Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparison of Efficacy between 120° and 180° Schlemm’s Canal Incision Microhook Ab Interno Trabeculotomy

We compared surgical outcomes in patients with either primary open-angle glaucoma or exfoliation glaucoma after undergoing combined phacoemulsification with either a 120° or 180° incision during a Schlemm’s canal microhook ab interno trabeculotomy (μLOT-Phaco). This retrospective comparative case series examined 52 μLOT-Phaco eyes that underwent surgery between September 2017 and December 2020. Surgical qualified success was defined as an intraocular pressure (IOP) of ≤20 mmHg, ≥20% IOP reduction with IOP-lowering medications, and no additional glaucoma surgery. Success rates were evaluated by Kaplan-Meier survival analysis. The number of postoperative IOP-lowering medications and occurrence of complications were also assessed. Mean preoperative IOP in the 120° group was 16.9 ± 7.6 mmHg, which significantly decreased to 10.9 ± 2.7 mmHg (p < 0.01) and 11.1 ± 3.1 mmHg (p = 0.01) at 12 and 24 months, respectively. The mean number of preoperative IOP-lowering medications significantly decreased from 2.8 ± 1.4 to 1.4 ± 1.4 (p < 0.01) at 24 months. Mean preoperative IOP in the 180° group was 17.1 ± 7.0 mmHg, which significantly decreased to 12.1 ± 3.2 mmHg (p = 0.02) and 12.9 ± 1.4 mmHg (p = 0.01) at 12 and 24 months, respectively. The mean number of preoperative IOP-lowering medications significantly decreased from 2.9 ± 1.2 to 1.4 ± 1.5 (p < 0.01) at 24 months. The probability of qualified success at 24 months in the 120° and 180° groups was 50.4% and 54.6%, respectively (p = 0.58). There was no difference observed for hyphema formation or IOP spikes. Surgical outcomes were not significantly different between the 120° and 180° incisions in Schlemm’s canal.
Systems Pharmacology-Based Precision Therapy and Drug Combination Discovery for Breast Cancer

Simple Summary Breast cancer (BC) is a typical global cancer and the second leading cause of cancer-related deaths among women worldwide. BC is a heterogeneous disease with several subtypes, and it is a challenge to use multi-omic data effectively to find suitable drugs for patients. In this paper, we used the GeneRank algorithm and gene dependency network to propose a precision drug discovery strategy that can recommend drugs for individuals and screen existing drug combinations that could be used to treat different BC subtypes. Our results showed that this precision drug discovery strategy identified important disease-related genes in individuals and specific groups, supporting its efficiency, high reliability, and practical application value in drug discovery. Abstract Breast cancer (BC) is a common disease and one of the main causes of death in females worldwide. In the omics era, researchers have used various high-throughput sequencing technologies to accumulate massive amounts of biomedical data and reveal an increasing number of disease-related mutations/genes. It is a major challenge to use these data effectively to find drugs that may protect human health. In this study, we combined the GeneRank algorithm and gene dependency network to propose a precision drug discovery strategy that can recommend drugs for individuals and screen existing drugs that could be used to treat different BC subtypes. We used this strategy to screen four BC subtype-specific drug combinations and verified the potential activity of combining gefitinib and irinotecan in triple-negative breast cancer (TNBC) through in vivo and in vitro experiments. The results of cell and animal experiments demonstrated that the combination of gefitinib and irinotecan can significantly inhibit the growth of TNBC tumour cells. The results also demonstrated that this systems pharmacology-based precision drug discovery strategy effectively identified important disease-related genes in individuals and special groups, which supports its efficiency, high reliability, and practical application value in drug discovery.
The Genetic Analyses of French Canadians of Quebec Facilitate the Characterization of New Cancer Predisposing Genes Implicated in Hereditary Breast and/or Ovarian Cancer Syndrome Families

Simple Summary The French Canadian population of the province of Quebec has been investigated because of its genetic attributes and is known for making significant contributions to the medical genetics field. Their unique genetic background has been attributed to a small number of early settlers from France that contributed to the majority of the gene pool. The French Canadian population has been investigated for the role of known breast and ovarian cancer predisposing genes, such as BRCA1 and BRCA2. In this review we describe the merits of studying this population with respect to the discovery of new such cancer predisposing gene. Abstract The French Canadian population of the province of Quebec has been recognized for its contribution to research in medical genetics, especially in defining the role of heritable pathogenic variants in cancer predisposing genes. Multiple carriers of a limited number of pathogenic variants in BRCA1 and BRCA2, the major risk genes for hereditary breast and/or ovarian cancer syndrome families, have been identified in French Canadians, which is in stark contrast to the array of over 2000 different pathogenic variants reported in each of these genes in other populations. As not all such cancer syndrome families are explained by BRCA1 and BRCA2, newly proposed gene candidates identified in other populations have been investigated for their role in conferring risk in French Canadian cancer families. For example, multiple carriers of distinct variants were identified in PALB2 and RAD51D. The unique genetic architecture of French Canadians has been attributed to shared ancestry due to common ancestors of early settlers of this population with origins mainly from France. In this review, we discuss the merits of genetically characterizing cancer predisposing genes in French Canadians of Quebec. We focused on genes that have been implicated in hereditary breast and/or ovarian cancer syndrome families as they have been the most thoroughly characterized cancer syndromes in this population. We describe how genetic analyses of French Canadians have facilitated: (i) the classification of variants in BRCA1 and BRCA2; (ii) the identification and classification of variants in newly proposed breast and/or ovarian cancer predisposing genes; and (iii) the identification of a new breast cancer predisposing gene candidate, RECQL. The genetic architecture of French Canadians provides a unique opportunity to evaluate new candidate cancer predisposing genes regardless of the population in which they were identified.
Reducing the Influence of Environmental Factors on Performance of a Diffusion-Based Personal Exposure Kit

Sensor technology has enabled the development of portable low-cost monitoring kits that might supplement many applications in conventional monitoring stations. Despite the sensitivity of electrochemical gas sensors to environmental change, they are increasingly important in monitoring polluted microenvironments. The performance of a compact diffusion-based Personal Exposure Kit (PEK) was assessed for real-time gaseous pollutant measurement (CO, O3, and NO2) under typical environmental conditions encountered in the subtropical city of Hong Kong. A dynamic baseline tracking method and a range of calibration protocols to address system performance were explored under practical scenarios to assess the performance of the PEK in reducing the impact of rapid changes in the ambient environment in personal exposure assessment applications. The results show that the accuracy and stability of the ppb level gas measurement is enhanced even in heterogeneous environments, thus avoiding the need for data post-processing with mathematical algorithms, such as multi-linear regression. This establishes the potential for use in personal exposure monitoring, which has been difficult in the past, and for reporting more accurate and reliable data in real-time to support personal exposure assessment and portable air quality monitoring applications.
Fabrication of an Anti-Reflective Microstructure on ZnS by Femtosecond Laser Bessel Beams

As an important mid-infrared to far-infrared optical window, ZnS is extremely important to improve spectral transmission performance, especially in the military field. However, on account of the Fresnel reflection at the interface between the air and the high-strength substrate, surface optical loss occurs in the ZnS optical window. In this study, the concave antireflective sub-wavelength structures (ASS) on ZnS have been experimentally investigated to obtain high transmittance in the far-infrared spectral range from 6 μm to 10 μm. We proposed a simple method to fabricate microhole array ASS by femtosecond Bessel beam, which further increased the depth of the microholes and suppressed the thermal effects effectively, including the crack and recast layer of the microhole. The influence of different Gaussian and Bessel beam parameters on the microhole morphology were explored, and three ASS structures with different periods were prepared by the optimized Bessel parameters. Ultimately, the average transmittance of the sample with the ASS microhole array period of 2.6 μm increased by 4.1% in the 6 μm to 10 μm waveband, and the transmittance was increased by 5.7% at wavelength of 7.2 μm.
A physiologic rise in cytoplasmic calcium ion signal increases pannexin1 channel activity via a C-terminus phosphorylation by CaMKII

Significance This work shows that rat and human pannexin1 channels are not intrinsically sensitive to membrane stretch and their activation, previously associated with a physiologic increase in cytoplasmic Ca2+ concentration, results from phosphorylation via CaMKII in the amino acid residue S394 located in the C terminus of pannexin1. This posttranslational modification does not significantly affect the unitary conductance of the channel but increases the permeability of lateral tunnels to adenosine triphosphate (ATP) and permits the influx of positively charged molecules, such as DAPI, via the external vestibule to the cytoplasm. This activation mechanism might explain the ATP release via pannexin1 channels in diverse cell types under numerous physiologic conditions. Pannexin1 (Panx1) channels are ubiquitously expressed in vertebrate cells and are widely accepted as adenosine triphosphate (ATP)-releasing membrane channels. Activation of Panx1 has been associated with phosphorylation in a specific tyrosine residue or cleavage of its C-terminal domains. In the present work, we identified a residue (S394) as a putative phosphorylation site by Ca2+/calmodulin-dependent kinase II (CaMKII). In HeLa cells transfected with rat Panx1 (rPanx1), membrane stretch (MS)-induced activation—measured by changes in DAPI uptake rate—was drastically reduced by either knockdown of Piezo1 or pharmacological inhibition of calmodulin or CaMKII. By site-directed mutagenesis we generated rPanx1S394A-EGFP (enhanced green fluorescent protein), which lost its sensitivity to MS, and rPanx1S394D-EGFP, mimicking phosphorylation, which shows high DAPI uptake rate without MS stimulation or cleavage of the C terminus. Using whole-cell patch-clamp and outside-out excised patch configurations, we found that rPanx1-EGFP and rPanx1S394D-EGFP channels showed current at all voltages between ±100 mV, similar single channel currents with outward rectification, and unitary conductance (∼30 to 70 pS). However, using cell-attached configuration we found that rPanx1S394D-EGFP channels show increased spontaneous unitary events independent of MS stimulation. In silico studies revealed that phosphorylation of S394 caused conformational changes in the selectivity filter and increased the average volume of lateral tunnels, allowing ATP to be released via these conduits and DAPI uptake directly from the channel mouth to the cytoplasmic space. These results could explain one possible mechanism for activation of rPanx1 upon increase in cytoplasmic Ca2+ signal elicited by diverse physiological conditions in which the C-terminal domain is not cleaved.
Spatio-temporally targeted in-situ electroporation of mammalian cells through SiO2 thin-film capacitive microelectrodes

Electroporation is a widely used non-viral technique for the delivery of molecules, including nucleic acids, into cells. Recently, electronic microsystems that miniaturize the electroporation machinery have been developed as a new tool for genetic manipulation of cells in vitro, by integrating metal microelectrodes in the culture substrate and enabling electroporation in-situ. We report that non-faradic SiO2 thin film-insulated microelectrodes can be used for reliable and spatially selective in-situ electroporation of mammalian cells. CHO-K1 and SH-SY5Y cell lines and primary neuronal cultures were electroporated by application of short and low amplitude voltage transients leading to cell electroporation by capacitive currents. We demonstrate reliable delivery of DNA plasmids and exogenous gene expression, accompanied by high spatial selectivity and cell viability. Finally, we show that SiO2 thin film-insulated microelectrodes support a double and serial transfection of the targeted cells.
A huggable device can reduce the stress of calling an unfamiliar person on the phone for individuals with ASD

Individuals with autism spectrum disorders (ASD) are often not comfortable during mobile-phone conversations with unfamiliar people. “Hugvie” is a pillow with a human-like shape that has been designed to provide users with the tactile sensation of hugging another person during phone conversations to promote feelings of comfort and trust in the speaker toward their conversation partners. Our primary aim was to examine whether physical contact by hugging a Hugvie could reduce the stress of speaking with an unfamiliar person on the phone in individuals with ASD. We enrolled 24 individuals and requested them to carry out phone conversations either using only a mobile phone or using a mobile phone along with the Hugvie. All participants in both groups completed questionnaires designed to evaluate their self-confidence while talking on the phone, and also provided salivary cortisol samples four times each day. Our analysis revealed that the medium of communication was a significant factor, indicating that individuals with ASD who spoke with an unfamiliar person on the phone while hugging a Hugvie had stronger self-confidence and lower stress levels than those who did not use Hugvie. Hence, we recommend that huggable devices be used as adjunctive tools to support individuals with ASD during telephonic conversations with unfamiliar people.
Solid-Contact Electrode with Composite PVC-Based 3D-Printed Membrane. Optimization of Fabrication and Performance

Intense interest in reference electrode design and fabrication has recently been enriched with the application of 3D printing of electrodes with salt-loaded PVC membranes. This type of material is attractive in sensor technology and is challenging to implement in 3D. In this report, several improvements and simplifications in the technology were focused on and supported by a fundamental electrochemical characterization.
Baricitinib, a JAK-STAT Inhibitor, Reduces the Cellular Toxicity of the Farnesyltransferase Inhibitor Lonafarnib in Progeria Cells

Hutchinson–Gilford progeria syndrome (HGPS) is an ultra-rare multisystem premature aging disorder that leads to early death (mean age of 14.7 years) due to myocardial infarction or stroke. Most cases have a de novo point mutation at position G608G within exon 11 of the LMNA gene. This mutation leads to the production of a permanently farnesylated truncated prelamin A protein called “progerin” that is toxic to the cells. Recently, farnesyltransferase inhibitor (FTI) lonafarnib has been approved by the FDA for the treatment of patients with HGPS. While lonafarnib treatment irrefutably ameliorates HGPS disease, it is however not a cure. FTI has been shown to cause several cellular side effects, including genomic instability as well as binucleated and donut-shaped nuclei. We report that, in addition to these cellular stresses, FTI caused an increased frequency of cytosolic DNA fragment formation. These extranuclear DNA fragments colocalized with cGAs and activated the cGAS-STING-STAT1 signaling axis, upregulating the expression of proinflammatory cytokines in FTI-treated human HGPS fibroblasts. Treatment with lonafarnib and baricitinib, a JAK-STAT inhibitor, not only prevented the activation of the cGAS STING-STAT1 pathway, but also improved the overall HGPS cellular homeostasis. These ameliorations included progerin levels, nuclear shape, proteostasis, cellular ATP, proliferation, and the reduction of cellular inflammation and senescence. Thus, we suggest that combining lonafarnib with baricitinib might provide an opportunity to reduce FTI cellular toxicity and ameliorate HGPS symptoms further than lonafarnib alone.
Reciprocal Relationships between Sleep Problems and Problematic Smartphone Use in Taiwan: Cross-Lagged Panel Study

Prior studies have suggested a link between sleep problems and problematic smartphone use. However, the causal relationships between these two variables have not been identified, particularly in adolescence. Utilizing longitudinal panel data from Taiwan, this report examined the temporal relationships between sleep problems and problematic smartphone use among adolescents. One thousand and thirty-nine students (Grades 7–12) were surveyed at two-time points with a 6-month interval. The results of cross-lagged panel analysis showed that sleep problems at Time 1 significantly predicted problematic smartphone use at Time 2. Problematic smartphone use at Time 1 also significantly predicted sleep problems at Time 2. These findings applied to boys and girls and suggested that temporal relationships between sleep problems and problematic smartphone use among teenagers are reciprocal. Accordingly, increasing sleep quality may prevent future problematic smartphone use, while reducing problematic smartphone use may prevent sleep problems in adolescents.
Waxy Starch to Replace Vegetable Fat in Extruded Snack Aromatisation and Different Salt Delivery Way to Decrease Sodium Intake

Paper Received: 14 October 2020; Revised: 16 March 2021; Accepted: 23 April 2021 Please cite this article as: Nakagawa A. , Raniero G.Z. , Berwig K.P., Monteiro C.C. , Sousa I. , Monteiro A.R. , 2021, Waxy Starch to Replace Vegetable Fat in Extruded Snack Aromatisation and Different Salt Delivery Way to Decrease Sodium Intake, Chemical Engineering Transactions, 87, 271-276 DOI:10.3303/CET2187046 CHEMICAL ENGINEERING TRANSACTIONS
Tipsy: How to Correct Password Typos Safely

— We implement and test a simple typo tolerant password authentication scheme as well as its personalised counterpart. Our experiments measure the security loss and give examples of the difference in security one could expect when moving from a “strict” authentication system to a typo tolerant one. In our tests, we use publicly available breached password datasets and mock exact knowledge attacker to mimic real-world scenarios and constraints. During our evaluation, we uncover ﬂaws in previously published security loss calculations and we suggest a reﬁned algorithm. Our results corroborate previous studies: in practice, typo tolerant systems offer a minimal decrease in security.
Linear Equation Solvers on GPU Architectures for Finite Element Methods in Structural Mechanics

Many scientific computing applications rely on linear equation solvers for numerical simulations. Moving away from traditional parallelization models, we investigate possibilities to accelerate linear equation solvers by using hybrid architectures consisting of CPUs and GPUs. The targeted equation systems originate from finite element method simulations in structural mechanics performed by CalculiX. We review existing iterative and direct solvers for shared memory and GPU parallelization. Iterative methods cannot compete with direct strategies for the given benchmark matrices because of stagnating convergence. Direct solvers are known to be memory demanding and thus a block-wise offloading scheme was identified as the most promising approach to utilize GPGPU. Instead of developing a new solver we evaluate that PaStiX implements this strategy very efficiently and performs well for relevant matrices. An in-depth analysis is conducted to find bottlenecks and potential enhancements. A general weakness is the amount of sequential and unaccelerated code before and after the factorization. To reduce the effect of Amdahl’s law, those sections are extended with OpenMP and CUDA. The PCI Express bus is the factorization’s bottleneck. Two optimizations are presented to relieve it. Firstly, a mixed precision strategy that allows computation in float instead of double and thus halves the amount of data to be sent. In total, this method leads to 46% and 20% higher performance in pure CPU and hybrid mode. Secondly, the effects of using pinned memory are analyzed. On average, the enhanced bandwidth leads to 20% faster factorization but does not improve the total computation time since allocating pinned memory is costly. For most matrices, an absolute speedup is achieved when using the same memory range for 7 or more factorizations. Finally, PaStiX is integrated into CalculiX and, in fact, reusing is not only possible for pinned memory buffers but also for reordering permutations. This way, the scalable numerical parts of PaStiX account for 66.1% instead of 26.8% of the computation time. Previously, CalculiX used the CPU-based library PARDISO. Depending on the input deck, the enhanced PaStiX solver runs between 2.6 and 12.7 times faster. Considering the entire CalculiX application, an average speedup of 3.1 for the CPU and 4.4 for the hybrid version is achieved based on the original implementation.
Propylene/Propane Separation Using SiCHA

Separation of propylene/propane mixture with new 8-ring zeolite, pure silica chabazite (SiCHA), has been studied in this work. Since the diffusion of propane molecules in SiCHA is extremely slow, thus equilibrium information for propane has been indirectly estimated using available uptake data at 80 °C and 600 Torr. Moreover, molecular simulation has been used to obtain equilibrium information of propylene and propane and verify our estimation. The ideal kinetic selectivity of propylene/propane mixture is ∼28 at 80 °C, which increases with decreasing temperature. A four-step, kinetically controlled pressure swing adsorption process has been suggested for this separation and studied in detail using a nonisothermal micropore diffusion model, developed and verified in an earlier study. In this model, Langmuir isotherm represents adsorption equilibrium and micropore diffusivity depends on adsorbate concentration in the micropores, according to chemical potential gradient as the driving force for diffusion.
Modular material system for the microfabrication of biocompatible hydrogels based on thiol–ene‐modified poly(vinyl alcohol)

Novel modifications of the synthetic polymer poly(vinyl alcohol) (PVA) were developed for application in the field of biomedical engineering. PVA was modified with allyl succinic anhydride, norbornene anhydride as well as with γ-thiobutyrolactone to produce macromers with reactive ene and thiol groups, respectively. Cytotoxicity studies have shown that the material exhibits almost no cell-toxicity, when used in concentrations of 1 and 0.1 wt % for 24 h. The obtained macromers were photocrosslinked via thiol–ene chemistry. Storage stability of the macromer mixtures with different concentrations of pyrogallol as stabilizer were investigated. Photorheometry was employed to optimize mixtures concerning reactivity based on their thiol-to-ene ratio, photoinitiator concentration, and macromer content. The crosslinked hydrogels were studied concerning their swellability. To form hydrogels with cellular structure two-photon-polymerization (2PP) was employed. Processing windows for 2PP of selected mixtures were determined. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016, 54, 2060–2070