bluuebunny/crossref_metadata_2025 huggingface dataset:
Incidence and genetic variants of inborn errors of metabolism identified through newborn screening: A 7‐year study in eastern coastal areas of China
Authors: Men Shuai , Liu Shuang , Zheng Qin , Yang Shuting , Mao Huafen , Wang Zhiwei , Gu Ying , Tang Xinxin , Wang Leilei
Published: February 2023

Background

The incidence of inborn errors of metabolism (IEM) varies across countries and areas. Currently, there are no studies on IEM using newborn screening (NBS) in eastern coastal areas of China. We aimed to estimate the incidence and genetic variants of IEM and understand the spectrum of diseases caused by IEM and variants among them in this area.

Methods

The NBS performed by tandem mass spectrometry (MS/MS) from 2016 to 2021 was retrospectively reviewed. Heel blood was collected from all newborns 72 h after birth. Targeted massively parallel sequencing was performed for genetic analysis.

Results

Among 245,194 newborns, 95 were diagnosed with IEM, the overall incidence observed was—IEM: 1/2581; amino acid metabolism disorder: 1/4715; organic acid metabolism disorder: 1/11676; and fatty acid metabolism disorder: 1/11145. The incidence of different IEM was in the range of 1/245194 to 1/6452. Phenylketonuria (PKU, 1/7211) was the most common IEM, followed by methylmalonic acidemia (MMA, 1/27244), short‐chain acyl‐CoA dehydrogenase deficiency (SCADD, 1/30649), and citrin deficiency (CD, 1/35028). For genetic variants, the common hotspot variants found were—PAH gene for PKU: c.728G > A, c.442‐1G > A, c.611A > G, c.721C > T; PTS gene for non‐classical PKU: c.259C > T; MMACHC gene for MMA: c.658_660delAAG, c.609G > A; MMUT gene for MMA: c.1663G > A; ACADS gene for SCADD: c.1031A > G and c.1130C > T; and SLC25A13 gene for CD: c.1638_1660dup, c.852_855del.

Conclusion

This study displayed the diseases and varied spectrum of IEM in eastern coastal areas of China. Implementing NBS for IEM by MS/MS combined with massively parallel sequencing can offer an improved plan for NBS to detect IEM.
Plant blindness represents the loss of generational knowledge and cultural identity
Authors: Blue Stacie , Hargiss Christina L. M. , Norland Jack , Dekeyser Edward S. , Comeau Paula
Published: February 2023

Plant blindness, the inability of people to notice plants, is of current interest in the natural sciences community. It has been hypothesized that communities of varying cultures may have improved plant sight. Researchers used an online survey to assess citizens ability to identify plants. The survey also intended to address the concern of elders from the Turtle Mountain Band of Chippewa Indians (TMBCI) who have seen reduced abundance of traditional plant species. The survey assessed knowledge of local wetland, grassland, and forest habitats; names of plants; and how citizens use plant features in identification. The survey gathered demographic data to determine trends across different demographic groups including age and ethnicity. A total of 216 participants took the survey, the majority classified themselves as female and Native American or Alaska Native. Our findings indicated that participants were able to identify forest and wetland plants the best, but struggled with grassland plants. Older individuals were more able to identify plants when compared to younger individuals. Ecologically, increasing plant knowledge is vital to rebuilding and maintaining the diversity of local habitats, but culturally the impacts are just as important. The practice of using traditional plants in medicine and ceremony is an integral part of the TMBCI culture. As both the knowledge and the plants disappear in younger generations, so does their unique cultural identity.
High‐strength/high‐modulus polyvinyl alcohol fiber reinforced poly(amino acid)/hydroxyapatite composite for load‐bearing orthopedics applications
Authors: Wu Yanan , Lyu Defu , Chen Lichao , Ren Haohao , Yan Yonggang
Published: February 2023

Bone defects in the load‐bearing area require bone reconstruction using strong biomaterial with mechanical properties like cortical bone. Herein, the high‐strength/high‐modulus polyvinyl alcohol fiber (PVA) was first designed to incorporate into poly(amino acid) (PAA)/hydroxyapatite (HA) to obtain a new poly(amino acid)/hydroxyapatite/polyvinyl alcohol fiber (PAA/HA/PVA) composite via a melt extrusion process. To improve the interfacial adhesive performance, the titanate coupling agent HY‐109 [isopropyl tris(dodecylbenzenesulfonyl) titanate] was used for simultaneously graft modification of the PVA fiber and HA (TPVA, THA). The effect of their components on the mechanical properties and degradation ability were investigated by electromechanical universal testing machine and in vitro phosphate buffer solution soaking. The results indicated that the PAA/30THA/20TPVA composite had the most ideal mechanical and degradation properties, which far exceed those of PAA and PAA/THA composite. In addition, in vitro simulated body fluid immersion and cell culture experiment showed the PAA/THA/TPVA composites boosted in vitro bioactivity and exhibited excellent cytocompatibility and osteogenic activity in cell attachment, proliferation, alkaline phosphatase activity, matrix mineralization, and osteogenesis‐related gene expression. These reports demonstrated that the developed PAA/THA/TPVA composite displayed comprehensive performance optimizations, which showed its potential as a novel biomaterial to be applied as load‐bearing implant in the field of orthopedics.
A Combination of Ion Implantation and High‐Temperature Annealing: Donor–Acceptor Pairs in Carbon‐Implanted AlN
Authors: Peters Lukas , Spende Hendrik , Wolter Stefan , Margenfeld Christoph , Ronning Carsten , Voss Tobias , Waag Andreas
Published: February 2023

Herein, carbon‐implanted high‐temperature annealed (HTA) AlN layers are analyzed and donor–acceptor pair (DAP) transitions probably between the two most abundant impurities, carbon and oxygen, are identified. Both are regarded as the main, hard‐to‐avoid impurities in crystal growth. Oxygen is believed to lead to absorption in the deep UV below a wavelength of 250 nm. In contrast, carbon is the most likely candidate to be responsible for a distinct absorption band around 265 nm. This interpretation has recently been challenged. In this study, carbon‐implanted and HTA AlN layers with ion fluences above 8.1 × 1015 cm−2 are analyzed using low‐temperature and time‐resolved cathodoluminescence spectroscopy. Due to the high concentration of oxygen inside the AlN, as a result of the HTA process, a DAP transition between a most likely carbon‐related acceptor and ON is observed. The measured temperature‐ and power‐dependent blueshift of the peak emission energy as well as the luminescence transients can be clearly explained by a continuous change from a DAP transition at low temperature to a free electron to acceptor transition with increasing temperature. The findings are supported by a configurational coordinate model that describes the measured behavior qualitatively.
Synthesis of Crosslinked Hydroxypropyl Methylcellulose with Methyl Gallate‐Poly(Ethylene Glycol) as a Gel Electrolyte for Dye‐Sensitized Solar Cells
Authors: Gunasekaran Ahalya , Sorrentino Andrea , Aljafari Belqasem , Anandan Sambandam
Published: February 2023

Hydroxypropyl methylcellulose (HPMC) is blended with methyl gallate (MG) encapsulated with poly(ethylene glycol) (PEG) and then mixed with a liquid electrolyte to prepare a polymer gel electrolyte. The structural and physical properties of prepared polymer gels are analyzed by various analytical instruments. The MG‐PEG‐HPMC hybrid is found to be able for entrapping a large amount of liquid electrolyte and is used to fabricate dye‐sensitized solar cells (DSSCs). This polymer gel electrolyte shows high ionic conductivity (5.43 × 10−4 S cm−1) and good triiodide diffusion coefficient (2.25 × 10−6 cm2 s−1). The resulting DSSCs show an efficiency of 6.96% at a light intensity of 85 mW cm−2. The long‐term stability test reveals that the fabricated DSSCs will be stable even after 500 h. The benefits of incorporating a gel electrolyte into DSSCs are highlighted along with factors affecting the stability of these devices. The use of these bio‐based materials has the potential to make a significant contribution to the widespread exploitation of stable, efficient, and low‐cost dye‐sensitive solar cells.
Bi‐homogeneous observers for uncertain 1‐DOF mechanical systems
Authors: Texis‐Loaiza Oscar , Moreno Jaime A. , Fridman Leonid
Published: February 2023

A global, bi‐homogeneous, observer for a class of 1‐DOF mechanical systems with Coriolis and centrifugal forces, dry and viscous frictions and non‐vanishing bounded uncertainties/perturbations is proposed, ensuring predefined upper bound of convergence time. The options for convergence acceleration are discussed in a simulation example.
Co‐Assembly of Peptide with G‐Quadruplex DNA: A Strategic Approach to Develop Anticancer Therapeutics
Authors: Biswas Soumi , Basak Shubhanwita , Samui Satyabrata , Pasadi Sanjeev , Muniyappa K. , Naskar Jishu
Published: February 2023

G‐quadruplex (G4) is one of the non‐canonical nucleic acid structures that regulate multiple key biological processes. The formation of G4 hinders the progression of cancer. The molecular entities which can stabilize the G4 structure are very important to design anticancer therapeutics. Herein, it is described that a synthetic dendron‐like peptide, Cδ3‐(YYEE)‐E co‐assembles with G4 DNA in aqueous buffer containing Na+ ions. Various orthogonal biophysical studies have established the co‐assembly phenomenon. In silico, molecular docking studies also corroborate the results obtained from biophysical experiments. Importantly, the co‐assembly enhances the thermal stability of G4 DNA compared to free G4 DNA. The peptide inhibits the activity of telomerase enzyme which is found to be over‐expressed in most of the cancer cells and also down‐regulates the c‐Myc oncogenic expression. The peptide exhibits significant cytotoxic effect on cancer cells (HeLa and U2OS) compared to non‐cancer cells (HEK293) under similar experimental conditions. The study highlights the applicability of a synthetic bioactive peptide as a putative anticancer therapeutic.
Identification of Potential Anti‐COVID‐19 Drug Leads from Medicinal Plants through Virtual High‐Throughput Screening
Authors: Firouzi Rohoullah , Ashouri Mitra
Published: February 2023

Natural compounds are widely used as attractive and valuable starting points for drug lead discovery. The present study aims to identify phytochemical compounds found in medicinal plants as potential COVID‐19 inhibitors, using ensemble docking simulations. To this end, a phytochemical library from the PHCD database – a database of natural chemical compositions of Persian medicinal herbs (https://persianherb.com) – have been virtually screened against four key protein targets in the SARS‐CoV‐2 life cycle – the Mpro and PLpro proteases and the Spike and human ACE2 proteins. Several potential antiviral lead candidates have been identified based on the “Computational Multitarget Screening” approach, in which favourite candidates interact simultaneously with all four targets. Four of the bioactive phytochemicals identified – Chelidimerine, Gallagyldilacton, Hinokiflavone, and Physalin Z – show the highest binding affinities to all the targets and are suggested to be the best choices for drug design research. Also, several important medicinal plants, including Chelidonium majus L., Punica granatum, Rhus coriaria, Capparis spinose, Cichorium intybus, and Cynara scolymus, with the most phytochemicals interacting with all the host and viral proteins, have been identified that can be considered as the most important herbal resources for drug development with the medicinal plant formulations against COVID‐19.
Synthesis of Enantiomers of Chiral Ester Derivatives Containing an Amide Group and Their Chiral Recognition by 1H NMR Spectroscopy
Authors: Li Yan‐Lin , Zhao Hong‐Mei , Ren Yu‐Qing , Qiu Meng , Zhang Hai‐Tong , Gao Guang‐Peng , Zheng Li , Stavropoulos Pericles , Ai Lin
Published: February 2023

Enantiomers of chiral ester derivatives containing an amide group, and possessing one or two stereogenic centers were prepared from L‐ and D‐α‐amino acids, and glycine with (S)‐ and (R)‐mandelic acid for probing their chiral recognition as a new class of chiral guests by 1H NMR spectroscopy, since chiral ester derivatives have been rarely used as chiral substrates for chiral recognition by 1H NMR technology. The results indicated that these chiral ester derivatives have been successfully differentiated in the presence of tetraaza macrocyclic chiral solvating agents (TAMCSAs) 1 a–1 c. In order to better understand their chiral discriminating behavior, Job plots, association constants (Ka), and theoretical calculations of (S,S)‐G1 and (R,R)‐G1, as a representative example, were performed, respectively. In order to evaluate their practical application, the 1H NMR spectra of G1 and G9 with various optical purities were measured (up to 98 % ee). In this work, a practical strategy has been effectively established for chiral recognition of chiral ester derivatives containing an amide group and possessing one or two chiral centers in the presence of tetraaza macrocyclic chiral solvating agents 1 a–1 c by means of 1H NMR spectroscopy.
Fluorenone Appended Colorimetric Sensor for Cascade Detection of Fluoride and Calcium Gluconate with Applications in Solid State and Logic Gate Systems
Authors: Sharma Neha , Kaur Navneet
Published: February 2023

A novel fluorenone derived Schiff base chemosensor (1) has been synthesized as a colorimetric sensor for fluoride (F−) ions in CH3CN and characterized by various analytical techniques. The chemosensor 1 perceived high selectivity for F− ion detection in the presence of other anions along with naked eye color change from yellow to orange‐red with quantitative detection limit of 900 nM. The UV‐vis changes, density functional theoretical (DFT) calculations and 1H NMR titration studies pointed to F− ion induced deprotonation of −OH of sensor 1 that has been proposed to be responsible for the observed absorption as well as color changes. The sensor 1 has also been efficiently applied for the solid state concentration dependent naked eye detection of F− ions in the form of filter paper strips and smartphone applications. The in‐situ generated 1‐F− complex was further utilized for cascade recognition of calcium gluconate (CG). The reversible and reproducible changes produced by the addition of F− ions and CG enabled 1 to be used as “INHIBIT” molecular logic system and “SET/RESET” memorized device at the molecular level.
Ethylenediamine Vapors‐Assisted Surface Passivation of Perovskite Films for Efficient Inverted Solar Cells
Authors: Haider Muhammad Irfan , Hu Hao , Seewald Tobias , Ahmed Safeer , Sultan Muhammad , Schmidt-Mende Lukas , Fakharuddin Azhar
Published: February 2023

Defects present at the surface or within the bulk of halide perovskites act as a barrier to charge transfer/transport, induce nonradiative recombination thereby limit open‐circuit voltage (VOC), and accelerate degradation in the perovskite solar cells (PSCs). Passivation of these defects at surfaces, interfaces, and grain boundaries to suppress the charge recombination is therefore imperative to improving photovoltaic performance in the PSCs. Herein, a facile posttreatment of perovskite surface by ethylenediamine (EDA) via mixed solvent vapor annealing method is reported. The results show that only a trace amount of EDA causes significant suppression of nonradiative recombination leading to over 100 mV increased VOC and ≈22% improvement in power conversion efficiency (PCE) of the inverted PSCs. The key reasons for this improvement are an upward shift in the Fermi energy level, reduced lattice strain and Urbach energy, and reduction in nonradiative recombination upon EDA passivation. These lead to a PCE exceeding 20% up from 16% for a nonpassivated film. The unencapsulated EDA‐modified PSCs also demonstrate an improved shelf‐life and retain 87% of the initial PCE after 850 h.
Graph Transformer with Reinforcement Learning for Vehicle Routing Problem
Authors: Fellek Getu , Farid Ahmed , Gebreyesus Goytom , Fujimura Shigeru , Yoshie Osamu
Published: February 2023

Vehicle routing problem (VRP) is one of the classic combinatorial optimization problems where an optimal tour to visit customers is required with a minimum total cost in the presence of some constraints. Recently, VRP is being solved with the use of deep reinforcement learning (DRL), with node sets considered (represented) as a graph structure. Existing Transformer based DRL solutions for VRP rely only on node information ignoring the role of information on the edges between nodes in the graph structure. In this paper, we proposed an attention‐based end‐to‐end DRL model to solve VRP which embeds edge information between nodes for rich graph representation learning. We used Transformer based encoder‐decoder framework with an edge information embedded multi‐head attention (EEMHA) layer in the encoder. The EEMHA‐based encoder learns underlying structure of the graph and generates an expressive graph topology representation by merging node and edge information. We trained our model using proximal policy optimization (PPO) with some code‐level optimization techniques. We conducted an experiment on randomly generated instances and on a real‐world data generated from road networks to verify the performance of our proposed model. The result from all experiments show that our model performs better than the existing DRL methods and most of the conventional heuristics with good generalizability from random instance training to real‐world instance testing of different problem size. © 2023 Institute of Electrical Engineers of Japan. Published by Wiley Periodicals LLC.
Spatial and thermal ecology of juvenile head‐started Blanding's turtlesEmydoidea blandingii
Authors: Cann Armand A. , Muñoz Andrés , Lentini Isabella , Benjamin Timothy , Thompson Daniel , Anne Harden Leigh , Milanovich Joseph R.
Published: February 2023

Declining reptilian populations has been a growing concern over the last couple of decades. One such declining species of concern, the Blanding's turtleEmydoidea blandingii, occurs as isolated populations in North American prairie‐wetlands and is at risk of extirpation due to habitat loss and fragmentation, and increased predator (e.g. racoons, coyotes) populations due to supplemented resources in urban environments. To help mitigate declining populations, wildlife managers have invested in the conservation of this species through head‐starting (i.e. reared in ex situ) and juvenile release programs to augment wild Blanding's turtle populations. However, much of their spatial and winter/thermal ecology is understudied, and data for juveniles, and juveniles reared ex situ is especially scarce, yet this information is imperative to understanding shortfalls and improving head‐starting efforts in the future. In spring 2016 (RR2016) and 2017 (RR2017) we released a cohort (n = 12 each year) of head‐started juvenile Blanding's turtles equipped with radio transmitters and temperature dataloggers into a prairie‐wetland in the greater Chicago region, North America. Using ground‐based radio telemetry, we determined seasonal movement areas (SMAs; spring, summer and fall) and annual home ranges (AHRs) for both RR2016and RR2017cohorts via kernel density (KD) estimates. We also investigated the thermal characteristics of overwintering for both juvenile cohorts. We found that SMAs for the RR2016cohort, but not for the RR2017cohort, significantly differed across seasons for most SMA estimators. We also found that juveniles in both cohorts not only survived overwintering, but also displayed similar overwintering phenology (i.e. initiation: October–November; termination: April) and temperature variation as Blanding's turtles adults in other studies. Overall, our results indicate that head‐started juvenile Blanding's turtles may be able to acclimatize quickly to their natural environment post‐release. Our study provides evidence to the efficacy of well‐developed head‐starting programs that aim to augment and preserve imperiled turtle populations.
A pH‐responsive Zr‐based metal organic framework PCN‐777 as a potential oral drug carrier
Authors: He Qing , Lu Wenwen , Jiang Xiaoying , Han Yuanbo , Yu Hongliu , Zhao Hong , Guan Xinghua , Lin Wenxin
Published: February 2023

A Zr‐based metal‐organic framework PCN‐777 with good biocompatibility was synthesized by solvothermal method using 2,4,6‐Tris(4‐Carboxyphenyl)‐1,3,5‐Triazine and ZrOCl2 ⋅ 8H2O as raw materials. Its structure was identified and the results showed that it had good crystallinity. Then the anti‐inflammatory drug ibuprofen sodium was loaded into PCN‐777 to establish an IBUNa@PCN‐777 compound and the maximum loading capacity was tested. When the mass ratio of IBUNa to PCN‐777 was 4 : 1, the loading of IBUNa in IBUNa@PCN‐777 reached the maximum value 72.53 wt %. Biocompatibility investigation indicated PCN‐777 and IBUNa@PCN‐777 had good biocompatibility. Moreover, the drug release behavior of IBUNa@PCN‐777 testified the drug release at pH 7.4(>80 %) was greater than that at pH 2.0(<20 %). indicated that IBUNa@PCN‐777 had good pH response in simulated digestive environments. The above results demonstrated that PCN‐777 had potential application prospects as an oral drug carrier.
Reconstruction of spectra and an algorithm based on the theorems of Darboux and Puiseux
Authors: Grozdanov Sašo , Lemut Timotej
Published: February 2023

Abstract

Assuming only a known dispersion relation of a single mode in the spectrum of a meromorphic two-point function (in the complex frequency plane at fixed wavevector) in some quantum field theory, we investigate when and how the reconstruction of the complete spectrum of physical excitations is possible. In particular, we develop a constructive algorithm based on the theorems of Darboux and Puiseux that allows for such a reconstruction of all modes connected by level-crossings. For concreteness, we focus on theories in which the known mode is a gapless excitation described by the hydrodynamic gradient expansion, known at least to some (preferably high) order. We first apply the algorithm to a simple algebraic example and then to the transverse momentum excitations in the holographic theory that describes a stack of M2 branes and includes momentum diffusion as its gapless excitation.
Embracing complexity: making sense of diet, nutrition, obesity and type 2 diabetes
Authors: Forouhi Nita G.
Published: February 2023

Nutrition therapy has been emphasised for decades for people with type 2 diabetes, and the vital importance of diet and nutrition is now also recognised for type 2 diabetes prevention. However, the complexity of diet and mixed messages on what is unhealthy, healthy or optimal have led to confusion among people with diabetes and their physicians as well as the general public. What should people eat for the prevention, management and remission of type 2 diabetes? Recently, progress has been made in research evidence that has advanced our understanding in several areas of past uncertainty. This article examines some of these issues, focusing on the role of diet in weight management and in the prevention and management of type 2 diabetes. It considers nutritional strategies including low-energy, low-fat and low-carbohydrate diets, discusses inter-relationships between nutrients, foods and dietary patterns, and examines aspects of quantity and quality together with new developments, challenges and future directions.

Graphical abstract
De novo tryptophanase-based indole production by metabolically engineered Corynebacterium glutamicum
Authors: Mindt Melanie , Ferrer Lenny , Bosch Dirk , Cankar Katarina , Wendisch Volker F.
Published: February 2023

Indole has an increasing interest in the flavor and fragrance industry. It is used in dairy products, tea drinks, and fine fragrances due to its distinct floral odor typical of jasmine blossoms. The current production of indole based on isolation from coal tar is non-sustainable and its isolation from plants is often unprofitable due to low yields. To offer an alternative to the conventional production, biosynthesis of indole has been studied recently. A glucose-based indole production was achieved by employing the Corynebacterium glutamicum tryptophan synthase α-subunit (TrpA) or indole-3-glycerol phosphate lyase (IGL) from wheat Triticum aestivum in a genetically-engineered C. glutamicum strain. In addition, a highly efficient bioconversion process using C. glutamicum heterologously expressing tryptophanase gene (tnaA) from Providencia rettgeri as a biocatalyst was developed. In this work, de novo indole production from glucose was enabled by expressing the P. rettgeri tnaA in a tryptophan-producing C. glutamicum strain. By metabolic engineering of a C. glutamicum shikimate accumulating base strain, tryptophan production of 2.14 ± 0.02 g L-1 was achieved. Introduction of the tryptophanase form P. rettgeri enabled indole production, but to low titers, which could be improved by sequestering indole into the water-immiscible solvent tributyrin during fermentation and a titer of 1.38 ± 0.04 g L-1 was achieved. The process was accelerated by decoupling growth from production increasing the volumetric productivity about 4-fold to 0.08 g L-1 h-1.

Key points

• Efficient de novo indole production via tryptophanases from glucose

• Increased indole titers by product sequestration and improved precursor supply

• Decoupling growth from production accelerated indole production
Utilization of delactosed whey permeate for the synthesis of ethyl acetate with Kluyveromyces marxianus
Authors: Hoffmann Andreas , Franz Alexander , Walther Thomas , Löser Christian
Published: February 2023

Ethyl acetate is an important organic solvent and currently produced from fossil carbon resources. Microbial synthesis of this ester from sugar-rich waste could be an interesting alternative. Therefore, synthesis of ethyl acetate by Kluyveromyces marxinanus DSM 5422 from delactosed whey permeate (DWP) was studied in an aerated stirred bioreactor at 40 °C. DWP is mainly composed of residual lactose and minerals. The minerals inhibited yeast growth, as witnessed by an increased lag period, a reduced growth rate, and an extended process duration. All experiments were therefore carried out with diluted DWP. In a series of batch experiments, the pH of iron-deficient DWP medium varied between 4.8 and 5.9. The pH of the cultivation medium significantly influenced cell growth and product syntheses, with the highest ethyl acetate yield of 0.347 g g–1 and lowest by-product formation achieved at pH 5.1. It is likely that this effect is due to pH-dependent iron chelation, which affects the iron bioavailability and the intracellular iron content, thus affecting growth and metabolite synthesis. The viability of yeast cells was always high despite the harsh conditions in DWP medium, which enabled extended usage of the biomass in repeated-batch and fed-batch cultivations. These two culture techniques increased the volume of DWP processed per time by 32 and 84% for the repeated-batch and the fed-batch cultivation, respectively, without a drop of the ester yield.

Key points

• Delactosed whey permeate was converted to ethyl acetate with a high rate and yield.

• The formation of ethyl acetate in DWP medium at iron limitation is pH-dependent.

• Highly active yeasts from batch processes enabled extension as fed and repeated batch.

Graphical Abstract
First clinical experience using a novel automated mapping algorithm for mapping of ventricular arrhythmias
Authors: Imnadze Guram , Sommer Philipp , Fink Thomas , Hamriti Mustapha El , Khalaph Moneeb , Braun Martin , Sciacca Vanessa , Isgandarova Khuraman , Guckel Denise , Sohns Christian
Published: February 2023

A new automated vector-based mapping algorithm (AMA) for 3-dimensional (3D) mapping has been introduced. The aim of this study was to present our experience using AMA to recognize additional catheter ablation targets in patients with ventricular arrhythmias (VA). A total of 16 patients (ICM; ischemic cardiomyopathy, n = 6; NICM; non-ischemic cardiomyopathy n = 10) suffering from VA underwent catheter ablation. Following bipolar voltage mapping, AMA was utilized to reveal zones of decelerated conduction velocity vectors (CVV) and this information was superimposed onto the 3D reconstructions and compared with the presence of scar. Mapping time was 28.1 ± 10 min for the endocardial reconstruction of the left ventricle (LV) and 17 ± 5.4 min for the epicardium (n = 6 patients). The mean area of LV low voltage was 13.9 ± 15% (endocardial) and 11.9 ± 5.7% (epicardial). Decelerating CVV zones were revealed in all patients (mean conduction velocity threshold of 39.3 ± 13%). Sustained VA have been terminated through ablation and substrate modification was performed in all patients. Correlation between the presence of CVV deceleration zones and areas of abnormal low voltage from bipolar mapping was revealed in only 37.5% of patients, but there was good correlation between scar from unipolar voltage mapping and the presence of CCV deceleration zones (94%; p = 0.008). The novel AMA may improve the understanding of individual VA substrates due to the visualization of decelerated CVV zones and their correlation with abnormal low voltage predominantly from unipolar mapping.
Are physical performance and frailty assessments useful in targeting and improving access to adjuvant therapy in patients undergoing resection for pancreatic cancer?
Authors: Powell-Brett S. , Hodson J. , Pande R. , Mann S. , Freer Alice , Wyrko Zoe , Hughes Clare , Isaac J. , Sutcliffe R. P. , Roberts K.
Published: February 2023

Background

Many patients fail to receive adjuvant chemotherapy following pancreatic cancer surgery. This study implemented a multimodal, multidisciplinary approach to improving recovery after pancreatoduodenectomy (the ‘Fast Recovery’ programme) and measured its impact on adjuvant chemotherapy uptake and nutritional decline. The predictive accuracies of a bundle of frailty and physical performance assessments, with respect to the recipient of adjuvant chemotherapy, were also evaluated.

Results

The N = 44 patients treated after the introduction of the ‘Fast Recovery’ programme were not found to have a significantly higher adjuvant chemotherapy uptake than the N = 409 treated before the pathway change (80.5 vs. 74.3%, p = 0.452), but did have a significantly lower average weight loss at six weeks post-operatively (mean: 4.3 vs. 6.9 kg, p = 0.013). Of the pre-operative frailty and physical performance assessments tested, the 6-min walk test was found to be the strongest predictor of the receipt of adjuvant chemotherapy (area under the ROC curve: 0.91, p = 0.001); all patients achieving distances ≥ 360 m went on to receive adjuvant chemotherapy, compared to 33% of those walking < 360 m.

Conclusions

The multimodal ‘Fast Recovery’ programme was not found to significantly improve access to adjuvant chemotherapy, but did appear to have benefits in reducing nutritional decline. Pre-operative assessments were found to be useful in identifying patients at risk of non-receipt of adjuvant therapies, with markers of physical performance appearing to be the best predictors. As such, these markers could be useful in targeting pre- and post-habilitation measures, such as physiotherapy and improved dietetic support.
The imbalance between Bregs, Tfh, and Tregs in patients with anti-N-methyl-D-aspartate receptor encephalitis
Authors: Li Yatong , Zhang Jing , Liu Lei , Cui Shilei , Sun Houliang , Jiang Hanqiu , Guo Yanjun , Zhang Jingxiao , Xie Zhuxiao , Wang Jiawei
Published: February 2023

Objective

To detect the alteration of regulatory B cells (Bregs), follicular helper T cells (Tfh), and regulatory T cells (Tregs) frequencies in patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. Analyze their association with clinical severity and activity, and explore the effects of different immunotherapies on those immune cell subsets.

Methods

We enrolled 21 patients with anti-NMDAR encephalitis, 22 patients with neuromyelitis optica spectrum disorder (NMOSD), 14 patients with idiopathic intracranial hypertension (IIH), and 20 healthy controls (HC) in our study. The frequencies of various immune cell subsets were determined using flow cytometry.

Results

Compared to patients with IIH and HC, the frequencies of CD24hiCD38hi transitional B cells as well as Tregs were significantly lower while the frequency of Tfh was significantly higher in patients with anti-NMDAR encephalitis. The frequency of CD24hiCD38hi transitional B cells was significantly lower in the acute stage than in the recovery stage, and was negatively correlated with the modified Rankin scale (mRS) and the clinical assessment scale for autoimmune encephalitis (CASE). The frequency of CD24hiCD38hi transitional B cells at the last follow-up after rituximab (RTX) treatment was significantly higher than those treated with oral immunosuppressants or untreated. There was no clear difference between anti-NMDAR encephalitis and NMOSD in the above immune cell subsets.

Conclusion

We suggested that the frequencies of CD24hiCD38hi transitional B cells and Tregs were decreased while the frequency of Tfh was increased in patients with anti-NMDAR encephalitis. CD24hiCD38hi transitional B cells frequency may be a potential indicator to estimate the disease activity and severity.
The Consequences of Financial Leverage: Certified B Corporations’ Advantages Compared to Common Commercial Firms
Authors: Paeleman Ine , Guenster Nadja , Vanacker Tom , Siqueira Ana Cristina O.
Published: February 2023

Firms usually need to attract debt to form and grow, but increasing financial leverage also entails increased risks and costs for stakeholders, such as customers and employees. Accordingly, past research suggests that for common commercial firms (CCFs), which prioritize profits, higher leverage leads to lower sales growth and higher employment costs. However, Certified B Corporations (CBCs) distinguish themselves by having a credible prosocial mission and, therefore, might be better insulated against the adverse effects of higher leverage. Using a European multi-country matched sample of 136 CBCs and 136 CCFs, we find that the negative relationship between leverage and sales growth and the positive relationship between leverage and employment costs are weaker for CBCs than CCFs. Taken together, due to their certified prosocial mission, CBCs enjoy an advantage in debt financing compared to CCFs.
Oxygen saturation in intraosseous sternal blood measured by CO-oximetry and evaluated non-invasively during hypovolaemia and hypoxia – a porcine experimental study
Authors: Näslund Erik , Lindberg Lars-Göran , Strandberg Gunnar , Apelthun Catharina , Franzén Stephanie , Frithiof Robert
Published: February 2023

Purpose: This study intended to determine, and non-invasively evaluate, sternal intraosseous oxygen saturation (SsO2) and study its variation during provoked hypoxia or hypovolaemia. Furthermore, the relation between SsO2 and arterial (SaO2) or mixed venous oxygen saturation (SvO2) was investigated. Methods: Sixteen anaesthetised male pigs underwent exsanguination to a mean arterial pressure of 50 mmHg. After resuscitation and stabilisation, hypoxia was induced with hypoxic gas mixtures (air/N2). Repeated blood samples from sternal intraosseous cannulation were compared to arterial and pulmonary artery blood samples. Reflection spectrophotometry measurements by a non-invasive sternal probe were performed continuously. Results: At baseline SaO2 was 97.0% (IQR 0.2), SsO2 73.2% (IQR 19.6) and SvO2 52.3% (IQR 12.4). During hypovolaemia, SsO2 and SvO2 decreased to 58.9% (IQR 16.9) and 38.1% (IQR 12.5), respectively, p < 0.05 for both, whereas SaO2 remained unaltered (p = 0.44). During hypoxia all saturations decreased; SaO2 71.5% (IQR 5.2), SsO2 39.0% (IQR 6.9) and SvO2 22.6% (IQR 11.4) (p < 0.01), respectively. For hypovolaemia, the sternal probe red/infrared absorption ratio (SQV) increased significantly from baseline (indicating a reduction in oxygen saturation) + 5.1% (IQR 7.4), p < 0.001 and for hypoxia + 19.9% (IQR 14.8), p = 0.001, respectively. Conclusion: Sternal blood has an oxygen saturation suggesting a mixture of venous and arterial blood. Changes in SsO2 relate well with changes in SvO2 during hypovolaemia or hypoxia. Further studies on the feasibility of using non-invasive measurement of changes in SsO2 to estimate changes in SvO2 are warranted.
On Transient Analysis of $$\Delta _N$$-Markov Chains
Authors: Reed Stephanie , Ziadé Elia
Published: February 2023

Consider a cyber-physical system which has the purpose of maintaining the security of some physical asset. A particularly relevant scenario is one in which the system must perform its functions while at the same time enduring malicious attacks for an extended amount of time without energy renewal. We will study a theoretical model analogous to this cyber-physical system with an arbitrary number of nodes. The nodes in this system are able to communicate with one another and have the task of maintaining the security of the system. Initially all nodes comprising this system are in working order, however, due to attacks they can eventually become corrupted and then work against the security of the system. Of particular interest is the calculation of a number of metrics related to reliability of the system including the reliability function and the mean-time to failure. A particular case of this model has been examined by many researchers in the past, mostly using numerical methods. The contribution of this paper is the presentation of explicit expressions for the transient-state transition probabilities, reliability function, and the mean-time to failure along with rigorous proofs for the validity of these expressions. A result such as this is stronger than previous results via numerical methods and is an extension of previous analytical results where additional constraints on the model were imposed.
Genomic-based microsatellite development for Ternstroemia (Pentaphylacaceae) and transferability to other Ericales
Authors: Alvarado-Sizzo Hernán , Alcántara-Ayala Othón , Espinosa David , Rivas Gerardo , Oyama Ken , Luna-Vega Isolda
Published: February 2023

Background

The genus Ternstroemia is associated with the vulnerable tropical montane cloud forest in Mexico and with other relevant vegetation types worldwide. It contains threatened and pharmacologically important species and has taxonomic issues regarding its species limits. This study describes 38 microsatellite markers generated using a genomic-based approach.

Methods and results

We tested 23 of these markers in a natural population of Ternstroemia lineata. These markers are highly polymorphic (all loci polymorphic with 3–14 alleles per locus and expected heterozygosity between 0.202 and 0.908), most of them (19 out of 23) are in Hardy-Weinberg Equilibrium and free of null alleles (18 out of 23). Also we found no evidence of linkage among them. Finally, we tested the transferability to six other American species of Ternstroemia, two other Pentaphylacaceae species, and four species from different families within the order Ericales.

Conclusions

These molecular resources are promising tools to investigate genetic diversity loss and as barcodes for ethnopharmacological applications and species delimitation in the family Pentaphylacaceae and some Ericales, among other applications.
Real-world outcomes of patients with renal cell carcinoma, surgically treated at regional hospitals, based on a prospective long-term survey of the pre-robotic era
Authors: Kawasaki Yoshihide , Saito Hideo , Ioritani Naomasa , Tochigi Tatsuo , Numata Isamu , Numahata Kenji , Soma Fumihiko , Kyan Atsushi , Ishidoya Shigeto , Ota Shozo , Namima Takashige , Orikasa Kazuhiko , Yamashita Shinichi , Mitsuzuka Koji , Arai Yoichi , Ito Akihiro
Published: February 2023

Purpose

Renal cancer surgery is frequently performed in small regional hospitals in Japan. This study evaluated the outcomes of renal cancer surgery, comparing results from the pre-robotic surgery era with those obtained with robotic surgery.

Methods

This prospective cohort study was conducted on patients who underwent renal cancer surgery between 2008 and 2013 at 14 hospitals, comprising 13 regional hospitals and a university hospital, registered in the Tohoku Urological Evidence-Based Medicine Study Group. The patients’ backgrounds; perioperative data; annual postoperative renal function; and prognostic surveys, performed over a median follow-up period of 10 years were obtained.

Results

In 930 surgical cases at the 14 registered hospitals, the 10-year recurrence-free survival rates of cT1a, cT1b, cT2, and cT3 were 0.9326, 0.8501, 0.5786, and 0.5101, respectively. Meanwhile, the 10-year overall survival rates were 0.9612, 0.8662, 0.7505, and 0.7209, respectively. Long-term observation in patients with cT1 showed that vessel involvement and high tumor grade were prognostic factors for recurrence. As a noteworthy fact, radical nephrectomy was performed in 53.3% of patients with cT1a at the regional hospitals. However, even in patients with preoperative chronic kidney disease stage 3, radical nephrectomy was not a prognostic factor of renal function. This indicates that compensatory mechanisms had been working for a long time in many patients who underwent radical nephrectomies without hypertension and preoperative proteinuria, which were predictors of end-stage renal disease.

Conclusion

Based on a prospective long-term survey of the pre-robotic era, our results suggested no difference of the survival outcomes between the university hospital and regional hospitals. Our study provides baseline data to evaluate the outcomes of renal cancer robotic surgery, performed at regional hospitals.
The Effects of Exposing Solea senegalensis to Microbeads with and Without Pesticides
Authors: Albendín M. Gemma , Alarcón Isabel , Coello M. Dolores , Rodríguez-Barroso Rocío , Aranda Vanessa , Quiroga José M. , Arellano Juana M.
Published: February 2023

Microplastics (MP) are contaminants able to cause adverse effects on organisms. MPs are capable to interact with other environmental contaminants, including pesticides, altering their toxicity. The objective of the study was to research the sublethal effects (enzymatic activity) of pesticides alone and in combination with MPs. Cholinesterase enzymes are used as biomarkers to determine and evaluate the effects produced in organisms after exposure to pollutants. This study showed the acetylcholinesterase (AChE) enzymatic activity in the tissue of Solea senegalensis exposed to two environmental pollutants, the insecticide chlorpyrifos (CPF) and antibacterial triclosan (TCS) with and without microplastics (MPs). Solea senegalensis was chosen because it is a species in high demand because of its high economic value in southern Europe, as well as the use of this species in ecotoxicology and its increasing use as sentinel species, which justify using it to assess biological effects of pollutants. Toxicity tests were performed in organisms exposed to concentrations of between 5 and 80 μg/L CPF and 0.1 and 0.4 mg/L TCS for 96 h. In addition, each test incorporated MPs that were added at different concentrations in order to evaluate their role as a possible enhancer of the effects caused by the previous pollutants. In the case of CPF, the head and muscle tissue cholinesterase activity was inhibited from a concentration of 5 μg/L both without and with MPs, and the AChE enzymatic activity for the treatment with MPs was approximately half the activity for the treatment without MPs in the tissues studied. Besides, TCS inhibited the cholinesterase activity at a concentration of 0.3 mg/L in the muscle of S. senegalensis. In contrast, no significant differences were observed in the TCS + MP treatment compared to the controls. These results showed the importance of studies in assessing the anticholinesterase effects of pesticides combined with microplastics due to the abundance of these contaminants in the marine environment and the role of cholinesterase activity (biomarker) in the neurotransmission of key physiological processes.
Effect of monosodium glutamate on fetal development and progesterone level in pregnant Wistar Albino rats
Authors: Shosha Hadeer M. , Ebaid Hala M. , Toraih Eman A. , Abdelrazek Heba M. A. , Elrayess Ranwa A.
Published: February 2023

Monosodium glutamate (MSG) is a widespread flavor enhancer and stabilizer in manufactured or packaged foods that possess myriad adverse effects. This study aimed to evaluate the effect of MSG on placental progesterone receptors and fetal development. Thirty pregnant Wistar Albino rats were divided into three groups (ten/each). The control group (G1) gavaged distilled water only, low-dose treated group (G2) gavaged 3 g/kg MSG, and high-dose treated group (G3) gavaged 6 g/kg MSG from 1st to 18th days of gestation, and all pregnant rats were sacrificed on the 19th day of gestation. The effect of MSG on fetal weights, crown vertebral length (CVL), placental weight, placental ghrelin expression, and fetal skeleton examination were estimated. MSG induced a significant decrease in fetal weights, CVL lengths, placental weight, and ghrelin expression in both treatment groups compared to the control group. Several parts of the fetal skeleton showed incomplete ossification and delayed chondrification in which high-dose maternally treated fetuses were more affected. Many degenerative changes were detected in both maternal and fetal liver and kidney tissues in MSG-treated groups. Moreover, MSG caused a significant increase in serum ALT, ALP, and creatinine levels in pregnant rats’ blood. Serum progesterone was only elevated in G3 on the 19th day of gestation. This study showed that the administration of MSG during pregnancy adversely influences fetal growth and skeletal development and caused several biochemical and histological changes in the maternal and fetal liver and kidney tissues which assure the toxic and teratogenic effects of MSG.
Deep drawability of additively manufactured sheets with a structured core
Authors: Rosenthal Stephan , Hahn Marlon , Tekkaya A. Erman
Published: February 2023

The deep drawability of additively manufactured stainless steel sheets with a core structure is investigated. By fracture forming limit diagrams it is shown that the additively manufactured sheets reveal good formability. The deep drawing process is analyzed numerically and the numerical models are validated experimentally. The main failure mode is a fracture of the face sheets. No severe deformation of the core structure was encountered, leading to the fact that the parts keep their structural integrity after the deep drawing process. It is shown that the process forces can reasonably be predicted by a modified Siebel’s method. A process window diagram is derived, e.g. showing a maximum deep drawing ratio βmax = 1.4 for honeycomb structures with a relative core density of ρcore = 0.22.