Long-read sequencing identifies novel structural variations in colorectal cancer.

Structural variations (SVs) are a key type of cancer genomic alterations, contributing to oncogenesis and progression of many cancers, including colorectal cancer (CRC). However, SVs in CRC remain difficult to be reliably detected due to limited SV-detection capacity of the commonly used short-read sequencing. This study investigated the somatic SVs in 21 pairs of CRC samples by Nanopore whole-genome long-read sequencing. 5200 novel somatic SVs from 21 CRC patients (494 SVs / patient) were identified. A 4.9-Mbp long inversion that silences APC expression (confirmed by RNA-seq) and an 11.2-kbp inversion that structurally alters CFTR were identified. Two novel gene fusions that might functionally impact the oncogene RNF38 and the tumor-suppressor SMAD3 were detected. RNF38 fusion possesses metastasis-promoting ability confirmed by in vitro migration and invasion assay, and in vivo metastasis experiments. This work highlighted the various applications of long-read sequencing in cancer genome analysis, and shed new light on how somatic SVs structurally alter critical genes in CRC. The investigation on somatic SVs via nanopore sequencing revealed the potential of this genomic approach in facilitating precise diagnosis and personalized treatment of CRC.

Recent advances of engineered oncolytic viruses-based combination therapy for liver cancer.

Liver cancer is a major malignant tumor, which seriously threatens human health and increases the economic burden on patients. At present, gene therapy has been comprehensively studied as an excellent therapeutic measure in liver cancer treatment. Oncolytic virus (OV) is a kind of virus that can specifically infect and kill tumor cells. After being modified by genetic engineering, the specificity of OV infection to tumor cells is increased, and its influence on normal cells is reduced. To date, OV has shown its effectiveness and safety in experimental and clinical studies on a variety of tumors. Thus, this review primarily introduces the current status of different genetically engineered OVs used in gene therapy for liver cancer, focuses on the application of OVs and different target genes for current liver cancer therapy, and identifies the problems encountered in OVs-based combination therapy and the corresponding solutions, which will provide new insights into the treatment of liver cancer.

PD-L2 mediates tobacco smoking-induced recruitment of regulatory T cells via the RGMB/NFκB/CCL20 cascade.

Programmed cell death ligand 2 (PD-L2), a ligand for the receptor programmed cell death 1 (PD-1), has an identity of 34% with its twin ligand PD-L1 and exhibits higher binding affinity with PD-1 than PD-L1. However, the role of PD-L2 in non-small cell lung cancer (NSCLC) progression, especially tobacco-induced cancer progression, has not been fully understood. Here, we found that PD-L2 promoted tumor growth in murine models with recruitment of regulatory T cells (Tregs). In patients with NSCLC, PD-L2 expression level in tumor samples was higher than in counterpart normal controls and was positively associated with patients' response to anti-PD-1 treatment. Mechanismly, PD-L2 bound its receptor Repulsive guidance molecule B (RGMB) on cancer cells and activated extracellular signal-regulated kinase (Erk) and nuclear factor κB (NFκB), leading to increased production of chemokine CCL20, which recruited Tregs and contributed to NSCLC progression. Consistently, knockdown of RGMB or NFκB p65 inhibited PD-L2-induced CCL20 production, and silencing of PD-L2 repressed Treg recruitment by NSCLC cells. Furthermore, cigarette smoke and carcinogen benzo(a)pyrene (BaP) upregulated PD-L2 in lung epithelial cells via aryl hydrocarbon receptor (AhR)-mediated transcription activation, whose deficiency markedly suppressed BaP-induced PD-L2 upregulation. These results suggest that PD-L2 mediates tobacco-induced recruitment of Tregs via the RGMB/NFκB/CCL20 cascade, and targeting this pathway might have therapeutic potentials in NSCLC.

Efficacy of Acupuncture for Chronic Spontaneous Urticaria : A Randomized Controlled Trial.

BACKGROUND: The effectiveness of acupuncture for patients with chronic spontaneous urticaria (CSU), reported in a few small-scale studies, is not convincing. OBJECTIVE: To investigate whether acupuncture leads to better effects on CSU than sham acupuncture or waitlist control. DESIGN: A multicenter, randomized, sham-controlled trial. (Chinese Clinical Trial Registry: ChiCTR1900022994). SETTING: Three teaching hospitals in China from 27 May 2019 to 30 July 2022. PARTICIPANTS: 330 participants diagnosed with CSU. INTERVENTION: Participants were randomly assigned in a 1:1:1 ratio to receive acupuncture, sham acupuncture, or waitlist control over an 8-week study period (4 weeks for treatment and another 4 weeks for follow-up). MEASUREMENTS: The primary outcome was the mean change from baseline in the Weekly Urticaria Activity Score (UAS7) at week 4. Secondary outcomes included itch severity scores, self-rated improvement, and Dermatology Life Quality Index scores. RESULTS: The mean change in UAS7 (range, 0 to 42) for acupuncture from baseline (mean score, 23.5 [95% CI, 21.8 to 25.2]) to week 4 (mean score, 15.3 [CI, 13.6 to 16.9]) was -8.2 (CI, -9.9 to -6.6). The mean changes in UAS7 for sham acupuncture and waitlist control from baseline (mean scores, 21.9 [CI, 20.2 to 23.6] and 22.1 [CI, 20.4 to 23.8], respectively) to week 4 (mean scores, 17.8 [CI, 16.1 to 19.5] and 20.0 [CI, 18.3 to 21.6], respectively) were -4.1 (CI, -5.8 to -2.4) and -2.2 (CI, -3.8 to -0.5), respectively. The mean differences between acupuncture and sham acupuncture and waitlist control were -4.1 (CI, -6.5 to -1.8) and -6.1 (CI, -8.4 to -3.7), respectively, which did not meet the threshold for minimal clinically important difference. Fifteen participants (13.6%) in the acupuncture group and none in the other groups reported adverse events. Adverse events were mild or transient. LIMITATION: Lack of complete blinding, self-reported outcomes, limited generalizability because antihistamine use was disallowed, and short follow-up period. CONCLUSION: Compared with sham acupuncture and waitlist control, acupuncture produced a greater improvement in UAS7, although the difference from control was not clinically significant. Increased adverse events were mild or transient. PRIMARY FUNDING SOURCE: The National Key R&D Program of China and the Science and Technology Department of Sichuan Province.

Association of High Body Mass Index With Postoperative Complications After Chest Masculinization Surgery.

PURPOSE: Body mass index (BMI) requirements for transgender and nonbinary patients undergoing chest masculinization surgery (CMS) are not standardized and based on small sample sizes. This is the largest and first national retrospective study to determine the association between BMI and postoperative complications. METHODS: The National Surgical Quality Improvement Program 2012-2020 was queried for CMS patients. The primary outcome was incidence of at least one complication within 30 days. Secondary outcomes were incidence of major and minor complications. Body mass index (in kilograms per square meter) was categorized as category 0 (<30), 1 (30-34.9), 2 (35-39.9), 3 (40-44.9), 4 (45-49.9), and 5 (≥50). Logistic regression was used to evaluate the association between BMI and outcomes. RESULTS: Of 2317 patients, median BMI was 27.4 kg/m 2 (interquartile range, 23.4-32.2 kg/m 2 ). Body mass index range was 15.6 to 64.9 kg/m 2 . While increasing BMI was significantly associated with greater odds of at least one complication, no patients experienced severe morbidity, regardless of BMI. Patients with BMI ≥50 kg/m 2 had an adjusted odds ratio [aOR, 95% confidence interval (CI)] of 3.63 (1.02-12.85) and 36.62 (2.96->100) greater odds of at least one complication and urinary tract infection compared with nonobese patients, respectively. Patients with BMI ≥35 kg/m 2 had an adjusted odds ratio (95% CI) of 5.06 (1.5-17.04) and 5.13 (1.89-13.95) greater odds of readmission and surgical site infection compared with nonobese patients, respectively. CONCLUSIONS: Chest masculinization surgery in higher BMI patients is associated with greater odds of unplanned readmission. Given the low risk for severe complications in higher BMI individuals, we recommend re-evaluation of BMI cutoffs for CMS patients.

Breast Surgery in Adolescents: Cisgender Breast Reduction Versus Transgender and Nonbinary Chest Masculinization.

PURPOSE: Both breast reduction surgery (BRS) in adolescent girls and chest masculinization surgery (CMS) transgender and nonbinary (TGNB) individuals improve physical discomfort and psychological well-being. Nonetheless, CMS in adolescents is highly contested due to concerns regarding safety and capacity for consent. Here, we compare both procedures to quantify trends in incidence, minimum age, and surgical outcomes. METHODS: The National Surgical Quality Improvement Program database was queried from 2018 to 2021 for cisgender and TGNB adolescents 18 years or younger who underwent BRS or CMS. Our primary outcome was the incidence of postoperative complications within 30 days of surgery. Multivariate logistic regression was performed to determine if CMS was associated with postoperative complications. RESULTS: Of 2504 adolescents, the majority (n = 2186 [87.3%]) were cisgender female patients who underwent BRS, compared with TGNB adolescents (n = 318 [12.7%]) who underwent CMS. BRS patients were younger at time of surgery (mean [SD] 16.7 [1.2], 17.5 [0.9]; P < 0.001). The minimum age for BRS was consistently 2 to 3 years younger than that for CMS (12.1 to 12.6 years vs 14.0 to 15.1 years). A comparable frequency of BRS and CMS patients developed 1 or more complications within 30 days of surgery (n = 98 [4.5%], n = 13 [4.1%]; P = 0.775). CONCLUSION: Cisgender female adolescents undergo breast surgery at a 7-fold rate compared with TGNB adolescents and do so at significantly younger ages. Given the favorable effects of BRS and CMS on psychosocial well-being and their comparable surgical risk of complications, our data help recontextualize the concerns surrounding adolescent CMS.

Traumatic Brain Injury and Its Association With Orbital Fracture Characteristics and Repair.

Traumatic brain injury (TBI) is common in up to 50% of patients with facial fractures. Orbital fractures account for 25% of all facial fractures. The authors sought to determine the prevalence and risk factors for TBI in patients undergoing orbital fracture repair (OFR) and assess the impact of TBI on surgical timing. A retrospective review of trauma patients who underwent OFR at a single trauma center from 2015 to 2020 was conducted. Excluded were patients <18 years old and those with unreported GCS on presentation. TBI was defined as GCS <15 or any neurological symptom on presentation. TBI was categorized into mild (GCS=14-15), moderate (GCS=9-13), and severe TBI (GCS=3-8). Our primary and secondary outcomes were the prevalence of TBI on presentation and duration from injury to surgery, respectively. Of the 200 patients analyzed, 99 (49.5%) had concomitant TBI on presentation. The most common neurological symptom on presentation was loss of consciousness [n=80 (40%)]. Patients with TBI were significantly more likely to have an orbital roof [n=11 (11.1%), n=4 (4.0%), P=0.048] and lateral wall fractures [n=25 (25.3%), n=14 (13.9%), P=0.031] compared with patients without TBI. Patients with severe TBI were more likely to have delayed OFR-a significantly greater proportion of patients who had severe TBI had OFR after 60 days of injury compared with those without TBI or with mild TBI [5 (39%), 12 (12%), 4 (5%), P=0.032]. Craniofacial surgeons must suspect and screen for TBI in patients presenting with facial trauma, especially those with orbital roof and lateral wall fractures.

Traumatic Brain Injury in Patients With Frontal Sinus Fractures.

Traumatic brain injury (TBI) is an insult to the brain from an external mechanical force that may lead to short or long-term impairment. Traumatic brain injury has been reported in up to 83% of craniofacial fractures involving the frontal sinus. However, the risk factors for TBI at presentation and persistent neurological sequelae in patients with frontal sinus fractures remain largely unstudied. The authors aim to evaluate the prevalence and risk factors associated with TBI on presentation and neurological sequelae in these patients. The authors retrospectively reviewed patients who presented with traumatic frontal sinus fractures in 2019. The authors' primary outcome was the prevalence of concomitant TBI on presentation, which authors defined as any patient with neurological symptoms/signs on presentation and/or patients with a Glasgow Coma Scale <15 with no acute drug or alcohol intoxication or history of dementia or other neurocognitive disorder. The authors' secondary outcome was the incidence of neurological sequelae after 1 month of injury. Bivariate analysis and multivariate logistic regression were performed. A total of 56 patients with frontal sinus fractures were included. Their median (interquartile range) age was 47 (31-59) years, and the median (interquartile range) follow-up was 7.3 (1.3-76.5) weeks. The majority were males [n = 48 (85.7%)] and non-Hispanic whites [n = 35 (62.5%)]. Fall was the most common mechanism of injury [n = 15 (26.8%)]. Of the 56 patients, 46 (82.1%) had concomitant TBI on presentation. All patients who had combined anterior and posterior table frontal sinus fractures [n = 37 (66.1%)] had TBI on presentation. These patients had 13 times the odds of concomitant TBI on presentation [adjusted odds ratio (95% CI): 12.7 (2.3-69.0)] as compared with patients with isolated anterior or posterior table fractures. Of 34 patients who were followed up more than 1 month after injury, 24 patients (70.6%) had persistent neurological sequelae, most commonly headache [n = 16 (28.6%)]. Patients who had concomitant orbital roof fractures had 32 times the odds of neurological sequelae after 1 month of injury [adjusted odds ratio (95% CI): 32 (2.4->100)]. Emergency physicians and referring providers should maintain a high degree of suspicion of TBI in patients with frontal sinus fractures. Head computed tomography at presentation and close neurological follow-up are recommended for patients with frontal sinus fracture with combined anterior and posterior table fractures, as well as those with concomitant orbital roof fractures.

The Association Between Craniofacial Fracture Patterns and Traumatic Optic Neuropathy.

Traumatic optic neuropathy (TON) is a rare but potentially devastating complication of craniofacial trauma. Approximately half of patients with TON sustain permanent vision loss. In this study, we sought to identify the most common fracture patterns associated with TON. We performed a retrospective review of craniomaxillofacial CT scans of trauma patients who presented to the R Adams Cowley Shock Trauma Center from 2015 to 2017. Included were adult patients who had orbital fractures with or without other facial fractures. Patients diagnosed with TON by a formal ophthalmologic examination were analyzed. Craniofacial fracture patterns were identified. Bivariate analysis and multivariate logistic regression were performed to identify craniofacial fracture patterns most commonly associated with TON. A total of 574 patients with orbital fractures who met inclusion criteria [15 (2.6%)] were diagnosed with TON. The median [interquartile range (IQR)] age was 44 (28-59) years. Patients with optic canal fractures and sphenoid sinus fractures had greater odds of TON compared with patients who did not have these fracture types [adjusted odds ratio (aOR) 95% confidence interval (CI) 31.8 (2.6->100), 8.1 (2.7-24.4), respectively]. Patients who sustain optic canal and sphenoid sinus fractures in the setting of blunt facial trauma are at increased odds of having a TON. Surgeons and other physicians involved in the care of these patients should be aware of this association.

Orbital Fracture Characteristics and Outcomes in Baltimore.

Fracture characteristics and postoperative outcomes of patients presenting with orbital fractures in Baltimore remain poorly investigated. The purpose of our study was to determine the fracture patterns, etiologies, and postoperative outcomes of patients treated for orbital fractures at 2 level I trauma centers in Baltimore. A retrospective cohort study was conducted on patients who underwent orbital fracture repair at the R Adams Cowley Shock Trauma Center and the Johns Hopkins Hospital from January 2015 to December 2019. Of 374 patients, 179 (47.9%) had orbital fractures due to violent trauma, 252 (67.4%) had moderate to near-total orbital fractures, 345 (92.2%) had orbital floor involvement, and 338 (90.4%) had concomitant neurological symptoms/signs. Almost half of the patients had at least one postoperative ocular symptom/sign [n = 163/333 (48.9%)]. Patients who had orbital fractures due to violent trauma were more likely to develop postoperative ocular symptoms/signs compared with those who had orbital fractures due to nonviolent trauma [n = 88/154 (57.1%), n = 75/179 (41.9%); P = 0.006]. After controlling for factors pertaining to injury severity, there was no significant difference in patient throughput or incidence of any postoperative ocular symptom/sign after repair between the two centers. Timely management of patients with orbital fractures due to violent trauma is crucial to mitigate the risk of postoperative ocular symptoms/signs.

Patient-Specific Implant Customization for Treatment of Internal Orbital Fractures Using Office-Based Three-Dimensional Printing.

OBJECTIVE: Three-dimensional (3D) modeling technology aids the reconstructive surgeon in designing and tailoring individualized implants for the reconstruction of complex craniofacial fractures. Three-dimensional modeling and printing have traditionally been outsourced to commercial vendors but can now be incorporated into both private and academic craniomaxillofacial practices. The goal of this report is to present a low-cost, standardized office-based workflow for restoring bony orbital volume in traumatic orbital fractures. METHODS: Patients with internal orbital fractures requiring open repair were identified. After the virtual 3D models were created by iPlan 3.0 Cranial CMF software (Brainlab), the models were printed using an office-based 3D printer to shape and modify orbital plates to correctly fit the fracture defect. The accuracy of the anatomic reduction and the restored bony orbital volume measurements were determined using postoperative computed tomography images and iPlan software. RESULTS: Nine patients fulfilled the inclusion criteria: 8 patients had unilateral fractures and 1 patient had bilateral fractures. Average image processing and print time were 1.5 hours and 3 hours, respectively. The cost of the 3D printer was $2500 and the average material cost to print a single orbital model was $2. When compared with the uninjured side, the mean preoperative orbital volume increase and percent difference were 2.7 ± 1.3 mL and 10.9 ± 5.3%, respectively. Postoperative absolute volume and percent volume difference between the orbits were -0.2 ± 0.4 mL and -0.8 ± 1.7%, respectively. CONCLUSIONS: Office-based 3D printing can be routinely used in the repair of internal orbital fractures in an efficient and cost-effective manner to design the implant with satisfactory patient outcomes.

Expansion of GGC Repeat in GIPC1 Is Associated with Oculopharyngodistal Myopathy.

Oculopharyngodistal myopathy (OPDM) is an adult-onset inherited neuromuscular disorder characterized by progressive ptosis, external ophthalmoplegia, and weakness of the masseter, facial, pharyngeal, and distal limb muscles. The myopathological features are presence of rimmed vacuoles (RVs) in the muscle fibers and myopathic changes of differing severity. Inheritance is variable, with either putative autosomal-dominant or autosomal-recessive pattern. Here, using a comprehensive strategy combining whole-genome sequencing (WGS), long-read whole-genome sequencing (LRS), linkage analysis, repeat-primed polymerase chain reaction (RP-PCR), and fluorescence amplicon length analysis polymerase chain reaction (AL-PCR), we identified an abnormal GGC repeat expansion in the 5' UTR of GIPC1 in one out of four families and three sporadic case subjects from a Chinese OPDM cohort. Expanded GGC repeats were further confirmed as the cause of OPDM in an additional 2 out of 4 families and 6 out of 13 sporadic Chinese individuals with OPDM, as well as 7 out of 194 unrelated Japanese individuals with OPDM. Methylation, qRT-PCR, and western blot analysis indicated that GIPC1 mRNA levels were increased while protein levels were unaltered in OPDM-affected individuals. RNA sequencing indicated p53 signaling, vascular smooth muscle contraction, ubiquitin-mediated proteolysis, and ribosome pathways were involved in the pathogenic mechanisms of OPDM-affected individuals with GGC repeat expansion in GIPC1. This study provides further evidence that OPDM is associated with GGC repeat expansions in distinct genes and highly suggests that expanded GGC repeat units are essential in the pathogenesis of OPDM, regardless of the genes in which the expanded repeats are located.

Machine learning-based establishment and validation of age-related patterns for predicting prognosis in non-small cell lung cancer within the context of the tumor microenvironment.

Lung cancer (LC) is a leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for over 80% of cases. The impact of aging on clinical outcomes in NSCLC remains poorly understood, particularly with respect to the immune response. In this study, we explored the effects of aging on NSCLC using 307 genes associated with human aging from the Human Ageing Genomic Resources. We identified 53 aging-associated genes that significantly correlate with overall survival of NSCLC patients, including the clinically validated gene BUB1B. Furthermore, we developed an aging-associated enrichment score to categorize patients based on their aging subtypes and evaluated their prognostic and therapeutic response values in LC. Our analyses yielded two aging-associated subtypes with unique profiles in the tumor microenvironment, demonstrating varying responses to immunotherapy. Consensus clustering based on transcriptome profiles provided insights into the effects of aging on NSCLC and highlighted the potential of personalized therapeutic approaches tailored to aging subtypes. Our findings provide a new target and theoretical support for personalized therapeutic approaches in patients with NSCLC, offering insights into the potential impact of aging on cancer outcomes.

Expression profiles and functional prediction of histone acetyltransferases of the MYST family in kidney renal clear cell carcinoma.

BACKGROUND: Histone acetyltransferases (HATs) of the MYST family are associated with a variety of human cancers. However, the relationship between MYST HATs and their clinical significance in kidney renal clear cell carcinoma (KIRC) has not yet been evaluated. METHODS: The bioinformatics method was used to investigate the expression patterns and prognostic value of MYST HATs. Western blot was used to detect the expression of MYST HATs in KIRC. RESULTS: The expression levels of MYST HATs except KAT8 (KAT5, KAT6A, KAT6B, and KAT7) were significantly reduced in KIRC tissues compared to normal renal tissues, and the western blot results of the KIRC samples also confirmed the result. Reduced expression levels of MYST HATs except KAT8 were significantly associated with high tumor grade and advanced TNM stage in KIRC, and showed a significant association with an unfavorable prognosis in patients with KIRC. We also found that the expression levels of MYST HATs were closely related to each other. Subsequently, gene set enrichment analysis showed that the function of KAT5 was different from that of KAT6A, KAT6B and KAT7. The expression levels of KAT6A, KAT6B and KAT7 had significant positive correlations with cancer immune infiltrates such as B cells, CD4+ T cells and CD8+ T cells. CONCLUSIONS: Our results indicated that MYST HATs, except KAT8, play a beneficial role in KIRC.

Single-cell RNA-seq analysis of mouse preimplantation embryos by third-generation sequencing.

The development of next generation sequencing (NGS) platform-based single-cell RNA sequencing (scRNA-seq) techniques has tremendously changed biological researches, while there are still many questions that cannot be addressed by them due to their short read lengths. We developed a novel scRNA-seq technology based on third-generation sequencing (TGS) platform (single-cell amplification and sequencing of full-length RNAs by Nanopore platform, SCAN-seq). SCAN-seq exhibited high sensitivity and accuracy comparable to NGS platform-based scRNA-seq methods. Moreover, we captured thousands of unannotated transcripts of diverse types, with high verification rate by reverse transcription PCR (RT-PCR)-coupled Sanger sequencing in mouse embryonic stem cells (mESCs). Then, we used SCAN-seq to analyze the mouse preimplantation embryos. We could clearly distinguish cells at different developmental stages, and a total of 27,250 unannotated transcripts from 9,338 genes were identified, with many of which showed developmental stage-specific expression patterns. Finally, we showed that SCAN-seq exhibited high accuracy on determining allele-specific gene expression patterns within an individual cell. SCAN-seq makes a major breakthrough for single-cell transcriptome analysis field.

Fluorescence detection of 4-nitrophenol and α-glucosidase activity based on 4-nitrophenol-regulated fluorescence of silicon nanoparticles.

A fluorescence assay for the detection of 4-nitrophenol (4-NP), α-glucosidase (α-Glu) activity and α-Glu inhibitors (AGIs) is developed based on the inner filter effect (IFE), a flexible and simple signal transfer strategy. In this assay, silicon nanoparticles (Si NPs) synthesized under mild and easily accessible conditions are employed as fluorescent indicators. 4-NP efficaciously quenches the fluorescence of Si NPs through the IFE at a very rapid rate, thus achieving 4-NP detection in a mix-to-read manner, which is suitable for on-site detection. The quenching mechanism has been comprehensively studied and confirmed. More significantly, based on the fact that 4-NP can be generated through α-Glu-catalyzed hydrolysis of 4-nitrophenyl-α-D-glucopyranoside (NPG), the fluorescence detection of α-Glu activity is legitimately achieved by employing NPG as the substrate. The linear ranges for 4-NP and α-Glu activity detection are 0.5-60 µM and 0.5-60 mU mL-1 with low detection limits of 0.074 µM and 0.094 mU mL-1, respectively. This method not only can preciously assay targets in real samples, but is also capable of screening AGIs as drugs as well as assessing their inhibition efficiency.

Long noncoding RNA LINC01088 inhibits esophageal squamous cell carcinoma progression by targeting the NPM1-HDM2-p53 axis.

Esophageal squamous cell carcinoma (ESCC) is characterized by extensive metastasis and poor prognosis. Long noncoding RNAs (lncRNAs) have been shown to play important roles in ESCC. However, the specific roles of lncRNAs in ESCC tumorigenesis and metastasis remain largely unknown. Here, we investigate LINC01088 in ESCC. Differentially expressed LINC01088 levels are screened from the GEO database. We find that LINC01088 is expressed at low level in collected clinical samples and is correlated with vascular tumor emboli and poor overall survival time of patients after surgery. LINC01088 inhibits not only ESCC cell migration and invasion in vitro, but also tumorigenesis and metastasis in vivo. Mechanistically, LINC01088 directly interacts with nucleophosmin (NPM1) and increases the expression of NPM1 in the nucleoplasm compared to that in the nucleolar region. LINC01088 decreases mutant p53 (mut-p53) expression and rescues the transcriptional activity of p53 by targeting the NPM1-HDM2-p53 axis. LINC01088 may also interfere with the DNA repair function of NPM1 by affecting its translocation. Our results highlight the potential of LINC01088 as a prognostic biomarker and therapeutic target of ESCC.

Perception of the Virtual Interview Format in Hand Surgery Fellowship Applicants.

PURPOSE: The Coronavirus disease 2019 pandemic occurred during the interview period for numerous surgical fellowships, resulting in most programs transitioning to a virtual interview format during the 2020-2021 application cycle. This study investigated modifications adopted by fellowship programs and perceptions of the virtual interview format among hand surgery fellowship applicants. METHODS: Voluntary, anonymous online surveys were emailed to all applicants to the Johns Hopkins hand surgery fellowship during the 2020-2021 interview cycle. The surveys were released after the rank order list certification deadline on May 6, 2021, and closed on May 18, 2021, before the match results were released. Descriptive statistics based on the overall cohort and primary outcome of an applicant's willingness to recommend virtual interviews in the future were conducted. RESULTS: Thirty-four of 112 (30.4%) applicants completed their surveys. Twenty-seven (79.4%) survey respondents recommended the virtual interview format in the future and 7 (20.6%) did not. Applicants who recommended virtual interviews were similar to those who did not on the basis of the number of interviews received and taken, information provided by programs, and self-rated competency with the virtual interview format. Those who recommended virtual interviews rated the effectiveness of self-advocacy higher compared with those who did not. All respondents agreed that cost savings and scheduling were more effective with virtual interviews. Perceived weaknesses differed between the 2 groups and included the lack of physical tour, difficulty with self-advocacy, and technical difficulties. The majority of survey respondents preferred in-person interviews before the interview cycle (n = 32, 94.1%), whereas nearly half of survey respondents preferred virtual interviews after the interview cycle (n = 16, 47.1%). CONCLUSIONS: Nearly 80% of survey respondents recommended virtual interviews in the future. Major benefits included effectiveness of scheduling and cost savings. CLINICAL RELEVANCE: Virtual interviews may be considered as an alternative or adjunct to in-person hand surgery fellowship interviews in the future.

Smart Transportation: An Overview of Technologies and Applications.

As technology continues to evolve, our society is becoming enriched with more intelligent devices that help us perform our daily activities more efficiently and effectively. One of the most significant technological advancements of our time is the Internet of Things (IoT), which interconnects various smart devices (such as smart mobiles, intelligent refrigerators, smartwatches, smart fire alarms, smart door locks, and many more) allowing them to communicate with each other and exchange data seamlessly. We now use IoT technology to carry out our daily activities, for example, transportation. In particular, the field of smart transportation has intrigued researchers due to its potential to revolutionize the way we move people and goods. IoT provides drivers in a smart city with many benefits, including traffic management, improved logistics, efficient parking systems, and enhanced safety measures. Smart transportation is the integration of all these benefits into applications for transportation systems. However, as a way of further improving the benefits provided by smart transportation, other technologies have been explored, such as machine learning, big data, and distributed ledgers. Some examples of their application are the optimization of routes, parking, street lighting, accident prevention, detection of abnormal traffic conditions, and maintenance of roads. In this paper, we aim to provide a detailed understanding of the developments in the applications mentioned earlier and examine current researches that base their applications on these sectors. We aim to conduct a self-contained review of the different technologies used in smart transportation today and their respective challenges. Our methodology encompassed identifying and screening articles on smart transportation technologies and its applications. To identify articles addressing our topic of review, we searched for articles in the four significant databases: IEEE Xplore, ACM Digital Library, Science Direct, and Springer. Consequently, we examined the communication mechanisms, architectures, and frameworks that enable these smart transportation applications and systems. We also explored the communication protocols enabling smart transportation, including Wi-Fi, Bluetooth, and cellular networks, and how they contribute to seamless data exchange. We delved into the different architectures and frameworks used in smart transportation, including cloud computing, edge computing, and fog computing. Lastly, we outlined current challenges in the smart transportation field and suggested potential future research directions. We will examine data privacy and security issues, network scalability, and interoperability between different IoT devices.

The effects of extra virgin olive oil or butter on cardiovascular biomarkers in European and Chinese males in the UK: A pilot randomised crossover trial.

Purpose: No dietary interventional studies have reported the impact of olive oil on cardiovascular risk markers in groups of different ethnic origins. We report a pilot randomised controlled trial of an intervention supplementing extra virgin olive oil (EVOO) on markers of cardiovascular risk among East Asian Chinese, and European Caucasian individuals. Methods: A cross-over, randomised controlled dietary intervention for 2 weeks was undertaken. Thirty-two adults, healthy, individuals of Chinese and European origin took part in this study. 24-h ambulatory systolic and diastolic blood pressure (SBP, DBP), and blood lipids, were assessed. Results: Positive benefits of EVOO consumption were observed in all participants. Lower 24-h ambulatory SBP (-4.3 mmHg; p = 0.020), and day-time SBP (5.528 mmHg; p = 0.008), night-time DBP (-3.784 mmHg; p = 0.008) and night-time MAP (-3.747 mmHg; p = 0.007) were seen in all participants independently of covariates. In addition, total cholesterol (7.9 mg/dL; p = 0.017) and LDL-cholesterol (6.5 mg/dL; p = 0.028) were increased with butter but not with olive oil. No significant difference in other cardiovascular risk factors were observed. However, differences were observed between Caucasians and East Asian individuals in the absence of significant differences in lifestyle. Conclusion: This pilot study suggests that consumption of EVOO should be advocated as a healthier dietary fat and recommended to replace butter as a dietary strategy to improve cardiovascular health in both Caucasians and East Asian individuals.