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Abstract Introduction Brodalumab is a human interleukin-17 receptor A antagonist indicated for the treatment of moderate-to-severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies. Although the US prescribing information for brodalumab includes a boxed warning regarding suicidal ideation and behavior, no causal association has been demonstrated. Here, we summarize 5 years of pharmacovigilance data, from August 15, 2017, through August 14, 2022, reported to Ortho Dermatologics by US patients and healthcare providers. Methods Prevalence of the most common adverse events (AEs) listed in the brodalumab package insert (incidence ≥ 1%) and AEs of special interest are described. Brodalumab exposure was estimated as the time from the first to last prescription-dispensing authorization dates. Data were collected from 4744 patients in the USA, with an estimated exposure of 5815 patient-years. Results Over 5 years, 11 cases of adjudicated major adverse cardiovascular events were reported (0.23 events/100 patients), a rate lower than that experienced by patients in the international Psoriasis Longitudinal Assessment and Registry. There were 106 serious infections. No serious fungal infections were reported. There were 40 confirmed and 2 suspected COVID-19 cases, with no new COVID-19-related deaths. Of 49 reported malignancies among 42 patients, 3 were deemed possibly related to brodalumab. No completed suicides and no new suicidal attempts were reported. Conclusion Five-year pharmacovigilance data are consistent with the established safety profile reported in long-term clinical trials and previous pharmacovigilance reports, with no new safety signals.

Abstract The Philippines as a tropical country is home to several indigenous berries that offer enough supply of health-promoting bioactive compounds like vitamin C. Vitamin C is an important micronutrient in the human diet that is usually supplied by fruits and vegetables. The amount of this vitamin in different products varies depending on the species, variety, maturity, processing, and other conditions. In this study, the vitamin C contents of selected Philippine indigenous berries such as bignay and lipote were evaluated as affected by fruit maturity and processing treatment. Fruits of two bignay (Antidesma bunius (Linn.) Spreng), varieties, ‘Common’ and ‘Kalabaw’, as well as of lipote (Syzygium polycephaloides (C. B. Rob.) Merr.), at three maturity stages (unripe, half-ripe, and fully ripe) were acquired in Laguna, Philippines. Samples were subjected to two processing treatments: blanched (90 ± 5 °C, 2 minutes) and steamed (105 ± 5 °C, 5 minutes), while control samples did not undergo processing treatment. The flesh and seeds were separated, lyophilized, extracted, and subjected to quantification of vitamin C using reversed-phase high performance liquid chromatography. Results showed that the vitamin C levels of both fruits were significantly affected by maturity, processing, and their interaction (P

Bignay (Antidesma bunius L. Spreng) is an indigenous fruit in the Philippines known for its bioactive compounds and is commonly preserved by conventional freezing. Processing can be done to improve its storage condition and convert it into functional ingredients. This study aimed to determine the effect of freeze-drying, oven drying (50°C), spray drying, and juice concentrating on the dietary fiber composition, phenolic compounds, and antioxidant activity of Bignay. Results showed that oven drying increased the total dietary fiber of Bignay by 29% while freeze drying resulted to an increase in total phenolics, total flavonoids, and total anthocyanin by 69%, 55%, and 66%, respectively, with an increase in antioxidant activity in terms of DPPH, FRAP, and ABTS by 57%, 15% and 31%, respectively. Spray drying was found to be the most detrimental method while juice concentration gave little to no significant effects. Epicatechin, catechin, and gallic acid were the main phenolic compounds quantified in the processed Bignay. The study recommends that freeze-drying is the best method followed by oven drying, concentration, and spray drying.

Abstract Bignay pomace is a processing byproduct that can be a source of bioactive compounds. However, a suitable dehydration method should be considered to efficiently valorize this waste material into high-value food ingredient and maximize its health-promoting properties. Bignay pomace was subjected to convection oven-drying and freeze-drying to investigate the effect of these pre-processing techniques on the physicochemical, bioactives, and antioxidant properties of the samples. Both drying methods significantly (p

Millions of Americans lack access to high-speed broadband, which is important for connectivity in the modern world. For me, as a Member of the House Committee on Energy and Commerce, closing this digital divide is a top priority. In this Essay, I discuss how a streamlined permitting process, as outlined by my American Broadband Deployment Act, can promote investment and innovation while also connecting more Americans with this vital service. [ABSTRACT FROM AUTHOR]

Purpose: Light affects a variety of non-image forming processes, such as circadian rhythm entrainment and the pupillary light reflex, which are mediated by intrinsically photosensitive retinal ganglion cells (ipRGCs). The purpose of this study was to assess the effects of long- and short-wavelength ambient lighting on activity patterns and pupil responses in rhesus monkeys.Methods: Infant rhesus monkeys were reared under either broadband “white” light (n = 14), long-wavelength “red” light (n = 20; 630 nm), or short-wavelength “blue” light (n = 21; 465 nm) on a 12-h light/dark cycle starting at 24.1 ± 2.6 days of age. Activity was measured for the first 4 months of the experimental period using a Fitbit activity tracking device and quantified as average step counts during the daytime (lights-on) and nighttime (lights-off) periods. Pupil responses to 1 s red (651 nm) and blue (456 nm) stimuli were measured after approximately 8 months. Pupil metrics included maximum constriction and the 6 s post-illumination pupil response (PIPR).Results: Activity during the lights-on period increased with age during the first 10 weeks (p < 0.001 for all) and was not significantly different for monkeys reared in white, red, or blue light (p = 0.07). Activity during the 12-h lights-off period was significantly greater for monkeys reared in blue light compared to those in white light (p = 0.02), but not compared to those in red light (p = 0.08). However, blue light reared monkeys exhibited significantly lower activity compared to both white and red light reared monkeys during the first hour of the lights-off period (p = 0.01 for both) and greater activity during the final hour of the lights-off period (p < 0.001 for both). Maximum pupil constriction and the 6 s PIPR to 1 s red and blue stimuli were not significantly different between groups (p > 0.05 for all).Conclusion: Findings suggest that long-term exposure to 12-h narrowband blue light results in greater disruption in nighttime behavioral patterns compared to narrowband red light. Normal pupil responses measured later in the rearing period suggest that ipRGCs adapt after long-term exposure to narrowband lighting.

The author attempts, for the first time, a chronological account of the different plant migrations, which have resulted in the present flora characteristic of the mountainous regions of the southern Appalachians. It studies the groups of flora and plant migrations that appear to have participated in the evolution of the modern flora of the southern Appalachians, and which are the following: 1) The ancient Paleozoic tlora, composed mainly of Pteridophytes and Pteridosperms, was modified, during the Appalachian Revolution, by the extermination and evolution of forms, to the primitive Mesozoic vegetation. 2) The almost flat Appalachian region was invaded in the early Cretaceous times by the new development and rapid spread of Angiosperms, which were then tropical in their distribution. 3) At the end of the Mesozoic era, the uprising caused the migration of these tropical forms towards the coastal plains that had recently emerged, leaving however numerous colonies, vestiges in the Appalachians. 4) The new high mountains were occupied by the arctotertiary forests, which were then circumboreal in extension, but are now limited to small geographically widely separated regions. 5) In the last Cenozoic era, the climates that became colder, caused the segregation of the originally homogeneous arctoterciary flora, in a coniferous forest in the north and a perishable forest in the south. 6) The Pleistocene glaciation caused migration to the southern mountains in many ways from the north. 7) The retreat of the ice allowed the migration of the coniferous forests to the north, reoccupying their original area, but leaving an extensive residue in the higher and colder southern Appalachian regions. Note that the individual work of many botanists will be required to fill in the gaps and supply evidence to modify the hypothesis discussed here.

The concept of liquid metal membranes for hydrogen separation, based on gallium or indium, was recently introduced as an alternative to conventional palladium-based membranes. The potential of this class of gas separation materials was mainly attributed to the promise of higher hydrogen diffusivity. The postulated improvements are only beneficial to the flux if diffusion through the membrane is the rate-determining step in the permeation sequence. Whilst this is a valid assumption for hydrogen transport through palladium-based membranes, the relatively low adsorption energy of hydrogen on both liquid metals suggests that other phenomena may be relevant. In the current study, a microkinetic modeling approach is used to enable simulations based on a five-step permeation mechanism. The calculation results show that for the liquid metal membranes, the flux is limited by the dissociative adsorption over a large temperature range, and that the membrane flux is expected to be orders of magnitude lower compared to the membrane flux through pure palladium membranes. Even when accounting for the lower cost of the liquid metals compared to palladium, the latter still outperforms both gallium and indium in all realistic scenarios, in part due to the practical difficulties associated with making liquid metal thin films.

Sugarcane and energy cane (Saccharum spp. hybrids) are ideal for plant-based production of recombinant proteins because their high resource-use efficiency, rapid growth and efficient photosynthesis enable extensive biomass production and protein accumulation at a cost-effective scale. Here, we aimed to develop these species as efficient platforms to produce recombinant Galanthus nivalis L. (snowdrop) agglutinin (GNA), a monocot-bulb mannose-specific lectin with potent antiviral, antifungal and antitumor activities. Initially, GNA levels of 0.04% and 0.3% total soluble protein (TSP) (0.3 and 3.8 mg kg–1 tissue) were recovered from the culms and leaves, respectively, of sugarcane lines expressing recombinant GNA under the control of the constitutive maize ubiquitin 1 (Ubi) promoter. Co-expression of recombinant GNA from stacked multiple promoters (pUbi and culm-regulated promoters from sugarcane dirigent5-1 and Sugarcane bacilliform virus) on separate expression vectors increased GNA yields up to 42.3-fold (1.8% TSP or 12.7 mg kg–1 tissue) and 7.7-fold (2.3% TSP or 29.3 mg kg–1 tissue) in sugarcane and energy cane lines, respectively. Moreover, inducing promoter activity in the leaves of GNA transgenic lines with stress-regulated hormones increased GNA accumulation to 2.7% TSP (37.2 mg kg–1 tissue). Purification by mannose-agarose affinity chromatography yielded a functional sugarcane recombinant GNA with binding substrate specificity similar to that of native snowdrop-bulb GNA, as shown by enzyme-linked lectin and mannose-binding inhibition assays. The size and molecular weight of recombinant GNA were identical to those of native GNA, as determined by size-exclusion chromatography and MALDI-TOF mass spectrometry. This work demonstrates the feasibility of producing recombinant GNA at high levels in Saccharum species, with the long-term goal of using it as a broad-spectrum antiviral carrier molecule for hemopurifiers and in related therapeutic applications.

Table of contents O1 Changes in peripheral refraction associated with decreased ocular axial growth rate in marmosets Alexandra Benavente-Perez, Ann Nour, Tobin Ansel, Kathleen Abarr, Luying Yan, Keisha Roden, David Troilo O2 PPARα activation suppresses myopia development by increasing scleral collagen synthesis--a new drug target to suppress myopia development Chanyi Lu, Miaozhen Pan, Min Zheng, Jia Qu, Xiangtian Zhou O3 Evidence and possibilities for local ocular growth regulating signal pathways Christine F Wildsoet O4 Myopia researches at Eye Hospital of Wenzhou Medical University Fan Lu, Xiangtian Zhou, Jie Chen, Jinhua Bao, Liang Hu, Qinmei Wang, Zibing Jin, Jia Qu O5 Color, temporal contrast and myopia Frances Rucker, Stephanie Britton, Stephan Hanowsky, Molly Spatcher O6 The impact of atropine usage on visual function and reading performance in myopic school children in Taiwan Hui-Ying Kuo, Ching-Hsiu Ke, I-Hsin Kuo, Chien-Chun Peng, Han-Yin Sun O7 Increased time outdoors prevents the onset of myopia: evidence from randomised clinical trials Ian G Morgan O8 Environmental risk factors and gene-environment interactions for myopia in the ALSPAC cohort Jeremy A. Guggenheim, Rupal L. Shah, Cathy Williams O9 Retinal metabolic profiling identifies declines in FP receptor-linked signaling as contributors to form-deprived myopic development in guinea pigs Jinglei Yang, Peter S. Reinach, Sen Zhang, Miaozhen Pan, Wenfeng Sun, Bo Liu, Xiangtian Zhou O10 The study of peripheral refraction in moderate and high myopes after one month of wearing orthokeratology lens Jun Jiang, Haoran Wu, Fan Lu O11 Axial length of school children around the earth’s equatorial area and factors affecting the axial length Kazuo Tsubota, Hiroko Ozawa, Hidemasa Torii, Shigemasa Takamizawa, Toshihide Kurihara, Kazuno Negishi O12 Processing of defocus in the chicken retina by retinal ganglion cells Klaus Graef, Daniel Rathbun, Frank Schaeffel O13 Blue SAD light protects against form deprivation myopia in chickens, by local signaling within the retina Ladan Ghodsi, William K. Stell O14 Contributions of ON and OFF pathways to emmetropization and form deprivation myopia in mice Machelle T. Pardue, Ranjay Chakraborty, Han na Park, Curran S. Sidhu, P. Michael Iuvone O15 Response of the human choroid to defocus Michael J Collins O16 What can RNA sequencing tell us about myopic sclera? Nethrajeith Srinvasalu, Sally A McFadden, Paul N Baird O17 Overview of dopamine, retinal function, and myopia P. Michael Iuvone O18 The eye as a "robust" optical system and myopia Pablo Artal O19 Effect of discontinuation of orthokeratology lens wear on axial elongation in children Pauline Cho, SW Cheung O20 Myopia prevention in Taiwan Pei-Chang Wu O21 Alternatives to ultraviolet light and riboflavin for in vivo crosslinking of scleral collagen Quan V. Hoang, Sally A. McFadden O22 Absence of intrinsically photosensitive retinal ganglion cells (ipRGC) alters normal refractive development in mice Ranjay Chakraborty, Duk C. Lee, Erica G. Landis, Michael A. Bergen, Curran Sidhu, Samer Hattar, P. Michael Iuvone, Richard A. Stone, Machelle T. Pardue O23 Scleral micro-RNAs in myopia development and their potential as therapeutic targets Ravi Metlapally O24 Effects of the long-wavelength filtered continuous spectrum on emmetropization in juvenile guinea pigs Ruiqin Li, Qinglin Xu, Hong Zhon, Chenglin Pan, Weizhon Lan, Xiaoning Li, Ling Chen, Zhikuan Yang O25 Ocular and environmental factors associated with eye growth in childhood Scott A. Read O26 Overview- prevention and prediction of myopia and pathologic myopia Seang-Mei Saw O27 New insights into the roles of retinal dopamine in form-deprivation myopia and refractive development in C57BL/6 mice Shi-Jun Weng, Xiao-Hua Wu, Kang-Wei Qian, Yun-Yun Li, Guo-Zhong Xu, Furong Huang, Xiangtian Zhou, Jia Qu, Xiong-Li Yang, Yong-Mei Zhong O28 The effects of the adenosine antagonist, 7-methylxanthine, on refractive development in rhesus monkeys Earl L Smith III, Baskar Arumugam, Li-Fang Hung, Lisa A. Ostrin, Klaus Trier, Monica Jong, Brien A. Holden O29 Application of SWATH™ based next generation proteomics (NGP) in studying eye growth: opportunities and challenges Thomas Chuen Lam, Bing Zuo, Samantha Shan, Sally A. McFadden, Dennis Yan-yin Tse, Jingfang Bian, King-Kit Li, Quan Liu, Chi-ho To O30 How could emmetropization make use of longitudinal chromatic aberration? Timothy J. Gawne, John T. Siegwart Jr., Alexander H. Ward, Thomas T. Norton O31 Balance effect of dopamine D1 and D2 receptor subtype activation on refraction development Xiangtian Zhou O32 BMP gene expression changes in chick rpe in response to visual manipulations Yan Zhang, Yue Liu, Carol Ho, Eileen Phan, Abraham Hang, Emily Eng, Christine Wildsoet

Purpose: Intrinsically photosensitive retinal ganglion cells (ipRGCs) contain the photopigment melanopsin, and are primarily involved in non-image forming functions, such as the pupillary light reflex and circadian rhythm entrainment. The goal of this study was to develop and validate a targeted ipRGC immunotoxin to ultimately examine the role of ipRGCs in macaque monkeys.Methods: An immunotoxin for the macaque melanopsin gene (OPN4), consisting of a saporin-conjugated antibody directed at the N-terminus, was prepared in solutions of 0.316, 1, 3.16, 10, and 50 μg in vehicle, and delivered intravitreally to the right eye of six rhesus monkeys, respectively. Left eyes were injected with vehicle only. The pupillary light reflex (PLR), the ipRGC-driven post illumination pupil response (PIPR), and electroretinograms (ERGs) were recorded before and after injection. For pupil measurements, 1 and 5 s pulses of light were presented to the dilated right eye while the left pupil was imaged. Stimulation included 651 nm (133 cd/m2), and 4 intensities of 456 nm (16–500 cd/m2) light. Maximum pupil constriction and the 6 s PIPR were calculated. Retinal imaging was performed with optical coherence tomography (OCT), and eyes underwent OPN4 immunohistochemistry to evaluate immunotoxin specificity and ipRGC loss.Results: Before injection, animals showed robust pupil responses to 1 and 5 s blue light. After injection, baseline pupil size increased 12 ± 17%, maximum pupil constriction decreased, and the PIPR, a marker of ipRGC activity, was eliminated in all but the lowest immunotoxin concentration. For the highest concentrations, some inflammation and structural changes were observed with OCT, while eyes injected with lower concentrations appeared normal. ERG responses showed better preserved retinal function with lower concentrations. Immunohistochemistry showed 80–100% ipRGC elimination with the higher doses being more effective; however this could be partly due to inflammation that occurred at the higher concentrations.Conclusion: Findings demonstrated that the OPN4 macaque immunotoxin was specific for ipRGCs, and induced a graded reduction in the PLR, as well as, in ipRGC-driven pupil response with concentration. Further investigation of the effects of ipRGC ablation on ocular and systemic circadian rhythms and the pupil in rhesus monkeys will provide a better understanding of the role of ipRGCs in primates.

Understanding gas flows in capillaries has many applications in modeling the transport of gases in nano-structured, porous, or fractured media. A network of capillaries can often approximate these media, and also information on gas-surface interactions obtained from capillary experiments can be used for modeling flows in these media. Experimental data on flows of different mixtures of He-Ar, He-N2, and He-air in the slip regime and in stainless steel capillaries at high temperatures were obtained by using a two-bulb apparatus. An accurate expression for the thermal creep slip coefficients with the Lennard-Jones potential parameters and diffuse-specular reflection gas-surface interaction conditions were then used to obtain the accommodation coefficients for the different gases. The experimental data are best described with values of accommodation coefficients in the range of 0.1–0.3 for He and 0.5–1.0 for Ar, N2, and air. The use of values in this range is suggested for modeling gaseous flows in capillaries and nano-structured, porous, or fractured media if other direct measured values for a particular medium are unavailable. [ABSTRACT FROM AUTHOR]

N-glycosylation profoundly affects the biological stability and function of therapeutic proteins, which explains the recent interest in glycoengineering technologies as methods to develop biobetter therapeutics. In current manufacturing processes, N-glycosylation is host-specific and remains difficult to control in a production environment that changes with scale and production batches leading to glycosylation heterogeneity and inconsistency. On the other hand, in vitro chemoenzymatic glycan remodeling has been successful in producing homogeneous pre-defined protein glycoforms, but needs to be combined with a cost-effective and scalable production method. An efficient chemoenzymatic glycan remodeling technology using a plant expression system that combines in vivo deglycosylation with an in vitro chemoenzymatic glycosylation is described. Using the monoclonal antibody rituximab as a model therapeutic protein, a uniform Gal2GlcNAc2Man3GlcNAc2 (A2G2) glycoform without α-1,6-fucose, plant-specific α-1,3-fucose or β-1,2-xylose residues was produced. When compared with the innovator product Rituxan®, the plant-made remodeled afucosylated antibody showed similar binding affinity to the CD20 antigen but significantly enhanced cell cytotoxicity in vitro. Using a scalable plant expression system and reducing the in vitro deglycosylation burden creates the potential to eliminate glycan heterogeneity and provide affordable customization of therapeutics’ glycosylation for maximal and targeted biological activity. This feature can reduce cost and provide an affordable platform to manufacture biobetter antibodies.

Bignay (Antidesma bunius (L.) Spreng) is an underutilised native berry grown in several Asian countries including the Philippines. Limited studies have been carried out on specific bignay cultivars and their fruit maturity stages. This study aimed to differentiate two cultivars of bignay with respect to their morphology, physicochemical properties, and proximate compositions at different maturity stages. Morphological characterisation showed that the kalabaw cultivar had a superior performance when compared to the common cultivar. Kalabaw's whole fruit weight (0.47 - 0.54 g), equatorial diameter (8.42 - 9.05 mm), thickness (7.08-7.40 mm), flesh weight (0.42 - 0.49 g), flesh thickness (1.58 - 2.20 mm) and edible portion (90.1 - 91.1%) were significantly higher when compared to corresponding common cultivar's performances; fruit weight 0.28 - 0.34 g, equatorial diameter 7.50 - 8.00 mm, thickness 6.30 - 6.95 mm, flesh weight 0.25 - 0.31 g, flesh thickness 1.33 - 1.90 mm and edible portion 88.5 - 89.5%. The superiority of kalabaw includes the measured seed parameters. For the physicochemical and proximate compositions, there is not much of a difference, while kalabaw had a lower sugar (3.40 - 8.00%) and acidity (0.36 - 0.65%) content, its moisture (13.7 - 18.3%), crude fat (4.64 - 5.66%) and crude fibre (5.37 - 10.10%) content were higher compared to the common cultivar. This study showed that kalabaw could be best used for the production of different value-added products. [ABSTRACT FROM AUTHOR]