Cell refractive index is a key biophysical parameter, which has been extensively studied. It is correlated with other cell biophysical properties including mechanical, electrical and optical ...properties, and not only represents the intracellular mass and concentration of a cell, but also provides important insight for various biological models. Measurement techniques developed earlier only measure the effective refractive index of a cell or a cell suspension, providing only limited information on cell refractive index and hence hindering its in-depth analysis and correlation. Recently, the emergence of microfluidic, photonic and imaging technologies has enabled the manipulation of a single cell and the 3D refractive index of a single cell down to sub-micron resolution, providing powerful tools to study cells based on refractive index. In this review, we provide an overview of cell refractive index models and measurement techniques including microfluidic chip-based techniques for the last 50 years, present the applications and significance of cell refractive index in cell biology, hematology, and pathology, and discuss future research trends in the field, including 3D imaging methods, integration with microfluidics and potential applications in new and breakthrough research areas.
Cell refractive index is an important biophysical parameter, which provides new biological and biomedical insight for disease diagnosis and cell biology.
To evaluate the functional and structural changes of the meibomian glands and ocular surface in immunoglobulin G4–related ophthalmic disease (IgG4-ROD) patients.
Cross-sectional, matched case-control ...comparison study.
This study included 64 patients with biopsy-proven IgG4-ROD (aged 63.4 ± 12.2 years, 39 male) and 64 sex- and age-matched healthy controls. Patients were managed by hospitals covering the publicly funded ophthalmology service in Hong Kong. Outcome measures included anterior segment examination and keratographic and meibographic imagings.
A total of 64 worst-affected eyes of the 64 IgG4-ROD patients were analyzed. Corneal fluorescein staining (P = .0187), lid margin telangiectasia (P = .0360), lid-parallel conjunctival folds (P = .0112), papillae (P = .0393), meibomian gland plugging (P = .0001), meibomian gland expressibility (P = .0001), and meibum quality (P = .0001) were more significant in IgG4-ROD patients compared with healthy controls. Both upper and lower meibomian gland dropouts (P = .001 and .0003), and tear meniscus height (P = .0001) were higher in IgG4-ROD patients. Non-invasive tear break-up time (NITBUT) (P = .0166) and Schirmer test results (P = .0243) were lower in IgG4-ROD patients. Upper (r = 0.336, P = .0140) meibomian gland dropouts and NITBUT (r = –0.293, P = .0497) were positively and negatively correlated with the IgG4-ROD onset age, respectively. The number of extraocular organ involvement was negatively correlated with the Schirmer test(r = –0.341, P = .0167). Lower NITBUT was found in IgG4-ROD eyes with lacrimal gland enlargement than in IgG4-ROD eyes without lacrimal gland enlargement radiologically (P < .0001).
IgG4-ROD patients showed features of both aqueous tear deficiency and evaporative dry eye disease. We recommend ocular surface evaluation to all patients newly diagnosed with IgG4-ROD. Further studies are warranted to clarify the mechanism of IgG4-related dry eye disease.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Particle trapping and binding in optical potential wells provide a versatile platform for various biomedical applications. However, implementation systems to study multi-particle contact interactions ...in an optical lattice remain rare. By configuring an optofluidic lattice, we demonstrate the precise control of particle interactions and functions such as controlling aggregation and multi-hopping. The mean residence time of a single particle is found considerably reduced from 7 s, as predicted by Kramer's theory, to 0.6 s, owing to the mechanical interactions among aggregated particles. The optofluidic lattice also enables single-bacteria-level screening of biological binding agents such as antibodies through particle-enabled bacteria hopping. The binding efficiency of antibodies could be determined directly, selectively, quantitatively and efficiently. This work enriches the fundamental mechanisms of particle kinetics and offers new possibilities for probing and utilising unprecedented biomolecule interactions at single-bacteria level.
Single chip integrated spectrometers are critical to bring chemical and biological sensing, spectroscopy, and spectral imaging into robust, compact and cost-effective devices. Existing on-chip ...spectrometer approaches fail to realize both high resolution and broad band. Here we demonstrate a microring resonator-assisted Fourier-transform (RAFT) spectrometer, which is realized using a tunable Mach-Zehnder interferometer (MZI) cascaded with a tunable microring resonator (MRR) to enhance the resolution, integrated with a photodetector onto a single chip. The MRR boosts the resolution to 0.47 nm, far beyond the Rayleigh criterion of the tunable MZI-based Fourier-transform spectrometer. A single channel achieves large bandwidth of ~ 90 nm with low power consumption (35 mW for MRR and 1.8 W for MZI) at the expense of degraded signal-to-noise ratio due to time-multiplexing. Integrating a RAFT element array is envisaged to dramatically extend the bandwidth for spectral analytical applications such as chemical and biological sensing, spectroscopy, image spectrometry, etc.
Epitheliotropic intestinal T-cell lymphoma (EITL, also known as type II enteropathy-associated T-cell lymphoma) is an aggressive intestinal disease with poor prognosis and its molecular alterations ...have not been comprehensively characterized. We aimed to identify actionable easy-to-screen alterations that would allow better diagnostics and/or treatment of this deadly disease. By performing whole-exome sequencing of four EITL tumor-normal pairs, followed by amplicon deep sequencing of 42 tumor samples, frequent alterations of the JAK-STAT and G-protein-coupled receptor (GPCR) signaling pathways were discovered in a large portion of samples. Specifically, STAT5B was mutated in a remarkable 63% of cases, JAK3 in 35% and GNAI2 in 24%, with the majority occurring at known activating hotspots in key functional domains. Moreover, STAT5B locus carried copy-neutral loss of heterozygosity resulting in the duplication of the mutant copy, suggesting the importance of mutant STAT5B dosage for the development of EITL. Dysregulation of the JAK-STAT and GPCR pathways was also supported by gene expression profiling and further verified in patient tumor samples. In vitro overexpression of GNAI2 mutants led to the upregulation of pERK1/2, a member of MEK-ERK pathway. Notably, inhibitors of both JAK-STAT and MEK-ERK pathways effectively reduced viability of patient-derived primary EITL cells, indicating potential therapeutic strategies for this neoplasm with no effective treatment currently available.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Intrinsic apoptosis is critical to prevent tumor formation and is engaged by many anti-cancer agents to eliminate tumor cells. BAX and BAK, the two essential mediators of apoptosis, are thought to be ...regulated through similar mechanisms and act redundantly to drive apoptotic cell death. From an unbiased genome-wide CRISPR/Cas9 screen, we identified VDAC2 (voltage-dependent anion channel 2) as important for BAX, but not BAK, to function. Genetic deletion of VDAC2 abrogated the association of BAX and BAK with mitochondrial complexes containing VDAC1, VDAC2, and VDAC3, but only inhibited BAX apoptotic function. Deleting VDAC2 phenocopied the loss of BAX in impairing both the killing of tumor cells by anti-cancer agents and the ability to suppress tumor formation. Together, our studies show that efficient BAX-mediated apoptosis depends on VDAC2, and reveal a striking difference in how BAX and BAK are functionally impacted by their interactions with VDAC2.
BACKGROUNDImmunoglobulin G4-related ophthalmic disease (IgG4-ROD) poses clinical challenges due to its heterogeneous ocular and systemic manifestations. We aim to report the systemic involvement and ...the clinical, serological and radiological associations of a cohort of Chinese patients.METHODSA territory-wide, biopsy-proven, Chinese cohort. A retrospective, masked chart review of medical records, orbital images, and histopathology reports.RESULTSA total of 122 (65 male) patients with a follow-up of 81 ± 49 (24 to 84) months were reviewed. Ninety (74%) patients presented bilaterally. Subacute upper eyelid swelling was the commonest presentation (82/122, 67%). During follow-up, 91/122 patients (75%) underwent extra-orbital imaging including computer tomography (692 films), ultrasonography (182 films), magnetic resonance imaging (76 films) and whole body FDG-PET scan (33 films). Eighty-six (95%) of these 91 patients had extra-orbital involvement radiologically (2.7 ± 1.6 regions, range: 0 to 9). Lymph node was the most prevalent (N = 60,66%), followed by salivary gland (N = 51,56%), lung (N = 49,54%), kidney (N = 22, 24%), hepatobiliary tree (N = 18, 20%) and pancreas (N = 17, 19%). Other organs include thyroid, aorta, meninges/brain and skin. Twenty-eight (23%) patients had allergic diseases (19 asthma, 16 allergic rhinitis, and 6 eczemas). Fifty-seven (48%) patients had paranasal sinusitis. Serum eosinophilia was associated with a higher number (3.24 versus 2.52, P = 0.0304) of organ involvement. Patients with deep organ involvement was associated with a higher age of IgG4-ROD onset (70 ± 12 versus 56 ± 13, P < 0.0001).CONCLUSIONS95% of the patients who underwent systemic imaging in our cohort had systemic organ involvement. An early physicians' assessment and radiological imaging are recommended after the diagnosis of IgG4-ROD.
Purpose
Clinical phenotypes in Immunoglobulin G4-related disease (IgG4-RD) according to the patterns of affecting organs have different risks of malignancies. We attempt to determine the association ...of malignancies with IgG4-related ophthalmic disease (IgG4-ROD).
Design
Retrospective cohort study.
Methods
Review of medical records, orbital images and histopathology reports in a territory-wide cohort of biopsy proven IgG4-ROD patients from 2005–2019.
Findings
Among 122 patients who had biopsies taken from adnexal lesions including lacrimal glands (n = 108), orbital mass (n = 30), infiltrated orbital fat (n = 10), conjunctiva (n = 2) or extraocular muscles (n = 3), 13% (16/122) developed malignancies over 73 ± 48months’ follow-up. There were 9 cases of ocular adnexal lymphoma (OAL) and 7 extra-orbital malignancies. Compared with the general population, the incidence of OAL was significantly higher (standardized incidence ratios, SIRs = 10.0, 95%CI = 4.5–17.6) while that of extra-orbital malignancies was similar. The SIRs was highest within the first year (SIR = 46.7, 95%CI = 18.5–87.6) when 7 OAL were concomitantly diagnosed. Patients who developed OAL or extra-orbital malignancies were older than other patients at IgG4-ROD diagnosis (64.9 ± 7.1, 68.3 ± 8.5 versus 55.2 ± 15.0 years, P < 0.05). Asymmetric lacrimal gland enlargement (78% versus 13%), lack of frontal (0% versus 12%) or infraorbital nerve enlargement (0% versus 36%) were associated with OAL (all P < 0.05). Pre-treatment serum IgG4 level or extra-orbital IgG4-RD involvement was similar among patients with or without malignancies.
Conclusion
In this biopsy-proven IgG4-ROD cohort, 7% developed OAL which was 10 times higher than the general population. Patients with asymmetric lacrimal gland enlargement or without trigeminal nerves involvement radiologically were associated with OAL.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Abstract
Laser probing remains invaluable to the semiconductor industry for isolating and diagnosing defects in silicon transistors in integrated circuits during electrical stress tests. However, ...continuous device miniaturization below the 20 nm technology node has crammed multiple transistors within the focal spot of the laser beam, resulting in signal crosstalk, poor beam positioning accuracy and degraded fault isolation capabilities. The challenge is analogous to focusing attention to a single speaker in a crowd despite the multiple simultaneous conversations in the background. Through algorithms introduced in this patented work, consisting of cross-correlations, clustering, and our previously developed combinational logic analysis, we achieved beam positioning accuracy to better than 10 nm, extracted electrooptic waveforms from a node of a group of transistors (~18 times beyond the optical resolution limit), and applied this to isolate and identify an actual fault on a defective device. While problems associated with probing with shorter wavelength lasers continue to be addressed, our approach enhances and enables the continued probing of ICs using sub-bandgap photon energies without hardware modification to existing technology at semiconductor technology nodes below 10 nm.
The COVID-19 pandemic constitutes a social crisis that will have long-term health consequences for much of the global population, especially for adolescents. Adolescents are triply affected as they: ...1) are experiencing its immediate, direct effects, 2) will carry forward health habits they develop now into adulthood, and 3) as future parents, will shape the early life health of the next generation. It is therefore imperative to assess how the pandemic is influencing adolescent wellbeing, identify sources of resilience, and outline strategies for attenuating its negative impacts.
We report the results of longitudinal analyses of qualitative data from 28 focus group discussions (FGDs) with 39 Canadian adolescents and of cross-sectional analyses of survey data from 482 Canadian adolescents gathered between September 2020 and August 2021. FGD participants and survey respondents reported on their: socio-demographic characteristics; mental health and wellbeing before and during the pandemic; pre- and during-pandemic health behaviours; experiences living through a crisis; current perceptions of their school, work, social, media, and governmental environments; and ideas about pandemic coping and mutual aid. We plotted themes emerging from FGDs along a pandemic timeline, noting socio-demographic variations. Following assessment for internal reliability and dimension reduction, quantitative health/wellbeing indicators were analyzed as functions of composite socio-demographic, health-behavioural, and health-environmental indicators.
Our mixed methods analyses indicate that adolescents faced considerable mental and physical health challenges due to the pandemic, and were generally in poorer health than expected in non-crisis times. Nevertheless, some participants showed significantly better outcomes than others, specifically those who: got more exercise; slept better; were food secure; had clearer routines; spent more time in nature, deep in-person social relationships, and leisure; and spent less time on social media.
Support for youth during times of crisis is essential to future population health because adolescence is a period in the life course which shapes the health behaviours, socio-economic capacities, and neurophysiology of these future parents/carers and leaders. Efforts to promote resilience in adolescents should leverage the factors identified above: helping them find structure and senses of purpose through strong social connections, well-supported work and leisure environments, and opportunities to engage with nature.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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