bluuebunny/crossref_metadata_2025 huggingface dataset:
Response of Phosphorus and Zinc on Yield and Economics of Wheat (Triticum aestivum)
Authors: Kumar Sunil , Singh Rajesh , Indu Thakur , Kumar Amit
Published: July 2023

The field experiment titled “Response of Phosphorus and Zinc on Yield and Economics of Wheat (Triticum aestivum)" was conducted during Rabi season, 2022 at Crop Research Farm in the Department of agronomy, Naini Agriculture Institute, Sam Higginbottom University of Agriculture, Technology and Sciences, Prayagraj, Uttar Pradesh.  The treatment consisted of three level of Phosphorus (60, 75 and 90 kg/ha), Zinc (15, 25 and 35 kg/ha) and control. The experiment was layout in Randomized Block Design (RBD) with 10 treatments and replicated thrice. The soil in the experimental area was sandy loam with pH (8.0), EC (0.56 dS/m), Organic Carbon (0.62%), Available N (225 kg/ha), Available P (38.2 kg/ha), and Available K (240.7 kg/ha). Application of Phosphorus 90 kg/ha and Zn 35 kg/ha produces higher Grain yield (4.90 t/ha), Straw yield (8.38 t/ha), Gross return (154405 INR/ha), Net return (103109.85 INR/ha) and B:C (2.01).
Economic Analysis of Cost of Production and Return of Groundnut in Jamnagar District of Gujarat, India
Authors: Hiren Pindariya , Ramchandra
Published: July 2023

In the years 2021–2022, researchers conducted the current study, which is named "An Economic Analysis of Production and Marketing of Groundnut in Jamnagar District of Gujarat. “The study chose 90 participants from among those 6 using a multistage sampling and random sampling technique a few villages. A well-structured questionnaire was used to collect the study's data.This study showed that the cost of production per hectare, gross income, net income from farm investments, cost of production, and input to output ratio of groundnut were calculated altogether. The findings showed that marginal, small, and semi-medium farms paid, respectively, Rs. 67984.59/ha, Rs. 66206.25/ha, and Rs. 64579.85/ha in costs. Marginal, small, and semi-medium farms received gross returns per hectare of (Rs. 103785/ha), (Rs. 111000/ha), and (Rs. 119325/ha), respectively. Marginal, small, and semi-medium farms reported net returns per hectare of 35800.41, 44793.75, and 54747.15 rupees, respectively. The ratio of marginal (1:1.53), small (1:1.68), and medium (1:1.85) input to output per hectare, respectively. For marginal, small, and semi-medium businesses, the cost of production per quintal was, respectively, Rs. 3635.54, Rs. 44793.75, and Rs. 54745.15.
Assessing the Feasibility of Gravitational Vortex Turbines for Sustainable Energy Production in Remote Hilly Areas of Bangladesh
Authors: Kyawo Aung , Khan M. Iltimas , Chowdhury Saqibul Islam , Rahaman Saymun
Published: July 2023

This research paper presents a comprehensive study of the design, optimization, and performance analysis of a gravitational vortex water turbine for small-scale hydropower applications in the Chittagong Hill Tracts of Bangladesh. The urgent need for cleaner and more efficient energy sources to address global energy challenges drives the development of innovative renewable energy solutions. The proposed turbine harnesses the power of gravity-induced water flow to efficiently convert rotational energy from a water vortex into electrical energy. The research employs advanced computational fluid dynamics (CFD) analysis using ANSYS Fluent to investigate the intricate flow behavior and velocity distribution. Through CFD calculations, the study provides valuable insights into the turbine's performance, allowing for optimization of its design parameters. The influence of blade numbers on turbine efficiency contributes to a better understanding of the turbine's operational characteristics. The paper discusses the advantages of decentralized energy systems and emphasizes the potential of gravitational vortex turbines for small-scale hydropower projects. It highlights the importance of mathematical analysis and performance results, further supported by the CFD analysis, demonstrating the turbine's capabilities. The power outputs achieved by the turbine align with or surpass the potential power capacities of identified small hydro sites, reinforcing its viability as a clean and reliable energy solution. While the research findings showcase the turbine's potential, it emphasizes the need for further feasibility studies and site-specific assessments to ensure successful real-life implementation. The study underscores the significance of utilizing advanced computational techniques in developing efficient and environmentally friendly hydropower solutions. The findings offer lessons for researchers, engineers, and policymakers for cleaner and more sustainable energy sources.
Ultra-wideband Metamaterial-based Rectangular Microstrip Antenna for Sub-6 GHz 5G and other Microwave Applications
Authors: Lambert Udoh Mary , Michael Udofia Kufre , Bernard Obot Akaninyene
Published: July 2023

This paper presents a novel design of an ultra-wideband metamaterial-based rectangular microstrip antenna for sub-6 GHz 5G and other microwave applications. The proposed antenna consist of a rectangular microstrip patch, two metamaterial unit cells, Flame Resistant (FR-4) substrate  and partial ground plane. The metamaterial unit cell comprises complementary split ring resonator (CSRR) with double negative characteristics (negative permeability and negative permittivity) as well as negative refractive index (NRI). The NRI medium enhanced the bandwidth and radiation efficiency of the antenna by reducing the surface waves and mutual coupling. The antenna operates over frequency range of 3.4009 to 11.721 GHz and 2.869 to 3.211 GHz, covering the sub-6 GHz 5G bands and other microwave applications such as Wi-Fi, WiMAX, and WLAN. Also, the proposed antenna had optimized dimensions of  and exhibited good impedance matching, omnidirectional radiation pattern, and stable gain across the operating band. From simulation results, a combined bandwidth of 8.66 GHz was achieved which shows good agreement with outlined objective. The proposed antenna is suitable for sub-6 GHz 5G and other microwave applications that require ultra-wideband performance and low-profile design.
Pembuatan Inverter Satu Fasa 100 Watt Menggunakan Konverter Buck
Authors: Adena Yeremia , Tumbelaka Hanny Hosiana , Khoswanto Handry
Published: July 2023

Tujuan dari penelitian ini adalah untuk merancang konverter dc – ac (inverter) satu fasa 100 watt yang menghasilkan bentuk gelombang output ac sinusoidal. Inverter ini menggunakan konverter buck yang didukung oleh inverter dorong-tarik dan dikontrol menggunakan modulasi lebar pulsa (Pulse Width Modulation). Penguat operasional (op-amp) memiliki kemampuan untuk menghasilkan gelombang PWM. Inverter yang telah dirancang mampu menghasilkan gelombang sinusoidal dengan tegangan ac 211 volt tanpa menggunakan beban.
Pemantauan Kualitas Udara Polutan CO dan CO2 Berbasis IoT
Authors: Putra Hardian Setya Dharma , Lim Resmana , Putro Iwan Handoyo
Published: July 2023

- Sebagian besar sistem pemantauan udara yang ada belum dapat terkoneksi melalui jaringan internet, oleh karenanya alat pemantau udara tersebut hanya dapat dipantau dan dikendalikan secara lokal. Dalam TA ini akan dibuat alat pemantau kualitas udara polutan CO dan CO2 berbasis IoT (Internet of Things). Dalam pembuatan alat pemantau polutan udara menggunakan sensor MQ-7 untuk mendeteksi gas CO dan menggunakan sensor MH-Z19 untuk memantau gas CO2. Perbedaan dengan alat-alat yang telah dibuat sebelumnya yang sebagian besar menggunakan sensor tipe TGS yaitu harga yang lebih murah. Dengan adanya alat pemantau kualitas udara yang dibuat dalam TA ini dapat diakses melalui website ataupun handphone dengan aplikasi Blynk. Hasil dalam pembuatan sistem pemantau polutan udara berbasi IoT adalah mudahnya pemantauan gas polutan udara khususnya gas CO dan CO2. Dalam pembacaan besaran gas CO dan CO2 alat pemantantau polutan udara berbasis IoT memiliki tingkat kesalahan pembacaan gas CO sebesar 0% dan gas CO2 sebesar 97%-98 %. Besar error pembacaan sensor gas CO2 dikarenakan sensor untuk kalibrasi tidak memiliki spesifikasi yang sama dengan sensor yang digunakan. Pemantauan polutan udara terdiri dalam tiga tampilan yaitu tampilan berupa website, aplikasi Blynk dan perangkat LCD 20x4.
Pembuatan Rak Komponen Semi Automatis Berbasis Raspbery Pi 3 dan Arduino Nano
Authors: Lukito Jonathan Pratama , Lim Resmana , Khoswanto Handry
Published: July 2023

Ide ini diambil dari masalah ketidakpraktisan toko komponen elektronika dalam memanagemen komponen yang dijual pada rak komponen dan sangat mengharapkan ketelitian penjual dalam mengetahui posisi komponen yang terletak. Sistem yang dibuat ini terdiri dari rak komponen dan simulasi rak komponen yang terdapat LED sebagai indikator drawer dan komponen-komponen pendukung didalamnya. Sistem ini memiliki sebuah halaman web pembelian sederhana sebagai antar muka pengguna yang terhubung didalam satu jaringan lokal. Seluruh sistem ini dikendalikan oleh Raspberry Pi 3 dan Arduino Nano. Berdasarkan hasil pengujian yang dilakukan, dapat diambil kesimpulan bahwa sistem yang dibuat ini telah berjalan dengan benar sesuai dengan pengujian
Perencanaan dan Pembangunan Pembangkit Listrik Tenaga Mikrohidro serta Instalasinya untuk Penerangan Kawasan Hutan Wisata di Desa Benu Kecamatan Takari Kabupaten Kupang
Authors: Gontani Arbi Darmawan , Rohi Daniel , Setiadji Julius Sentosa
Published: July 2023

Kawasan hutan wisata desa Benu, Kabupaten Kupang, merupakan jalan penghubung ke daerah persawahan penduduk. Di kawasan ini juga sering diadakan acara adat oleh penduduk setempat. Sehingga dinas kehutanan berinisiatif untuk memberikan penerangan di kawasan tersebut, dengan memanfaatkan potensi sumber air yang terdapat di sekitar kawasan hutan. Survei lokasi dilakukan untuk mendapatkan nilai debit air dan head yang disesuaikan dengan kondisi lokasi yang akan dilakukan pembangunan PLTMH. Metode yang dilakukan untuk mendapatkan debit air adalah dengan menggunakan metode cross-section sedangkan besarnya head ditentukan dengan menggunakan tape-measure. Kawasan hutan wisata desa Benu memiliki debit air sebesar 0.039 m3 /s dan head yang ditentukan sesuai lokasi sebesar 3 meter. Daya listrik yang dapat dihasilkan dari debit air dan head tersebut adalah sebesar 135 watt
Pemberi Makan Ikan dan Pengurasan Otomatis pada Akuarium berbasis IoT
Authors: Suwanto Yansen , Santoso Petrus
Published: July 2023

Hal utama dalam merawat ikan adalah pemberian makan yang teratur dan menjaga kualitas kebersihan air agar ikan dapat hidup dengan sehat. Merawat ikan saat ini dengan cara memberi makan ikan dilokasi tempat akuarium berada dan mengurasnya ketika air sudah terlihat keruh.

Oleh karena itu proyek ini bertujuan untuk menggantikan cara merawat ikan dengan sistem otomatis yang dapat dipantau dari jarak jauh. Sistem otomatis menggunakan Wemos D1 mini terintegrasi ESP8266 sebagai mikrokontroler yang digunakan untuk membaca tingkat kekeruhan air, persediaan makanan ikan, dan tingkat air dalam akuarium. Sistem membutuhkan jaringan wifi untuk koneksi ke internet agar alat dapat bekerja dengan baik. Pemantauan kondisi akuarium dapat dilihat pada LCD 16x2 dan aplikasi mobile yang dapat memberikan notifikasi.

 

Kata Kunci — pemberi makan ikan otomatis, pengurasan akuarium otomatis, aplikasi android, ESP8266, IoT
State Restrictions and Geographic Access to Gender-Affirming Care for Transgender Youth
Authors: Borah Luca , Zebib Laura , Sanders Hayley M. , Lane Megan , Stroumsa Daphna , Chung Kevin C.
Published: July 2023

This study estimates changes in geographic access and drive times to gender clinics following legislation enacted to restrict puberty-suppressing medications and hormones for those younger than 18 years.
Validation of the multidimensional bystander responses to racist hate speech scale and its association with empathy and moral disengagement among adolescents
Authors: Wachs Sebastian , Bilz Ludwig , Wettstein Alexander , Espelage Dorothy L.
Published: July 2023

Our understanding of how bystanders respond to hate speech is limited. This may be due, in part, to the lack of available measurement tools. However, understanding adolescents’ responses to hate speech is critical because this kind of research can support schools in empowering students to exhibit courageous moral behavior. Thus, the purpose of the present study was to investigate the psychometric properties of the newly developed Multidimensional Bystander Responses to Hate Speech Scale (MBRHS) and to explore demographic differences and correlates of bystander behavior in school hate speech. The sample consisted of 3225 seventh to ninth graders from Germany and Switzerland. Exploratory and confirmatory factor analyses supported a model with seven factors. We found that adolescents with immigrant background and boys showed particularly unfavorable response patterns. In addition, our study suggests that empathy is positively correlated with the factorscomforting the victim, seeking help at school, andcountering hate speechbut negatively correlated withhelplessness,revenge,reinforcing, andignoring. Moral disengagement showed the opposite correlational pattern. The findings indicate that the MBRHS is a psychometrically valid and reliable measure that could aid in measuring varied responses to hate speech. In addition, this work highlights the relevance of empathy and moral engagement training in anti‐hate speech prevention programs.
Direct Introduction of −OCD3 into the Hantzsch Pyrrole Synthesis via Multicomponent Cascade Cyclization: Synthesis of Fully Substituted Pyrrole Derivatives
Authors: Wang Li‐Sheng , Zhou You , Lei Shuang‐Gui , Tang Bo‐Cheng , Yu Zhi‐Cheng , Tang Yong‐Xing , Wu Yan‐Dong , Wu An‐Xin
Published: July 2023

A I2‐DMSO mediated approach to introduce −OCD3 into pyrroles in situ via multicomponent cascade cyclization reaction using methyl ketones, aniline, ethyl benzoylacetate and CD3OD as readily available substrates is reported. This process realizes introduction of −OCD3 into the Hantzsch pyrrole synthesis and synthesis of deuterated alkoxy‐substituted pyrroles with formation of one C−C bond, one C−O bond and two C−N bonds in one pot. Notably, this conversion has good substrate compatibility (62 examples) and eliminates of the need for anhydrous and anaerobic operation.
Decomposition of phenotypic variation of white oats by meteorological and geographic covariables
Authors: Schmidt Aline Luiza , Carvalho Ivan Ricardo , da Silva José Antonio Gonzalez , Lângaro Nadia Canali , de Oliveira Antonio Costa , Pradebon Leonardo Cesar , Loro Murilo Vieira , Roza João Pedro Dalla , Bruinsma Gabriel Mathias Weimer
Published: July 2023

White oat (Avena sativa L.) is a cold season grass, with a very important role, both in animal and human food, due to the chemical composition of its grains, which have, among other beneficial components, fiber soluble food products, beta‐glucans. Therefore, the demand for grains of the crop is maximized, and it is important to increase grain production. This can be achieved through the adequate positioning of the genotypes in the growing environments to maximize the agronomic performance of the crop. Thus, the objective of this work was to decompose meteorological and geographic variables in the positioning of white oat genotypes. The study took place considering 39 genotypes of white oats in 21 environments (in 13 years), in six municipalities of Rio Grande do Sul, two locations in the state of Santa Catarina, 10 in Paraná, and three municipalities in the state of São Paulo. The average grain yield (GY) (kg ha−1) of the genotypes in each environment was used to determine the adaptability and stability of the genotypes through the application of the genotype and genotype by environment interaction (GGE biplot) biometric method and the reaction norm. The reaction norm pointed out that the genotypes UPFPS Farroupilha, UPFA Gaudéria, and URS Guará demonstrated general adaptability to all environments, whereas FAEM 006 and URS Charrua expressed stability, high GY, and higher than average genetic value. The GGE biplot graphically demonstrated that the genotypes URS Monarca and IPR Artemis demonstrated the highest GY and high stability in the environments Eldorado do Sul—RS (E7) and Pelotas—RS. Identifying genotypes with superior agronomic performance in specific environments minimizes the effects of genotype × environment interaction. These white oat genotypes can be used as sources of alleles for the development of new genotypes.
Improving decision support systems with machine learning: Identifying barriers to adoption
Authors: Brugler Skye , Gardezi Maaz , Dadkhah Ali , Rizzo Donna M. , Zia Asim , Clay Sharon A.
Published: July 2023

Precision agriculture (PA) has been defined as a “management strategy that gathers, processes and analyzes temporal, spatial and individual data and combines it with other information to support management decisions according to estimated variability for improved resource use efficiency, productivity, quality, profitability and sustainability of agricultural production.” This definition suggests that because PA should simultaneously increase food production and reduce the environmental footprint, the barriers to adoption of PA should be explored. These barriers include (1) the financial constraints associated with adopting decision support system (DSS); (2) the hesitancy of farmers to change from their trusted advisor to a computer program that often behaves as a black box; (3) questions about data ownership and privacy; and (4) the lack of a trained workforce to provide the necessary training to implement DSSs on individual farms. This paper also discusses the lessons learned from successful and unsuccessful efforts to implement DSSs, the importance of communication with end users during DSS development, and potential career opportunities that DSSs are creating in PA.
Background, rationale, and methodological overview of the REACT project—return‐to‐action on growth, motor development, and health after the COVID‐19 pandemic in primary school children
Authors: Pereira Sara , Katzmarzyk Peter T. , Hedeker Donald , Barreira Tiago V. , Garganta Rui , Farias Cláudio , Garbeloto Fernando , Tani Go , Chaput Jean‐Philippe , Stodden David F. , Maia José
Published: July 2023

Objectives

The REACT project was designed around two main aims: (1) to assess children's growth and motor development after the COVID‐19 pandemic and (2) to follow their fundamental movement skills' developmental trajectories over 18 months using a novel technological device (Meu Educativo®) in their physical education classes. In this introductory article, the first of the Journal's special issue dedicated to REACT, our goal was to present the project rationale, its methodology, training and certification of the team, statistical approach, quality control, governance, and study management.

Methods

We sampled 1000 children (6–10 years of age) from 25 of the 32 primary schools in Matosinhos, northern Portugal. The protocol included a set of variables clustered around the child (growth, physical fitness, fundamental movement skills, and health behaviors), family (demographics, socioeconomic status, parental support for sports participation and physical activity), school (policies and practices for health behaviors, infrastructure for physical education and sports practices), and neighborhood and home environments (safety, sidewalks, sports facilities, as well as children electronic devices and play equipment at home). A set of standard protocols were implemented in REACT together with a rigorous system of training and certification of all members of the research team. This was complemented with a pilot study to assess, in loco, the quality of data acquisition, data entry, and control.

Discussion

Results from REACT will provide school administrators and teachers with novel and far‐reaching information related to children's growth and motor development as well as health behaviors after the COVID‐19 pandemic. It will also provide city‐hall education officials with insight regarding children's physical fitness, fundamental movement skills, and sports practices that will be of great importance in devising novel intervention programs to increase health‐enhancing physical activity, and combat sedentariness and obesity. Finally, it will offer parents a wealth of information regarding their children's growth, motor development, and health.
Differences in sperm morphology between Alouatta palliata and Alouatta pigra are consistent with the intensity of sperm competition in each species
Authors: Hirst Molly A. , Rodas‐Martínez Alba Z. , Milich Krista M. , Cortés‐Ortiz Liliana
Published: July 2023

The intensity of sperm competition, in which sperm compete within the female reproductive tract to reach and fertilize her eggs, varies in species with different mating systems. Sperm competition is more intense in species where males cannot monopolize access to reproductive females and females mate with multiple males. In this scenario, a morphological change that increases the ability of sperm to reach and fertilize eggs should rapidly spread in the population, leading to sperm morphological differences between closely related species. Differences in sperm morphology have been reported among primate species with different mating systems. However, due to the inherent logistical and ethical difficulties to sample sperm from wild primates, the extent of variation in sperm morphology within species and among closely related species remains understudied. Here, we compared sperm morphological traits from two sister howler monkey species (Alouatta palliata and Alouatta pigra) that have different mating systems to investigate the effect of sperm competition on sperm morphological traits. We predicted that sperm from A. palliata, where females have more opportunities to mate with multiple males, would show differences in traits associated with increase sperm competitiveness compared to A. pigra where females mostly mate with the central male. We used linear mixed models to determine species differences in sperm morphology, controlling for individual variation. We found that midpieces and heads in A. palliata sperm were on average 26.2% and 11.0% longer, respectively, than those of A. pigra. Differences in these traits are important for sperm speed and hydrodynamic movement in other species and can affect fertilization success. This study provides empirical evidence of sperm morphological traits that evolved through sexual selection in sister primate species with different mating systems.
Feasibility and Validity of the Coma Recovery Scale‐Revised for Accelerated Standardized Testing: A Practical Assessment Tool for Detecting Consciousness in the Intensive Care Unit
Authors: Bodien Yelena G. , Vora Isha , Barra Alice , Chiang Kevin , Chatelle Camille , Goostrey Kelsey , Martens Geraldine , Malone Christopher , Mello Jennifer , Parlman Kristin , Ranford Jessica , Sterling Ally , Waters Abigail B. , Hirschberg Ronald , Katz Douglas I. , Mazwi Nicole , Ni Pengsheng , Velmahos George , Waak Karen , Edlow Brian L. , Giacino Joseph T.
Published: July 2023

We developed and validated an abbreviated version of the Coma Recovery Scale‐Revised (CRS‐R), the CRS‐R For Accelerated Standardized Testing (CRSR‐FAST), to detect conscious awareness in patients with severe traumatic brain injury in the intensive care unit. In 45 consecutively enrolled patients, CRSR‐FAST administration time was approximately one‐third of the full‐length CRS‐R (mean [SD] 6.5 [3.3] vs 20.1 [7.2] minutes, p < 0.0001). Concurrent validity (simple kappa 0.68), test–retest (Mak's ρ = 0.76), and interrater (Mak's ρ = 0.91) reliability were substantial. Sensitivity, specificity, and accuracy for detecting consciousness were 81%, 89%, and 84%, respectively. The CRSR‐FAST facilitates serial assessment of consciousness, which is essential for diagnostic and prognostic accuracy. ANN NEUROL 2023;94:919–924
Comparison of CT Perfusion Software Packages for Thrombectomy Eligibility
Authors: Pisani Leonardo , Haussen Diogo C. , Mohammaden Mahmoud , Perry da Camara Catarina , Jillella Dinesh V. , Rodrigues Gabriel M. , Bouslama Mehdi , Al‐Bayati Alhamza , Prater Adam , Liberato Bernardo , Frankel Michael R. , Nogueira Raul G.
Published: July 2023

Introduction

Computed tomography perfusion (CTP) has played an important role in patient selection for mechanical thrombectomy (MT) in acute ischemic stroke. We aimed to investigate the agreement between perfusion parametric maps of 3 software packages – RAPID (RapidAI‐IschemaView), Viz CTP(Viz.ai), and e‐CTP(Brainomix) – in estimating baseline ischemic core volumes of near completely/completely reperfused patients.

Methods

We retrospectively reviewed a prospectively maintained MT database to identify patients with anterior circulation large vessel occlusion strokes (LVOS) involving the internal carotid artery or middle cerebral artery M1‐segment and interpretable CTP maps treated during September 2018 to November 2019. A subset of patients with near‐complete/complete reperfusion (expanded thrombolysis in cerebral infarction [eTICI] 2c–3) was used to compare the pre‐procedural prediction of final infarct volumes.

Results

In this analysis of 242 patients with LVOS, RAPID and Viz CTP relative cerebral blood flow (rCBF) < 30% values had substantial agreement (ρ = 0.767 [95% confidence interval [CI] = 0.71–0.81]) as well as for RAPID and e‐CTP (ρ = 0.668 [95% CI = 0.61–0.71]). Excellent agreement was seen for time to maximum of the residue function (Tmax) > 6 seconds between RAPID and Viz CTP (ρ = 0.811 [95% CI = 0.76–0.84]) and substantial for RAPID and e‐CTP (ρ = 0.749 [95% CI = 0.69–0.79]). Final infarct volume (FIV) prediction (n = 136) was substantial in all 3 packages (RAPID ρ = 0.744; Viz CTP ρ = 0.711; and e‐CTP ρ = 0.600).

Conclusion

Perfusion parametric maps of the RAPID, Viz CTP, and e‐CTP software have substantial agreement in predicting final infarct volume in near‐completely/completely reperfused patients. ANN NEUROL 2023;94:848–855
Anakinra‐Associated Systemic Amyloidosis
Authors: Alehashemi Sara , Dasari Surendra , Metpally Anvitha , Uss Kat , Castelo‐Soccio Leslie A. , Heller Theo , Kellman Peter , Chen Marcus Y. , Ahlman Mark , Kim Jeff , Wargo Susannah , Kuhns Douglas B. , Fink Danielle , de Jesus Adriana , Martin Paul S. , Chang Richard , Bolanos Jonathan , Lee Chyi‐Chia Richard , Nasr Samih H. , Goldbach‐Mansky Raphaela , McPhail Ellen
Published: July 2023

Objective

To describe a 41‐year‐old woman with a history of neonatal onset multisystem inflammatory disease, on treatment with daily subcutaneous injections of 600 mg of recombinant interleukin‐1 receptor antagonist (IL‐1Ra) protein, anakinra, since the age of 28, who presented with golf‐ball size nodules at the anakinra injection sites, early satiety, new onset nephrotic syndrome in the context of normal markers of systemic inflammation.

Methods

Clinical history and histologic evaluation of biopsies of skin, gastric mucosa, and kidney with Congo‐red staining and proteomic evaluation of microdissected Congo red–positive amyloid deposits by liquid chromatography‐tandem mass spectrometry.

Results

The skin, stomach, and kidney biopsies all showed the presence of Congo red–positive amyloid deposits. Mass spectrometry‐based proteomics demonstrated that the amyloid deposits in all sites were of AIL1RAP (IL‐1Ra protein)‐type. These were characterized by high spectral counts of the amyloid signature proteins (apolipoprotein AIV, apolipoprotein E, and serum amyloid P‐component) and the amyloidogenic IL‐1Ra protein, which were present in Congo red–positive areas and absent in Congo red–negative areas. The amino acid sequence identified by mass spectrometry confirmed that the amyloid precursor protein was recombinant IL‐1Ra (anakinra) and not endogenous wild‐type IL‐1Ra.

Conclusion

This is the first report of iatrogenic systemic amyloidosis due to an injectable protein drug, which was caused by recombinant IL1Ra (anakinra).
Tau, microtubule dynamics, and axonal transport: New paradigms for neurodegenerative disease
Authors: Cario Alisa , Berger Christopher L.
Published: July 2023

The etiology of Tauopathies, a diverse class of neurodegenerative diseases associated with the Microtubule Associated Protein (MAP) Tau, is usually described by a common mechanism in which Tau dysfunction results in the loss of axonal microtubule stability. Here, we reexamine and build upon the canonical disease model to encompass other Tau functions. In addition to regulating microtubule dynamics, Tau acts as a modulator of motor proteins, a signaling hub, and a scaffolding protein. This diverse array of functions is related to the dynamic nature of Tau isoform expression, post‐translational modification (PTM), and conformational flexibility. Thus, there is no single mechanism that can describe Tau dysfunction. The effects of specific pathogenic mutations or aberrant PTMs need to be examined on all of the various functions of Tau in order to understand the unique etiology of each disease state.
Improving phytase production in Pichia pastoris fermentations through de‐repression and methanol induction optimization
Authors: Luna‐Flores Carlos H. , Weng Yilun , Wang Alexander , Chen Xiaojing , Peng Bingyin , Zhao Chun‐Xia , Navone Laura , von Hellens Juhani , Speight Robert E.
Published: July 2023

Pichia pastoris (Komagataella phaffii) is a fast‐growing methylotrophic yeast with the ability to assimilate several carbon sources such as methanol, glucose, or glycerol. It has been shown to have outstanding secretion capability with a variety of heterologous proteins. In previous studies, we engineered P. pastoris to co‐express Escherichia coli AppA phytase and the HAC1 transcriptional activator using a bidirectional promoter. Phytase production was characterized in shake flasks and did not reflect industrial conditions. In the present study, phytase expression was explored and optimized using instrumented fermenters in continuous and fed‐batch modes. First, the production of phytase was investigated under glucose de‐repression in continuous culture at three dilution factors, 0.5 d−1, 1 d−1, and 1.5 d−1. The fermenter parameters of these cultures were used to inform a kinetic model in batch and fed‐batch modes for growth and phytase production. The kinetic model developed aided to design the glucose‐feeding profile of a fed‐batch culture. Kinetic model simulations under glucose de‐repression and fed‐batch conditions identified optimal phytase productivity at the specific growth rate of 0.041 h−1. Validation of the model simulation with experimental data confirmed the feasibility of the model to predict phytase production in our newly engineered strain. Methanol was used only to induce the expression of phytase at high cell densities. Our results showed that high phytase production required two stages, the first stage used glucose under de‐repression conditions to generate biomass while expressing phytase, and stage two used methanol to induce phytase expression. The production of phytase was improved 3.5‐fold by methanol induction compared to the expression with glucose alone under de‐repression conditions to a final phytase activity of 12.65 MU/L. This final volumetric phytase production represented an approximate 36‐fold change compared to the flask fermentations. Finally, the phytase protein produced was assayed to confirm its molecular weight, and pH and temperature profiles. This study highlights the importance of optimizing protein production in P. pastoris when using novel promoters and presents a general approach to performing bioprocess optimization in this important production host.
Sodium chloride impacts glycosylation and N‐ and O‐glycan site occupancy of an Fc‐fusion protein
Authors: Bohl Susanne , Le Mignon Maxime , Kilian Thomas , Zimmer Aline
Published: July 2023

Fc‐fusion proteins are highly complex molecules, difficult to manufacture at scale. In this work, undesired proteoforms were detected during the manufacture of a therapeutic fusion protein produced in CHO cells. These species were characterized using gel electrophoresis, size exclusion chromatography and liquid chromatography‐mass spectrometry leading to the identification of low molecular weight proteoforms presenting low N‐ and O‐glycan site occupancy, as well as a low sialylation content. Upstream process parameters were investigated, and fusion protein quality was shown to be linked to the sodium chloride content of the medium. A mitigation strategy was developed to avoid formation of unwanted glyco‐variants, resulting in an increased yield of highly glycosylated Fc‐fusion protein. The effect of sodium chloride was shown to be independent of the osmolality increase and was hypothesized to be linked to a modulation of Golgi acidity, which is required for the correct localization and function of glycosyltransferases. Altogether, this study highlights the importance of the salt balance in cell culture media used to produce highly sialylated and occupied glycoproteins, helping to maximize the yield and increase robustness of processes aiming at producing biopharmaceutical complex therapeutic molecules.
Brands are calling your AVATAR in Metaverse–A study to explore XR‐based gamification marketing activities & consumer‐based brand equity in virtual world
Authors: Arya Vikas , Sambyal Rachita , Sharma Anshuman , Dwivedi Yogesh K
Published: July 2023

Brands are moving towards the Metaverse (3D immersive virtual spaces), where the growth of intangible products and nonfungible tokens (NFTs) are evolving into a new type of hybrid experience for the users. This paper aims to establish the role of a “gamification of marketing activities” and its influence on consumer‐based brand equity for intangible products (NFTs) in the Metaverse and examine the mediating role of consumers' brand engagement and brand love. To evaluate the conceptual model based on the cross‐cultural data from two emerging countries in Asia and Africa, the study followed a two‐stage, hybrid mechanism using PLS‐SEM and neural network modeling. This study provides insights into the Metaverse–a new taxonomy of technology, in the context of embodiment, presence of AVATAR, and interactivity in the virtual world, supported by the social exchange theory. This study also suggests practitioners focus on brand authenticity while projecting their brand in the Metaverse.
Caulobacter segnis Dioxygenase CsO2: A Practical Biocatalyst for Stilbenoid Ozonolysis
Authors: De Vitis Valerio , Cannazza Pietro , Mattio Luce , Romano Diego , Pinto Andrea , Molinari Francesco , Laurenzi Tommaso , Eberini Ivano , Contente Martina L.
Published: July 2023

Ozonolysis is a useful as well as dangerous reaction for performing alkene cleavage. On the other hand, enzymes are considered a more sustainable and safer alternative. Among them, Caulobacter segnis dioxygenase (CsO2) known so far for its ability to catalyze the coenzyme‐free oxidation of vinylguaiacol into vanillin, was selected and its substrate scope evaluated towards diverse natural and synthetic stilbenoids. Under optimized conditions, CsO2 catalyzed the oxidative cleavage of the C=C double bonds of various trans‐stilbenes, providing that a hydroxyl moiety was necessary in para‐position of the phenyl group (e. g., resveratrol and its derivatives) for the reaction to take place, which was confirmed by modelling studies. The reactions occurred rapidly (0.5–3 h) with high conversions (95–99 %) and without formation of by‐products. The resveratrol biotransformation was carried out on 50–mL scale thus confirming the feasibility of the biocatalytic system as a preparative method.
Base‐Stabilized Phosphinidene Oxide, Imide and Sulfide
Authors: Baradzenka Aliona G. , Vyboishchikov Sergei F. , Pilkington Melanie , Nikonov Georgii I.
Published: July 2023

Oxidation of a base‐stabilized phosphinidene (κ2‐NNP)P (12, NNP=phosphinoamidinate) with N2O afforded a labile phosphinidene oxide (κ2‐NNP)P=O (16) which was characterized by NMR spectroscopy. Further oxidation of 16 by N2O or reaction of 12 with two equivalents of pyridine oxide afforded the isolable dioxide (κ2‐NNP)PO2 which was characterized by NMR and SC XRD. Trapping of 16 with tolyl isocyanate resulted in P=O/N=C metathesis, eventually affording a urea‐ligated phosphine (κ1‐NNP)P(NTol)2C=O (17) The mechanism of this reaction was elucidated by DFT calculations. Reactions of phosphinidene 12 with azides generated transient imines (NNP)P=NR, which in the case of R=Tol underwent cycloaddition with tolyl Isocyanate to afford the urea product 17, and in the case of R=SiMe3 reacts with N3SiMe3 via the addition of N−Si across the P=N bond affording, after the extrusion of dinitrogen, a P,N‐heterocyclic compound. Both products of the reactions with azides have been fully characterized, both in solution and the solid‐state. Finally, reaction of phosphinidene 12 with one equivalent of sulfur resulted in the isolation of the base‐stabilized phosphinidene sulfide (κ2‐NNP)P=S that has also been fully characterized.
Strain‐Driven, Non‐Catalysed Ring Expansion of Silicon Heterocycles
Authors: Müller Maximilian P. , Hinz Alexander
Published: July 2023

Silacycles are ubiquitous building blocks. Small silacycles can typically be expanded catalytically. A silirane, silirene and phosphasilirene as well as a siletane and a silolene were prepared starting from the base‐free bromosilylene [(dtbpCbz)SiBr] (dtbpCbz=1,8‐bis(3,5‐ditertbutylphenyl)‐3,6‐ditertbutylcarbazolyl). As these heterocycles were derived from a dicoordinated silylene, they are susceptible to reactions with an external base. The three‐membered silacycles readily undergo non‐catalysed ring expansion reactions with isonitriles yielding the related four‐membered silacycles. Surprisingly, the ring‐expanded derivatives of the silirane undergo up to two further isomerisation reactions, first by enamine formation and then by another ring expansion. DFT computations were utilised to gauge the scope of this reactivity pattern. Three‐membered silacycles should essentially universally undergo a ring expansion with isonitriles, while for four‐membered silacycles, only very few instances are predicted to accommodate more challenging kinetic requirements of this ring expansion. Larger silacycles lack the ring strain energy required for this ring expansion reaction and are not expected to be expanded.
Low‐Energy Driven Ring‐Opening Behavior of Benzocyclobutene Derivatives
Authors: Yuan Ziwei , Sun Quan , Xiao Jinchong , Zhang Pingxia , Levchenko Konstantin S. , Demin Dmitry Y. , Fu Wenxin
Published: July 2023

Comprehensive Summary

It's urgent to develop benzocyclobutene (BCB)‐based polymers with low curing temperature for temperature‐sensitive applications such as liquid crystal displays (LCDs) and flexible electronics. Herein, the effect of substituents on the ring‐opening behavior of BCB derivatives was investigated. The ring‐opening activation energy barriers (ΔGA) of BCB derivatives with one or two substituents on the four‐membered alkyl ring were systematically calculated using the B3LYP function. Both mono‐ and di‐substituted BCBs adopted the conrotatory ring‐opening process, obeying the Woodward‐Hoffmann's Rules upon heating. The mono‐/di‐substituted BCBs exhibited 8.2%—69% lower ΔGA compared with BCB, attributed to the electronic effects of the substituents. Disubstituted BCBs with both electron‐donating and electron‐withdrawing groups, e.g., 1‐NH2‐8‐NO2‐BCB, demonstrated the lowest ΔGA. In addition, BCB derivatives with amide/ester/acyloxy group modified on C1 position were synthesized as model molecules, and their ring‐opening temperature can be decreased by 20 °C compared to the unsubstituted one, also consistent with our calculation results. This work combined theoretical calculation methods with experimental results to provide valuable insights into the design and synthesis of BCB derivatives and next‐generation BCB functional packaging materials with low ring‐opening temperature.
Engaging Black sexual minority women in breast cancer research: Lessons in community partnerships
Authors: Geffen Sophia R. , Poteat Tonia , Dean Lorraine T. , Malone Jowanna , Greene Naomi , Adams Mary Anne
Published: July 2023

Background

Black sexual minority women (BSMW) face significant breast cancer health inequities and are underrepresented in health research because of historical and present‐day exclusion. However, there exists no peer‐reviewed literature on best practices for the inclusion of BSMW in cancer research. “Our Breast Health: The Access Project” was a national primary data collection study in June 2018 through October 2019 that aimed to identify facilitators and barriers to breast cancer care among BSMW, and that successfully recruited the highest number of BSMW for any national breast cancer screening study at the time of its publication.

Methods

The present analysis highlights best practices for reaching BSMW by examining by how effective various recruitment sources were at recruiting BSMW. Recruitment partners were grouped into several categories: (1) cancer focused, (2) Black women or sexual minority women focused, (3) BSMW focused, (4) social media, and (5) other. Then logistic regression was used to estimate the odds that a particular recruitment source category could recruit BSMW compared with other categories.

Results

Partnerships with community‐based organizations led by and intended for BSMW were the most successful at recruiting BSMW, demonstrating the importance of an intersectional approach to recruitment. Community‐based organizations focused on BSMW specifically were 26 times more successful in recruiting BSMW to the study compared with recruiting Black women who were not sexual minorities (odds ratio, 26.43 [95% CI, 7.50–93.10]).

Conclusions

Successful recruitment enables breast cancer research grounded in the perspectives of BSMW, which can generate key findings that have the potential to remedy longstanding health inequities for this population.
A portable C++ library for memory and compute abstraction on multi‐core CPUs and GPUs
Authors: Incardona Pietro , Gupta Aryaman , Yaskovets Serhii , Sbalzarini Ivo F.
Published: July 2023

We present a C++ library for transparent memory and compute abstraction across CPU and GPU architectures. Our library combines generic data structures like vectors, multi‐dimensional arrays, maps, graphs, and sparse grids with basic generic algorithms like arbitrary‐dimensional convolutions, copying, merging, sorting, prefix sum, reductions, neighbor search, and filtering. The memory layout of the data structures is adapted at compile time using C++ tuples with optional memory double‐mapping between host and device and the capability of using memory managed by external libraries with no data copying. We combine this transparent memory layout with generic thread‐parallel algorithms under two alternative common interfaces: a CUDA‐like kernel interface and a lambda‐function interface. We quantify the memory and compute performance and portability of our implementation using micro‐benchmarks, showing that the abstractions introduce negligible performance overhead, and we compare performance against the current state of the art in a real‐world scientific application from computational fluid mechanics.
Integrated single‐cell and spatial transcriptomic profiling reveals higher intratumour heterogeneity and epithelial–fibroblast interactions in recurrent bladder cancer
Authors: Shi Zhen‐Duo , Sun Zhuo , Zhu Zuo‐Bin , Liu Xing , Chen Jun‐Zhi , Hao Lin , Zhu Jie‐Fei , Pang Kun , Wu Di , Dong Yang , Liu Yu‐Fei , Chen Wei‐Hua , Liang Qing , Zhuo Shi‐Chao , Han Cong‐Hui
Published: July 2023

Background

Recurrent bladder cancer is the most common type of urinary tract malignancy; nevertheless, the mechanistic basis for its recurrence is uncertain. Innovative technologies such as single‐cell transcriptomics and spatial transcriptomics (ST) offer new avenues for studying recurrent tumour progression at the single‐cell level while preserving spatial data.

Method

This study integrated single‐cell RNA (scRNA) sequencing and ST profiling to examine the tumour microenvironment (TME) of six bladder cancer tissues (three from primary tumours and three from recurrent tumours).

Findings

scRNA data‐based ST deconvolution analysis revealed a much higher tumour heterogeneity along with TME in recurrent tumours than in primary tumours. High‐resolution ST analysis further identified that while the overall natural killer/T cell and malignant cell count or the ratio of total cells was similar or even lower in the recurrent tumours, a higher interaction between epithelial and immune cells was detected. Moreover, the analysis of spatial communication reveals a marked increase in activity between cancer‐associated fibroblasts (CAFs) and malignant cells, as well as other immune cells in recurrent tumours.

Interpretation

We observed an enhanced interplay between CAFs and malignant cells in bladder recurrent tumours. These findings were first observed at the spatial level.
Multifunctional cytokine production marks influenza A virus‐specific CD4 T cells with high expression of survival molecules
Authors: Westerhof Lotus M. , Noonan Jonathan , Hargrave Kerrie E. , Chimbayo Elizabeth T. , Cheng Zhiling , Purnell Thomas , Jackson Mark R. , Borcherding Nicholas , MacLeod Megan K. L.
Published: July 2023

Cytokine production by memory T cells is a key mechanism of T cell mediated protection. However, we have limited understanding of the persistence of cytokine producing T cells during memory cell maintenance and secondary responses. We interrogated antigen‐specific CD4 T cells using a mouse influenza A virus infection model. Although CD4 T cells detected using MHCII tetramers declined in lymphoid and non‐lymphoid organs, we found similar numbers of cytokine+ CD4 T cells at days 9 and 30 in the lymphoid organs. CD4 T cells with the capacity to produce cytokines expressed higher levels of pro‐survival molecules, CD127 and Bcl2, than non‐cytokine+ cells. Transcriptomic analysis revealed a heterogeneous population of memory CD4 T cells with three clusters of cytokine+ cells. These clusters match flow cytometry data and reveal an enhanced survival signature in cells capable of producing multiple cytokines. Following re‐infection, multifunctional T cells expressed low levels of the proliferation marker, Ki67, whereas cells that only produce the anti‐viral cytokine, interferon‐γ, were more likely to be Ki67+. Despite this, multifunctional memory T cells formed a substantial fraction of the secondary memory pool. Together these data indicate that survival rather than proliferation may dictate which populations persist within the memory pool.
Highly sensitive glucose electrochemical sensor using sugar‐lectin interactions
Authors: Sugiyama Kyoko , Sato Fumiya , Komatsu Sachiko , Kamijo Toshio , Yoshida Kentaro , Kawabe Yusuke , Nishikawa Hiromi , Fujimura Tsutomu , Takahashi Yasufumi , Sato Katsuhiko
Published: July 2023

In this study, glucose oxidase (GOx) was immobilized on the electrode surface by layer‐by‐layer and gel membrane technique and characterized the GOx immobilized film morphology, H2O2 permeability, and glucose response. Concanavalin A (Con A)‐GOx multilayer electrodes showed higher glucose‐related current response than GOx‐bovine serum albumin gel membrane‐coated electrode, a common modification method. The thin thickness of the Con A/GOx multilayer film efficiently catalyzed the enzymatic reaction, and H2O2 was produced near the electrode surface, resulting in an immediate electrode response.