Evidence for Admixture and Rapid Evolution During Glacial Climate Change in an Alpine Specialist.

The pace of current climate change is expected to be problematic for alpine flora and fauna, as their adaptive capacity may be limited by small population size. Yet, despite substantial genetic drift following post-glacial recolonization of alpine habitats, alpine species are notable for their success surviving in highly heterogeneous environments. Population genomic analyses demonstrating how alpine species have adapted to novel environments with limited genetic diversity remain rare, yet are important in understanding the potential for species to respond to contemporary climate change. In this study, we explored the evolutionary history of alpine ground beetles in the Nebria ingens complex, including the demographic and adaptive changes that followed the last glacier retreat. We first tested alternative models of evolutionary divergence in the species complex. Using millions of genome-wide SNP markers from hundreds of beetles, we found evidence that the N. ingens complex has been formed by past admixture of lineages responding to glacial cycles. Recolonization of alpine sites involved a distributional range shift to higher elevation, which was accompanied by a reduction in suitable habitat and the emergence of complex spatial genetic structure. We tested several possible genetic pathways involved in adaptation to heterogeneous local environments using genome scan and genotype-environment association approaches. From the identified genes, we found enriched functions associated with abiotic stress responses, with strong evidence for adaptation to hypoxia-related pathways. The results demonstrate that despite rapid demographic change, alpine beetles in the N. ingens complex underwent rapid physiological evolution.

Comprehensive analyses of a CD8+ T cell infiltration related gene signature with regard to the prediction of prognosis and immunotherapy response in lung squamous cell carcinoma.

Lung squamous cell carcinoma (LUSC) is associated with a worse prognosis than other histological subtypes of non-small cell lung cancer. Due to the vital role of CD8+ T cells in anti-tumor immunity, the characterization of CD8+ T cell infiltration-related (CTLIR) gene signature in LUSC is worthy of in-depth exploration. In our study, tumor tissues of LUSC patients from Renmin Hospital of Wuhan University were stained by multiplex immunohistochemistry to evaluate the density of infiltrated CD8+ T cells and explore the correlation with immunotherapy response. We found that the proportion of LUSC patients who responded to immunotherapy was higher in the high density of CD8+ T cell infiltration group than in the low density of CD8+ T cell infiltration group. Subsequently, we collected bulk RNA-sequencing data from The Cancer Genome Atlas (TCGA) database. The abundance of infiltrating immune cells in LUSC patients was analyzed by using CIBERSORT algorithm, and weighted correlation network analysis was performed to identify the co-expressed gene modules related to CD8+ T cells. We then developed a prognostic gene signature based on CD8+ T cell co-expressed genes and calculated the CTLIR risk score, which stratified LUSC patients into high-risk and low-risk groups. With univariate and multivariate analyses, the gene signature was identified as an independent prognostic factor in LUSC patients. The overall survival of LUSC patients in the high-risk group was significantly shorter than that of the low-risk group in the TCGA cohort, which was validated in Gene Expression Omnibus datasets. We analyzed immune cell infiltration in the tumor microenviroment and found fewer CD8+ T cells and more regulatory T cell infiltration in the high-risk group, which is characterized as an immunosuppressive phenotype. Furthermore, the LUSC patients in the high-risk group were predicted to have a better response to immunotherapy than those in the low-risk group when treated with PD-1 and CTLA4 inhibitors. In conclusion, we performed a comprehensive molecular analysis of the CTLIR gene signature in LUSC and constructed a risk model for LUSC patients to predict prognosis and immunotherapy response.

The effect of physical activity on sleep disturbance in various populations: a scoping review of randomized clinical trials.

BACKGROUND: Promoting physical activity (PA) in different populations experiencing sleep disturbance may increase population PA levels and improve sleep. This scoping review aimed to examine the effect of various PA intervention strategies on sleep across different populations, identify key sleep outcomes, and analyze knowledge gaps by mapping the relevant literature. METHODS: For this study, we systematically searched articles published till March 2022 from PubMed, Web of Science, Cochrane Library, and Embase databases for randomized clinical trials (RCTs) regarding the effect of physical activity on sleep. Two authors extracted key data and descriptively analyzed the data. Thematic analysis was used to categorize the results into themes by all authors. Arksey and O'Malley's scoping review framework was used to present the findings. RESULTS: Twenty-one randomized controlled trials out of 3052 studies were finally included with 3677 participants (2852 females (78%)). Five trials were conducted in healthy working-age adults with sleep disturbance but without the diagnosis of insomnia, five in healthy older adults, two in perinatal women, four in patients with cancer, three in mental illness related subjects, and another two in other disease-related areas. PA interventions were diverse, including walking, resistance training, aerobic exercise, housework, water exercise, basketball, smartphone/tablet "apps", web, online videos or wearable actigraphy, and self-determined exercise. Three major themes were identified: (1) Sleep environment may be important to address prior to instituting PA interventions, (2) All types of PA were effective for improving sleep in all populations studied, (3) Self-tolerated PA is safe for improving sleep in the elderly and in co-morbid or perinatal populations. CONCLUSIONS: PA is effective and safe for improving sleep in both healthy and co-morbid populations with sleep disturbance by increasing daily activity levels using a variety of strategies, even low intensity, such as housekeeping, sit-to-stand repetitions, along with encouraging PA through web pages, videos, and self-goal setting apps. In addition, this scoping review identifies the need for further therapeutic research and future exploration in populations with sleep initiation or sleep maintenance disturbance.

Development and evaluation of time-resolved fluorescent immunochromatographic assay for quantitative detection of SARS-CoV-2 spike antigen.

BACKGROUND: The spread of COVID-19 worldwide caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has necessitated efficient, sensitive diagnostic methods to identify infected people. We report on the development of a rapid 15-minute time-resolved fluorescent (TRF) lateral flow immunochromatographic assay for the quantitative detection of the SARS-CoV-2 spike protein receptor-binding domain (S1-RBD). OBJECTIVES: Our objective was to develop an efficient method of detecting SARS-CoV-2 within 15 min of sample collection. METHODS: We constructed and evaluated a portable, disposable lateral flow device, which detected the S1-RBD protein directly in nasopharyngeal swab samples. The device emits a fluorescent signal in the presence of S1-RBD, which can be captured by an automated TRF instrument. RESULTS: The TRF lateral flow assay signal was linear from 0 to 20 ng/ml and demonstrated high accuracy and reproducibility. When evaluated with clinical nasopharyngeal swabs, the assay was performed at >80% sensitivity, >84% specificity, and > 82% accuracy for detection of the S1-RBD antigen. CONCLUSION: The new S1-RBD antigen test is a rapid (15 min), sensitive, and specific assay that requires minimal sample preparation. Critically, the assay correlated closely with PCR-based methodology in nasopharyngeal swab samples, showing that the detected S1-RBD antigen levels correlate with SARS-CoV-2 virus load. Therefore, the new TRF lateral flow test for S1-RBD has potential application in point-of-care settings.

Drainage basins serve as multiple glacial refugia for alpine habitats in the Sierra Nevada Mountains, California.

The evolutionary histories of alpine species are often directly associated with responses to glaciation. Deep divergence among populations and complex patterns of genetic variation have been inferred as consequences of persistence within glacier boundaries (i.e., on nunataks), while shallow divergence and limited genetic variation are assumed to result from expansion from large refugia at the edge of ice shields (i.e., massifs de refuge). However, for some species, dependence on specific microhabitats could profoundly influence their spatial and demographic response to glaciation, and such a simple dichotomy may obscure the localization of actual refugia. In this study, we use the Nebria ingens complex (Coleoptera: Carabidae), a water-affiliated ground beetle lineage, to test how drainage basins are linked to their observed population structure. By analysing mitochondrial COI gene sequences and genome-wide single nucleotide polymorphisms, we find that the major drainage systems of the Sierra Nevada Mountains in California best explain the population structure of the N. ingens complex. In addition, we find that an intermediate morphotype within the N. ingens complex is the product of historical hybridization of N. riversi and N. ingens in the San Joaquin basin during glaciation. This study highlights the importance of considering ecological preferences in how species respond to climate fluctuations and provides an explanation for discordances that are often observed in comparative phylogeographical studies.

Validation of the five-tier Taiwan Triage and Acuity Scale for prehospital use by Emergency Medical Technicians.

OBJECTIVES: This study aimed to determine the inter-rater reliability of the five-level Taiwan Triage and Acuity Scale (TTAS) when used by emergency medical technicians (EMTs) and triage registered nurses (TRNs). Furthermore, it sought to validate the prehospital TTAS scores according to ED hospitalisation rates and medical resource consumption. METHODS: This was a prospective observational study. After training in five-level triage, EMTs triaged patients arriving to the ED and agreement with the nurse triage (TRN) was assessed. Subsequently, these trained research EMTs rode along on ambulance calls and assigned TTAS scores for each patient at the scene, while the on-duty EMTs applied their standard two-tier prehospital triage scale and followed standard practice, blinded to the TTAS scores. The accuracy of the TTAS scores in the field for prediction of hospitalisation and medical resource consumption were analysed using logistic regression and a linear model, respectively, and compared with the accuracy of the current two-tier prehospital triage scale. RESULTS: After EMT's underwent initial training in five-level TTAS, inter-rater agreement between EMTs and TRNs for triage of ED patients was very good (κw=0.825, CI 0.750 to 0.900). For the outcome of hospitalisation, TTAS five-level system (Akaike's Information Criteria (AIC)=486, area under the curve (AUC)=0.75) showed better discrimination compared with TPTS two-level system (AIC=508, AUC=0.66). Triage assignments by the EMTs using the the five-level TTAS was linearly associated with hospitalisation and medical resource consumption. CONCLUSIONS: A five-level prehospital triage scale shows good inter-rater reliability and superior discrimination compared with the two-level system for prediction of hospitalisation and medical resource requirements.

Impact of the caller's emotional state and cooperation on out-of-hospital cardiac arrest recognition and dispatcher-assisted cardiopulmonary resuscitation.

OBJECTIVE: This study determined the impact of the caller's emotional state and cooperation on out-of-hospital cardiac arrest (OHCA) recognition and dispatcher-assisted cardiopulmonary resuscitation (DA-CPR) performance metrics. METHODS: This was a retrospective study using data from November 2015 to October 2016 from the emergency medical service dispatching centre in northern Taiwan. Audio recordings of callers contacting the centre regarding adult patients with non-traumatic OHCA were reviewed. The reviewers assigned an emotional content and cooperation score (ECCS) to the callers. ECCS 1-3 callers were graded as cooperative and ECCS 4-5 callers as uncooperative and highly emotional. The relation between ECCS and OHCA recognition, time to key events and DA-CPR delivery were investigated. RESULTS: Of the 367 cases, 336 (91.6%) callers were assigned ECCS 1-3 with a good inter-rater reliability (k=0.63). Dispatchers recognised OHCA in 251 (68.4%) cases. Compared with callers with ECCS 1, callers with ECCS 2 and 3 were more likely to give unambiguous responses about the patient's breathing status (adjusted OR (AOR)=2.6, 95% CI 1.1 to 6.4), leading to a significantly higher rate of OHCA recognition (AOR=2.3, 95% CI 1.1 to 5.0). Thirty-one callers were rated uncooperative (ECCS 4-5) but had shorter median times to OHCA recognition and chest compression (29 and 122 s, respectively) compared with the cooperative caller group (38 and 170 s, respectively). Nevertheless, those with ECCS 4-5 had a significantly lower DA-CPR delivery rate (54.2% vs 85.9%) due to 'caller refused' or 'overly distraught' factors. CONCLUSIONS: The caller's high emotional state is not a barrier to OHCA recognition by dispatchers but may prevent delivery of DA-CPR instruction. However, DA-CPR instruction followed by first chest compression is possible despite the caller's emotional state if dispatchers are able to skilfully reassure the emotional callers.

Features of hospital and emergency medical service in out-of-hospital cardiac arrest patients with shockable rhythm.

OBJECTIVE: Predicting the outcome of out-of-hospital cardiac arrest (OHCA) patients is crucial. We examined hospital characteristics and parameters of emergency medical service (including scene time interval and direct ambulance delivery to intensive heart hospitals) as survival or outcome predictors. STUDY DESIGN: Data from 546 consecutive OHCA shockable patients treated between January 2012 and December 2015 in Taoyuan City (Taiwan, ROC) were collected. In addition to demographic data, location of arrest, initial rhythm, availability of a hospital with or without 24/7 percutaneous coronary intervention (PCI), emergency medical service (EMS) time, provision of cardiopulmonary resuscitation by a bystander, presence of a witness at collapse, and level of life support were analysed. RESULTS: Multivariate analysis showed that hospitalisation with immediate PCI availability was an independent predictor (OR: 4.32; 95% CI: 1.27-14.70) solely for the outcome of survival until discharge. The presence of a witness while collapsing (OR: 3.52; 95% CI: 1.03-11.98), EMS response time (OR: 0.83; 95% CI: 0.70-0.98), and scene time interval (STI; OR: 0.89; 95% CI: 0.81-0.99) were valuable for predicting the neurological outcome. CONCLUSIONS: Direct ambulance delivery to intensive heart hospitals that had 24/7 PCI availability was associated with a higher probability of surviving until discharge in OHCA patients with shockable rhythms. Similarly, a witnessed collapse was correlated with being discharged alive from hospital and recovering with good cerebral performance. In addition, longer response time and scene time interval indicated poorer survival and neurological outcome.

Validation of a Dispatch Protocol with Continuous Quality Control for Cardiac Arrest: A Before-and-After Study at a City Fire Department-Based Dispatch Center.

BACKGROUND: An optimized protocol to help dispatchers identify potential cases of cardiac arrest and provide phone instructions for cardiopulmonary resuscitation (CPR) may increase the provision of bystander CPR, further improving the survival rate and neurological outcomes. OBJECTIVE: We assessed a revised dispatcher-assisted (DA)-CPR protocol with a continuous quality-improvement feature in a county fire department-based emergency medical services system. METHODS: This was a before-and-after intervention prospective study conducted in Taoyuan City, Taiwan. The participants were out-of-hospital cardiac arrest (OHCA) patients from November 2014 to February 2016. Interventional quality control started in August 2015. Approximately 10% of the telephone calls from these OHCA patients were reviewed. RESULTS: In total, 66 and 64 cases were included in the before- and after-intervention groups, respectively. No significant differences were observed in sex, age, day, and time of events, or languages spoken by the callers. After the intervention, we found significant improvements in the rates at which cardiac arrests were recognized (54.5% vs. 68.8%; p = 0.007) and normal breathing was checked (51.5% vs. 76.6%, p = 0.003). Moreover, the frequency with which DA-CPR was provided by the dispatchers improved significantly (50.0% vs. 72.7%; p = 0.046). Significant improvement in patient outcomes was observed with regard to 24-h survival (7.6% vs. 20.3%, p = 0.036) but not with regard to survival to discharge (3.0% vs. 10.9%, p = 0.076). CONCLUSIONS: The study found this DA-CPR protocol, which includes continuous quality control, is promising as it improved the successful recognition of cardiac arrests.

Comparison of prehospital triage and five-level triage system at the emergency department.

OBJECTIVE: There is lack of scientific evidence regarding the effectiveness of prehospital triage systems. This study compared the two-level Taiwan Prehospital Triage System (TPTS) with the five-level Taiwan Triage and Acuity Scale (TTAS) at ED arrival regarding the prediction of patient outcomes and the utilisation of medical resources. DESIGN: This was a retrospective cohort study. Adult patients transported via the emergency medical service (EMS), who arrived at the ED of a medical centre in northern Taiwan during the study period were enrolled. TTAS acuity levels 1-2 were considered comparable to the designation of 'emergent' by the prehospital TPTS system. The outcomes were analysed by comparing TPTS and TTAS by acuity levels. RESULTS: Among 4430 enrolled patients, 25.2% and 74.8% were classified as emergent and non-emergent by TPTS; 44.1% and 55.9% were classified as levels 1-2 and levels 3-5 by TTAS. Of the TPTS emergent patients, 15.2% were classified as TTAS levels 3-5, whereas 30.4% of TPTS non-emergent transports were classified as TTAS levels 1-2 at the ED. TTAS levels 1-2 showed better predictability than TPTS emergent level for hospitalisation rate with a sensitivity of 70.3% (95% CI 68.3% to 72.2%) versus 41.1% (95% CI 39.0% to 43.2%), and a negative predictive value of 74.8% (95% CI 73.4% to 76.0%) versus 62.6% (95% CI 61.7% to 63.5%). CONCLUSION: The current prehospital triage system is insufficient and inappropriate in classifying patients transported to the ED. The present study offers supporting evidence for the introduction of a five-level triage system to prehospital EMS systems.

Rescuer factors predict high-quality CPR--a manikin-based study of health care providers.

BACKGROUND: In the provision of high-quality cardiopulmonary resuscitation (CPR) by health care providers, factors associated with high-quality CPR should be explored. METHODS: This is a post hoc analysis using data from a manikin-based survey of CPR quality among volunteer emergency medical technicians (EMTs) from 2 county fire departments in northern Taiwan. RESULTS: Among the 95 enrolled EMTs, 36 (37.9%) performed high-quality CPR on a manikin. The baseline characteristics that differed significantly between groups were board-certified EMT levels (P = .010), body mass index (BMI, P = .029), average exercise frequency (P = .001), and average exercise duration (P = .005). Average total exercise time per week, which uses frequency times exercise duration, was independently associated with high-quality CPR performance after adjusting for variables via logistic regression analysis (odds ratio, 1.004; P = .044). An index was developed (BMI × ExeTime) based on the product of BMI and average total exercise time per week. A comparison of the area under curve for the different indices showed that BMI × ExeTime was a significant predictor of high-quality CPR, with an area under curve of 0.718 (95% confidence interval, 0.613-0.824; P < .001; Fig. 2) and a cutoff value of 4136.7 kg·min/m(2) (sensitivity, 0.722; specificity, 0.678). CONCLUSIONS: This study identified factors associated with the performance by health care providers of high-quality CPR, including BMI and exercise habits. To optimize CPR quality, a program of exercise frequency and duration adjusted according to individual's BMI should be considered in such populations.

Is 15 minutes an appropriate resuscitation duration before termination of a traumatic cardiac arrest? A case-control study.

BACKGROUND: Previous guidelines suggest up to 15 minutes of cardiopulmonary resuscitation (CPR) accompanied by other resuscitative interventions before terminating resuscitation of a traumatic cardiac arrest. The current study evaluated the duration of CPR according to outcome using the model of a county-based emergency medical services (EMS) system in Taiwan. METHODS: This study was performed as a prospectively defined retrospective review from EMS records and cardiac arrest registration between June 2011 and November 2012 in Taoyuan, Taiwan. RESULTS: A total of 396 patients were enrolled. Among the blunt injuries, most incidents were traffic accidents (66.5%) followed by falls (31.5%). Bystander CPR was performed in 34 patients (8.6%). Of the patients, 18.4% were sent to intermediate to advanced level traumatic care hospitals. Although 4.8% of patients survived for 24 hours, only 2.3% survived to discharge, and 0.8% achieved cerebral performance category 1 or 2. Among all patients who developed return of spontaneous circulation (ROSC), 14.3% of ROSC was achieved within 15 minutes since CPR. Except for 1, most patients who developed ROSC over 24 hours but did not survive to discharge received CPR more than 15 minutes. Four of 6 patients who survived to discharge achieved ROSC after CPR for more than 15 minutes (16, 18, 22, and 24 minutes). Three patients discharged with cerebral performance category 1 or 2 received CPR for 6, 16, and 18 minutes, respectively. CONCLUSIONS: Fifteen minutes of CPR before terminating resuscitation is inappropriate for patients undergoing traumatic cardiac arrsests, as longer duration resuscitation increases ROSC and survival.

Factors associated with ED length of stay during a mass casualty incident.

BACKGROUND: The aim of this study was to examine the factors associated with emergency department (ED) length of stay (LOS) using the patient registry data from a medical burns center during a burn injury mass casualty incident (MCI) after a dust explosion in New Taipei City, Taiwan. METHODS: This was a retrospective cohort study conducted at an urban, tertiary care teaching hospital during an MCI event that occurred on June 27, 2015. A celebratory party was held at the Formosa Fun Water Park in New Taipei City, Taiwan. At 20:32, the was an explosion caused by an overheated spotlight accidentally igniting colored cornstarch powder that had been sprayed on the stage. Factors associated with ED LOS were compared. RESULTS: In total, 48 burn injury patients were enrolled for study analysis. The median total body surface area of second- to third-degree burns was 35.0% (interquartile range [IQR], 15.8%-55.0%). The median ED LOS was 121.5 minutes (IQR, 38.3-209.8 minutes). The output time interval accounted for the longest interval with a median time of 56.0 minutes (IQR, 15.3-117.3 minutes). In multivariate analysis of the variables, triage level (level III; hazard ratio, 0.06; 95% confidence interval, 0.01-0.52) and output time (hazard ratio, 0.97; 95% confidence interval, 0.96-0.98) were significant influential factors. CONCLUSIONS: The triage level and output time intervals were significantly associated with ED LOS in a burn-related MCI. Time effectiveness analyses, using a patient flow model, might serve as an important indicator during a hospital MCI response.

The impact of physical fitness and body mass index in children on the development of acute mountain sickness: A prospective observational study.

BACKGROUND: Acute mountain sickness (AMS) is commonly found among people traveling above 2500 m. We investigated whether the occurrence of AMS is related to differences in individual physical fitness and BMI in subjects 11-13 years of age. METHODS: This study was conducted at Xue Mountain, Taiwan (elevation of 3886 m) between June 13, 2011 and June 17, 2011. Subjects were asked to ascend from Taipei City (25 m) to the summit (3886 m) over 3 days and 2 nights. Gender, age, weight, height, and fitness index (determined using a 3-minute step test) were recorded at sea level before ascent. The Lake Louise AMS score was used to record symptoms and diagnose AMS. RESULTS: A total of 179 subjects (mean age: 11.8 years; 102 males, 77 females) were included in the analysis. A total of 44.7% of subjects were diagnosed with AMS. Male gender (p = 0.004) and elevated body mass index (BMI) (p < 0.001) were each associated with the development of AMS. However the physical fitness index was comparable in subjects with and without AMS (67.8 ± 10.1 vs. 68.0 ± 9.3, p = 0.9). CONCLUSIONS: This study shows that both BMI and male gender were associated with the development of AMS in 11-13 year old children. Physical fitness was not associated with the occurrence of AMS.

Rate of ascent and acute mountain sickness at high altitude.

OBJECTIVE: To examine the effect of ascent rate on the induction of acute mountain sickness (AMS) in young adults during a climb to Jiaming Lake (3350 m) in Taiwan. DESIGN: Prospective, nonrandomized. SETTING: Climb from 2370 to 3350 m. PARTICIPANTS: Young adults (aged 18 to 26 years) (N = 91) chose to participate in either the fast ascent (3 days; n = 43) or slow ascent (4 days; n = 48) group (1 and 2). ASSESSMENT OF RISK FACTORS: Two criteria were used to define AMS. A Lake Louise score ≥3 and Lake Louise criteria [in the setting of a recent gain in altitude, the presence of headache and at least 1 of gastrointestinal discomfort (anorexia, nausea, or vomiting), fatigue or weakness, dizziness or lightheadedness, or difficulty sleeping]. MAIN OUTCOME MEASURES: Heart rate, blood oxygen saturation (SaO2), and symptoms of AMS were monitored each morning and evening. RESULTS: Baseline characteristics were similar between groups, except for significant differences in history of alcohol consumption (P = 0.009) and climbing experience above 3000 m (P < 0.001). The incidence of AMS was not associated with the rate of ascent. Acute mountain sickness was most prevalent in group 1 on day 2 in the evening and in group 2 on day 3 in the evening. In both groups, AMS correlated with the initial reduction in SaO2. Body mass index (BMI) >24 kg/m was identified as a significant risk factor for AMS. CONCLUSIONS: The development of AMS was closely associated with an initial reduction in SaO2. A BMI >24 kg/m also contributed to the occurrence of AMS. CLINICAL RELEVANCE: These findings indicate that factors other than ascent rate should be considered when trying to ameliorate the risk of AMS.

Neural stem cells improve intracranial nanoparticle retention and tumor-selective distribution.

AIM: The purpose of this work is to determine if tumor-tropic neural stem cells (NSCs) can improve the tumor-selective distribution and retention of nanoparticles (NPs) within invasive brain tumors. MATERIALS & METHODS: Streptavidin-conjugated, polystyrene NPs are surface-coupled to biotinylated human NSCs. These NPs are large (798 nm), yet when conjugated to tropic cells, they are too large to passively diffuse through brain tissue or cross the blood-tumor barrier. NP distribution and retention was quantified 4 days after injections located either adjacent to an intracerebral glioma, in the contralateral hemisphere, or intravenously. RESULTS & CONCLUSION: In all three in vivo injection paradigms, NSC-coupled NPs exhibited significantly improved tumor-selective distribution and retention over free-NP suspensions. These results provide proof-of-principle that NSCs can facilitate the tumor-selective distribution of NPs, a platform useful for improving intracranial drug delivery.

Implementation of multiple strategies for improved door-to-balloon time in patients with ST-segment elevation myocardial infarction.

Several strategies have been found to be associated with a significant reduction in door-to-balloon (D2B) time in the management of ST-segment elevation myocardial infarction (STEMI). The objective of this retrospective cohort study was to assess D2B time before and after specific hospital strategies, including a computerized provider order entry (CPOE), were implemented to reduce D2B time. Patients who presented to the emergency department within 12 h of STEMI were enrolled. Strategies adopted included: (1) electrocardiography during triage for patients with chest pain; (2) implementing a CPOE; (3) activating the catheterization laboratory by sending a cell phone notification via the computer system; (4) using an open real-time on-line STEMI registry; and (5) conducting a monthly meeting to review registration. A total of 134 patients were included in the study (preintervention, n = 69; postintervention, n = 65). Median D2B time improved from 83 to 63 min after the new strategies were implemented (P = 0.001). Median door-to-electrocardiogram (5-2 min) and door-to-laboratory time (60-41 min) also significantly improved (P < 0.001). The proportion of patients with a D2B time within 90 min increased from 59.4 % to 98.5 % (P < 0.001). In conclusion, our findings suggest that implementing specific strategies can substantially improve D2B time for patients with STEMI and increase the proportion of patients with D2B time less than 90 min.

Comparison of 3 scoring systems to predict mortality from unstable upper gastrointestinal bleeding in cirrhotic patients.

OBJECTIVE: We aimed to compare the performance of Glasgow-Blatchford, preendoscopic Rockall, and model for end-stage liver disease (MELD) scores in cirrhotic patients with unstable upper gastrointestinal bleeding (UGIB) in the emergency department (ED). METHODS: This was a retrospective cohort study conducted at a university-affiliated teaching hospital. Adult cirrhotic patients who presented with acute UGIB and unstable vital signs (heart rate >100 beats/min or systolic blood pressure <100 mm Hg) between January 2009 and February 2011 were included. Patients who were transferred from another hospital, received no emergency endoscopy study, or had incomplete medical records were excluded. Data were retrieved from the admission list of the ED critical zone using international classification of disease code via computer registration. RESULTS: Among enrolled visits, the initial median hemoglobin level was 8.6 (interquartile range, 7.2-10.1) mg/dL in the ED. The median heart rate and systolic blood pressure were 111.0 beats/min and 94.0 mm Hg, respectively. The endoscopic diagnosis of variceal bleeding accounted for 86.6% of the events. The mortality rate was 16.0% (19/119). Model for end-stage liver disease score performed better with an area under the curve (AUC) of 0.736 (95% confidence interval [CI], 0.629-0.842; P = .001) compared with other scoring systems (Glasgow-Blatchford score: AUC, 0.527; 95% CI, 0.393-0.661; P = .709; preendoscopic Rockall score: AUC, 0.591; 95% CI, 0.465-0.717; P = .208). CONCLUSION: Model for end-stage liver disease score performed better in terms of predicting mortality of unstable UGIB in cirrhotic patients compared with Glasgow-Blatchford and preendoscopic Rockall scores in the ED.

De-novo long-read genome assembly and annotation of the luna moth (Actias luna) fully resolves repeat-rich silk genes.

We present the first long-read de-novo -assembly and annotation of the luna moth (Actias luna) and provide the full characterization of heavy chain fibroin (h-fibroin)--, a long and highly repetitive gene (>20 Kbp) essential in silk fiber production. There are more than 160,000 described species of moths and butterflies (Lepidoptera), but only within the last five years have we begun to recover high-quality annotated whole genomes across the order which capture h-fibroin. Using PacBio HiFi reads, we produce the first high-quality long-read reference genome for this species. The assembled genome has a length of 532 Mbp, a contig N50 of 16.8 Mbp, an L50 of 14 contigs, and 99.4% completeness (BUSCO). Our annotation using Bombyx mori protein and A.luna RNAseq evidence captured a total of 20,866 genes at 98.9% completeness with 10,267 functionally annotated proteins and a full-length h-fibroin annotation of 2,679 amino acid residues.

Integrated multi-omics analysis and machine learning identify hub genes and potential mechanisms of resistance to immunotherapy in gastric cancer.

BACKGROUND: Patients with gastric cancer respond poorly to immunotherapy. There are still unknowns about the biomarkers associated with immunotherapy sensitivity and their underlying molecular mechanisms. METHODS: Gene expression data for gastric cancer were gathered from TCGA and GEO databases. DEGs associated with immunotherapy response came from ICBatlas. KEGG and GO analyses investigated pathways. Hub genes identification employed multiple machine algorithms. Associations between hub genes and signaling pathways, disease genes, immune cell infiltration, drug sensitivity, and prognostic predictions were explored via multi-omics analysis. Hub gene expression was validated through HPA and CCLE. Multiple algorithms pinpointed Cancer-Associated Fibroblasts genes (CAFs), with ten machine-learning methods generating CAFs scores for prognosis. Model gene expression was validated at the single-cell level using the TISCH database. RESULTS: We identified 201 upregulated and 935 downregulated DEGs. Three hub genes, namely CDH6, EGFLAM, and RASGRF2, were unveiled. These genes are implicated in diverse disease-related signaling pathways. Additionally, they exhibited significant correlations with disease-associated gene expression, immune cell infiltration, and drug sensitivity. Exploration of the HPA and CCLE databases exposed substantial expression variations across patients and cell lines for these genes. Subsequently, we identified CAFs-associated genes and established a robust prognostic model. The analysis in the TISCH database showed that the genes in this model were highly expressed in CAFs. CONCLUSIONS: The results unveil an association between CDH6, EGFLAM, and RASGRF2 and the immunotherapeutic response in gastric cancer. These genes hold potential as predictive biomarkers for gastric cancer immunotherapy resistance and prognostic assessment.