Enhancing the Efficacy of Radiomics-Based Prediction of Fuhrman Pathological Grading in Renal Clear Cell Carcinoma Using Multilayer Spiral CT Imaging.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most prevalent subtype of renal cell carcinoma (RCC). Conventional pathological methods of Fuhrman pathological grading system have limitations. This study aims to investigate the efficacy of radiomics-based multilayer spiral computed tomography (CT) imaging of Fuhrman pathological grading in ccRCC. METHODS: A retrospective analysis was conducted on the clinical data of ccRCC patients admitted in our hospital from March 2023 to March 2024. The patients were classified as low-grade (Fuhrman pathological grades I and II) or high-grade (Fuhrman pathological grades III and IV). Statistical methods, including correlation analysis, receiver operating characteristic (ROC) curves and construction of a joint predictive model, were utilised to assess the predictive value of these imaging omics indicators for Fuhrman pathological grading in ccRCC. The primary outcome assessment parameter in this study was the predictive value of these imaging omics indicators for Fuhrman pathological grading in ccRCC. RESULTS: The clinical data from 101 ccRCC patients were examined, with 56 cases classified as low-grade and 45 cases as high-grade. The grey-level co-occurrence matrix (GLCM) features between low and high Fuhrman grading groups, including contrast (0.24 ± 0.08 vs. 0.33 ± 0.09), energy (0.73 ± 0.05 vs. 0.67 ± 0.06) and homogeneity (0.63 ± 0.05 vs. 0.57 ± 0.05), showed notable distinctions (p < 0.001). The CT imaging characteristics between low and high Fuhrman grading groups, including enhancement homogeneity (0.34 ± 0.08 vs. 0.26 ± 0.08) and washout half-time (28.57 ± 4.35 vs. 34.72 ± 5.62) demonstrated a substantial variation between the groups (p < 0.001). The enhancement homogeneity (r = 0.476), washout half-time (r = -0.519), contrast (r = 0.454), energy (r = -0.453) and homogeneity (r = -0.541) showed significant correlations with Fuhrman pathological grading. The predictive value of these features was evident, with a combined imaging genomics model exhibiting an area under the curve of 0.929. CONCLUSIONS: This study demonstrated the potential of radiomics-based prediction using multilayer spiral CT imaging for accurately predicting Fuhrman pathological grading in ccRCC.

A novel multimodal, intraoperative cognitive workload assessment of cardiac surgery team members.

OBJECTIVE: To characterize cognitive workload (CWL) of cardiac surgery team members in a real-world setting during coronary artery bypass grafting (CABG) surgery using providers' heart rate variability (HRV) data as a surrogate measure of CWL. METHODS: HRV was collected from the surgeon, anesthesiologist, perfusionist, and scrub nurse, and audio/video recordings were made during isolated, nonemergency CABG surgeries (n = 27). Eight surgical phases were annotated by trained researchers, and HRV was calculated for each phase. RESULTS: Significant differences in CWL were observed within a given role across surgical phases. Results are reported as predicted probability (95% confidence interval [CI]). CWL was significantly higher for anesthesiologists during "preparation and induction" (0.57; 95% CI, 0.42-0.71) and "anastomoses" (0.44; 95% CI, 0.30-0.58) compared to other phases, and the same held for nurses during the "opening" (0.51; 95% CI, 0.37-0.65) and "postoperative" (0.68; 95% CI, 0.42-0.86) phases. Additional significant differences were observed between roles within a given surgical phase. For example, surgeons had significantly higher CWL during "anastomoses" (0.81; 95% CI, 0.69-0.89) compared to all other phases, and the same was true of perfusionists during the "opening" (0.79; 95% CI, 0.66-0.88) and "prebypass preparation" (0.50; 95% CI, 0.36-0.64) phases. CONCLUSIONS: Our innovative analysis demonstrates that CWL fluctuates across surgical procedures by role and phase, which may reflect the distribution of primary tasks. This corroborates earlier findings from self-report measures. The data suggest that team-wide, peak CWL during a phase decreases from early phases of surgery through initiation of cardiopumonary bypass (CPB), rises during anastomosis, and decreases after termination of CPB. Knowledge of these trends could encourage the adoption of behaviors to enhance team dynamics and performance.

Clinical relevance of SCN and CyN induced by ELANE mutations: a systematic review.

Introduction: According to the PRISMA criteria, a systematic review has been conducted to investigate the clinical relevance between patients with severe congenital neutropenia (SCN) and cyclic congenital neutropenia (CyN) induced by ELANE mutations. Methods: We have searched PubMed, EMBASE, Web of Science, Scopus, Cochrane, CNKI, Wanfang Medicine, and VIP for ELANE mutation related literature published from 1997 to 2022. Using Microsoft Excel collect and organize data, SPSS 25, GraphPad Prism 8.0.1, and Omap analyze and plot statistical. Compare the gender, age, geography, mutation sites, infection characteristics, treatment, and other factors of SCN and CyN patients induced by ELANE mutations, with a focus on exploring the relationship between genotype and clinical characteristics, genotype and prognosis. Results: This study has included a total of 467 patients with SCN and 90 patients with CyN. The onset age of SCN and CyN are both less than 1 year old, and the onset and diagnosis age of SCN are both younger than CyN. The mutation of ELANE gene is mainly missense mutation, and hot spot mutations include S126L, P139L, G214R, c.597+1G>A. The high-frequency mutations with severe outcomes are A57V, L121H, L121P, c.597+1G>A, c.597+1G>T, S126L, C151Y, C151S, G214R, C223X. Respiratory tract, skin and mucosa are the most common infection sites, Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli are the most common. Discussion: Patients with refractory G-CSF are more likely to develop severe outcomes. The commonly used pre-treatment schemes for transplantation are Bu-Cy-ATG and Flu-Bu-ATG. The prognosis of transplantation is mostly good, but the risk of GVHD is high. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/. PROSPERO, identifier CRD42023434656.

Efficacy and safety of ivermectin for treatment of non-hospitalized COVID-19 patients: A systematic review and meta-analysis of 12 randomized controlled trials with 7,035 participants.

INTRODUCTION: We systematically assessed benefits and harms of the use of ivermectin in non-hospitalized patients with early COVID-19. METHODS: Five databases were searched until October 17, 2023, for randomized controlled trials (RCTs) in adult patients with COVID-19 treated with ivermectin against standard of care (SoC), placebo, or active drug. Primary outcomes were hospitalization, all-cause mortality, and adverse events (AEs). Secondary outcomes included mechanical ventilation (MV), clinical improvement, clinical worsening, viral clearance, and severe adverse events (SAEs). Random effects meta-analyses were performed, with quality of evidence (QoE) evaluated using GRADE methods. Pre-specified subgroup analyses (ivermectin dose, control type, risk of bias, follow-up, and country income) and trial sequential analysis (TSA) were performed. RESULTS: Twelve RCTs (n = 7,035) were included. The controls were placebo in nine RCTs, SoC in two RCTs, and placebo or active drug in one RCT. Ivermectin did not reduce hospitalization (relative risk [RR], 0.81, 95% confidence interval [95% CI] 0.64-1.03; 8 RCTs, low QoE), all-cause mortality (RR 0.98, 95% CI 0.73-1.33; 9 RCTs, low QoE), or AEs (RR 0.89, 95% CI 0.75-1.07; 9 RCTs, very low QoE) vs. controls. Ivermectin did not reduce MV, clinical worsening, or SAEs and did not increase clinical improvement and viral clearance vs. controls (very low QoE for secondary outcomes). Subgroup analyses were mostly consistent with main analyses, and TSA-adjusted risk for hospitalization was similar to main analysis. CONCLUSIONS: In non-hospitalized COVID-19 patients, ivermectin did not have effect on clinical, non-clinical or safety outcomes versus controls. Ivermectin should not be recommended as treatment in non-hospitalized COVID-19 patients.

Endobronchial Phenylephrine in Airway Bleeding During Bronchoscopy Does not Cause Hypertension: A Retrospective Observational Study.

BACKGROUND: Bleeding is a known complication during bronchoscopy, with increased incidence in patients undergoing a more invasive procedure. Phenylephrine is a potent vasoconstrictor that can control airway bleeding when applied topically and has been used as an alternative to epinephrine. The clinical effects of endobronchial phenylephrine on systemic vasoconstriction have not been clearly evaluated. Here, we compared the effects of endobronchial phenylephrine versus cold saline on systemic blood pressure. METHODS: In all, 160 patients who underwent bronchoscopy and received either endobronchial phenylephrine or cold saline from July 1, 2017 to June 30, 2022 were included in this retrospective observational study. Intra-procedural blood pressure absolute and percent changes were measured and compared between the 2 groups. RESULTS: There were no observed statistical differences in blood pressure changes between groups. The median absolute change between the median and the maximum intra-procedural systolic blood pressure in the cold saline group was 29 mm Hg (IQR 19 to 41) compared with 31.8 mm Hg (IQR 18 to 45.5) in the phenylephrine group. The corresponding median percent changes in SBP were 33.6 % (IQR 18.8 to 39.4) and 28% (IQR 16.8 to 43.5) for the cold saline and phenylephrine groups, respectively. Similarly, there were no statistically significant differences in diastolic and mean arterial blood pressure changes between both groups. CONCLUSIONS: We found no significant differences in median intra-procedural systemic blood pressure changes comparing patients who received endobronchial cold saline to those receiving phenylephrine. Overall, this argues for the vascular and systemic safety of phenylephrine for airway bleeding as a reasonable alternative to epinephrine.

Altered development of face recognition among infants born amid the COVID-19 pandemic.

To effectively contain the spread of COVID-19, public health agencies mandated special regulations. Although they protected us from COVID-19, these restrictions have inevitably changed the environment around us. It remains unclear how these changes may have affected early cognitive development among infants born during the pandemic. Thus, this study examined how the COVID-19 restrictions have affected infants' face recognition ability, a hallmark of their cognitive capacities. Specifically, we used the familiarization and visual pair comparison paradigm to examine face recognition performance among infants aged 6 to 14 months amid the second wave of the pandemic (February to July 2021). Experiment 1 investigated the recognition of unmasked faces and found that only younger infants, but not older infants, recognized faces by showing a novelty preference. Experiment 2 examined the recognition of faces wearing masks and found that only older infants, but not younger ones, recognized faces by exhibiting a familiarity preference. These results suggest that with limited interactions during the pandemic, infants could have developed an overly specialized face processing ability that failed to recognize the faces of strangers. Moreover, infants could have obtained more information on masked faces during the pandemic and adapted to the current situation. In Expreiment 3, we further confirmed the restriction on infants' interpersonal experiences with a survey conducted both before and during the pandemic. Overall, these findings demonstrated how the pandemic altered early perceptual development and further confirmed that interpersonal experiences during infancy are critical in their cognitive development.

Using the ROX Index to Predict Treatment Outcome for High-Flow Nasal Cannula and/or Noninvasive Ventilation in Patients With COPD Exacerbations.

BACKGROUND: The ratio of oxygen saturation index (ROX index; or SpO2 /FIO2 /breathing frequency) has been shown to predict risk of intubation after high-flow nasal cannula (HFNC) support among adults with acute hypoxemic respiratory failure primarily due to pneumonia. However, its predictive value for other subtypes of respiratory failure is unknown. This study investigated whether the ROX index predicts liberation from HFNC or noninvasive ventilation (NIV), intubation with mechanical ventilation, or death in adults admitted for respiratory failure due to an exacerbation of COPD. METHODS: We performed a retrospective study of 260 adults hospitalized with a COPD exacerbation and treated with HFNC and/or NIV (continuous or bi-level). ROX index scores were collected at treatment initiation and predefined time intervals throughout HFNC and/or NIV treatment or until the subject was intubated or died. A ROX index score of ≥ 4.88 was applied to the cohort to determine if the same score would perform similarly in this different cohort. Accuracy of the ROX index was determined by calculating the area under the receiver operator curve. RESULTS: A total of 47 subjects (18%) required invasive mechanical ventilation or died while on HFNC/NIV. The ROX index at treatment initiation, 1 h, and 6 h demonstrated the best prediction accuracy for avoidance of invasive mechanical ventilation or death (area under the receiver operator curve 0.73 [95% CI 0.66-0.80], 0.72 [95% CI 0.65-0.79], and 0.72 [95% CI 0.63-0.82], respectively). The optimal cutoff value for sensitivity (Sn) and specificity (Sp) was a ROX index score > 6.88 (sensitivity 62%, specificity 57%). CONCLUSIONS: The ROX index applied to adults with COPD exacerbations treated with HFNC and/or NIV required higher scores to achieve similar prediction of low risk of treatment failure when compared to subjects with hypoxemic respiratory failure/pneumonia. ROX scores < 4.88 did not accurately predict intubation or death.

Early Mobility Index and Patient Outcomes: A Retrospective Study in Multiple Intensive Care Units.

BACKGROUND: Early mobility interventions in intensive care units (ICUs) are safe and improve outcomes in subsets of critically ill adults. However, implementation varies, and the optimal mobility dose remains unclear. OBJECTIVE: To test for associations between daily dose of out-of-bed mobility and patient outcomes in different ICUs. METHODS: In this retrospective cohort study of electronic records from 7 adult ICUs in an academic quarternary hospital, multivariable linear regression was used to examine the effects of out-of-bed events per mobility-eligible day on mechanical ventilation duration and length of ICU and hospital stays. RESULTS: In total, 8609 adults hospitalized in ICUs from 2015 through 2018 were included. Patients were mobilized out of bed on 46.5% of ICU days and were eligible for mobility interventions on a median (IQR) of 2.0 (1-3) of 2.7 (2-9) ICU days. Median (IQR) out-of-bed events per mobility-eligible day were 0.5 (0-1.2) among all patients. For every unit increase in out-of-bed events per mobility-eligible day before extubation, mechanical ventilation duration decreased by 10% (adjusted coefficient [95% CI], -0.10 [-0.18 to -0.01]). Daily mobility increased ICU stays by 4% (adjusted coefficient [95% CI], 0.04 [0.03-0.06]) and decreased hospital stays by 5% (adjusted coefficient [95% CI], -0.05 [-0.07 to -0.03]). Effect sizes differed among ICUs. CONCLUSIONS: More daily out-of-bed mobility for ICU patients was associated with shorter mechanical ventilation duration and hospital stays, suggesting a dose-response relationship between daily mobility and patient outcomes. However, relationships differed across ICU subpopulations.

A Rare Prolactin-secreting Pituitary Carcinoma With Epidural and Thecal Metastases.

Pituitary carcinomas are rare but associated with significant morbidity and mortality. They remain challenging to diagnose and manage. In this case, we describe a 56-year-old man who presented with erectile dysfunction and binocular vertical diplopia. He had central hypogonadism, secondary adrenal insufficiency, and central hypothyroidism on biochemical testing. His serum prolactin was 1517 mcg/L (1517 ng/mL; reference range 4-15 mcg/L), and his sellar magnetic resonance imaging showed a 2.0 × 2.2 × 3.1 cm pituitary tumor. Pathology revealed a prolactin-secreting carcinoma. Despite treatment with a high-dose dopaminergic, 2 transsphenoidal resections, and 1 course of radiation, prolactin levels continued to rise. He developed metastases to the epidural space and thecal sac from the thoracic to sacral spine, for which he received 12 cycles of temozolomide chemotherapy with initial clinical and biochemical response. This was followed by disease escape and progression. We discuss the clinical and imaging features that warrant a high index of suspicion for pituitary carcinoma and review contemporary treatment.

Next-Generation Photodetectors beyond Van Der Waals Junctions.

With the continuous advancement of nanofabrication techniques, development of novel materials, and discovery of useful manipulation mechanisms in high-performance applications, especially photodetectors, the morphology of junction devices and the way junction devices are used are fundamentally revolutionized. Simultaneously, new types of photodetectors that do not rely on any junction, providing a high signal-to-noise ratio and multidimensional modulation, have also emerged. This review outlines a unique category of material systems supporting novel junction devices for high-performance detection, namely, the van der Waals materials, and systematically discusses new trends in the development of various types of devices beyond junctions. This field is far from mature and there are numerous methods to measure and evaluate photodetectors. Therefore, it is also aimed to provide a solution from the perspective of applications in this review. Finally, based on the insight into the unique properties of the material systems and the underlying microscopic mechanisms, emerging trends in junction devices are discussed, a new morphology of photodetectors is proposed, and some potential innovative directions in the subject area are suggested.

Maintained imbalance of triglycerides, apolipoproteins, energy metabolites and cytokines in long-term COVID-19 syndrome patients.

Background: Deep metabolomic, proteomic and immunologic phenotyping of patients suffering from an infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have matched a wide diversity of clinical symptoms with potential biomarkers for coronavirus disease 2019 (COVID-19). Several studies have described the role of small as well as complex molecules such as metabolites, cytokines, chemokines and lipoproteins during infection and in recovered patients. In fact, after an acute SARS-CoV-2 viral infection almost 10-20% of patients experience persistent symptoms post 12 weeks of recovery defined as long-term COVID-19 syndrome (LTCS) or long post-acute COVID-19 syndrome (PACS). Emerging evidence revealed that a dysregulated immune system and persisting inflammation could be one of the key drivers of LTCS. However, how these biomolecules altogether govern pathophysiology is largely underexplored. Thus, a clear understanding of how these parameters within an integrated fashion could predict the disease course would help to stratify LTCS patients from acute COVID-19 or recovered patients. This could even allow to elucidation of a potential mechanistic role of these biomolecules during the disease course. Methods: This study comprised subjects with acute COVID-19 (n=7; longitudinal), LTCS (n=33), Recov (n=12), and no history of positive testing (n=73). 1H-NMR-based metabolomics with IVDr standard operating procedures verified and phenotyped all blood samples by quantifying 38 metabolites and 112 lipoprotein properties. Univariate and multivariate statistics identified NMR-based and cytokine changes. Results: Here, we report on an integrated analysis of serum/plasma by NMR spectroscopy and flow cytometry-based cytokines/chemokines quantification in LTCS patients. We identified that in LTCS patients lactate and pyruvate were significantly different from either healthy controls (HC) or acute COVID-19 patients. Subsequently, correlation analysis in LTCS group only among cytokines and amino acids revealed that histidine and glutamine were uniquely attributed mainly with pro-inflammatory cytokines. Of note, triglycerides and several lipoproteins (apolipoproteins Apo-A1 and A2) in LTCS patients demonstrate COVID-19-like alterations compared with HC. Interestingly, LTCS and acute COVID-19 samples were distinguished mostly by their phenylalanine, 3-hydroxybutyrate (3-HB) and glucose concentrations, illustrating an imbalanced energy metabolism. Most of the cytokines and chemokines were present at low levels in LTCS patients compared with HC except for IL-18 chemokine, which tended to be higher in LTCS patients. Conclusion: The identification of these persisting plasma metabolites, lipoprotein and inflammation alterations will help to better stratify LTCS patients from other diseases and could help to predict ongoing severity of LTCS patients.

Concurrent versus terminal feedback: The effect of feedback delivery on lumbar puncture skills in simulation training.

INTRODUCTION: Simulation-based medical education (SBME) is widely used to teach bedside procedural skills. Feedback is crucial to SBME but research on optimal timing to support novice learners' skill development has produced conflicting results. METHODS: We randomly assigned 32 novice medical students to receive feedback either during (concurrent) or after (terminal) trialing lumbar puncture (LP). Participants completed pre- and post-acquisition tests, as well as retention and transfer tests, graded on a LP checklist by two blinded expert raters. Cognitive load and anxiety were also assessed, as well as learners' perceptions of feedback. RESULTS: Participants who received concurrent feedback demonstrated significantly higher LP checklist scores (M = 91.54, SE = 1.90) after controlling for baseline levels, than those who received terminal feedback (M = 85.64, SE = 1.90), collapsed across post, retention, and transfer tests. There was no difference in cognitive load and anxiety between groups. In open-ended responses, participants who received concurrent feedback more often expressed satisfaction with their learning experience compared to those who received terminal feedback. DISCUSSION AND CONCLUSIONS: Concurrent may be superior to terminal feedback when teaching novice learners complex procedures and has the potential to improve learning if incorporated into SBME and clinical teaching. Further research is needed to elucidate underlying cognitive processes to explain this finding.

Portable nanopore-sequencing technology: Trends in development and applications.

Sequencing technology is the most commonly used technology in molecular biology research and an essential pillar for the development and applications of molecular biology. Since 1977, when the first generation of sequencing technology opened the door to interpreting the genetic code, sequencing technology has been developing for three generations. It has applications in all aspects of life and scientific research, such as disease diagnosis, drug target discovery, pathological research, species protection, and SARS-CoV-2 detection. However, the first- and second-generation sequencing technology relied on fluorescence detection systems and DNA polymerization enzyme systems, which increased the cost of sequencing technology and limited its scope of applications. The third-generation sequencing technology performs PCR-free and single-molecule sequencing, but it still depends on the fluorescence detection device. To break through these limitations, researchers have made arduous efforts to develop a new advanced portable sequencing technology represented by nanopore sequencing. Nanopore technology has the advantages of small size and convenient portability, independent of biochemical reagents, and direct reading using physical methods. This paper reviews the research and development process of nanopore sequencing technology (NST) from the laboratory to commercially viable tools; discusses the main types of nanopore sequencing technologies and their various applications in solving a wide range of real-world problems. In addition, the paper collates the analysis tools necessary for performing different processing tasks in nanopore sequencing. Finally, we highlight the challenges of NST and its future research and application directions.

The development of a paper-based distance sensor for the detection of Pb2+ assisted with the target-responsive DNA hydrogel.

Due to the serious risks of lead pollution to human health, it plays a great role in constructing a simple, inexpensive, portable, and user-friendly strategy for Pb2+ detection in environmental samples. Herein, a paper-based distance sensor is developed to detect Pb2+ assisted with the target-responsive DNA hydrogel. Pb2+ can activate DNAzyme to cleave its substrate strand, which results in the hydrolysis of the DNA hydrogel. The released water molecules trapped in the hydrogel can flow along the patterned pH paper due to the capillary force. The water flow distance (WFD) is significantly influenced by the amount of water released from the collapsed DNA hydrogel triggered by the addition of various Pb2+ concentrations. In this way, Pb2+ can be quantitatively detected without using specialized instruments and labeled molecules, and the limit of detection (LOD) of Pb2+ is 3.0 nM. Additionally, the Pb2+ sensor works well in lake water and tap water. Overall, this simple, inexpensive, portable, and user-friendly method is very promising for quantitative and in-field detection of Pb2+ with excellent sensitivity and selectivity.

OOCDB: A Comprehensive, Systematic, and Real-time Organs-on-a-chip Database.

Organs-on-a-chip is a microfluidic microphysiological system that uses microfluidic technology to analyze the structure and function of living human cells at the tissue and organ levels in vitro. Organs-on-a-chip technology, as opposed to traditional two-dimensional cell culture and animal models, can more closely simulate pathologic and toxicologic interactions between different organs or tissues and reflect the collaborative response of multiple organs to drugs. Despite the fact that many organs-on-a-chip-related data have been published, none of the current databases have all of the following functions: searching, downloading, as well as analyzing data and results from the literature on organs-on-a-chip. Therefore, we created an organs-on-a-chip database (OOCDB) as a platform to integrate information about organs-on-a-chip from various sources, including literature, patents, raw data from microarray and transcriptome sequencing, several open-access datasets of organs-on-a-chip and organoids, and data generated in our laboratory. OOCDB contains dozens of sub-databases and analysis tools, and each sub-database contains various data associated with organs-on-a-chip, with the goal of providing researchers with a comprehensive, systematic, and convenient search engine. Furthermore, it offers a variety of other functions, such as mathematical modeling, three-dimensional modeling, and citation mapping, to meet the needs of researchers and promote the development of organs-on-a-chip. The OOCDB is available at http://www.organchip.cn.

Messenger RNA in lipid nanoparticles rescues HEK 293 cells from lipid-induced mitochondrial dysfunction as studied by real time pulse chase NMR, RTPC-NMR, spectroscopy.

Analytical tools to study cell physiology are critical for optimizing drug-host interactions. Real time pulse chase NMR spectroscopy, RTPC-NMR, was introduced to monitor the kinetics of metabolite production in HEK 293T cells treated with COVID-19 vaccine-like lipid nanoparticles, LNPs, with and without mRNA. Kinetic flux parameters were resolved for the incorporation of isotopic label into metabolites and clearance of labeled metabolites from the cells. Changes in the characteristic times for alanine production implicated mitochondrial dysfunction as a consequence of treating the cells with lipid nanoparticles, LNPs. Mitochondrial dysfunction was largely abated by inclusion of mRNA in the LNPs, the presence of which increased the size and uniformity of the LNPs. The methodology is applicable to all cultured cells.

Nedosiran, a Candidate siRNA Drug for the Treatment of Primary Hyperoxaluria: Design, Development, and Clinical Studies.

Due to the lack of treatment options for the genetic disease primary hyperoxaluria (PH), including three subtypes PH1, PH2, and PH3, caused by accumulation of oxalate forming kidney stones, there is an urgent need for the development of a drug therapy aside from siRNA drug lumasiran for patients with PH1. After the recent success of drug therapies based on small interfering RNA (siRNA), nedosiran is currently being developed for the treatment of three types of PH as a siRNA-based modality. Through specific inhibition of lactate dehydrogenase enzyme, the key enzyme in biosynthesis of oxalate in liver, phase 1, 2, and 3 clinical trials of nedosiran have achieved the desired primary end point of reduction of urinary oxalate levels in patients with PH1. More PH2 and PH3 patients need to be tested for efficacy. It has also produced a favorable secondary end point on safety and toxicity in PH patients. In addition to common injection site reactions that resolved spontaneously, no severe nedosiran treatment-associated adverse events were reported. Based on the positive results in the clinical studies, nedosiran is a candidate siRNA drug to treat PH patients.

Integrating bioinformatic strategies in spatial life science research.

As space exploration programs progress, manned space missions will become more frequent and farther away from Earth, putting a greater emphasis on astronaut health. Through the collaborative efforts of researchers from various countries, the effect of the space environment factors on living systems is gradually being uncovered. Although a large number of interconnected research findings have been produced, their connection seems to be confused, and many unknown effects are left to be discovered. Simultaneously, several valuable data resources have emerged, accumulating data measuring biological effects in space that can be used to further investigate the unknown biological adaptations. In this review, the previous findings and their correlations are sorted out to facilitate the understanding of biological adaptations to space and the design of countermeasures. The biological effect measurement methods/data types are also organized to provide references for experimental design and data analysis. To aid deeper exploration of the data resources, we summarized common characteristics of the data generated from longitudinal experiments, outlined challenges or caveats in data analysis and provided corresponding solutions by recommending bioinformatics strategies and available models/tools.

Chronic pain in children and adolescents in Manitoba: A retrospective chart review to inform the development of a provincial service for pediatric chronic pain.

Background: In the absence of an interdisciplinary service for pediatric chronic pain in Manitoba, pain management has been offered through a single provider outpatient setting with consultative services from physiotherapy, occupational therapy, and psychiatry since October 2015. Aims: The aim of this study was to characterize the patient population of this clinic to understand needs and inform future service development for pediatric chronic pain. Methods: Demographics and disease characteristics of all patients seen in this clinic between October 1, 2015, and February 28, 2019, were analyzed retrospectively from electronic medical records. Results: A total of 157 patients, mean age 13.1 (sd ±3.0) years, 75.2% female, with a median duration of pain of 20.5 (interquartile range [IQR] = 10.0-45.8) months at their first visit were included in the study. At baseline, 74.0% of patients experienced insomnia, 76.6% fatigue, 86.5% symptoms of anxiety, and 58.69% symptoms of depression; 80.1% showed withdrawal from physical activity, 67.1% missed school, and 10.2% reported opioid usage. Throughout their care in clinic, 83.4% of patients received physiotherapy, 17.8% occupational therapy, 49.7% mental health support, and 51.6% care from multiple services. The clinic experienced a significant increase in median referrals from 1.0 to 5.0 (IQR = 2.0-9.0) per month and wait time from 35.0 to 97.0 (IQR = 88.0-251.0) days during the observation period. Conclusions: Developing an interdisciplinary service for pediatric chronic pain will provide an opportunity to improve access, coordination, and comprehensiveness of care and to employ culturally sensitive services to improve care for children and youth living with chronic pain in Manitoba and possibly other jurisdictions with similar demographics and needs.

Contexte: En l'absence d'un service interdisciplinaire pour la douleur chronique pédiatrique au Manitoba, la prise en charge de la douleur est proposée par un seul prestataire ambulatoire qui offre des services consultatifs de physiothérapie, d'ergothérapie et de psychiatrie depuis octobre 2015.Buts: Le but de cette étude était de caractériser la population de patients de cette clinique pour comprendre les besoins et éclairer le développement futur de services pour la douleur chronique pédiatrique.Méthodes: Les données démographiques et les caractéristiques de la maladie de tous les patients vus dans cette clinique entre le 1er octobre 2015 et le 28 février 2019 ont été analysées rétrospectivement à partir des dossiers médicaux électroniques.Résultats: Un total de 157 patients, dont l'âge moyen était de 13,1 ans (é.-t. ±3,0) ans, 75,2 % de femmes, avec une durée de la douleur médiane de 20,5 mois (écart interquartile [IQR] = 10,0-45,8) à leur première visite étaient inclus dans l'étude. À l'inclusion, 74,0 % des patients présentaient de l'insomnie, 76,6 % de la fatigue, 86,5 % des symptômes d'anxiété et 58,69 % des symptômes de dépression ; 80,1 % montraient un retrait de l'activité physique, 67,1 % avaient manqué l'école et 10,2 % ont déclaré avoir consommé des opioïdes. Tout au long de leur traitement en clinique, 83,4 % des patients ont reçu de la physiothérapie, 17,8 % de l'ergothérapie, 49,7 % un traitement de soutien à la santé et 51,6 % des soins dispensés par de multiples services. La clinique a connu une augmentation significative des références médianes de 1,0 à 5,0 (IQR = 2,0-9,0) par mois et du temps d'attente de 35,0 à 97,0 (IQR = 88,0-251,0) pendant la période d'observation.Conclusions : La mise sur pied d'un service interdisciplinaire pour la douleur chronique pédiatrique permettra d'améliorer l'accès, la coordination et l'exhaustivité des soins de même que le recours à des services adaptés à la culture pour améliorer les soins aux enfants et aux jeunes souffrant de douleur chronique au Manitoba et possiblement dans d'autres provinces et territoires ayant des caractéristiques démographiques et des besoins semblables.