bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pushing the boundaries of phosphorylase cascade reaction for cellobiose production I: Kinetic model development
Authors: Sigg Alexander , Klimacek Mario , Nidetzky Bernd 
Published: November 2023

AbstractOne‐pot cascade reactions of coupled disaccharide phosphorylases enable an efficient transglycosylation via intermediary α‐d‐glucose 1‐phosphate (G1P). Such transformations have promising applications in the production of carbohydrate commodities, including the disaccharide cellobiose for food and feed use. Several studies have shown sucrose and cellobiose phosphorylase for cellobiose synthesis from sucrose, but the boundaries on transformation efficiency that result from kinetic and thermodynamic characteristics of the individual enzyme reactions are not known. Here, we assessed in a step‐by‐step systematic fashion the practical requirements of a kinetic model to describe cellobiose production at industrially relevant substrate concentrations of up to 600 mM sucrose and glucose each. Mechanistic initial‐rate models of the two‐substrate reactions of sucrose phosphorylase (sucrose + phosphate → G1P + fructose) and cellobiose phosphorylase (G1P + glucose → cellobiose + phosphate) were needed and additionally required expansion by terms of glucose inhibition, in particular a distinctive two‐site glucose substrate inhibition of the cellobiose phosphorylase (from Cellulumonas uda). Combined with mass action terms accounting for the approach to equilibrium, the kinetic model gave an excellent fit and a robust prediction of the full reaction time courses for a wide range of enzyme activities as well as substrate concentrations, including the variable substoichiometric concentration of phosphate. The model thus provides the essential engineering tool to disentangle the highly interrelated factors of conversion efficiency in the coupled enzyme reaction; and it establishes the necessary basis of window of operation calculations for targeted optimizations toward different process tasks.
Genetic variation of the 5‐HT1A rs6295, 5‐HT2A rs6311, and CNR1 rs1049353 and an altered endocannabinoid system in depressed patients
Authors: Obermanns Jasmin , Meiser Hanna , Hoberg Saskia , Vesterager Cynthia Segura , Schulz Frank , Juckel Georg , Emons Barbara 
Published: November 2023

AbstractBackgroundThe reasons for developing depression are not fully understood. However, it is known that the serotonergic system plays a role in the etiology, but the endocannabinoid system receives attention.MethodIn this study, 161 patients with a depressive disorder and 161 healthy participants were examined for the distribution of the CNR1 rs4940353, 5‐HT2A rs6311, and 5‐HT1A rs6295 by high‐resolution melting genotyping. The concentration of arachidonoyl ethanolamide (AEA) and 2‐arachidonoylglycerol (2‐AG) in the blood was measured by liquid chromatography–tandem mass spectrometry. Additionally, depression and anxiety symptoms were evaluated based on self‐questionnaires. Fifty‐nine patients participated in a second appointment to measure the concentration of AEA, 2‐AG, and symptoms of depression and anxiety.ResultsWe observed higher AEA and decreased 2‐AG concentrations in patients with depression compared to healthy participants. During the treatment, the concentrations of AEA and 2‐AG did not change significantly. In patients higher symptoms of anxiety correlated with lower concentrations of 2‐AG. Gender differences were found concerning increased 2‐AG concentration in male patients and increased anxiety symptoms in female patients. Genotypic variations of 5‐HT1A rs6295 and 5‐HT2A rs6311 are associated with altered serotonergic activity and serotonin content in patients.ConclusionIn conclusion, it seems that the endocannabinoid system, especially the endocannabinoids 2‐AG and AEA, and genetic variations of the 5‐HT1A and 5‐HT2A could play a role in patients with depression and may be involved in a depressive disorder.
Depth filtration for clarification of intensified lentiviral vector suspension cell culture
Authors: Mayani Mukesh , Nellimarla Srinivas , Mangalathillam Ratish , Rao Hema , Patarroyo‐White Susannah , Ma Junfen , Figueroa Bruno 
Published: November 2023

AbstractDepth filtration significantly impacts efficiency of lentiviral (LV) vector purification process. However, it is often deprioritized in the overall scope of viral vector manufacturing process optimization. The demand for LV vectors has increased with the rise in disease indications, making it crucial to improve current manufacturing processes. Upstream bioreactor process intensification has enabled cell densities of over 107 viable cells/mL, creating challenges for harvest unit operations. The larger size of LV vectors and their physiochemical similarity to host cell‐DNA (HC‐DNA) and poor clarification performance causes significant challenges for the subsequent chromatography‐based purifications. As a result, a robust and scalable harvest of LV process is needed, especially for LV in vivo therapeutic quality needs. In this study, we systematically evaluated the overlooked yet important issue of depth filtration systems to improve enveloped LV functional vector recovery. We found that an established depth filtration system in process A that provided 94% (n = 6) LV functional recovery could not be translated to intensified Process B cell culture. Hence, the depth filtration process became a bottleneck for the purification performance in an intensified process. We demonstrated an improvement in LV functional vector recovery from 34% to 82% via filter train optimization for an intensified suspension cell culture system (>107 cells/mL with higher titer), while still maintaining a loading throughput of ≥82 L/m2 and turbidity ≤20 NTU. It was demonstrated that the two or three‐stage depth filtration scheme is scalable and more suitable for high cell density culture for large scale for LV manufacturing process.
CDIO‐CT collaborative strategy for solving complex STEM problems in system modeling and simulation: An illustration of solving the period of mathematical pendulum
Authors: Zhang Hong‐Yan , Zhou Yu , Li Yu‐Tao , Li Fu‐Yun , Jiang Yong‐Hui 
Published: November 2023

AbstractThe problem‐project‐oriented STEM education plays a significant role in training students' ability of innovation. Although the conceive‐design‐implement‐operate (CDIO) approach and computational thinking (CT) are hot topics in recent decades, there are still two deficiencies: the CDIO approach and CT are discussed separately and a general framework of coping with complex STEM problems in system modeling and simulation is missing. In this paper, a collaborative strategy based on the CDIO and CT is proposed for solving complex STEM problems in system modeling and simulation with a general framework, in which the CDIO is about “how to do,” CT is about “how to think,” and the project means “what to do.” As an illustration, the problem of solving the period of mathematical pendulum is discussed in detail. The most challenging task involved in the problem is to compute the complete elliptic integral of the first kind (CEI‐1). In the philosophy of STEM education, all problems have more than one solution. For computing the CEI‐1, four methods are discussed with a top‐down strategy, which includes the infinite series method, arithmetic‐geometric mean method, Gauss–Chebyshev method, and Gauss‐Legendre method. The algorithms involved can be utilized for R & D projects of interest and be reused according to the requirements encountered. The general framework for solving complex STEM problems in system modeling and simulation is worth recommending to college students and instructors.
Perigraftitis and implant therapy: A case report
Authors: Do Jonathan H. , Cobb Charles M. 
Published: November 2023

AbstractBackgroundA previous case study reported periimplantitis and concomitant perigraftitis of a second implant placed at a site that had alveolar ridge preservation three decades earlier. Infection at the site persisted 4 months after implant removal by flapless implant reversal. A flap was subsequently reflected, the grafted bone was removed, and a second alveolar ridge preservation was performed with a freeze‐dried bone allograft. The publication reported infection resolved, and the site healed uneventfully. However, it is unknown if placement of another implant at the site would be successful. The purpose of this paper is to report on the findings at surgical reentry and outcome of the third implant.MethodsEleven months after the second alveolar ridge preservation, the site was reentered. The bone graft was found to be partially soft tissue encapsulated. All encapsulated graft materials and soft tissue were removed. An implant was placed, and the alveolar defect was grafted with a demineralized bone allograft. Seventeen months after implant placement, a buccal free gingival graft was performed during which the crestal bone adjacent to the implant was found to be hard and corticated. The implant was deemed to be osseointegrated and restored after soft tissue healing.ResultsTwenty‐five months after implant placement, the third implant remained functional and asymptomatic with the peri‐implant bone exhibiting normal trabeculation.ConclusionsImplant therapy can be successful following treatment and resolution of perigraftitis.Key points
Perigraftitis may play a contributing role in the biologic complications of implants that have been placed into grafted bone.
Perigraftitis may be successfully resolved by completely removing all grafted bone.
Once perigraftitis has been eliminated, an implant may be successfully placed.
Translational approach to tooth autotransplantation: A 27‐year case study
Authors: Pini Prato GiovanPaolo , Franceschi Debora , Pace Riccardo , Di Gianfilippo Riccardo 
Published: November 2023

AbstractBackgroundThe aim of this case report was to present a translational approach to tooth autotransplantation using jiggling forces to enlarge the periodontal ligament (PDL) space before autotransplantation, with the goal of improving treatment success and long‐term survival.MethodsA 23‐year‐old patient, undergoing orthodontic therapy and with an unrestorable maxillary first molar, was proposed to have a healthy and fully‐erupted maxillary third molar transplanted in the socket of the first molar. Jiggling forces were applied to the third molar to enlarge the PDL space and facilitate the preservation of PDL fibers on the root surfaces during the extraction.ResultsJiggling forces induced hypermobility and widened PDL space of the third molar. The autotransplantation was successful and the patient was followed regularly over a 27‐year period. At the 27‐year visit, the patient showed optimal chewing function, oral plaque control, and absence of gingivitis. The transplanted molar exhibited periodontal health and absence of mobility. Probing depth of 5 mm and radiographic external root resorption was noted on a localized area of the transplanted tooth which had experienced traumatic and unintentional removal of PDL fibers during the extraction.ConclusionsA translational approach was proposed by integrating knowledge from the fields of orthodontics, trauma from occlusion, and replantation. It validated the crucial importance of maintaining healthy PDL fibers on the root surface and demonstrated clinically the successful autotransplantation of a fully formed third molar into the socket of a first molar with a retention of 27 years.Key pointsWhy is this case new information?

This case provided evidence of successful autotransplantation of a molar with complete root formation. It reported the longest‐term follow‐up (27 years) present in the literature. Most importantly, it used a translational medicine approach to apply concepts from the fields of orthodontics and traumatic occlusion to improve the success of the autotransplantation procedure.
What are the keys to the successful management of this case?

Jiggling forces induced tooth hypermobility and increased the PDL space of the tooth planned for autotransplantation. In turn, they facilitated the atraumatic extraction and preservation of the PDL fibers on the transplanted tooth, improving the success of the reattachment of periodontal fibers.
What are the primary limitations to success in this case?

Traumatic extraction resulting in the unintended removal of PDL fibers from the tooth planned for autotransplantation, or intentional removal of PDL fibers with root planing are expected to decrease the success rate of the autotransplantation procedure. This is due to the lack of viable PDL cells necessary for reattachment.
The social value and financial benefits of providing preventive and timely counselling to people with sight loss in Wales, UK
Authors: Anthony Bethany F. , Hartfiel Ned , Edwards Rhiannon T. 
Published: November 2023

AbstractBackgroundAlmost 2 million people in the UK live with sight loss, and this number is predicted to double by 2050. There is increasing recognition of the need to provide counselling services to people living with sight loss.AimThe aim of this research was to assess whether there is an unmet need for counselling services for people living with sight loss in North Wales and to estimate the social value and budget impact of the potential roll‐out of counselling services to this population.MethodBetween December 2020 and May 2021, a telephone survey was completed by 192 people living with sight loss in North Wales, UK. The survey instrument was a 19‐item questionnaire, which included the Short Warwick–Edinburgh Mental Well‐being Scale (SWEMWBS). Using data from the SWEMWBS and published statistics, a social return on investment (SROI) and budget impact analysis were conducted.ResultsMost respondents (84%, n = 161) had never been offered counselling in relation to sight loss. Thirty‐nine per cent (n = 74) stated that they would use a new counselling service if it were available. Fifty‐one per cent (n = 97) indicated that counselling could be especially beneficial for people who have recently been registered or diagnosed with sight loss (the timely window). Of those who completed the SWEMWBS, approximately 25% reported low mental well‐being or probable depression. Social return on investment analysis estimated that providing counselling services for people with sight loss in North Wales could generate a social value of £3.42 for every £1 invested.ConclusionTimely counselling may improve an individual's ability to cope with sight loss and improve their quality of life over time.
γ‐Glutamylation of Isopropylamine by Fermentation
Authors: Benninghaus Leonie , Zagami Laura , Tassini Giulio , Meyer Florian , Wendisch Volker F. 
Published: November 2023

AbstractGlutamylation yields N‐functionalized amino acids in several natural pathways. γ‐Glutamylated amino acids may exhibit improved properties for their industrial application, e. g., as taste enhancers or in peptide drugs. γ‐Glutamyl−isopropylamide (GIPA) can be synthesized from isopropylamine (IPA) and l‐glutamate. In Pseudomonas sp. strain KIE171, GIPA is an intermediate in the biosynthesis of l‐alaninol (2‐amino‐1‐propanol), a precursor of the fluorochinolone antibiotic levofloxacin and of the chloroacetanilide herbicide metolachlor. In this study, fermentative production of GIPA with metabolically engineered Pseudomonas putida KT2440 using γ‐glutamylmethylamide synthetase (GMAS) from Methylorubrum extorquens was established. Upon addition of IPA during growth with glycerol as carbon source in shake flasks, the recombinant strain produced up to 21.8 mM GIPA. In fed‐batch bioreactor cultivations, GIPA accumulated to a titer of 11 g L−1 with a product yield of 0.11 g g−1 glycerol and a volumetric productivity of 0.24 g L−1 h−1. To the best of our knowledge, this is the first fermentative production of GIPA.
Infection of tendon sheaths, joints, bursae, soft tissue, and tendon rapture by brucella: A case report
Authors: Zangeneh Mehrangiz , Rezvanfar Kiana , Khosravani‐Nejad Yasamin , Faghani Yazdanali , Dezfulinejad Manije , Saadat Fakhr Masoud , Ghorbani Parastoo 
Published: November 2023

Key Clinical MessageArthritis is one of the main presentations of chronic brucellosis, but bursitis and tendon rupture are also caused by brucellosis. Therefore, brucellosis should be considered in the differential diagnosis of arthritis, bursitis, and tendon rupture by physicians. In addition, early diagnosis and treatment are very important in the prevention of disability.AbstractBrucellosis is a zoonotic disease common in the Middle East. Manifestations of acute disease are fever, sweating, myalgia, and arthralgia. However, bone joint involvement occurs in 10%–85% of patients, and sacroiliac involvement occurs in up to 80% and vertebral joint involvement in up to 54%. A 57‐year‐old woman was admitted to the hospital of Islamic Azad University on February 26, 2021, with a history of one‐month pain and limited movement of the right shoulder joint with fever for surgery of the shoulder ligament. The standard agglutination titer (Wright) for brucellosis at first was 1/640 and then increased. MRI of the shoulder showed a supraspinatus tendon and anterosuperior labral of the glenoid labrum tear. Although the patient was a candidate for shoulder joint ligament surgery, with a diagnosis of brucellosis, the treatment of brucellosis was prescribed, symptoms disappeared with anti‐brucellosis antibiotic therapy without surgery, and the patient recovered. Supraspinatus tendon and antero superior labral of glenoid labrum tear of the shoulder joint in brucellosis is generally very rare. Failure or delay in the treatment of brucellosis can cause ligament rupture or joint disability. Sometimes, there are no symptoms except osteoarticular manifestations in brucellosis; therefore, brucellosis should be one of the differential diagnoses in osteoarticular diseases.
Accelerated Synthesis of Nanolayered MWW Zeolite by Interzeolite Transformation
Authors: Pornsetmetakul Peerapol , Coumans Ferdy J. A. G. , Heinrichs Jason M. J. J. , Zhang Hao , Wattanakit Chularat , Hensen Emiel J. M. 
Published: November 2023

AbstractHierarchical zeolites can offer substantial benefits over bulk zeolites in catalysis. A drawback towards practical implementation is their lengthy synthesis, often requiring complex organic templates. This work describes an accelerated synthesis of nanolayered MWW zeolite based on the combination of interzeolite transformation (IZT) with a dual‐templating strategy. FAU zeolite, hexamethyleneimine (HMI), and cetyltrimethylammonium bromide (CTAB) were respectively employed as Al source and primary zeolite, structure directing agent, and exfoliating agent. This approach allowed to reduce the synthesis of nanolayered MWW to 48 h, which is a considerable advance over the state of the art. Tracking structural, textural, morphological, and chemical properties during crystallization showed that 4‐membered‐ring (4MR) units derived from the FAU precursor are involved in the faster formation of MWW in comparison to a synthesis procedure from amorphous precursor. CTAB restricts the growth of the zeolite in the c‐direction, resulting in nanolayered MWW. Moreover, we show that this approach can speed up the synthesis of nanolayered FER. The merits of nanolayered MWW zeolites are demonstrated in terms of improved catalytic performance in the Diels‐Alder cycloaddition of 2,5‐dimethylfuran and ethylene to p‐xylene compared to bulk reference MWW sample.
Theoretical and Experimental Aspects of Electrocatalysts for Oxygen Evolution Reaction
Authors: Zhu Shifan , Song Lili , Xu Zhiheng , Chen Feida , Tao Haijun , Tang Xiaobin , Wang Yuqiao 
Published: November 2023

AbstractScientists are increasingly paying attention to using theoretical design as a guide combined with modern in‐situ characterization techniques to develop catalysts with high activity, low cost, and long‐term life. The review discusses the progress of catalyst theoretical design and corresponding experiments based on three typical oxygen evolution catalytic mechanisms, including the adsorbate evolution, lattice oxygen‐mediated, and unconventional bifunctional mechanisms. This work briefly describes the commonly used tools and descriptors in theory as well as the electrochemical techniques and characterizations in experiments. Our purpose is to sort out the ways to closely integrate the theoretical method and experimental verification from the perspective of reaction mechanism, and to provide some experience reference for the future development of theoretical tools and experimental technologies.
Generation of Molecular Counterfactuals for Explainable Machine Learning Based on Core‐Substituent Recombination
Authors: Lamens Alec , Bajorath Jürgen 
Published: November 2023

AbstractThe use of black box machine learning models whose decisions cannot be understood limits the acceptance of predictions in interdisciplinary research and camouflages artificial learning characteristics leading to predictions for other than anticipated reasons. Consequently, there is increasing interest in explainable artificial intelligence to rationalize predictions and uncover potential pitfalls. Among others, relevant approaches include feature attribution methods to identify molecular structures determining predictions and counterfactuals (CFs) or contrastive explanations. CFs are defined as variants of test instances with minimal modifications leading to opposing predictions. In medicinal chemistry, CFs have thus far only been little investigated although they are particularly intuitive from a chemical perspective. We introduce a new methodology for the systematic generation of CFs that is centered on well‐defined structural analogues of test compounds. The approach is transparent, computationally straightforward, and shown to provide a wealth of CFs for test sets. The method is made freely available.
Design of Dual EP2/EP4 Antagonists through Scaffold Merging of Selective Inhibitors
Authors: Corminboeuf Olivier , Diethelm Stefan , Zumbrunn Cornelia , Lyothier Isabelle , Niggli Nadja , Gnerre Carmela , Jeay Sébastien , Lehembre François , Boss Christoph 
Published: November 2023

AbstractProstaglandin E2 (PGE2) plays a key role in various stages of cancer. PGE2 signals through the EP2 and the EP4 receptors, promoting tumorigenesis, metastasis, and/or immune suppression. Dual inhibition of both the EP2 and the EP4 receptors has the potential to counteract the effect of PGE2 and to result in antitumor efficacy. We herein disclose for the first time the structure of dual EP2/EP4 antagonists. By merging the scaffolds of EP2 selective and EP4 selective inhibitors, we generated a new chemical series of compounds blocking both receptors with comparable potency. In vitro and in vivo profiling suggests that the newly identified compounds are promising lead structures for further development into dual EP2/EP4 antagonists for use in cancer therapy.