Unveiling IL6R and MYC as Targeting Biomarkers in Imatinib-Resistant Chronic Myeloid Leukemia through Advanced Non-Invasive Apoptosis Detection Sensor Version 2 Detection.

The management of chronic myelogenous leukemia (CML) has seen significant progress with the introduction of tyrosine kinase inhibitors (TKIs), particularly Imatinib. However, a notable proportion of CML patients develop resistance to Imatinib, often due to the persistence of leukemia stem cells and resistance mechanisms independent of BCR::ABL1 This study investigates the roles of IL6R, IL7R, and MYC in Imatinib resistance by employing CRISPR/Cas9 for gene editing and the Non-Invasive Apoptosis Detection Sensor version 2 (NIADS v2) for apoptosis assessment. The results indicate that Imatinib-resistant K562 cells (K562-IR) predominantly express IL6R, IL7R, and MYC, with IL6R and MYC playing crucial roles in cell survival and sensitivity to Imatinib. Conversely, IL7R does not significantly impact cytotoxicity, either alone or in combination with Imatinib. Further genetic editing experiments confirm the protective functions of IL6R and MYC in K562-IR cells, suggesting their potential as therapeutic targets for overcoming Imatinib resistance in CML. This study contributes to understanding the mechanisms of Imatinib resistance in CML, proposing IL6R and MYC as pivotal targets for therapeutic strategies. Moreover, the utilization of NIADS v2 enhances our capability to analyze apoptosis and drug responses, contributing to a deeper understanding of CML pathogenesis and treatment options.

Clinical and Microbiological Characteristics of Culture-Positive, Influenza-Associated Pulmonary Aspergillosis: A Single-Center Study in Southern Taiwan, 2016-2019.

This study delineated the characteristics of 24 (11.2%) culture-positive, influenza-associated pulmonary aspergillosis (IAPA) patients out of 215 patients with severe influenza during 2016-2019 in a medical center in southern Taiwan. Twenty (83.3%) patients did not have EORTC/MSG-defined host factors. The mean time from influenza diagnosis to Aspergillus growth was 4.4 days, and 20 (83.3%) developed IAPA within seven days after influenza diagnosis. All patients were treated in intensive care units and all but one (95.8%) received mechanical ventilation. Aspergillus tracheobronchitis was evident in 6 (31.6%) of 19 patients undergoing bronchoscopy. Positive galactomannan testing of either serum or bronchoalveolar lavage was noted in all patients. On computed tomography imaging, IAPA was characterized by peribronchial infiltrates, multiple nodules, and cavities superimposed on ground-glass opacities. Pure Aspergillus growth without bacterial co-isolation in culture was found in 17 (70.8%) patients. A. fumigatus (15, 62.5%), A. flavus (6, 25.0%), and A. terreus (4, 16.7%) were the major causative species. Three patients had mixed Aspergillus infections due to two species, and two had mixed azole-susceptible and azole-resistant A. fumigatus infection. All patients received voriconazole with an all-cause mortality of 41.6%. Of 14 survivors, the mean duration of antifungal use was 40.5 days. In conclusion, IAPA is an early and rapidly deteriorating complication following influenza that necessitates clinical vigilance and prompt diagnostic workup.

The Impacts of Polyisoprene Physical Interactions on Sorting of Single-Wall Carbon Nanotubes.

Conjugated polymer sorting is currently the best method to select large-diameter single-walled carbon nanotubes (SWCNTs) with tunable narrow chirality in the adaption of highly desired electronics applications. The acceleration on conjugated polymers-SWCNTs interaction with long-term stability through different molecular designs; for example, longer alkyl side-chains or conjugation moieties have been extensively developed in recent years. However, the importance of the macromolecules with abundant van der Waals (VDW) interaction in the conjugated-based block copolymer system acting during SWCNTs sorting is not clearly demonstrated. In this work, a conjugated diblock copolymer involving polyisoprene (PI) and highly dense π-interaction of poly (9,9-dioctylfluorene) (PFO) is utilized to investigate the impact of natural rubber PI physical interaction on sorting effectiveness and stability. Through the rational design of diblock copolymer, PFO with ≈1200 isoprene units can remarkably enhance SWCNTs sorting ability and selected few chiralities with a diameter of ≈0.83-1.1 nm and highly stable solution for more than 1 year. The introduction of long-chain PI system is attributed not only to form weak VDW force with SWCNTs and strengthen the wrapping of PFO around the semiconducting SWCNTs but also to act as a barrier among nanotubes to prevent reaggregation of sorted SWCNTs.

End-to-End Deep Learning by MCU Implementation: An Intelligent Gripper for Shape Identification.

This paper introduces a real-time processing and classification of raw sensor data using a convolutional neural network (CNN). The established system is a microcontroller-unit (MCU) implementation of an intelligent gripper for shape identification of grasped objects. The pneumatic gripper has two embedded accelerometers to sense acceleration (in the form of vibration signals) on the jaws for identification. The raw data is firstly transferred into images by short-time Fourier transform (STFT), and then the CNN algorithm is adopted to extract features for classifying objects. In addition, the hyperparameters of the CNN are optimized to ensure hardware implementation. Finally, the proposed artificial intelligent model is implemented on a MCU (Renesas RX65N) from raw data to classification. Experimental results and discussions are introduced to show the performance and effectiveness of our proposed approach.

Right ventricular dysfunction is associated with the development of chronic thromboembolic pulmonary hypertension but not with mortality post-acute pulmonary embolism.

Chronic thromboembolic pulmonary hypertension (CTEPH), a late complication of pulmonary embolism (PE), is associated with high mortality. However, whether the right ventricular (RV) echocardiographic parameters can predict - in the short- and long-term - the development of CTEPH and mortality after PE remains unknown. Herein, we aim to investigate the incidence of CTEPH after acute PE and to evaluate the risk factors of CTEPH. In this retrospective cohort, patients with PE were followed for 10 years for the onset of CTEPH. The screening was initially conducted through echocardiography and confirmed by right heart catheterization. Also, transient and permanent risk factors were identified. Among 358 patients with PE, 8 patients (4%) were subsequently diagnosed with CTEPH at a median time of 36 months and 47 died during the follow-up period. Notably, both short- and long-term RV dilatation, hypertrophy, and increased pulmonary pressure increased the incidence of CTEPH. However, RV echocardiographic parameters failed to differentiate survivors from non-survivors. Instead, malignancy, respiratory, or chronic heart failure was strongly associated with post PE mortality in the multivariable analysis. According to our findings, post PE screening of CTEPH may facilitate early diagnosis and intervention for patients at high risk of developing CTEPH. Also, RV echocardiographic parameters are associated with subsequent CTEPH, but mortality is mainly dependent on underlying comorbidities.

Enhanced Thermoelectric Properties of Boron-Substituted Single-Walled Carbon Nanotube Films.

Atomic doping is the most fundamental approach to modulating the transport properties of carbon nanotubes. In this paper, we demonstrate the enhanced thermoelectric properties of boron-substituted single-walled carbon nanotube (B-SWCNT) films. The developed two-step synthesis of large quantities of B-SWCNTs readily enables the measurements of thermoelectricity of bulk B-SWCNT films. Complementary structural characterization implies the unique configuration of boron atoms at the doping sites of SWCNTs, successfully enabling carrier doping to SWCNTs. The developed boron substitution, in combination with chemical doping, is found to substantially improve the thermoelectric properties.

HOTAIR lncRNA SNPs rs920778 and rs1899663 are associated with smoking, male gender, and squamous cell carcinoma in a Chinese lung cancer population.

The abnormal expression of the long noncoding RNA (lncRNA) HOX transcript intergenic antisense RNA (HOTAIR) plays an important role in the development of various cancers; however, single nucleotide polymorphisms (SNPs) in HOTAIR and their association with primary lung cancer susceptibility have not yet been reported. Here, we performed a case-control study including 262 primary lung cancer patients and 451 cancer-free control individuals to investigate the association between four haplotype-tagging SNPs (rs920778, rs12826786, rs4759314, and rs1899663) in the HOTAIR lncRNA and the risk of developing primary lung cancer. We found a significant association between the SNPs rs920778 and rs1899663 in the HOTAIR and primary lung cancer susceptibility (P < 0.05). Moreover, homozygous C/T (C/T + TT) for rs920778 (C > T) sites was significantly associated with gender, smoking history, and pathological type. In addition, linkage disequilibrium and haplotype analysis of HOTAIR gene polymorphisms for susceptibility to lung cancer revealed a high degree of linkage disequilibrium between the rs920778 and rs1899663 loci (D' = 0.86, r2 = 0.52). The population of rs920778, rs1899663, and rs4759314 had a significantly increased risk of lung cancer (P < 0.001). In summary, the present study provides persuasive evidence that SNP rs920778 is closely correlated with susceptibility to primary lung cancer. Future studies are warranted to validate and expand these findings, and to further dissect the importance of these SNPs in the development of primary lung cancer.

Lupus myocarditis receiving the rituximab therapy-a monocentric retrospective study.

Despite high-dose corticosteroids alone or with immunosuppressive agents as the standard therapy in lupus myocarditis (LM), an immune complex-mediated critical setting, such management is still associated with resistant disease and even mortality. A retrospective study was performed for the refractory LM patients treated with rituximab (RTX), a very limited experience in English literatures. A retrospective review of the myocarditis manifestation was carried out in hospitalized Han Chinese patients with SLE from February 2007 to January 2017. This study analyzed lupus patients who met the diagnosis of LM for their demographic, clinical, laboratory, and radiological data including cardiac magnetic resonance imaging and echocardiography as well as the medication profiles. Among 802 SLE patients, 13 female (1.6%) aged 19 to 52 years (31.9 ± 10.7), fulfilled the LM diagnostic criteria. Under the indications of LM or multi-organic flares with myocarditis refractory to the conventional therapy, three cases received the RTX therapy. All had improved myocardial function as demonstrated by clinical and imaging presentations as well as a decrease in lupus activity. In this 10-year retrospective monocentric cohort, improved myocardial function is demonstrated in refractory LM patients receiving the RTX therapy.

Lrp, a global regulator, regulates the virulence of Vibrio vulnificus.

BACKGROUND: An attenuated mutant (designated NY303) of Vibrio vulnificus, which causes serious wound infection and septicemia in humans, was isolated fortuitously from a clinical strain YJ016. This mutant was defective in cytotoxicity, migration on soft agar and virulence in the mouse. The purpose of this study was to map the mutation in this attenuated mutant and further explore how the gene thus identified is involved in virulence. METHODS: The whole genome sequence of mutant NY303 determined by next-generation sequencing was compared with that of strain YJ016 to map the mutations. By isolating and characterizing the specific gene-knockout mutants, the gene associated with the phenotype of mutant NY303 was identified. This gene encodes a global regulator, Lrp. A mutant, YH01, deficient in Lrp was isolated and examined in vitro, in vivo and ex vivo to find the affected virulence mechanisms. The target genes of Lrp were further identified by comparing the transcriptomes, which were determined by RNA-seq, of strain YJ016 and mutant YH01. The promoters bound by Lrp were identified by genome footprinting-sequencing, and those related with virulence were further examined by electrophoretic mobility shift assay. RESULTS: A mutation in lrp was shown to be associated with the reduced cytotoxicity, chemotaxis and virulence of mutant NY303. Mutant YH01 exhibited a phenotype resembling that of mutant NY303, and was defective in colonization in the mouse and growth in mouse serum, but not the antiphagocytosis ability. 596 and 95 genes were down- and up-regulated, respectively, in mutant YH01. Many of the genes involved in secretion of the MARTX cytotoxin, chemotaxis and iron-acquisition were down-regulated in mutant YH01. The lrp gene, which was shown to be negatively autoregulated, and 7 down-regulated virulence-associated genes were bound by Lrp in their promoters. A 14-bp consensus sequence, mkCrTTkwAyTsTG, putatively recognized by Lrp was identified in the promoters of these genes. CONCLUSIONS: Lrp is a global regulator involved in regulation of cytotoxicity, chemotaxis and iron-acquisition in V. vulnificus. Down-regulation of many of the genes associated with these properties may be responsible, at least partly, for loss of virulence in mutant NY303.

Performance of the microscopic observation drug susceptibility assay in pyrazinamide susceptibility testing for Mycobacterium tuberculosis.

BACKGROUND: Drug susceptibility assay is very important in tuberculosis therapy. Pyrazinamide is a first line antituberculosis drug and diagnosis of its resistance in Mycobacterium tuberculosis (M. tuberculosis) is difficult and time consuming by conventional methods. In this study, we aimed to evaluate the performance of the microscopic observation drug susceptibility (MODS) assay in the detection of pyrazinamide resistance in M. tuberculosis relative to the conventional Wayne assay and Lowenstein-Jensen (LJ) proportion method. METHODS: M. tuberculosis clinical isolates (n = 132) were tested by the MODS and the Wayne assay: the results were compared with those obtained by the LJ proportion method. Mutations in the gene were identified by direct sequencing of the pncA genes of all isolates in which pyrazinamide resistance was detected by any of the three methods. RESULTS: Compared to the LJ results, the sensitivity and specificity of the MODS assay were 97.8% and 96.5% respectively; the sensitivity and specificity of the Wayne assay were 87.0% and 97.7% respectively. Mutations in the pncA gene were found in 41 of 46 strains that were pyrazinamide resistant (3 tests), in 1 of the 4 strains (LJ only), in 42 of 48 strains (at least 1 test), but no mutations in 1 strain sensitive according to the MODS assay only. The MODS assay, Wayne assay and LJ proportion method provided results in a median time of 6, 7 and 26 days respectively. CONCLUSIONS: MODS assay offers a rapid, simple and reliable method for the detection of pyrazinamide resistance in M. tuberculosis and is an optimal alternative method in resource limited countries.

Chylous ascites and chylothorax: an unusual manifestation of cardiac amyloidosis.

Restrictive cardiomyopathy is an extremely rare cause of massive chylous ascites and chylothorax. We report a 56-year-old man patient who presented with chylous ascites and bilateral chylothorax; 12-lead electrocardiography and echocardiography revealed restrictive cardiomyopathy. Endomyocardial biopsy disclosed amyloidosis.

Judicious use of transthoracic echocardiography in infective endocarditis screening.

BACKGROUND: Patients with a very low probability of infective endocarditis (IE) do not benefit from transthoracic echocardiography (TTE). Because the term 'very low probability' has not yet been defined, the present prospective study sought to identify the population with a 'very low probability'. METHODS: TTE was performed between July 2005 and October 2006 in consecutive patients clinically suspected of having IE. Clinical parameters suggestive of IE and presence of infectious focus were recorded. RESULTS: Twenty-four (15.5%) of 155 patients studied had positive findings on TTE. Significant positive predictors were embolic events, intravenous drug use, the presence of a prosthetic valve, positive blood cultures and immunological phenomena. The significant negative predictor was confirmed infection sites other than endocardium. Sixty-three (40.6%) of 155 patients without positive predictors were found to have no vegetation. Thus, the collective absence of these predictors indicated a zero probability of TTE showing evidence of IE. A significant negative predictor was a definite etiology of infection other than IE. Only one in 76 patients was diagnosed with both IE and infection at another site. CONCLUSIONS: The absence of positive predictors or the presence of a negative predictor indicate a near-zero probability of IE being detected by TTE. Use of clinical parameters may avoid up to 41% of unnecessary TTE examinations, increasing the likelihood that such a diagnosis will be correct.

Uric acid is an independent predictor of arterial stiffness in hypertensive patients.

Increased arterial stiffness is an important marker for target organ damage in essential hypertension. Both serum uric acid (UA) and C-reactive protein (CRP) were reported to be associated with target organ damage. However, the influences of UA and CRP on large arterial stiffness were not well elucidated. This study included 200 essential hypertension patients (64 women) whose age was between 20 and 50 years old (mean age 41 +/- 8 years). None of the patients had diabetes mellitus or overt end-organ damage. Arterial stiffness was assessed by pulse-wave velocity (PWV) measured by tonometry from carotid to radial artery. Serum UA, high-sensitivity CRP (hsCRP), glucose, insulin, and lipid profiles were measured at the same time in each patient. PWV levels were significantly correlated with mean blood pressure (r = 0.245, P < 0.001), diastolic blood pressure (r = 0.323, P < 0.001), high-density lipoprotein (r = -0.169, P = 0.016), and UA (r = 0.234, P = 0.001), but not age, body mass index, blood sugar, insulin, low-density lipoprotein, triglyceride, and hsCRP. Pulse-wave velocity levels were significantly higher in males (8.9 +/- 1.2 vs 8.2 +/- 1.2 m/s, P < 0.001) and smokers (9.3 +/- 1.1 vs 8.5 +/- 1.2 m/s, P < 0.001). Uric acid was significantly correlated with hsCRP (r = 0.294, P < 0.001). After multivariate analysis controlling for all possible confounding factors, UA (odds ratio 1.28, 95% confidence interval 1.02-1.61, P = 0.032) was still independently associated with increased PWV. In conclusion, UA but not hsCRP was independently associated with increased PWV in essential hypertension. Although UA was correlated with hsCRP, the association between UA and PWV was not through the effect of enhanced inflammation.

Association of left atrial strain and strain rate assessed by speckle tracking echocardiography with paroxysmal atrial fibrillation.

BACKGROUND: We hypothesized that contraction of the LA wall could be documented by speckle tracking and could be applied for assessment of LA function. This study tried to identify the association between LA longitudinal strain (LAS) and strain rate (LASR) measured by speckle tracking with paroxysmal atrial fibrillation (PAF). METHODS: Fifty-two patients (61 +/- 17 years old, 23 men) with sinus rhythm at baseline referred for the evaluation of episodic palpitation were included. Standard four-chamber and two-chamber views were acquired and analyzed off-line. Peak LAS and LASR were carefully identified as the peak negative inflection of speckle tracking waves after P-wave gated by electrocardiography. RESULTS: Ten patients (19%) had PAF. LAS, LASR, age, left ventricular end-diastolic dimension, left ventricular mass, LA volume, and mitral early filling-to-annulus early velocity ratio were different between patients with and without PAF. After multivariate analysis, LASR was significantly independently associated with PAF (OR 8.56, 95% CI 1.14-64.02, P = 0.036). CONCLUSION: Speckle tracking echocardiography could be used in measurements of LAS and LASR. Decreased negative LASR was independently associated with PAF.

Usefulness of real-time three-dimensional echocardiography for diagnosis of infective endocarditis.

OBJECTIVES: To compare transthoracic 2-dimentional echocardiography (2DE) and real-time three-dimensional echocardiography (RT-3DE) evaluation of clinically suspected infective endocarditis (IE) and to determine the feasibility of RT-3DE in vegetation detection. DESIGNS: There were 46 patients (mean age 61+/-17 years, 54% male) enrolled. We acquired 2DE and RT-3DE with full volume images. RT-3DE images were analyzed by 3D QLAB software. Parameters suggestive of vegetation for RT-3DE assessment included mobile nodules, focal thickness, and uneven surface. The diagnosis of IE was made according to the Duke criteria. RESULTS: The sensitivity and specificity were 91.6% and 88.2% for 2DE, and 91.6% and 100% for RT-3DE. Among three parameters of RT-3DE, presence of mobile nodule (83.3% vs. 0%, p < 0.001) were significantly higher in IE patients but not focal thickness (75% vs. 65%, p = 0.723), or uneven surface (33% vs. 10%, p = 0.064). CONCLUSION: The sensitivity of RT-3DE and 2DE was similar for endocarditis diagnosis, but the specificity of RT-3DE was higher. Mobile nodules viewed by RT-3DE might be a useful finding for vegetation detection.

Association of adiponectin with procollagen type I carboxyterminal propeptide in non-diabetic essential hypertension.

OBJECTIVE: The serum concentration of procollagen type I carboxyterminal propeptide (PICP) is a good marker for collagen deposition in hypertension. Increased collagen deposition was associated with myocardial fibrosis and increased arterial stiffness. A decreased adiponectin level is associated with increased atherosclerosis. The role of adiponectin and its relation to PICP in essential hypertension have rarely been studied before. METHODS: We recruited 188 non-diabetic uncomplicated hypertensive patients (mean age: 41+/-7 years; 128 men). No patient had vascular complications or renal or liver diseases. Overnight fasting blood samples were collected to assess patient lipid profiles, blood sugar, insulin, high-sensitivity C-reactive protein (hsCRP), PICP and adiponectin. Carotid to radial pulse wave velocity (PWV) measured using tonometry was used as an index of arterial stiffness. RESULTS: Adiponectin (r = -0.216, p = 0.003) and male gender (p<0.001) were independent determinants of PICP. Diastolic blood pressure (r = 0.422, p<0.001) and current smoking (p = 0.005) were independent determinants of PWV. PWV was significantly correlated with PICP (r = 0.156, p = 0.034). Adiponectin was significantly correlated with triglyceride (r = -0.276, p<0.001), high-density lipoprotein (r = 0.262, p<0.001), the homeostasis model assessment (HOMA) index (r = -0.220, p = 0.002), hsCRP (r = -0.207, p = 0.004) and the body mass index (BMI) (r = -0.202, p = 0.005). After compensation with possible confounding factors, adiponectin was still significantly correlated with PICP (beta = -0.196, p = 0.006). CONCLUSION: Serum adiponectin may be a marker for metabolic syndrome in essential hypertension. Adiponectin was significantly negatively correlated with PICP. Metabolic syndrome probably plays an important role in increased collagen synthesis and arterial stiffness through the effects of decreased adiponectin in non-diabetic essential hypertension.

Intracardiac thrombosis in multiple chambers and descending aorta manifested as systemic and pulmonary thromboembolism.

We report a case with multiple thrombosis that underwent sudden circulatory collapse due to acute pulmonary embolism and ischemic stroke. Further confirmed by transesophageal echocardiography, the thrombus in both atria was detected by transthoracic echocardiography. In addition, patent foramen ovale and another thrombus in the descending aorta were readily identified by transesophageal echocardiography. Aspirin was prescribed and thrombi disappeared 1 month later. Our case report suggests that patients undergoing sudden collapse with unexplained hypoxemia and new neurological deficit secondary to coexistence of pulmonary and systemic embolism should be promptly evaluated by echocardiography, especially transesophageal one, with high suspicion for paradoxical embolism.