Proteogenomics of Non-smoking Lung Cancer in East Asia Delineates Molecular Signatures of Pathogenesis and Progression.

Lung cancer in East Asia is characterized by a high percentage of never-smokers, early onset and predominant EGFR mutations. To illuminate the molecular phenotype of this demographically distinct disease, we performed a deep comprehensive proteogenomic study on a prospectively collected cohort in Taiwan, representing early stage, predominantly female, non-smoking lung adenocarcinoma. Integrated genomic, proteomic, and phosphoproteomic analysis delineated the demographically distinct molecular attributes and hallmarks of tumor progression. Mutational signature analysis revealed age- and gender-related mutagenesis mechanisms, characterized by high prevalence of APOBEC mutational signature in younger females and over-representation of environmental carcinogen-like mutational signatures in older females. A proteomics-informed classification distinguished the clinical characteristics of early stage patients with EGFR mutations. Furthermore, integrated protein network analysis revealed the cellular remodeling underpinning clinical trajectories and nominated candidate biomarkers for patient stratification and therapeutic intervention. This multi-omic molecular architecture may help develop strategies for management of early stage never-smoker lung adenocarcinoma.

Enhancing Zinc Electrode Stability Through Pre-Desolvation and Accelerated Charge Transfer via a Polyimide Interface for Zinc-Ion Batteries.

Aqueous zinc-based energy storage devices possess superior safety, cost-effectiveness, and high energy density; however, dendritic growth and side reactions on the zinc electrode curtail their widespread applications. In this study, these issues are mitigated by introducing a polyimide (PI) nanofabric interfacial layer onto the zinc substrate. Simulations reveal that the PI nanofabric promotes a pre-desolvation process, effectively desolvating hydrated zinc ions from Zn(H2O)6 2+ to Zn(H2O)4 2+ before approaching the zinc surface. The exposed zinc ion in Zn(H2O)4 2+ provides an accelerated charge transfer process and reduces the activation energy for zinc deposition from 40 to 21 kJ mol-1. The PI nanofabric also acts as a protective barrier, reducing side reactions at the electrode. As a result, the PI-Zn symmetric cell exhibits remarkable cycling stability over 1200 h, maintaining a dendrite-free morphology and minimal byproduct formation. Moreover, the cell exhibits high stability and low voltage hysteresis even under high current densities (20 mA cm-2, 10 mAh cm-2) thanks to the 3D porous structure of PI nanofabric. When integrated into full cells, the PI-Zn||AC hybrid zinc-ion capacitor and PI-Zn||MnVOH@SWCNT zinc-ion battery achieve impressive lifespans of 15000 and 600 cycles with outstanding capacitance retention. This approach paves a novel avenue for high-performance zinc metal electrodes.

Surgical Management of Full-Thickness Macular Holes in Macular Telangiectasia Type 2: A Global Multicenter Study.

PURPOSE: To report on macular hole repair in macular telangiectasia type 2 (MacTel2). DESIGN: Global, multicenter, retrospective case series. PARTICIPANTS: Patients undergoing surgery for MacTel2-associated full-thickness macular hole (MTMH). METHODS: Standardized data collection sheet distributed to all surgeons. MAIN OUTCOME MEASURES: Anatomic closure and visual outcomes of MTMH. RESULTS: Sixty-three surgeries in 47 patients with MTMH were included from 30 surgeons. Mean age was 68.1 years, with 62% female, 72% White, 21% East or South Asian, 2% African American, and 2% Hispanic or Latino. Procedures included 34 internal limiting membrane (ILM) peeling alone, 22 ILM flaps, 5 autologous retinal transplantations (ARTs), 1 retinotomy, and 1 subretinal bleb. For ILM peeling, preoperative visual acuity (VA) was 0.667 ± 0.423 logarithm of the minimum angle of resolution (logMAR). Minimum hole diameter (MHD) was 305.5 ± 159.4 µm (range, 34-573 µm). Sixteen of 34 ILM peels (47%) resulted in MTMH closure. At postoperative month 6, VA was stable at 0.602 ± 0.516 logMAR (P = 0.65). VA improved by at least 2 lines in 43% and at least 4 lines in 24%. For ILM flaps, preoperative VA was 0.878 ± 0.552 logMAR. MHD was 440.8 ± 175.5 µm (range, 97-697 µm), which was significantly larger than for ILM peels (P < 0.01). Twenty of 22 ILM flaps (90%) resulted in MTMH closure, which was significantly higher than for ILM peels (P < 0.01). At postoperative month 6, VA improved to 0.555 ± 0.405 logMAR (P < 0.05). VA improved by at least 2 lines in 56% and at least 4 lines in 28%. For ARTs, preoperative VA was 1.460 ± 0.391 logMAR. MHD was 390.2 ± 203.7 µm (range, 132-687 µm). All 5 ARTs (100%) resulted in MTMH closure. At postoperative month 6, VA was stable at 1.000 ± 0.246 logMAR (P = 0.08). Visual acuity improved at least 2 lines in 25%. CONCLUSIONS: Surgical closure of macular holes improved VA in 57% of MTMHs. Internal limiting membrane flaps achieved better anatomic and functional outcomes than ILM peeling alone. Autologous retinal transplantation may be an option for refractory MTMHs. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Lessons learned: establishing a CLIA-equivalent laboratory for targeted mass spectrometry assays - navigating the transition from research to clinical practice.

Mass spectrometry (MS) assays offer exceptional capabilities in high multiplexity, specificity, and throughput. As proteomics technologies continue advancements to identify new disease biomarkers, transition of these innovations from research settings to clinical applications becomes imperative. To meet the rigorous regulatory standards of clinical laboratories, development of a clinical protein MS assay necessitates adherence to stringent criteria. To illustrate the process, this project focused on using thyroglobulin (Tg) as a biomarker and an immuno-multiple reaction monitoring (iMRM) MS-based assay as a model for establishing a Clinical Laboratory Improvement Amendments (CLIA) compliant laboratory within the Centers of Genomic and Precision Medicine, National Taiwan University. The chosen example also illustrates the clinical utility of MS assays to complement conventional immunoassay-based methods, particularly in cases where the presence of autoantibodies in 10-30% of patients hinders accuracy. The laboratory design entails a comprehensive coordination in spatial layout, workflow organization, equipment selection, ventilation systems, plumbing, electrical infrastructure, documentation procedures, and communication protocols. Practical aspects of the transformation process, including preparing laboratory facilities, testing environments, instrument validation, assay development and validation, quality management, sample testing, and personnel competency, are discussed. Finally, concordant results in proficiency testing demonstrate the harmonization with the University of Washington Medical Center and the quality assurance of the CLIA-equivalent Tg-iMRM MS assay established in Taiwan. The realization of this model protein MS assay in Taiwan highlights the feasibility of international joint development and provides a detailed reference map to expedite the implementation of more MS-based protein assays in clinical laboratories for patient care.

Association of sodium-glucose cotransporter-2 inhibitors and the risk of retinal vascular occlusion: A real-world retrospective cohort study in Taiwan.

AIMS: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are proposed to alleviate the development of inflammatory eye diseases. However, the association between SGLT2i and retinal vascular occlusion remains unclear. Therefore, this study aims to explore the effects of SGLT2i on the incidence of retinal vascular occlusion. MATERIALS AND METHODS: This retrospective cohort study analysed electronic medical records data from the largest multi-institutional database in Taiwan. Individuals who initiated SGLT2is and dipeptidyl peptidase 4 inhibitors (DPP4is) between 2016 and 2019 were included in our analysis. To conduct a homogenous comparison, inverse probability of treatment weighting with propensity scoring was employed. The primary outcome was retinal vascular occlusion, and the secondary outcomes were retinal vascular occlusion-related complications (macular oedema, vitreous haemorrhage, and tractional retinal detachment) and conditions requiring vitreoretinal intervention (intravitreal injection, retinal laser therapy, and vitrectomy). RESULTS: In total, 12,074 SGLT2i users and 39,318 DPP4i users were included. The incidence rate of retinal vascular occlusion in the SGLT2i and DPP4i groups was 1.2 (95% confidence interval [CI], 0.9-1.4) and 1.6 (95% CI, 1.3-1.8) events per 1000 person-years, respectively, which yielded a subdistribution hazard ratio (SHR) of 0.74 (95% CI, 0.55-0.99). Similar risk reductions were observed in the retinal vascular occlusion-related complications (SHR, 0.76; 95% CI, 0.69-0.84) and conditions requiring vitreoretinal intervention (SHR, 0.84; 95% CI, 0.77-0.94). CONCLUSIONS: In this multi-institutional study in Taiwan, SGLT2i use was associated with a reduced risk of retinal vascular occlusion. Further prospective studies are required to ascertain this association.

Risk of age-related macular degeneration in men receiving 5α-reductase inhibitors: a population-based cohort study.

BACKGROUND: Recent studies suggest that 5α-reductase inhibitors (5ARIs) for benign prostate hyperplasia (BPH) result in abnormal retinal anatomical alteration. OBJECTIVE: To compare age-related macular degeneration (AMD) incidence in BPH patients receiving 5ARIs or tamsulosin. DESIGN: Retrospective, population-based cohort study using new-user and active-comparator design. SETTING: General population. SUBJECTS: Males with BPH, newly receiving 5ARIs or tamsulosin from 2010 to 2018. METHODS: Data were extracted from Taiwan's National Health Insurance Research Database. We used Cox proportional hazards model with 1:4 propensity score (PS) matching, based on intention-to-treat analysis to determine the risk of incident AMD. Sensitivity analyses included an as-treated approach and weighting-based PS methods. We also separately reported the risks of incident AMD in patients receiving finasteride and dutasteride to determine risk differences among different 5ARIs. RESULTS: We included 13 586 5ARIs users (mean age: 69 years) and 54 344 tamsulosin users (mean age: 68.37 years). After a mean follow-up of 3.7 years, no differences were observed in the risk of incident AMD between 5ARIs and tamsulosin users [hazard ratio (HR): 1.06; 95% confidence intervals (95% CI): 0.98-1.15], with similar results from sensitivity analyses. However, increased risk of incident age-related macular degeneration was observed in patients receiving dutasteride [HR: 1.13; 95% CI: 1.02-1.25], but not in those receiving finasteride [HR: 0.99; 95% CI: 0.87-1.12], in the subgroup analyses. CONCLUSIONS: We found no difference between 5ARIs and tamsulosin regarding the incidence of AMD in BPH patients. However, the risk profiles for AMD differed slightly between dutasteride and finasteride, suggesting that the potency of androgen inhibition is a factor related to AMD incidence.

A comparative study of stereopsis in term and preterm children with and without retinopathy of prematurity.

PURPOSE: To evaluate stereopsis in term-born, preterm, and preterm children with and without retinopathy of prematurity (ROP) and its treatment. METHODS: The cross-sectional study included 322 children between 3 and 11 years of age born term or preterm, with or without ROP, and with or without treatment for ROP. The ROP treatments were laser therapy, intravitreal injection (IVI) of anti-vascular endothelial growth factor, or their combination. Stereoacuity was measured using the Titmus Stereo Test, and the results among various age groups were analyzed. RESULTS: Stereopsis was found to improve with increasing age at testing (P < 0.001) across the entire study population. The term group exhibited significantly better stereoacuity than the preterm group (P < 0.001). At 3-5 years and 6-8 years, the preterm children without ROP exhibited significantly better stereoacuity than did those with ROP (P < 0.001 and P = 0.02, respectively); however, at 9-11 years, both groups exhibited similar stereoacuity (P = 0.34). The stereoacuity in the children with untreated ROP was similar to that of the children with treated ROP in all age groups (P > 0.05). No significant differences in stereopsis were identified between children with ROP treated with laser versus with IVI (P > 0.05). From multivariate analysis, younger age at testing (P = 0.001) and younger gestational age (P < 0.001) were associated with poorer stereopsis. CONCLUSIONS: Stereopsis development gradually improved with age in all groups. The children born preterm exhibited poorer stereoacuity than those born term. Children with ROP treated with laser photocoagulation versus IVI may exhibit similar levels of stereoacuity. Younger age at testing and gestational age were independent risk factors for poorer stereoacuity.

LONGITUDINAL CHANGES IN CHOROIDAL THICKNESS IN CHILDREN WITH A HISTORY OF PREMATURITY: An 18-Month Prospective Cohort Study.

PURPOSE: To evaluate choroidal changes over time in school-age children with a history of prematurity. METHODS: A study of 416 eyes of 208 eligible participants, including 88, 190, 36, 56, and 46 eyes in the full-term control, preterm, spontaneously regressed retinopathy of prematurity, intravitreal bevacizumab (injection of bevacizumab)-treated retinopathy of prematurity, and laser-treated retinopathy of prematurity groups, respectively, were enrolled in this study. The choroidal thickness was measured 4 times at 6-month intervals using optical coherence tomography. RESULTS: Of all the groups, the laser-treated children had the thinnest choroid compared with full-term children (-52.3 µ m, P = 0.04). Preterm children exhibited greater attenuation in choroidal thickness over time than did full-term children (-6.3 ± 26.9 and -1.1 ± 12.8 µ m/year, P = 0.03), whereas no difference was observed between injection of bevacizumab and laser treatments (-4.6 ± 18.9 and -2.0 ± 15.7 µ m/year, P = 0.46). In all groups, the changes in axial length were negatively associated with the changes in choroidal thickness (all P < 0.05). CONCLUSION: A greater attenuation in choroid thickness over time was observed in preterm children than in full-term children, but this attenuation did not differ between injection of bevacizumab and laser treatments. Axial elongation was associated with choroidal thinning in school-age children.

PRESENTATIONS AND FACTORS AFFECTING OUTCOME OF RHEGMATOGENOUS RETINAL DETACHMENT WITH CHOROIDAL DETACHMENT: An Indo-Taiwanese Study.

PURPOSE: To report the clinical settings, management, and factors associated with outcomes of rhegmatogenous retinal detachment with concurrent choroidal detachment. METHODS: Retrospective, consecutive, multicenter case series from January 2014 to January 2021 were included. Cases were from a tertiary eye care center in India and Taiwan. RESULTS: Overall 303 eyes were included. Mean age was 43.72 ± 20.64 years (median 46). Best-corrected presenting visual acuity was 1.79 ± 0.92 logMAR (median 2.10) (Snellen 20/1,233). Forty-four patients (17.91%) received preoperative steroids. Final visual acuity was 1.33 ± 0.94 logMAR (median 1.10) (Snellen 20/427). Favorable anatomic outcome was seen in 200/303 (66%), whereas favorable functional outcome was seen in 128/303 (42.20%). Factors predicting favorable anatomic outcome were absence of phakic lens status (odds ratio [OR] 2.76), absence of proliferative vitreoretinopathy worse than Grade A (OR 7.69), use of preoperative steroids (OR 4.50), and use of an encircling band (3.85). Factors predicting favorable functional outcome were better presenting visual acuity (OR 3.03), absence of phakic lens status (OR 4.93), absence of proliferative vitreoretinopathy worse than Grade A (OR 10.41), and use of preoperative steroids (OR 7.24). CONCLUSION: Administration of preoperative steroids, use of an encircling band during surgery, and pseudophakic status of the eye were found to have better outcomes in rhegmatogenous retinal detachment with concurrent choroidal detachment.

Administering Intravitreal Bevacizumab for Retinopathy of Prematurity: 8-Year Cognitive Outcomes in a Prospective Cohort.

PURPOSE: Determine whether intravitreal injection of bevacizumab (IVB) exerts long-term effects on neurodevelopmental outcomes in children with retinopathy of prematurity (ROP) when reaching the age of 8 years. METHODS: We enrolled 277 children. Patients were stratified into the groups full-term, preterm without ROP, ROP without treatment, or ROP with treatment, based on gestational age (GA) and ROP status. Children under GA of 37 weeks were considered premature. Patients' cognitive outcomes were evaluated using Full-Scale Intelligence Quotient (FIQ) (full score and percentile) generated by the Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) every 1 to 2 years. RESULTS: At the mean age of 7.8 years, ROP without and with treatment groups demonstrated lower FIQ scores and percentiles, compared with full-term and premature groups (both p<0.05). FIQ scores and percentiles didn't significantly differ between patients who received different treatments for ROP (full score p=0.19; percentile p=0.37). After adjusting for GA, LogMAR best corrected visual acuity (BCVA) was negatively associated with FIQ scores (p=0.0008) and percentiles (p=0.0002). CONCLUSIONS: At the mean age of 8 years, patients with ROP undergoing IVB didn't exhibit worse cognitive outcomes than those who underwent laser photocoagulation or both treatments. GA and BCVA correlated with cognitive development in children.

Neonatal gut microbiota profile and the association with retinopathy of prematurity in preterm infants.

BACKGROUND: To explore the role of gut microbiota in preterm infants at high risk of developing retinopathy of prematurity (ROP). METHODS: Preterm infants with gestational age (GA) < 32 weeks and/or birth weight (BW) < 1500 g born between 2020 and 2021 were prospectively enrolled. Their faecal samples were collected and analysed at different postnatal ages of life using 16S rRNA gene sequencing on the Miseq platform. The main outcome measures were the microbial diversity, taxonomy, relative abundance, bacterial predicted functional analysis, and their associations with different ROP groups. Subgroup analyses were performed by matching their GA and BW across different ROP groups. RESULTS: A total of 268 stool samples were collected from 110 preterm infants, including 13 with type 1 ROP, 44 with type 2 or mild ROP, and 53 without ROP. Type 1 ROP showed no significant difference in microbial diversity up to 8 postnatal weeks (p = 0.057), while type 2 and no ROP groups displayed increased diversity (p = 0.0015 and p = 0.049, respectively). Bifidobacterium genera was notably less abundant in type 1 ROP group at first postnatal week (p = 0.022) and remained low in subsequent weeks. Predicted functional analysis revealed enriched pathways in membrane transport, carbohydrate metabolism, amino acid metabolism, and replication and repair. CONCLUSIONS: Reduced gut microbial diversity may be associated with ROP development in high-risk preterm infants. Further research is needed to comprehend how early-life Bifidobacterium reduction affects metabolism and how targeting microbiome may help for ROP prevention and management.

Exploring the Location of Corneal Pigmented Arc and Myopia Control Efficacy in Orthokeratology-Treated Children Using Pentacam Measurements.

OBJECTIVES: To determine the location and intensity of the corneal pigmented arc in orthokeratology (ortho-k)-treated children and its relationship with annual axial length (AL) change using Pentacam. METHODS: This retrospective cohort study enrolled children aged 9 to 15 years who had been followed up for at least one year after ortho-k treatment for myopia control. A Pentacam was used to determine the location and intensity of pigmented arc after lens wear. Annual AL changes were further used as the outcome measurement to determine their relationships with the location and intensity of pigmented arc using generalized estimating equations (GEE). RESULTS: In total, 62 eyes from 33 patients (mean age 10.9 years) were included in our final analysis. The mean follow-up time was 30.6 months. The mean annual AL changes were 0.10 mm. Age statistically correlated with annual AL change (GEE, P= 0.033). In addition, the annual AL change was negatively associated with the relative vertical distance of the lowest density of pigmented arc point based on the visual center, pupil center, and corneal thinnest point after adjustment with age ( P =0.005, P =0.004, and P< 0.001, respectively). CONCLUSIONS: Pentacam could be a useful tool for evaluating the location and intensity of the corneal pigmented arc. In addition, there was a negative correlation between the vertical distance of the pigmented arc and annual AL change. These findings may provide important information regarding myopia control, next-generation ortho-k design, and prescription.

Nutritional deficiency anemia and post-acute sequelae in patients with severe acute respiratory syndrome coronavirus 2 infection: A six-month retrospective cohort analysis of 30 892 patients.

The effect of anemia on the post-acute outcome of patients with severe acute respiratory syndrome coronavirus 2 infection was unclear. This study aimed to investigate the potential association between nutritional deficiency anemia (NDA) status and post-acute sequelae of patients with SARS-CoV-2 infection. This retrospective cohort study included patients with coronavirus disease (COVID-19) from January 1, 2022 to November 30, 2022 using the TriNetX research network. The patients were grouped into the NDA group comprising patients diagnosed with NDA and the control group comprising patients without NDA, and propensity score matching (PSM) was performed to balance the two groups. The primary outcome was a composite of post-COVID-19 condition, all-cause hospitalization, and all-cause death. The secondary outcomes were any individual outcomes of the primary composite. The follow-up period was set at 90-180 days after COVID-19 diagnosis. Two cohorts comprising 15 446 nonhospitalized patients with COVID-19 in each group with balanced baseline characteristics were created using PSM. During the follow-up period, the NDA group demonstrated a higher risk of the composite primary outcome, including post-COVID-19 condition, all-cause hospitalization, or all-cause death (hazard ratio [HR], 1.896; 95% confidence interval [CI] = 1.757-2.045). Regarding secondary outcomes, the NDA group was associated with worse outcomes, including post-COVID-19 condition (HR, 1.992; 95% CI = 1.403-2.828), all-cause hospitalization (HR, 1.856; 95% CI = 1.714-2.009), and all-cause death (HR, 3.922; 95% CI = 2.910-5.285) compared to the control group. Among nonhospitalized patients with COVID-19, NDA was associated with a higher risk of post-COVID-19 condition, all-cause hospitalization, and all-cause death during the 90-180-day follow-up period.

Antiviral therapy reduces hepatocellular carcinoma through suppressing hepatitis B virus replication may improve ER stress, mitochondrial and metabolic dysfunctions and decrease p62 in hybridized mice with single HBV transgene and miR-122.

Hepatitis B virus (HBV) hijacks autophagy for its replication. Nucleos(t)ide analogs (NUCs) treatment suppressed HBV replication and reduced hepatocellular carcinoma (HCC) incidence. However, the use of NUCs in chronic hepatitis B (CHB) patients with normal or minimally elevated serum alanine aminotransferase (ALT) levels is still debated. Animal models are crucial for studying the unanswered issue and evaluating new therapies. MicroRNA-122 (miR-122), which regulates fatty acid and cholesterol metabolism, is downregulated during hepatitis and HCC progression. The reciprocal inhibition of miR-122 with HBV highlights its role in HCC development as a tumor suppressor. By crossbreeding HBV-transgenic mice with miR-122 knockout mice, we generated a hybrid mouse model with a high incidence of HCC up to 89% and normal ALT levels before HCC. The model exhibited early-onset hepatic steatosis, progressive liver fibrosis, and impaired late-phase autophagy. Metabolomics and microarray analysis identified metabolic signatures, including dysregulation of lipid metabolism, inflammation, genomic instability, the Warburg effect, reduced TCA cycle flux, energy deficiency, and impaired free radical scavenging. Antiviral treatment reduced HCC incidence in hybrid mice by approximately 30-35% compared to untreated mice. This effect was linked to the activation of ER stress-responsive transcription factor ATF4, clearance of autophagosome cargo p62, and suppression of the CHOP-mediated apoptosis pathway. In summary, this study suggests that despite minimal ALT elevation, HBV replication can lead to liver injury. Endoplasmic reticulum stress, reduced miR-122 levels, mitochondrial and metabolic dysfunctions, blocking protective autophagy resulting in p62 accumulation, apoptosis, fibrosis, and HCC. Antiviral may improve the above-mentioned pathogenesis through HBV suppression.

Optimal lattice depth on lifetime of D-band ultracold atoms in a triangular optical lattice.

Ultracold atoms in optical lattices are a flexible and effective platform for quantum precision measurement, and the lifetime of high-band atoms is an essential parameter for the performance of quantum sensors. In this work, we investigate the relationship between the lattice depth and the lifetime of D-band atoms in a triangular optical lattice and show that there is an optimal lattice depth for the maximum lifetime. After loading the Bose-Einstein condensate into D band of optical lattice by shortcut method, we observe the atomic distribution in quasi-momentum space for the different evolution time, and measure the atomic lifetime at D band with different lattice depths. The lifetime is maximized at an optimal lattice depth, where the overlaps between the wave function of D band and other bands (mainly S band) are minimized. Additionally, we discuss the influence of atomic temperature on lifetime. These experimental results are in agreement with our numerical simulations. This work paves the way to improve coherence properties of optical lattices, and contributes to the implications for the development of quantum precision measurement, quantum communication, and quantum computing.

Spatially adaptive calibrations of airbox PM2.5 data.

The Taiwan air quality monitoring network (TAQMN) and the AirBox network both monitor PM2.5 in Taiwan. The TAQMN, managed by Taiwan's Environmental Protection Administration (EPA), provides high-quality PM2.5 measurements at 77 monitoring stations. The AirBox network launched more recently consists of low-cost, small internet-of-things (IoT) microsensors (i.e., AirBoxes) at thousands of locations. While the AirBox network provides broad spatial coverage, its measurements are unreliable and require calibrations. However, applying a universal calibration procedure to all AirBoxes does not work well because the calibration line varies with local factors, including the chemical compositions of PM2.5 , which are not homogeneous in space. Therefore, different calibrations are needed at different locations to adapt to their local environments. Unfortunately, AirBoxes and EPA locations are misaligned, challenging the calibration task. In this paper, we propose a spatial model with spatially varying coefficients to account for the heterogeneity in the data. Our method gives spatially adaptive calibrations of AirBoxes and produces accurate PM2.5 concentration estimates with their error bars at any location, incorporating two types of measurements. In addition, the proposed method is robust to outliers, requires no colocated data, and provides calibration formulas for new AirBoxes once they are added to the network. We illustrate our approach using hourly PM2.5 data in 2020. After the calibration, the results show that the PM2.5 prediction improves by about 38%-68% in root-mean-squared prediction error. Once the calibration formulas are established, we can obtain reliable PM2.5 values even if we ignore EPA data.

PEELING AND INTERNAL LIMITING MEMBRANE REPOSITION (PAIR) FOR MYOPIC FOVEOSCHISIS.

PURPOSE: To report the outcomes of the Peeling and Internal Limiting Membrane Reposition (PAIR) technique in myopic foveoschisis. METHODS: A retrospective case series of eyes with myopic foveoschisis that underwent vitrectomy and PAIR. Visual acuity, fundus photographs, and optical coherence tomography measurements were obtained and analyzed. Data are presented as medians (ranges). RESULTS: A total of seven eyes underwent PAIR and were followed up for 339 days (188-436 days). No intraoperative complications were noted. One eye exhibited postoperative macular hole formation, but the hole was healed through fluid-gas exchange. At the last follow-up, the visual acuity had improved from 20/66 (20/332-20/40) to 20/40 (20/100-20/25), and the central foveal thickness had decreased from 576 µ m to 269 µ m. A repositioned internal limiting membrane (ILM) was observed in six of the eyes, and inner retinal dimples were noted in only two eyes. However, retinal wrinkles under the repositioned or perifoveal ILM were noted in five eyes. CONCLUSION: The PAIR technique relieved traction, restored the ILM, and achieved functional and morphological improvement in eyes with myopic foveoschisis. Limited occurrence of inner retinal dimples and retinal thinning was noted, but retinal wrinkles occurred, likely due to ILM contracture.

Unbiased optical mapping of telomere-integrated endogenous human herpesvirus 6.

Next-generation sequencing technologies allowed sequencing of thousands of genomes. However, there are genomic regions that remain difficult to characterize, including telomeres, centromeres, and other low-complexity regions, as well as transposable elements and endogenous viruses. Human herpesvirus 6A and 6B (HHV-6A and HHV-6B) are closely related viruses that infect most humans and can integrate their genomes into the telomeres of infected cells. Integration also occurs in germ cells, meaning that the virus can be inherited and result in individuals harboring the virus in every cell of their body. The integrated virus can reactivate and cause disease in humans. While it is well established that the virus resides in the telomere region, the integration locus is poorly defined due to the low sequence complexity (TTAGGG)n of telomeres that cannot be easily resolved through sequencing. We therefore employed genome imaging of the integrated HHV-6A and HHV-6B genomes using whole-genome optical site mapping technology. Using this technology, we identified which chromosome arm harbors the virus genome and obtained a high-resolution map of the integration loci of multiple patients. Surprisingly, this revealed long telomere sequences at the virus-subtelomere junction that were previously missed using PCR-based approaches. Contrary to what was previously thought, our technique revealed that the telomere lengths of chromosomes harboring the integrated virus genome were comparable to the other chromosomes. Taken together, our data shed light on the genetic structure of the HHV-6A and HHV-6B integration locus, demonstrating the utility of optical mapping for the analysis of genomic regions that are difficult to sequence.

The prognostic utility of preoperative geriatric nutritional risk index on survival outcomes of locally advanced oral cancer.

PURPOSE: This retrospective cohort study was to assess the prognostic value of preoperative geriatric nutritional risk index (GNRI) on survival outcomes for patients with locally advanced oral squamous cell carcinoma (LAOSCC). METHODS: Patients with LAOSCC receiving upfront radical surgery at a single institute from January 2007 to February 2017 were enrolled. The primary outcomes in the study were 5-year overall survival (OS) and cancer-specific survival (CSS) rates, and a nomogram based on GNRI and other clinical-pathological factors was established for individualized OS prediction. RESULTS: There were 343 patients enrolled in this study. The optimal cut-off value of GNRI was observed to be 97.8. Patients in the high-GNRI group (GNRI ≥97.8) had statistically significantly better outcomes in 5-year OS (74.7% vs. 57.2%, p = 0.001) and CSS (82.2% vs. 68.9%, p = 0.005) when compared with the low-GNRI group (GNRI <97.8). In Cox models, low GNRI remained an independent negative prognosticator of OS (HR: 1.6; 95% CI: 1.124-2.277; p = 0.009) and CSS (HR: 1.907; 95% CI: 1.219-2.984; p = 0.005). The c-index of the proposed nomogram, incorporating assorted clinicopathological factors and GNRI, had a statistically significant increase compared with the predictive nomogram constructed by the TNM staging system alone (0.692 vs. 0.637, p < 0.001)." CONCLUSION: Preoperative GNRI is an independent prognostic factor of OS and CSS in patients with LAOSCC. A multivariate nomogram that includes GNRI may better help us to accurately estimate individual survival outcomes.

Paper-Based Exosomal MicroRNA-21 Detection for Wound Monitoring: A Proof of Concept and Clinical Validation Trial Study.

Emerging evidence has shown that microRNAs play pivotal roles in wound healing. MicroRNA-21 (miR-21) was previously found to upregulate in order to fulfill an anti-inflammation role for wounds. Exosomal miRNAs have been identified and explored as essential markers for diagnostic medicine. However, the role of exosomal miR-21 in wounds has yet to be well studied. In order to facilitate the early management of poorly healing wounds, we developed an easy-to-use, rapid, paper-based microfluidic-exosomal miR-21 extraction device to determine wound prognosis in a timely manner. We isolated and then quantitatively examined exosomal miR-21 in wound fluids from normal tissues and acute and chronic wounds. Eight improving wounds displayed lower levels of exosomal miR-21 expression after wound debridement. However, four instances of increased exosomal miR-21 expression levels were notably associated with patients with poor healing wounds despite aggressive wound debridement, indicating a predictive role of tissue exosomal miR-21 for wound outcome. Paper-based nucleic acid extraction device provides a rapid and user-friendly approach for evaluating exosomal miR-21 in wound fluids as a means of monitoring wounds. Our data suggest that tissue exosomal miR-21 is a reliable marker for determining current wound status.