Ultrasound-guided protein delivery is promising for site-specific control of cellular functions in the deep interior of the body in a noninvasive manner. Herein, we propose a method for cytosolic protein delivery based on ultrasound-guided intracellular vaporization of perfluorocarbon nano-droplets. The nano-droplets were conjugated with cargo proteins through a bio-reductively cleavable linker and introduced into living cells via antibody-mediated binding to a cell-surface receptor, which gets internalized through endocytosis. After the cells were exposed to ultrasound for endosomal escape of proteins, the ultrasound-responsive cytosolic release of a cargo enzyme was confirmed by visualizing the hydrolysis of the fluorogenic substrate using confocal microscopy. Moreover, a significant decrease in cell viability was achieved via the release of a cytotoxic protein in response to ultrasound treatment. The results of this study provide the proof of a principle that protein-conjugated nano-droplets can be used as carriers in ultrasound-guided cytosolic delivery of proteins.

Here we describe a male infant with non-immune hydrops fetalis associated with congenital cardiomyopathy diagnosed prenatally. Whole-exome sequencing detected compound heterozygous c.1688+1G>A and p.(Asn759Ilefs*41) variants in the PKP2 gene inherited independently from his asymptomatic parents. Our present case supports the severe phenotype of biallelic inheritance of PKP2 gene pathogenic variants

Here, we report a case of endovascular treatment in which optical frequency domain imaging (OFDI) evaluated the scoring balloon elements shift when three inflations without shaft rotation performed with a scoring balloon.

Takayasu arteritis is a granulomatous inflammation of the aorta and its major branches.Can present as an isolated, atypical,and/or catastrophic disease.The disease has been reported around the world, although it appears to be more prevalent in Asians.We report case of a 29-year-old pregnant lady presented with TA.

Fusobacterium nucleatum is an anaerobic Gram-negative rod commonly found in the oral cavity. We report a woman recently living in a Puerto Rican cult, presenting with abdominal pain and weight loss, found to have a liver abscess growing F. nucleatum extending to the pericardium, as well as a tubo-ovarian abscess.

Machine learning-based code smell detection has been demonstrated to be a valuable approach for improving software quality and enabling developers to identify problematic patterns in code. However, previous researches have shown that the code smell datasets commonly used to train these models are heavily imbalanced. While some recent studies have explored the use of imbalanced learning techniques for code smell detection, they have only evaluated a limited number of techniques and thus their conclusions about the most effective methods may be biased and inconclusive. To thoroughly evaluate the effect of imbalanced learning techniques on machine learning-based code smell detection, we examine 31 imbalanced learning techniques with seven classifiers to build code smell detection models on four code smell data sets. We employ four evaluation metrics to assess the detection performance with the Wilcoxon signed-rank test and Cliff’s δ. The results show that (1) Not all imbalanced learning techniques significantly improve detection performance, but deep forest significantly outperforms the other techniques on all code smell data sets. (2) SMOTE (Synthetic Minority Over-sampling TEchnique) is not the most effective technique for resampling code smell data sets. (3) The best-performing imbalanced learning techniques and the top-3 data resampling techniques have little time cost for code smell detection. Therefore, we provide some practical guidelines. First, researchers and practitioners should select the appropriate imbalanced learning techniques (e.g., deep forest) to ameliorate the class imbalance problem. In contrast, the blind application of imbalanced learning techniques could be harmful. Then, better data resampling techniques than SMOTE should be selected to preprocess the code smell data sets.

During the Late Pleistocene, major parts of North America were periodically covered by ice sheets. However, there are still open questions about whether ice-free refugia were present in the Alexander Archipelago along the Southeast (SE) Alaska coast during the Last Glacial Maximum (LGM). Numerous subfossils have been recovered from caves in SE Alaska, including American black (Ursus americanus) and brown (U. arctos) bears, which today are found in the Alexander Archipelago but are genetically distinct from mainland bear populations. Hence, these bear species offer an ideal system to investigate long-term occupation, potential refugial survival, and lineage turnover. Here we present genetic analyses based on 99 new complete mitochondrial genomes from ancient and modern brown and black bears spanning the last ~45,000 years. Black bears form two SE Alaskan subclades that diverged >100,00 years ago, one preglacial and one postglacial. All postglacial ancient brown bears are closely related to modern bears in the archipelago, while a single preglacial brown bear is found in a distantly related clade. A hiatus in the bear subfossil record around the LGM and the deep split of their pre- and post-glacial subclades fail to support a hypothesis of continuous occupancy in SE Alaska throughout the LGM for either species. Our results are consistent with an absence of refugia along the SE Alaska coast, but indicate that vegetation quickly expanded after deglaciation, allowing bears to recolonize the area after a short-lived LGM peak.

In this case report, we are presenting a man with intermittent fever for three months with a history of aortic and pulmonary valve replacement and also recurrent blood culture-negative endocarditis. After several evaluations based on endemic epidemiology, the Real-time PCR and IFA (indirect immunofluorescence assay) were positive for Q fever.

Aim Dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) remains the standard of care. CYP2C19 genetic polymorphisms results in variable Clopidogrel bioactivation. Increased function (CYP2C19*17) allele carriers (rapid metabolizers (RM) or ultrarapid metabolizers (UM)), are Clopidogrel hyper-responders and hence more susceptible to Clopidogrel related bleeding. Since current guidelines recommend against routine genotyping following PCI, data on the clinical utility of CYP2C19*17 genotype guided strategy are sparce. Our study provides real-world data on the 12-month follow-up of CYP2C19 genotyping in patients post-PCI. Methods This is a cohort study within an Irish population receiving 12 months of DAPT following PCI for ACS or CCS. It identifies the prevalence of CYP2C19 polymorphisms within an Irish population and describe the ischaemic and bleeding outcomes after 12 months of Clopidogrel DAPT. Results 129 patients were included with the following CYP2C19 polymorphism prevalence: 30.2% hyper-responders (26.4% RM (1*/17*), 3.9% UM (17*/17*)) and 28.7% poor-responders (22.5% IM (1*/2*), 3.9% IM (2*/17*), 2.3% PM (2*/2*)). Total bleeding incidence at 12-months increased from poor-responders (0.0%) to normal-responders (15.0%), to hyper-responders (25.0%). Compared to poor-responders, hyper-responders were significantly more likely to experience a bleeding event (25.0% vs 0.0%, P = 0.044). Conclusions The prevalence of CYP2C19 polymorphisms in Ireland is 58.9% (30.2% CYP2C19*17, 28.7% CYP2C19*2) with approximately 1 in 3 chance of being a Clopidogrel hyper-responder. The trend of increasing bleeding with increasing CYP2C19 activity, suggests a genotype guided strategy may have clinical utility identifying high-bleeding-risk with Clopidogrel in CYP2C19*17 carriers but further studies are required.

This paper studies to secure closed-form optical solitons moving using the optical fibers of the Biswas-Arshed model (BAM) with nonlinear Kerr law using the modified G ’ / G -expansion scheme. The obtained results current optical periodic wave shape, double periodic optical solitons, optical shock wave, the interaction between lump wave shape and periodic optical wave shape, the interaction between rough wave shape and optical soliton wave shapes for the model constructions. We display some two- and three-dimensional results from the nonlinear model under study. In communication sciences and optical fiber communications, mathematical findings plainly show the proposed algorithm’s total honesty and high performance through three-dimensional, two-dimensional, and contour graphical illustration.

Drug-drug interactions inducing adverse drug reactions remain a significant, avoidable health risk to cystic fibrosis (CF) patients. With increasingly complex CF exacerbation treatment regimens being used, the risk of clinically important drug-drug interactions has in turn increased. Cardiovascular medications have reportedly been commonly implicated in severe CF exacerbation drug-drug related reactions. Therefore, knowledge of these potential drug-drug interactions is essential for improvement of medication safety and preventing patient harm. Drug-drug interactions can be classified into either pharmacokinetic or pharmacodynamic. This article, using the British National Formulary, details the drug-drug interactions between commonly prescribed CF exacerbation medications and cardiac medications. For each respective drug-drug interaction, the potential consequence, management strategy and interaction severity have been described.

Aims: The aim of the present meta-analysis was to evaluate the effectiveness and safety of non–vitamin K antagonist oral anticoagulants (NOACs) vs. vitamin K antagonists (VKAs) in atrial fibrillation (AF) patients with polypharmacy. Methods and results: Randomized controlled trials or observational studies reporting the data about the NOACs and VKAs therapy among AF patients with polypharmacy were included. The search was performed in the PubMed and Embase databases up to November 2022. There were no differences in the rates of SSE but increased risk of all-cause death and major bleeding between moderate polypharmacy and severe polypharmacy versus no-polypharmacy patients. The use of NOACs compared with VKAs was significantly associated with reduced risks of stroke or systemic embolism (SSE) in AF patients with moderate polypharmacy (hazard ratios [HRs], 0.77 [95% confidence intervals [CIs], 0.69–0.86]) and severe polypharmacy (HR, 0.76 [95% CI, 0.69–0.82]) and there was no significant difference in major bleeding (moderate polypharmacy: HR, 0.87 [95% CI, 0.74–1.01]; severe polypharmacy: HR, 0.91 [95% CI, 0.79–1.06]) between the two groups. There were no differences in the rates of ischemic stroke, all-cause death, and gastrointestinal bleeding but reduced risk of any bleeding between the NOACs and VKAs users. Compared with VKAs, the risk of intracranial hemorrhage was reduced in patients with moderate polypharmacy but not in patients with severe polypharmacy in NOACs users. Conclusion: In patients with AF and polypharmacy, NOACs showed advantages over VKAs in SSE and bleeding, and non-inferiority in major bleeding, ischemic stroke, all-cause death, intracranial hemorrhage, and gastrointestinal bleeding.

NLR family pyrin domain containing 2 (NLRP2) is a novel member of the Nod-like receptor (NLR) family. However, our understanding of NLRP2 has long been ambiguous. NLRP2 may have a role in the innate immune response, but its specific  functions remain controversial. Although NLRP2 can initiate inflammasome and promote inflammation, it can also downregulate inflammatory signals. Additionally, NLRP2 has been reported to function in the reproductive system and shows high expression in the placenta. However, the exact role of NLRP2 in the reproductive system is unclear. Here, we highlight the most current progress on NLRP2 in inflammasome activation, effector function, and regulation of nuclear factor-κB. And we discuss functions of NLRP2 in inflammatory diseases, reproductive disorders, and the potential implication of NLRP2 in human diseases.

Quantifying spatiotemporally explicit interactions within animal populations facilitates the understanding of social structure and its relationship with ecological processes. Data from animal tracking technologies (Global Positioning Systems [“GPS”]) can circumvent longstanding challenges in the estimation of spatiotemporally explicit interactions, but the discrete nature and coarse temporal resolution of data mean that ephemeral interactions that occur between consecutive GPS locations go undetected. Here, we developed a method to quantify individual and spatial patterns of interaction using continuous-time movement models (CTMMs) fit to GPS tracking data. We first applied CTMMs to infer the full movement trajectories at an arbitrarily fine temporal scale before estimating interactions, thus allowing inference of interactions occurring between observed GPS locations. Our framework then infers indirect interactions – individuals occurring at the same location, but at different times– while allowing the identification of indirect interactions to vary with ecological context based on CTMM outputs. We assessed the performance of our new method using simulations and illustrated its implementation by deriving disease-relevant interaction networks for two behaviorally differentiated species, wild pigs (Sus scrofa) that can host African Swine Fever and mule deer (Odocoileus hemionus) that can host Chronic Wasting Disease. Simulations showed that interactions derived from observed GPS data can be substantially underestimated when temporal resolution of movement data exceeds 30-minute intervals. Empirical application suggested that underestimation occurred in both interaction rates and their spatial distributions. CTMM-Interaction method, which can introduce uncertainties, recovered the majority of true interactions. Our method leverages advances in movement ecology to quantify fine-scale spatiotemporal interactions between individuals from lower temporal resolution GPS data. It can be leveraged to infer dynamic social networks, transmission potential in disease systems, consumer-resource interactions, information sharing, and beyond. The method also sets the stage for future predictive models linking observed spatiotemporal interaction patterns to environmental drivers.

Minimal change nephrotic syndrome (MCNS) is more common among children. However, there is limited literature associating MCNS and COVID-19 infection. We present a 2 year old boy with anasarca who tested positive for COVID-19 prior to admission. Workup was consistent with nephrotic syndrome. He responded well to steroids and diuretics.

1. Researchers generally ascribe demographic drivers in a single or few sub-populations and presume they are representative. With this information, practitioners implement blanket conservation measures across metapopulations to reverse declines. However, such approaches may not be appropriate in circumstances where sub-populations are spatiotemporally segregated and exposed to different environmental variation. 2. The Greenland White-fronted Goose Anser albifrons flavirostris is an Arctic-nesting migrant that largely comprises two sub-populations (delineated by northerly and southerly breeding areas in west Greenland). The metapopulation has declined since 1999 but this trend is only mirrored in one sub-population and the causes of this disparity are unclear. Here we compare the drivers and trends of productivity in both sub-populations using population- and individual-level analysis. 3. We examined how temperature and precipitation influenced population-level reproductive success and whether there was a change in the relationship when metapopulation decline commenced. In addition we used biologging devices to reconstruct incubation events and modelled how phenology and environmental conditions influenced individual-level nest survival. 4. Correlations between reproductive success and temperature/precipitation on the breeding grounds have weakened for both sub-populations. This has resulted in lower reproductive success for the northerly, but not southerly breeding sub-population, which at the individual-level appears to be driven by lower in nest survival. Earlier breeding ground arrival and less precipitation during incubation increased nest survival in the northerly breeding population, while no factors examined were important for the southerly breeding sub-population. This suggests reproductive success is now driven by different factor(s) in the two sub-populations. 5. Demographic rates and their environmental drivers differ between the sub-populations examined here and consequently we encourage further decomposition of demography within metapopulations. This is important for conservation practitioners to consider as bespoke conservation strategies, targeting different limiting factors, may be required for different sub-population.

The potential use of Spirulina subsalsa in marine cultivation is important for biomass and phycocyanin production; however, little is known about its mechanism of salt adaptation. Here we present a draft genome sequence for the halotolerant cyanobacterium Spirulina subsalsa FACHB-351 (5.3 Mbp). The sequence is predominantly distributed in signal transduction, cell growth and adaptation, and carbohydrate metabolism, which possibly allows the strong salt adaptation of FACHB-351. No genes directly related to bacterial toxins suggests a low risk of FACHB-351 threatening human or animal health. A set of genes annotated in the GO database were not assigned in the KEGG database, and some genes of essential enzymes, like HO and DVR for phycocyanin and chlorophyll, were not found, which suggests a presence of possible yet-to-be-discovered pathways in FACHB-351. The availability of a genome sequence will facilitate investigations into S. subsalsa phycocyanin biosynthesis and permit optimal strategies to improve commercial phycocyanin production.

Presentation of High Altitude Pulmonary Edema (HAPE) in accordance with its usual natural history is a diagnostic clue. In resource-limited settings, distinguishing HAPE from other respiratory illnesses is challenging; especially when the presentation deviates from the natural history. Here we have discussed those three rare presentations of HAPE at 4371m.

Objective: This study aimed to investigate the effect of the disease on the middle ear resonance frequencies with wide-band tympanometry in the people with temporomandibular disorder (TMD). Methods: A total of 40 individuals (24 patients, 16 control groups), 18 years of age and older, 25 females and 15 males, were included in the study. For the patients who came to the Oral Diagnosis Department of XXXX University with the complaint of TMD, the patient’s history and detailed examination were taken by the specialist dentist. Pure tone audiometry (125-8000 Hz air-way, 250-4000 Hz bone conduction thresholds) and speech audiometry, acoustic immitance and middle ear resonance measurements, outer ear resonance test were applied. Results: TMD ipsilateral and contralateral middle ear resonance values for each individual of the study group and control group and statistical data were determined. No difference was observed in the mean values of the 3 groups for middle ear resonance. However, there was a significant difference between the middle ear resonance values of the TMD ipsilateral and control groups. Conclusion: In a patient population with TMD the increase in middle ear RF values in the ipsilateral ears of the lesion may provide evidence of an increase in the stiffness of the middle ear system, offering a new perspective on the pathophysiology of the disease. KEY POINTS 1) Middle ear canal resonance frequency can be determined with wideband tympanometry (WBT). 2) There was no difference in the mean values of the three groups for the ipsilateral of the temporamandibular disorder, the contralateral of the temporamandibular disorder and the middle ear resonance values of the control group. 3) It was observed that there was a significant difference between the ipsilateral resonance values of the TMD patient group and the middle ear resonance values of the control group. 4) This study aims to present additional findings and methods for differential diagnosis by showing the differences between clinical tests applied to individuals with TMD and middle ear findings of normal individuals. 5) This study will also provide the first findings of minor middle ear pathology in patients with TMJ disorders by WBT.

Disseminated adenovirus infections in patients who received chemotherapy alone for lymphoma are extremely rare, however, should be included in differential diagnosis for those who received T cell suppressive agents. We report a fatal case of disseminated adenovirus disease in a patient who had received chemotherapy and presented with hypoxia

High-temperature metal nanostructure endows various potential applications in optical communication, aerospace and other fields. In this letter, periodical nanostructure with high-temperature metal is proposed to enhance spectrum absorption. The absorption characteristics and mechanism were investigated and analyzed in the range of 360 ∼ 760 nm wavelength based on the finite difference time domain (FDTD) method. The results indicate that particle shape, material, and period are the main factors affecting absorption. After optimization, the peak and average absorption reach 68.6% and 61.32% respectively. The coupling between surface plasmon polaritons (SPPs) and local surface plasmon resonance (SPR) enhances the optical properties obviously. The results have certain reference value for the application of high-temperature metal nanostructure in special environments.

Background: Low bone mineral density (BMD) is prevalent in individuals with β-thalassemia which might be related to increased circulating dickkopf-1 (Dkk-1). These data are limited in α-thalassemia. Objectives: To evaluate the prevalence of low BMD in adolescents with non-deletional hemoglobin (Hb) H disease. Additionally, we aimed to examine the association between serum Dkk-1 concentration and BMD. Methods: Participant medical records were reviewed. The lumbar spine (LS) and total body (TB) BMD were measured and converted into height-adjusted z-scores. Serum Dkk-1, osteocalcin and C-telopeptide of type-I collagen (CTX) concentrations were also analyzed. Results: Thirty-seven participants (59% female, 86% Tanner stage ≥2, 95% regularly transfused) had mean age 14.6 ± 3.2 years, and average pretransfusion Hb and ferritin concentrations of 8.8 ± 1.0 g/dL and 958 ± 513 ng/mL, respectively. No participants had experienced fracture. The prevalence of low LSBMD and TBBMD was 42% and 17%, respectively. LSBMD z-score was lower in males vs. females (p-value = 0.029). LSBMD and TBBMD z-scores were correlated positively with BA, Tanner stage, and BMI, and negatively with Dkk-1 (p-values <0.05). Dkk-1 was correlated positively with history of delayed puberty, and negatively with transfusion interval (p-values = 0.038). Osteocalcin and CTX did not correlate with BMD or Dkk-1. Multiple regression analysis showed Dkk-1 inversely associated with TBBMD z-score adjusting for confounders (p-value = 0.009). Conclusions: We demonstrated a high prevalence of low BMD in adolescents with non-deletional Hb H disease. Moreover, Dkk-1 inversely associated with TBBMD suggesting it may serve as bone biomarker in thalassemia.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive disorder due to mutations in the TYMP gene. Clinical findings are characterized by neurologic manifestations and severe gastrointestinal dysfunction. The syndrome is usually fatal, the most effective treatment appears to be hematopoietic stem cell transplantation (HSCT). Aim:In this retrospective study, we evaluated HSCT that was performed using a reduced toxicicity myeloablative conditioning regimen in patients with MNGIE at our center. Results: A total of 6 allogeneic transplant procedures were performed in 4 patients. Three patients’ donors had fully matched donors, and one patients’ donor was haploidentical. Treosulfan-based myeloablative conditioning regimen was applied in 5 of 6 transplants. Bone marrow was used as a stem cell source. One patient is being followed up in the 4th year of posttransplant with full chimeric and without Graft versus host disease (GVHD). One patient died of acute stage IV GIS GVHD. Two patients underwent second transplantation due to engraftment failure, one of which was the patient who had a haploidentical transplant. Conclusions: Treosulfan-based regimen is well tolerated. Engraftment failure with this conditioning regimen can be a significant problem. We share our haploidentical transplant experience, which will be the first reported case in the literature.

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