bluuebunny/crossref_metadata_2025 huggingface dataset:
DataverseNO
Authors: Conzett Philipp , Leif Longva , Nilsen Karl Magnus
Published: November 2022

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Evaluation and characterization of indigenous rice (Oryza sativa L.) landraces resistant to brown planthopper Nilaparvata lugens (Stål.) biotype 4
Authors: Roy Debashis , Biswas Abhisek , Sarkar Sukamal , Chakraborty Gautam , Gaber Ahmed , Kobeasy Mohamed I. , Hossain Akbar
Published: November 2022

Evaluation and identification of resistant donors for brown planthopper (BPH) Nilaparvata lugens (Stål.), an economically important insect pest of rice, is a continuous process to develop new resistant rice varieties. However, several rice landraces of north-eastern India are not yet characterized for BPH resistance. In the present study, a set of 218 rice landraces were screened in both greenhouse and open-field conditions for three consecutive years, and thereafter forty selected promising entries were explored to evaluate their phenotypic and genotypic reactions against BPH biotype 4. Based on phenotypic evaluations, five landraces were identified as resistant, while 31 were moderately resistant, and grouped under the major cluster I and II, respectively, in a circular dendrogram. Antixenosis and antibiosis studies of these landraces divulged that, compared to the susceptible check variety, resistant landraces exhibited the lowest feeding rate, survival, and nymphal and adult settling, but higher frequency of unhatched eggs of BPH. Un-infested resistant landraces registered higher levels of ascorbic acid, oxalic acid and crude silica, however, elevated levels of total free amino acid, potassium and crude silica were observed under BPH herbivory. The present study focuses on identifying new donors having BPH resistance resources which could be useful in genomic studies for the development of BPH biotype 4 resistant rice varieties.
The Tobacco Industry and Harm Reduction
Authors: Koh Howard K. , Fiore Michael C.
Published: November 2022

This Viewpoint discusses the ways in which the tobacco industry can advance their stated goals of harm reduction and a smoke-free future.
Coverage and Prior Authorization Policies for Medications for Opioid Use Disorder in Medicaid Managed Care
Authors: Abraham Amanda J. , Andrews Christina M. , Harris Samantha J. , Westlake Melissa M. , Grogan Colleen M.
Published: November 2022

Importance

Medicaid is a key policy lever to improve opioid use disorder treatment, covering approximately 40% of Americans with opioid use disorder. Although approximately 70% of Medicaid beneficiaries are enrolled in comprehensive managed care organization (MCO) plans, little is known about coverage and prior authorization (PA) policies for medications for opioid use disorder (MOUD) in these plans.

Objective

To compare coverage and PA policies for buprenorphine, methadone, and injectable naltrexone across Medicaid MCO plans and fee-for-service (FFS) programs and across states.

Design, Setting, and Participants

This cross-sectional study analyzed MOUD data from 266 Medicaid MCO plans and FFS programs in 38 states and the District of Columbia in 2018.

Main Outcomes and Measures

For each medication, the percentages of MCO plans and FFS programs that covered the medication without PA, covered the medication with PA, and did not cover the medication were calculated, as were the percentages of MCO, FFS, and all (MCO and FFS) beneficiaries who were covered with no PA, covered with PA, and not covered. In addition, MCO plan coverage and PA policies were mapped by state. Analyses were conducted from January 1 through May 31, 2022.

Results

Coverage and PA policies were compared for MOUD in 266 MCO plans and 39 FFS programs, representing approximately 70 million Medicaid beneficiaries. Overall, FFS programs had more generous MOUD coverage than MCO plans. However, a higher percentage of FFS programs imposed PA for the 3 medications (47.0%) than did MCOs (35.9%). Furthermore, although most Medicaid beneficiaries were enrolled in a plan that covered MOUD, 53.2% of all MCO- and FFS-enrolled beneficiaries were subject to PA. Results also showed wide state variation in MCO plan coverage and PA policies for MOUD and the percentage of Medicaid beneficiaries subject to PA.

Conclusions and Relevance

This cross-sectional study found variation in MOUD coverage and PA policies across Medicaid MCO plans and FFS programs and across states. Thus, Medicaid beneficiaries’ access to MOUD may be heavily influenced by their state of residency and the Medicaid plan in which they are enrolled. Left unaddressed, PA policies are likely to remain a barrier to MOUD access in the nation’s Medicaid programs.
Efficacy of a Hip Brace for Hip Displacement in Children With Cerebral Palsy
Authors: Kim Bo Ryun , Yoon Jin A. , Han Hyun Jung , Yoon Young Il , Lim Jiwoon , Lee Seungeun , Cho Seon , Shin Yong Beom , Lee Hyun Jung , Suh Jee Hyun , Jang Joonyoung , Beom Jaewon , Park Yulhyun , Choi Jung-Hwa , Ryu Ju Seok
Published: November 2022

Importance

There is no consensus on interventions to slow the progress of hip displacement in patients with cerebral palsy.

Objective

To investigate the efficacy of a novel hip brace in preventing progressive hip displacement in patients with cerebral palsy.

Design, Setting, and Participants

This 2-group randomized clinical trial was conducted at 4 tertiary hospitals in South Korea from July 2019 to November 2021. Participants included children aged 1 to 10 years with nonambulatory cerebral palsy (Gross Motor Function Classification System level IV or V). Block randomization was used to assign an equal number of patients to the study and control groups via computerized random allocation sequences. Data were analyzed from November to December 2021.

Interventions

The intervention group wore the hip brace for at least 12 hours a day for the study duration (ie, 12 months). Follow-up evaluations were performed after 6 and 12 months of wearing the brace. Both groups proceeded with conventional rehabilitation therapy during the trial.

Main Outcomes and Measures

The primary outcome was the Reimers migration index (MI) on radiography, as assessed by 3 blinded investigators. Primary outcome variables were analyzed using linear mixed models. Secondary outcomes include change in the Caregiver Priorities & Child Health Index of Life with Disabilities, on which lower scores indicate better quality of life.

Results

A total of 66 patients were included, with 33 patients (mean [SD] age, 68.7 [31.6] months; 25 [75.8%] boys) randomized to the intervention group and 33 patients (mean [SD] age, 60.7 [24.9] months; 20 [60.6%] boys) randomized to the control group. The baseline mean (SD) MI was 37.4% (19.3%) in the intervention group and 30.6% (16.3%) in the control group. The mean difference of the MI between the intervention group and control group was −8.7 (95% CI, −10.2 to −7.1) percentage points at 6 months and −12.7 (95% CI, −14.7 to −10.7) percentage points at 12 months. The changes in the Caregiver Priorities & Child Health Index of Life with Disabilities were favorable in the study group and reached statistical significance at the 6-month follow-up compared with the control group (difference, −14.2; 95% CI, −25.2 to −3.3).

Conclusions and Relevance

In this randomized clinical trial, the novel hip brace was significantly effective in preventing the progression of hip displacement, compared with the control group. It effectively improved quality of life in patients with nonambulatory cerebral palsy. Therefore, hip brace use could be a promising treatment method to delay hip surgery and improve the quality of life of patients with nonambulatory cerebral palsy.

Trial Registration

ClinicalTrials.gov Identifier: NCT04033289
A Narrowing Mortality Gap: Temporal Trends of Cause‐Specific Mortality in a National Matched Cohort Study in US Veterans With Rheumatoid Arthritis
Authors: Johnson Tate M. , Yang Yangyuna , Roul Punyasha , Sauer Brian C. , Cannon Grant W. , Kunkel Gary , Michaud Kaleb , Baker Joshua F. , Mikuls Ted R. , England Bryant R.
Published: November 2022

Objective

To examine temporal trends in all‐cause and cause‐specific mortality in patients with rheumatoid arthritis (RA) in the Veterans Health Administration (VHA).

Methods

We conducted a matched cohort study in the VHA from January 1, 2000 to December 31, 2017. Incident RA patients were matched up to 1:10 on age, sex, and VHA enrollment year to non‐RA patients, then followed until death or end of study period. Cause of death was obtained from the National Death Index. Multivariable Cox regression models stratified by RA diagnosis years were used to examine trends in RA‐related risk of all‐cause and cause‐specific mortality.

Results

Among 29,779 incident RA patients (matched to 245,226 non‐RA patients), 9,565 deaths occurred. RA patients were at increased risk of all‐cause (adjusted hazard ratio [HRadj] 1.23 [95% confidence interval (95% CI) 1.20–1.26]), cardiovascular (HRadj 1.19 [95% CI 1.14–1.23]), cancer (HRadj 1.19 [95% CI 1.14–1.24]), respiratory (HRadj 1.46 [95% CI 1.38–1.55]), and infection‐related mortality (HRadj 1.59 [95% CI 1.41–1.80]). Interstitial lung disease was the cause of death most strongly associated with RA (HRadj 3.39 [95% CI 2.88–3.99]). Nearly 70% of excess deaths in RA were attributable to cardiopulmonary disease. All‐cause mortality risk related to RA was lower among those diagnosed during 2012–2017 (HRadj 1.10 [95% CI 1.05–1.15]) compared to 2000–2005 (HRadj 1.31 [95% CI 1.26–1.36]), but still higher than for non‐RA controls (P < 0.001). Cause‐specific mortality trends were similar.

Conclusion

Excess RA‐related mortality was driven by cardiovascular, cancer, respiratory, and infectious causes, particularly cardiopulmonary diseases. Although our findings support that RA‐related mortality risk is decreasing over time, a mortality gap remains for all‐cause and cause‐specific mortality in RA.
Multiscale Biofabrication: Integrating Additive Manufacturing with DNA‐Programmable Self‐Assembly
Authors: Jäkel Anna C. , Heymann Michael , Simmel Friedrich C.
Published: November 2022

Structure and hierarchical organization are crucial elements of biological systems and are likely required when engineering synthetic biomaterials with life‐like behavior. In this context, additive manufacturing techniques like bioprinting have become increasingly popular. However, 3D bioprinting, as well as other additive manufacturing techniques, show limited resolution, making it difficult to yield structures on the sub‐cellular level. To be able to form macroscopic synthetic biological objects with structuring on this level, manufacturing techniques have to be used in conjunction with biomolecular nanotechnology. Here, a short overview of both topics and a survey of recent advances to combine additive manufacturing with microfabrication techniques and bottom‐up self‐assembly involving DNA, are given.
A Manganese‐Based Metal–Organic Framework as a Cold‐Adapted Nanozyme
Authors: Chen Yao , Tian Qing , Wang Haoyu , Ma Ruonan , Han Ruiting , Wang Yu , Ge Huibin , Ren Yujing , Yang Rong , Yang Huimin , Chen Yinjuan , Duan Xuezhi , Zhang Lianbing , Gao Jie , Gao Lizeng , Yan Xiyun , Qin Yong
Published: November 2022

The development of cold‐adapted enzymes with high efficiency and good stability is an advanced strategy to overcome the limitations of catalytic medicine in low and cryogenic temperatures. In this work, inspired by natural enzymes, a novel cold‐adapted nanozyme based on a manganese‐based nanosized metal–organic framework (nMnBTC) is designed and synthesized. The nMnBTC as an oxidase mimetic not only exhibits excellent activity at 0 °C, but also presents almost no observable activity loss as the temperature is increased to 45 °C. This breaks the traditional recognition that enzymes show maximum activity only under specific psychrophilic or thermophilic condition. The superior performance of nMnBTC as a cold‐adapted nanozyme can be attributed to its high‐catalytic efficiency at low temperature, good substrate affinity, and flexible conformation. Based on the robust performance of nMnBTC, a low‐temperature antiviral strategy is developed to inactivate influenza virus H1N1 even at −20 °C. These results not only provide an important guide for the rational design of highly efficient artificial cold‐adapted enzymes, but also pave a novel way for biomedical application in cryogenic fields.
A Smart “Energy NanoLock” Selectively Blocks Oral Cancer Energy Metabolism through Synergistic Inhibition of Exogenous Nutrient Supply and Endogenous Energy Production
Authors: Xu Yurui , Zhang Xiaomin , Zhou Anwei , Cheng Can , Chen Kerong , Zhou Xinyuan , Zhang Gui , Ding Likang , Wu Xiaotong , Ge Haixiong , Wu Heming , Ning Xinghai
Published: November 2022

The major challenge in oral cancer is the lack of state‐of‐the‐art treatment modality that effectively cures cancer while preserving oral functions. Recent insights into tumor metabolic dependency provide a therapeutic opportunity for exploring optimal treatment approaches. Herein, a smart responsive “Energy NanoLock” is developed to improve cancer metabolic intervention by simultaneously inhibiting nutrient supply and energy production. NanoLock is a pomegranate‐like nanocomplex of cyclicRGD‐modified carboxymethyl chitosan (CyclicRC, pI = 6.7) encapsulating indocyanine green and apoptotic peptides functionalized gold nanoparticles (IK‐AuNPs), which together form a dual pH‐ and photoresponsive therapeutic platform. NanoLock exhibits good stability under physiological conditions, but releases small‐size CyclicRC and IK‐AuNPs in response to the tumor acidic microenvironment, leading to deep tumor penetration. CyclicRC targets integrins to inhibit tumor angiogenesis, and consequently blocks tumor nutrient supply. Meanwhile, IK‐AuNPs specifically induce apoptotic peptides and photothermally mediated mitochondrial collapse, and consequently inhibits endogenous energy production, thereby facilitating cell death. Importantly, in both xenograft and orthotopic oral cancer models, NanoLock selectively eliminates tumors with little cross‐reactivity with normal tissues, especially oral functions, resulting in prolonged survival of mice. Therefore, NanoLock provides a novel metabolic therapy to exploit synergistic inhibition of exogenous nutrient supply and endogenous energy production, which potentially advances oral cancer treatment.
A Therapeutic Nanovaccine that Generates Anti‐Amyloid Antibodies and Amyloid‐specific Regulatory T Cells for Alzheimer's Disease
Authors: Jung Mungyo , Lee Songmin , Park Sohui , Hong Jihye , Kim Cheesue , Cho Illhwan , Sohn Hee Su , Kim Kyunghwan , Park In Wook , Yoon Soljee , Kwon Sungpil , Shin Jisu , Lee Donghee , Kang Mikyung , Go Seokhyung , Moon Sangjun , Chung Yeonseok , Kim YoungSoo , Kim Byung‐Soo
Published: November 2022

Alzheimer's disease (AD), the most common cause of dementia, is a complex condition characterized by multiple pathophysiological mechanisms including amyloid‐β (Aβ) plaque accumulation and neuroinflammation in the brain. The current immunotherapy approaches, such as anti‐Aβ monoclonal antibody (mAb) therapy, Aβ vaccines, and adoptive regulatory T (Treg) cell transfer, target a single pathophysiological mechanism, which may lead to unsatisfactory therapeutic efficacy. Furthermore, Aβ vaccines often induce T helper 1 (Th1) cell‐mediated inflammatory responses. Here, a nanovaccine composed of lipid nanoparticles loaded with Aβ peptides and rapamycin is developed, which targets multiple pathophysiological mechanisms, exhibits the combined effects of anti‐Aβ antibody therapy and adoptive Aβ‐specific Treg cell transfer, and can overcome the limitations of current immunotherapy approaches for AD. The Nanovaccine effectively delivers rapamycin and Aβ peptides to dendritic cells, produces both anti‐Aβ antibodies and Aβ‐specific Treg cells, removes Aβ plaques in the brain, alleviates neuroinflammation, prevents Th1 cell‐mediated excessive immune responses, and inhibits cognitive impairment in mice. The nanovaccine shows higher efficacy in cognitive recovery than an Aβ vaccine. Unlike anti‐Aβ mAb therapy and adoptive Treg cell transfer, both of which require complicated and costly manufacturing processes, the nanovaccine is easy‐to‐prepare and cost‐effective. The nanovaccines can represent a novel treatment option for AD.
3D Printing of Hierarchical Porous Steel and Iron‐Based Materials
Authors: Carpenter Julia A. , Passaleva Neri , Häring Magali , Mikl Gregor , Studart André R.
Published: November 2022

Iron is a cheap and environmentally friendly metal that is produced at the gigaton scale every year. While porous metals have long been used as filters in chemical processes and electrodes in functional devices, steel and iron‐based structures with highly tunable porosity have only recently been explored as sustainable, lightweight materials for a variety of structural, biomedical, and energy‐related applications. Here, an extrusion‐based 3D printing process is reported to manufacture steel‐ and iron‐based structures with ultrahigh porosity distributed over three hierarchical levels. Using particle‐stabilized foams as printing inks, pores are generated at multiple length scales by controlling the print path, the concentration of air bubbles in the ink, and the thermal reduction and sintering process of the metal oxide precursor particles. This enables the manufacturing of iron and iron‐based alloys with an elastic modulus above 300 MPa and a density below 1 g cm−3 while keeping the mechanical efficiency expected for porous structures. The potential applications of such hierarchical porous iron and iron alloys are illustrated by printing structures with tunable chemical compositions that are ultra‐lightweight, magnetoresponsive, and capable of spontaneously absorbing oil spills and of vaporizing liquids using low electric power.
Achieving 34.3% External Quantum Efficiency for Red Thermally Activated Delayed Fluorescence Organic Light‐Emitting Diode by Molecular Isomer Engineering
Authors: Yang Tong , Liang Jixiong , Cui Yuanyuan , Li Zhiqiang , Peng Xiaomei , Su Shi‐Jian , Wang Yue , Li Chenglong
Published: November 2022

The development of red organic emissive materials with high‐efficiency and low‐cost is of great significance but formidable challenge for organic light‐emitting diodes (OLEDs). Herein, through isomer engineering, a pair of red thermally activated delayed fluorescence (TADF) isomers with Y‐shape and cruciform structures, namely TPA‐APQDCN‐Y and TPA‐APQDCN‐C, are developed by integrating two triphenylamine (TPA) donor moieties into different positions of rigid planar acenaphtho[1,2‐b]quinoxaline‐9,10‐dicarbonitrile (APQDCN) acceptor core. Compared to common Y‐shape structure, the unique cruciform structure can result in the formation of intramolecular H‐bonding, the limited molecular packing, the balance of the contradiction between the small spatial overlap of frontier molecular orbitals, and high oscillator strength, contributing to a higher photoluminescence quantum yield of 95%, a smaller singlet–triplet energy split of 0.24 eV and a larger horizontal emitting dipole ratio of 86%. An external quantum efficiency of 34.3% with an emission peak at 610 nm is achieved for TPA‐APQDCN‐C based red electroluminescent device, which is the highest value for red TADF‐OLEDs with emission maximum beyond 600 nm ever reported.
Fabrication of Gyroid‐Structured Metal/Semiconductor Nanoscaffolds with Ultrasensitive SERS Detection via Block Copolymer Templating
Authors: Lu Ying‐Chun , Tseng Pei‐Chieh , Yang Min‐Jung , Wang Cheng‐Jie , Ling Yi‐Chun , Lin Chia‐Feng , Hsueh Han‐Yu
Published: November 2022

Surface‐enhanced Raman scattering (SERS) is a label‐free and powerful technique for monitoring dynamic molecular processes with high sensitivity and reproducibility. SERS has diverse applications in medicine, molecular science, biology, and chemical sensing. In this study, a template‐based approach to create an ultrasensitive SERS‐active substrate is proposed which involves combining nanostructured semiconductors and noble metals. A nanoporous polymer obtained from hydrolyzed gyroid‐forming polystyrene‐block‐poly(l‐lactide) (i.e., PS‐b‐PLLA) is used as a template for Ag reduction and TiO2 sol–gel reaction. After calcination to remove the polymeric template, TiO2 nanoscaffolds appear as self‐supporting 3D nanoobjects with homogeneously and closely distributed Ag nanoparticles, providing a high density of regions with intense local field enhancement (hotspots). Rhodamine 6G molecules are used as probe molecules to demonstrate the SERS performance, revealing a markedly high average enhancement factor of up to 1014. The intrinsic photocatalytic properties of TiO2 can degrade target organic chemicals for the self‐cleaning and reproduction of SERS‐active substrates. Moreover, a simple hydrazine reduction‐based approach is applied for the formation of regenerated Ag/TiO2 nanoscaffolds to reduce the use of Ag‐based SERS‐active substrates, decreasing the costs associated with relevant industrial processes.
Toward Sustainable and Cost‐Effective CO2 Conversion Processes to Propylene Carbonate Based on Ionic Liquids
Authors: Hernández Elisa , Belinchón Alejandro , Pachón Elia Ruiz , Navarro Pablo , Palomar José
Published: November 2022

The use of ionic liquids (ILs) for CO2 capture and utilization into a valuable product is attracting interest even though literature evaluating their sustainability is scarce. A liquid–liquid extraction (LLE)‐based separation is recently proposed as an alternative to the high energy‐consuming distillation‐based reference approach to produce propylene carbonate (PC). In this work, the environmental impacts associated to the distillation‐based reference and two proposed LLE‐based approaches to produce PC are evaluated by means of process modeling and life cycle impact assessment tools. Simulations prove that tuning operating variables in terms of environmental benefits also improves the cost‐effectiveness of the process. In addition, sustainability of the processes is nearly not altered by the IL selection when an effective recovery is designed. The emissions associated to the proposed approaches vary between 0.12 and 0.22 kg CO2 equiv. per kgPC, while the operational costs range from 3 to 8 $ per tPC. The water‐mediated LLE‐based approach imposes the best environmental, capital expenditures, and operating expenses performance.
Boosting the Fill Factor through Sequential Deposition and Homo Hydrocarbon Solvent toward Efficient and Stable All‐Polymer Solar Cells
Authors: Wang Yan , Yu Han , Wu Xin , Zhao Dan , Zhang Shoufeng , Zou Xinhui , Li Bo , Gao Danpeng , Li Zhen , Xia Xinxin , Chen Xiankai , Lu Xinhui , Yan He , Chueh Chu‐Chen , Jen Alex K.‐Y. , Zhu Zonglong
Published: November 2022

All‐polymer solar cells (all‐PSCs) have achieved impressive progress in photovoltaic performance and stabilities recently. However, their power conversion efficiencies (PCEs) still trail that of small‐molecular acceptor‐based organic solar cells (>19%) mainly because of the inferior fill factor (FF). Herein, a combined homo hydrocarbon solvent and sequential deposition (SD) strategy is presented to boost the FF of rigid all‐PSCs to 77.7% and achieve a superior PCE of 17.7% with excellent stability, which is among the highest efficiencies reported for all‐PSCs thus far. Meanwhile, a remarkable PCE of 14.5% is realized for flexible all‐PSCs with outstanding mechanical stability. The blend film morphologies measurements suggest that the SD method enables the formation of an ideal pseudo‐bilayer film with bicontinuous interdigitated structure and ordered polymer packing. The numerical simulation result indicates that the FF enhancement mainly results from the efficient exciton diffusion dynamics, increased carrier mobilities, and more balanced electron/hole mobility ratio induced by the developed SD method. This is also confirmed by the FF loss analysis, which manifests that the reduced series resistance and increased shunt resistance are the main reasons for the reduction of FF loss. This work provides a promising strategy to fabricate highly efficient and stable all‐PSCs to promote their future development and practical manufacturing.
The implementation of an enhanced clinical model to improve the diagnostic yield of exome sequencing for patients with a rare genetic disease: A Canadian experience
Authors: Ediae Grace Uwaila , Lemire Gabrielle , Chisholm Caitlin , Hartley Taila , Eaton Alison , Osmond Matthew , Rojas Samantha K. , Huang Lijia , Gillespie Meredith ,   Care4Rare Canada Consortium, Sawyer Sarah L. , Boycott Kym M.
Published: November 2022

The introduction of clinical exome sequencing (ES) has provided a unique opportunity to decrease the diagnostic odyssey for patients living with a rare genetic disease (RGD). ES has been shown to provide a diagnosis in 29%–57% of patients with a suspected RGD, with as many as 70% remaining undiagnosed. There is a need to advance the clinical model of care by more formally integrating approaches that were previously considered research into an enhanced diagnostic workflow. We developed an Exome Clinic, which set out to evaluate a workflow for improving the diagnostic yield of ES for patients with an undiagnosed RGD. Here, we report the outcomes of 47 families who underwent clinical ES in the first year of the clinic. The diagnostic yield from clinical ES was 40% (19/47). Families who remained undiagnosed after ES had the opportunity for follow‐up studies that included phenotyping and candidate variant segregation in relatives, genomic matchmaking, and ES reanalysis. This enhanced diagnostic workflow increased the diagnostic yield to 55% (26/47), predominantly through the resolution of variants and genes of uncertain significance. We advocate that this approach be integrated into mainstream clinical practice and highlight the importance of a coordinated translational approach for patients with RGD.
Hydrogeological Knowledge from Below: Water Expertise as a Republican Common in Early‐Modern Venice**
Authors: Omodeo Pietro Daniel
Published: November 2022

This essay looks at early‐modern Venice hydroculture as a case of episteme from below. The forms of water knowledge it developed were multilayered and collective in their essence and solidly rested on a social experiential basis that was rooted in labour (especially fishing) and practices (especially water surveying and engineering). In accordance with the city's republican esprit (and correspondent political values), its episteme emerged as the encounter and negotiation between various institutions and groups: the fishermen of San Niccolò in Venice, the practitioners of the water magistrature and political authorities. This essay explores the institutional settings of this water culture, seen as an instance of bottom‐up epistemic construction. It especially addresses three historical instances: firstly, a seventeenth century program to map public waters in order to block their alienation for private fish farming; secondly, water officers’ interviews with fishermen aimed to assess the state of the lagoon hydromorphology and, thirdly, fishing regulations. Venice communitarian and circular forms of knowledge production are here contrasted to an opposite paradigm, which was embodied by the Galileian mathematician and Rome courtier, Benedetto Castelli. His interactions with the Republic of Venice on water management and his approach to hydraulic problems are revealing of an elitist and abstract understanding of scientific knowledge that guided political decisions from above without taking in any consideration the opinions of the ‘vulgar’. While his science was the expression of a top‐down political epistemology, Venetian water knowledge was more egalitarian. It left room for exchange, inclusiveness and bottom‐up codification; it valued the gathering of different experiences (including the fishermen's practical knowledge of their waters) and rested on a concrete and systemic (organicist) understanding of natural‐anthropic processes.
Autofluorescence prediction model for fluorescence unmixing and age determination
Authors: Eigenfeld Marco , Kerpes Roland , Whitehead Iain , Becker Thomas
Published: November 2022

Background

Flow cytometry is a powerful tool for identifying and quantifying various cell markers, such as viability, vitality, and individual cell age, at single‐cell stages. However, cell autofluorescence and marker fluorophore signals overlap at low fluorescence intensities. Thus, these signals must be unmixed before determining the age fraction.

Methods and Results

A comparison was made between principal component regression (PCR) and random forest (RF) to predict autofluorescence signals of Saccharomyces pastorianus var. carlsbergensis in a flow cytometer. RF provided better prediction results than the PCR and was therefore determined to be better suited for unmixing signals. In the subsequent application for unmixing the autofluorescence signal from the marker fluorophore signal, the Gaussian mixture analysis based on RF was in better agreement with the microscopy‐determined replicative age distribution than the PCR‐based method.

Conclusion

The proposed approach of single‐laser spectral unmixing and subsequent Gaussian mixture analysis showed that the microscopy data was consistent with the unmixed fluorescence spectra. The demonstrated approach enables fast and reliable unmixing of flow cytometric spectral data using a single‐laser spectral unmixing method. This analysis method enables age determination of cells in industrial processes. This age determination allows for quantifying the yeast cell's age fractions, providing a detailed view of age‐related changes. Additionally, the bud scar labeling technique can be used to determine age‐related changes in Pichia pastoris yeast for biotechnological applications or recombinant protein expression.
Purification of Polysaccharides from Orostachys cartilaginous Cell Cultures by Macroporous Resin Absorption and Bioactivities of the Purified Polysaccharides
Authors: Xu Ya‐Nan , An Xiao‐Li , Han Lu , Piao Xuan‐Chun , Hao Yue‐Jun , Meng Wan , Lian Mei‐Lan
Published: November 2022

Orostachys cartilaginous is a traditional herbal medicine and its cell cultures contain large amounts of polysaccharides. To utilize the cultured O. cartilaginous cells, this study purified the crude polysaccharides of O. cartilaginous cells by macroporous resin absorption and optimized the purification process in the experiment of orthogonal design with four factors (sample concentration and volume, and eluent concentration and volume) and three levels; the antibacterial and anti‐cancer effects of the purified polysaccharides (OTP) were further examined. The results showed that polysaccharide purity reached 95 % in the optimized group, i. e., 1.6 mg/mL of sample (crude polysaccharides) concentration, 3.0 bed volume (BV) of sample volume, 65 % eluent (ethanol) concentration, and 3.0 BV of eluent volume. In the antibacterial experiment, the growth of three bacterial species, i. e., Pseudomonas aeruginosa, Staphylococcus aureus, and Bacillus subtilis was inhibited by OTP, whereas that of Escherichia coli was not affected; the largest diameter of the inhibitory zone was found on B. subtilis; the extracellular alkaline phosphatase activity and the electrical conductivity, nucleic acid, and protein levels of B. subtilis increased after OTP treatment, indicating that the inhibition of B. subtilis growth was caused by the leakage of cell contents. In the anti‐cancer experiment, OTP decreased the cell viabilities of the tested human cancer cells, i. e., AGS (gastric cancer), HCT116 (colon cancer), HepG2 (liver cancer), and HeLa (cervical cancer), and the highest inhibitory effect was on HCT116. OTP promoted HCT116 apoptosis and affected the expression of apoptosis‐related proteins, i. e., the expression of B‐cell lymphoma‐2 decreased and that of bcl‐2 associated X protein, cytochrome c, caspase 9 and caspase 3 increased. The findings of the present study suggest that O. cartilaginous cell cultures have a potential application in food or drug production.
Cytotoxic Sesquiterpenoids from Atractylodes chinensis (DC.) Koidz.
Authors: Zhuang Lei‐Xin , Liu Yan , Wang Si‐Yi , Sun Ye , Pan Juan , Guan Wei , Hao Zhi‐Chao , Kuang Hai‐Xue , Yang Bing‐You
Published: November 2022

Four new sesquiterpenoids named atrchiterpenes A–D (1–4), a new natural product (5), and twelve known compounds (6–17) were isolated from Atractylodes chinensis (DC.) Koidz. Compound 1 was a rare N‐containing eudesmane‐type sesquiterpenoid. Structure elucidation was performed by spectroscopic techniques, including 1D, 2D NMR spectra, and HR‐ESI‐MS. Compounds 6–11, 14, and 17 were reported from Atractylodes for the first time. All the isolated compounds were evaluated for cytotoxicity activity. Compound 16 showed moderate cytotoxicity against HepG2 cells with an IC50 value of 5.81±0.47.
Epigenetics and mitochondrial dysfunction insights into the impact of the progression of non‐alcoholic fatty liver disease
Authors: Guha Shreyoshi , Sesili Selvam , Mir Ishfaq Hassan , Thirunavukkarasu Chinnasamy
Published: November 2022

A metabolic problem occurs when regular functions of the body are disrupted due to an undesirable imbalance. Nonalcoholic fatty liver disease (NAFLD) is considered as one of the most common in this category. NAFLD is subclassified and progresses from lipid accumulation to cirrhosis before advancing to hepatocellular cancer. In spite of being a critical concern, the standard treatment is inadequate. Metformin, silymarin, and other nonspecific medications are used in the management of NAFLD. Aside from this available medicine, maintaining a healthy lifestyle has been emphasized as a means of combating this. Epigenetics, which has been attributed to NAFLD, is another essential feature of this disease that has emerged as a result of several sorts of research. The mechanisms by which DNA methylation, noncoding RNA, and histone modification promote NAFLD have been extensively researched. Another organelle, mitochondria, which play a pivotal role in biological processes, contributes to the global threat. Individuals with NAFLD have been documented to have a multitude of alterations and malfunctioning. Mitochondria are mainly concerned with the process of energy production and regulation of the signaling pathway on which the fate of a cell relies. Modulation of mitochondria leads to elevated lipid deposition in the liver. Further, changes in oxidation states result in an impaired balance between the antioxidant system and reactive oxygen species directly linked to mitochondria. Hence mitochondria have a definite role in potentiating NAFLD. In this regard, it is essential to consider the role of epigenetics as well as mitochondrial contribution while developing a medication or therapy with the desired accuracy.
Probable posttransplant lymphoproliferative disorder after pediatric living donor liver transplantation: Is a biopsy still needed?
Authors: Matsumura Muneyuki , Miyagi Shigehito , Tokodai Kazuaki , Kashiwadate Toshiaki , Fujio Atsushi , Miyazawa Koji , Sasaki Kengo , Saito Yoshikatsu , Kanai Norifumi , Unno Michiaki , Kamei Takashi
Published: November 2022

Posttransplant lymphoproliferative disorder (PTLD) is a complication of solid organ transplantation and is associated with Epstein‐Barr virus (EBV). Recently, EBV‐related PTLD was defined as probable PTLD or proven PTLD. Probable PTLD involves significant lymphadenopathy, hepatosplenomegaly, or other end‐organ manifestations, without a histological diagnosis, together with significant EBV DNAemia. Proven PTLD is the detection of EBV‐encoded proteins in a tissue specimen, together with symptoms and/or signs originating from the affected organ. Probable PTLD after pediatric liver transplantation has not been well documented. Therefore, here, we aimed to describe cases of five pediatric patients with probable PTLD after liver transplantation, who were successfully treated with preemptive immunosuppression reduction with or without rituximab. All five patients (age range, 1–4 years; two girls and three boys) had EBV DNAemia. Three patients developed probable PTLD within 12 months of transplantation. Further, three patients had a significantly high EBV viral load, but the other two patients with lymphadenopathy and end‐organ manifestation had a relatively low EBV viral load. Early onset pediatric PTLD with significant EBV DNAemia is almost universally EBV‐related. Biopsy was not performed in any patient due to the relative inaccessibility of the lesion and young age of the patients. If the patient’s symptoms are too mild, if excisional biopsy is too difficult to perform, or if the patient is too sick to undergo an invasive procedure, initiating preemptive treatment without a histological diagnosis could be the treatment option.
Challenges in Elucidating the Free Energy Scheme of the Laccase Catalyzed Reduction of Oxygen
Authors: den Boer Daan , de Heer Hendrik C. , Buda Francesco , Hetterscheid Dennis G. H.
Published: November 2022

Artificial redox catalysts are typically limited by unfavorable scaling relations of reaction intermediates leading to a significant overpotential in multi‐electron redox reactions such as for example the oxygen reduction reaction (ORR). The multicopper oxidase laccase is able to catalyze the ORR in nature. In particular the high‐potential variants show a remarkably low overpotential for the ORR and apparently do not suffer from such unfavorable scaling relations. Although laccases are intensively studied, it is presently unknown why the overpotential for ORR is so low and a clear description regarding the thermodynamics of the catalytic cycle and the underlying design principles is lacking. In order to understand the laccase catalyzed ORR from an electrochemical perspective, elucidation of the free energy scheme would be of high value. This article reviews the energetics of the proposed laccase catalyzed ORR mechanisms based on experimental and computational studies. However, there are still remaining challenges to overcome to elucidate the free energy scheme of laccase. Obtaining thermodynamic data on intermediates is hard or even impossible with analytical techniques. On the other hand, several computational studies have been performed with significantly different parameters and conditions, thus making a direct comparison difficult. For these reasons, a consensus on a clear free energy scheme is still lacking. We anticipate that ultimately conquering these challenges will result in a better understanding of laccase catalyzed ORR and will allow for the design of low overpotential redox catalysts.
Evolving a P450BM3 Peroxygenase for the Production of Indigoid Dyes from Indoles
Authors: Kong Fanhui , Chen Jie , Qin Xiangquan , Liu Chuanfei , Jiang Yiping , Ma Li , Xu Huifang , Li Shengying , Cong Zhiqi
Published: November 2022

Herein, we describe an environmentally benign enzymatic approach for the preparation of indigoid from indole derivatives. A series of beneficial P450BM3 mutants were obtained using a stepwise approach involving site‐directed, random, and combinatory hot‐site mutations. Using H2O2 as the terminal oxidant and N‐(ω‐imidazolyl)‐hexanoyl‐L‐phenylalanine as a co‐catalyst, the quadruple‐mutant F87G/T268V/F77I/E140D efficiently catalyzed the 3‐hydroxylation of indole and subsequent autooxidation to indigo with higher efficiency than the flavin‐containing monooxygenase, PTDH‐mFMO, which was the best oxidizing enzyme for indigo synthesis reported to date. Following this procedure, 12 indigoid compounds were prepared using indole derivatives with various substituents as starting materials with moderate to high isolated yields (31.3–79.5 %). The catalytic efficiencies (kcat/Km) of the beneficial mutants for typical indole substrates ranged from 182–2849 mM−1 ⋅ min−1, almost 2‐ to 712‐fold higher than those of the reported P450 enzymes. This study provides a new enzymatic approach for the biosynthesis of indigoid dyes from indole derivatives.
Hierarchical Porous Carbon Anchored Atomic/Clustered Cobalt for Boosting Oxygen Reduction Electrocatalysis
Authors: Lyu Xiao , Gu Xiang , Li Gen , Chen Hao , Hou Huijie , Hu Jingping
Published: November 2022

Hierarchical porous carbon with highly active sites has emerged as an ideal support for high‐performance oxygen reduction reaction (ORR) electrocatalysts. By tuning the geometric size and coordination environment of transition metals on hierarchical porous carbon to optimize the catalytic performance for ORR, cobalt (Co) single atoms and Co nanoclusters were synthesized respectively on N‐doping and vacancy‐defective hierarchical porous carbon. Benefited from the high surface area and enhanced mass transfer, cobalt nanoclusters on nitrogen doped hierarchical porous carbon shows a high four‐electron selectivity for ORR. It presents a half wave potential of 0.854 V vs. RHE, which is comparable to that of commercial Pt/C catalysts (0.852 V vs. RHE). Meanwhile, the single‐atomic cobalt coordinated with vacancy‐defective carbon favors the two‐electron reduction of O2 to hydrogen peroxide (H2O2). It exhibits an apparent promotion on selectivity of two‐electron route with a high H2O2 selectivity of around 90 %. This work demonstrates that hierarchical porous carbons could be effectively tuned for applications that favors either four‐electron or two‐electron ORR pathway.
Categorization of Sprays by Image Analysis with Convolutional Neuronal Networks
Authors: Pieloth Damian , Rodeck Matthias , Schaldach Gerhard , Thommes Markus
Published: November 2022

Spray characterization has been an issue for process and product characterization for decades. Because of this, a convolutional neuronal network was developed to determine the droplet size from spray images. The images were taken using a digital camera, a light source, and a dark room. These were subsequently employed to design and train a convolutional neuronal network using open‐source software packages and a desktop computer. The accuracy of the network droplet size determinations was checked with additional, independent images. The median drop size was assessed with a high accuracy of more than 99.8 % as the mean spray performance indicator. Additionally, the droplet size distribution measurements from the neural network method deviated from those from the reference method (laser diffraction) by less than 1.5 %. Convolutional neuronal networks can be applied to determine the spray performance using spray cone images. This approach could be useful for multiple applications.
Unveiling the Metal Incorporation Effect of Steady‐Active FeP Hydrogen Evolution Nanocatalysts for Water Electrolyzer
Authors: Wang Yongsheng , Wang Xinyu , Wei Hailong , Huang Junling , Yin Likun , Zhu Wei , Zhuang Zhongbin
Published: November 2022

Metal phosphides are promising noble metal‐free electrocatalysts for hydrogen evolution reaction (HER), but they usually suffer from inferior stability and thus are far from the device applications. We reported a facile and controllable synthetic method to prepare metal‐incorporated M‐FeP nanoparticles (M=Cr, Mn, Co, Fe, Ni, Cu, and Mo) with the guide of the density functional theory (DFT). The evaluated HER activity sequence was consistent with the DFT predictions, and cobalt was revealed to be the appropriate dopant. With the optimization of the Co/Fe ratio, the Fe0.67Co0.33P/C only required overpotentials of 67 mV and 129 mV to obtain the cathodic current density of 10 and 100 mA cm−2, respectively. It maintained the initial activity in the 10 h stability test, surpassing the other Co‐FeP/C catalysts. Ex situ experiments demonstrated that the decreased element leaching and the increased surface phosphide content contributed to the high stability of the Fe0.67Co0.33P/C. A proton exchange membrane water electrolyzer was assembled using the Fe0.67Co0.33P/C as the cathodic catalyst. It showed a current density of 0.8 A cm−2 at the applied voltage of 2.0 V and retained the initial activity in the 1000 cycles’ stability test, suggesting the potential application of the catalysts.
Rhodium‐Catalyzed Transannulation of 1,2,3‐Thiazoles with Alkynes for the Direct Synthesis of Thiochromenones
Authors: Pan Jun , Zhang Ziyao , Chen Lili , Jiao Ning
Published: November 2022

Comprehensive Summary

A rhodium‐catalyzed denitrogenative carbonylation of 1,2,3‐thiadiazole with alkynes to construct (benzo)thiochromenones is developed. Both terminal and internal alkynes were compatible in this [3+2+1] cycloaddition, affording a broad range of poly‐substituted thiochromenones. Unsymmetrical alkyne substrates exhibited good regioselectivity. It is noteworthy that the present strategy could be used to construct both monocyclic and benzo‐thiochromenones, and it is a novel example of denitrogenative transannulation with CO insertion.
Population Pharmacokinetics of Oral Migalastat in Adolescents and Adults With and Without Renal Impairment
Authors: Leonowens Cathrine , Schmith Virginia , Zhou Jie , Wu Yi Shuan , Ivaturi Vijay , Johnson Franklin K.
Published: November 2022

Migalastat is approved for the treatment of Fabry disease (FD) with amenable variants. Objectives were to characterize effects of estimated glomerular filtration rate (eGFR) on oral clearance (CL), predict doses in mild to moderate renal impairment and in pediatric patients with FD, and to improve designs of FD studies. A 2‐compartment model was fit to data from 260 subjects with/without FD and iteratively refined with evolving data. FD, eGFR, and weight affected CL, while weight and FD affected volume. Optimal sampling theory was used to choose pharmacokinetic sampling times for pediatric studies. Doses in patients with renal impairment and in pediatrics were determined by targeting exposure in adults receiving migalastat 123 mg every other day. A clinical study was conducted in 20 adolescent patients with FD ≥45 kg. eGFR had the largest effect on CL. Simulations showed that exposures in moderate renal impairment were within phase 2–3 exposures; patients aged 2–17 years require weight‐based dosing; and predicted exposures in adolescent patients ≥45 kg receiving migalastat 123 mg every other day were similar to adults (data confirmed in a clinical study). Model‐informed drug development optimized dosing and design of clinical studies and supported that no dose adjustments were needed in patients with mild to moderate renal impairment or in adolescent patients ≥45 kg.