bluuebunny/crossref_metadata_2025 huggingface dataset:
High‐density adherent culture of CHO cells using rolled scaffold bioreactor
Authors: YekrangSafakar Ashkan , Mehrnezhad Ali , Wu Tongyao , Park Kidong
Published: March 2022

Rapid expansion of biopharmaceutical market calls for more efficient and reliable platforms to culture mammalian cells on a large scale. Stirred‐tank bioreactors have been widely used for large‐scale cell culture. However, it requires months of trials and errors to optimize culture conditions for each cell line. In this article, we extend our earlier studies on rolled scaffold (RS) bioreactors for high‐density adherent cell culture and report two new implementations of RSs with greatly enhanced mass‐manufacturability, termed as Mesh‐RS and Fiber‐RS. CHO‐K1 cells were successfully expanded in Mesh‐RS and Fiber‐RS bioreactors with an average growth rate of 1.09 ± 0.04 1/day and 0.95 ± 0.07 1/day, which were higher than those reported in similar studies. Fiber‐RS bioreactor exhibited a very high cell density of 72.8 × 106 cells/ml. Besides, a dialyzer was integrated into the RS bioreactor to remove cellular waste and to replenish nutrients without disturbing the cells. By collecting the dialyzed media separately, the dialysis efficiency was significantly improved. In conclusion, the developed RS bioreactor has a strong potential to provide a highly reliable and easily scalable platform for large‐scale cell culture in the biopharmaceutical industry.
Optimization of VSV‐ΔG‐spike production process with the Ambr15 system for a SARS‐COV‐2 vaccine
Authors: Rosen Osnat , Jayson Avital , Goldvaser Michael , Dor Eyal , Monash Arik , Levin Lilach , Cherry Lilach , Lupu Edith , Natan Niva , Girshengorn Meni , Epstein Eyal
Published: March 2022

To face the coronavirus disease 2019 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) virus, our institute has developed the rVSV‐ΔG‐spike vaccine, in which the glycoprotein of vesicular stomatitis virus (VSV) was replaced by the spike protein of SARS‐CoV‐2. Many process parameters can influence production yield. To maximize virus vaccine yield, each parameter should be tested independently and in combination with others. Here, we report the optimization of the production of the VSV‐ΔG‐spike vaccine in Vero cells using the Ambr15 system. This system facilitates high‐throughput screening of process parameters, as it contains 24 individually controlled, single‐use stirred‐tank minireactors. During optimization, critical parameters were tested. Those parameters included: cell densities; the multiplicity of infection; virus production temperature; medium addition and medium exchange; and supplementation of glucose in the virus production step. Virus production temperature, medium addition, and medium exchange were all found to significantly influence the yield. The optimized parameters were tested in the BioBLU 5p bioreactors production process and those that were found to contribute to the vaccine yield were integrated into the final process. The findings of this study demonstrate that an Ambr15 system is an effective tool for bioprocess optimization of vaccine production using macrocarriers and that the combination of production temperature, rate of medium addition, and medium exchange significantly improved virus yield.
A dynamic air–liquid interface system for in vitro mimicking of the nasal mucosa
Authors: Capuana Elisa , Fucarino Alberto , Burgio Stefano , Intili Giorgia , Manna Olga Maria , Pitruzzella Alessandro , Brucato Valerio , La Carrubba Vincenzo , Carfì Pavia Francesco
Published: March 2022

The development of an in vitro 3D model for the growth of the nasal mucosa cells can improve the therapy and the study of pathological states for subjects with chronic airway conditions. We have previously characterized a system consisting of a scaffold with an internal channel and a perfusion bioreactor with two independent flows provided by an external and an internal circuit, respectively. In this paper, this system was designed as a model of the nasal cavity, in which cells, grown on the inner surface of the scaffold channel, would be in contact at the same time with both culture medium, supplied by the external circuit, and air, provided with the internal flow. To ensure adequate nutrient supply to the cells in the scaffold channel, the radial diffusion of the culture medium through the porous matrix was evaluated first in qualitative and, then, in quantitative terms, demonstrating the capability of the system to control the value and direction of this flux. As a preliminary study, the culture of epithelial cells in the scaffold channel is also discussed in static, maintaining the air–liquid interface condition for up to 3 weeks. Despite minor abnormalities, such as a gap between cell layers and some detachments from the scaffold, the scaffold ensured cell survival and growth during the experimental time.
Secondary cancers after carbon‐ion radiotherapy and photon beam radiotherapy for uterine cervical cancer: A comparative study
Authors: Nitta Yuki , Murata Hiroto , Okonogi Noriyuki , Murata Kazutoshi , Wakatsuki Masaru , Karasawa Kumiko , Kato Shingo , Yamada Shigeru , Nakano Takashi , Tsuji Hiroshi
Published: March 2022

Background

There are limited studies on the risk of secondary cancers after carbon‐ion radiotherapy (CIRT). We assessed the incidence of secondary cancers in patients treated with CIRT for cervical cancer. We also evaluated the incidence of secondary cancers in patients who received standard photon radiotherapy (RT) throughout the same period.

Methods

This retrospective study included patients with cervical cancer who underwent curative RT at our hospital. All cancers discovered for the first time after RT were classified as secondary cancers. To compare the risk of secondary cancers among cervical cancer survivors to the general population, standardized incidence ratios (SIRs) were calculated.

Results

The analysis included a total of 197 and 417 patients in the CIRT and photon RT groups, respectively. The total person‐years during the observation period were 1052.4 in the CIRT group and 2481.5 in the photon RT group. The SIR for all secondary cancers was 1.1 (95% confidence interval [CI], 0.6–2.1) in the CIRT group and 1.4 (95% CI, 1.0–2.1) in the photon RT group. The 10‐year cumulative incidence of all secondary cancers was 9.5% (95% CI, 4.0–21.5) in the CIRT group and 9.4% (95% CI, 6.2–14.1) in the photon RT group. The CIRT and photon RT groups were not significantly different in incidence (p = 0.268).

Conclusions

The incidence of secondary cancers after CIRT for cervical cancer was similar to that after photon RT. Validation of our findings after long‐term observation is warranted.
Self‐organisation in dialogical patterns of a patient with borderline personality disorder and their therapist: A case study from nonlinear dynamics perspective
Authors: Mellado Augusto , Guastello Stephen J. , Martínez Claudio , Tomicic Alemka , Krause Mariane
Published: March 2022

Objective

The purpose of this study was to identify self‐organised dynamics in sessions with dialogical patterns (i.e. reflective interactions of self‐states associated with psychological change) within long‐term psychotherapy. One of the hallmarks of self‐organisation is the presence of an Inverse Power Law (IPL) in the frequency distribution of relevant events, which reflect better adaptation to internal and environmental changes, produced by psychotherapy.

Methods

A case study of successful psychotherapy (44 weekly sessions) with a patient diagnosed with borderline personality disorder (BPD) and the therapist was conducted. The expressions of the subjectivity (i.e. voices) in the patient and therapist were identified through the Model of Analysis of Discursive Positioning in Psychotherapy (MAPP). State Space Grids (SSG) identified sessions that presented dialogical patterns acting as attractors (8 sessions) and those with non‐dialogical patterns acting as attractors (12 sessions). Finally, Orbital Decomposition (ORBDE) produced statistics of self‐organisation in both groups of sessions and the degree of fit to an IPL.

Results

Both groups of sessions presented an acceptable fit to the IPL distributions (R2 = .853 and .938), and statistics placed them in different self‐organised regions.

Conclusions

Although dialogical patterns are an emergent property of therapy, their structure is similar to sessions of other types, in that dynamic processes occur in them that can be empowered in patients to consolidate psychological change. The nonlinear and emergent character of these self‐organised processes and their clinical implications for activating the patients' psychological resources are discussed.
Chemoenzymatic Isolation and Characterization of High Purity Mammalian Melanin
Authors: Kalaj Brianna N. , Ni Qing Zhe , La Clair James J. , Deheyn Dimitri D. , Burkart Michael D.
Published: March 2022

Although melanin is one of the most ubiquitous polymers in living systems, our understanding of its molecular structure, biosynthesis and biophysical properties has been limited to only a small number of organisms other than humans. This is in part due to the difficulty associated with isolating pure melanin. While purification methods exist, they typically involve harsh treatments with strong acid/base conditions combined with elevated temperatures that can lead to the polymer backbone degradation. To be successful, a viable isolation method must deliver a selective, yet complete degradation of non‐melanin biopolymers as well as remove small molecule metabolites that are not integrative to the melanin backbone. Here, we demonstrate the use of chemoenzymatic processing guided by fluorescent probes for the purification and isolation of native mammalian melanin without significant induction of chemical degradation. This multi‐step purification‐tracking methodology enables quantitative isolation of pure melanin from mammalian tissue for spectroscopic characterization.
Isolation of Tobacco Mosaic Virus‐Binding Peptides for Biotechnology Applications
Authors: Chan Soo Khim , Steinmetz Nicole F.
Published: March 2022

Tobacco mosaic virus (TMV) was the first virus to be discovered and it is now widely used as a tool for biological research and biotechnology applications. TMV particles can be decorated with functional molecules by genetic engineering or bioconjugation. However, this can destabilize the nanoparticles, and/or multiple rounds of modification may be necessary, reducing product yields and preventing the display of certain cargo molecules. To overcome these challenges, we used phage display technology and biopanning to isolate a TMV‐binding peptide (TBPT25) with strong binding properties (IC50=0.73 μM, KD=0.16 μM), allowing the display of model cargos via a single mixing step. The TMV‐binding peptide is specific for TMV but does not recognize free coat proteins and can therefore be used to decorate intact TMV or detect intact TMV particles in crude plant sap.
Functional Groups Assisted Tunable Dielectric Permittivity of Guest‐Free Zn‐Based Coordination Polymers for Gate Dielectrics
Authors: Kamal Saqib , Inamdar Arif I. , Chiou Kuan‐Ru , Sainbileg Batjargal , Usman Muhammad , Chen Jenq‐Wei , Luo Tzuoo‐Tsair , Hayashi Michitoshi , Hung Chen‐Hsiung , Liaw Wen‐Feng , Lu Kuang‐Lieh
Published: March 2022

The dielectric properties of coordination polymers has been a topic of recent interest, but the role of different functional groups on the dielectric properties of these polymers has not yet been fully addressed. Herein, the effects of electron‐donating (R=NH2) and electron‐withdrawing (R=NO2) groups on the dielectric behavior of such materials were investigated for two thermally stable and guest‐free Zn‐based coordination polymers, [Zn(L1)(L2)]n (1) and [Zn(L1)(L3)]n (2) [L1=2‐(2‐pyridyl) benzimidazole (Pbim), L2=5‐aminoisophthalate (Aip), and L3=5‐nitroisophthalate (Nip)]. The results of dielectric studies of 1 revealed that it possesses a high dielectric constant (κ=65.5 at 1 kHz), while compound 2 displayed an even higher dielectric constant (κ=110.3 at 1 kHz). The electron donating and withdrawing effects of the NH2 and NO2 substituents induce changes in the polarity of the polymers, which is due to the inductive effect from the aryl ring for both NO2 and NH2. Theoretical results from density functional theory (DFT) calculations, which also support the experimental findings, show that both compounds have a distinct electronic behavior with diverse wide bandgaps. The significance of the current work is to provide information about the structure‐dielectric property relationships. So, this study promises to pave the way for further research on the effects of different functional groups on coordination polymers on their dielectric properties.
Theoretical Studies on a Rotating Film Reactor for Hydrogen Production from Methane
Authors: Becker Tobias , Agar David W.
Published: March 2022

A film of liquid metal can protect the reactor wall from carbon deposits during methane pyrolysis, discharge carbon from the reactor and prevent blocking. The film can be generated by rotation in a rotating film reactor. Parameters such as liquid volume flow, operating mode or the diameter of the reactor can have an influence on the reaction behavior. A design of experiments was used to investigate the rotating film reactor in more detail and to characterize the influence of various parameters.
The SQ HDM SLIT‐Tablet is safe and well tolerated in patients with House Dust Mite allergic rhinitis with or without asthma: A “real‐life” French study
Authors: Demoly Pascal , Leroyer Christophe , Serrano Elie , Le Maux Annelore , Magnier Gabrielle , Chartier Antoine
Published: March 2022

Background

The SQ House Dust Mite (HDM) SubLingual ImmunoTherapy (SLIT)‐Tablet (Acarizax) is the only allergen immunotherapy authorized by European regulatory authorities to treat HDM‐induced allergic asthma (AA) that is not well‐controlled by inhaled corticosteroids and associated with mild‐to‐severe HDM allergic rhinitis (AR). The aim of this study was to add evidence on the safety of the SQ HDM SLIT‐Tablet in patients with AR, alone or with AA, under real‐life conditions.

Methods

This was a French “real‐life”, multicenter, non‐comparative, longitudinal, prospective study. It included patients initiating the SQ HDM SLIT‐Tablet for either persistent moderate‐to‐severe HDM AR or AA not well‐controlled by inhaled corticosteroids and associated with mild‐to‐severe HDM AR. Adverse Events (AEs) were collected at the first intake and throughout the study. Logistic regression was used to compare safety according to asthma control before treatment initiation.

Results

Between May 09, 2018 and May 29, 2019, 1526 patients were enrolled at 185 sites and 1483 were included in the safety population (SAF). Of them, 33.6% had suspected clinical manifestations of AA. Asthma was uncontrolled for 18.2% of the patients, partially controlled for 27.9% and well‐controlled for 53.8%. Overall, 31.9% of the SAF patients experienced at least one AE. The percentage of patients with AEs was 29.9% among patients with AR alone and 35.9% among those with AA (p = 0.0193). No significant difference was observed in the rate of AE or SAE depending on asthma control at inclusion (2.2% of SAEs reported for patients with uncontrolled asthma, 1.4% for partly controlled and 1.1% for well‐controlled).

Conclusions

The overall results indicate a good SQ HDM SLIT‐Tablet safety profile consistent with that reported in previous studies, regardless of asthma control.
Durvalumab and tremelimumab with definitive chemoradiotherapy for locally advanced esophageal squamous cell carcinoma
Authors: Park Sehhoon , Oh Dongryul , Choi Yoon‐La , Chi Sang Ah , Kim Kyunga , Ahn Myung‐Ju , Sun Jong‐Mu
Published: March 2022

Background

The current standard treatment for patients with inoperable, locally advanced esophageal squamous cell carcinoma (ESCC) is definitive concurrent chemoradiotherapy (CCRT).

Methods

Patients with locally advanced ESCC received 2 cycles of 5‐fluorouracil, cisplatin, durvalumab, and tremelimumab every 3 weeks with concurrent radiation therapy (60.2 or 64.5 grays). After completing CCRT plus immunotherapy, patients received 2 cycles of consolidative durvalumab and tremelimumab followed by durvalumab monotherapy every 4 weeks for 2 years after enrollment. Their survival outcomes were compared with those from a propensity score‐matched historical control group that had received CCRT alone.

Results

In total, 40 patients were enrolled and analyzed. The 24‐month progression‐free survival (PFS) and overall survival rates were 57.5% and 75%, respectively. Compared with the historical control group (n = 75), the study population had significantly longer PFS (hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.28‐0.97; P = .040) and overall survival (HR, 0.49; 95% CI, 0.25‐0.98; P = .043). In the study population, patients who had PD‐L1–positive tumors (n = 28) had significantly longer PFS (HR, 0.20; 95% CI, 0.07‐0.54; P < .001) and overall survival (HR, 0.16; 95% CI, 0.05‐0.56; P = .001) compared with those who had PD‐L1–negative tumors (n = 11). However, there was no difference in survival outcomes according to PD‐L1 status in the historical control group, indicating a strong interaction between PD‐L1–positive status and survival outcomes in the treatment groups (PFS, P for interaction = .003; overall survival, P for interaction = .002).

Conclusions

Durvalumab and tremelimumab with definitive CCRT had promising efficacy in patients with locally advanced ESCC. In addition, PD‐L1 expression had strong predictive value in the study population.
Darknet on OpenCL: A multiplatform tool for object detection and classification
Authors: Sowa Piotr , Izydorczyk Jacek
Published: March 2022

The goal of this article is to overview the challenges and problems on the way from the state‐of‐the‐art CUDA accelerated neural network code to multi‐GPU code. For this purpose, the authors describe the journey of porting that existing in GitHub, a fully featured CUDA‐accelerated Darknet engine, to OpenCL. This article presents the lessons learned and the techniques that were put in place for this porting. There are few other implementations on GitHub that leverage the OpenCL standard, and a few have tried to port Darknet as well. Darknet is a well‐known convolutional neural network (CNN) framework. The authors of this article investigated all aspects of porting and achieved a fully featured Darknet engine on OpenCL. The effort was focused not only on classification using YOLO1, YOLO2, YOLO3, and YOLO4 CNN models. Other aspects were also covered, such as training neural networks and benchmarks to identify weak points in the implementation. Compared with the standard CPU version, the GPU computing code substantially improves the Darknet computing time by using underutilized hardware in existing systems. If the system is OpenCL‐based, it is practically hardware‐independent. The authors also improved the CUDA version as Darknet‐vNext.
A Review on Carbon Quantum Dot Based Semiconductor Photocatalysts for the Abatement of Refractory Pollutants
Authors: M. Athulya , John Bony K. , Chacko Anu Rose , Mohan Chitra , Mathew Beena
Published: March 2022

Photocatalysis is a green approach frequently utilised to eliminate a variety of environmentally hazardous refractory pollutants. Accordingly, the modification of semiconductor photocatalysts with Carbon Quantum Dots (CQDs) is of great importance for the treatment of such pollutants due to their attractive physical and chemical properties. CQDs are a perfect candidate to handle photocatalysts of high‐performance since they operate as co‐catalysts and as visible light harvesters. The higher separation rate of electron‐hole pairs in the photocatalytic system is attributable to better photodegradation efficiency. This review classifies CQD based photocatalysts as pure, doped and composite materials and discusses the specific advantages of CQDs in visible light‐driven photocatalysis. In this work, the versatile roles of CQDs in CQD‐based photocatalytic systems are thoroughly discussed and summarised.
The influence of corporate social responsibilities on sustainable financial performance: Mediating role of shared vision capabilities and moderating role of entrepreneurship
Authors: Luo Wenbo , Zhang Chuan , Li Minxin
Published: March 2022

This study examined the roles of economic, social, and environmental proactive corporate social responsibility (CSR) on sustainable financial performance among small and medium‐sized enterprises (SMEs) in China. The study also explored the moderating role of entrepreneurship and mediating role of shared vision capabilities in the relationships between economic, social, and environmental proactive CSR and sustainable financial performance for SMEs in China. This quantitative study used questionnaires to collect data from respondents. The PLS‐SEM method was used to analyse a sample of 490 Chinese SMEs in the manufacturing sector. The results indicated that economic, social, and environmental proactive CSR were positively associated with sustainable financial performance. The results also showed that shared vision capabilities positively mediated the relationships between economic, social, and environmental proactive CSR and sustainable financial performance. Entrepreneurship significantly moderated the relationships between economic and social proactive CSR and sustainable financial performance. The findings of this study are suitable for policymakers when developing policies related to CSR, entrepreneurship, and sustainable financial performance.
Advancements of Polyvinylpyrrolidone‐Based Polymer Electrolyte Membranes for Electrochemical Energy Conversion and Storage Devices
Authors: Li Wen , Wang Haining , Zhang Jin , Xiang Yan , Lu Shanfu
Published: March 2022

Polymer electrolyte membranes (PEMs) play vital roles in electrochemical energy conversion and storage devices, such as polymer electrolyte membrane fuel cell (PEMFC), redox flow battery, and water electrolysis. As the crucial component of these devices, PEMs need to possess high ion conductivity and electronic insulation, remarkable mechanical and chemical stability, and outstanding isolation function for the materials on both sides of the cathode and anode. Polyvinylpyrrolidone has received widespread attention in the research of PEMs owing to its tertiary amine basic groups and exceptional hydrophilic properties. This review focuses on the application status of polyvinylpyrrolidone‐based PEMs in PEMFC, vanadium redox flow battery, and alkaline water electrolysis, and describes in detail the key scientific problems in these fields, providing constructive suggestions and guidance for the application of polyvinylpyrrolidone‐based PEMs in electrochemical energy conversion and storage devices.
A weighted range‐free localization algorithm for irregular multihop networks
Authors: Yan Xiaoyong , Zhou Jian , Huang Haiping , Wu Chenhuang , Sun Lijuan , Song Aiguo
Published: March 2022

Range‐free localization is a widely concerned technique that supports many essential network applications like coverage and clustering. Most existing localization technologies assume that nodes are uniformly distributed in a regular network with no obstacles and that propagation paths between pairwise nodes are close to straight lines. However, in real‐world scenarios, network topology is usually irregular, resulting in estimated distances that differ significantly from the corresponding physical distances and poor anchor deployment. These will lead to erroneous distance measurement and inaccurate localization results. This paper proposes a new algorithm, called the weighted range‐free localization algorithm (WRL for short), to improve the localization performance in irregular networks. Specifically, we first present a feasible scheme that can fulfill the information exchange and relative distance estimation for each node simultaneously. We then employ an optimal weight function to suppress the effect of cumulative errors and introduce the weighted bounding‐box algorithm to mitigate outlier location estimation induced by probably collinear anchor nodes. Simulation results show that, compared to state‐of‐the‐art methods, WRL improves localization accuracy while incurring lower computation and communication overheads in various irregular network topologies.
Ontogenetic shift and feeding habits of the European hake (Merluccius merluccius L., 1758) in Central and Southern Tyrrhenian Sea (Western Mediterranean Sea): A comparison between past and present data
Authors: D’Iglio Claudio , Porcino Nunziatina , Savoca Serena , Profeta Adriana , Perdichizzi Anna , Armeli Minicante Enrico , Salvati Davide , Soraci Francesco , Rinelli Paola , Giordano Daniela
Published: March 2022

The present paper aims to investigate the ecological role of Merluccius merluccius, Linnaeus, 1758, in southern and central Tyrrhenian Sea (GSA 10, Resolution GFCM/33/2009/2 General Fisheries Commission for the Mediterranean), analyzing ontogenetic diet shifts, geographical variations on prey composition, and feeding habits. A total of 734 hake specimens ranging in size between 6 cm and 73 cm (Total Length, TL) were collected in 2018. In order to evaluate ontogenetic shifts in prey composition, samples were divided into five size classes and for each class the quantitative feeding indices have been calculated. The statistical analysis, based on index of relative importance percentage (%IRI), resulted in three trophic groups. The most abundant prey found in the immature hake specimens (size class I) were the Euphausiids, Stylocheiron longicorne and Mysidacea, while for samples with a total length over 10.5 cm were crustaceans and fish. Engraulis encrasicolus was the most abundant fish prey identified, followed by Boops boops and Myctophids. The high presence of Euphausiids, Mysids, Myctophidae, and Sternoptychidae in classes I, II, II, and IV (6–23 cm) showed the relevant role of mesopelagic fauna in hake diets, with an essential organic matter and energy flow from the mesopelagic to the epipelagic environment. Additionally, decapod crustaceans were found in the stomach contents of hakes belonging to class V (with size over 36 cm TL), which is notable considering that our study area includes an important decapod crustacean fishing area.
We are what we eat, plus some per mill: Using stable isotopes to estimate diet composition inGypsvultures over space and time
Authors: Baino Allan A. , Hopcraft Grant G. J. C. , Kendall Corinne J. , Newton Jason , Behdenna Abdelkader , Munishi Linus K.
Published: March 2022

Dietary studies in birds of prey involve direct observation and examination of food remains at resting and nesting sites. Although these methods accurately identify diet in raptors, they are time‐consuming, resource‐intensive, and associated with biases from the feeding ecology of raptors likeGypsvultures. Our study set out to estimate diet composition inGypsvultures informed by stable isotopes that provide a good representation of assimilated diet from local systems.

We hypothesized that differences inGypsvulture diet composition is a function of sampling location and that these vultures move between Serengeti National Park and Selous Game Reserve to forage. We also theorized that grazing ungulates are the principal items inGypsvulture diet.

Through combined linear and Bayesian modeling, diet derived from δ13C inGypsvultures consisted of grazing herbivores across sites, with those in Serengeti National Park consuming higher proportions of grazing herbivores (>87%). δ13C differences in vulture feather subsets did not indicate shifts in vulture diet and combined with blood δ13C, vultures fed largely on grazers for ~159 days before they were sampled. Similarly, δ15N values indicatedGypsvultures fed largely on herbivores. δ34S ratios separated where vultures fed when the two sites were compared. δ34S variation in vultures across sites resulted from baseline differences in plant δ34S values, though it is not possible to match δ34S to specific locations.

Our findings highlight the relevance of repeated sampling that considers tissues with varying isotopic turnover and emerging Bayesian techniques for dietary studies using stable isotopes. Findings also suggested limited vulture movement between the two local systems. However, more sampling coupled with environmental data is required to fully comprehend this observation and its implications toGypsvulture ecology and conservation.
Diet DNA reveals novel African Forest elephant ecology on the grasslands of the Congo Basin
Authors: Meyer Jordana M. , Honig Naftali , Hadly Elizabeth A.
Published: March 2022

Elephants are essential ecological engineers, creating and maintaining landscape structure and ecosystem function. The recently distinguished and critically endangered forest elephant is currently classified as a selective, non‐destructive frugivorous browser that maintains forest diversity, while the savanna elephant is a mixed feeder, often pushing over trees while maintaining grasslands. The presence and diets of forest elephants on grasslands and the potential maintenance of these systems remain largely unexplored. In the ecotone between the Guinea‐Congolian forest and Sudanian‐Guinean savanna ecosystems in Garamba National Park, DRC, we investigated forest elephant diet selection as a function of sex, age, and habitat using diet DNA (dDNA) metabarcoding of non‐invasively collected dung. GPS collar data were used to determine annual habitat use. Dietary niche partitioning was assessed among megaherbivores in the grasslands. Fecal samples represented the diet of individuals within each habitat, providing valuable insight into the plant biodiversity. Ecological patterns of diet were also revealed using a taxonomically free exact sequence variance approach, highlighting useability in a poorly characterized region. In the early wet season, these typically frugivorous forest elephants were consuming mostly grasses in both the woodland and grassland habitats and showing no sexual dimorphism in diet selection when in the same habitats. However, males were greater risk‐takers, entering the human‐altered landscape to forage on fruit. The forest elephants play a distinctive role within this tropical grassland when compared to other megaherbivores and utilize the unique ecosystem throughout the year. This elephant population is exhibiting behavioral plasticity and shifting their gardening efforts to a novel resource in the grasslands as opposed to their standard role in the forests, which is key to understanding their impact as ecosystem drivers within this landscape. This shift in behavior may result in this recovering elephant population playing a functional role in the restoration and maintenance of these grasslands.
Mechanistic Insights of Photocatalytic CO2 Reduction: Experimental versus Computational Studies
Authors: Masdeu‐Bultó Anna M. , Reguero Mar , Claver Carmen
Published: March 2022

To stop the global warming, a complementary alternative to the decrease of CO2 production is the reduction of its amount in the atmosphere by capture and transformation into consumer products. One of the most interesting primary products is CO, used to synthesise liquid fuels. Perhaps the most attractive way of reducing CO2 to CO is the photocatalytic route. To know the details of the mechanism of this reaction can help in the design of more efficient catalytic systems. In this review, we compile the studies, undertaken from both computational and experimental approaches, of the reaction mechanism of the photoreduction of CO2 to CO by molecular catalytic systems based on transition metal complexes. The combination of experimental and computational studies can be crucial to achieve the goal aimed.
Transition Metal‐Catalyzed Regiodivergent C−H Arylations of Aryl‐Substituted Azoles
Authors: Liu Linhao , Durai Manisha , Doucet Henri
Published: March 2022

The metal‐catalyzed direct functionalization of two different C−H bonds of the same organic molecule – also called regiodivergent C−H bond functionalization – is an important research topic in organic chemistry. Over the last decades, the number of tools to control such regiodivergent C−H bond functionalizations has increased significantly. One of the most effective tools consists of employing different metal sources as the catalysts. Palladium and copper catalysts are very effective to promote the direct arylation of 5‐membered ring heteroarenes, whereas the direct arylation using ruthenium and rhodium catalysts generally relies on the coordination of heteroelements to the metal. Therefore, in the presence of several aryl‐substituted azoles, the arylation of both the aryl unit using Ru‐ or Rh‐catalysis and of the azole unit using Pd‐ or Cu‐catalysts is possible. In this review, we will describe the scope and current limits of the use of this tool for the regiodivergent direct arylation of aryl‐substituted azoles.
The Structure of Hemicalide from the Marine Sponge Hemimycale sp
Authors: Marcourt Laurence , Massiot Georges
Published: March 2022

Hemicalide is a marine natural product isolated from the sponge Hemimycale sp., collected near the Torres Islands of Vanuatu. It is characterized by cytotoxicity in the sub‐nanomolar range, with an original mode of action. This article describes the establishment of the planar structure of hemicalide, based on extensive use of 2D‐NMR experiments. The molecule belongs to the polyketide class with an irregular combination of acetates and propionates and adorned with two unusual hydroxylated six‐membered ring lactones. After publication of the original patent, groups in Paris and Cambridge (UK) launched synthetic programmes with the aim of elucidating the configurations of some of the 21 stereogenic centers. The second part of the article discusses these achievements and presents the best hypothesis, to date, for hemicalide.
Structure‐Activity Studies of Nitroreductase‐Responsive Near‐Infrared Heptamethine Cyanine Fluorescent Probes
Authors: Morsby Janeala J. , Atkinson Kirk M. , Shradha Reddy Kommidi Sai , Freel Tristan , Janeková Hana , Štacko Peter , Smith Bradley D.
Published: March 2022

Two new classes of near‐infrared molecular probes were prepared and shown to exhibit “turn on” fluorescence when cleaved by the nitroreductase enzyme, a well‐known biomarker of cell hypoxia. The fluorescent probes are heptamethine cyanine dyes with a central 4‘‐carboxylic ester group on the heptamethine chain that is converted by a self‐immolative fragmentation mechanism to a 4‘‐caboxylate group that greatly enhances the fluorescence brightness. Each compound was prepared by ring opening of a Zincke salt. The chemical structures have either terminal benzoindolinenes or propargyloxy auxochromes, which provide favorable red‐shifted absorption/emission wavelengths and a hyperchromic effect that enhances the photon output when excited by 808 nm light. A fluorescent probe with terminal propargyloxy‐indolenines exhibited less self‐aggregation and was rapidly activated by nitroreductase with large “turn on“ fluorescence; thus, it is the preferred choice for translation towards in vivo applications.
DC‐electrokinetic motion of colloidal cylinder(s) in the vicinity of a conducting wall
Authors: Atay Atakan , Beşkök Ali , Çetin Barbaros
Published: March 2022

The boundary effects on DC‐electrokinetic behavior of colloidal cylinder(s) in the vicinity of a conducting wall is investigated through a computational model. The contribution of the hydrodynamic drag, gravity, electrokinetic (i.e., electrophoretic and dielectrophoretic), and colloidal forces (i.e., forces due to the electrical double layer and van der Waals interactions) are incorporated in the model. The contribution of electrokinetic and colloidal forces are included by introducing the resulting forces as an external force acting on the particle(s). The colloidal forces are implemented with the prescribed expressions from the literature, and the electrokinetic force is obtained by integrating the corresponding Maxwell stress tensor over the particles' surfaces. The electrokinetic slip‐velocity together with the thin electrical double layer assumption is applied on the surfaces. The position and velocity of the particles and the resulting electric and flow fields are obtained and the physical insight for the behavior of the colloidal cylinders are discussed in conjunction with the experimental observations in the literature.
Wildlife gardening: an urban nexus of social and ecological relationships
Authors: Mumaw Laura , Mata Luis
Published: March 2022

Biodiversity in urban environments continues to decline, alongside diminution of human connections with nature and community. An integrated ethic and practice of caring for one’s human and ecological community could help address these issues. Here, we describe how wildlife gardening can be such a pathway. We provide an overview of related social dynamics and benefits to human well‐being, highlighting a case study that reveals an array of connections and well‐being aspects derived from wildlife gardening, and their relationship with several activities, including time spent in the garden. We outline how positive biodiversity outcomes can be attained through habitat improvement in gardens, and describe how integration of nature and human community stewardship can function across physical and political boundaries when municipal governments and local communities work collaboratively. We contend that wildlife gardening conducted in this manner can involve urban residents in crafting and enacting an intertwined ethic and practice of caring for nature and humanity.
Perceived risk and vaccine hesitancy: Quasi‐experimental evidence from Italy
Authors: Deiana Claudio , Geraci Andrea , Mazzarella Gianluca , Sabatini Fabio
Published: March 2022

In March 2021, Italian health authorities suspended the Vaxzevria vaccine (VA) for 4 days over reports of very rare blood disorders among recipients. We exploit the quasi‐experimental setting arising from this break to study the drivers of vaccine hesitancy. Before the suspension, the VA vaccination trend followed the same pattern as Pfizer‐Biontech (PB). After the suspension, VA and PB injections started to diverge, with VA daily decreasing by almost 60 doses per 100,000 inhabitants for the following 3 weeks. The resulting vaccination rate was 60 percent lower than the value that would have stemmed from the VA pre‐suspension pattern. We show that the slowdown was weaker and less persistent in regions with higher COVID penetration and steadier and more pronounced in regions displaying greater attention to vaccine side effects as detected through Google searches. The public's interest in vaccine adverse events negatively correlates with COVID cases and deaths across regions.
Correspondence in reference to the previously published manuscript: Reduction of cycles of bendamustine plus rituximab therapy in the cases with good response for indolent B‐cell lymphomas
Authors: Autore Francesco , Fresa Alberto , Innocenti Idanna , Principe Maria Ilaria Del , Maglione Raffaele , Stefanizzi Caterina , Pelliccia Sabrina , Romeo Azzurra , Cimino Giuseppe , Papa Elena , Padua Laura De , Andriani Alessandro , Mengarelli Andrea , Tafuri Agostino , Ditto Concetta , Mauro Francesca Romana , Del Poeta Giovanni , Laurenti Luca
Published: March 2022

Takezaki et al. analyzed the outcome of 57 patients with indolent lymphomas treated with Bendamustine plus Rituximab (BR) according to the number of cycles received, showing that patients who discontinued BR after four cycles had similar outcomes compared to patients who received five or six cycles. Considering the similarities but also the differences between indolent lymphomas and chronic lymphocytic leukemia (CLL), we enriched the results obtained with a cohort of CLL patients treated with BR starting from the experience of the Lazio region group on CLL. Out of 115 patients, 97 (84%) received 4–6 cycles of BR, while 18 (16%) received 1–3 cycles. The outcome of the group of patients who received at least 4 cycles was superior in terms of response rate (ORR 96% vs. ORR 83%, p = 0.041; CR 58% vs. CR 28%, p = 0.052 respectively) and PFS [median PFS 52.6 (40.3–64.9) versus 26.2 (19.3–33.0) months, p < 0.001]. The number of patients undergoing 4 cycles of BR (4‐cycles group) and 5–6 cycles (over‐4‐cycles group) was 9 and 88, respectively. Compared to analysis conducted by the Japanese group in indolent lymphomas, in CLL we did not observe any difference between the outcome of the 4‐cycles group and the over‐4‐cycles group in terms of ORR (89% vs. 97%, p = 0.268) and in survival [median PFS 40.8 (13.7–67.8) versus 52.6 (38.7–66.5) months, p = 0.117]. Moreover, we observed that patients who achieved a clinical CR showed overlapping outcomes with patients who received more than 4 cycles [CR vs. non‐CR median PFS not reached vs. 11.0 months; over‐4‐cycles group median PFS 52.6 months (40.3–64.9); p < 0.001]. Nowadays chemoimmunotherapy with BR is reserved to fit elderly CLL patients, and there are many chemo‐free treatment options available; therefore, discontinuation after 4 cycles may be permissible in patients who obtained a CR in order to limit toxicity as much as possible.
Relapse during the treatment of pediatric feeding disorders
Authors: Haney Sarah D. , Greer Brian D. , Mitteer Daniel R. , Randall Kayla R.
Published: March 2022

Resurgence and renewal are treatment‐relapse phenomena in which previously extinguished behavior returns after the conditions for an alternative response worsen or the context changes, respectively. Recently, researchers have evaluated the prevalence of resurgence and renewal when treating destructive behavior with functional communication training. However, resurgence of inappropriate mealtime behavior has yet to be evaluated; perhaps because treatments involve qualitatively different resurgence opportunities (e.g., increased bite‐presentation rate). We evaluated the prevalence of resurgence and renewal of inappropriate mealtime behavior across 22 and 25 applications of extinction‐based treatments, respectively. Resurgence occurred in 41% (9/22) of applications, most often following presentation‐rate increases. Renewal occurred in 52% (13/25) of applications, most often following feeder changes from therapist to caregiver. We discuss these findings in terms of their ability to inform relapse‐mitigation strategies for resurgence and renewal of inappropriate mealtime behavior.
Size‐dependent osteogenesis of black phosphorus in nanocomposite hydrogel scaffolds
Authors: Xu Haocheng , Liu Xifeng , Park Sungjo , Terzic Andre , Lu Lichun
Published: March 2022

A promising new strategy emerged in bone tissue engineering is to incorporate black phosphorus (BP) into polymer scaffolds, fabricating nanocomposite hydrogel platforms with biocompatibility, degradation controllability, and osteogenic capacity. BP quantum dot is a new concept and stands out recently among the BP family due to its tiny structure and a series of excellent characteristics. In this study, BP was processed into nanosheets of three different sizes via different exfoliation strategies and then incorporated into cross‐linkable oligo[poly(ethylene glycol) fumarate] (OPF) to produce nanocomposite hydrogels for bone regeneration. The three different BP nanosheets were designated as BP‐L, BP‐M, and BP‐S, with a corresponding diameter of 242.3 ± 90.0, 107.1 ± 47.9, and 18.8 ± 4.6 nm. The degradation kinetics and osteogenic capacity of MC3T3 pre‐osteoblasts in vitro were both dependent on the BP size. BP exhibited a controllable degradation rate, which increased with the decrease of the size of the nanosheets, coupled with the release of phosphate in vitro. The osteogenic capacity of the hydrogels was promoted with the addition of all BP nanosheets, compared with OPF hydrogel alone. The smallest BP quantum dots was shown to be optimal in enhancing MC3T3 cell behaviors, including spreading, distribution, proliferation, and differentiation on the OPF hydrogels. These results reinforced that the supplementation of BP quantum dots into OPF nanocomposite hydrogel scaffolds could potentially find application in the restoration of bone defects.
Impact of preparation pH and temperature on amino acid stability of highly concentrated cell culture feed media
Authors: Cui Wanyue , Ou Jianfa , Xu Jianlin , Anderson Nadine , Borys Michael , Li Zhengjian , Khetan Anurag , Liu Shijie
Published: March 2022

BACKGROUND

The stability of amino acids (AAs) in a highly concentrated cell culture medium is affected by medium preparation and storage conditions. Variability in the concentration of medium components (including AAs) can influence cell culture performance and product quality attributes.

RESULTS

In this report, the impact of preparation pH, preparation temperature, and storage temperature was evaluated on the stability of 16 AAs in a highly concentrated cell culture feed medium. Optimizing the medium pH enabled an increase in the initial feed medium concentration by 30% plus 3.9 g L−1 tyrosine with no observed precipitation after 28 days. Up to 6.0 g L−1 tyrosine can be supplemented in the medium at ~pH 10 without precipitation. Moreover, preparing the medium at 40–50 °C prevented precipitation during storage at 4–8 °C. A slight negative impact on AA stability during this high‐temperature preparation was observed, but this impact was negligible relative to the AA degradation observed during extended storage of media prepared at 37 °C. The optimal preparation pH and temperature allowed the concentrated medium to be stored at 4–8 °C with minimal AA degradation and without precipitation. These discoveries were further supported by principal component analysis of AA profile similarity before and after storage at different pH and temperature conditions.

CONCLUSION

This study describes the medium preparation parameters to improve AA stability and mitigate precipitation issues. The optimization strategy will facilitate the development of robust cell culture production processes. © 2022 Society of Chemical Industry (SCI).
Glycogen storage disease type IIIa in pregnant women: A guide to management
Authors: Beneru Demi , Tchan Michel C. , Billmore Kate , Nayyar Roshini
Published: March 2022

Glycogen storage disease type IIIa (GSD‐IIIa) is an autosomal recessive disorder that impairs glycogenolysis, producing ketotic hypoglycaemia, hepatomegaly, cardiac and skeletal myopathy. During pregnancy, increased metabolic demand requires careful management. There are few case reports about pregnancy in GSD‐IIIa, however none detail management during caesarean section. This case describes a 25‐year‐old women with GSD‐IIIa diagnosed at 5 months of age. She had modest metabolic control with complications including hepatomegaly, mild skeletal myopathy and poor enteral function requiring multiple operative interventions. She had a planned pregnancy managed by a multidisciplinary team, which included a metabolic geneticist, maternal–fetal medicine specialist and metabolic dietitian. Nocturnal cornstarch was provided to meet basal carbohydrate requirements and a high protein diet with regular carbohydrates was consumed throughout the day. The woman remained well during the antenatal period and had an induction of labour at 38 weeks gestation. She had an emergency caesarean section in early labour due to an abnormal cardiotocography (CTG). The intraoperative and postoperative period were uncomplicated. A live baby boy was born in good condition, weighing 2440 g with APGARs of 9 and 9 at 1 and 5 min. She was managed in labour with glucose 10% IV at 3.5 mg/kg/min, hourly blood sugar level (BSL) monitoring and early epidural anaesthetic. The aim of the first 24‐h post‐partum was prevention of hypoglycaemia, which required strict management with dextrose 10% IV at 3.5 mg/kg/min, oral carbohydrate supplementation and BSL monitoring. This case highlights the complexity of GSD‐IIIa as well as provides a proposed plan for management during pregnancy.