JETTA/index.html
Aboriginal and Torres Strait Islander peoples experience greater cancer incidence rates, unmet information needs, and poorer cancer outcomes compared to the general Australian population. This environmental scan evaluated cancer websites for Aboriginal and Torres Strait Islander peoples in Australia. An environmental scan using eight Google searches was conducted in July 2025 to identify cancer-related websites targeted toward Aboriginal and Torres Strait Islander peoples in Australia. Patient-facing resources were assessed for readability, understandability, and actionability using grade level assessments of readability and the Patient Education Materials Assessment Tool. Cultural relevance was assessed using an Aboriginal cultural relevance measure. Of 239 search results, twelve websites were patient facing and contained material for Aboriginal and Torres Strait Islander readers, primarily on common cancers. Readability generally exceeded the recommended Grade 6 reading level, with only one resource below Grade 6 level. Resources were considered understandable with scores of > 80% for 7/12 websites (range 50-100%); 2/12 included summaries and 7/12 plain language. Actionability scores ranged from 0 to 100% (M = 63.6%, SD = 37.0), with wide variation. Cultural relevance averaged 3.8/7 (SD = 1.9) with only one resource meeting all criteria (7/7). Most lacked culturally specificity and did not provide Aboriginal and Torres Strait Islander languages translations. Our results necessitate co-design with Aboriginal and Torres Strait Islander peoples for resources appropriate to community needs and including information on a broad range of cancers. Websites should optimise the readability and cultural safety of information for Aboriginal and Torres Strait Islander peoples seeking cancer information.
Children and young people with chronic kidney disease (CKD) are at risk for deficiency or excess of magnesium and trace elements. Kidney function, dialysis, medication, and dietary and supplemental intake can affect their biochemical status. There is much uncertainty about the requirements of magnesium and trace elements in CKD, which leads to variation in practice. The Pediatric Renal Nutrition Taskforce is an international team of pediatric kidney dietitians and pediatric nephrologists, formed to develop evidence-based clinical practice points to improve the nutritional care of children with CKD. PICO (patient, intervention, comparator, and outcomes) questions led the literature searches, which were conducted to ascertain current biochemical status, dietary intake, and factors leading to requirements differing from healthy peers, and to guide nutritional care of children with CKD stages 2-5, on dialysis, and post-transplantation. We address the assessment and intervention of magnesium and the trace elements chromium, copper, fluoride, iodine, manganese, selenium, and zinc. We suggest routine biochemical assessment of magnesium. Trace element assessment is based on clinical suspicion of deficiency or excess and their risk factors, including accumulation, losses, medications, nutrient interactions, and comorbidities. In particular, we suggest assessing magnesium, copper, iodine, and zinc when growth is poor, and evaluating magnesium, copper, selenium, and zinc in the presence of proteinuria. A structured approach to magnesium and trace element management, including biochemical, physical, and dietary assessment, is beneficial in the paucity of evidence. Research recommendations are suggested.
Narcolepsy is a rare, chronic neurological disorder characterized by a dysregulated sleep-wake cycle, with core clinical features including excessive daytime sleepiness (EDS), cataplexy, hypnopompic/hypnagogic hallucinations, and sleep paralysis. Several treatment options are available for the symptomatic management of narcolepsy, but they have limitations. Comorbidities of narcolepsy further limit the treatment choices. Blocking of histamine 3 (H3) receptors has been demonstrated to be a viable approach for the management of symptoms of narcolepsy. Samelisant (SUVN-G3031) is a new H3 receptor inverse agonist. The efficacy, safety, tolerability, and pharmacokinetics of Samelisant in narcolepsy patients were evaluated in a phase 2, double-blind, placebo-controlled study (ClinicalTrials.gov identifier: NCT04072380). Patients diagnosed with narcolepsy according to the International Classification of Sleep Disorders criteria and having an Epworth Sleepiness Scale (ESS) score of ≥12 and a mean Maintenance of Wakefulness Test (MWT) time of <12 min across the 4 sessions at baseline were enrolled. The total study duration was up to 7 weeks, which included a screening period of 4 weeks, a treatment period of 2 weeks, and a safety follow-up 1 week after the last study drug administration. The primary efficacy measure was the change in total ESS score compared to placebo. Secondary and exploratory assessments included the Clinical Global Impression of Severity, MWT, Clinical Global Impression of Change, Patient Global Impression of Change and cataplexy rate. Safety assessments included monitoring adverse events (AEs) and laboratory assessments. Of the 426 patients screened, 190 were randomized. The safety and intention-to-treat population included 188 and 164 patients, respectively. A statistically significant treatment effect of Samelisant was observed on the primary endpoint, indicating improvements in EDS. The treatment's impact on EDS was also evident on the other patients' and clinicians' perspectives scales. The AEs reported in ≥5 % patients in any treatment groups were insomnia, abnormal dreams, nausea, and hot flush. Global phase 3 studies and long-term safety and efficacy assessments of Samelisant are planned to reaffirm the current findings.
SUVN-1105 is a novel formulation of abiraterone acetate which was developed to demonstrate improved bioavailability, compared to Zytiga and Yonsa, and to reduce the dose and eliminate the food effect. A Phase 1 study was conducted to assess the bioequivalence, food effect, and comparative pharmacokinetics of SUVN-1105 to Zytiga in healthy male subjects. The study comprised of 2 segments. Segment 1 was a single-center, 4-period crossover, open-label, fixed treatment sequence, single-dose study to evaluate the safety and pharmacokinetics of SUVN-1105 (N = 12 subjects per period). Segment 2 was a single-center, open-label, single-dose, randomized, 4-period, 4-treatment, 4-sequence crossover study to evaluate bioequivalence and comparative pharmacokinetics of SUVN-1105 against Zytiga (N = 44) under overnight fasted, modified fasted, and fed conditions. Abiraterone exposures appeared to increase proportionately with SUVN-1105 dose (200 mg vs. 250 mg) in Segment 1. In Segment 2, abiraterone exposures of 250 mg SUVN-1105 in the fasted or fed conditions were higher than those of Zytiga 1000 mg in the overnight fasted conditions. Abiraterone exposures of 250 mg SUVN-1105 decreased in the fed conditions (64% and 29% decrease in Cmax and AUC, respectively) compared to overnight fasted conditions. The abiraterone exposures of 250 mg SUVN-1105 in the fasted or fed conditions fall within the abiraterone exposures of 1000 mg Zytiga in fasted and modified fasted conditions. Single doses of SUVN-1105 were safe and well-tolerated in healthy males both in the fasted and fed conditions.
Local substrate stiffness is one of the major mechanical inputs for tissue organization during its development and remodeling. It is widely recognized that adherent cells use transmembrane proteins (integrins) at focal adhesions to translate ECM mechanical cues into intracellular bioprocess. Here we show that epithelial cells respond to substrate stiffening primarily via actin cytoskeleton organization, that requires activation of mechanosensitive Piezo1 channels. Piezo1 Knockdown cells eliminated the actin stress fibers that formed on stiff substrates, while it had minimal effect on cell morphology and spreading area. Inhibition of Piezo1 channels with GsMTx4 also significantly reduced stiffness-induced F-actin reorganization, suggesting Piezo1 mediated cation current plays a role. Activation of Piezo1 channels with specific agonist (Yoda1) resulted in thickening of F-actin fibers and enlargement of FAs on stiffer substrates, whereas it did not affect the formation of nascent FAs that facilitate spreading on the soft substrates. These results demonstrate that Piezo1 functions as a force sensor that couples with actin cytoskeleton to distinguish the substrate stiffness and facilitate epithelial adaptive remodeling.
Reports an error in "The modal suicide decedent did not consume alcohol just prior to the time of death: An analysis with implications for understanding suicidal behavior" by Michael D. Anestis, Thomas Joiner, Jetta E. Hanson and Peter M. Gutierrez (Journal of Abnormal Psychology, 2014[Nov], Vol 123[4], 835-840). The institutional affiliation in the byline for Jetta E. Hanson was incorrectly listed as Military Suicide Research Consortium, Tallahassee, Florida. Jetta E. Hanson's correct institutional affiliation is provided in the erratum.
The effects of masupirdine on the neuropsychiatric symptoms were explored. Masupirdine (SUVN-502) was evaluated for its effects on cognition in patients with moderate AD. The prespecified primary outcome showed no drug-placebo difference. Post hoc analyses of domains of the 12-item neuropsychiatric inventory scale were carried out. In a subgroup of patients (placebo, n = 57; masupirdine 50 mg, n = 53; masupirdine 100 mg, n = 48) with baseline agitation/aggression symptoms ≥1, a statistically significant reduction in agitation/aggression scores was observed in masupirdine 50 mg (95% confidence interval (CI), -1.9 to -0.5, p < 0.001) and masupirdine 100 mg (95% CI, -1.7 to -0.3, p = 0.007) treated arms at Week 13 in comparison to placebo and the effect was sustained for trial duration of 26 weeks in the masupirdine 50 mg treatment arm (95% CI, -2.3 to -0.8, p < 0.001). Similar observations were noted in the subgroup of patients (placebo, n = 29; masupirdine 50 mg, n = 30; masupirdine 100 mg, n = 21) with baseline agitation/aggression symptoms ≥3. In the subgroup of patients (placebo, n = 28; masupirdine 50 mg, n = 28; masupirdine 100 mg, n = 28) who had baseline psychosis symptoms and/or symptom emergence, a significant reduction in psychosis scores was observed in the masupirdine 50 mg (Week 4: 95% CI, -2.8 to -1.4, p < 0.001; Week 13: 95% CI, -3.3 to -1.3, p < 0.001) and masupirdine 100 mg (Week 4: 95% CI, -1.4 to 0, p = 0.046; Week 13: 95% CI, -1.9 to 0.1, p = 0.073) treatment arms in comparison to placebo. Further research is warranted to explore the potential beneficial effects of masupirdine on NPS.
Ropanicant hydrochloride (previously known as SUVN-911, hereinafter referred to as ropanicant) is a novel alpha4 beta2 nicotinic acetylcholine receptor (α4β2 nAchR) antagonist being developed for the treatment of major depressive disorder. The objectives of the present studies were to evaluate the safety, tolerability, and pharmacokinetics of ropanicant after single and multiple ascending doses and to evaluate the effect of food, sex, and age on its pharmacokinetics in healthy subjects. Two phase I studies have been conducted for ropanicant. Study 1 is a randomized, double-blind, placebo-controlled, first-in-human study to evaluate the safety, tolerability, and pharmacokinetics of single ascending doses (0.5, 6, 15, 30, and 60 mg) and multiple ascending doses (15, 30, and 45 mg) of ropanicant administered orally for 14 days to healthy male subjects. In Study 2, the effect of food, sex, and age on ropanicant pharmacokinetics was evaluated following a single 30-mg oral dose. Ropanicant at single doses up to 60 mg and multiple doses up to 45 mg once daily was found to be safe and well tolerated in healthy subjects. The most frequently reported adverse events were headache and nausea. Ropanicant exposures were more than dose proportional following single and multiple administrations. Urinary excretion of unchanged ropanicant was low across the doses. Upon multiple dosing, 1.5- to 2.5-fold higher exposures for maximum concentration and 1.6- to 4.0-fold higher exposures for area under the concentration-time curve from time 0-24 h were observed on day 14 as compared with day 1. Sex had an effect on the pharmacokinetics of ropanicant as a 64% higher area under the concentration-time curve from time 0 to 24 h and a 26% higher maximum concentration was observed in female adults when compared with male adults. Plasma exposures were comparable in fasted versus fed conditions and in adult versus elderly subjects. Ropanicant was found to be safe and well tolerated following single and multiple oral administrations in healthy subjects. Ropanicant showed nonlinear pharmacokinetics and accumulation following multiple dosing. Urinary excretion represents an insignificant elimination pathway for ropanicant. Ropanicant pharmacokinetics were sex dependent, and food and age had no effect on its pharmacokinetics. NCT03155503 and NCT03551288.
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive deterioration in cognition, memory and activities of daily living. Selective blockade of serotonin-6 (5-HT6) receptors, which are exclusively localized to the central nervous system, is reported to play an important role in learning and memory. Masupirdine is a potent and selective 5-HT6 receptor antagonist with pro-cognitive properties in animal models of cognition. The efficacy and safety of masupirdine were evaluated in patients with moderate AD concurrently treated with donepezil and memantine. A total of 564 patients were randomized in a 1:1:1 ratio. The study consisted of a 26-week double-blind treatment period. The primary efficacy outcome was the 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog 11). Changes from baseline were analyzed using a mixed effects model for repeated measures (MMRM). In exploratory post hoc analyses, patients were subdivided based on the use of memantine dosage forms and memantine plasma concentrations, to evaluate the impact of memantine on the efficacy of masupirdine. In an exploratory post hoc analysis, less worsening in cognition (ADAS-Cog 11 scores) was observed with masupirdine treatment as compared with placebo in patients whose trough memantine plasma concentrations were ≤ 100 ng/mL. Although prespecified study endpoints of the phase 2 study were not met, these exploratory post hoc subgroup observations are hypothesis-generating and suggest that the efficacy of masupirdine was adversely affected by concurrent therapy with memantine. Further assessment of masupirdine to determine its potential role as a treatment option for cognitive deficits associated with AD is warranted. The study was registered at ClinicalTrials.gov (NCT02580305).
This study explored the efficacy and safety of a serotonin-6 receptor antagonist, masupirdine, as adjunct treatment in patients with moderate Alzheimer's disease (AD) concomitantly treated with donepezil and memantine. The effects of masupirdine were evaluated in patients with moderate AD dementia on background treatment with donepezil and memantine. Five hundred thirty-seven patients were expected to be randomized in a 1:1:1 ratio, using permuted blocked randomization. After a 2- to 4-week screening period, the study consisted of a 26-week double-blind treatment period, and a 4-week washout period. The primary efficacy measure was the 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog 11). Secondary efficacy measures were Clinical Dementia Rating Scale-Sum of Boxes, Mini-Mental State Examination, 23-item Alzheimer's Disease Co-operative Study Activities of Daily Living, and 12-item Neuropsychiatric Inventory. Changes from baseline were analyzed using a mixed effects model for repeated measures (MMRM). A total of 564 patients were randomized to receive either daily masupirdine 50 mg (190 patients), masupirdine 100 mg (185 patients), or placebo (189 patients). The study is registered at ClinicalTrials.gov (NCT02580305). The MMRM results showed statistically non-significant treatment differences in change from baseline in ADAS-Cog 11 scores at week 26, comparing each masupirdine dose arm to the placebo arm. No significant treatment effects were observed in the secondary evaluations. Masupirdine was generally safe and well tolerated. Possible reasons for the observed trial results are discussed. Masupirdine was evaluated in moderate Alzheimer's disease patients.First trial in class with background treatment of donepezil and memantine.Masupirdine was generally safe and well tolerated.Possible reasons for the observed trial results are discussed.
On a sweltering summer morning, throngs of people filed into Jones Theatre at Baylor University in Waco for the graduate student orientation. One could look around and notice the diversity of not only the student population, but also the disciplines being represented. Many students had stepped off planes only hours prior, but even those who had been traveling for days could not contain their excitement. As for me, I was nowhere near any of this. I was still 40 miles north of Waco in Waxahachie, having been pulled over for speeding. After 4 days of traveling with my life in my Volkswagon Jetta, all the way from San Francisco, on one of the most important days of my life, I was late. When I finally arrived at the Hooper Schafer Fine Arts Auditorium, out of breath from running all the way from the parking structure, all of the graduate students were quietly listening to the first introductory speech. I snuck into the back and sat down. My mind was racing, as I knew very little about Waco and Baylor University except for the growing accomplishments of the biomedical studies program. What little I did know about Baylor seemed so different from my very liberal upbringing in California. What would this experience be like for me? But, as I listened to the talks, met with other students, and finally met the entire biomedical studies entering class of 2007, I knew that I had made the right decision in coming to Baylor. This would be an experience unlike any other, and I was wholeheartedly open to embracing it. -Christine Morel, PhD candidate, Institute of Biomedical Studies.
The basic treatment for cow's milk allergy (CMA) is the elimination of all cow's milk proteins (CMP) from the diet. This study aimed at characterizing the diet of children with a diagnosis of CMA, to assess the degree of adherence to the elimination diet and to evaluate the factors associated with the adherence and age of recovery. From a birth cohort study, food records of 267 children diagnosed with CMA were studied to define how strictly the elimination diet was adhered to. Subsequent food records were studied to assess the age at reintroduction of milk products in the child's diet. The families adhered to the elimination diet of the child with extreme accuracy in 85% of the cases. Older and monosensitized children had more often small amounts of CMP in their diet, possibly because of the absence of nutritional information by a dietitian/nutritionist. Adherence to the diet was neither related to any other sociodemographic factor studied nor to the age at reintroduction of milk products into the diet. The therapeutic elimination diet of children diagnosed with CMA was well adhered to. Low intakes of vitamin D, calcium, and riboflavin are of concern in children who follow or have followed a cow's milk-free diet.
A third of parents suspect food allergy in their children. Questionnaire-based studies usually overestimate the occurrence of food allergies. The aim of the present study was to validate a study questionnaire by comparing children's use of special diets as reported by parents with patient records at the hospital. A population-based cohort with genetic susceptibility to type 1 diabetes (15% of those screened) was recruited in the Tampere area between 1997 and 2001, and followed for development of food allergy for 3 years. Food allergies and other special diets were queried at the age of 3 years with a structured questionnaire. The hospital records of the children, whose parents had reported an elimination diet of the child, were studied to validate the parental reports of food allergies. The hospital database was also checked for the respective diagnosis codes to estimate underreporting. Altogether, 1122 parents returned the questionnaire at the study center visit when the child was 3 years old. Food allergy was reported by 15.0% of the parents. In 10.6% of the children food allergy had been diagnosed or confirmed at the hospital. Hospital-confirmed food allergy was unreported in 0.9% of the cases. The measure of agreement between reported and hospital-confirmed food allergies, using crosstabulation with Cohen's Kappa, was within 0.71-0.88 for cow's milk allergy, 0.74-0.82 for cereal allergy and 0.66-0.86 for any reported food allergy. We found that the validity of the questionnaire obtaining information on food allergies of infants and young children was good to excellent based on a comparison between parental reports and information obtained from patient records.
SUVN-G3031 is a novel, potent, and selective histamine-3 receptor (H3R) inverse agonist in development for the treatment of narcolepsy. Our objective was to characterize the safety, tolerability, and pharmacokinetics of SUVN-G3031 in healthy young adults after single and multiple doses, and to evaluate the effect of food, gender, and age on the pharmacokinetics. A single ascending dose (SAD) and a multiple ascending dose (MAD) study for 14 days was conducted in healthy young adults using a randomized, double-blind study design. The effect of food, gender, and age on SUVN-G3031 pharmacokinetics (6 mg as a single dose) was evaluated using an open-label, two-period, randomized, crossover design in fed and fasted states. Pharmacokinetics and safety assessments were conducted throughout the study. Single doses of SUVN-G3031 up to 20 mg and multiple doses up to 6 mg once daily were found to be safe and well tolerated in healthy young adults. The most frequently reported adverse events were abnormal dreams, dyssomnia, and hot flushes. SUVN-G3031 exposure was dose proportional across the tested doses. Steady state was achieved on day 6 after once-daily dosing. Renal excretion (~ 60%) of unchanged SUVN-G3031 was the major route of elimination. Food, gender, and age did not have any clinically meaningful effect on SUVN-G3031 exposure. SUVN-G3031 was found to be safe and well tolerated in healthy human subjects without any effect of age, gender, and food on the pharmacokinetics and safety profile. Clinical Trials Registration (https://clinicaltrials.gov): NCT04072380 and NCT02342041.
All hospitalized patients should be screened for malnutrition risk. No universal method exists for pediatric patients. We performed a cross-sectional study comparing three published malnutrition risk screening tools (PYMS, STAMP, and STRONGkids), applying them to each inpatient aged 1 month to 17 years over a period of five consecutive weekdays in Helsinki University Hospital, Finland. Of the eligible patients, 67% (n = 69) participated. We found that 6.2% of the children were acutely malnourished and accurately categorized by the three tools. STRONGkids showed the highest specificity (100%) and positive predictive value (36%). Acute malnutrition seemed to be associated with longer hospital stay (p = 0.051). STRONGkids was the most accurate screening tool for detecting acute malnutrition and was therefore chosen as the screening method in our hospital. Routine screening for the risk of malnutrition in pediatric inpatients is important in detecting at-risk children who would otherwise be left without dietary intervention.
Suitable pumping methods for flow control remain a major technical hurdle in the path of biomedical microfluidic systems for point-of-care (POC) diagnostics. A vacuum-driven power-free micropumping method provides a promising solution to such a challenge. In this review, we focus on vacuum-driven power-free microfluidics based on the gas solubility or permeability of polydimethylsiloxane (PDMS); degassed PDMS can restore air inside itself due to its high gas solubility or gas permeable nature. PDMS allows the transfer of air into a vacuum through it due to its high gas permeability. Therefore, it is possible to store or transfer air into or through the gas soluble or permeable PDMS in order to withdraw liquids into the embedded dead-end microfluidic channels. This article provides a comprehensive look at the physics of the gas solubility and permeability of PDMS, a systematic review of different types of vacuum-driven power-free microfluidics, and guidelines for designing solubility-based or permeability-based PDMS devices, alongside existing applications. Advanced topics and the outlook in using micropumping that utilizes the gas solubility or permeability of PDMS will be also discussed. We strongly recommend that microfluidics and lab-on-chip (LOC) communities harness vacuum energy to develop smart vacuum-driven microfluidic systems.
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