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Racial/ethnic disparities mar NSCLC care and treatment outcomes. While socioeconomic factors and access to healthcare are important drivers of NSCLC disparities, a deeper understanding of genetic ancestry-associated genomic landscapes can better inform the biology and the treatment actionability for these tumors. We present a comprehensive ancestry-based prevalence and co-alteration landscape of genomic alterations and immunotherapy-associated biomarkers in patients with KRAS and EGFR-altered non-squamous (non-Sq) NSCLC. KRAS was the most frequently altered oncogene in European (EUR) and African (AFR), while EGFR alterations predominated in East Asian (EAS), South Asian (SAS), and Admixed American (AMR) groups, consistent with prior studies. As expected, STK11 and KEAP1 alterations co-occurred with KRAS alterations while showing mutual exclusivity with EGFR alterations. EAS and AMR KRAS-altered non-Sq NSCLC showed lower rates of co-occurring STK11 and KEAP1 alterations relative to other ancestry groups. Ancestry-specific co-alterations included the co-occurrence of KRAS and GNAS alterations in AMR, KRAS, and ARID1A alterations in SAS, and the mutual exclusivity of KRAS and NF1 alterations in the EUR and AFR ancestries. Contrastingly, EGFR-altered tumors exhibited a more conserved co-alteration landscape across ancestries. AFR exhibited the highest tumor mutational burden, with potential therapeutic implications for these tumors., (© 2024. The Author(s).)

Objectives: To investigate the effects of different angles of pulmonary surfactant (PS) administration on the incidence of bronchopulmonary dysplasia and intracranial hemorrhage in preterm infants., Methods: A prospective study was conducted on 146 preterm infants (gestational age <32 weeks) admitted to the Department of Neonatology, Provincial Hospital Affiliated to Anhui Medical University from January 2019 to May 2023. The infants were randomly assigned to different angles for injection of pulmonary surfactant groups: 0° group (34 cases), 30° group (36 cases), 45° group (38 cases), and 60° group (38 cases). Clinical indicators and outcomes were compared among the groups., Results: The oxygenation index was lower in the 60° group compared with the other three groups, with shorter invasive ventilation time and oxygen use time, and a lower incidence of bronchopulmonary dysplasia than the other three groups ( P <0.05). The incidence of intracranial hemorrhage was lower in the 60° group compared to the 0° group ( P <0.05). The cure rate in the 60° group was higher than that in the 0° group and the 30° group ( P <0.05)., Conclusions: The clinical efficacy of injection of pulmonary surfactant at a 60° angle is higher than other angles, reducing the incidence of intracranial hemorrhage and bronchopulmonary dysplasia in preterm infants.

Purpose: To explore the differential diagnosis of salivary gland tumors by multimodal ultrasound and to establish a preliminary scoring system by assigning meaningful parameters., Methods: Seventy-seven tumors from 69 patients with salivary gland tumors were examined by two-dimensional gray-scale ultrasound, color Doppler flow imaging (CDFI), superb microvascular imaging(SMI), real time tissue elastography(RTE) and acoustic radiation force impulse (ARFI). Different scoring schemes were obtained for the assignment and combination of meaningful parameters. The ROC curve of each scheme was drawn, and the one with the largest area under the curve was taken as the best scoring scheme. SPSS 25.0 software package was used for statistical analysis of the data., Results: There were significant differences in tumor shape, boundary, posterior echo, blood flow resistance index, RTE grade and ARFI average value between benign and malignant salivary gland tumors(P<0.05). The scoring scheme 7, which was composed of the above 6 parameters, was the best scoring scheme. When each parameter was assigned a score of 1, the total score was 6, and the area under the curve was 0.944. The sensitivity, specificity and accuracy of distinguishing benign and malignant salivary gland tumors with ≥4 points were 80.0%, 98.4% and 94.8%, respectively., Conclusions: Application of multimodal ultrasound and establishment of a scoring system can effectively improve the ability of ultrasound in the differential diagnosis of benign and malignant salivary gland tumors.

Objective: Hypoglycaemia leads to significant morbidity and impacts negatively on quality-of-life, especially in elderly people with increased frailty. The aims of this study were to determine the prevalence of low interstitial fluid glucose (IFG) in patients with tightly controlled type 2 diabetes (T2D), and to evaluate whether there were differences in burden of low IFG between sulphonylurea and insulin treated groups., Methods: A Freestyle Libre-Pro sensor was used for sampling of the IFG continuously. Patients were blinded to the IFG levels. The sensor was returned to the investigators after a 2-week period and the data were downloaded for analysis., Results: There was a total of 69 patients (median age 72 years (IQR = 69-74)) - 40 were sulfonylurea-treated and 29 insulin-treated. In total, 781 low sensor glucose events (<4.0 mmol/L) were detected, of which 254 were very low sensor glucose events (<2.8 mmol/L). Twenty-six out of 29 insulin-treated (89.6%) and 36 out of 40 sulphonylurea-treated patients (90%) contributed to the 781 events of low sensor glucose. Twenty out of 29 insulin-treated (69%) and 26 out of 40 sulphonylurea-treated patients (65.0%) contributed to the 254 very low sensor glucose events. Only 9% of all events were identified by patients. Nocturnal events represented 55.8% of low sensor glucose events and 61.0% of very low sensor glucose events. At a cut-off of <2.8 mmol/L, it was found that the insulin group had a significantly greater number of such events as compared to the sulfonylurea group., Conclusions: This study demonstrates that elderly patients with tightly-controlled T2D have a significant number of low sensor glucose events which go by undetected.

Purpose: To explore the differential diagnosis of salivary gland tumors by multimodal ultrasound and to establish a preliminary scoring system by assigning meaningful parameters., Methods: Seventy-seven tumors from 69 patients with salivary gland tumors were examined by two-dimensional gray-scale ultrasound, color Doppler flow imaging (CDFI), superb microvascular imaging(SMI), real time tissue elastography(RTE) and acoustic radiation force impulse (ARFI). Different scoring schemes were obtained for the assignment and combination of meaningful parameters. The ROC curve of each scheme was drawn, and the one with the largest area under the curve was taken as the best scoring scheme. SPSS 25.0 software package was used for statistical analysis of the data., Results: There were significant differences in tumor shape, boundary, posterior echo, blood flow resistance index, RTE grade and ARFI average value between benign and malignant salivary gland tumors(P<0.05). The scoring scheme 7, which was composed of the above 6 parameters, was the best scoring scheme. When each parameter was assigned a score of 1, the total score was 6, and the area under the curve was 0.944. The sensitivity, specificity and accuracy of distinguishing benign and malignant salivary gland tumors with ≥4 points were 80.0%, 98.4% and 94.8%, respectively., Conclusions: Application of multimodal ultrasound and establishment of a scoring system can effectively improve the ability of ultrasound in the differential diagnosis of benign and malignant salivary gland tumors.

Background: The clinical utility of malignant pleural effusion (MPE) to detect mutation has been well documented; however, routine practice of the use of MPE involves collection of the cell pellet to detect mutation, and limited studies have interrogated the MPE supernatant as an alternative source of tumor-derived DNA for mutation profiling. In this study, we investigated the potential of MPE supernatant as a liquid biopsy specimen by comparing its mutation profile with that of matched MPE cell pellets, tissue, and plasma samples., Methods: Sequencing data from 17 patients with matched lung tissue, plasma, and MPE samples were retrospectively analyzed. Capture-based targeted sequencing was performed on matched plasma and MPE supernatant samples obtained from 154 patients with advanced lung adenocarcinoma., Results: MPE supernatants had significantly higher median maximum allelic fractions (maxAFs) than their corresponding cell pellets (P = 0.008) and plasma samples (P = 0.036), and a comparable maxAF value to that of tissue samples (P = 0.675). Comparison of MPE supernatant and matched plasma samples from the larger cohort (n = 154) revealed a comparable mutation detection rate; however, MPE supernatant had a significantly higher median maxAF than plasma (20.3% vs. 1.13%; P < 0.001). Furthermore, the concordance rates between MPE supernatant and plasma for single-nucleotide and copy number variations were 56% and 18%, respectively, suggesting that MPE supernatant reveals a more comprehensive mutation spectrum, particularly for copy number variations., Conclusion: Overall, our study shows that MPE supernatant is an optimal alternative source of tumor-derived DNA for comprehensive mutation profiling., (© 2019 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

The binding of PRDM9 to chromatin is a key step in the induction of DNA double-strand breaks associated with meiotic recombination hotspots; it is normally expressed solely in germ cells. We interrogated 1879 cancer samples in 39 different cancer types and found that PRDM9 is unexpectedly expressed in 20% of these tumors even after stringent gene homology correction. The expression levels of PRDM9 in tumors are significantly higher than those found in healthy neighboring tissues and in healthy nongerm tissue databases. Recurrently mutated regions located within 5 Mb of the PRDM9 loci, as well as differentially expressed genes in meiotic pathways, correlate with PRDM9 expression. In samples with aberrant PRDM9 expression, structural variant breakpoints frequently neighbor the DNA motif recognized by PRDM9, and there is an enrichment of structural variants at sites of known meiotic PRDM9 activity. This study is the first to provide evidence of an association between aberrant expression of the meiosis-specific gene PRDM9 with genomic instability in cancer., (© 2018 Ang Houle et al.; Published by Cold Spring Harbor Laboratory Press.)

Recombination promotes genomic integrity among cells and tissues through double-strand break repair, and is critical for gamete formation and fertility through a strict regulation of the molecular mechanisms associated with proper chromosomal disjunction. In humans, congenital defects and recurrent structural abnormalities can be attributed to aberrant meiotic recombination. Moreover, mutations affecting genes involved in recombination pathways are directly linked to pathologies including infertility and cancer. Recombination is among the most prominent mechanism shaping genome variation, and is associated with not only the structuring of genomic variability, but is also tightly linked with the purging of deleterious mutations from populations. Together, these observations highlight the multiple roles of recombination in human genetics: its ability to act as a major force of evolution, its molecular potential to maintain genome repair and integrity in cell division and its mutagenic cost impacting disease evolution.This article is part of the themed issue 'Evolutionary causes and consequences of recombination rate variation in sexual organisms'., (© 2017 The Author(s).)

Pleiotrophin (PTN) is a growth factor with both pro-angiogenic and limited pro-tumorigenic activity. We evaluated the potential for PTN to be used for safe angiogenic gene therapy using the full length gene and a truncated gene variant lacking the domain implicated in tumorigenesis. Mouse myoblasts were transduced to express full length or truncated PTN (PTN or T-PTN), along with a LacZ reporter gene, and injected into mouse limb muscle and myocardium. In cultured myoblasts, PTN was expressed and secreted via the Golgi apparatus, but T-PTN was not properly secreted. Nonetheless, no evidence of uncontrolled growth was observed in cells expressing either form of PTN. PTN gene delivery to myocardium, and non-ischemic skeletal muscle, did not result in a detectable change in vascularity or function. In ischemic hindlimb at 14 days post-implantation, intramuscular injection with PTN-expressing myoblasts led to a significant increase in skin perfusion and muscle arteriole density. We conclude that (1) delivery of the full length PTN gene to muscle can be accomplished without tumorigenesis, (2) the truncated PTN gene may be difficult to use in a gene therapy context due to inefficient secretion, (3) PTN gene delivery leads to functional benefit in the mouse acute ischemic hindlimb model.

Objectives: Pediatric myocarditis is a known cause of dilated cardiomyopathy and is associated with significant mortality. Our primary objective was to describe the frequency of presenting symptoms, signs, and investigation results among children diagnosed with acute myocarditis. Our secondary objective was to review these patients' initial diagnoses by the emergency physicians., Methods: This was a retrospective chart review of all patients younger than 16 years who were diagnosed with acute myocarditis in our hospital over a 10-year period (January 2001 to December 2010). The symptoms and signs were stratified according to age (infants, 1-5 years, 6 years or older)., Results: Thirty-nine children met the search criteria, of whom 10 patients (25.6%) were definite cases proven by myocardial biopsy. The average age was 5.4 years (SD, 4.3 years). The most common symptom complex was that of hypoperfusion (61.5%), which consisted of lethargy (53.8%), syncope (23.1%), and seizure (23.1%). Only 4 patients had cardiac symptoms, and all were older than 6 years old. Hepatomegaly was present in 16 patients (41.0%), whereas gallop rhythm or cardiac murmur was heard only in 5 patients (12.8%), Chest radiographs showed abnormalities in only 21 cases (53.8%), whereas all had abnormal electrocardiogram findings. Fifteen cases (38.5%) were diagnosed correctly at initial presentation, whereas the most common misdiagnosis was that of respiratory tract infections (20.5%)., Conclusions: Pediatric myocarditis rarely presents with specific cardiac symptoms in the younger population. Any child with symptoms and signs of hypoperfusion, especially unexplained seizure or syncope, should have an electrocardiogram performed.

Mycobacteriophages are viruses that infect mycobacterial hosts such as Mycobacterium smegmatis and Mycobacterium tuberculosis. All mycobacteriophages characterized to date are dsDNA tailed phages, and have either siphoviral or myoviral morphotypes. However, their genetic diversity is considerable, and although sixty-two genomes have been sequenced and comparatively analyzed, these likely represent only a small portion of the diversity of the mycobacteriophage population at large. Here we report the isolation, sequencing and comparative genomic analysis of 18 new mycobacteriophages isolated from geographically distinct locations within the United States. Although no clear correlation between location and genome type can be discerned, these genomes expand our knowledge of mycobacteriophage diversity and enhance our understanding of the roles of mobile elements in viral evolution. Expansion of the number of mycobacteriophages grouped within Cluster A provides insights into the basis of immune specificity in these temperate phages, and we also describe a novel example of apparent immunity theft. The isolation and genomic analysis of bacteriophages by freshman college students provides an example of an authentic research experience for novice scientists.