mtDNA analysis using Mitopore.

Mitochondrial DNA (mtDNA) analysis is crucial for the diagnosis of mitochondrial disorders, forensic investigations, and basic research. Existing pipelines are complex, expensive, and require specialized personnel. In many cases, including the diagnosis of detrimental single nucleotide variants (SNVs), mtDNA analysis is still carried out using Sanger sequencing. Here, we developed a simple workflow and a publicly available webserver named Mitopore that allows the detection of mtDNA SNVs, indels, and haplogroups. To simplify mtDNA analysis, we tailored our workflow to process noisy long-read sequencing data for mtDNA analysis, focusing on sequence alignment and parameter optimization. We implemented Mitopore with eliBQ (eliminate bad quality reads), an innovative quality enhancement that permits the increase of per-base quality of over 20% for low-quality data. The whole Mitopore workflow and webserver were validated using patient-derived and induced pluripotent stem cells harboring mtDNA mutations. Mitopore streamlines mtDNA analysis as an easy-to-use fast, reliable, and cost-effective analysis method for both long- and short-read sequencing data. This significantly enhances the accessibility of mtDNA analysis and reduces the cost per sample, contributing to the progress of mtDNA-related research and diagnosis.

MICROSURGICAL REIMPLANTATION OUTCOMES FOR COMPLETE AND INCOMPLETE AMPUTATIONS OF DISTAL PHALANGES OF FINGERS.

Introduction: The intricate endeavor of replanting the distal phalanx of the finger remains a persistent challenge. In the pursuit of addressing this concern, microsurgical replantation procedures have been systematically examined for distal phalanx injuries encircling the distal interphalangeal (DIP) joint, conducted at the Orthopaedic Hospital situated in Ho Chi Minh City. Materials and Methods: This investigation encompassed a cohort of 31 patients, comprising individuals with 17 instances of complete and 21 instances of incomplete amputations of the distal phalanges. The subjects' ages spanned a range from 3 to 56 years. Results: The study divulged that eight fingers, involving four complete amputations and four incomplete amputations, did not achieve successful outcomes. In contrast, the remaining 30 fingers exhibited survival. A meticulous long-term follow-up of 17 fingers, extending over a period exceeding six months, unveiled commendable achievements encompassing satisfactory sensory recovery, cosmetic enhancement, and the resumption of pre-injury occupational activities by the patients. Discussion: Vein anastomosis was revealed as a notably challenging aspect of the surgical procedures. In scenarios where conventional vein suturing was rendered unfeasible, the innovative recourse of one-way drainage emerged as a viable alternative. Conclusion: The endeavor to replant the distal phalanx of the finger engenders a substantial level of complexity, particularly in the realm of venous anastomosis. This research underscores the need for focused efforts to address and surmount the intricacies associated with this aspect of surgical intervention.

Mitochondrial DNA integrity and metabolome profile are preserved in the human induced pluripotent stem cell reference line KOLF2.1J.

Quality control of human induced pluripotent stem cells (iPSCs) is critical to ensure reproducibility of research. Recently, KOLF2.1J was characterized and published as a male iPSC reference line to study neurological disorders. Emerging evidence suggests potential negative effects of mtDNA mutations, but its integrity was not analyzed in the original publication. To assess mtDNA integrity, we conducted a targeted mtDNA analysis followed by untargeted metabolomics analysis. We found that KOLF2.1J mtDNA integrity was intact at the time of publication and is still preserved in the commercially distributed cell line. In addition, the basal KOLF2.1J metabolome profile was similar to that of the two commercially available iPSC lines IMR90 and iPSC12, but clearly distinct from an in-house-generated ERCC6R683X/R683X iPSC line modeling Cockayne syndrome. Conclusively, we validate KOLF2.1J as a reference iPSC line, and encourage scientists to conduct mtDNA analysis and unbiased metabolomics whenever feasible.

Ridge resonators with compact guided mode coupling.

Ridge resonators are a recently introduced integrated photonic circuit element based on bound states in the continuum (BICs) which can produce a single, sharp resonance over a broad wavelength range with high extinction ratio. However, to excite these resonators, a broad beam of laterally unbound slab mode is required, resulting in a large device footprint, which is not attractive for integrated photonic circuits. In this contribution, we propose and numerically validate a guided-mode waveguide structure that can be analogue to the BIC-based ridge resonators. Our simulations show that the proposed guided-mode waveguide structure can produce resonances with similar characteristics, yet with a significantly reduced footprint. Furthermore, we investigate the influence of the resonator's dimensions on the bandwidth of the resonance, demonstrating that resonances with Q-factors from low to very high (> 10000) are feasible. We believe that the reduced footprint and ability to design filters systematically make the guided-mode waveguide resonators an attractive photonic circuit component with particular value for foundry fabricated silicon photonic circuits.

Integrated lithium niobate optical mode (de)interleaver based on an asymmetric Y-junction.

Lithium niobate on insulator (LNOI) platforms promise unique advantages in realizing high-speed, large-capacity, and large-scale photonic integrated circuits (PICs) by leveraging lithium niobate's attractive material properties, which include electro-optic and nonlinear optic properties, low material loss, and a wide transparency window. Optical mode interleavers can increase the functionality of future PICs in LNOI by enabling optical mode division multiplexing (MDM) systems, allowing variable mode assignment while maintaining high channel utilization and capacity. In this Letter, we experimentally demonstrate an optical mode interleaver based on an asymmetric Y-junction on the LNOI platform, which exhibits an insertion loss of below 0.46 dB and modal cross talk of below -13.0 dB over a wavelength range of 1500-1600 nm. The demonstrated mode interleaver will be an attractive circuit component in future high-speed and large-capacity PICs due to its simple structure, scalability, and capacity for efficient and flexible mode manipulation on the LNOI platform.

Safe and effective profile of the VSTENT bioresorbable polymer sirolimus-eluting stent in the treatment of patients with de novo coronary artery lesions: a prospective, cohort, multicenter study.

Background: The drug-eluting stent was a significant stride forward in the development of enhanced therapeutic therapy for coronary intervention, with three generations of increased advancement. VSTENT is a newly developed stent manufactured in Vietnam that aims to provide coronary artery patients with a safe, effective, and cost-efficient option. The purpose of this trial was to determine the efficacy and safety of a new bioresorbable polymer sirolimus-eluting stent called VSTENT. Methods: This is a prospective, cohort, multicenter research in 5 centers of Vietnam. A prespecified subgroup received intravascular ultrasound (IVUS) or optical coherence tomography (OCT) imaging. We determined procedure success and complications during index hospitalization. We monitored all participants for a year. Six-month and 12-month rates of major cardiovascular events were reported. All patients had coronary angiography after 6 months to detect late lumen loss (LLL). Prespecified patients also had IVUS or OCT performed. Results: The rate of device success was 100% (95% CI: 98.3-100%; P<0.001). Major cardiovascular events were 4.7% (95% CI: 1.9-9.4%; P<0.001). The LLL over quantitative coronary angiography (QCA) was 0.08±0.19 mm (95% CI: 0.05-0.10; P<0.001) in the in-stent segment and 0.07±0.31 mm (95% CI: 0.03-0.11; P=0.002) in 5 mm within the two ends of the stent segment. The LLL recorded by IVUS and OCT at 6 months was 0.12±0.35 mm (95% CI: 0.01-0.22; P=0.028) and 0.15±0.24 mm (95% CI: 0.02-0.28; P=0.024), respectively. Conclusions: This study's device success rates were perfect. IVUS and OCT findings on LLL were favorable at 6-month follow-up. One-year follow-up showed low in-stent restenosis (ISR) and target lesion revascularization (TLR) rates, reflecting few significant cardiovascular events. VSTENT's safety and efficacy make it a promising percutaneous intervention option in developing nations.

Trends in Cardiogenic Shock-Related Mortality in Patients With Acute Myocardial Infarction in the United States, 1999 to 2019.

Data on mortality trends in patients with acute myocardial infarction (AMI) with cardiogenic shock (CS) are scant. This study aimed to assess the trends in CS-AMI-related mortality in United States (US) subjects over the latest 21 years. Mortality data of US subjects with AMI listed as the underlying cause of death and CS as contributing cause were obtained from the Centers for Disease Control and Prevention WONDER (Wide-Ranging Online Data for Epidemiologic Research) dataset from January 1999 to December 2019. CS-AMI-related age-adjusted mortality rates (AAMRs) per 100,000 US population were stratified by gender, race and ethnicity, geographic areas, and urbanicity. Nationwide annual trends were assessed as annual percent change (APC) and average APC with relative 95% confidence intervals (CIs). Between 1999 and 2019, CS-AMI was listed as the underlying cause of death in 209,642 patients, (AAMR of 3.01 per 100,000 people [95% CI 2.99 to 3.02]). AAMR from CS-AMI remained stable from 1999 to 2007 (APC -0.2%, [95% CI -2.0 to 0.5], p = 0.22) and then significantly increased (APC 3.1% [95% CI 2.6 to 3.6], p <0.0001), especially in male patients. Starting in 2009, the AAMR increase was more pronounced in those <65 years, Black Americans, and residents of rural areas. The higher AAMRs were clustered in the South (average APC 4.5%, [95% CI 4.4 to 4.6]) of the country. In conclusion, CS-AMI-related mortality in US patients increased from 2009 to 2019. Targeted health policy measures are needed to address the rising burden of CS-AMI in US subjects.

Development of taste-masking microcapsules containing azithromycin by fluid bed coating for powder for suspension and in vivo evaluation.

This research aims to develop bitter taste-masking microcapsules containing azithromycin (AZI) by a simpler and familiar method, fluid-bed coating technology, in comparison with Zithromax®. Cores of microcapsules, AZI microparticles, were prepared by fluid-bed granulation, then taste-masking polymer was covered on by fluid-bed coating technique. Eudragit L100, Eudragit RL100, and ethyl cellulose in single and combined with Eudragit L100 and Eudragit E100 were used as taste-masking polymers. The obtained microcapsules were characterised by taste-masking ability, in vitro release, SEM, coating thickness, and coating efficiency. Combination of ethyl cellulose and Eudragit E100 (3:1) in coating thickness of 45.13 ± 2.12% w/w prevents AZI release from microcapsules below bitter taste threshold (1.78 ± 1.17 µg/ml). Bioavailability of powders containing AZI microcapsules and pH modulators (50 mg Na3PO4 and 35 mg Mg(OH)2) was not significantly different from the reference product (Zithromax®, Pfizer, New York, NY) in the rabbit model (p > 0.05). These results support the possibility of developing a generic product containing AZI.

A Novel Alginate Film Based on Nanocoating Approach for Enteric-Release Tablets.

The objective of this study was to propose a new coating film for biodegradable polymers and environmentally friendly processing. Here, a novel implementation of solid lipid nanoparticles (SLN) into a biodegradable alginate (ALG) film composition created a new gastric-resistant film for an enteric-release tablet. Experiments were performed on a water-soluble substance (thiamine nitrate) to characterize the effects of SLN upon the addition of the ALG coating formulation. The coated tablets or cast films were characterized based on delayed-release properties, surface morphology, moisture resistance, and chemical interactions. The SLN-ALG film displayed gastric-resistant properties (< 10% drug substance dissolved at pH 1.2) and rapid disintegration in the intestinal medium (pH 6.8). Morphological analysis using a microscope and scanning electron microscope confirmed the uniformity and smoothness of the SLN-ALG film, which improved the mechanical properties of the film. Fourier transform infrared spectroscopy and differential scanning calorimetry indicated that SLN contributed to the formation of the film, which maintained free carboxylic groups, making the SLN-ALG film a higher acid resistance, but soluble in pH 6.8 buffer. These promising results suggest a novel nanotechnology-based coating formulation for various enteric-release dosage forms. Because of their biodegradability, the proposed ingredients and processes are safe and environment-friendly.

Synergistic effect of miscible cellulose-based microparticles and pH modulators on the bioavailability of a weakly basic drug and its metabolites.

This study aimed to evaluate the miscibility of cellulose derivatives to improve the release rate and stability of microparticles containing the weakly basic drug itraconazole (ITZ). We also investigated the effect of some organic acids on the microenvironmental pH (pHm) and the release rate of ITZ from the cellulose-based microparticles. The synergistic effect of cellulose-based microparticles and pHm modulators on the bioavailability of ITZ compared with the reference product was investigated in a rabbit model. Differential scanning calorimetry and Fourier-transform infrared spectroscopy (FTIR) analysis showed that ITZ, hydroxypropyl methylcellulose, and hydroxypropyl methylcellulose phthalate were miscible at a ratio of 1.5:3:1 (w/w/w), and the stability of the microparticles was maintained for 6 months under accelerated conditions. In addition, X-ray diffraction, FTIR, and scanning electron microscopy were used to characterize the properties of the microparticles. Through the titration technique and determination of pHm, the combination of fumaric acid and maleic acid (1:2, w/w) was found to be the most effective pHm modulator for microparticles. The integration of cellulose-based microparticles and pHm modulators showed a synergistic effect on the flux and relative bioavailability of ITZ and its active metabolite OH-ITZ (182.60 % and 217.67 %, respectively) when compared with the reference product.

Ridge waveguide couplers with leaky mode resonator-like wavelength responses.

Integrated photonic resonators based on bound states in the continuum (BICs) on the silicon-on-insulator (SOI) platform have the potential for novel, mass-manufacturable resonant devices. While the nature of BIC-based ridge resonators requires the resonators to be extended in the (axial) propagation direction of the resonant mode, the requirement for excitation from the quasi-continuum extends the resonator structures also in the lateral dimensions, resulting in large device footprints. To overcome this footprint requirement, we investigate the translation of BIC-based ridge resonators into a guided mode system with finite lateral dimensions. We draw analogies between the resulting waveguide system and the BIC-based resonators and numerically demonstrate that, analog to the BIC-based resonators, such a waveguide system can exhibit spectrally narrow-band inversion of its transmissive behavior.

Integrated lithium niobate polarization beam splitter based on a photonic-crystal-assisted multimode interference coupler.

Lithium niobate on insulator (LNOI) is a promising platform for high-speed photonic integrated circuits (PICs) that are used for communication systems due to the excellent electro-optic properties of lithium niobate (LN). In such circuits, the high-speed electro-optical modulators and switches need to be integrated with passive circuit components that are used for routing the optical signals. Polarization beam splitters (PBSs) are one of the fundamental passive circuit components for high-speed PICs that can be used to (de)multiplex two orthogonal polarization optical modes, enabling on-chip polarization division multiplexing (PDM) systems, which are suitable for enhancing the data capacity of PICs. In this Letter, we design and experimentally demonstrate a high-performance PBS constructed by a photonic crystal (PC)-assisted multimode interference (MMI) coupler. The measured polarization extinction ratio (ER) of the fabricated device is 15 dB in the wavelength range from 1525 to 1565 nm, which makes them suitable for the high-speed and large data capacity PICs required for future communication systems.

Lateral supramalleolar flap for soft-tissue coverage of ankle and foot defects.

The reconstruction of soft tissue defects in the foot and ankle remains a big challenge due to the anatomical characteristics of this area. This study evaluated the long-term effectiveness of covering by lateral supramalleolar flap in patients with soft tissue defects around the ankle and foot. We conducted a retrospective study from January 2017 to December 2020 at the Hospital for Traumatology and Orthopedics, Ho Chi Minh City, Vietnam. Data about patients' characteristics, detailed injuries, perioperative information, intraprocedural dossier, and complications of this method were recorded and analyzed. There were 31 male and 17 female patients, with an average age of 39.8 (ranging from 11 to 77) years. The skin defects ranged from 8 cm2 to 120 cm2. The blood supply for the flap included a mixed-flow pattern (n = 30) and retrograde flow (n = 18). The success rate was 94%. Forty-two patients had been successfully covered, five patients had partial flap necrosis (in which two cases needed skin graft afterwards and three cases got spontaneous healing), only one patient had total flap necrosis. In conclusion, the lateral supramalleolar flap can cover the soft tissue of ankle and foot defects in both mixed-blood supply pattern or retrograde pattern with high success rates. However, the risk of venous congestion should be considered, particularly when using the retrograde pattern flap.

Carbon nanoparticles adversely affect CFTR expression and toxicologically relevant pathways.

Cystic fibrosis is an autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) that can lead to terminal respiratory failure. Ultrafine carbonaceous particles, which are ubiquitous in ambient urban and indoor air, are increasingly considered as major contributors to the global health burden of air pollution. However, their effects on the expression of CFTR and associated genes in lung epithelial cells have not yet been investigated. We therefore evaluated the effects of carbon nanoparticles (CNP), generated by spark-ablation, on the human bronchial epithelial cell line 16HBE14o- at air-liquid interface (ALI) culture conditions. The ALI-cultured cells exhibited epithelial barrier integrity and increased CFTR expression. Following a 4-h exposure to CNP, the cells exhibited a decreased barrier integrity, as well as decreased expression of CFTR transcript and protein levels. Furthermore, transcriptomic analysis revealed that the CNP-exposed cells showed signs of oxidative stress, apoptosis and DNA damage. In conclusion, this study describes spark-ablated carbon nanoparticles in a realistic exposure of aerosols to decrease CFTR expression accompanied by transcriptomic signs of oxidative stress, apoptosis and DNA damage.

Rapid and simple analysis of short and long sequencing reads using DuesselporeTM.

Transcriptome analysis experiments enable researchers to gain extensive insights into the molecular mechanisms underlying cell physiology and disease. Oxford Nanopore Technologies (ONT) has recently been developed as a fast, miniaturized, portable, and cost-effective alternative to next-generation sequencing (NGS). However, RNA-Seq data analysis software that exploits ONT portability and allows scientists to easily analyze ONT data everywhere without bioinformatics expertise is not widely available. We developed DuesselporeTM, an easy-to-follow deep sequencing workflow that runs as a local webserver and allows the analysis of ONT data everywhere without requiring additional bioinformatics tools or internet connection. DuesselporeTM output includes differentially expressed genes and further downstream analyses, such as variance heatmap, disease and gene ontology plots, gene concept network plots, and exports customized pathways for different cellular processes. We validated DuesselporeTM by analyzing the transcriptomic changes induced by PCB126, a dioxin-like PCB, and a potent aryl hydrocarbon receptor (AhR) agonist in human HaCaT keratinocytes, a well-characterized model system. DuesselporeTM was specifically developed to analyze ONT data, but we also implemented NGS data analysis. DuesselporeTM is compatible with Linux, Microsoft, and Mac operating systems and allows convenient, reliable, and cost-effective analysis of ONT and NGS data.

Arbitrary access to optical carriers in silicon photonic mode/wavelength hybrid division multiplexing circuits.

The manipulation of optical modes directly in a multimode waveguide without affecting the transmission of undesired signal carriers is of significance to realize a flexible and simple structured optical network-on-chip. In this Letter, an arbitrary optical mode and wavelength carrier access scheme is proposed based on a series of multimode microring resonators and one multimode bus waveguide with constant width. As a proof-of-concept, a three-mode (de)multiplexing device is designed, fabricated, and experimentally demonstrated. A new, to the best of our knowledge, phase-matching idea is employed to keep the bus waveguide width constant. The mode coupling regions and transmission regions of the microring resonators are designed carefully to selectively couple and transmit different optical modes. The extinction ratio of the microring resonators is larger than 21.0 dB. The mode and wavelength cross-talk for directly (de)multiplexing are less than -12.8 dB and -19.0 dB, respectively. It would be a good candidate for future large-scale multidimensional optical networks.

Identification of genome edited cells using CRISPRnano.

Genome engineering-induced cleavage sites can be resolved by non-homologous end joining (NHEJ) or homology-directed repair (HDR). Identifying genetically modified clones at the target locus remains an intensive and laborious task. Different workflows and software that rely on deep sequencing data have been developed to detect and quantify targeted mutagenesis. Nevertheless, these pipelines require high-quality reads generated by Next Generation Sequencing (NGS) platforms. Here, we have developed a robust, versatile, and easy-to-use computational webserver named CRISPRnano (www.CRISPRnano.de) that enables the analysis of low-quality reads generated by affordable and portable sequencers including Oxford Nanopore Technologies (ONT) devices. CRISPRnano allows fast and accurate identification, quantification, and visualization of genetically modified cell lines, it is compatible with NGS and ONT sequencing reads, and it can be used without an internet connection.